Regeneron Pharmaceuticals Aktie

Conference call announcing their expanded collaboration to include next-generation Type 2 medicines. My name is Michelle, and I'll be your operator for today's call. [Operator Instructions] Please note this call is being recorded. I would now like to turn the call over to Ryan Crowe, Senior Vice President, Investor Relations at Regeneron.

Thank you, Michelle. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for joining today's call to announce the expansion of the collaboration between Regeneron and Sanofi. We have members from the management teams from both Regeneron and Sanofi here today. But before we get started with introductions and our meeting agenda, both companies will read their forward-looking statements.

For Regeneron investors, I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, changes to drug pricing regulations and requirements and our drug pricing strategy, intellectual property, pending litigation and other proceedings, and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarter ended June 30, 2026. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Regarding Sanofi's forward-looking statement, please refer to the language on the slide.

For Sanofi investors, we would like to remind you that information presented in this call contains forward-looking statements, which are subject to substantial risks and uncertainties that may cause actual results to differ materially. We encourage you to read the disclaimer in the presentation, and we also refer you to our Form 20-F on file with the U.S. SEC on our French universal registration documents. Let me turn the call over to Ryan.

Thank you, François. Now moving to today's speakers and our agenda. Joining me on today's call are Dr. Leonard Schleifer, Regeneron's Co-Founder, Board Co-Chair, President and Chief Executive Officer; Dr. Belen Garijo, Sanofi's Chief Executive Officer; Dr. George D. Yancopoulos, Regeneron's Co-Founder, Board Co-Chair, President, Chief Scientific Officer, and perhaps most pertinent for this call, the visionary and principal inventor and developer of Dupixent as well as for the technologies that have delivered not only Dupixent but all of the new assets being added to the alliance today. And finally, we also have François Roger, Executive Vice President, Chief Financial Officer at Sanofi.

For the presentation today, Len and Belen will begin with a high-level overview of the deal, and strategic rationale, highlight the productivity of the Regeneron-Sanofi collaboration over the past 2 decades as well as how the alliance intends to leverage the R&D engine and commercial platform the companies have jointly built over the years. Then, George will discuss the antibodies that the companies will now jointly develop as well as their development timelines.

Finally, François will review the key financial and operational terms for the transaction. After prepared remarks conclude, the remaining time will be available for Q&A. Additional members of the management teams from both Regeneron and Sanofi will also be made available to answer questions at that time.

With that, let me turn the call over to Len and Belen to begin today's discussion -- presentation.

Thank you, Ryan, and thanks to everyone for joining our call today. It's an exciting day for Regeneron and Sanofi as we extend our highly successful collaboration by adding differentiated assets that have the potential to address Type 2 inflammatory diseases. For more than 2 decades, our alliance with Sanofi has been one of the most productive collaborations in the history of the bio-pharmaceutical industry. Together, we have developed and commercialized Dupixent, which redefined what was possible for the treatment of Type 2 inflammatory diseases. Like any long-standing partnership, our journey has not been without challenges, but we have worked through them and are now focused on the renewed momentum of our alliance and the opportunities ahead.

Today, we are opening a new chapter. Our agreement extends our shared leadership well beyond Dupixent. Regeneron is contributing four fully human next-generation long-acting antibodies. The lead candidate targets IL13 and is currently in the clinic for atopic dermatitis. Regeneron is also contributing three preclinical candidates, including an IL4/IL13 bispecific as well as antibodies to the IL4 receptor alpha and interleukin-4. These are also long-acting. George will provide more details on these opportunities later in his presentation.

Sanofi, in turn, is contributing an option for lunsekimig, their IL13/TSLP Nanobody to potentially be added to the alliance at Regeneron's discretion pending Phase II results in chronic obstructive pulmonary disease.

Together, we are combining both companies' development capabilities to bring forward this next wave of innovation for Type 2 inflammatory diseases. Assuming successful development and regulatory approval, we will launch these medicines by leveraging our jointly built global commercial platform that currently serves more than 1.5 million Dupixent patients worldwide. The deal construct is also deliberately simple and aligns our shared motivations to advance the standard of care for Type 2 inflammatory diseases.

Regeneron and Sanofi will equally share development and commercialization costs while splitting any global profits 50-50. In addition, Regeneron will receive a $1 billion upfront payment from Sanofi, along with the opportunity to earn up to $7 billion in additional milestone payments upon the achievement of specified development, regulatory and commercial milestones.

Moving to Slide 7. Together, Regeneron and Sanofi have built something remarkable. What started nearly 20 years ago as a modest collaboration combining Regeneron's antibody platform with Sanofi's global development and commercial reach has become one of the most productive alliances in our industry. We now look forward to the next decade and beyond, building upon the success of Dupixent with the ambition to maintain our long-standing leadership within immunology.

Briefly to Dupixent, the standard of care for Type 2 inflammatory diseases, which is now one of the most widely used antibody medicines in the world, invented at Regeneron by George Yancopoulos and developed by George and his team in collaboration with Sanofi. Based on second quarter 2026 global net sales of EUR 5.2 billion as recorded by Sanofi, Dupixent is now annualizing above EUR 20 billion across 9 indications. In the U.S., Dupixent is the #1 biologic prescribed by dermatologists, pulmonologists, allergists and ENTs and leads in total prescription share in 8 of its 9 approved indications.

As we look to the next generation of Type 2 medicines, extending the alliance beyond Dupixent is about more than simply adding new antibodies. It is about pairing these next-generation assets with a proven global development platform and a sophisticated commercial engine that has already established leadership in Type 2 inflammation and is well positioned to sustain that leadership into the future. Let me turn the call over now to Belen to further discuss how we will build on our strong commercial position in immunology.

Thank you, Len, and hello, everyone. I am super excited with our announcement today since this is an important strategic step forward for both companies as we aim to sustain leadership in atopic dermatitis with a novel long-acting IL13 antibody as well as the next-generation pipeline candidates. And let me tell you why we are so excited with the journey ahead.

First of all, is the market potential. While advanced therapy penetration has significantly grown over the last few years, thanks in large part to Dupixent, only about 20% of eligible U.S. patients are being treated on advanced therapy today. There are many opportunities for growth, and we expect the market to nearly double over the next 5 years. Despite the very successful development and commercialization of Dupixent, there is still a need for meaningfully longer dosing intervals without compromising efficacy or safety. And this is what we intend to address with our novel long-acting IL13. And we see an attractive opportunity here as we will leverage our established commercial footprint, the prescriber relationships that we have developed over many years as well as the patient support infrastructure to accelerate our next generation of alliance products.

Moving into Slide #10. Let's take a closer look at the atopic dermatitis market. AD is a large market with more than 2.5 million patients suffering from moderate to severe atopic dermatitis in the U.S. alone. We are projecting the U.S. market reaching approximately $20 billion in sales by 2032 and to continue to increase thereafter with advanced therapy penetration exceeding 50% by 2040, consistent with what we have seen in other mature immunological diseases such as rheumatoid arthritis or Crohn's disease.

AD is not a saturated market. It is a market in early stages of growth with a large untreated population and a significant growth trajectory ahead. Yet, there is a clear unmet need around treatment burden. For a chronic condition, this is the opportunity our long-acting IL13 program is designed to capture. Superior dosing convenience without compromising efficacy or safety.

Let me now further elaborate on Slide #11, how we will continue to build on our successful development and commercial platforms, honing in on each partner's strengths. On R&D, Regeneron brings a pioneering, highly innovative antibody discovery platform. We will also leverage our leading immunology and atopic dermatitis development expertise across both companies. We have built deep and trusted relationships with health care providers across dermatology, allergy and pulmonology, just to name a few.

We operate a comprehensive patient services platform and have an industry-leading global supply and device capability that is serving patients across more than 60 countries. Our long-standing relationship with payers and our strong market access capabilities globally will serve as a competitive advantage and further support the acceleration of our next-generation medicines as part of this highly successful alliance.

Finally, on Slide 12, it is important to keep in mind something that Len already mentioned is that we have strengthened the governance of our expanded alliance and simplified the way we plan to operate this to further drive our successful collaboration. On development, Regeneron will hold final decision-making authority while both partners have aligned financial commitments to support that development. On commercial, Sanofi will continue to have final commercial decision rights, including access and pricing, while Regeneron will now have increased participation in key payer engagements.

I'm very pleased with the progress we have made to expand our collaborations with clear roles and clear accountability. This strengthened alliance setup will no doubt, better position us to bring these next-generation medicines to patients. And last but not least, mutual trust will be the guiding principle in this extended relationship.

Now let me pass it along the call over to George to discuss and build on these next-generation antibodies.

Thanks, Belen. Let's move to the next slide. Before I discuss the new antibodies being added to the alliance, I'd like to briefly reflect on the incredible Dupixent development journey that Regeneron and Sanofi have jointly shared over the past decade plus. We used our VELOCIMMUNE platform to invent dupilumab, an interleukin-4 receptor alpha blocker, working from the hypothesis that interleukin-4 and interleukin-13 are the key regulators of Type 2 inflammation.

Over the years, we gathered more and more evidence that all these diseases share dysregulation of the same pathway. And in fact, it is the remarkable and consistent efficacy of Dupixent across all these diseases that has definitively proven that IL4 and IL13 are the key central and shared drivers of all of these interrelated diseases from atopic dermatitis to asthma to eosinophilic esophagitis and beyond. Dupixent has indeed proved to be a breakthrough for so many of these patients, as I see every day with my own daughter.

It took not only great science and technology to bring this remarkable first-in-class and best-in-class drug to so many diseases and to so many patients, but an innovative and creative clinical development effort that broke new ground many times, addressing disease populations that, in many cases, had never been studied before at large scale. To do this, Regeneron and Sanofi joined forces and study by study, patient by patient, indication by indication, delivered a series of positive pivotal trials.

Dupixent is now FDA approved for nine distinct diseases spanning the skin, gut and respiratory systems for patients ranging from infants as young as 6 months to the elderly. And in many of these indications and settings, Dupixent became the first and leading therapeutic. The clinical results across these nine distinct diseases and age ranges have strongly validated the key central role of IL4 and IL13 in the underlying Type 2 inflammation driving all these diseases. We will continue to apply these learnings and insights to design the next generation of medicines.

On Slide 15, you can see the four molecules Regeneron is contributing to the expanded alliance. All are fully human antibodies, naturally derived using the same VELOCIMMUNE technology that delivered Dupixent and more than a dozen other approved antibodies, and all are highly and specifically selected to meet the goal of increasing patient convenience by dramatically extending dosing intervals for Type 2 diseases. All programs are on an expedited development path. Our long-acting IL13 antibody is already in the clinic, where we have already confirmed its remarkable long-lived pharmacokinetic properties. It is now being tested in atopic dermatitis patients with registrational studies on track to begin in late 2027 or early 2028.

Unlike Dupixent, our antibody to IL13 is a ligand blocker with a substantially prolonged half-life with a target dosing interval of at least every 3 to 6 months. Our proprietary VELOCIMMUNE technology enabled us to invent the only fully human, naturally-derived non-heavily engineered IL13 antibody with a naturally strong target affinity and a favorable pharmacokinetic profile that supports an extended dosing interval, positioning it to be potentially best-in-class.

The three other programs are expected to be clinic ready next year. The long-acting IL4/IL13 bispecific blocks both cytokines, and we believe it can produce a therapeutic effect similar to Dupixent in diseases requiring blockade of both. This bispecific was also uniquely enabled by our proprietary VELOCIMMUNE technology. This common approach, resulting in shared biopharmaceutical properties, greatly accelerates clinical development of this bispecific as well as of all of our related assets. The IL4 receptor antibody blocks the same target as Dupixent, but is expected to have a significantly longer dosing interval. The antibody to IL4 binds the ligands and may have distinct applications with extended dosing opportunities as well.

By targeting the IL4 and IL13 pathways at both the ligand and receptor levels and across monotherapy and combination approaches, we are building a highly versatile portfolio, providing flexibility to select the right molecule for the right disease while creating multiple opportunities for future clinical development and commercialization, and all were invented with the same VELOCIMMUNE platform, which we believe has proven that it produces the world's best fully human antibodies with the best biopharmaceutical properties.

Moving to the next slide. With these next-generation programs, we are building on the successful development model that Regeneron and Sanofi have built over the years. By combining our complementary capabilities and deep expertise in Type 2 inflammatory diseases, we intend to accelerate clinical development to potentially bring new treatment options to patients in the coming years.

Importantly, these programs will advance on parallel tracks. Learnings from each program will inform the others, allowing us to apply insights across these programs as data emerge. Moreover, Regeneron and Sanofi also bring a distinct advantage with our vast clinical experience and success that led to nine approved Dupixent indications across multiple age groups from infants and beyond. Our deep experience with these diseases, clinical endpoints, regulators and investigator networks gives us a meaningful advantage in designing and executing these programs efficiently.

Let me now turn the call over to François to review financial terms for the transaction. François?

Thank you, George, and hello, everyone. Moving to Slide 18. Let me share with you the main financial terms of this transaction. Sanofi may pay up to $8 billion of total considerations to Regeneron. That amount includes an upfront payment of $1 billion upon signing as well as a certain number of milestone payments linked to development, regulatory and commercial achievements. The financial terms of this agreement reflect a genuine partnership of equals. Both R&D costs and global profits will be shared 50-50 between Regeneron and Sanofi for the new alliance medicines.

This means that there will not be any R&D development balance for the new antibodies since the R&D costs would be equally financed by both partners as they are incurred over time. That symmetry of the economics reflects a balanced partnership where both companies have aligned incentives around commercial success. Net sales will continue to be recorded as per our existing reporting practice, meaning that Sanofi will record net sales. The transaction will be reflected in both Regeneron and Sanofi fourth quarter 2026 financials.

Let me add one final important comment about the prior agreement that covers Dupixent. The terms of the original agreement remain unchanged, including the Dupixent profit sharing. Let me now hand over back to Belen and Len for their final remarks.

Thank you, François. Before I turn it over to Belen, let me offer just a few brief closing thoughts. We are excited about the future of Regeneron's strengthened alliance with Sanofi. First, it adds four Regeneron invented next-generation antibodies to the alliance that has developed and commercialized Dupixent. It also establishes a simple aligned framework for sharing risk and reward. Global profits will be split 50-50 with additional payments tied to development, regulatory and commercial milestones.

In summary, I am confident that this strengthened alliance gives our next-generation programs the best opportunity to move rapidly through development, reach patients around the world, and extend our leadership in Type 2 inflammatory diseases for years to come. Let me now pass it along to Belen for a few additional closing remarks.

Len, thank you very much. I'm equally pleased and enthusiastic about the expanded alliance and the opportunities that we will be able to create together. This agreement brings a stronger and more durable framework for our alliance, clearer governance, greater transparency and the resolution of the litigation between our companies. It allows both organizations to move forward together and focus fully on advancing the science and importantly, delivering for patients.

Finally, this extended alliance positions both companies to sustain our leadership in immunology, capitalizing on Regeneron's next-generation science with the global development and commercial platform that we have built together over the years for Dupixent. And in relation to this, we have a very solid foundation to bring these potential new medicines to patients. This is also a first step into the transformation of Sanofi, and we are excited about the opportunities that lie ahead. We look forward to sharing the progress in the months and years ahead.

And with this, I would like to turn the call back to Ryan to begin the question-and-answer session. Ryan?

Thank you, Belen. This concludes our prepared remarks. We will now open the call for Q&A. Before we go to our first question, let me first introduce additional members of the Regeneron and Sanofi management teams that will also be available to answer questions. From Regeneron, joining Len and George are Marion McCourt, Executive Vice President, Commercial; Christopher Fenimore, Executive Vice President, Finance and Chief Financial Officer; and Joseph LaRosa, Executive Vice President, General Counsel and Corporate Secretary. And from Sanofi, joining Belen and François are Manuela Buxo, Executive Vice President, Head of Specialty Care; Paulo Fontoura, Executive Vice President, Head of Research and Development; and Jamie Haney, Executive Vice President, General Counsel.

[Operator Instructions] Michelle, can we please go to the first question?

[Operator Instructions] Our first question comes from Evan Seigerman with BMO Capital Markets.

Congrats on the updated partnership. So a question for the Regeneron management team. So you clearly have a lot of cash on your balance sheet and adding $1 billion more only adds more to that. Why did you kind of accept the $1 billion upfront to kind of restructure this? Was there anything else that you could have done potentially to strengthen your position? I'd love for color on that.

Yes. Thanks for the question, Evan. Look, we do have a lot of money on the balance sheet. I like to say because we're lucky to have George as a genius inventing our molecules, so we don't have to throw out money on poor business development discussions. But we're always open-minded. And as far as the transaction with Sanofi, it was just a matter of creating a fair relationship, and that's what the payment was intended to be part of.

Our next question comes from Luisa Hector with Berenberg.

Congratulations. So my question is really on the sort of overlap in the mechanisms versus Dupixent and whether you considered other mechanisms, perhaps any thoughts on trispecifics and whether there was any attempt to add external assets as you were renegotiating? Or is this essentially you're tied to the original mechanism from Dupi and therefore, that's the reason for that persisting all the way through?

Well, we have done an enormous amount of science, biology, human genetics based on our data -- Our proprietary data set involving millions of humans that have been sequenced and characterized with multiomics and for their EHRs and medical records. And I think the overwhelming data demonstrates the critical central roles for IL4 and IL13 in all of these Type 2 diseases. And the evidence suggests that right now, there are not other pathways that are strongly driving or can supplement the remarkable efficacy and safety profiles that we've seen with Dupixent. So our goal was to build on what we've learned, but to create molecules that create and give more benefit to patients, particularly by maintaining the efficacy and safety, but providing more convenience.

By creating all of these molecules using the same format that doesn't depend on human engineering that invariably results in compromising the biopharmaceutical properties of molecules, increasing propensities for anti-drug antibodies and creating all sorts of other problems. By using the same uniform platform, but by creating agents that deliver much longer action, we think we really have an opportunity here to change the treatment landscape for already the diseases we've identified as well as more potentially.

So I guess the bottom line is all the science suggests, and we're the ones who delivered it, that these are the central drivers. Everything else in the history of the science here does not support that adding other mechanisms is going to further enhance the efficacy without also hampering the safety profile. Let me remind you, the safety profile of addressing this mechanism through Dupixent is really essentially unprecedented.

Unlike almost any other biologics, we're not causing immunosuppression. We're actually, if anything, benefiting and correcting immune deficiencies or distractions that are seen in these patients. And so the science really supports exactly what we're doing, and we created the science. So we know it best.

As far as adding any outside molecules, I think the scientists feel that it makes sense. We, of course, are able to consider that.

Our next question comes from Tyler Van Buren with TD Cowen.

This is Nick on for Tyler. Congrats on the deal. $7 billion is a significant amount of downstream milestones, but I'm curious about the breakdown of the milestones over time. Could a significant portion of those be near term? Just a rough idea on timing for some of these would be great.

Yes. Those milestones are spread out over development, approvals, sales. I'm not going to go through all of them. The most near term we'll mention is start of Phase III. That will be the first $1 billion milestone. François, anything to add?

Nothing to add. I think that you got access to the details of the milestones very transparent anyway, but I agree with what Len said.

Our next question comes from Victor Floch with BNP Paribas.

This is Victor Floch from BNP Paribas on behalf of Peter Welford. On lunsekimig, actually, it would be very nice if I can get Regeneron and Sanofi to comment on that. So first, for Regeneron, I was just wondering why was lunsekimig not entered into collaboration at this stage given the Phase II data that we've seen? And secondly, for Sanofi management, what are the development plans for lunsekimig in asthma and CRS moving forward?

I think we were very sensitive as an alliance not to create situations where we'll be competing with each other on our own additional assets outside of the alliance. The TSLP/IL13 bispecific or DuoBody technically that you referred to is in Phase III, and it does address one of the targets in the alliance. So there is an option for us to bring it into the alliance if the data suggests it's worth moving forward.

Yes. And just to build on -- this is Manuela, Victor. Just to build on Len's point, we felt that in the interest of the partnership and with the COPD program being the one that is already in Phase III and the most advanced, to give an option to Regeneron to bring that into the partnership makes a lot of sense. And then for other programs, we will wait until we see the COPD data and then decide whether we continue for other indications as well.

But that will be a joint decision further down the road when we have more data. But we're excited about that potential, and we'll make that decision when we see the Phase III.

Our next question comes from Brian Abrahams with RBC Capital Markets.

This is Kevin on for Brian. We just wanted to ask maybe if you can comment on -- for Regeneron management team. If you can comment on the kinds of targets that the agreement covers. I know you mentioned the IL4/IL13 pathway. But if you can comment perhaps on whether any upstream or downstream targets to the cytokine receptor interaction itself could perhaps make sense should any encouraging data be seen along the way?

Yes. We certainly can look beyond what the alliance is now focused on. But I think as George eloquently said, focusing on IL13, IL4 or the IL4 receptor is where our initial efforts will be. We will, of course, look at opportunities that could be complementary downstream, upstream or left stream, right stream. But right now, we're focused for the reasons George said.

Well, if you're talking about targets upstream or downstream in the same pathway, for example, a STAT6 or so forth, I think what we have to understand is that we find those types of targets interesting and exciting, but they are not going to be delivering any better efficacy than blocking the actual target molecules themselves. And of course, there's always going to be safety concern with new modalities of action. And I think that what we have to consider when we consider potentially bringing in or discussing those sorts of approaches in terms of -- really in terms of what's in the patient's interest, the medical health care system's interest and so forth and what is really more convenient, a twice a year subcutaneous injection or having to remember to take a daily pill. If, and it's a long way if it could possibly even be competitive in terms of both efficacy and safety.

So of course, we're thinking about all these things and so forth. But it's not as if we're talking about new targets that are going to somehow enhance efficacy and safety here. We're talking about alternative ways to somehow treat something that is now so elegantly and beautifully and safely and effectively treated with the existing approaches, but now with these new approaches that may enable a twice a year or even less intensive dosing interval. It's hard for me to imagine convenience regimens that are going to be able to compete against, I think, what we may have to offer going forward.

I should just add that while we're not at the moment thinking about new mechanisms, we do have some really interesting ideas about new indications and new approaches using the same molecules. We'll have more to say about that in the future.

Our next question comes from Florent Cespedes with ODDO BHF.

Florent Cespedes with ODDO BHF. A quick one on the long-acting IL4 combinations. Maybe -- I know it's early days, but could you share with us what you have in mind in terms of potential targets and diseases with this product?

Well, as we all know and as our science has demonstrated that out of the nine diseases that we're already approved for, some of them might only need blockade of one ligand or another, while other ones require for optimal efficacy and safety blockade of both ligands. We have now put ourselves in the alliance in a position, as we outlined, to really specifically select and pick and put into the right position, the right reagents for the right diseases.

But because they're all generated from exactly the same platform, sharing very similar biopharmaceutical properties, in fact, they all share extensive sequence identity amongst themselves and so forth. This will greatly expedite clinical development programs when you're dealing with molecules that can be chosen and picked correctly for the right setting and the right indication, but that in many other ways are very similar biopharmaceutically allowing us to really learn from one and apply to the other.

I also want to add to what Len said in terms of the playbook that everybody else is following. Everybody else is essentially following the playbook that we've been writing together with Sanofi over the last 10 to 15 years. They're just trying to do what we've already done. As Len said, we wrote that playbook, and we have a lot of ideas about how we can rewrite the playbook going forward, particularly by having these very unique and special assets from which we can specifically pick and choose for the right setting and the right indication. So expect a lot more innovation going forward in this field from Regeneron and Sanofi.

Our next question comes from Akash Tewari with Jefferies.

So I think we're going to get, we already saw some data with Zumi in asthma, where we did see some pretty robust FeNO reduction. And I think in the next couple of years, we're going to get asthma data with just a long-acting IL13. Let's say that looks in line with what we've seen with Dupixent. How does that change your team's view in terms of prioritizing these four assets if it becomes a bit more clear that IL13 alone would be sufficient in a lot of these Dupixent-like indications?

And just for the Sanofi team, the confidence for the bispecific going into COPD, given we've seen strong atopic dermatitis data from the Pfizer trispecific this morning, and we didn't necessarily see the same signal with your drug.

Well, let me just say that you all have to remember that the newest IL13 blockers are essentially just reengineered, more highly engineered, which is more likely to cause problems as opposed to advantages than already existing IL13 antibodies. So the new IL13 antibody is just a rehumanized version of lebrikizumab or Ebglyss, which actually already failed in asthma and other respiratory indications.

So despite the possibility that it would have -- which we know, partial activity in some of these respiratory indications, it is highly unlikely to match the unmatched efficacy profile and safety profile of Dupixent in these respiratory settings, whereas we think this is exactly why we endowed our pipeline and these assets with the particular ability for the right setting to block either one cytokine or both effectively together.

So people can take shots and hope that a new IL13 antibody that is just essentially a reengineered version with no different fundamental activities than an old version is going to behave differently or one can build on the tried and true mechanistic understanding that we have convincingly delivered over the last 10 to 15 years.

Paulo, can you comment on the lunsekimig question, please? We cannot hear you.

We can't hear you, Paulo. Maybe when he gets back on, we can come back to him.

Our next question comes from Naresh Chouhan with Intron Health.

Just want to get some color on what the deal economics imply. I would have thought that, and presumably, this is a question for Belen and François, but I'm happy to hear from all of you. I would have thought that one of the key assumptions when you were agreeing the deal would have been around the Dupixent rebates and any kind of flexibility that might allow future commercialization of the new asset.

On our analysis, the $8 billion total deal and the $1 billion upfront can only really be justified if you still got Dupixent without biosimilars when the new drugs launch. So should our base case given this deal now be that the Dupi LOE is now pushed towards mid-2030s?

I think we have consistently repeated what we have said, which is the LOE anyway is coming in March 2031 as far as the U.S. is concerned, anyways, the U.S. is what matters. We are working actively in order to extend the LOE of Dupixent. There is no certainty at this stage, but we are reasonably confident on the fact that we should be able to extend it by a few years. And if you look at similar cases, I mean, on average, it has been extended by a few more years. Once again, there is no certainty at this point in time, but we are actively working to extend the LOE of Dupixent a few years behind the original LOE.

And let me add to what François mentioned and what I said during the introduction, this is a deliberate first step in the transformation of Sanofi and the alliance is now in a much stronger position to offer and progress a number of promising medicines as George and Len were discussing. Obviously, this doesn't preclude that we are going to be moving our strategic road map moving forward. And without preannouncing anything, you will be hearing from us on how do we optimally prepare for the loss of exclusivity of Dupixent by 2031, 2032.

Sorry. But can you hear me now?

Sorry. Paulo, we can hear you. Please go ahead and address that lunsekimig question.

Yes, exactly. So really sorry about that. I was logged out and needed to log back in. Paulo Fontoura, Head of R&D at Sanofi. And just to comment on the lunsekimig question. What I think we, our belief right now, and that's very much the spirit of the alliance that we want to make decisions based on data. Obviously, the data in the mild to moderate asthma is the only one in CRS with NP, the data that we have now. We still believe that the trial in COPD is worthwhile to pursue. These are Phase II/III design trials, very robustly powered and designed to really clearly demonstrate the signal there.

So at this point, it's not really about excitement. It's really about delivering the data that allow us to make a good decision. I think both mechanisms have shown in COPD that they have the potential to be beneficial for these patients. So again, our focus right now is really on delivering data for that experiment.

Our next question comes from Salveen Richter with Goldman Sachs.

Could you speak to the base case here for timing of market entry for these assets and how you could potentially accelerate development?

I would simply say -- just a couple of words on that, as soon as possible.

Yes, we anticipate a pivotal study start for the long-acting IL13 either in late '27 or early '28. And obviously, we'll be moving as quickly as we can through that program to enable registration.

You have to recall, Salveen, [ tumor side ]. The FDA understands what these molecules, based on what Dupixent has delivered. We understand through the work that we've done together this pathway better than anybody else. We know how to get the patients. We know what the endpoints are. We know what the trial designs should be. So we really do feel we can go very rapidly here, but the proof will be in the pudding.

We have to remember, as Len said, I mean, we're the ones who identified and defined pharmacodynamic features, biomarkers, everything that you have to understand to best optimize dosing profiles and regimens to achieve optimal efficacy and safety as we've proven over and over and over again in our Phase III trials. All of those learnings are going into the expedited clinical development program. And thus, anybody should expect that the people who invented and created this entire field will know how to make sure that they take advantage of all of these learnings in terms of expediting things going forward.

Okay, Michelle, I think we have time for 3 more questions.

Our next question comes from Richard Vosser with JPMorgan.

Just wanted to go back to STAT6. It seems very clear that STAT6 is not a part of, or going to be a part of the collaboration. Just wanted to ask on Sanofi's STAT6, where this fits in, therefore, and how that could be commercialized within the framework or outside the framework of the collaboration. Just thoughts on that program.

Thank you, Richard. This is Manuela. So I think on the -- first of all, as Belen said earlier, our immunology strategy is a core strategic focus area for us, both inside of the alliance as well as outside of the alliance. So this program that you mentioned and some of the other programs that we have ongoing, will continue and are not impacted by this. We are looking at several disease areas here. And the truth is also in immunology, there's so much unmet need and so many areas for opportunity that we're really looking at it very broadly and are committed to immunology, both, of course, with Regeneron in the alliance, but also outside of the alliance.

Thanks, Manuela.

Our next question comes from Alexandria Hammond with Wolfe Research.

So you and your competitor showed some data this morning at EADV, and that drug is now moving into Phase III trials to demonstrate superiority over Dupixent. So I guess in this growing environment, how are you thinking about putting these alliance drugs head-to-head versus Dupixent with the primary endpoint of showing superiority?

I didn't quite understand the question. I heard you say that somebody is trying to take on Dupixent, and good luck. It's always great if patients can get something better than the remarkable safety and efficacy that Dupixent brings. But I didn't get the second part of your question.

Just, will you run head-to-head trials with your new alliance drug?

I think George and the team will be unfolding the strategy fairly quickly. And so maybe you can just be a little patient there.

More to come on that, Alex. Let's move to our last question, please, Michelle.

Our last question comes from Graham Parry with Citi.

Just -- it's a commercial question really because what evidence you have or payer discussions you have that dosing interval would be sufficient to retain reimbursement and market share in a biosimilar Dupixent or dupilumab market. So the 50% of advanced therapies by 2040 that you're talking about, how much of that do you think would be dupilumab biosimilar and how much would be the non-dupilumab?

Yes. So thanks, Graham. First of all, remember that the atopic dermatitis market, first of all, it's a highly heterogeneous market. It's a large market. And as Belen said earlier, you're talking right now about 20% advanced therapy penetration. So there's a lot of room for growth. We know that there, for some patients, there's a preference for longer dosing drugs. And this is what obviously, the IL13, the long-acting IL13 and potentially some of the other drugs we'll offer. And you also have to remember that the capabilities that we have built in the alliance around the commercial infrastructure, the deep relationships that we have with health care providers, but also capabilities around access and payer relationships, we will leverage those for any of the new assets that will hopefully come to fruition. And that is a real competitive advantage, we believe.

We'll also, as we discussed earlier, look at how do we design the programs, the trials in a way to drive that level of differentiation. But there's definitely opportunities given patient needs and different patient preferences for different products, whether it -- again, efficacy and safety is a must, right? But then some people will prefer longer dosing drugs, other people will prefer other things. It depends a little bit on patient preference, but there is a big opportunity in this market that is currently still to be unlocked, and we believe we have a real opportunity to do that within the alliance given what we have built collectively.

Thanks, Manuela. Len, do you have any closing thoughts?

Well, so I just want to say that we've talked a lot about drugs. We've talked a lot about diseases. We've talked a lot about markets. I just want to say a few words about people. At Regeneron, we're particularly lucky to have the guy who invented all these technologies and these drugs. George Yancopoulos is here, who's going to continue to lead this development effort. So we're really fortunate and proud of that. And we are very pleased to welcome Belen to our alliance that I hope will continue to make a difference for the patients because it really is about making a difference for the patients.

Thanks, Len. And thank you, Michelle, our operator, and thanks to everyone who joined the call today. We apologize to the many folks who are in the queue. We don't have time to get to you today. But as always, the Investor Relations teams at Regeneron and Sanofi are available to answer any other questions that you may have. Thank you, everyone, and have a great day.

Thank you for your participation. You may now disconnect.

Thank you so much for our next conversation with health care leaders and disruptors. I have the pleasure of speaking with Regeneron Pharmaceuticals. My name is Jeffrey Walch. I'm one of the analysts at Bernstein, I cover U.S. Biotechnology. And I'm very excited today to talk to 2 of the senior leaders at Regeneron, Chris Fenimore, EVP, Finance and CFO; and Ryan Crowe, SVP, Investor Relations. Before we kick off, I think, Ryan, you have something to read.

I sure do, Jeffrey. Thank you so much for having us. And I'll just briefly read a forward-looking statement reminder that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. And with that, Jeffrey, why don't we hop into your questions?

Perfect. Well, thank you once again, both of you for chatting with us today. I'll sort of ask the question and whoever or both of you that would like to answer, feel free to do so. So first off, congrats on a great quarter. Strong print. Maybe we could start with EYLEA. What are your thoughts on the most recent print and specifically the performance of EYLEA?

Thanks, Jeffrey, again. Thanks for having us. I think if you look -- as you referenced, overall, we had very strong financial performance, putting EYLEA aside for a second. If you look at both the top line and the bottom line, we had double-digit year-over-year growth. if you look at the performance of our 3 major growth drivers, whether it's EYLEA HD, Dupixent or Libtayo, we basically had the achievement of all-time quarterly net sales for each of those 3 products. And in addition to that, we paid off the Sanofi development balance in the second quarter, which historically had impacted our share of collaboration profits with Sanofi. And then going forward in third quarter and beyond, that will obviously be an uplift on our earnings, particularly related to the Sanofi collaboration profits. Turning to EYLEA HD, you're right. Very, very strong performance from EYLEA HD, great commercial execution on the part of our team.

If you recall, we had basically label enhancements that were approved in the fourth quarter of 2025, where it was every 4-week dosing. That was something as well as an additional indication in RVO. If you look at every 4-week dosing, that was something that the physician community was looking for because it provided them with reimbursement confidence. It was very important for them to know that if they needed the flexibility of going down to potentially every 4 weeks that they would get reimbursed. So the fact that we had both every 4-week dosing as well as the addition of the RVO indication has resulted in what we've seen in terms of very good performance in the first half of 2026. If you look at proportion of sales, EYLEA HD in the second quarter was roughly 60% of net sales of the EYLEA franchise, which is obviously very, very encouraging. In terms of market share, we were the only innovative brand to actually grow share in the second quarter.

And we're obviously very proud of that. The other thing that we're seeing in terms of EYLEA HD is just real-world experience. The docs have obviously had the ability to use their product now for quite a while with patients, and they're actually seeing durability gains out there. I think it's roughly on average that when patients switch from another product to EYLEA HD, they're seeing an extension of treatment, roughly an increase of, let's say, close to 4 weeks, which is great in terms of what's happening out there in the marketplace. So again, very encouraged about the performance of EYLEA HD.

That's great to hear. Look as a forward-looking basis, I'm curious what your perspective is on the potential for EYLEA to maintain and grow market share in the class.

We did say on our second quarter call that we expect sequential demand growth in both the third and the fourth quarter in the low to mid-teens. So this is reflective of obviously some of the things that I just spoke about in terms of what's happening out there in the marketplace. Very encouraged and constructive on the brand to continue to grow. But our team has a lot of work out there to obviously continue to execute. There are additional biosimilars that are entering the 2-milligram space, and there are challenges to go out there and continue to convince both providers as well as other constituents out there that EYLEA HD should be their innovative brand of choice.

Sounds great. Well, switching gears to Libtayo. It would be great to hear your thoughts on the most recent performance last quarter for both within non-small cell and also non-melanoma skin cancers.

Jeffrey, that's an overlooked product in my view. So thank you for asking about Libtayo. Last quarter, we had growth over 30% year-over-year. And in the U.S., revenues coming from the cutaneous squamous cell carcinoma and basal cell carcinoma indications comprise about 60% of sales, where non-small cell lung cancer comprised about 40%. So we're seeing a pretty significant contribution in the lung cancer segment. We're now second in new-to-brand share as well as total share for lung cancer in the U.S. And that -- in terms of new-to-brand share now outpacing Opdivo, Imfinzi, and Tecentriq combined. So we continue to see and make inroads in the lung cancer segment, which is very exciting.

Of course, we added about a year ago, adjuvant CSCC to the label. We are now the only approved immunotherapy for that particular setting. And we believe there's around 10,000 patients in the U.S. that can benefit from Libtayo with that particular disease. So we're very excited about the future of Libtayo in the non-melanoma skin as well as the lung cancer segments and certainly anticipate growth to continue there.

That's great. And immunotherapy is really a cornerstone treatment for a lot of patients, especially non-small cell. And there's going to be some changes coming up with KEYTRUDA going LOE. And curious how you're thinking about what potential risks or not may be posed by KEYTRUDA's upcoming LOE, especially in terms of your non-small cell sales.

Yes, that's a great question and one that's kind of hard to predict. You need a pretty good crystal ball to be able to confidently project how it's going to impact the market in which KEYTRUDA plays, which is virtually all settings. But lung cancer, in particular, where they have a very large share of the market. What we've seen in a lot of biosimilar cases is that oftentimes, the impact is greatest on the reference product as opposed to those that are adjacent in class. So that may be the case here. I do think there is some differentiation with regard to Libtayo, particularly in squamous cell lung cancer.

That particular segment, the data is strong. And if you compare it across trial with KEYTRUDA, you can make an argument that it might even be better. So we have some ability to counter detail a biosimilar pembrolizumab when it comes, which I'm not sure we even know when that will be. But it's certainly -- it's a when, not an if. So we're certainly preparing for that event. And of course, we're also looking beyond just biosimilar PD-1 and PD-L1s at some of the next wave of innovation in the immunotherapy space that could also disrupt the lung cancer market. So we'll keep our eyes on that as well.

Yes. And on that point, no worries if you can't disclose anything, but anything of interest there that you're thinking about and no worries if it's too early to disclose it.

Well, I think we'd be blind not to acknowledge that PD-1 by VEGF is becoming -- coming closer and closer to generating data in Western patients that could be potentially transformative for the space. So we need to keep our eyes on that. Of course, there's also the ADCs that can penetrate different markets as well. So there's a lot of different competition either in place or coming that could potentially impact Libtayo. But we're focused on continuing to drive growth in the segments that we can play in, in terms of the approved indications and really leaning into the data that we think is quite strong.

That's great. Well, then switch gears to Dupixent, another cornerstone drug for the company. What are your thoughts on the most recent print and how we should be thinking about the Dupixent moving forward?

So Dupixent is a remarkable drug, right, Jeffrey. I mean, if you think at what -- between our partnership or alliance with Sanofi and also in collaboration with our commercial team at Regeneron, have done amazing things of really growing and continuing to execute on the brand. Product annualizing with roughly $24 billion a year. I think it's approximately about $18 billion in the U.S. alone. So -- and if you look at the breadth of the indications, and Len and George have talked about basically having a pipeline and a product that's approved in 9 indications in the U.S. right now, 4 of them have achieved blockbuster status. If you look at historically, as the product has grown, atopic dermatitis was obviously the first blockbuster indication, but that has now obviously expanded into other indications.

I think the most recent data that we've seen is if you look at TRxs, a little more than 40% of the TRxs are outside of atopic dermatitis. And if you look at NBRxs, it's roughly 50% of NBRxs are outside of atopic dermatitis. So continue to believe in what the brand has done, obviously, in joint execution by our collective teams. And we think it's wonderful in terms of what the product has done for both patients and physicians out there. If you look at just even the breadth of the physician community that this product touches. I think it's the #1 prescribed biologic among dermatologists, pulmonologists, allergists and ENTs. So this is clearly a product that we're very proud of with our collaborators in Sanofi.

Absolutely. Dupixent LOE is coming up maybe in the next few to several years. Curious what you're thinking about that as it approaches in terms of -- is there any potential to extend that? Any thoughts as you near the Dupixent LOE?

That's a complicated question and one that we're not prepared to answer today in terms of date certainty for biosimilar launches of dupilumab. But what I can say is that we have composition of matter patent in the U.S. that expires in March of 2031. And then in Europe, it's in 2033. In Japan, it's 2034. So we still have a few years left before even the earliest potential biosimilar launches, which would be reflected by those dates. We have a very layered state covering the innovations around dupilumab, including methods of treatment patents, manufacturing patents, formulation patents, some of which extend into the early to mid-2040s. And of course, these are inventions that we invested in and worked hard on with Sanofi to bring to market to help patients, and we're going to assert and defend them to the extent -- to the greatest extent possible to extend the durability of this important franchise for both companies.

The dosing patents for asthma and atopic dermatitis begin to expire towards the middle part of the 2030s. So certainly, that's an important inflection potentially in terms of the runway for the exclusivity period. But I think we're going to continue to press on with all of the IP in the hopes of extending it as long as possible. Us and Sanofi are fully aligned on defending all of the patents, and we will probably gain more clarity on when biosimilars can launch as we approach those initial competition matter expiry dates in each of these big regions.

You highlight the partnership with Sanofi. And curious from a business development perspective, is there any potential or thoughts on expanding that collaboration with Sanofi beyond Dupixent.

So you heard from both ourselves and Sanofi on our respective second quarter calls that there is interest in pursuing some sort of expansion of the collaboration and that we continue to make progress at that point on such a relationship. We continue to make such progress and both parties are in active discussions. It makes a significant amount of sense as we talked about the value that's been generated for Dupixent in terms of the relationships with both providers, payers and then just the reputation of the brand amongst even the patient community to try and leverage what's been built between both parties. We'll obviously continue to have those discussions with our colleagues at Sanofi. And then once there's more to update, we will obviously update the investment community.

Perfect. Maybe taking a step back and thinking about you have a couple of near-term readouts over the next year. It's a really important year for the development side. And maybe you could highlight what you would consider to be Regeneron's drug development strategy, which underpins these upcoming programs that we're going to maybe touch on C5, you have your Factor XI program. So I just love to hear what you would say is your overarching strategy in terms of drug development.

So maybe I'll start, and I'll let Ryan maybe talk about some of the specifics about some of the programs that you've mentioned. The underlying sort of foundation of Regeneron is obviously science, right? It's deep rooted in everything that we do. We'd like to say that the commercial organization, while extremely valued at Regeneron is not what drives the development of drugs at Regeneron. It's really George Yancopoulos and his team and their ability to basically discover and develop drugs. And a lot of that foundation is in some of the investments that we've made over basically the past almost nearly 40 years that the company has been in existence.

And things like genetics, we have what we call the Regeneron Genetics Center. It's been in existence over a decade at this point, where we have invested in building the database associated with the Regeneron Genetics Center, where it's more than 3 million exomes have been sequenced at this point. They're linked to electronic health records. We're now expanding into proteomics to expand even the power of the database. And that is really fundamental in a lot of what we do in terms of target identification, validation, selection of indications for clinical trials. It drives a lot of what we do. And that fundamentally, we believe, provides us with a competitive advantage and has yielded the roughly 50-plus things that are in the clinic at this point. I know, Ryan, some specifics and things that you'd like to talk about.

Yes. I think our antibody engineering platform is also a competitive advantage for Regeneron. And manufacturing, of course, we have plenty of scale to manufacture our products and get them to patients. In terms of the pipeline, you mentioned a couple of the near-term pipeline readouts that we're going to have, C5 being one that's going to have an exciting end of year with a PDUFA date for the cemdisiran, which is an siRNA to C5 for generalized myasthenia gravis that is in November, and we look forward to potentially launching, we think, a very differentiated product with great efficacy and safety data as well as an extended dosing interval where we would only require 4 administrations per year. Within the C5 franchise, we also anticipate registration-enabling data for a study in PNH, which should be reading out in the fourth quarter as well as an interim analysis for geographic atrophy that will evaluate a couple of -- a combination with an antibody C5 and cemdisiran as well as cemdisiran monotherapy compared to placebo. So we can talk more about that momentarily.

We're also looking at a very broad program in hem/onc, specifically within myeloma as well as in lymphomas. Linvoseltamab now known as Lynozyfic is approved in late-line multiple myeloma. We're looking to advance that program into earlier lines of therapy as well as in premalignant conditions. With odronextamab, we have ongoing studies in follicular lymphoma as well as DLBCL, diffuse large B-cell lymphoma and are excited about potentially filing that drug and getting approval in the U.S. soon. So those are 2 examples.

I guess we can talk about Factor XI, which is another genetically validated target, we believe, that can address various thrombotic conditions, hopefully, without increasing the risk of bleeding, which is what the genetics suggests. Obesity, a very obviously huge commercial category and one that is becoming more understood in terms of how the incretins can really reduce weight loss and improve outcomes for diabetics as well. So we're playing in all of these large categories. We have several others that I'm sure we'll talk about as well. But the pipeline is vast. You've got over 50 programs, but it all comes down to genetics and trying to figure out the immune system and antibody engineering is kind of the 3 cores of Regeneron science that we really have built around.

That's a great deep overview and nice to hear. And yes, let's maybe dive into a couple of those in more detail. You mentioned the upcoming Phase III readout in PNH. Maybe walk us through what constitutes success from that readout? Any sort of risk that you want to qualify, if any?

Sure. Yes, PNH is a disease currently being addressed with a couple of antibodies that are approved from AstraZeneca, ravulizumab and eculizumab. What we are evaluating in our study is a combination of a C5 siRNA called cemdisiran as well as an antibody to C5 called pozelimab. And we are running that combination head-to-head against eculizumab over a 26-week period, where we'll be evaluating co-primary endpoints, one being disease control as measured by LDH as well as transfusion avoidance. In terms of LDH and disease control, we have pretty good early indicators from the Part A of this study where we compared the same combination head-to-head against ravulizumab and demonstrated that 96% of patients could reach normalized levels of LDH versus about 80% for ravulizumab.

And then we took those same patients who are uncontrolled on ravulizumab and switched them to the combination. I believe all but one went to LDH control very quickly after switching to our combination. So I feel very comfortable with the profile that can be demonstrated for LDH control. The second -- the co-primary endpoint of transfusion avoidance is trickier. And we believe that it introduces some risk to the study because not all transfusions are driven by intravascular hemolysis, which is really the only mechanism you would expect C5 inhibition to prevent. So that is one that we're going to be watching very closely. We should get the data in the next few months. We're excited about the trial and getting the results, but I would point that out as one potential risk for the study.

Absolutely. And always going to be some risk with every trial. So it's good to identify potential one and be prepared. Maybe switching gears then to geographic atrophy, which you just mentioned, the interim analysis coming up. Maybe give your thoughts on that upcoming analysis.

Sure. Geographic atrophy is another disease that we believe is driven by complement and how it inflames the choriocapillaris. And our approach is different than the approved agents, which are administered intravitreally. We will be evaluating systemic administration of either that C5, I keep talking about -- C5 siRNA, I keep talking about cemdisiran or the combination that we're using in the PNH study, cemdisiran plus pozelimab compared to placebo. And we're running, I would call it, a seamless Phase II/III study here with the first 225 patients enrolled comprising the Phase II cohort and then starting with the 226 patient enrolled, that would be the registration-enabling cohort, which ultimately should be around 750 patients.

So back to the Phase II cohort, the first 225 patients. They're going to be randomized 1:1:1, so around 75 patients per arm. And after 6 months, we're going to evaluate geographic lesion slope across all 3 arms to determine if there's any efficacy at all. Systemic approaches in GA have historically been very challenging. We have reason to believe that we could have a different outcome based on the inhibitory profile demonstrated in our gMG study, where we demonstrated with the combination 99% inhibition of CH50 assay to C5 at week 12. So that's a really remarkable result and a very quick result. But at 26 weeks with a disease like geographic atrophy, which is very slowly progressing, are we going to see meaningful slowdown of these geographic lesions. We will have to see.

Our hope is that we are at least on trend with the approved intravitreal agents. And if we are, I think we'd be confidently moving forward. We can also get some information about maybe one arm is stronger than the other that could inform how we proceed in that Phase III cohort. But we're just hoping to see some activity in terms of geographic slope -- geographic lesion size and slowdown in the slope. We'll also evaluate secondary endpoints and of course, safety with this being an elderly and especially vulnerable population inhibiting complement to the extent we think we can do with this combination could introduce infection risk. We need to be cognizant of that as well. So we'll learn a lot. Again, this is a fourth quarter readout, too. So C5 is going to have a big couple of months upcoming.

Yes. Absolutely. And maybe talking about a broad program, siRNA, it's a broad program in development. Maybe give us an overview of next steps, some data release and then target indications that maybe you've -- where you see most likely to play.

Yes, another probably overlooked franchise at Regeneron. And we talked a lot about the Sanofi collaboration earlier, but the siRNA portfolio at Regeneron is built from a collaboration with Alnylam, which we started, I don't know, 6, 7, 8 years ago, and it's been a lot of work. But we're at a place now where we've got kind of 3 different, I'd say, buckets with cemdisiran being one, C5 being one. Regeneron purchased the rights -- the global rights of cemdisiran from Alnylam. So we own all development and commercialization rights there and are obviously advancing it in C5 indications. The second bucket I would call out is liver, where we have 3 different siRNAs that are targeting MASH. Two of these targets were actually discovered by the Regeneron Genetics Center, HSD17B13 being one and CIDEB being the other.

We will have data for these programs later this year that we're excited to share. For CIDEB, it will be the first clinical data presented to date. And obviously, we'll be looking at liver fat and some other endpoints in our single ascending dose study. So the other program within the liver portfolio is for PNPLA3 mutants, which is a subsegment of the NASH population. We have previously presented some data there. It looks very promising, and we're excited about advancing that one as well. The third bucket is in neuroscience, the CNS. And we've already brought to the clinic, I'll say, 4 or 5 siRNAs to various targets in the CNS. The lead one was ALN-APP for amyloid precursor protein in Alzheimer's as well as cerebral amyloid angiopathy.

Regeneron opted out of this program. We are entitled to royalties, but Alnylam is solely advancing that one in terms of development and hopefully commercialization. The other programs include ALS, SOD1 mutants, where Regeneron is leading that development. We began dosing patients in 2024. We generated some data in-house, looks very promising. We'll probably be sharing that maybe probably in 2027. We also have programs for Huntington, for Parkinson's, and these are all in the clinic as well. So we're beginning to really accumulate patients in these studies. These are high unmet need disease areas. We're really hopeful that we can really change the course of these diseases in a meaningful way with these different interventions, and are really excited to be working with Alnylam on all of them at this point. So that's the siRNA portfolio as it stands today. We have a ton of other work that we're -- that's preclinical with Alnylam with different other targets that we're also excited about, but we'll save those for another time.

Okay. Well, we look forward to hearing about those great mechanism, and it's really -- it sounds like a fantastic partnership. Maybe switching then to your Factor XI program. Could you highlight why or why not it could be a step change improvement above Factor Xa?

Yes. Factor XI is another one that I think we're really excited about. We are actually advancing 2 antibodies into registration-enabling programs across, I'll say, a half a dozen, maybe more different thrombotic conditions running the gamut from VTE prevention following knee replacement surgery to atrial fibrillation to Cancer-associated thrombosis. So there's a lot -- peripheral artery disease, following revascularization. There's a lot of different conditions that current anticoagulants attempt to treat, but I would say, actually end up not making, not fully recognizing the size of these markets because of bleeding risk that some of these agents introduce.

So we have 2 different antibodies. We think one will be -- or has some of the best pharmacokinetic, pharmacodynamic data in class in terms of the Factor XIs and I'm talking specifically about assays for APTT as well as thrombin blockade. That one, we expect to have the best anticoagulation activity among the Factor XIs and with -- and hopefully better than even the Factor Xas, but also versus the Xas not introduce an increased risk of bleeding, which is critical for this class. The other antibody, we think will have comparable activity to approved antithrombotics and other Factor XI antibodies, but targets a different epitope on the Factor XI called A2, which we believe is a functional Factor XII blocker and could actually be even safer in terms of bleeding risk, but perhaps not as powerful as our catalytic domain antibody.

So we've kind of -- we want to be able to introduce a couple of antibodies to address the different needs of the patients that are in the space across these various conditions. Choice is good. Patients like it, doctors like it. That's what we hope to bring to anticoagulation with these. And we're beginning to generate data, expect to have initial Phase III data in the VTE prevention studies starting next year. We should also have Phase II data, short duration Phase II data in atrial fibrillation towards the middle part of next year as well.

This will give us a sense for activity against clotting in this disease as well as what the safety profile looks like only after 3 months, but it should give us a good sense for where we stand in that market as well. A lot of these other programs are just getting started. So we have a few years before the data will read out, but a huge category, $25 billion, $30 billion today. We think there's probably half the patients that should be on anticoagulants aren't because of bleeding risk or fear of bleeding. And we hope that the Factor XI class and our antibodies, in particular, can overcome those challenges in the current market.

Great overview. We've talked about the big hitters. We talked about EYLEA and Dupixent. We've also talked about some programs that you stated maybe not talked about as much like Libtayo, siRNA. So one more that probably isn't talked about as much, but your PD-1, LAG-3 program, there's 2 ongoing Phase III trials, one adjuvant melanoma, one in metastatic melanoma. Just curious if you don't mind giving us an overview of status of both and then also the strategy there, just like you did for some of the other programs.

Yes. This was a disappointing result for us earlier this year when we read out the first-line metastatic melanoma data comparing our combination LAG-3, PD-1, fianlimab plus Libtayo compared to pembrolizumab, where, unfortunately, despite showing over 5 months of benefit, didn't reach statistical significance. So that was certainly surprising and disappointing for us. We are continuing with this combination in the trials that you mentioned. The head-to-head study against Opdualag, which is Bristol-Myers' LAG-3 PD-1 combination continues to enroll patients. We are in discussions with regulators about how to convert that into a registration-enabling study, and we will learn more about that once those discussions conclude. But for now, the study continues to enroll.

The adjuvant melanoma trial fully enrolled several months ago, and we expect data either late this year or in early 2027. I would caution that this is a setting where Opdualag failed and had a hazard ratio of 1, essentially no benefit versus OPDIVO, so we're running our study head-to-head against pembrolizumab, KEYTRUDA. But again, because there was no activity in the trial that Bristol ran, I'm a little cautious on the results here. But we'll get our answer in a few months and see what that looks like.

Great overview. You had mentioned -- also you had mentioned a broader hem/onc portfolio. Anything else that you want to highlight that maybe we touched on several programs here, but give you a chance in case there was anything else, not just in hem/onc, but anything else across the board in Regeneron in terms of the pipeline that you'd like to highlight?

Perhaps I could mention we have a couple of very, I'd say, mid-stage programs that I'm excited about, one being in postural orthostatic tachycardia syndrome or POS. We have an antibody to NPR1, an antagonist that has Phase II data we intend to present later this year that looks very promising. This disease without any approved drugs. And it seems like the prevalence continues to increase. Perhaps this is a post-COVID phenomenon or one that's just becoming more recognized by physicians. But right now, standard of care is like drinking saltwater and hoping for the best.

We hope that this drug can really become a better option for those patients, and we'll need to figure out a regulatory path because there really isn't one at this point, but we're working with the FDA on that now and hope to share more with that program next year.

That's great. We've talked a lot about the pipeline, and maybe we could switch gears a bit to your approach to business development, what guides that approach and how you may or may not be differentiated versus other large cap pharmas in terms of your approach to business development.

Sure. So we obviously have a large business development effort. We have a team out there that's constantly scouring and looking at opportunities that are out there. We're not particularly wed to either doing an outright acquisition or basically doing a standard type of collaboration agreement. It's all rooted in, as I said before, as we're talking about the internal aspects of our pipeline, it's rooted in the science. So we're looking at opportunities that in some form or fashion will augment things that we already have ongoing in the pipeline, could potentially be a platform-based approach and additional technology that we'd like to get access to or it doesn't necessarily need to meet all those criteria.

It could be a very interesting opportunity from a scientific perspective that could be a later-stage type of asset that has the ability to generate revenue nearer term. But it all has to be linked to making sure that the science is sound and that we believe in the opportunity that we're potentially evaluating.

That makes sense. Curious if there's been -- in the past, has there been anything that may have held you back from prior deals? Anything that -- any factors that you want to highlight that may have prevented you from completing deals or completing deals in the past?

As I said, we've been very, very active. There's been some competitive processes that we've been involved in for some opportunities there that we didn't get there for a variety of reasons. Some of it can be linked to when we actually looked at the underlying data that was in the data room, just didn't find the opportunity as appealing as others may have thought. And other opportunities where we couldn't get there on valuation. I think there's a lot of competition out there looking for the same thing, looking for later-stage assets that have the ability to generate revenue sooner rather than later. We obviously have a very sound, disciplined approach to evaluating opportunities. And at the end of the day, when we kind of looked at what we thought the risk-adjusted returns, we were going to be relative to the value that the target was interested in obviously receiving, we just couldn't get there.

And obviously, we've seen some of the announcements and some of the processes that we've been involved in and some of the values just really outstretched where we were able to get to. But we continue to be out there looking. Our capital allocation philosophy, as you've heard from Ryan described, some of the specifics on the pipeline, drug development is expensive, right? When you've got 50-plus things in the pipeline, you need to advance not only the later-stage things that you heard from Ryan, but even the earlier stage things. So that takes a lot of resources and requirements to not only run the clinical studies, but obviously to manufacture the drug in order to basically ensure that you've got adequate clinical supply for those studies. And we ensure that we're doing all that we can to move the pipeline as quickly as possible. But beyond the internal investment from a capital allocation perspective, we are constantly evaluating external opportunities.

There's been a variety of things that we've announced even thus far in 2026, more on the collaboration type of relationships. And then after external opportunities, it's returning capital to shareholders. We started a dividend program in 2025, fairly modest in size by design. It was intended to basically broaden the investor base of those investors that have a dividend mandate, but we're unable to participate in investing in Regeneron. So we are obviously with a program that pays out roughly, say, $400 million a year, given some of those investors that flexibility.

And then obviously, the last component of our capital allocation priorities is share buybacks. We basically bought back roughly $2 billion worth of our shares in the first half, $1.2 billion in the second quarter alone. We, on average, basically get reauthorization from the Board in the neighborhood of about $3 billion each reauthorization. That's re-upped somewhere between every 12 to 18 months. We continue to be opportunistic buyers of our shares, obviously, in a valuation-sensitive perspective, depending on where the share price is.

That's great. Last 2 minutes, maybe from both of you. Any last thoughts, anything you didn't think we had a chance to talk about today? Anything else you'd like to share about the company?

I mean we have -- we're bringing to the clinic, I think, this year, 4 novel targets that were all discovered or validated by the Regeneron Genetics Center. And these are opportunities in immunology, in ophthalmology, in oncology. And this is going to continue to drive our discovery engine is genetics. So we continue to add to our database. We continue to make really interesting findings. We just published one on obesity for a new gene linked to obesity. So we continue to make these discoveries and develop around that, and that really drives the future of Regeneron. And I couldn't be more optimistic about the work that we're doing and the help that we're going to bring to all of these patients and over the long term, deliver the value to shareholders as well. So I'll turn it over to Chris for any closing remarks.

I would say, I mean, if you look at Regeneron in addition to it being deeply rooted in the science, we're guided by what we call the Regeneron way. You'll often hear Len state, do well by doing good. And if you look at the philosophy at Regeneron, we're trying to improve patients' lives. Obviously, we want to do all that we can to provide returns to shareholders, but the guiding principle is also do all that we can for patients. And I think what you've seen from Regeneron in terms of -- we had DB-OTO approved, right, which is a product for genetic hearing loss. We, in conjunction with the U.S. government, decided to provide that to patients for free and which I don't think there's many companies out there that would do that.

We are basically have a product for FOP called garetosmab. And again, a very, very small patient population, but it's an indication of kind of the ethos at Regeneron in terms of what we're trying to do in addition to -- for the investment community, but what we're trying to do for patients. And it's really deep rooted in the tone at the top in terms of what drives a lot of the things that make Regeneron do as well as we're doing.

That's great. It was a wonderful discussion with both of you. Thank you so much for sharing this with our community today, and thanks again.

Thank you Jeffrey.

All right. Good afternoon, everybody. Thanks for joining us. I'm Terence Flynn, Morgan Stanley's U.S. biopharma analyst.

For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures.

If you have any questions, please reach out to your Morgan Stanley sales representative. Very pleased to be hosting Regeneron this afternoon. Joining us from the company, we have Chris Fenimore, EVP, Finance and CFO; Marion McCourt, EVP and Head of Commercial; and Ryan Crowe, SVP, IR and Portfolio Strategy and Intelligence. I'm going to turn it over to Ryan for his disclosures, and then we'll get started. But thanks so much for being here.

Terence, thanks for having us. Always a pleasure to be here at the Morgan Stanley Healthcare Conference. I have a quick disclaimer to read as well, and then we'll get started.

I would like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. With that, Terence, let's get started.

Great. Again, thanks so much for joining us this afternoon. I figured we'd start with DUPIXENT, which has become one of the company's most important growth drivers. And Sanofi, your partner recently raised their 2030 guidance to EUR 25 billion from EUR 22 billion. I think sales this year are expected to be on our model is about USD 22 billion. So maybe high level, you could talk about some of the key drivers to achieve that new guidance, and then we'll dig in from there.

Happy to, Terence, and I'll share, we share a great ambition for DUPIXENT. The $25 billion was obviously independent guidance given by Sanofi.

But to the opportunity to bring DUPIXENT to so many more patients worldwide, that growth opportunity is driven by the amazing results that patients are seeing across now 9 indications in the U.S. marketplace.

So certainly, all the indications are growing. Our very first launch was in atopic dermatitis, as all of you know, continues to grow across the range of indications that we have in market today, which include various age groups, various geographies. So certainly, the trajectory of performance going forward is very strong, and we share that view.

Great. On atopic derm, I know that's the largest indication. And again, you were the first company to bring a biologic to that market. How much headroom is left in that area? And then as you think about treatment duration, where does that stand now? That's another question I think we get frequently?

Sure. So on atopic dermatitis, certainly tremendous advances for patients with DUPIXENT, but still the market is only penetrated to about in the U.S., as an example, high teens, maybe 20%.

So there's so much unmet need still in the marketplace. So we see an opportunity to help many more patients with DUPIXENT. Adherence to product is also very strong. If patients who are being treated for atopic dermatitis or the host of DUPIXENT indications, they will feel the disease coming back. Often atopic dermatitis patients talk about itch returning, lesions returning. Adherence to therapy is very, very high.

I would also point to the fact that with DUPIXENT, there are situations where people have comorbidities because of type 2 disease. So they might benefit in atopic dermatitis, but they notice, for example, their asthma is better, or the asthma patient that also has nasal polyps or chronic rhinosinusitis. It's the combination of indications to treat the individual condition, but then the host of other problems the patient might be experiencing as well. So adherence tends to be very, very high.

And I know, again, like I said, you guys have kind of blazed the trail in atopic derm. There is some competition. So as we think about the breadth of label, how important is that as we think about the competitive landscape here?

Sure. So often, our key opinion leaders share with me, unlike other categories where you see advances come along with DUPIXENT in atopic dermatitis, they often refer to it being first and best.

I would share the competition coming into the marketplace is always something we as Regeneron highly respect and recall when the JAK inhibitors came into atopic dermatitis as an example. There have been other companies more recently. But I do think it's helping a lot with educating and bringing more patients into the care continuum, where DUPIXENT can be selected as the option for them or for another reason, another product.

But certainly, we've seen the overall trajectory of DUPIXENT performance in atopic dermatitis is very strong. It's about half of overall DUPIXENT net sales now in atopic dermatitis, but also pleased to say we have many other blockbuster indications across the 9 approved indications.

Great. And if you had to pick some of those where you think there's the most potential upside, can you point to some of those outside of atopic derm, like or maybe what are the key growth drivers within the subset of indications?

Yes, I'm very happy to. I mean, DUPIXENT has done very well in crowded markets like biologic asthma. More recently, we also launched in COPD, which has been actually our most successful respiratory launch for DUPIXENT.

The various themes, Len's words were correct when he talked about a portfolio and a product. And the teams really pride themselves in helping patients correctly and quickly with market education and customer-facing activities. CSU is a newer indication. It's probably our second best trajectory with dermatologists, but certainly across all the indications. I don't want to neglect any because they're all important, but you see people who are not able to, or children, eat correctly with eosinophilic esophagitis or patients who have struggled with problems with skin lesions from bullous pemphigoid, prurigo nodularis. Each of the indications is really helpful and important in helping patients that often previously did not have an opportunity for care.

It brings more patients into the fold and certainly creates a bigger opportunity for DUPIXENT on a worldwide basis. As I share often, even for our patients who have indications that tend to more frequently be in older age groups, they really so appreciate hearing that DUPIXENT is a self-administered biologic that can be used in children as young as 6 months in atopic dermatitis or 1-year old in eosinophilic esophagitis. So the combination of efficacy, safety, ease of use, reimbursement is really important.

Great. Maybe you guys could elaborate on just the status of the Sanofi collaboration. I think given kind of commentary from both of the company's second quarter calls, it seems like there is a willingness to find some common ground here on kind of the forward state of that. And what would be the timing of a potential update there?

So Terence, again, thanks for having us. As you heard from Marion, there's been a tremendous amount of value built by both companies in terms of what both teams have been able to do in terms of building DUPIXENT in all the approved indications and just think about the relationships with providers, payers, as well as the reputation with patients and consumers that we want to do all that we can on a combined basis to leverage that value that's been created.

We continue to make progress with our colleagues at Sanofi. And there's just certain aspects of a transaction where 2 parties need to get together and basically come to a resolution where they both feel that they got something out of that transaction. There are certain aspects from both an economic perspective that we'd like to see in a new agreement, and there's certain aspects operationally that Marion and her team would like to see.

And we're continuing to have dialogue. In terms of timing, I don't think there's much we can say as of right now, other than that both teams are working extremely hard. And as soon as we have more to communicate, we'll obviously communicate that out at the appropriate time.

And as we think about -- I mean, obviously, the DUPIXENT line extension strategy is a pretty important piece of that. And you guys have outlined the 4 different programs you have there. But how important is it to have more scale in immunology? When I think about some of your peer companies, again, at J&J or AbbVie, they have a lot of scale in immunology. And so where does that fall in kind of like priorities of the collaboration?

I think part of the -- our goal is to maintain and sustain leadership in I&I. We have a pipeline in the type 2 diseases beyond DUPIXENT, including a long-acting IL-13 antibody that's currently being dosed in healthy volunteers soon to be atopic dermatitis patients.

We have a longer-acting antibody that targets the same receptor as DUPIXENT that we're excited to be hopefully bringing to the clinic by end of year or in early 2027. And a couple after that in 2027, entering the clinic targeting the IL-4 ligand, as well as a bispecific to the ligands for IL-4 and IL-13.

So we feel that between those 4 antibodies, an ability to really cover most, if not all, of the ground that DUPIXENT currently does, as well as potentially some other indications we have in mind for these programs.

Beyond that, we have an antibody for which the target has not yet been named, but we believe could address several genetically linked diseases that have significant comorbidities across them, including diseases like primary biliary cholangitis, systemic lupus, ulcerative colitis, Sjogren's disease. There's about 7 or 8 of these that we have found a pretty strong genetic linkage, and we're excited to advance that. It's currently dosing in healthy volunteers. We hopefully advance that into Phase II study sometime in 2027. So I&I leadership is certainly front of mind for us. We think DUPIXENT has helped us get to that point, and we believe we can build from there. And certainly, that's one of the company's goals.

Yes. What about -- Ryan, you mentioned UC. So is IBD another priority? Because I imagine you have the whole derm focus already, obviously, that you can leverage the pulmonology, but it seems like IBD is one where maybe there's not much of a presence right now on the Dupixent footprint.

Yes. We haven't had a lot of success with Dupixent in ulcerative colitis. There is an ongoing Phase II program for select patients, I believe, with certain biomarkers. But I wouldn't say there's any particular, like, goal to enter the IBD space. We are a company that really follows the science. And should one of our mechanisms take us to an IBD condition, we pursue it aggressively. It just hasn't happened yet.

Yes. Okay. Maybe it's a good segue to a more strategic business development question. I think there's a perception, at least based on some of my conversations that the company typically will only consider kind of platform or early-stage deals when we think through that business development lens. But obviously, the company has matured in terms of a diversified portfolio. You look at your cash on the balance sheet, paying a dividend, much different situation now. So as you think about the flavor of types of deals that you guys consider, how is that evolving?

Yes. I would say the word used, only, is probably not the right way to characterize it, Terence. We definitely think there's an advantage, right, to the extent that you can acquire an asset that can generate more than one product because it's a platform, that's obviously helpful and justifies the value that you're willing to pay rather than just one product that you're acquiring. And if that doesn't work out, then you don't have any other shots on goal.

With that being said, we will look at other opportunities that make sense. We've got a very active business development team. They are constantly out there scouring the landscape and looking at things that are out there. We have kicked the tires on, and we've talked about this publicly, several opportunities that were later stage in nature that weren't necessarily platform types of transactions. Our big thing is we're very disciplined in making sure that we ascribe appropriate value where we see value.

And sometimes we just can't get there in terms of where others are -- have a willingness to pay for certain assets. So I would say we're extremely disciplined. We're open to those areas that make sense. We're not limited by any therapeutic area. We're not limited by any modality within reason, things that are complementary to what we do, and we continue to look. And we are not afraid to put capital to work if and when it makes sense.

You mentioned that you had looked at some later-stage assets. Is it -- probably hard to characterize, but if you had to bucket it, is it more so getting over the hurdle of like implied POS? Or is it more about the commercial opportunity when you think about what -- I know you guys are being disciplined. So which of those 2 is more likely going to -- the higher hurdle, I guess?

I think if you think about Regeneron in totality, science really drives our business. You hear that from Len and George all the time. So fundamentally, it's what do we think about the science? How likely do we think it's going to work to your point. But then also, it's heavily weighted, I would say, by what do we think the commercial opportunity is? And what is it going to cost to develop it and how quickly can we get it to market? Marion is -- as we look at various opportunities, is the first one to say, the faster we can bring something to the market, the more excited we would potentially get about an opportunity. But it all depends. It all depends on what we're looking at and evaluating.

Okay. Great. Maybe one more for you, Chris. Just on what's the latest on rate of dividend growth and then outlook for share repos. I think you did about $2 billion in the first half of the year. So maybe just how do you balance both of those? And then also, preserve some capital for the deals?

Yes. I mean, when we talk about our capital allocation priorities, they haven't changed. It's first and foremost, investment in our internal R&D capabilities and George and his team. And we've obviously just talked about external opportunities, which we don't limit them to just M&A opportunities. We obviously have done a fair number of, I would say, more traditional business development collaboration types of arrangements. We'll continue to look at those.

When looking at returning capital to shareholders, I'll start with the dividend first. The dividend was always intended to be a way to access additional shareholders that had a dividend mandate. It was not about dividend yield. If you look at basically, when we started the program in 2025, it was $0.88 per share. We increased that thus far in 2026 to $0.94 a share. Total annual payouts in the neighborhood of $400 million. So it's not a major component of how we view our return of capital to shareholders. And I wouldn't expect there to be much change in that philosophy. And it's not really going to be at least in the short and medium term, a dividend growth story.

In terms of share buybacks, we bought back roughly $2 billion of our shares in the first half of the year, $1.2 billion alone in the second quarter, reduced the shares outstanding in the first half of the year by something like 2.4 million shares. And we've got $2.5 billion of authorization remaining. So we continue to be opportunistic buyers of our shares. It's a grid that we put in place that's valuation sensitive. So when the stock is lower, we're out there buying more. And when it creeps up, there's a certain point where we take our foot off the accelerator. But we continue to view share buybacks as a way to return capital to shareholders.

Okay. Great. Maybe just moving on to one of the pipeline assets that I think is coming more in focus now is cemdisiran in MG. You have an upcoming PDUFA date in November. So maybe, Marion, you could just talk about confidence in the approval decision, but also expectations for the label. I think that's a question we get more frequently now as we approach this decision.

Sure. Very helpful. And we do look forward to November. The team will be launch ready. And certainly, with an FDA approval, we'll be set to go. Pleased to share with you that we've built out the neurology business unit. We've had some talent for years at Regeneron. In fact, some origins as you know, Regeneron in neurology. So we've had some individuals become part of this new business group and also have been very successful in attracting new talent to our headquarter team and to our field team. So we look forward to the launch.

In terms of cemdisiran and this competitive market that we'll be entering, we're really excited about it. The market opportunity is a large one. There have been products that have helped patients a great deal. We believe with cemdisiran, we'll be able to pick up on some of that incremental opportunity, not only with our clinical profile, our mode of action, our safety profile, dosing frequency, which is every 3 months, which is highly attractive to patients. So we'll be launch ready and ready to participate.

And then I think the label is one question I get some questions. Is it possible that you guys have a more favorable vaccination requirement versus some of the other C5 agents?

Yes. I mean, I would keep the base case of what we have typically seen for C5, but I do think we have different design in our clinical studies and different opportunity potentially to look at. So that would be an interesting point of potential discussion. But I think it's early to define. And I also believe there are other characteristics of cemdisiran that are just so effective to patients in terms of the level of efficacy, safety and convenience of dosing.

Okay. And as we think about the potential commercial opportunity, is Ultomiris the best analog? Or are there any other good analogs when we think about like the peak sales opportunity, the ramp, what that looks like? How are you guys framing that?

So when we go through -- and you know Regeneron, we've had a lot of launch experience over many years now. So we look at the range and certainly inclusive of products and category today, when they launched, how they launched, what the trajectory was. So I wouldn't limit it to one product, but to share with you that we look in a very comprehensive way across launch readiness and how to participate in a new marketplace to make sure that we're meeting the needs of the physicians and the offices that are treating these patients and the patients themselves and some of the experiences they're having today and what they'd like to see in new therapies that maybe they don't have today.

And is the strategy more about the kind of newly diagnosed patients about switch patients? Like how do you kind of balance the near-term dynamic for the launch?

We're looking across, and I will be delighted to share launch strategy with you as we get to an approval and entry into the marketplace, but there are a range of opportunities. And we want to be very thoughtful about how we direct our strategies as we launch into the market. And certainly, our final label will be helpful to us as well in determining that.

And anything you can share about the kind of talent you guys have hired? You mentioned the neurology business unit you guys built out. Any more details you can provide there?

I would share that they're very excited about the potential approval. Obviously, it's coming soon in the U.S. in November. We also look to second half of '27 for some of the European markets and potential EMA approval. So we'll be ready to go.

Okay. Great. The other, I think, interesting angle of the asset is that you have other indications that are going to be reading out. So you have some PNH data later this year, Phase III and then some interim data for GA. Obviously, you guys know the retina space very well. So maybe just talk to us about expectations for both of these readouts. Like what are you guys hoping to see? What's a win look like?

Sure. Maybe I'll take that one, Terence. Starting with PNH, this is a study that will evaluate the combination of 2 assets, cemdisiran, the siRNA to C5 as well as pozelimab, an antibody specific to C5. It will be compared against eculizumab over 26 weeks. These dual co-primary endpoints, one is disease control using LDH as the measurement as well as transfusion avoidance. And so they both need to hit in order for us to have a positive study. We certainly are looking forward to seeing the data sometime in the fourth quarter.

I think the disease control, we have a lot of data from previous studies that suggest that patients can reach normalization on this combination. Transfusion avoidance is a trickier endpoint. Of course, there's many reasons one can receive a transfusion, some of which are driven by intravascular hemolysis, which would be on mechanism for C5. But then there are other reasons for transfusions that you wouldn't expect a C5 blocker to stop. So we'll see what we have in a few months in the fourth quarter here on PNH, certainly looking hopeful for a positive readout there.

Regarding GA, this is -- we've designed our clinical program for systemic administration. This is actually a 3-arm study that looks at cemdisiran monotherapy, the combination I just mentioned between cemdisiran and pozelimab against placebo. So this is, again, systemic, not intravitreal, which is what the approved GA agents are in the U.S. The interim time point will evaluate the first 225 patients enrolled in this program. We will, at 26 weeks, evaluate the slope of GA lesion size and also evaluate secondary endpoints as well as safety. So this is a very early time point to be evaluating a GA medicine. This is a very slowly progressing disease.

But our goal with this is to show that we are on trend with the approved intravitreal GA agents at their time point in their respective clinical studies. So that -- the results of this interim will inform what we do with the registration-enabling cohort, which basically began at patient that was enrolled, number 226. And so we have the same 3 arms, we're going to enroll 750 patients across those 3 as part of the registrational cohort, and that enrollment is already underway. But this interim analysis that we'll conduct in the fourth quarter should inform the next steps for that program. And so we will see what we have in a few months.

So I think pretty clear in PNH in terms of what -- either it's a positive study looks better than Soliris or it doesn't. And again, you don't move forward. But I guess on the GA side, what's the span of outcomes there? Like is it the same? Is it very binary? Or are there shades of gray in between?

I think especially because of the timing of our analysis, there's going to perhaps be some gray. I mean, it could not work at all. Let's be very clear. Systemic approaches in the past have failed. We're optimistic this one may work because we've demonstrated over 99% knockdown of CH50 in our gMG pivotal study. So we know this combination is very effective at blocking C5. Whether that manifests into slowing of lesions remains to be determined.

One other analysis that we'll conduct is sort of is one arm -- is one of the active arms outperforming the other active arm? And could that lead us to dropping that arm in the registrational cohort? That's something we intend to learn. It could not work at all. It could be a huge success. We really are going to have to wait for the data to make any determinations. And of course, safety is another important thing to look at. This is an especially vulnerable population being at an advanced age. And of course, blocking C5 can lead to infection risk. So we'll be looking at a lot of things from this interim analysis that should inform our next steps.

Okay. Maybe the other one is some of these are combinations and then again, cemdisiran for MG as a monotherapy. So how does that inform, I guess, pricing decision? I know you're not going to guide on pricing. That's not what I'm asking, but how do you think about the optionality around having either monotherapy versus combination again, across multiple different diseases. It seems like it makes it maybe a little bit more complicated from a pricing decision.

I think there's -- I mean, there's tremendous opportunity in the various indications, some mono, some combination product. I welcome that problem with clinical success across all the indications so we can bring them into the marketplace.

And certainly, the fact that the monotherapy cemdisiran worked in myasthenia gravis, and we will find out if the combination works in PNH would allow us some price discrimination between those 2 indications. And then with GA, we haven't disclosed dosing. So there may be an ability to have a third price for a third brand depending on results.

Okay. And what -- maybe just talk to us about what the commercial build would look like on the PNH side? Because I imagine in GA, very straightforward. You have the EYLEA infrastructure already in place. You just talked about the neuro side for MG. But in PNH, what does that look like?

So that would be a launch into hematology. We've seen hematology, obviously, a product in hematology/oncology. We see this as different and certainly potentially something we could combine into our neurology business unit. There are a couple of different options. We also have a rare disease group, but I think most likely, we would want to keep the combination product with cemdisiran and understanding similarity and competition as well. We never want to be redundant in how we build our business units or build our expertise, but very much look forward to it.

So it sounds like it would be more leverage -- there's a lot of leverage from that. It doesn't sound like it would be a totally new build per se?

Correct. It would not need to be an entirely new build, which is good.

Okay. Great. Maybe moving on to EYLEA, again, which well-established franchise. We've been switching it over to the high-dose formulation now, some really nice momentum in the second quarter. Maybe just talk about the puts and takes here, not only for back half of this year, but also as we go into 2027.

So very happy to. So thank you, Terence, and we are pleased to report the uptake of EYLEA HD in our second quarter results. Certainly, second quarter, you come up generally in the anti-VEGF category, a lighter first quarter because of patient reauthorizations. But beyond that, EYLEA HD performed very well in the innovative branded category. The product that pleased to share on behalf of my team grew more than other brands in category in that window of time.

Certainly, we feel that the label enhancements of November -- late November last year with the Q4 weekly dosing, RVO indication, more recently, the Q20 weekly dosing for greater durability. That combination of factors gives us the broadest label in the anti-VEGF category. We see physicians across large practices, midsized, small using more EYLEA HD. And it's the experience that they have with patients and the meaningful clinical results, the safety that's known with Regeneron. And then also this notion of durability is really, really important. So we still have a lot of work to do, but see EYLEA HD becoming the next standard of care in the anti-VEGF category.

Today, or as I reported in the second quarter, EYLEA HD makes up about 60% of overall EYLEA and EYLEA HD franchise net sales. It was about 50% in the first quarter. So we continue to make inroads. And I think also we showed that our overall EYLEA HD and EYLEA performance was strong in the second quarter. There will be more competition in the second half of the year. So we guided appropriately based on a variety of different factors, but still feel we'll be bringing forward some important growth with EYLEA HD.

Okay. Got it.

Terence, you asked about next year, too. So I always like to get a little further into this year before we start talking a lot about next year. But I just would flag that over that course of time, just for fair balance, we would be expecting to see potential additional 2-milligram biosimilars coming into the marketplace, creating additional pricing pressure on EYLEA.

Okay. Understood. And then the other thing we're waiting on is still the prefilled syringe. So maybe just any update to provide there or still just kind of waiting by year-end?

So on our second quarter call, we basically stated that we're expecting to have approval for the prefilled syringe by the end of the year at one or more CMOs. That has not changed. We are still sticking to those time lines. And once again, once we have more information, we'll update the Street accordingly.

And I know you guys have worked on internal fill/finish as well. I know that's another area where you guys have been building out and scaling. So any progress or updates on that side to share?

Yes. So we are expanding manufacturing in upstate New York right outside of Saratoga as well as on our existing campus outside of Albany and Rensselaer, New York. In Saratoga, that's actually going to be more bulk manufacturing capacity to be able to meet the demands of our pipeline. With regards to the fill/finish capabilities that you asked about, it's a facility that has -- the first line that will be up will be a smaller scale line that is designed for doing more clinical types of runs and capacity. And then we have several lines beyond that, that would be for more larger scale commercial fill/finish capabilities.

Team continues to work very, very hard on that. And hopefully, by the end of the year, we'll start to be able to make some product out of that smaller scale line and then obviously continue to work on that in '27 and beyond and getting those larger scale facilities up and running. With that being said, we will always continue to have relationships with CMOs just for risk and diversification purposes.

Okay. Great. Maybe just the last one I had on EYLEA is just how to think about competition from high-dose biosimilars. I mean, that's another question we get increasingly going into next year.

High-dose biosimilars? Okay. Timing for a potential biosimilar for the 8-milligram version of aflibercept is very difficult to predict, and I'm not going to speculate on that today. I would say that next year is very, very, very unlikely considering no one has completed any clinical programs for that. But we have a very broad and growing intellectual property estate around aflibercept 8-milligram, its formulation, its methods of treatment, its manufacture. There is an ongoing review of that patent by the patent office via the post-grant review process.

There was a petition filed by Alvotech, and that process is playing out now. We're currently in the deposition phase of this with experts on both sides. That will culminate in oral arguments that will be held on December 4 with a decision by the PTAB in early March. I think there's 3 outcomes here. One is that the entire patent is upheld. The other is the entire patent is invalidated and then there's sort of the mixed opinion where certain claims are upheld and found to be valid while others are invalidated. So we'll let the process play out and see where it lands.

I would add that it's not the only patent in the estate that's been issued. We have another patent related to aflibercept 8-milligram's formulation that also expires in 2039 as well as patents that we have filed for and are expecting to be issued over the next months and years. So strong patent estate. We think it will be important for biosimilar manufacturers to consider the entire estate when looking at the biosimilar launch timing. And so we'll take it from there.

Great. Great. Maybe just in the last minute, Marion, back to you. So Lynozyfic for multiple myeloma, again, another important new product launch for you guys. Maybe just tell us what you're seeing kind of current competitive dynamics here in late line and then how to think about moving this to earlier lines because that's where I think the bigger opportunity is.

Absolutely. I appreciate the question on oncology, hematology and the prior discussion there. This is part of our overall oncology business unit, where we have Libtayo, now a multibillion-dollar product on a worldwide basis. But the onc-heme group has done a really nice job with launching Lynozyfic. The feedback I get from the physicians' key opinion leaders when I meet with them is the product profile in terms of efficacy, safety, ease of use, lower hospitalization requirement is really important for these late-stage patients.

But to your point, the thing I also hear most often is the importance of our completing the clinical studies so we can apply for indications to move to earlier lines of therapy. So that will be an important opportunity to unleash more use of Lynozyfic. But early days in the heavily pretreated population, fourth line plus, where we have an indication today, the feedback has been very, very strong. Obviously, this market becomes increasingly competitive, but look forward to moving to potentially earlier lines of therapy with Lynozyfic.

Great. Well, I think we're up against time, but really appreciate it.

Yes. Thank you, Terence.

Thanks, Terence.

Thank you.

All right. Welcome, Welcome, Welcome. My name is Mohit Bansal. I'm one of the biotech and pharma analysts here at Wells Fargo. And I have the pleasure to start the day with the Regeneron management team, fifth year in a row. My 5 years at Wells Fargo. Regeneron has come here every year.

So with us, we have Marion McCourt, the Chief Commercial Officer of the company; and Ryan Crowe, Head of IR at the company. So I'll give the podium to Ryan to talk about some...

Yes. I appreciate you having us, Mohit, 5 years. It's flown by a lot of successes that we've been able to report at this very conference and excited to be back. So thank you. Thank you. Before we begin, I just need to make a couple of forward-looking statement disclaimers. I would like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements.

A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

With that, I'll just make a couple of opening comments, and then we'll get to your questions, Mohit. Going back to the second quarter earnings report that we had in late July, I think we had a really strong financial performance that was driven by exceptional commercial execution, double-digit growth on the top and bottom lines, driven by EYLEA HD's

outstanding performance in the U.S. DUPIXENT really setting a new high watermark globally in terms of revenues as well as LIBTAYO.

In fact, all the hit all-time high for quarterly sales in -- for a quarter. Additionally, at the end of the second quarter, we finished repaying the Sanofi development balance right? So going forward, we will be able to record our full share of the profits from DUPIXENT and Kevzara as part of our Sanofi collaboration revenues. So that should give us a little uplift going forward, and we're excited to finally get to that point.

Looking ahead, for the rest of 2026, we have some exciting pipeline catalysts mainly around the C5 franchise. We have a PDUFA date for cemdisiran monotherapy for generalized Myasthenia Gravis which is in November, a huge and growing market, and we think we have a differentiated product there and are looking forward to hopefully launching that by the end of this year. We also have a pivotal data readout in proximal PNH which is another area where we're going to evaluate the combination of pozelimab and cemdisiran head-to-head against eculizumab or Soliris. And then we also have an interim readout for geographic atrophy that's looking at the combination that I just mentioned as well as some distant monotherapy. This will be kind of a peak at the data that will inform next steps for that program. We're currently enrolling a pivotal cohort, and this included a form powering as well as whether one arm performs better than another and perhaps we can move forward with just 2 arms as opposed to 3 in our pivotal study. We also expect to have approval for the EYLEA HD prefilled syringe before the end of this year. And we're working with multiple contract manufacturers on issues related to their facilities as opposed to the product. So we hope that they can resolve them and the FDA can ultimately sign off on our application to get this important delivery mechanism into the market. We also are reporting some early data in the metabolic portfolio, the siRNAs that we have been working on in MASH as well as for an antibody that targets the NPR1 receptor and antagonizes it for poststatic tachycardia syndrome or POTS. Those are earlier-stage programs, but we're excited about both. We also anticipate initiating our pivotal studies for obesity and type 2 diabetes with olatorepatide, which we in-licensed from Hansoh last year. And then finally, I think we're also working towards hopefully expanding our collaboration with Sanofi to go beyond DUPIXENT and potentially other assets.

So I'm sure we'll talk about a lot of these. I'll leave it there, and we'll jump into Mohit's questions.

Awesome. Thank you very much for the intro. I really appreciate it. So Mike, I think the broader question that I want to ask is that Regeneron in the last 5 years or so, it's becoming like a multi-franchise company, not just from the top line point of view. Now with the Sanofi profit realization, we are seeing that even for the bottom line, it is not as much dependent on EYLEA as it was in the past.

So given that -- I mean when you look like longer term, what do you think investors still underappreciate in Regeneron story investors, including me as well. So like we would love to understand that.

Maybe I'll start, and I'll let Marion certainly jump in. I'm sure she'll have some thoughts on this. But honestly, it comes back to the pipeline and I mentioned a few of the programs that we think are fundamentally undervalued in the C5 franchise alone. We see relatively modest expectations at peak year sales for this Myasthenia Gravis opportunity. I don't think there's anything in models for GA. Admittedly, that's a higher risk program, but we'll see what we have in a few months here, hemonc with our BCMA bispecific Lynozyfic, which is currently approved in late line settings, but we're rapidly advancing it into earlier line settings. This is a $40 billion therapeutic area that we fully intend to take some share and especially in the earlier stages and in precursor conditions where we have some advantages in terms of how we're developing our antibody.

Factor XI, another really large category in anticoagulation. We think we have 2 differentiated antibodies that can address the disease without increasing -- with various diseases without increasing the risk of bleeding, which would be an advance from where the Factor Xa is currently are able to do. I think another one that's really under the radar, I think, is our genetics database. And when you think about AI in biotech. I think large language models, I think most believe are going to be relatively commoditized over the years, there's going to be a convergence in how differentiated they are. I think that right now, maybe you have some advantages for one versus another, but over time, those are likely to converge. What's going to win in AI in our view, is proprietary data sets. And Regeneron has been working for the last 12 years to build the biggest genetics database in the world that's all linked to electronic health records. And now we're beginning to layer in proteomics so that we can have even more information about human biology and human genetics to help inform how to not only find new targets to address disease but also how to manage costs in the system for disease.

So all these things are things we're working on in the background that certainly hasn't really been fully appreciated, if appreciated at all by analysts and investors. So we're looking forward to advancing all those efforts and maybe a few that Marion has in mind as well.

Sure. And I just would add to that, and good morning, everyone. Ryan describes the scientific platform, which is so exciting for our future and whether you talk about the application of the Regeneron Genetic Center or therapeutic areas that we'll launch in, hopefully, in the future, cardiometabolic obesity thrombosis, neurology, additional indications in hematology. I just would remind everyone if I go back with you, 5 years, 10 years at Regeneron, when we were the EYLEA company only in every therapeutic area, we've entered, whether immunology, oncology, rare disease, certainly still in ophthalmology.

Our teams have been able to prepare the market through commercialization and medical affairs, but then also execute our launches by indication in highly competitive categories, also creating categories where we're first to market like atopic dermatitis. So we'll bring the power of that commercialization ability to our scientific platform for the future. And I'm very pleased to report to you from my perspective, that commercialization ability gets stronger every year. And I would point to the recent results we shared with you in the most recent quarter, the last several quarters and what we intend to do in the future to demonstrate that.

So exciting times at Regeneron, powered by our science.

Commercial, we definitely all of us underappreciated in the last couple of quarters. So you've done an amazing job here. And then similarly for cemdisiran like no one really thought there will be such a success. So kudos to you. So let's just talk a little bit about EYLEA here HD because we saw a strong quarter in second quarter. There seems to be a little bit delayed uptake or inflection in this franchise, like the product has been in the market for 3 years, but we got label expansion last year, but then all of a sudden in the second quarter went to double digits. So can you talk a little bit about what actually clicked with physicians, all of a sudden? And obviously, there was a lot of work behind that, but talk a little bit about that.

Very happy to, Mohit. So I'll remind everyone that we talked a lot about the importance of the label enhancements to include Q4 weekly dosing, the RVO indication and also durability with every 20-week dosing.

Obviously, that being the most recent enhancement, but the Q4 weekly dosing in RVO occurred towards the end of November there is some time where you need to make sure that the payer updates have taken place. So certainly, the results that we saw in the first half of the year and into the second quarter were a result of that label enhancement. At the same time though, I would also share with you the physician experience that they're seeing with EYLEA HD is very positive, very good. They're coming to see it as the product that truly has greatest durability in the category, a product that they can use now across indications, RVO, obviously, is about 20% of the market.

EYLEA has been the standard of care very quickly, we're seeing a lot of switch patients to EYLEA HD and RVO. And in fact, across the entire anti-VEGF category, more switches are going to EYLEA HD than any other product. We're also getting a share of naive patients, but obviously, that's the smaller, about 10% of the overall market at any given point in time.

So overall, strong performance. We still have a lot of work to do. It's a highly competitive market. Certainly, we're conscious of additional potential biosimilar to the EYLEA 2-milligram program. But I think we've got a very strong profile on our EYLEA HD, pleased with the performance and obviously also looking forward to the label enhancement of prefilled syringe.

Got it. So like how -- what are they coming like favorite question on the prefilled syringe. Like where are you right now on this? And then how should investors think about, one, the timing of this; and two, the importance of this at this point?

I'll maybe start with the timing and kind of where we are and Marion can talk about the impact it might have in the market. We don't have much of an update to provide today. We continue to work with multiple contract manufacturers on rectifying some of the issues the FDA has identified in their facilities. So until they are fixed, we're not going to be able to be approved. But we believe we're still on track for an approval by the end of this year at one or more of those CMOs. And certainly, I think that will be helpful to the commercial efforts that Marion can now talk about.

Thanks Ryan. And I just would add maybe a couple of points that I missed is, with EYLEA HD proud to report that it is the innovative branded product growing more than any other in the category. In addition, we were able to report to you in the second quarter that EYLEA HD makes up 60% of our overall Regeneron franchise sales. That's up from about 50% the quarter before. So it's an example of where you see EYLEA HD truly making a mark.

Got it. So second quarter was crucial in the sense that, now people do understand that the HD's growth is kind of overcoming whatever decline you are going to face in standard dose EYLEA. The remaining question is how should we think about the durability of the franchise in the face of new biosimilars coming. And where are you in terms of RVO patients turning over to like what percentage of turnover to HDA versus like how much it is left right now?

So I don't think we've given exact percentages. Ryan will add to my answer. But when it comes to switch patients, because EYLEA is a bigger product, more of our switch patients come from EYLEA. Second source of business will be switches from faricimab, where physicians aren't seeing the durability or they're seeing not the clinical types of results they'd hope to or they think they can do better with EYLEA HD. We see switches from Avastin for obvious reasons. We see switches from biosimilar too. So it's really across the board the benefit of wanting to go to an improved product for better clinical results, safety and durability that EYLEA HD achieves.

Obviously, a highly competitive market. So our execution is paramount. We have a highly respected team in the marketplace that's been really important to us. So we've got a lot of work to do, but I think we're making nice progress.

I think the only thing I would add is that the aflibercept 2-milligram segment, I believe, is separate and distinct from that of EYLEA HD. While they are biosimilars and more to come in the 2-milligram segment. EYLEA HD stands alone on its durability profile. And I think there will be switches to biosimilar 2-milligram aflibercept, that still -- that remains a good opportunity for switching to EYLEA HD over time. So just because a patient may switch out of branded EYLEA to a biosimilar does not make them a great candidate to eventually switch to HD, and that will be part of our strategy.

I'll make a quick comment to characterize the market. I think retina specialists across practices, large, medium and small, are really sophisticated in terms of their ability of managing their practice, making sure that they get to choose the drug that they want for their patients. They're very aggressive in terms of making sure that they have the opportunity to control treatment of patients, product selection. And of course, when they're treating blinding eye disease, they're injecting in one eye, very important decisions go into how they elect to treat their patients.

Got it. Very helpful. So now turning to the other products, small products you have DUPIXENT. So it's already at $24 billion annualized run rate, multiple indications, probably close to one of the biggest products in the market like KEYTRUDA, these obesity drugs and DUPIXENT now.

So how much more -- but again, like you pointed out in your prepared remarks at earnings call like there is still -- the penetration is still not very high in some of those markets. So how do you think about the net lag of growth? Is it earlier patient? Is it like earlier lines of use or continued penetration? Like how should we think about where will you grow next.

So I would encourage thinking about DUPIXENT as to your point, such a large product easily top 5 in the world, it was #4 last year, something of that sort. But across indications, we are still underpenetrated, even in atopic dermatitis, we approach the high teens.

So there's a lot of opportunity for additional patients to come to marketplace. And if roughly atopic dermatitis is about half the patient population for DUPIXENT, the other really large indications, whether biologic asthma, COPD, eosinophilic esophagitis, as you know, across 9 indications. So more recently launched like CSU, we have such tremendous unmet potential benefit of as the KOLs always point out to me, first and best in category, but also because we treat type 2 disease patients with comorbidities or patients with a single type 2 inflammation are being helped in a way that other products can't. And often patients that have, as an example, COPD, they've often had a touch of asthma patients with atopic dermatitis.

It's not uncommon for them to have had another type 2 comorbidity. We treat to the indication in the specialists, so we're now the leading biologic across allergists, dermatologists, there are so many categories where DUPIXENT is now the leading biologic product in practice. But certainly, we have a lot of opportunity because of unmet need in the market, whether it's because of geographies where we've launched more recently, indications where we've just launched, age groups as well, we treat patients, obviously, up into their later years with COPD and prurigo nodularis [indiscernible] so many indications, but also it's reassuring to hear the safety to patients as young as 6 months in atopic dermatitis or patients as young as a 1 year old in eosinophilic esophagitis.

So we create this opportunity for multiple patient types and really tremendous opportunity for future growth. Having said that, DUPIXENT is a big product today so that the -- obviously, the percentage churn on growth has to be considered based on the size of the product and size of the brand today.

Got it. Helpful. So I mean, like this talking to KOLs and experts basically, like the safety is the main -- the clean safety for a mAb is one of the sale-in points for DUPIXENT and it works really well.

And safety and I would there, too, it's overall safety, multiple indications, but not an immunosuppressant is incredibly important in the market today as well because that creates a whole host of concerns for potential unwanted effects in the future.

Got it. So the question I was getting to was, basically, for years, it was like -- it is considered a durable franchise, and it is a doable franchise. But at the same time, this emergence of YTE drugs like longer acting and all that. They're not necessarily better, but they are probably longer acting. So how do you see a challenge from a drug -- theoretical challenge from a drug which is YTE and not better versus something which is slightly better for whatever magical clinical reason. But like how do you think about that?

So I think we always have to be really cautious and very thoughtful about competitive entries. We do a lot to prepare our field teams, both commercial and medical for education on competitive products. So we're in a better position to talk about the unique differentiation of DUPIXENT, the safety, the experience in market, over 1.5 million patients treated. It really is a tremendous product in terms of what DUPIXENT has created and the remarkable results for patients.

Having said that, competitors coming into the market have actually helped educate populations to seek treatment from their specialists that probably helps DUPIXENT quite a lot as well because we do have such unmet need. So certainly, there's a thoughtfulness on products coming in that potentially have aspects of durability or other elements.

Having said that, it's really hard to compete with DUPIXENT based on the track record, the history, payer coverage, ease of use and the convenience of dosing hasn't been difficult for patients to give those injections every 2 weeks or in the case of EoE on a weekly basis, because the results are so spectacular. Think of EoE, these are patients, children and adults who have not been able to enjoy normal meals. There's a nutritional aspect to that. There's a social aspect to that, it really is difficult even for children going to school, it changes the world for these patients when -- whether they're skin, they're breathing, they're eating, pick the indication has been approved to a point where they can participate more normally in the world.

Got it. makes sense. And then also, it is approved in multiple indications, they are kind of coexist as well. It's not like someone has one indication. Some people may have multiple diseases as well.

Correct.

Very helpful. So let's just talk a little bit about Sanofi collaboration. So in the past, you talked about the new collaboration framework should evolve to reflect where both companies are today, not in 2007, right? So how you are thinking about like what are the principles for rules of engagement going forward, so to speak. So how would you think about that?

I think, Mohit, the guiding principle for any potential broadening of our alliance is going to be what it was almost 20 years ago when we signed the original deal. It's about developing and commercializing life-changing drugs for patients and delivering value for shareholders. So that is the core of the crux of the entire discussion we're having. I think we're coming at it in an angle with open minds, mutual respect and a reset of the relationship.

So I think we're working towards something, but it's hard to predict when or what that will look like in terms of what we want versus what they want. I prefer to keep that between the companies at this point. But I can promise you that it's certainly something that's a high priority for both sides, and we think it makes a lot of sense. We've had a lot of success not only developing DUPIXENT now with 9 approved indications and now being used by over 1.5 million patients globally today in active use. We've also are annualizing, as you said, a $24 billion. I don't think either of those could have been achieved by either company alone.

So the 1 plus 1 equals 3, I think, certainly applies for this collaboration, I think expanding it has strategic rationale for both sides and now it's a matter of working out the details.

Yes. I would echo Ryan's comments that together, we've done remarkable things with DUPIXENT. Both companies tremendous results with the co-commercialization of DUPIXENT. For the future, it would be amazing. I think there's a great dialogue going on between our senior leaders, obviously, new CEO at Sanofi, encouraging comments you heard on their most recent earnings call and from Len. And if we can come to an agreement that makes sense for both companies, potentially we can do more great things together.

Got it. So I mean, mechanistically for this collaboration, IL-4 subunit is already part of the collaboration. And that's a Supi-Dupi. So if you take that forward, do you have to renegotiate at all? Or you can just take it forward without any new renegotiations?

So yes, that's a great question. There are -- we're working on multiple long-acting antibodies within the IL-4, IL-13 axis. The lead antibody is one that we own full rights to the IL-13 long-acting antibody currently being dosed in healthy volunteers, hopefully moving to patients with atopic dermatitis very soon.

That one we hope to have advanced potentially Phase III as early as end of next year or early 2028, putting us into the mix for potential approval around the end of the decade, maybe in 2031. You mentioned Supi-Dupi, the long-acting antibody that targets the IL-4 receptor alpha. That is a very important receptor because it is already covered by the agreement to your point. We're still in preclinical development work there, expect to advance it to be clinic ready by end of year or in early '27. And in order to advance it into the clinic, we would need to work with Sanofi.

So that's where we need to have some discussions with them about how to move that forward. We also have a long-acting IL-4 ligand blocker as well as an IL-4, IL-13 biospecific. We expect both of those to reach the clinic sometime next year and are obviously working as quickly as we can on all of these in various -- and we have various development plans for each so that we can begin to advance care for patients with these different diseases.

Got it. I do want to talk about cemdisiran. So PDUFA is approaching here. Neuro is a new area for you. So one the -- like is there specific things you are looking for in the label that would help you as a commercial team or -- and then beyond that, I mean, this is a market where AZ, Alexion, they are far entrenched. So how do you -- what do you -- what is the -- what are the attributes of the product that will actually help you go deep in that market?

So Mohit, delighted to comment. So it really has been exciting to build out the neurology business unit. Obviously, not the first business unit you've seen us build out over the last handful of years. We do have a number of individuals who had prior experience in neurology with some of the leading companies at Regeneron. And then in addition, we've had some really strong external talent with neurology experience and expertise joined the company recently.

So not only our headquarter team, but our field teams are being deployed and will be launch-ready look forward to PDUFA date towards the second half of November. In terms of overall attributes of cemdisiran and the label we hope to achieve would be one that certainly gives us an opportunity to be competitive in this market based on efficacy of product, safety of product, convenience of dosing, established efficacy profile.

So that patients truly have the type of coverage and durability and product that they need to have Myasthenia Gravis is, obviously, a multibillion-dollar marketplace today, growing rapidly. We've done a lot of assessment and understanding of competitive products in the marketplace today, recognizing as we launch, they'll probably be about 9 products in market, 2 leading products from AZ and also with VYVGART market from argenx products that have been highly successful, but there's always room for potential differentiation improvement not only for existing patients who might be looking for different aspects of treatment and our switch candidates or potentially in naive patients coming into the marketplace as well.

Got it. I also want to touch upon the obesity franchise. So you have a really good molecule with MGA PGIP, though I think it is probably more of a question of commercial execution than the clinical side of things. You've done an amazing job by combining or co-formulating these 2 complete different modalities, so to speak. But when you think about commercially being -- or like related to market, but having a PCSK9+ approach, like how do you think it's resonating with both primary care as well as the -- like primary care is treating most of the -- using GLP-1s right now. So how do you think about this approach here?

So maybe let Ryan start on some of the clinical rationale and then I would be delighted to talk about combination product in the market to address obesity and cardiovascular disease with highly effective agents at the same time.

Yes. So we in-licensed in 2025, a peptide called olatorepatide from a Chinese company called Hansoh. We own the global ex-China rights to that. And we're starting to see data be reported from Hansoh that certainly supports a profile that resembles that of the approved agents in terms of weight loss and potentially differentiation on GI tolerability. So we think we have a sound backbone and we'll be, as I mentioned earlier, launching our pivotal studies in obesity as well as in obese patients with type 2 diabetes before the end of this year.

The co-formulation work with Praluent been underway. We are currently running a clinical trial of a weekly dose for Praluent. Praluent currently a biweekly subcutaneous injection. We'll have to move that to a weekly so you can co-administer and then we're going to have a co-administered -- I'm sorry, a co-formulated drug at all titration levels, which is another complexity to this program, but one we feel is important to bring to market.

So the clinical program is on track. I think our view on the market is you better bring something more to the table than like 1 or 2 percentage points on weight loss. So whether it's potentially better GI tolerability or whether it's a dramatic reduction in LDLs, which we've already seen demonstrated with Praluent. We think that's important to winning share in this highly competitive market.

And I'll let Marion talk more about the commercial dynamics as she sees them.

Sure. So you have the opportunity to combine weight loss, which for most patients they want to look better, they want to feel better. But at the same time doing that, becoming more healthy, they could be neglecting their heart health entirely. And it could be that the elevated lipids frankly, are more serious than the weight and I think for physicians, whether cardiologists or primary care or internal medicine is very conscious that leading cause of cardiovascular death is a result often from elevated lipids and other comorbidities.

If you had the opportunity to easily within the same injection to address both, why not effect looking good and being healthier at the same time. It's not a difficult message to understand. We're in a unique position with Praluent is a product to bring it into that kind of a combination therapy and truly think that, that would be an opportunity for the future and the window of time where we potentially would have an approval and be able to launch.

Got it. Very helpful. I have a lot more questions, but we have 3 minutes. So have to talk about BD, given the cash position here. So what is the message here -- it does seem like you are more open to this or equally open? Like how would you characterize this at this point?

I think we've always been open. But I do say -- I would say that our approach to capital allocation remains consistent where internal investment is always going to be the priority. We have a very healthy balance sheet and a cash position that is growing. And we need to be able to deploy that to where we think we can have -- get good value. It's something that we can leverage our different capabilities, whether it's clinical development, commercialization, leaning on genetics to inform our decision-making, manufacturing, you name it. We want to be able to add something to an asset and create value that way. We've been involved in many competitive processes over the last year or 2. Just haven't been willing to pay the most.

So I think we continue to look, be very active in terms of evaluating various opportunities across the biotech ecosystem. And so I think over time, if we can find a deal that makes sense for our shareholders and for our company, we will certainly do it. And we have the financial capability to do that, the flexibility to do that, and I expect us to do that over time.

Got it. Very helpful and Marion. So 1 year from now, I ask this question, I'm probably you are used to it now. So 2027 Wells Fargo conference, same day, 8 to 10 September, but this time, it is Wednesday to Friday.

That's a good plug, Mohit.

So we are sitting here, hopefully, both of us. And what would make you look back at the year and say it was a great year for us?

So look forward to being here. It will be 6 years you comment at the opening that we've been here. And I think it will be a continuation of the in-line product performance you've seen from Regeneron so far this year across our ophthalmology, immunology, oncology, hematology, rare disease portfolio. And then on top of that, really look forward to some launches, look forward to a prefilled syringe launch for EYLEA HD, very much look forward to the neurology launch potentially with an approval for cemdisiran in Myasthenia Gravis. We look forward to upcoming clinical data that we'll be reading out and certainly continuing to make sure that we bring science through our medicines to patients in a way that Regeneron has come to hold the values and the spirit of our organization, the culture we've created, the partnership with our stakeholders to do great things in the marketplace and continue the strong performance you've seen.

Awesome. On that high note, thank you very much, and all the best.

Thank you. Mohit.

Welcome to the Regeneron Pharmaceuticals Second Quarter 2026 Earnings Conference Call. My name is Michelle, and I'll be your operator for today's call. Please note that this conference call is being recorded.

I will now turn the call over to Ryan Crowe, Senior Vice President, Investor Relations. You may begin.

Thank you, Michelle. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron, and welcome to our second quarter 2026 earnings conference call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after our call concludes. Joining me on today's call are Dr. Leonard Schleifer, Co-Founder, Board, Co-Chair, President and Chief Executive Officer; Dr. George Yancopoulos, Co-Founder, Board, Co-Chair, President and Chief Scientific Officer; Marion McCourt, Executive Vice President, Commercial; and Chris Fenimore, Executive Vice President, Finance and Chief Financial Officer.

For our call today, Len will briefly review key second quarter performance drivers, highlight important upcoming pipeline catalysts and provide a few comments on capital allocation. George will then detail our recent pipeline progress, followed by Marion, who will review our commercial portfolio. And finally, Chris will discuss our financial results and outlook. After our prepared remarks, the remaining time will be available for Q&A.

I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, changes to drug pricing regulations and requirements and our drug pricing strategy, intellectual property, pending litigation and other proceedings and competition.

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarter ended June 30, 2026, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call.

Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results press release and our corporate presentation, both of which can be found on the Regeneron Investors Relations website. Once our call concludes, the IR team will be available to answer any further questions.

With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len?

Thanks, Ryan, and thanks to everyone for joining today's call. Before we begin, I would like to acknowledge with deep sadness to pass in earlier this week of financial industry luminary and longtime Regeneron Director, Arthur Art Ryan. Art served on our board for more than 2 decades and was a trusted adviser whose judgment, integrity and business insight helped guide the company through many important milestones. Prior to joining Regeneron's Board, he built a distinguished career in financial services, including serving as Chairman and CEO of Prudential Financial and previously as President and COO of Chase Manhattan Bank.

In addition, at left an enduring legacy of civic engagement in philanthropy throughout Newark and Essex County in New Jersey. On behalf of everyone at Regeneron, I want to express a gratitude for its many contributions and years of service. We joined his family and all he knew him is celebrating his life and legacy. We will miss his wisdom and unparalleled support of Regeneron's mission.

Turning now to our business. Regeneron delivered another strong quarter with total revenues up 17% and non-GAAP earnings per share up 11% compared to the second quarter of 2025 making our second consecutive quarter of double-digit growth on both the top and bottom lines. Dupixen, EYLEA HD and Libtayo all set new all-time highs for quarterly net sales and are carrying strong momentum into the second half of the year. Dupixen Global and product sales, as reported by Sanofi, were $6 billion, up 38% compared to the second quarter of last year on a constant currency basis. Demand trends across all approved indications remained robust and accounted for the majority of the year-over-year growth. We and Sanofi continue to see a low runway for Dupixen growth driven by further penetration of existing indications, expansion into additional age groups and international growth opportunities. Beyond Dupixen, we are rapidly advancing a broad portfolio of next-generation programs that we believe can build on the foundation we've established with Dupixen.?

George will discuss some of our recent progress in this area, including encouraging early clinical data from our long-acting Interleukin 13 antibody. Our collaboration with Sanofi spans nearly 2 decades and has been one of the most successful in the biopharmaceutical industry. Together, we have built a highly productive development and commercialization engine and the continued success of Dupixen in 9 FDA-approved indications across specialties ranging from dermatology, pulmonology, gastroenterology, ENT and allergy highlights the value that this model can create. Given that success, I can report that we have had productive early discussions with Sanofi to identify potential opportunities for further collaboration, including for several of Regeneron's Dupixen follow-on programs.

LHD in the U.S. continued to gain momentum, with net product sales in the second quarter of nearly $600 million, up 52% compared to the prior year. Importantly, this quarter marked the first time EYLEA HD net sales exceeded EYLEA, highlighting the continued strength of the conversion to our next-generation product. Physician unit demand for EYLEA HD in the second quarter increased 24% sequentially, reflecting continued strong uptake following recent FDA label expansions and growing prescriber appreciation for EYLEA HD differentiated profile and dosing flexibility. We continue to work towards obtaining approval for yet another product enhancement for EYLEA HD, the EYLEA HD prefilled syringe. We expect launch of this enhancement to drive even further adoption of EYLEA HD, and we are continuing to work closely with the FDA and multiple contract manufacturers with a goal of approval before the end of the year.

All in all, EYLEA HD has performed extremely well, and we look forward to continuing to grow this product. Luthin maintained its strong growth trajectory in the second quarter. Global net product sales reached nearly $500 million, up 29% compared to last year on a constant currency basis. Growth was driven by continued strong adoption in its approved non-melanoma skin cancer indications and further penetration in non-small cell lung cancer, where the tire now captures 20% of new-to-brand prescriptions in the U.S. Beyond its growing patient impact and commercial contribution, the time remains the strategic backbone of our ongoing efforts to expand and strengthen our oncology portfolio.

Turning to the rest of the pipeline. I firmly believe that one of Regeneron's core strengths is that we do not rely on any single program or a platform. Our pipeline is broad, diversified and highly productive. And while not every program will succeed we are confident that it will create many substantial value for patients and shareholders. With approximately 50 active clinical programs and many rapidly advancing preclinical candidates, we have one of the largest R&D portfolios in the entire industry. George will have more details on our pipeline progress in his remarks, but I want to highlight a few important programs where we expect near-term regulatory and clinical milestones.

We anticipate multiple milestones for our C5 complement programs, including an FDA decision in November for our new drug application for cemdisiran and siRNA that target C5 in general is myasthenia gravis, which we believe has the potential to offer a differentiated profile for patients living with this serious autoimmune disease. We also continue to make meaningful progress across several longer-term value drivers, including Factor XI for coagulation disorders, limboceltumab in multiple myeloma and premalignant conditions and our obesity portfolio, where we expect multiple Phase III study initiations later this year.

Now to a few comments on capital allocation, where our framework remains consistent. First and foremost, we believe the highest return opportunities to continue from investing in our own science. At the same time, we remain active in evaluating external opportunities. We're casting a wide net across the universe of business development options with particular interest in areas where we can leverage Regeneron's differentiated expertise in genetics, antibody engineering, clinical development, manufacturing and product commercialization. While we remain disciplined on valuation and strategic fit, we believe our financial strength, scientific capabilities, operational infrastructure and long-term perspective position us well to capitalize on compelling opportunities as they emerge.

In closing, our ability to repeatedly discover, develop and deliver important medicines has been a defining strength of Regeneron for decades. This quarter's performance, together with the important milestones ahead, reinforces our confidence in the company's long-term outlook. We have a thriving commercial business, a deep and diverse pipeline and a talented team committed to improving patients' lives through science. Together, these trends position us well to continue delivering meaningful innovation for patients and sustainable value for our shareholders.

With that, let me turn the call over to George.

Thanks, Len. Today, I'll focus on the key updates from our development pipeline. For a comprehensive summary of our mid- and late-stage pipeline, please refer to the programs in clinical development section of our 10-Q. I'll start with our complement-mediated disease franchise, beginning with some district. Our C5 siRNA. Regulatory submissions for cemdisiran monotherapy in generalized myasthenia gravis or GMG, have been accepted for review by both the FDA and the EMA. The FDA target action date is in November of this year while a European Commission decision is anticipated in the second half of 2027.

If approved, Symdistern would represent a highly differentiated treatment option in GMG and be the first sIRNA approved for this disease. We believe some dystront's efficacy, safety and convenient 4 times per year subcutaneous dosing profile, highly differentiated from C5 antibodies and other modalities approved for GMG. For some distant in combination with pozelimab, our C5 antibody, we continue to expect registrational data in paroxysmal lateral hemoglobinuria, or PNH in the fourth quarter of this year. Our Phase III lead-in cohort that compared this combination with revlizumab. an FDA-approved antibody to C5 for the treatment of PNH suggested that our combination could provide a more convenient, monthly subcutaneous regimen that could also improve disease control based on LDL measures and support our hypothesis that complete complement blockade in this disease is required for sustained disease control.

As a reminder, the registrational study is evaluating noninferiority of our C5 combination versus eculizumab, the other C5 antibody that is FDA approved for the treatment of PNH using co-primary endpoints of intravascular and loses control as well as transfusion avoidance. In ophthalmology, our C5 approach in geographic atrophy, or GA, remains on track to read out 26-week data from our exploratory cohort in the fourth quarter of 2026, which will help inform our pivotal strategy. As a reminder, we are evaluating systemic administration of cemdisiran with or without pozelimab with the goal of slowing the rate of GA lesion growth and associated declines in visual acuity, while avoiding the ocular safety issues that have been observed with certain FDA-approved therapies.

We are also evaluating intravitreal pozelimab in GA to provide optionality and are aggregately developing coformulations of this with other agents such as aflibercept to address comorbid retinal disease settings. Immunology and inflammation to follow on, on Dupixen's success, we continue to advance a series of next-generation fully human anomized and bispecific designed to build on Dupixen by extending duration, enhancing target coverage and potentially improving efficacy. We have enrolled initial healthy subjects in our first-in-human trial for a long-acting IL-13 antibody and expect to begin dosing patients with atopic dermatitis later this quarter, with plans to execute an expedited path to starting registration-enabling studies potentially by the end of next year or early 2028.

Our initial clinical data indicate that this antibody has a prolonged halflife that has the potential to extend the dosing interval well beyond those achieved with currently approved products in this category. First-in-human studies of our other next-generation long-acting antibodies are planned with next-generation Dupixen or spud expected to be clinic ready by early 2027 and additional candidates, including our IL-13 specific next year. Briefly on to oncology. ubamatamab, or MUC16 continues to demonstrate promising monotherapy activity in low-grade serous ovarian cancer, a subset of advanced ovarian cancers, and we plan to present detailed data in this setting at a medical meeting this fall. We also continue to advance pivotal studies for, our BCMAxCD3 bispecific in multiple myeloma and premalignant conditions including a newly initiated pivotal study in high-risk smoldering multiple myeloma.

We expect results next year from the LINKER-MM3 study, our confirmatory trial of Innospec monotherapy versus standard of care and patients have received at least one but no more than 4 lines of therapy. In 2028, we expect minimal residual disease or MRD negativity results from our first-line study in transplant in myeloma patients as well as our linozific, carfilzomib combination study in myeloma patients who have received one or more prior line of therapy. At the American side of Clinical Oncology or the ASCO meeting, we presented first results from the Phase I/II LINKER AL2 trial of linoleic monotherapy in patients with second-line plus systemic light chain or AL amyloidosis. Normalization of free light chain occurred by day 15 across all doses and 100% of patients achieved a hematologic complete response at the highest dose test. The majority of patients with renal or cardiac involvement demonstrated improvement in organ function despite short follow-up.

The Phase II study which has registrational intent is now ongoing, a Phase III study in first-line light chain amyloidosis is planned to start early next year. Moving to anticoagulation. We are on track to initiate the remaining Phase III studies from our comprehensive Factor XI program this year, featuring Synvassabart, our catalytic antibody formerly known as REGN7508 and Reserva our A2 antibody formerly known as REGN9933, give results from our studies in venous thromboembolism or VTE prevention following total knee replacement surgery are expected in the first half of 2027. Also in 2027, we anticipate results from the Phase II Roxy ATLAS study, which evaluates both Factor XI antibodies against a fixed bed in stroke prevention in patients with atrial fibrillation or staff which is expected to provide us with important insights into bleeding risks at 3 months of observation.

We have also begun enrolling patients in our Phase III SPAF trial, Roxy incline that will evaluate both of our antibodies against placebo in patients who are not candidates for conventional anticoagulant dirty. We remain excited about our program and favor antibias as opposed to a small molecule approach as we believe antibodies enable greater and more specific inhibition of Factor XI leading to improved antithrombotic activity without increased bleeding risk or other off-target safety issues. Turning to obesity. Oloreptitide, our dual GLP gift receptor agonist in license for HANSO continues to advance data from Hansa's Phase III study of oloreftadide in Chinese patients with obesity, which top line in March, will be presented as a late breaker at the European Society for the Study of Diabetes Conference, or EASD in October.

Acknowledging the inherent limitations of cross-trial comparisons, oloreftadide generated weight loss that was comparable to the weight loss observed in a similar study tazepatide in China while demonstrating a favorable gastrointestinal tolerability profile, including meaningfully lower rates of diarrhea, nausea and bombing. remain on track to commence Phase III studies later this year in addition in patients with obesity as well as patients with obesity and type 2 diabetes. In addition to the altorepotide monotherapy program, we also continue to advance our combination of olatorepatide and Praluent, our PCSK9 antibody to address patients with obesity or type 2 diabetes that have comorbid hypercholesterole -- also at the ASD, we will present 52-week results from the car study, including accompanying MRI findings in a subset of patients and trigrubat to semaglutide did not drive additional weight loss but did show encouraging skeletal muscle mass preservation versus semaglutide alone.

These findings reinforce our belief they're presenting -- preventing muscle mass loss may become increasingly important as obesity treatment evolves, particularly in older patients with sarcopenic obesity. In rare disease, we expect an FDA decision in August for garituzimab, our Activ/Block antibody in Fibrodysplasia Ossificans Progressiva or FOP. If approved, gartusimab would be the first treatment shown to reduce the number of new abnormal bone formation lesions as well as clinician-assessed flare-ups in FOP patients. From our earlier-stage pipeline, we are planning to present at medical meetings this fall, some promising clinical data from our pipeline of siRNAs for metabolic dysfunction associated sthepattitis or MASH and for our NPE R1 antagonist antibody for the treatment of postural orthostatic tachycardia syndrome syndrome or pots.

Finally, we continue to work with the U.S. government and international health organization to deliver potential new treatments for the devastating recent Ebola virus at DaVita is driving the current outbreak to the democratic Republic of the Congo. Regeneron developed antibodies are now being tested in nonhuman primates with early data showing they can prevent mortality when it's administered even after clinical symptoms have already appeared. We are talking with the international health organizations to see whether we will be able to once again help with the current Ebola outbreak as we have in previous outbreaks. In summary, we remain focused on rapidly advancing our broad diverse pipeline, which we firmly believe has the potential to change the practice of medicines across many diseases with high unmet need.

And with that, I'll turn it over to Marion.

Thanks, George. Our second quarter results reflect strong commercial execution across our portfolio, delivering meaningful growth from our market-leading brands in multiple therapeutic categories. Starting with our retinal franchise. In the second quarter, EYLEA HD and EYLEA delivered just over $1 billion in combined U.S. net sales up 7% quarter-over-quarter. We also achieved an important milestone in the second quarter with more than 100 million doses of EYLEA HD and EYLEA administered to patients since EYLEA's launched in 2011.

Second quarter EYLEA HD net sales in the U.S. were $96 million, representing a 52% year-over-year increase and 27% growth quarter-over-quarter. These results reflect strong physician demand, which grew 24% from the prior quarter. EYLEA HD has the broadest label and greatest system flexibility of any anti-VEGF medicine following last year's label enhancements to include retinal vein occlusion and additional dosing options that range from every 4 weeks through to every 20 weeks. EYLEA HD now comprises approximately 60% of U.S. franchise net sales compared to 34% in the second quarter of last year. Within the innovative branded category, EYLEA HD and EYLEA captured 57% share in the second quarter, and EYLEA HD was the only innovative brand that achieved quarter-over-quarter share growth. Physicians increasingly recognized an EYLEA HD for its efficacy safety and durability profile, initial uptake of EYLEA HD and RVO has been strong, driven by its differentiated label and clinical data. EYLEA HD is the only product that offers every 8-week dosing in this indication and was the only product to demonstrate numerical improvement in visual acuity in clinical studies compared to EYLEA, the prior gold standard in RVO.

EYLEA U.S. net sales in the second quarter were $412 million, representing a 45% year-over-year decline and a 13% decline quarter-over-quarter, primarily driven by ongoing conversion to EYLEA HD and competitive dynamics. Looking to the second half of 2026 for EYLEA, we expect sequential quarterly demand declines in the low to mid-teens due to the factors mentioned as well as additional competition primarily from multiple aflibercept 2-milligram biosimilar launches. With an EYLEA HD label that now includes wet AMD, DME, DR and RVO as well as the broadest dosing interval in the category retina specialists increasingly recognize EYLEA HD as the next standard of care in the anti-VEGF category. We expect this will drive sequential demand for EYLEA HD in the low to mid-teens in the third and fourth quarters of 2026.

Turning to Dupixen, which continues to deliver significant patient benefit to patients globally with more than 1.5 million patients actively treated worldwide, Dupixen has had a tremendous impact across these 9 approved indications, and it is the #1 biologic medicine prescribed by dermatologists and pulmonologist, allergists and ENTs, Second quarter net sales were $6 billion, reflects 38% growth on a constant currency basis and the U.S., sales grew 42% year-over-year to $4.6 billion, primarily driven by continued growth across our blockbuster indications and uptake in recent launches. In addition, as reported by Sanofi this morning, a favorable gross to net adjustment also boosted U.S. net sales in the quarter. Dupixen continues to drive strong growth across blockbuster indications, including atopic dermatitis, asthma, nasal plastic esophagitis, supported by its clinical efficacy and safety profile uptake is also growing in our new indications of COPD, chronic spontaneous articaria, bolus pemphigoid and allergic fungal rhinositis.

With significant opportunity to improve the lives of even more patients, Dupixen is well positioned for sustained growth over the near and long term across approved indications. In the second half of the year, we expect year-over-year global net sales growth to remain strong but to moderate relative to the first half of 2026 as we annualize recent indication launches and faced stronger prior year comparisons. Turning to Libtayo, which delivered worldwide net sales of $489 million, up 29% year-over-year on a constant currency basis. In the U.S., sales grew 38% year-over-year to $343 million, with growth across both non-melanoma skin cancers and non-small cell lung cancer. The recent launch in adjuvant cutaneous chemo cell carcinoma has generated positive feedback on the paradigm-changing treatment and has been accompanied by increasing use across all approved CSCC settings.

In first-line non-small cell lung cancer, Libtayo is now firmly established as a second list prescribed immunotherapy treatment in the U.S. where Libtayo's share of new patient starts has doubled since early 2025 to 20% as physicians increasingly recognize its strong clinical profile. We expect continued growth for Libtayo in the second half of 2026 as we strive to gain incremental share in lung cancer and drive uptake across all approved stages of CSCC. On to linazipiC, which is now in its third full quarter on the market, physician feedback in this late line treatment setting is positive based on Lenoific's differentiated efficacy and safety profile, lower hospitalization requirements and convent dosing. Despite its strong profile, we expect Lenisific growth to remain modest in this small late-line setting as we work to advance into earlier lines of therapy.

Turning to our disease where Regeneron is expanding our portfolio of life-changing medicines for patients with significant unmet medical need. Our homozygous familial hypercholesteremia market medicine Evkeeza delivered net sales of $53 million in the second quarter, representing 29% year-over-year growth. I'm also delighted to inform you that first patients have been dosed with Tamini, the first and only gene therapy for children born with genetic hearing loss and our early launch efforts continue. We are looking forward to adding daratuzimab to our rare disease portfolio with a potential FDA approval in August for FOP. FOP is a serious life-threatening disease where garitostumab would be the first treatment shown to reduce the number of new abnormal bone formation lesions as well as clinician-assessed flare-ups in FOP patients.

We are also excited about the potential FDA approval of cemdisiran in generalized myasthenia gravis later this year. We see significant opportunity in a large and growing category based on some distant clinical profile demonstrated in this pivotal study including rapid, deep and sustained clinical benefit, favorable safety profile and convenient quarterly subcutaneous dosing. In closing, our second quarter results reflect focused commercial execution across therapeutic areas we continue to drive growth for our in-line brands and are preparing for upcoming launches. We remain well positioned to deliver meaningful benefit to patients worldwide across many different diseases.

And with that, I'll turn the call to Chris.

Thank you, Mario. My comments today for Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron delivered a strong second quarter, highlighted by continued momentum across our key growth drivers and disciplined execution across the business. Second quarter total revenue increased 17% from the prior year to $4.3 billion, driven by higher Sanofi collaboration revenue, reflecting the continued strength of Dupixen as well as strong growth for EYLEA HD in the U.S. and Libtayo globally. Second quarter diluted net income per share grew 11% to $14.29 on net income of $1.5 billion. This included a $0.99 negative impact from acquired in-process research and development expense, reflecting upfront and opt-in payments associated with collaboration and licensing agreements.

Beginning with the Sanofi collaboration. Second quarter total Sanofi collaboration revenue reached an all-time high of $2.2 billion, of which $2 billion related to our share of collaboration profits. Regeneron's share of profits grew 59% versus the prior year driven by Dupixen growth and improving collaboration margins. We've now fully repaid the Sanofi development balance, which was approximately $3.1 billion when the Sanofi antibody collaboration agreement was amended as part of the 2022 Libtayo transaction. That amendment accelerated repayment of the balance, which further reduced our share of collaboration profits as it was paid down. The repayment lowered our reported Sanofi collaboration revenue by approximately $930 million in 2025 and $530 million in the first half of this year. Given full repayment of the Sanofi development balance starting in the third quarter, we expect Sanofi collaboration revenue to step up as we record our full share of collaboration profits.

Moving to buyer. Second quarter net sales of EYLEA HD 8 mg and EYLEA outside the U.S. were $667 million, inclusive of $366 million of EYLEA 8 mg sales. Total buyer collaboration revenue was $276 million, of which $227 million related to our share of net profits outside the U.S. Other revenue in the second quarter increased 5% to $193 million of which royalty income from Alaris combined with our share of profits from Arcelis totaled $157 million, an increase of 44% versus the prior year. Now to our operating expenses. R&D expense was $1.5 billion in the second quarter, reflecting continued investment support Regeneron's innovative pipeline, which has approximately 50 product candidates, including mid- and late-stage programs across hem-onc, anticoagulation and complement-mediated diseases. Second quarter SG&A was $574 million, reflecting investments to support our commercial portfolio including continued growth of EYLEA HD HD and Libtayo as well as ongoing launch activities across our broader product portfolio. Non-GAAP gross margin on net product sales was 87% in the second quarter. Our GAAP gross margin was 78%, which similar to the first quarter, was negatively impacted by unabsorbed manufacturing costs related to the temporary interruption in both manufacturing production at our Limerick Ireland facility.

Production at this facility resumed to normal levels as of the end of the second quarter. Regeneron generated $1.4 billion of free cash flow through the first half of 2026 and ended the second quarter with $15.1 billion of cash and marketable securities net of debt. During the first half of the year, we deployed approximately $2.5 billion to share repurchases, business development and dividends. Within that, we repurchased $1.2 billion of our shares in the second quarter alone, bringing total repurchases to approximately $2 billion for the first half resulting in a net reduction of 2.4 million shares outstanding since the end of 2025. As of June 30, we had $2.5 billion of share repurchase authorization remaining and we continue to be opportunistic buyers of our stock.

Finally, we made modest refinements through our 2026 financial guidance as we enter the second half of the year. A full summary of our guidance can be found in our earnings press release published earlier this morning. In conclusion, Regeneron's strong second quarter results position us well to continue investing in our differentiated pipeline delivering important medicines to patients and prudently deploying capital to drive long-term value for shareholders. With that, I'll pass the call back to Ryan.

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A. I'm sure we are able to address as many questions as possible, we will answer one question from each caller before moving to the next.

Our first question comes from Chris Raymond with Raymond James.

Just on cash management. So you guys have about $8 million on hand now with the Sanofi obligation sort of rolling off. I guess it seems that, that will be accelerating pretty meaningfully hearing what you guys have said about R&D and share repurchases and other uses of cash, even with pretty robust investment, that outlook is pretty sizable. Len, I'm wondering if you could maybe square that dynamic with some of the aversion to M&A that you've expressed in the past as a primary use of cash?

Thanks for the question. I don't think I expressed the conversion to M&A. I think I expressed the inversion to overpaying in M&A settings. And we have been involved in many of these interested transactions, and we have seen people pay for one, and we think the value we're justify. We deploy a lot of our R&D money, and I think we'll talk more about that later in the year, and Chris give some guidelines. But if you look at what we spend on R&D, both internally and externally, we're really kind of in line with what other people spend, but we tilt more towards the internal R&D. We are not allergic to any external opportunity.

We look at them all, but we are pretty disciplined in trying to create value with these transactions. So no version whatsoever. We can do small, we can do large, but we want to make sense and make money for our shareholders over the long term.

Our next question comes from Chris Scott with JPMorgan.

This is Taylor Hanley on for Chris Schott from JPMorgan. We were just wondering, given some of the recent updates in the broader I&I space, can you talk a bit more about your latest thoughts on expanding the Sanofi collaboration to include additional assets? And then also what steps you could take to accelerate the development of those assets?

Right. Thanks for the question. I think as you heard from Sanofi today, -- they talked about the productivity of our alliance, and we agree with that, that this has been perhaps 1 of the, if not the most productive alliance in the history of our industry with Dupixent driving remarkable returns for both Sanofi and Regeneron. We do have some follow-on opportunities Dupixen, as George mentioned in the store, including our IL-13 reenacting antibody, which we now confirmed with the very early PK data, supp, and we have several others that are related to the Dupixen portfolio.

We have had productive early discussions. The new CEO, and I have talked multiple times, we are looking to see what might make sense and what kind of transaction might make sense for the 2 companies to get together on further assets, where some of those assets might be best owned in the Dupixen portfolio. We'll keep you posted on those discussions as they progress.

And when you asked about development and expediting it. We should just remind you we have led the most innovative development program, probably in the history of the industry in terms of with Dupixen getting it approved for 9 different indications, including many of them, the first approved biologic in many of these indications. Obviously, we know this field, we created field better than anyone else. And just as we've been very innovative with the first-in-class Dupixen, you can imagine that will be just as, if not more innovative going forward.

Our next question comes from Tyler Van Buren with TD Cowen.

Great. Congratulations on the tremendous quarterly performance. So can you provide additional details on the ongoing EYLEA HD prefilled syringe review with overall approval by year-end now? And when you say working with multiple contract manufacturers, does that mean there is now a third CMO in the mix? And if so, why did you feel the need to add another? Or is it still just the 2? And is the second one most likely to receive approval by the end of the year? .

Thanks, Tyler. Look, a lot of things have been changing at the FDA. People have been changing. Leadership has changed. We had thought that we would get some action perhaps an approval by the end of the second quarter. That obviously didn't happen. -- but we have now had renewed discussions. We are looking at every -- leaving no stone unturn, multiple and that means more than two are in the mix.

We could always use backups if we succeed on 1 3, 1 and 2, 2 and 3 or 3 and so forth. But we're doing everything we can. We've had some good conversations recently. We know what the path is. We could see this ending by the end of the year or sooner.

Our next question comes from Cory Kasimov with Evercore ISI....

Before you begin, I neglected to point out, if you think about EYLEA HD and how it's progressed, we had a great product. The product itself really made a difference to patients. in terms of durability, the doctors really appreciate it. But we felt that we could bring on additional enhancements to really make the product even more attractive to patients and their doctors. Those enhancements included getting the Q4 monthly indication in the label, it included getting the RVO indication with a favorable and the only one favorable interval and getting the long-term durability intervals in the label.

Those 3 enhancements have really driven EYLEA HD, and it's really the only product in the branded space that has had this remarkable growth recently. We think that can continue, but we do believe we can add another enhancement, it would go even set another leg up. But anybody should understand that the product is doing great. I just look at the numbers, look at the growth, look at how the other products in this space are doing, it's really doing very, very well.

Let's move to -- Josh, are you still on the line from Evercore.

From the market research you've done in Mycena Gravis, what percent of the market is currently served by IV C5 therapies? And do you expect a robust switch market developments in the and reaching the market before the end of the year?

We very much look forward to the potential approval of cemdisiran in bringing our product into the marketplace from GMG patients very important market, certainly therapies in market today, but we do believe our clinical profile, our safety profile, convenience of dosing will be very meaningful. We have experts working on the commercialization launch strategy. We know the market well through them. We've had an amazing ability to attract talent to the organization for this launch. Specifics on launch strategy, market size opportunity will hold to later times. But just to assure everybody, the we look forward to the launch and we're preparing for it actively. And obviously, as we mentioned today, potential approval from FDA in November.

Just to amplify a tiny bit on what Marion said, to address some part of your question. Look, the switch population is obvious what some might say in the business, one of the lower-hanging fruits in this space. But we're not going to only focus on that because if you look at the FcRN approach, the our data in terms of convenience, potentially being given very infrequently to be able to have a continuous effect on myasthenia gravis patients in their ability to function. I think this can compete in all segments. But of course, there's some easier versus hardest parts of the market.

Let's move to the next question, please, Michelle. Our next question comes from Salveen Richter with Goldman Sachs.

You'll be presenting data from one of your ceRNA programs in MASH this year. Could you just speak to the expected differentiation of this asset versus approved targeted agents such as redefine and then maybe put the commercial opportunity in context for us, especially with the uptake of Glip in this category as well.

Right. All other agents in this in this field are not really directly addressing the mechanism of NASH itself. They're working indirectly by decrease, for example, food intake through the glips and other mechanisms. What I want to remind you is due to the investment we made in the Regeneron Genetic Center, we have actually redefined the field. We invented, but we discovered actual genetic mechanisms that are protective for the actual basis of this disease.

And the genetics would suggest that if you could come up with a medicine that could mimic the genetics like we've done in other areas, then we could directly impact the actual mechanism of this disease and perhaps reverse it more quickly and more deeply than other indirect approaches, which are not directly working on the mechanism itself, but working indirectly with, as I said, by decreasing food intake and so forth. So these would be results using the first agents that are directly addressing the meters of action of this disease as defined genetically.

So we will be very excited to see based on this potential, how these agents will have performed in these clinical studies.

Thanks, George, and clearing data to come. Our next question comes from Alexandra Hammond with Wolf.

So on DMD and PNH, we're expecting that readout later this year. So if you can kind of help us think about the incremental data points beyond LDH control maybe transfusion avoidance that you need to see to kind of support a best-in-class label claim. And assuming a clean readout, what does the regulatory and commercial path look like from here and time line?

Well, we strongly believe that improved control of intravascular hemolysis is the most relevant and validated endpoint because it's directly reflects to C5 mechanism of action and it's directly related to preventing what are the most devastating consequences of these disease, which is thrombosis and clotting and so forth. And that is what we're really looking for. We think that, that would most strongly demonstrate whether this product is really differentiated and perhaps superior to existing therapies in addition to providing a much more convenient dosing regimen.

So that's what we're really focused on here and in that, that is what everybody should focus on because it directly addresses the C5 mechanism of action, and it's related to what are the devastating consequences of this disease.

Thank you, George. Let's go to the next question. Our next question comes from Tazeen Ahmad from Bank of America.

I wanted to get your thoughts on temdisiran on how you're thinking about the launch trajectory in GMG. So you would be entering a market that has quite a few options. So can you just give us your thoughts about what you think doctors in particular, could respond to a differentiating factor relative to, let's say, the market leader, which is this right now? .

So certainly, as we launch into the market, we study it carefully in the competitive dynamic. As I mentioned, with some distrain we're very excited about the potential launch in November in the U.S. marketplace, certainly working towards that. In terms of the overall uptake, it's probably early to predict. But I would point to some of the characteristics of cimdisiran that are really exciting not only to Regeneron, but to the key opinion leaders and physicians who have been involved in the clinical trials and that is the efficacy, the safety, the convenience of dosing. And those elements certainly have the opportunity to create differentiation that will be meaningful in that market.

Just to add that from a clinical point of view, I don't feel it's optimal to chase symptoms it's much better to have a steady improvement. We're not cycling on and off. And some of the -- clearly in the FCRNs, you see this cycling even though you can even give repeat cycles now, you still have seen evidence of loss of control. And we think that the unpredictable nature of all that compared to giving something every quarter by a simple injection is really going to be changing the practice and the way patients think about it. Convenience does matter. We know that.

As Len said, it's important that a significant proportion of the FCRN treated patients do lose efficacy over time and have to be switched to another therapy. We think that we have obviously an optimal option for patients and physicians to consider. We think that we have best efficacy across studies shown in the field. But as Len said, we have consistent efficacy over time. We are convenient. But we should also not to suggest that one of the concerns of all the treatments here is the impact on complete complement mission and also immunosuppression with FCRN and we have to remind you, and this is something that we have to remain to demonstrate.

But what we have demonstrated, which is very clear. And for the first time, is that we are achieving best-in-class efficacy in cross-study comparisons, while doing this using this siRNA approach without complete complement inhibition which is really stunning. And that may, over time, represent another benefit to patients that will have to demonstrate probably using real-world evidence and so forth over time. But I think this is a very, very exciting and very differentiated profile that has the opportunity not only to capture by switch a lot of the C5 class but also all the patients who, over time, be due to lose efficacy using the FCRN approaches.

Our next question comes from Evan Seigerman with BMO Capital Markets.

I want to follow up on your partnership with Sanofi. It's been a very successful partnership for Dupixen as you think about the next phase of the relationship, what are the key elements you want to preserve from the original collaboration? And where do you see opportunities to improve the structure going forward?

It's a very stop question. event. I'll answer in more general terms, then we'll satisfy these are ongoing negotiations. But -- what we want to do is capture the joint learned capabilities and experience in developing and commercializing Dupixen. And that -- those learnings are substantial and together, if we're able to reach an agreement, they would, I think, drive success of these follow-on products.

I think as may have mentioned in her Q&A today, we need to make some adjustments when we were a first partner with Sanofi, I can George probably remembers either, but it was got to be a couple of decades ago. We were quite a different company. And so the rules of the game were a little bit different and so we have to I think tick together and be open-minded, and I think Balan is to have a relationship that reflects where the companies are now. So I'm cautiously optimistic that we can get there.

But I think importantly, the companies have complementary as well as overlapping strikes and so forth. And I think that proposed deal opportunities will take advantage of both the complementary but also overlapping strengths of both companies.

Our next question comes from Gregory Renza with Truist Securities.

Congrats on a nice quarter. I just wanted to follow up on the obesity programs. And certainly, that path, you commented certainly on this evolving quick landscape here. Just given the maturity landscape, what is the realistic time line for the GLP-1/GIP and probably one combination? And how should we be thinking about that potential and differentiation to carve an up share here? Thank you very much.

Well, as we've announced, we're going to be initiating the Phase III program over the next few months and we're continuing to advance the combination. The way that we're looking at it, and I think the way we've turned it is, everybody is trying to compete by getting a few more percentage points of weight loss and so forth, where what we're trying to do is provide a fundamentally a substantially different profile -- so imagine if somebody had invented a GLP that could also lower your bad cholesterol by 50% to 60% and substantially in addition, further you reduce your risk of cardiovascular disease.

Well, that's what we're offering and our program is advancing quickly in this area. In addition, providing co treatments that counter some of the negative aspects of GLP induced weight loss such as muscle loss would be once again a fundamentally different profile and we're moving those programs along well be releasing more data from those programs and so forth. So we think it's very different to not just be going after a few more points of weight loss, but substantially enhancing the profile that you get along with it, whether you're addressing a related comorbidity that many of these patients also suffer from, which is cardiovascular disease or a side effect that causes and is being increasing problems, especially for sarcopenic patients, that is patients who are already starting with low muscle mass.

Those are the sort of things that we're actually going for. But we also, as we discussed, at least in cross-sending comparisons, the GLP that we're working on might have indeed favorable profile on its own as well. I should also remind you that we have a very additional deep and slightly earlier stage pipeline using many other approaches as well that we're very excited about, but we don't have time to discuss right now.

We have time for 2 more questions, please, Michelle. Our next question comes from Carter Gould with Cantor.

I think this probably falls on shortage here. On the back of the samimab setbacks and Costin progress, which has been relatively paced, I was wondering if you kind of use that as an opportunity to step back, reassess your solid tumor portfolio, clearly was less of a point of focus on the call today and maybe just how you see that going forward? And if that's still going to warrant the same sort of spend and attention and effort in the past couple of years?

Yes. Well, obviously, cancer is a challenge. I mean, the United States put out a warren cancer in the 1960s. I don't know you realize it, but back in the 60s, they get a survey and 90% of the U.S. population thought that based on the oral cancer would be cured. 90% of the U.S. population thought cancer would be cured by the year to fast. Clearly, we celebrate incremental advances in the field. I mean getting a few more months here and there. We think that, obviously, featunab demonstrated that it was an active agent, numerically, you did add about 5 months in PFS.

And as you saw, we just missed on our primary endpoint. We have a lot of programs, many programs both in solid and liquid tumors -- we continue to be very excited about them and moving them forward. And if anything, we are continue to advance and continue to take more shots in many different ways, both in monotherapies and combinations using a lot of our unique and first-in-class agents against this very tough and devastating disease, and we hope to be delivering successes going forward. But as we all know, it's a challenging field, but we need progress, and we're not going to stop focusing on.

Last question, Michelle. Our last question comes from Geoff Meacham with Citi.

Thanks, for the question. Just overall, maybe a bigger picture on ophthalmology. Just trying to get a sense for you guys strategy, obviously, beyond VEGF, how do you think about kind of the investments, the strategy, looking at complement and glaucoma and others. Is this like a vertical that we should expect you guys to add a lot of resources to in terms of R&D investments? Or is it really hem/onc is the primary focus in I&I? .

No. We have a huge investment belief in our ophthalmology portfolio as I like to put it, we're hoping to deliver the sort of successes and differentiated advances that we did with EYLEA HD for AMD and all those associated diseases and bring those elsewhere, as I like saying we want to deliver the EYLEA for glaucoma. We want to deliver the EYLEA for thyroid eye disease. And as you just said, for geographic atrophy and related diseases, we want to deliver those sorts of successes.

We think that there is still so much opportunity in both of these areas -- but since we're further advanced right now in geographic atrophy, we know the field needs safer agents, the field needs longer acting agents, the field needs to address the fact that many of these patients suffer from comorbid diseases. There are many patients with GA, who also have wet AMD. We need to be simultaneously treated with multiple injections to try to control both sides of the disease, and obviously, we know the devastating consequences that are possible with some of the current complement treatments for this disease.

So we think that there's many, many, many ways that we can really help patients out here because there is a crying need, just like as I said, just like in cancer, we have so much unmet need, and we're going to continue to focus on that. We're going to continue to focus on eye. We're going to continue to focus on all the many areas in I&I and that's as Len started the show today. He highlighted the thing that distinguishes us is we don't take one shot. We don't focus on one thing. Why? Because many times, the one thing doesn't work out, but when you look over the years, at the many shots that we've taken, so many of them have delivered so much benefit to so many patients that have literally change the practice of medicine. That's what we continue to do. We don't just focus on eye or on one disease and odd. We don't just focus on one nation in immunology, we don't just focus on one setting in cancer. We focus on everything, and that's why we have the deepest and broadest and I think most exciting pipeline in the history of the industry.

Thank you, George, and thanks to everyone who dialed in for your interest in Regeneron. We apologize to those who remain in the Q&A Q, who did not have a chance to -- who we did not have a chance to hear fell today. As always, the Investor Relations team is available to answer any remaining questions that you may have. Thank you once again, and have a great day.

Thank you for your participation. This does conclude the call. You may now disconnect.

Good afternoon, everyone. Thank you so much for joining us. Really pleased to have with us the Regeneron team. Next to me is Chris Fenimore, CFO; Andres Sirulnik, SVP, Clinical Development Unit Head of Hematology and Ryan Crowe, IR and strategic analysis. And Ryan, let me turn it over to you.

Just to get this out of the way. And Salveen, thank you very much for having us. Great to be back in Miami again to see a lot of familiar faces and excited to have this chat. But first, let me get through this forward-looking statement disclaimer.

I'd like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings that are on our website. And with that, Salveen, let's jump in.

Great. Chris, to start here, Regeneron has been challenged recently on both the earnings front, driven by headwinds facing the EYLEA franchise. And on the pipeline, most recently for fianlimab Phase III failure. In that context, how do you see the company positioned from here for second half of the year and into the end of the decade? And maybe touch on the key priorities for the company at this point.

Thanks, Salveen, and I hope we have plenty of time for Andres because he's got a lot of exciting things to talk about. So if you look at the Regeneron business, it's fundamentally strong, resilient, coupled with a balance sheet that provides us with a tremendous amount of flexibility to allocate capital in a way that we think will drive the most long-term value for our shareholders. If you look at the first quarter alone, we had strong double-digit growth, both on the top and bottom line, driven by our core franchises.

So continued strong performance from Dupixent. We basically saw Libtayo, which I have to say, our commercial team has done a remarkable job of really driving and executing on Libtayo since we took that product back from Sanofi in the middle of 2022. And it really just goes to show you that when we, as a management team, sort of put the execution behind it and the focus, what you can do with the brand in our hands. And then lastly, continued strength and momentum that we're seeing in the EYLEA HD franchise following the approval of the enhancements to the label at the end of last year in both retinal vein occlusion and every 4-week dosing.

So a lot of the reasons to be excited about the current core business as well as what the future holds. You mentioned fianlimab. Fianlimab is one of basically 50 things in our pipeline. We historically and will continue to be very focused on driving what we think is a world-class pipeline. If you look at the perspective, it's always been multiple shots on goal, spreading those shots across multiple therapeutic areas and having opportunities where we think in the short, medium and long term, have significant commercial opportunities. So we're very excited about what the pipeline will be able to deliver over the next few cycles.

If you look at the balance of the year, there's a few catalysts that we're also very, very focused on delivery. Some of them are regulatory catalysts. So we've got the approval for the prefilled syringe. We've got an approval for cemdisiran in myasthenia gravis, and then we've got the approval for garetosmab in FOP.

Looking at clinical catalysts, and I'm sure Andres will talk about these. We've got data coming in our complement franchise in both PNH and geographic atrophy. So a lot of catalysts coming in the second half of this year.

We're also, at the same time, laser-focused on commercial execution. So I touched upon, obviously, our 3 growth drivers. We will continue in the remainder of the year to really stay focused on driving that commercial execution and doing it, obviously, in as efficient way as possible and continuing to drive growth. One thing not to forget about as well is the repayment of the Sanofi development balance, which will be repaid by the end of the second quarter, which will allow an inflection in our share of collaboration profits, basically in the second half of this year.

If you just think about other things that are there in the pipeline in terms of where we think we've got some exciting opportunities. I think Ryan and the IR team, coupled with members of management have done, I think, a very good job using the Regeneron Roundtable as an opportunity to highlight where we have exciting near-term opportunities with large commercial potential in areas like multiple myeloma, anticoagulation, complement mediated diseases and obesity. And those are just some of the nearer-term opportunities.

If you then turn and focus to a pipeline with 50 different sort of candidates in there, there are plenty of earlier stage opportunities that will eventually become mid- and late-stage opportunities as we continue to drive those forward in exciting areas like inflammatory and immunology, ophthalmology, cardiovascular, metabolic and even neuroscience. So there's a lot going on at Regeneron and a lot to be excited about.

Just touch on strategy here. It does seem like the company is increasingly open to larger M&A. Just speak to your view here regarding size of deal and modalities and therapeutic areas and stages of development. And you've also spoken to valuations in cases being prohibitive in the context of return on investment and acknowledge competitive dynamics amongst acquirers. How do you think about all these factors when you put it together?

Yes, it's a very good question, Salveen. I don't -- the way we view it, we're not limited by either the size of the transaction. As I said, we've got the balance sheet with an enormous amount of flexibility. We're not necessarily limited by therapeutic area. We really look at things and evaluate opportunities where we think the science really makes a lot of sense and that can translate into commercial opportunities where there's unmet medical need.

I think if you look historically, we've done more in the traditional collaboration sort of side of things and not necessarily traditional M&A. And those historically have been opportunities where they are complementary technologies or things that augment some of our capabilities as recently as in the past couple of months, we did a deal with Telix in radiopharmaceuticals. We did a deal with Parabilis, using their Helicon technology, coupled with our ability to conjugate them to antibodies to allow potentially targeting those Helicons in interesting ways. And we will continue to do those sorts of things.

We are also very active looking at larger-scale M&A or even smaller types of transactions. You alluded to the fact that we've talked about being involved in some competitive processes as we've evaluated them and kicked the tires. What ends up happening in some of those situations are you have companies that probably don't have necessarily the discipline or don't evaluate the opportunities the way we look at them that when you look at the value that was sort of where those deals actually transacted relative to what we saw as the opportunity on a risk-adjusted basis, we just couldn't get there. But that doesn't mean we won't get there in the future. It really depends on the opportunities that present themselves. We have the ability to basically in a disciplined fashion execute if something makes sense, and we'll continue to evaluate things going forward.

Great. Could we also touch on the Sanofi collaboration here from 2 standpoints, 1 from the IP, but also from the openness you've talked to about working with your partner to potentially add more assets into the collaboration. Where do these efforts stand? And to what extent are you looking externally for assets to bring in? And what characteristics are you looking for in terms of these assets? And if I could just add, how long will this process take?

Maybe I could start with the Dupixent loss of exclusivity question. Clearly, that's of importance to investors given the impressive scale of the product and its continued very strong growth trajectory. Dupixent has a very broad and layered intellectual property estate that has expiries beginning in the early 2030s, including its composition of matter patent in March of 2031, but additional patents that go into the mid-2040s. And these cover other facets of dupilumab, including its manufacturing, its formulation as well as its methods of treatment for various diseases, which really underscores the clinical work that's gone into this antibody that's now approved in 9 distinct diseases. So this -- it's not -- there is no date certainty at this point. I think it's important to consider all of these different patents when trying to figure out when eventually biosimilars could launch. So the most important for us is continuing to drive the growth along with Sanofi and then put up a vigorous defense of the patents that we do have and feel very strongly can extend the runway meaningfully beyond the composition of matter patent in 2031.

Updates will probably come as we approach that date. And as the patent challenges and litigation processes get underway. We're still a few years away from that really happening. So unfortunately, today, I can't tell you when biosimilars will launch, but I can assure you, we are going to mount a very vigorous defense of all of the intellectual property that we have to extend Dupixent's marketing exclusivity for as long as we can.

And just on the maybe 2 aspects. One, the ability to expand upon the collaboration with Sanofi, but also on the life cycle front, the extended IL-13, when could we expect to see data from this agent or the other agents? And when could they [indiscernible].

I'll take the collaboration aspects of it and I'll ask Ryan to IL-13. I think if you look at what we and Sanofi have built with the Dupixent franchise, there's a tremendous amount of value that's been built there. If you just look at relationships with the provider community, relationships with the payer community, even just patients themselves in terms of the trust and confidence that they have in Dupixent in terms of what it's been able to do for them, in terms of, in a lot of instances, changing their lives, in terms of the therapeutic efficacy there.

Being able to leverage that is extremely valuable and it makes a lot of sense if we can do that. With that being said, it's got to make, obviously, strategic and financial sense for both parties. I will tell you with Sanofi's new CEO joining, we've had some initial conversations along those lines. And we'll have to see where those conversations evolve. There are, I think you've alluded to it, a number of different opportunities that we basically have in the pipeline that we can bring as well as whatever Sanofi might be able to bring as well as external opportunities. But we've got the long-acting IL-13, which Ryan will talk about, a long-acting IL-4, basically a [ supi-dupi ] as we call it internally as well as a bispecific. So there's a lot of opportunities to really grow and develop what's there in terms of from an I&I perspective.

Thanks. So Chris, thanks for that. And I think the long-acting IL-13 antibody is the first in a wave of Dupixent, I'll call them next-generation opportunities for us. The long-acting IL-13 antibody went into its first patient earlier this -- last month or earlier this month, the last couple of weeks. And so that will begin a Phase I study in normal healthy volunteers initially. But then move into patients with varying degrees of atopic dermatitis where we hope to learn what the clinical activity looks like and what the durability profile is. We think that this fully human VelocImmune-derived antibody has an opportunity to meaningfully extend the dosing interval that Dupixent currently has without reducing its efficacy and have -- and maintain a similar safety profile.

So we're very excited to be in the clinic. We're moving in as quickly as we can. We believe we have the expertise, the experience, the relationships, all the capabilities to run this program very efficiently start to finish. And to Chris' earlier point on the collaboration, this is an opportunity that Regeneron wholly owns. And we intend to run this program to maximum effect and make sure we get it to the clinic or get it to patients commercially as quickly as possible and in a competitive time frame.

Just switch before we go to the pipeline, just switching over to EYLEA HD. For the [ prefilled syringe ], what are current expectations in the context of both sites?

We don't really have an update to provide, really no change from the information we provided on our Q1 earnings call. We have 2 pending applications with the FDA, 1 with Catalent and another with an alternative vial filler for the prefilled syringe. We continue to expect a decision on one or both of those applications before the end of the second quarter. But I'd say, importantly, the momentum for the product continues to be very strong in its current presentation. And the prefilled syringe is -- we're not dependent on a prefilled syringe to continue to drive growth for this franchise. It's becoming increasingly recognized as the best-in-class product.

The label enhancements that were added in November of last year only continue to add to the bolus of patients on therapy. So we're very excited about the revenue result in Q1 and then hope for a very strong 2026.

And what are the scenarios from here, just given the observations at Catalent, but also the PDUFA being passed for the other site?

So I'm sure Catalent is working very hard to resolve the observations that were noted during their April inspection, and we would expect them to continue to dialogue with the FDA in order to tick all the boxes required to get that facility back to VAI status.

In our alternate manufacturer, as you noted, the PDUFA date was in late April, the FDA opted not to act. There's been continued engagement between this manufacturer and the FDA, and hopefully, progress is being made, and they can approve that file at some point in the future.

And just looking back at the first quarter sales for EYLEA HD, there was impact from pricing and inventory and seasonality. Maybe speak to which factors are specific to 1Q and how to think about that read-through to 2Q from them and beyond?

So as you look at the performance in the first quarter, we talked about the underlying demand approaching basically 10% sequentially and as we talked about, obviously seeing continued momentum just based on the current product profile, as Ryan talked about. The biggest factor that we saw was definitely attributable to inventory. Wholesaler inventory is something that's totally at the discretion of the wholesalers. It was at an elevated level at the end of Q4. They drew down those levels in Q1, which impacted the net sales relative to the demand.

There is pricing headwinds out there. It's a very competitive category, and we obviously are -- have to operate in that environment and do what we feel is necessary to maintain our competitive position out there in the marketplace. So if you look at historical pricing and what you see in the class, we would expect similar competitive pricing pressure to continue going forward.

As we pivot over to the pipeline here, you do have a lot of programs that are reading out over the next 12 months and beyond. Where do you have the most conviction in terms of those programs translating to meaningful revenue?

I think a lot of them are actually being managed by Andres, and I can't wait to get into some of his programs. So certainly, C5, BCMA in myeloma are 3 and then obesity, which we can certainly talk about as not only about weight loss, but also about better managing kind of cardiovascular risk. So those are the 3 that I'm probably most -- 3 or 4 that I'm most excited about. And hopefully, we can have Andres dive into a few.

Perfect. Andres, I'll turn it over to you for any comments here, and we'll jump into some of the -- maybe we could start with the C5 pipeline here.

Great, Salveen. Thank you for having me and the opportunity to share what we are doing in hematology. Quite a lot going on, as was just said. So C5, we are very excited with the prospects of our C5 assets and the approach that we are taking in exploring how different degrees of C5 inhibition may translate in defined and clinical outcomes for patients. We span indications from in hematology, PNH, paroxysmal nocturnal hemoglobinuria, to myasthenia gravis and to geographic atrophy, diseases that are driven by complement dysregulation. And from the earlier on, we hypothesized that maximal C5 inhibition will be required and [ tested ] that question to benefit patients. And we have learned a lot throughout these programs.

I think the one that really the readout taught us a lot about how the degree of complement inhibition may translate or not in clinical benefit has been in myasthenia gravis. And maybe we can go a little bit into the results of our data in myasthenia gravis, which essentially is driving a launch at the end of the year in this disease. And this is where we tested either driving full complement inhibition by combining siRNA that inhibits the production of C5 with an antibody that inhibits the activation of whatever remaining C5 is in the circulation. And what we learned in myasthenia is that you don't need full complement inhibition to actually benefit patients.

Furthermore, the study -- the NIMBLE study demonstrated that single-agent siRNA benefits the vast majority of the patients in the trial. And this was done with what we call a potentially sweet spot. We observed a 70% inhibition of complement while in PNH, we know that we want to drive 100% inhibition of complement to decrease hemolysis. Here, we learned that in this disease that was not necessary. And we are very excited with the results of the clinical trial. We think that we have the potential for the best-in-class in terms of the C5 inhibition. We're looking across different studies where we observed a sustained benefit and improvement in symptomatology to patients. This was -- and when I say sustained, why is this important? Because we observed the benefit throughout the dosing period from beginning to the next dose where patients sustained their symptomatic relief.

And doing so with an administration that is very convenient to patients every 3 months, given subcutaneously, which we think will drive a lot of the future market opportunity for cemdisiran in this disease. Importantly, also, when we look at the study, the safety was very manageable. And when we look at serious -- we have no serious adverse events in single-agent cemdisiran. We had no discontinuations throughout the study period and when we reported at 24-week outcomes, which we think is very favorable within the class. So we think that there is a tremendous potential for cemdisiran there.

Where do you see it being positioned versus the FcRns or Amgen's UPLIZNA?

So that's a great question. So let's start first with why it's different and what is the differentiation. One of the critical, I think, differentiation is, [indiscernible], a very efficacious drug, yes. We have comparable, if not better, to C5 inhibitors in terms of symptomatic improvement. When we look at the duration of that improvement vis-a-vis FcRn is sustained, it's not cyclical. And even in C5 inhibition, it has been observed that you may see worsening of the symptoms as you get closer to the end of the dosing period.

So sustained inhibition and then convenience, of course. We are looking at subcutaneous administration 4 doses a year, which I think, again, will be critical in terms of driving the success of this drug. But I think that one aspect that sometimes goes unrecognized, and we should pay a lot of attention is about safety. We are hypothesizing and based on the data that we observed with minimal adverse events or not minimal, but with no cases of meningitis, with no SAEs throughout the treatment is the fact that potentially the sweet spot that we found where you don't necessarily need to drive full inhibition of complement allows for some remaining complement activity that may potentially help in fighting infections. So we have to generate more data to demonstrate this point. But I think the data from the clinical trial already suggests based on infections, SAEs and so forth that there might be an advantage of cemdisiran.

When you look at where FcRns are depleting all immunoglobulins with other potential for infections, viral infections and so forth, which you don't see with complement inhibition. And when you look at the CD19 inhibitor targeting plasma cells, again, we think that the complement inhibition may be associated with less infections and so forth.

And lastly, I want to highlight the rapid onset of benefit that we observe. We looked at symptomatic relief when we assessed this was at 2 weeks. And in fact, the vast majority of patients already start experiencing symptomatic relief within 14 days of initiation of therapy. CD19s can take months. In fact, it takes half a year to get to that steady state of improvement. And as we know, FcRns and other C5s potentially delay a little bit vis-a-vis what we observed here, but with the problem of this losing of benefit towards the end of dosing.

And in geographic atrophy, you're going to disclose 26-week data. Could you just discuss the desired clinical profile here and the differentiation that you need to see to support further development and the likelihood of this given it's systemically delivered?

Absolutely. And this is an excellent question. So what are we going to learn from the first 225 patients really? The first one is C5, systemic C5 inhibition have an effect on the slope of progression of the growth of the lesions in the eye. That's the first thing that we're going to learn. Also, we're going to learn whether monotherapy or double inhibition with the antibody and siRNA is necessary in this disease. We learn in myasthenia, it's not. We know and we strongly believe that in PNH that's necessary, but we don't know yet in the eye.

Those are the first 2 things that we're going to learn, but I think that the data that is going to emerge also is going to help us further refine the ongoing clinical program in GA.

Now moving to what is that we are looking for. So we're looking at the slope of growth of the lesion. But importantly, in this study, prospectively, we are going to be looking at [Audio Gap] as you know, that has not been done prospectively in any of the clinical trials with injected C5 or C3 inhibitors.

So I want to point out, however, we are looking at 24 weeks. It's a bit early. As you know, most of the benefits are observed longer term, but we're looking at the slope of 24 weeks, and we may get a hint on a potential benefit in terms of visual acuity. Those are the 2 important aspects that we're going to learn towards the end of the year, and we're going to be sharing with all of you as the data becomes available. Of course, we're going to learn about safety, which is always very important. But we think that we will learn more towards the end of the year.

Perfect. Ryan, you touched on obesity being a key focus for the team and we'll see some data by year-end. Maybe help us understand what proof of concept could play out with that data set and then the overall strategy for the obesity portfolio.

Yes. I mean I think for the strategy, it's really about more than just weight loss. I think that's patient -- that has largely been solved, right? I think we're going to focus on other elements, including improving tolerability as well as addressing comorbid conditions and starting with cardiovascular disease. So Hansoh, the company that we in-licensed olatorepatide from, disclosed earlier this year top-line data in their Chinese patients with obesity with weight loss on par with leading agents. But with the GI tolerability profile that was much more favorable than [ like-run ] studies in China were. So we're very encouraged by that, and we're in the process of enrolling a small Phase II study in the U.S. to see if that GI tolerability profile can be replicated. And should it be replicated, I think we will have an impressive competing agent within a category that has room for many, many therapies.

Beyond just the monotherapy opportunity in obesity and type 2 diabetes, we're also in the process of co-formulating olatorepatide with our PCSK9 antibody, Praluent. Of all the miracles that GIPs and GLPs have produced, one that it has not is lowering LDL in the pivotal studies for those agents, something like a placebo-adjusted decline in LDLs was only in the mid-single-digit percentile. So not really having much of an effect on lipids. However, we think that about half of these patients actually have elevated LDL levels and could benefit from being on a PCSK9 inhibitor like Praluent.

So our approach is going to combine these into the same weekly injection that many patients are already used to. And in addition to lowering their weight, we would also expect their LDL to lower on par with what we saw in the Praluent monotherapy studies, which were in the range of 50% to 60% at 6 months. So this is a way for us to enter the market, a large and growing market in a differentiated way. We have other potential combinations to address other comorbidities of obesity that we will talk about at a later time. But certainly, we feel this could be a differentiated opportunity and make a nice -- take a nice part of a large market.

And you announced collaborations on radiopharmaceutical therapies with your agreement with Telix and Antibody-Helicon Conjugates by your agreement with Parabilis. Can you discuss your interest in these technologies and how you envision integrating them into your platform?

Yes. I think this is, as Chris was talking about, opportunities that really complement Regeneron's core strength, which is antibody development as well as genetics, but in this case, primarily focused on antibodies. We're going to use these antibodies that we make with our platform to better direct these radioligands and these Helicons that Parabilis makes in an effort to, in the case of Parabilis, address intracellular pathways that antibody simply can't address. So this is a way of kind of enhancing a core strength that Regeneron already has, but take us to places that we couldn't go with antibodies alone.

So we're very excited to get started with both a lot of work to do, but this could be a very important expansion of our capability set to address some of these different types of opportunities.

Great. With that, thank you so much.

Thank you, Salveen.

Thank you, Salveen.

Thanks, Salveen.

Thank you for joining us. Welcome back to the Bank of America Healthcare Conference. It's my pleasure to have with me our next presenting company, Regeneron Pharmaceuticals. Up here on stage with me are two members that we'll be talking to you for the next 30 minutes. Marion McCourt, who is, of course, Executive Vice President of Commercial, as well as Ryan Crowe, who is Senior Vice President, Investor Relations. Guys, thanks for making the trip over from the East Coast...

[Audio Gap] In exchange, we are not going to be subject to future government pricing mandates, and we'll also have tariff relief through at least January of 2029. So all in all, a very similar construct to the previous deals that were announced. Perhaps one detail that we've included in some of our disclosures is that this includes products that are wholly owned by Regeneron in the United States. So that excludes certain of our alliance products from this agreement.

Are those exclusions inclusive of EYLEA and DUPIXENT?

So we have never made any comments about specific products and because of the confidentiality around these agreements, I can't name specific products, but what I will say is we wholly own EYLEA and EYLEA HD in the U.S., but we do not wholly own DUPIXENT in the U.S.

Okay. So you talked about this $27 billion plan to invest in R&D and manufacturing in the U.S. Can you talk to us over what time frame and how that's going to be invested?

Yes, there's a little bit of mixing and matching of time frames and numbers and exactly what is what. But maybe I can just do a quick summary of that. So we've committed to approximately $9 billion of capital investment through at least the end of the decade, probably 2030, 2031. We expect that to all have been completed. That includes R&D facilities in our Tarrytown headquarters expanding our R&D footprint in Upstate New York as well as with some contract manufacturers we're working with in the United States.

On top of that, so that's around 1/3 of it. The other 2/3 are related to expenses for R&D that will be incurred in the U.S. as well as for manufacturing expenses that will be incurred in the U.S. through approximately the end of the decade as well. So there's a bit of mixing and matching in terms of investment versus what we're going to spend. But all in all, I think very supportive of the U.S. economy, which was one of the objectives of this deal.

Okay. So let's move on to DUPIXENT. Can you just talk about the evolution of the different indications? Rightly or wrongly focus remains on AD. What's your penetration in that indication? And how should we be thinking about uptake. We do our own survey work. We do a lot of checks with physicians. One thing that we've noted is a particular level of excitement, for example, around COPD. So we'd like to hear, maybe Marion and your thoughts on where you are and where you think it's going to go from here.

Sure. Very happy to talk about DUPIXENT. I also thought really briefly just to share with you. Ryan talked about Otarmeni, the product that we're giving for free to patients in the U.S. marketplace. It has been launched. It's a small population of patients babies that have this in young children, this profound hearing loss. Some of you may have seen in the report from the Oval Office as Len and George we're talking about our MFN plan, but also sharing the story of young Travis who is there with his mom and for the first time, hearing her words as she was able to share things like I love you to her son.

So I mentioned Otarmeni, fortunately, it's a very small number of patients and families, but incredibly important that we can make a difference for them.

Over to DUPIXENT, which helps so many patients. So there are 1.4 million patients on therapy right now worldwide. We have nine indications in the U.S. marketplace. I'll give you kind of a brief tour of a product that's at a run rate of about $20 billion a year right now. It's been an amazing journey. My time at Regeneron has been spent with all of our portfolio, but certainly launching DUPIXENT across indications, atopic dermatitis was the first blockbuster indication. Today, we have four because in addition to atopic dermatitis, we also have asthma, nasal polyps, eosinophilic esophagitis. And then more recently, we've launched five more indications I'll talk about the original launches in every indication, we lead the market in new-to-brand prescriptions, total prescriptions.

In some cases, like asthma, we launched it to a very competitive market and quickly the physician experience and the patient experience with DUPIXENT was so remarkable that it became the leading product in category. Atopic dermatitis, I come to you weeks off being at the American Academy of Dermatology and pretty much every KOL I met with didn't -- well, they didn't always use the exact same words, but everyone had the same message is that DUPIXENT is first and best in category. Unlike so many other categories in our industry, sometimes follow-on products give improvements. In the case of DUPIXENT is seen as the standard of care, the gold standard and has helped so many patients with atopic dermatitis.

Children as young as 6 months are being helped by the product in atopic dermatitis and children as young as a year of age eosinophilic esophagitis. So whether it's one of our established, more blockbuster -- all the indications are growing or newer launches, to your point in COPD or bullous pemphigoid, prurigo nodularis, CSU, in all these indications, it's so important that there's a product that's been so well experienced. DUPIXENT, I'm pleased to share with you is the leading biologic for allergists, pulmonologists, respiratory therapists and also for physicians who are treating eosinophilic esophagitis for that particular indication.

But the product, in addition to helping the indication, which has brought the patient to see their physician, it also helps across type 2 allergic conditions. And it's not uncommon for example, that a patient that is suffering with asthma also has nasal polyps or the atopic dermatitis patient who also has some other type of type 2 illness. So I hope I've gotten to answer all your questions.

Maybe just one more moment on COPD. The launch is going very, very well there. Obviously, first biologic to launch four COPD patients and we continue to see great reports from physicians, their patients and continue to help those patients.

So one question I'll throw in there since you mentioned COPD, and it's in line with what we're hearing from physicians is that -- what do you think is the undermet need there? What are the therapies that are approved, not addressing the patients? And what's particularly appealing that you're hearing from your field force on why docs want to try it.

Sure. and directly from physicians as well. I would say the first element for COPD is the unmet need in patients who are on triple therapies but not getting the level of relief, the exacerbations, the difficulty of many patients having to be on oxygen therapy, which is really, really difficult for patient, family and their caregivers. We hear stories of patients coming back in to see their physicians after being on DUPIXENT for COPD and coming off their oxygen therapy, feeling better than they have in years in terms of dealing with their condition. And all the while a product that is convenient to use and is safe to use, so it's made a remarkable difference in these patients.

If I could just add, the competing biologic in the market for COPD has never demonstrated any lung function improvement, whereas DUPIXENT and its pivotal studies demonstrated on approximately 80 ml improvement in FEV1, which is the gold standard for measuring lung function.

So these patients are not only exacerbating less, but they're feeling better. And I think that's probably what they noticed the most. As Maria mentioned, a lot of patients are able to either discontinue or significantly reduce their reliance on oxygen.

So you've been picking up a lot of real estate with all the different indications that you've launched on for DUPIXENT over the last several years. And so naturally, I think people are thinking two things. Number one, your partner Sanofi and extending the IP, which seems like it's largely in their court. But also you as a company have talked about next generation, so what we affectionately call supi-dupi. So maybe you can quickly tell us what you think would be an attractive profile for a next-generation drug.

Yes, sure. I can probably start with that. I think we believe that DUPIXENT as Marion mentioned, is first and best-in-class. But these next-generation opportunities that we've developed in our preclinical pipeline are looking to at least improve on the dosing interval that DUPIXENT currently has, which is every 2 weeks in most indications. So our goal is to extend on that.

And supi-dupi happens to hit the exact same receptor that DUPIXENT does. The issue was trying to put more drug and just trying to get a longer dosing interval simply by adding more drug is a receptor-mediated clearance is something that happens with the IL-4 receptor, which means that you can put more drug into it, but it's unlikely to meaningfully extend the dosing interval.

So we've come up with a new approach using a new antibody that seeks to avoid or at least mitigate this target mediated clearance issue that the IL-4 receptor presents. We haven't discussed exactly how that approach works publicly yet, but I'm sure we'll get into that once we reach the clinic. And we do expect that antibody to be clinic ready by year-end or perhaps in early 2027.

Perhaps in the backing up in terms of what's in the collaboration with Sanofi versus what is not, that supi-dupi , the IL-4 receptor next-generation opportunity is covered by this collaboration because it is the exact same target as dupilumab does today. Other opportunities like the long-acting IL-13, which is about to enter the clinic is not part of the collaboration. So we certainly are working collaboratively with Sanofi in certain areas, but then independently in others. So we look forward to continuing with that.

Would you want to do parallel development of both mechanisms at the same time?

Yes, I think that's -- I think it's in both companies' best interest to maximize all the commercial infrastructure we built, all the commercial leverage that DUPIXENT has established. So -- and I'm sure there's discussions that have taken place and will take place about expanding the collaboration. But I think it's premature to get into exactly what form that takes.

Okay. Now I think partly -- well, definitely because of the success of DUPIXENT, lots of other companies have tried to make tweaks, if you will, and make adjustments to this drug, whether it be an oral version or, let's say, or an oral compound or less frequently dosed. So as you think about the evolution of this market opportunity, knowing what you just said about moving into clinic in the nearer term, does it change the level of differentiation you think you need to achieve just because there might be other options coming around in the beginning part of the 2030s?

So let me start, and I'm sure Ryan has some comments to and you had asked this before, when it comes to penetration in the market for atopic dermatitis, there's only about high teens percentage penetration for patients who could and probably would benefit their lives if they were treated with DUPIXENT.

So what we found is more products have come into the marketplace it actually helps grow the market, educate the market, bring more patients into the treatment continuum.

Obviously, today, DUPIXENT is incredibly highly held by physicians and patients if we're able to bring additional enhancements to product profile in the future, with Sanofi, as Regeneron, that will be incredibly important to the market as well. And I think we're in a good position to do that. We obviously understand the market very well. We have a really experience...

[Audio Gap] differentiation on efficacy, at least in a meaningful way because when you think about the biologic cascade, it really starts at IL-4. So even STAT6 inhibition or degrading is further down the cascade. So perhaps an oral option will be desirable for some patients. But to think it's likely to outperform on skin clearance or itch seems unlikely to us biologically.

So yes, there's going to be perhaps improvements on certain convenience properties or the convenience profile for some of these. But we believe that DUPIXENT, as Marion said, is kind of the top of the cascade and it's going to be very difficult to beat if you're in the space.

Marion, maybe I wanted to ask you, what is the latest that you've heard about patients that are needle phobic, let's say, for AD?

So it's interesting. The evolution of DUPIXENT across indications has demonstrated that for better efficacy for safety and for what is a very easy self-administration for most patients themselves or for family members with children, it has not been a barrier to care as you can see evidence in DUPIXENT performance. It's interesting in the world as well. I think injectables have become more a mainstay across so many different disease areas.

Having said that, if in the future, Regeneron is able to keep everything great about DUPIXENT and give other options for use. Some patients actually now prefer injectables because it's not something they have to remember daily others potentially might be more drawn towards an oral therapy or the -- I think the number of pure needle phobic is probably not what it was in years past. But certainly, we want to be on the cutting edge of that delivery options for patients and doing the right thing.

Is that something that you'd be willing to try to acquire if you thought you found a good asset?

I don't think anything is off the table for us in terms of M&A. I don't want to speak to specific therapeutic areas or targets, but we certainly cast a broad net, look at everything that's going on out there and what we think is interesting scientifically and can be complementary to what Regeneron has, we'd certainly take a look.

Okay. Maybe let's do a couple of questions on EYLEA before we go on to LAG-3, which I get a couple of questions on here and there now. So the HD launch, I think going back a year ago, I think people were still of the view that with the biosimilar for 2mg EYLEA, it was unclear how that franchise in general would survive biosimilar launch. But it does look like from our work, and I'd love to hear your thoughts from your feedback from the field that HD is something that's very appealing to physicians and patients. So maybe can you give us a little bit of color on that?

Without question, certainly, EYLEA HD has the profile of product to be standard of care as EYLEA has been in category. Together, they are the overall innovative branded franchise leaders I'm pleased to report that EYLEA HD is almost half of that in terms of net sales now. The product grew nicely in the last quarter based on demand increases that we shared with you. And certainly, the approval towards the end of November of having Q4 weekly dosing in the label, the RVO indication and also dosing durability out to 20 weeks is really, really important to physicians in choosing the product that is best for their patients.

So we see good performance there, very solid performance and certainly look forward to potentially bringing prefilled syringe into the market as well.

But in spite of that, we still guided and I guided to you on the most recent earnings call that we expect to see in the coming quarter demand growth in the range of about that 10% as we produced prior quarter.

Similarly, we also guided that we would expect to see continued decline -- demand decline in EYLEA, the 2-milligram product in the range of the mid- to high teens.

Okay. And as you think about the market moving forward, what do you think is the most attractive about the HD or even from your competitor, Vabysmo? Is it that it's more efficacious or is it the convenience of less frequent dosing?

So I'd say with EYLEA HD and EYLEA long now the standard of care. Physicians really like the profile of EYLEA HD. They trust the safety. They like the clinical efficacy in indications like RVO. EYLEA had always been the standard of care. There was never wavering of that and it was based on performance. We also see EYLEA HD referred to as the product that's got the greatest durability for patients who can have the extension of dosing. That coupled back to safety and efficacy are the ingredients that the retina community is most looking at.

What on average is the dosing frequency are you hearing right now? It's early.

It really varies by patient, but I can share with you that, when we look at data, looking at durability, EYLEA HD is the product that can achieve the greatest durability for patients when you look at totality of care.

I like very much that we have the Q4 weekly dosing available now because physicians can't always determine after three loading doses on EYLEA HD. They can't always determine which patients can get out to a 7-week dosing interval which is required in most instances for payer coverage. They just didn't know. Now having this assuredness is really helpful. Additionally, having the indication for RVO, where they really wanted to use have been using EYLEA really wanted to use EYLEA HD. That certainly now is something that is available to them as well.

So at EYLEA HD, if you look in totality, has the broadest label, greatest dosing flexibility of any product in the category.

And based on what you said, you do think that when the PFS does come online, that would be meaningful improvement in terms of how doctors see it for patients.

We do think it's important. Physicians as you can see, want to use EYLEA HD, but we do think that flexibility of having the prefilled syringe will be important a reference point for you within EYLEA, about 95% of the use is with prefilled syringe opposite vials. I think what is also remarkable and very, very important is that EYLEA HD is highly held in the minds of physicians. So even though we've had the vial only delivery physicians are using the product, they're having a great experience for patients. And you can imagine for blinding eye disease, efficacy, safety and durability are key ingredients.

Okay. Perfect. So now let's move on to fianlimab to the LAG-3 study. Maybe, Ryan, can you level set for us metastatic melanoma? What do you think is the rough total addressable market opportunity here? And how does that compare to the products that we just talked about, EYLEA, DUPIXENT for Regeneron?

We believe the global metastatic melanoma market opportunity is somewhere in the range of $2 billion to $3 billion. Obviously, there's standards of care, including PD-1 monotherapy, PD-1 plus CTLA-4 and the incumbent PD-1 LAG-3 product that's out there. With fianlimab, Libtayo, we believe that we have a potentially differentiated efficacy profile relative to that incumbent LAG-3 PD-1 product and we expect to get our data very near term. We certainly were encouraged by the promising Phase I data that we generated across three independent cohorts that when pooled, generated a median PFS of about 24 months and a complete response rate of 25%. And those compare very favorably to the incumbent LAG 3 product that had around 10 months of median PFS and around 12% or 13% complete response.

And the differentiator against the CTLA-4 PD-1 combination, I think, is going to hopefully be efficacy as well. But certainly, on the safety side, we see a lot of toxicity with that combination. But at 11.7 months, the median PFS has set the highest bar for efficacy in this setting. So we're very encouraged. We are looking forward to getting this data and hopefully sharing with you guys shortly thereafter.

And what level of top line information should we expect?

That's TBD, but I think Regeneron typically errors on the side of providing more detail in our top line press releases than most other companies. I think it's safe to assume we'll say more than positive study and see a medical conference in 6 months. I would think providing the medians across all arms would be an appropriate level of disclosure and perhaps more depending on the interim overall survival readout and the objective response rates. So we'll see exactly what we get from the DMC when the data reads out and put together a fulsome disclosure, I'm sure.

Okay. After that, I think all eyes will move on to the adjuvant setting. So I think we've all talked about this, but love to hear your updated thoughts on what do you think the read-through is going to be from the metastatic study onto the adjuvant study. And again, as a reminder, you are going to be taking interim looks -- another interim look before year-end?

The adjuvant setting is quite different. I mean with Opdualag, the incumbent LAG-3 PD-1 combination product, the Bristol markets, obviously, they had a positive readout in advanced melanoma but an adjuvant generated a hazard ratio of 1.01 compared to nivolumab monotherapy. So literally, no efficacy whatsoever.

And the biologic rationale that their investigators came up with was that by resecting the tumor, you've essentially removed a lot of the T cells that you're looking to activate with LAG-3 blockade. So that biologically makes some sense to us, but we think that perhaps since we're able to dose much higher than relatlimab can be dosed in an Opdualag maybe there will be residual T cells that we can block that will enable us to generate a positive readout in adjuvant.

I do think it's much higher risk than the advanced melanoma setting. We don't have any Phase I data to support this. But it did enroll very quickly, and we will have a second interim analysis early in the second half of this year, and if necessary, a final analysis before the end of 2026 for this adjuvant melanoma opportunity.

I'll just add, as Ryan was talking about future product. Just a quick reminder to everyone. We obviously have a very experienced oncology team in the marketplace today with Libtayo across our non-melanoma skin indications of basal cell carcinoma, cutaneous squamous cell carcinoma Libtayo has been a really important product to Regeneron into the oncology community and patients.

There, we did recently secure the adjuvant CSCC indication, which has been launched has been incredibly well received. And obviously, we've made a lot of progress in IO therapy in lung. Second most frequently used product today with oncologists. So we look forward to future launches and certainly, potentially, we'll be ready if we have the clinical readout we hope for and an approval to follow.

Okay. And maybe we will wrap it up with this last question, which I think you might have gotten a couple of times in the last week or so. You did make that recent change to the statistical analysis plan. So that's going to now include all patients with at least 6 months of follow-up.

Len and George talked about this a little bit, but maybe can you just reiterate what the genesis of that was when it started? When the idea came and why you think it's important to have it be the case as you go into the readout that this change was made?

Yes. Thanks, Tazeen, for the question. I think there's certainly been some confusion out there about what actually happened, what the time lines for the decisions were. So let me kind of start from the beginning.

We ran this study with originally with two cohorts, a PFS cohort, which was to include the first 1,175 patients or so across four arms, and that was going to be the population that contributed to the primary analysis of progression-free survival.

Upon the 1,176 patient, we were going to begin enrolling a 360 patient cohort that was only going to contribute to the overall survival, secondary endpoint. And that enrollment ran from essentially January through late summer of 2025.

As we move through 2025, we saw a very slow accumulation of PFS events in the PFS cohort, which went for several consecutive months into the second half of 2025. And we were beginning to get concerned about when exactly the readout would occur.

So what we decided to do, and this was in the fall of 2025 was to add the patients that were originally only going to contribute to the overall survival, secondary endpoint to the primary analysis, without changing the number of events required to trigger the readout.

We also added the requirement that every patient would have the opportunity for at least 6 months of follow-up. And we did that because we didn't want to drop in those patients from the old OS cohort and then immediately read out the data when some of those patients would have just begun treatment.

So all patients will have at least 6 months of treatment. We need to reach 399 events in high-dose fianlimab plus Libtayo plus pembro. That analysis and then the low-dose fianlimab versus pembrolizumab. Each of those need to equal 399 and the last patient first dose needs to be at least 6 months beyond that first -- that last patient first dose in order for us to lock the database and read it out.

So it was done because of slow event rates, we made the protocol amendment towards the end of last year. I believe we submitted it to all the global regulatory authorities in November, December time frame. We had to wait until it was signed off by all of them before we began talking about it. And the EU member states that are involved in the study only approved this protocol amendment at the beginning -- towards the beginning of April, so only about a month ago. which is why it only became public then.

So we're now locked and loaded. As I mentioned, we're fast approaching this readout. We're really looking forward to it, certainly have high hopes for this data set and look forward to sharing it with you as soon as we can.

Okay. With that, we're out of time. So thank you, guys, for making the trip over again, and thanks, everybody, for listening. Thank you.

Thank you.

Welcome to the Regeneron Pharmaceuticals First Quarter 2026 Earnings Conference Call. My name is Kevin, and I'll be your operator for today's call. [Operator Instructions] Please note this conference is being recorded.

I will now turn the call over to Ryan Crowe, Senior Vice President, Investor Relations. You may begin.

Thank you, Kevin. Good morning, good afternoon and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our first quarter 2026 earnings conference call. An archived and transcript of this call will be available on the Regeneron Investor Relations website shortly after our call concludes.

Joining me on today's call are Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Executive Vice President of Commercial; and Chris Fenimore, Executive Vice President and Chief Financial Officer.

After our prepared remarks, the remaining time will be available for Q&A. I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement changes to drug pricing regulations and requirements and our drug pricing strategy, intellectual property, pending litigation and other proceedings and competition.

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarter ended March 31, 2026, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available on our quarterly results press release and corporate presentation, both of which can be found on the Regeneron Investor Relations website. Once our call concludes, the IR team will be available to answer any further questions.

With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len?

Thanks, Ryan. Thanks to everyone for joining today's call. We were pleased with Regeneron's performance to start 2026, highlighted by strong commercial execution across our key growth products, continued pipeline progress, a disciplined approach to capital allocation and our agreement with the U.S. government to lower drug prices for American patients while preserving innovation.

Starting with the financials. We delivered double-digit growth across both revenues and earnings. Total revenues increased 19% compared to the first quarter of 2025 and non-GAAP earnings per share increased 15% demonstrating our ability to deliver strong operating performance while continuing to invest in our science and long-term growth opportunities.

Global DUPIXENT net sales increased 31% on a constant currency basis to $4.9 billion in the quarter. Growth was broad-based and driven by continued strong demand across multiple approved indications and geographies, reinforcing DUPIXENT's position as the foundation of our immunology franchise. We also continue to advance our efforts with next-generation therapeutic approaches to strengthen our leadership position in inflammation and immunology.

EYLEA HD U.S. net product sales increased 52% year-over-year to $468 million. We continue to see encouraging physician adoption of EYLEA HD, reflecting confidence in its clinical profile and dosing flexibility. We resubmitted an application seeking FDA approval for filing -- for filling of the EYLEA HD prefilled syringe at Catalent Indiana, where the FDA has recently conducted a site reinspection. In addition, the FDA did not act by the April 2026 PDUFA date for the company's regulatory application for a second contract manufacturer for the PFS. Therefore, this application remains pending. Regeneron and both third-party filling manufacturers are working closely with the FDA to resolve all outstanding issues and we anticipate a regulatory decision on one or both applications during this quarter.

In oncology, global Libtayo product sales grew 54% to $438 million, driven by continued uptake in advanced cutaneous squamous cell carcinoma and advanced non-small cell lung cancer as well as early contributions from the adjuvant CSCC indication, which received FDA approval in the fourth quarter of 2025.

Turning briefly to our pipeline before George provides more details in his remarks, we've continued to make meaningful progress across multiple therapeutic areas so far in 2026. Last week, we received FDA approval of Otarmeni for genetic hearing loss, marking an important milestone for patients with this ultra-rare condition, and we have committed to offering this product for free. While this may seem like an unconventional decision, we believe it's the right one for Regeneron, and it reflects the ethos that we live by, pushing the boundaries of science to benefit humanity.

Moving to other advances in our pipeline. We presented positive Phase III data for cemdisiran, our investigational siRNA that targets C5 in generalized myasthenia gravis, which demonstrated a differentiated efficacy, safety and convenience profile relative to approved myasthenia gravis therapies. We submitted a new application utilizing a priority review voucher and anticipate an FDA decision in the fourth quarter.

In metabolic disease, we enhance or announced positive Phase III data in China for olatorepatide, our in-licensed GLP/GIP receptor agonist with full data expected to be presented by Hansoh later this year.

DUPIXENT achieved multiple regulatory milestones, expanding the eligible patient population to younger age groups and to new diseases. In addition, the FDA accepted our biologics license application for garetosmab and granted priority review with the decision in August, representing another important step forward for our rare disease portfolio.

Briefly on capital allocation. We continue to take an approach that balances internal investment which we believe offers the greatest long-term return for shareholders with direct return of capital through share repurchases and dividends as well as business development. In support of that approach our Board authorized a new $3 billion share repurchase program, reflecting confidence in our business and financial position.

We also recently entered into strategic collaborations with Telix and TriNetX. Finally, last week, we entered into a Most Favored Nation pricing agreement with the United States government, achieving our shared goals of ensuring timely and affordable access to groundbreaking medical advancements for [ Medicare ] patients, maintaining the United States leadership in biotechnology, innovation and manufacturing and addressing the imbalance in the distribution of cost for medical innovation, which we have long argued has placed a disproportionate burden on American patients.

In closing, we've made so far in -- the progress we've made so far in 2026 reflects the strength of our science and execution and sets a solid foundation for an exciting remainder of the year.

With that, I'll turn the call over to George to discuss our R&D progress in more detail.

Thanks, Len. I'll start with our differentiated approach to treating complement-mediated diseases, which was highlighted last week at our latest Regeneron roundtable investor event. Our core strategy is to deploy customized approaches using an siRNA, an antibody or a combination approach, depending on the level and durability of complement inhibition required for each disease. For example, it appears that in generalized myasthenia gravis or GMG, the partial blockade with the C5 siRNA alone delivers optimal efficacy, safety and convenience. While in PNH, complete blockade requiring a combination of the siRNA with our C5 antibody is required to optimize efficacy.

For myasthenia gravis, we presented results from the Phase III NIMBLE trial at the American Academy of Neurology Conference, which were also simultaneously published in The Lancet. Cemdisiran, our investigational C5 siRNA as monotherapy -- as monotherapy, met the primary and all key secondary endpoints with subcutaneous delivery every 12 weeks delivering a 2.3 point placebo-adjusted improvement in the MG-ADL endpoint at week 24.

In registrational clinical trials for the leading approved C5 inhibitors, which are administered as large volume intravenous infusions dosed every 2 weeks or every 8 weeks, placebo adjusted improvements in the same MG-ADL endpoints have ranged from 1.6 to 1.9 points at similar time points.

For cemdisiran, clinically meaningful efficacy was demonstrated by week 2. Moreover, these improvements deepened over time and were sustained through week 24 with no indication of waning efficacy between doses. The totality of the data, including mostly mild to moderate adverse events support a compelling profile for cemdisiran as a stand-alone quarterly therapy for this disease. These data have been submitted to the FDA, and we expect a regulatory decision in the fourth quarter of this year.

In PNH, our Phase III lead-in results reinforce the requirement for the combination of cemdisiran plus pozelimab, our C5 antibody, to deliver complete and sustained disease control, lead-in results suggest that our combination will provide best-in-class control based on LDH measures, and that patients who are uncontrolled on ravulizumab can largely be controlled when switched to our combination. Enrollment in the registrational enabling cohort of the Phase III study is now complete and results are expected late in the fourth quarter of this year.

Additionally, in PNH and as part of our ongoing complement strategy, we recently initiated a first-in-human study evaluating siRNA that targets complement factor B. This approach is initially intended for the 20% to 30% of patients who, despite optimal C5 therapy remain anemic due to extravascular hemolysis but also has the potential to expand to a broader PNH population. If successful, siRNA targeting of CFB could overcome the limitations associated with current CFB inhibitors, which require daily dosing and carry the risk of catastrophic hemolysis if doses are missed.

In ophthalmology, our C5 approach in Geographic Atrophy is on track to deliver interim data from the exploratory cohort of our Phase III study in the fourth quarter of this year, which will help inform our pivotal strategy. As a reminder, we are evaluating cemdisiran with or without pozelimab administered systemically with the goal of slowing the growth rate of GA lesions while avoiding ocular safety issues that have been observed with certain approved intravitreal therapies. However, to ensure that we have optionality depending on what we learned clinically, we have also recently begun clinical development of an intravitreal formulation of pozelimab, and we'll also follow up with a co-formulation of pozelimab with aflibercept since some of the patients also developed wet AMD while being treated for their GA.

Now turning to immunology and inflammation and starting with DUPIXENT. In the United States, DUPIXENT was recently approved as the first and only medicine for allergic fungal rhinosinusitis, or AFRS in adults and children 6 years and older. AFRS is a specific type of chronic rhinosinusitis with nasal polyps that more often require surgery and is associated with higher rates of postoperative recurrence. DUPIXENT was also approved in the United States and Europe as the first targeted medicine for children 2 to 11 years of age with chronic spontaneous urticaria, expanding the eligible patient population beyond adolescents and adults. This approval reinforces the expanding role of DUPIXENT across diseases driven in large part by type 2 inflammation and across a broad range of ages.

Regarding our efforts to develop next-generation approaches to DUPIXENT pathway, we have previously disclosed that we have developed innovative VelocImmune derived fully human, long-acting antibodies and bispecifics that target the IL-4 receptor itself as does DUPI as well as the IL-13 and IL-4 cytokines that act through this receptor. We are on track to initiate a first-in-human trial for our IL-13 antibody by the middle of this year, both in healthy volunteers and in patients with atopic dermatitis, with plans to execute an expedited path to regulatory approvals.

Beyond DUPIXENT life cycle opportunities, we continue to advance our next wave of immunology and inflammation programs. Our goal is to keep exploring genetically validated targets that have the potential to become future pipeline and product opportunities. We're initiating a first-in-human study of an antibody to a target identified by the Regeneron Genetic Center as being genetically linked to several diseases such as lupus, Sjogren and primary biliary cholangitis.

We're also continuing to evaluate the best path forward across respiratory and sinonasal diseases for Itepekimab, our interleukin-33 antibody. In chronic rhinosinusitis with nasal polyp, our Phase III studies are ongoing with the results expected in 2027. Regarding COPD, we, Sanofi and global regulators continue to discuss a potential third Phase III study, though no decision has been made on whether to move forward.

Turning to oncology. On fianlimab, our LAG-3 antibody in combination with Libtayo. Our Phase III study in metastatic melanoma remains on track with results expected later in the second quarter of this year. The primary analysis of progression-free survival will now consider all patients enrolled in the study with a minimum follow-up of 6 months. In adjuvant melanoma, the study continues following the first interim analysis, with the second interim analysis and if necessary, a final analysis, both expected in the second half of this year.

We also continue to advance pivotal studies for Lynozyfic in multiple myeloma and premalignant conditions and expect to have results by early 2027 from our study in multiple myeloma patients that have received at least one prior line of therapy as well as MRD negativity results in 2028 from our study in first-line myeloma patients who are ineligible for stem cell transplant. Our first-line study for odronextamab in first-line follicular lymphoma is fully enrolled. This is the only study exploring a bispecific as monotherapy versus the current standard of care, which is RCHOP, across this bispecific arena.

Moving to anti-coagulation. We initiated additional factor XI registrational studies in stroke prevention in patients with atrial fibrillation who are not candidates for direct oral anticoagulants as well as cancer-associated venous thromboembolism. Additional studies in peripheral arterial disease, peripherally inserted central catheter-associated thrombosis, secondary stroke prevention as well as [indiscernible] in DOAC eligible patients are all expected to commence this year. Initial registrational studies from studies in venous thromboembolism prevention following new replacement surgery are expected in the first quarter of 2027.

Turning to obesity. In March, Hansoh reported positive Phase II results for olatorepatide, or in-licensed GLP/GIP agonist in Chinese patients with obesity, which compared favorably cross-trial to a previous Chinese study of tirzepatide for obesity. In this is randomized double-blind placebo-controlled trials of 604 adults across 33 sites, olatorepatide met its co-primary endpoints and delivered up to 19% mean body weight loss at week 48. We are also encouraged by the safety results, in particular, the gastrointestinal tolerability profile. Hansoh is planning on presenting these promising results at a medical meeting later this year.

Building on this momentum, our olatorepatide Phase II study in obesity is enrolling rapidly and later this year, we expect to initiate 2 global Phase III programs, one in patients with obesity and in other patients with obesity, type 2 diabetes. In parallel, our work on the olatorepatide Praluent combination continues with our first clinical study of weekly Praluent initiating shortly.

In rare diseases, Len already mentioned the FDA approval of Otarmeni formerly known as DB-OTO. This was an incredibly meaningful moment for the company as is not only our first gene therapy approval but one of the most striking successes with gene therapy in history, restoring for this first time a sensory function in humans. As published in the New England Journal of Medicine, nearly half the children who are born profoundly deaf were able to regain hearing at normal levels within one year of treatment. The mother of one of these children recently told the President of the United States, a heartwarming story, of how her son is now able to hear her say that she loved him.

We decided to make Otarmeni free in the United States because we believe it was the right thing to do for these families. We hope this highlights and reminds the world that it is the biopharma industry, which is frequently viewed so negatively that is often responsible for delivering such medical miracles to humanity. Regeneron is a different type of company that attracts the best and the brightest to join our fight against disease because we have a heart and a soul as well as a mission and a willingness to play the long game.

Another rare disease that we have been studying for many years is Fibrodysplasia Ossificans Progressiva, or FOP, a devastating condition in which muscle and soft tissues are progressively invaded and replaced by abnormal bone formation. The FDA has accepted for priority review the BLA for garetosmab or [ active-NAD ] blocking antibody with a PDUFA date in August of 2026. If approved, garetosmab will become the first and only available treatment shown to prevent abnormal bone formation in FOP patients.

In genetic medicines, our first-in-human trials testing siRNAs targeting Superoxide Dismutase or SOD1 in amyotrophic lateral sclerosis, alpha-synuclein for Parkinson's disease and [ MAPT ] Tau for Alzheimer's disease, enrolling patients and our initial NASH siRNA program readings targeting [indiscernible] PNPLA3 and HSD17B13 are expected by the end of this year. Concluding with recent early-stage research updates, the Regeneron Genetics Center recently announced a collaboration with TriNetX to access de-identified electronic health record data from a global network representing 300 million patients, creating an opportunity to connect large-scale genomic and proteomic cohorts to real-world clinical data in ways that can accelerate drug discovery, translation, development as well as providing new ways of addressing digital health issues.

Regeneron also announced a strategic collaboration with Telix to codevelop and commercialize next-generation radiopharmaceutical therapies combining Regeneron's antibody discovery and oncology capabilities with Telix' radiopharmaceutical development and manufacturing expertise. In summary, we remain focused on advancing our late-stage, mid-stage and early-stage programs as well as innovative research, which we firmly believe has the potential to continue to change the practice of medicine.

With that, let me turn it over to Marion.

Thanks, George. Our first quarter results represent a strong start to 2026. Our market-leading brands, EYLEA HD, DUPIXENT and Libtayo, delivered ongoing growth based on their clinical profile and our ability to execute effectively in competitive markets. We begin 2026 well positioned to advance our portfolio and are excited by upcoming opportunities to change the lives of even more patients.

Starting with EYLEA HD and EYLEA, which delivered combined U.S. net sales of $942 million in the first quarter. EYLEA HD net sales were $468 million, representing 52% year-over-year growth. During the quarter, physician demand for EYLEA HD increased sequentially by 10% despite typical first quarter seasonality. Additionally, in the first quarter, wholesaler inventory levels were reduced to the normal range. EYLEA HD now has the broadest label and greatest dosing flexibility of any anti-VEGF medicine following recent label enhancements to include retinal vein occlusion and additional dosing options that range from every 4 weeks through every 20 weeks.

We are encouraged by physician adoption following these label enhancements. Importantly, we also look forward to the upcoming FDA decision for the EYLEA HD prefilled syringe, which if approved, would bring what we believe is a best-in-class device to retina specialists and help drive continued uptake for EYLEA HD.

In the first quarter, EYLEA's U.S. net sales were $473 million, representing a 36% year-over-year decline. This reflects ongoing conversion to EYLEA HD, competitive pressures and patient affordability issues Additionally, during the first quarter, there was only a modest reduction in EYLEA inventory and continued inventory absorption is expected to negatively impact net product sales in the second quarter by approximately $20 million. Looking ahead to the second quarter, we expect to achieve sequential unit demand growth for EYLEA HD that is consistent with the 10% sequential demand growth in the first quarter. Conversely, for EYLEA, we anticipate the demand will decline in the mid- to high teens in the second quarter ahead of the potential launch of additional biosimilars in the second half of the year, coupled with the factors that I highlighted earlier.

Together, EYLEA HD and EYLEA lead the innovative branded anti-VEGF category with more than 100 million injections by EYLEA HD and EYLEA administered worldwide since launch. Additionally, in the U.S., EYLEA HD now contributes half of net sales for our retina franchise.

Turning to DUPIXENT, which continues to transform the lives of more than 1.4 million patients worldwide with type 2 inflammatory diseases that are currently on treatment. In the first quarter, DUPIXENT net sales were $4.9 billion, representing 31% year-over-year growth on a constant currency basis. U.S. net sales grew 35% year-over-year to $5.6 billion sic [ $3.6 billion]. We continue to see growth across all line indications, including recent launches, making DUPIXENT the #1 biologic medicine prescribed by dermatologists, pulmonologists, allergists and ENTs, across the blockbuster indications of atopic dermatitis, asthma nasal polyps and [indiscernible], DUPIXENT continues to drive strong growth based on its differentiated clinical efficacy, safety profile and physicians strong preference for this brand.

Uptake is also strong across more recent launches, including chronic obstructive pulmonary disease, chronic spontaneous urticaria, polyps [indiscernible] and allergic fungal rhinosinusitis. These launches across a growing range of age groups provide a runway for even more patients to benefit from DUPIXENT. With annualized global net sales of nearly $20 billion and significant room for further market penetration across indications, DUPIXENT is well positioned for sustained growth over the near and long term.

Turning to Libtayo, which delivered $438 million in global net sales in the first quarter. In the U.S., net sales were $286 million as Libtayo continues its strong trajectory as the leading immunotherapy for advanced non-melanoma skin cancers. The recent launch of Libtayo in adjuvant CSCC is also an emerging growth driver with encouraging uptake and positive feedback on this paradigm-changing treatment. Libtayo is the only NCCN Category 1 preferred immunotherapy open for eligible adjuvant CSC patients. In non-small cell lung cancer, Libtayo is established as the second most prescribed first-line immunotherapy treatment in the U.S., and we expect continued growth through 2026 as we gain incremental share in lung cancer and drive uptake in adjuvant CSCC.

On to linvoseltamab, which is in its second full quarter on the market, early launch momentum has been driven by positive physician experience, a differentiated clinical profile, lower hospitalization requirements and convenient dosing schedule. We expect continual continued gradual uptake as we work to advance our clinical program in earlier lines of therapy.

I also wanted to spend a moment highlighting our expanding rare disease portfolio. Evkeeza is now in its fifth year on market in the U.S. and delivered net sales of $46 million for the quarter, representing 48% growth year-over-year. Evkeeza is well established as a leading treatment for homozygous familial hypercholesterolemia with more than half of all diagnosed U.S. patients currently on Evkeeza or in the process of starting of Evkeeza.

As highlighted by Len, we are also launching Otarmeni, which is the first and only gene therapy for children born with genetic hearing loss. In addition, we look forward to the anticipated FDA decision on garetosmab in August. Garetosmab is our potential treatment for FOP and has been shown to prevent 99% of abnormal bone formation, influencing our strong first quarter results demonstrate growth potential across our portfolio.

We continue to advance our in-line brands while also preparing for multiple potential indications and new product launches including for cemdisiran for generalized myasthenia gravis, where there is significant commercial opportunity in this large and growing market. We remain well positioned to deliver meaningful benefit to patients worldwide across a growing number of diseases.

And with that, I'll turn the call over to Chris.

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron performed well in the first quarter, highlighted by double-digit growth on both the top and bottom line. First quarter 2026 total revenues grew 19% from the prior year to $3.6 billion, driven by higher Sanofi collaboration revenue as well as strong growth in net sales of EYLEA HD in the U.S. and Libtayo globally. First quarter diluted net income per share grew 15% to $9.47 on net income of $1 billion.

Beginning with the Sanofi collaboration, first quarter total Sanofi collaboration revenues were $1.6 billion, of which $1.5 billion related to our share of collaboration profits. Regeneron's share of profits grew 42% versus the prior year driven by DUPIXENT sales growth and improving collaboration margins. We now expect the Sanofi development balance to be fully repaid by the end of the second quarter. As a result, we expect Sanofi collaboration revenue to step up to reflect our full share of collaboration profits starting in the third quarter.

Moving to Bayer. First quarter net sales of EYLEA and EYLEA 8 mg outside the U.S. were $729 million, inclusive of $333 million of EYLEA 8 mg sales. Total Bayer collaboration revenue was $287 million of which $240 million related to our share of net profits outside the U.S. Other revenue grew 109% in the first quarter to $171 million. This included $101 million related to our share of profits from ARCALYST and royalty income from Ilaris.

Now to our operating expenses. R&D expense was $1.4 billion in the first quarter reflecting continued investments to support Regeneron's innovative pipeline, including pivotal programs across late-stage opportunities in hematology/oncology, complement-mediated diseases at anticoagulation. First quarter SG&A was $560 million, reflecting investments to support the launch of Libtayo and adjuvant CSCC and to drive continued growth of our EYLEA HD. First quarter matching contribution to good days and independent nonprofit patient assistance foundation were de minimis. We remain committed to matching up to $200 million in 2026 to support patient access and affordability.

Non-GAAP gross margin on net product sales was 86% in the first quarter. Our GAAP gross margin was 76%, which was negatively impacted by costs incurred due to a temporary interruption in bulk manufacturing at our Limerick Ireland site. We have now resumed initial production in the facility and expect to resume full production by the end of the second quarter. As a result, we anticipate our GAAP gross margin will continue to be negatively impacted in the second quarter as production returns to normal levels. This interruption has not impacted and is not expected to impact the availability of any products.

Regeneron generated $848 million of free cash flow in the first quarter of 2026 and ended the quarter with cash and marketable securities less debt of $15.8 billion. We repurchased $800 million of our shares in the first quarter and announced this morning that the Board of Directors has authorized a new $3 billion share repurchase program. With this new authorization, we have approximately $3.4 billion available for share repurchases as of today, and we remain opportunistic buyers of our shares.

We have made some minor changes to our 2026 financial guidance including updating our GAAP gross margin guidance to be in the range of 77% to 78%. This reflects actual and expected costs incurred as a result of the aforementioned temporary manufacturing interruption. A full summary of our guidance can be found in our earnings press release published earlier this morning.

In conclusion, Regeneron is off to a strong start in 2026 with financial results that position us well to continue investing in our pipeline delivering breakthroughs for patients and driving long-term value for shareholders.

With that, I'll pass the call back to Ryan.

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A. To ensure we are able to address as many questions as possible, we will answer one question from each caller before moving to the next.

Kevin, can we go to the first question, please?

[Operator Instructions] Our first question comes from Tyler Van Buren with TD Cowen.

So DUPIXENT continues to be a monster delivering strong performance this quarter after quarter after quarter. And it now looks like it will well exceed $30 billion of global sales. So given that we get a lot of questions from investors, not just on life cycle expansion but the Sanofi collaboration, so can you discuss your willingness to work on life cycle expansion efforts within the Sanofi collaboration or come to an agreement on commercializing these assets together in order to take advantage of the DUPIXENT rebate wall and the status of that as opposed to moving life cycle expansion candidates for yourself and potentially further building out the commercial infrastructure?

Tyler, it's Len. Thanks for that very pointed question. Maybe to give me an opportunity to publicly thank Paul Hudson for all the work he did on DUPIXENT since 2019. Thank you, Paul. We wish you good luck in your next chapter. Also as of today, Sanofi's new CEO, Belen Garijo is officially, I think, the CEO today. So we want to welcome Belen and wish her luck, and we look forward to working with her and the rest of her team.

Tyler, you're right, DUPIXENT is a remarkable product. As Marion detailed and George outlined, it's helping so many different people with some -- millions of people with different diseases and is a financial juggernaut for the company. We are always open-minded to transactions certainly leveraging what we've built in terms of both development capabilities as well as commercial capabilities has merit to it. We can do these things ourselves. We've had interest for many different places to sort of take on some of the next opportunities with us. But we're open-minded, and I look forward to talking with Belen and her team in the coming weeks and months, et cetera.

Our next question comes from Terence Flynn with Morgan Stanley.

Great. This is Chris on for Terence. We have a question about fianlimab in metastatic melanoma. Is the PFS differentiation enough to capture majority share? Or do you think you need OS as well?

Well, it obviously depends on the results. it depends on exactly what the PFS results are. But the study is also designed so that -- if we have a substantial OS benefit, we will see that as well. And so the hope, of course, is that the study will show both the PFS and an OS benefit. But the results remain to be seen.

Our next question comes from Chris Raymond with Raymond James. .

This is Sam Lee on for Chris Raymond. Just one on the EYLEA prefilled syringe. So any commentary on why FDA missed the April PDUFA and was that a request for more information or a backlog issue? And then you noted there was a reinspection at Catalent, Indiana, and you've resubmitted. Can we read in between the lines and assume that means the site inspection was positive? And what's kind of your overall guidance on timing for either of these applications?

Yes. So thanks for the question. I think we've told you what we know. We don't -- if the inspection turns out to be positive, then I think they will approve the drug. So we await and both applications are pending. And the only thing I can say is that based on our conversations and how hard everybody is working at this and the FDA, I think, desire to get these sites up to the standards they want as well as get the products out there that are waiting that we anticipate action on one or both of these during this quarter.

Our next question comes from Cory Kasimov with Evercore ISI.

I wanted to ask about Lynozyfic and kind of the outlook in the multiple myeloma space. When we talk with docs, there's obviously excitement about the potential of BCMA bispecifics, the main pushback on [indiscernible] spread adoption is the infection risk they carry, especially in earlier-stage patients. So curious what you make of the debate and how you're trying to mitigate this in your trials going forward?

So the debate of their use compared to what?

Existing standards of care like [indiscernible], et cetera?

So obviously, all of these approaches carry significant infectious risks. As we've shown in our study, the disease itself carries substantial infectious risk. And if you actually look at our detailed data and publications on the matter, it actually turns out that the longer you treat these patients, the more you control your disease, the more functional their bone marrow becomes actually infectious risk goes down over time, which is actually quite stunned. So I think that the profile, if you really look at it, of the bispecifics in general and our bispecific in particular, are very, very promising not only in terms of their impressive efficacy. But in terms of their overall side effect and tolerability profile, including, of course, the infectious risk. So we think that this is going to become the dominant class for the treatment of this disease as well as its precursors. And we believe that if you look at the data that our agent is certainly competitive, if not indeed best-in-class across all parameters here.

Our next question comes from Tazeen Ahmad with Bank of America.

As you think about next-gen DUPI, how are you thinking about the importance of having a late-stage program clearly defined before the U.S. IP for DUPIXENT goes away whenever that might be? Just given the increasing number of potential long-acting injectables and other oral agents that might come online.

Yes. Look, we don't know how long the patent life will be for DUPI because we have lots and lots of intellectual property out there, lots of different types of patents, used patents, formulation patents, in addition, obviously, to the composition patent. In terms of how we think about this, to us, we want to leverage our knowledge and immunology. We don't necessarily think about having to exactly replace or work on. We have nearly 50 things in the pipeline and we're looking forward to bringing as many important ones forward as we can. But we do have a number of these that George, I think, talked about the extended interval DUPIXENT going after long-acting IL-13, IL-4, other diseases that we haven't even covered with DUPI such as allergic diseases, in general food allergies and so forth. So I think there's a lot of opportunity and one shouldn't just focus on a simple replacement or what have you and one shouldn't assume when the patent for DUPI will actually expire.

Our next question comes from Carter Gould with Cantor.

Maybe change it up a bit. For George, as you spoke about the co-injection of C5 with aflibercept, should we think about that as more of a convenience play sort of with the co-administration or potentially more of, I guess, a label expansion as you think about potentially preventing wet AMD, I guess, forming for lack of a better term?

I think those are both interesting possibilities. It could be used to actually prevent the development of the wet AMD and/or to treat the patients who develop it. And very importantly, as you probably know, there's a lot of evidence and suggestions about the causes of the occlusive retinal vasculitis that is seen with the other agents that are, for example, totally different kinds of molecules [indiscernible] and so forth. And these -- some of the characteristics of those molecules are associated with this occlusive retinal vasculatis.

We hope and we believe based on our experience with biologics, with EYLEA and with this particular antibody that we may not only have these convenience benefits. But perhaps most importantly, we may also avoid the very tragic, very horrific side effects that are seen with the existing agents, which would allow them to be much more broadly used. Moreover, we would think, once again, as our experience indicates the history with EYLEA that we can have much longer-acting versions. And moreover, depending on how the data looks with the systemic as well as the local, one could imagine even combined to allow for a very long-acting injections [indiscernible]. So there's a lot of possibilities that could address better safety profile as well as convenience as well as potential even efficacy.

Our next question comes from Evan Seigerman with BMO Capital Markets.

I'd love for you to walk me through the commercial considerations for developing your combo GLP-1/GIP plus Praluent. And how can you accelerate the development to remain competitive in this rapidly evolving market?

Well, the way we look at it, and I think Len came up with this terminology, imagine if you invented a GLP that was as good as the currently best-in-class agent, let's say, tirzepatide, and acted very much the same, but also lowered your bad cholesterol by more than 50% and was shown to decrease your risk of cardiovascular outcomes like heart attacks and death, that GLP would become the preferred GLP on the planet, especially if you priced it at a very similar price.

Why would anybody take any other GLP. We are very by the data that we see coming from our collaborators in China, where the cross trial comparisons show that as we predicted based on our due diligence of the molecule, that it behaves if anything as well as tirzepatide. And of course, our folks in the lab have been busy working developing coformulated forms of this GLP together with our [indiscernible], which we believe we can be delivering by a very similar convenient autoinjector approach using the same approach as the are delivered as well.

And we believe that we can price it very competitively to the GLPs. And we would think that, honestly, any physician prescribing it or any patient thinking about it would say that why would they ever take a GLP, especially since we know of the profound co-morbidities associated with cardiovascular risk and hyperlipidemia in the same population. Why would they ever take a GLP if they had an option of taking a GLP that also lowered their lipids and also decrease the risk of bad cardiovascular outcomes.

To us, honestly, it sort of seems like a no-brainer. Obviously, there will be competition, but we believe we have potentially a best-in-class and a best-in-class PCSK9 and the convenience for many people of these auto injectors is now becoming so pervasive that we think a large segment of the population, we'll offer them. Now this is, of course, not even presuming that the side effect profile that we see in China more broadly pertains in our upcoming global studies. So we think this is a very, very exciting and a very, very large opportunity.

George, could you just correct the misunderstanding about weight loss, not lowering lipids?

Yes. So -- it's -- thank you, Len. It's a great point. As many people obviously know, weight loss and the GLPs can provide cardiovascular outcome benefits. But they do this by creating benefits across a wide variety of different risk factors, and they only lower your bad cholesterol by a few points in contrast to the 50% to 60% lowering that we see with the PCSK9 blockers. So this will be a real add-on in terms of the cardiovascular benefit and the lipid benefit compared to just GLP loans, which, by themselves, though they benefit outcomes, they do very little in terms of your lipid profile. So many patients are obviously left with still high risk based on their lipid profile if they're either obese or especially obese with type 2 diabetes where dyslipidemia there is a very serious and common comorbidity concern.

Finally, the use of cost of lowering drugs is now finally catching up, I think, to the science, where the recommendations are to start earlier and longer. So I think that you've indicated population to lower cholesterol and lose weight is going to be even broader. So as George said, this is a really significant opportunity.

Well, and very importantly, from the public health perspective, though recommendations are all about how focus on your lipids, much earlier, widespread use of lipid-lowering medications. They are dramatically underutilized in the world. Unfortunately, this caused us incredible morbidity and death, heart disease is still the leading cause of death in the United States, in part because of the underutilization of these incredible weapons we have, we think in a Trojan horse sort of way, this will provide incredible public health benefit by having [indiscernible] people who are really so worried about their weight loss also get the lipid benefit, which will have this dramatic benefit, which is unfortunately underutilized and underappreciated.

Our next question comes from Alexandria Hammond with Wolfe.

Can you share a little bit more on your clinical strategy to exhibit that development of your next-gen I&I assets, particularly [ Supi-dupi ]? How do you expect to be able to kind of leverage the changes within FDA to further speed this development up? And has there been an ongoing dialogue with the regulators?

Well, we've obviously -- we're world leaders in this field. We created the field. We did the first studies in atopic dermatitis in the field. And we are well positioned, we believe, to expedite and accelerate the programs as rapidly as possible, and we feel very good about our position and our plans here.

Next question comes from Salveen Richter with Goldman Sachs.

Just regards to the life cycle strategy for DUPIXENT, which is broad and multipronged, where do you feel you have the most line of sight? And how are you optimizing the IL-4 agent or [ Supi-dupi ]?

Yes. I think what George said is that we have a lot of experience here. We don't need to give out all of our details to help any competition that might be out there. But the team knows what they're doing. [ Supi-dupi ] is one that Sanofi and Regeneron have mutual agreement can add to the collaboration. We have the knowledge, the capabilities and the desire to do this as efficiently as possible.

Next question comes from Christopher Schott with JPMorgan.

This is Taylor Hanley on for Chris Schott. We were just wondering on Libtayo. Can you provide any color on the drivers of performance this quarter? Was there anything onetime in there? How much of this was driven by the new indication, CSCC? And is this a good baseline to think about growing off of going forward?

So sure, very happy to take the question. And I think the Libtayo performance certainly is strong. I would characterize the strength based on certainly the advances that we've seen in our our skin indications. Now with adjuvant CSCC, very exciting to help this group of patients with Libtayo. There's been a lot of enthusiasm. And certainly, the clinical profile of Libtayo in this indication is highly distinguishing. We also see performance in our lung cancer indication, U.S. and international performance are strong. I would characterize the quarter though by comparison to a year-over-year comparison in a quarter that had some movement in inventory. We can certainly go back and share more of the details with you on that. But it's a very strong quarter, but there is some comparison [indiscernible] this quarter.

Next question comes from David Risinger with Leerink Partners.

Len and George, my question is for you. So Regeneron spends aggressively on R&D, but the investment community lacks confidence that the company's candidates will move the needle commercially in particular versus established competitors. So could you please highlight the pipeline candidates in late-stage development that we'll have cards turning over in the near term or relative near term, i.e., in the next, I don't know, 18 months or so that you have the greatest confidence in that can generate multibillion-dollar peak sales that investors will be able to see more clearly in the next 18 months or so.

That's perhaps the most penetrating -- in the 160-odd conference calls have done, penetrating in detailed question. But unfortunately, David, probably take several hours to answer. We have a robust pipeline. We do have, obviously, highlighting the C5 franchise, where we'll have more data and an approval action. We will have 11, I think, Phase III trials ongoing in anticoagulation program. which is a massive opportunity. We have our Lynozyfic and our ogenextomab, our bispecifics in myeloma, in lymphoma are ongoing. I think George just talked about our [ ola plus and ola plus ally ] as the near term. And obviously, even in this quarter, we have fianlimab plus Libtayo with metastatic melanoma. So we -- maybe that I'll leave that for openers, but we -- and we have more and more things. But we've got some exciting data coming out that we haven't even talked about, and I didn't just mention. So lots going on when you have 48 exciting things in development.

Can I just say, I mean I want to comment that past performance should be the strongest indicator of future performance. There's only one company in recent history that of its own labs produced two $10 billion plus blockbusters. And let me remind you that I think you and probably a lot of other investors never saw those coming or ignored what we were saying about them. So I think that Investor confidence, I think, should in large part be reflecting historical performance and the recognition that where blockbusters come from sometimes for the investor community can't be directly anticipated

And the best way of producing very important big drugs is by having very exciting molecules across all stages of development that have enormous opportunity. And if you just look at our oncology programs, whether it's the [indiscernible], whether you look at Lynozyfic, whether you also look at odronextamab in follicular lymphoma. These are all potential blockbusters. The C5 franchise is a pipeline in a franchise, multiple blockbuster opportunities there are factor XI customized approaches are looking more and more exciting, especially based on competitive data using, we think, inferior and less convenient approaches. And we just covered the obesity opportunity, which arguably to become the preferred obesity approach that not only addresses obesity, but more aggressively addresses cardiovascular morbidity. So I know it's hard to think of a more exciting pipeline in the entire industry.

We have time for 2 more questions, Kevin.

Our next question comes from Geoff Meacham with Citi.

On fianlimab and lung, I just wanted to see if you guys can give us a bit more context for not moving to Phase III, maybe what was observed in the data? And from a tolerability perspective, is there any read-through to melanoma or broader solid tumor in terms of strategy?

Yes. I think that we've been talking about this for a long time. I mean we never indicated that we were excited about this opportunity. Our data from earlier-stage studies was always pointing us to the melanoma opportunity. Once we see that data, it will certainly guide our thinking forward and in terms of going into additional cancer settings as well. But as we've been saying for a while, we never had any reason to really believe that this was going to be a game changer in the lung cancer space.

And Geoff, there's no negative read-through from any new side effects or anything unanticipated.

Last question, please, Kevin.

Our last question comes from Brian Abrahams with RBC Capital Markets.

We were intrigued with the inclusion of milder patients in your long-acting IL-13 study versus contemporary AD trials. So I was wondering if you could talk about the potential untapped opportunity for systemic biologics here and the degree to which you can broaden the market even beyond where DUPI is used now?

Just certainly in patients with mild disease, there's a lot of unmet need. So this is a potential area for greater understanding in advance for treatment. I think we'll have to wait and take a look at clinical profile and opportunities and determine from there, but it is a large population. And when the patient or the parent of the child with mild disease, it really isn't mild, it's aggravating, it's difficult. And certainly, there's a lot of unmet need and potential.

And I have to say there was certainly in the early days of bias by investigators and the agency against using a powerful biologic. It could be immunosuppressive. Remember, we did find it to be immunosuppressive. In fact, in the moderate to severe cases of atopic dermatitis, we actually saw less infections in patients who had skin lesion healing. It is not immunosuppressive on the side of the immune axis, which deals with the kind of infections that people are used to with biologics or might be with some of the orals that suppress both arms of the immune system, as George has talked many times, the type 2 immunity is not something we rely on to keep us healthy from infections, might play some role in parasitic infections. But you've got so many people having been treated now and now thinking about going earlier makes some sense.

All right. That's all the time we have for today. Thanks to everyone who dialed in for your interest in Regeneron. We apologize to those folks remaining in the Q&A queue, who did not have a chance to hear from today. As always, the Investor Relations team at Regeneron is available to answer any remaining questions you may have. Thank you once again, and have a great day.

Thank you. Ladies and gentlemen, this does conclude today's presentation. We thank you for your participation. You may now disconnect, and have a wonderful day.

Welcome to Regeneron's conference call to discuss its C5 Complement Development Program. My name is Shannon, and I will be your operator for today's call. [Operator Instructions] Please note that this conference call is being recorded.

I will now turn the call over to Ryan Crowe, Senior Vice President, Investor Relations. You may begin.

Thank you, Shannon. Good morning, and welcome to our Regeneron Roundtable investor event, a series of presentations spotlighting key opportunities across Regeneron's pipeline. Today, we will focus on our C5 Complement Development Program built around cemdisiran, an siRNA that targets C5, and pozelimab, an antibody that also targets C5.

Before we begin, I would like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Now let's begin. Regeneron has 5 key late-stage programs that are poised to deliver meaningful advances over the near, medium and long-term across diverse therapeutic areas, including solid tumor oncology, myeloma, complement-mediated diseases, anticoagulation and obesity. Additionally, our early-stage pipeline includes opportunity spanning inflammation and immunology, ophthalmology, cardiovascular and metabolic disease and neurology. We anticipate featuring many of these programs in Regeneron Roundtables in the months and years ahead, reflecting the excitement we have for this next wave of innovation.

We have used the Regeneron Roundtable series to provide focused program level deep dives on some of our most important late-stage development programs rather than trying to cover the entire pipeline in a single event. Today's C5 Roundtable follows the November 2025 Roundtable on the Factor XI development program for anticoagulation disorders and the December 2025 Roundtable on the Lynozyfic development program in multiple myeloma and premalignant conditions. We believe these late-stage programs are all poised to deliver meaningful advances over the next few years, bringing value to both patients and shareholders.

Today's roundtable will cover our C5 development program and in particular, how cemdisiran and pozelimab can be utilized to treat multiple complement-mediated diseases by matching the right therapeutic approach to disease biology with the goal of optimizing efficacy while mitigating safety events. And paroxysmal nocturnal hemoglobinuria or PNH, the combination of cemdisiran and pozelimab is designed to deliver rapid, complete and uninterrupted C5 inhibition addressing persistent hemolysis associated with current standards of care. Registrational data in PNH is expected in late 2026.

In generalized myasthenia gravis, or gMG, the disease biology supports only partial C5 inhibition that can be achieved with some cemdisiran monotherapy. We recently submitted an NDA taking approval from the FDA using a priority review voucher and expect a decision in the fourth quarter. And in geographic atrophy, we're exploring both monotherapy and combination approaches with initial Phase III lead-in data anticipated late this year. Taken together, this program highlights the flexibility of our siRNA antibody approach and positions our C5 franchise for multiple meaningful near-term clinical and regulatory catalysts.

Now let me introduce our speakers and the topics they will discuss during today's roundtable. This cross functional speaker panel consists of leaders across Regeneron's research, clinical development and commercial areas. First, Dr. George Yancopoulos, Regeneron's Board Co-Chair, President and Chief Scientific Officer, will provide a strategic overview of the C5 program including our siRNA with or without an antibody approach and how we believe it offers different levels of complement inhibition for different diseases. Next, Dr. Andres Sirulnik, Senior Vice President and Clinical Development Unit Head for Hematology will discuss the ongoing PNH and geographic atrophy development programs, which are both in late-stage clinical development. Following Andres will be Dr. Umesh Chaudhari, Vice President and Global Program Head of our C5 program, who will discuss generalized myasthenia gravis, where cemdisiran monotherapy has demonstrated robust efficacy with quarterly dosing, supporting a differentiated clinical and convenience profile.

This follows yesterday's publication of results in the Lancet and data presentation at the American Academy of Neurology for positive Phase III NIMBLE results were presented for the first time. And finally, Soma Gupta, Vice President, Commercial New Products, will lead the discussion on the commercial strategy and outlook focusing primarily on the upcoming potential of cemdisiran launch in gMG. We will then use the remaining time for Q&A.

With that, let me now turn the call over to George.

Thank you, Ryan. Our pioneering C5 program is the first time an antibody and an siRNA that target a single pathway have been combined, in this case, to inhibit complement. Pozelimab, a fully human antibody, which was derived using our VelocImmune technology was FDA approved in 2023 for the treatment of CHAPLE disease, an ultrarare indication. Cemdisiran is an sRNA designed and initially developed with our collaborator, Alnylam. Regeneron has licensed cemdisiran for use as both a monotherapy and in combination with pozelimab. Each of these reagents serves a different role in inhibiting complement. Cemdisiran reduces C5 production in the liver, where the majority of C5 is synthesized while pozelimab neutralizes any residual C5 protein in the circulation that was not already blocked by cemdisiran. This combination completely blocks the C5 pathway. There are several advantages to this dual approach compared to other complement inhibiting therapies.

First, having the 2 reagents gives us the flexibility to treat different diseases that require different levels of target inhibition to maximize efficacy. We also have data suggest that the combination approach will provide complete rapid and durable C5 inhibition that is not achievable with other therapies even at higher doses. Additionally, our antibody plus sRNA combination may enable lower antibody dosing in a highly convenient subcutaneous formulation. We believe these advantages will be critical across these distinct diseases.

Our C5 program's flexibility is reflected in the range of therapeutic areas and indications that we are pursuing. Because complement-mediated diseases require different levels of C5 inhibition, we can tailor the dose and the modality, siRNA alone, antibody alone or combination based on the disease biology and clinical need. CHAPLE disease is an ultra-rare, life-threatening pediatric disease caused by CD55 deficiency, where pozelimab monotherapy at high doses has demonstrated clear clinical benefit. In PNH, we believe the disease biology requires near complete uninterrupted C5 inhibition to prevent breakthrough hemolysis. The combination of the cemdisiran sRNA and the pozelimab antibody enabled deeper and more durable control of C5 than ravulizumab, a leading C5 antibody on its own, supporting our dual mechanism approach.

In generalized myasthenia gravis, we have now demonstrated that robust and sustained efficacy can be achieved with only partial complement inhibition using cemdisiran monotherapy, which delivered strong clinical benefit in this disease, while preserving residual complement activity, supporting a potential best-in-class efficacy and safety balance with quarterly subcutaneous dosing. In geographic atrophy, the biology and optimum level of complement suppression is still being explored. Thus, we are evaluating both cemdisiran monotherapy and the cemdisiran/pozelimab combination to identify the right balance of efficacy and safety in a large heterogeneous population. The key takeaway is that this is not a one-size-fit-all C5 program. We believe the flexibility of having an sRNA and an antibody allows us to match the treatment intensity to disease biology, creating a pipeline and a product opportunity across multiple disease settings.

Slide 10 illustrates the difference in C5 inhibition between cemdisiran monotherapy and the cemdisiran/pozelimab combination as well as why different complement-mediated diseases may require different levels of C5 inhibition to achieve optimal clinical benefit. The CH50 graph on the left was presented yesterday at AAN from the cemdisiran Phase III NIMBLE trial in generalized myasthenia gravis. Cemdisiran monotherapy delivered rapid and durable complement inhibition, which reached 77% by week 24, but was sufficient to drive robust clinical efficacy in generalized myasthenia gravis. The combination of cemdisiran and pozelimab achieved near complete C5 inhibition as early as week 12. That's important in diseases like PNH that require near complete uninterrupted C5 inhibition, which is where the siRNA and antibody combination becomes critical.

In contrast, efficacy in generalized myasthenia gravis was achieved without full complement inhibition, supporting the concept of preserving residual complement activity may be both effective and potentially favorable from a safety perspective. This precision-based approach underpins our strategy, match the right level of C5 suppression to the biology of each disease rather than forcing a one-size-fit-all solution.

Now I will turn it over to Andres to discuss PNH and geographic atrophy.

Thank you, George. Paroxysmal nocturnal hemoglobinuria or PNH is an acquired life-threatening hematologic disorder driven by uncontrolled C5 activation due to loss of CD55, CD59 on red blood cells, resulting in chronic intravascular hemolysis, thrombosis and substantial morbidity. Current standard of care therapies improved survival, but often fail to fully normalize ADH or prevent breakthrough hemolysis and patients with extravascular hemolysis remain inadequately served by existing C5 inhibitors or require complex multidrug regimens. The PNH landscape now spans multiple mechanisms, including inhibitors for complement Factor V, Factor III, Factor B and Factor D, yet no current approach consistently delivers complete sustained terminal complement inhibition with convenient dosing highlighting an opportunity for differentiation.

The cemdisiran/pozelimab combination is designed to address these gaps by reducing C5 production in the liver with cemdisiran and blocking residual circulating C5 with pozelimab, thereby enabling continuous durable C5 separation with subcutaneous dosing. The Phase III leading data, which I will review shortly, suggests this dual mechanism approach is needed to achieve potentially best-in-class disease control and improve on current standards of care.

Slide 13 is the trial design for the ongoing Phase III ACCESS-1 trial in PNH patients. This head-to-head study directly compares cemdisiran plus pozelimab against ravulizumab in cohort A and eculizumab in the registrational cohort B, enabling a rigorous assessment of disease control versus established C5 inhibitors that are considered today's standard of care for PNH. We are announcing today that enrollment in cohort B is complete, positioning the program for a registration-enabling data readout by the end of this year.

Taken together, the Phase III design, comparator choice and endpoint selection are intended to demonstrate that cemdisiran plus pozelimab can deliver more complete and consistent disease control than current standards of care, supporting best-in-class potential in PNH.

As a reminder, the exploratory cohort A from the registrational PNH trial readout in late 2024, supporting the combination's potential in this setting.

Now let's take a look at the results of cohort A. Slide 15 showcases the 26-week data generated from this exploratory cohort. Patients treated with our C5 combination achieved greater disease control compared to the current standard of care, ravulizumab and nearly all patients on the cemdisiran plus pozelimab combination were able to achieve normal LDH levels. Through week 26, cemdisiran plus pozelimab combo leads to average LDH levels of 0.8x below the upper limit of normal with 96% of patients maintaining adequate control of hemolysis. This compares favorably to ravulizumab with average LDH levels of 1.2x the upper limit of normal at week 26, with 80% of patients maintaining adequate control of hemolysis. Patients on ravulizumab were then switched to the cemdisiran/pozelimab combination in the extension study. At the start of the extension study, 13 out of 19 patients treated with ravulizumab had adequate control of LDH. After switching to the combo, all but 1 patient achieved LDH control, including 4 of 5 patients who had failed to achieve LDH control while on ravulizumab.

Our novel C5 combo approach enable complete rapid and interrupted and durable inhibition of terminal complement.

And as I mentioned before, enrollment in cohort B is complete, and we now anticipate reporting data from this registration cohort in the fourth quarter of this year. And Regeneron is still pursuing additional agents for PNH patients given the high unmet need. We recently initiated a first-in-human study of our siRNA targeting complement Factor V initially intended for 20% to 30% of patients who remain anemic despite optimal C5 therapy due to extravascular hemolysis with the potential to expand to a broader PNH population. We hope to share data from this ongoing program in the near future.

And now to geographic atrophy, starting on Slide 19. Geographic atrophy is a late-stage irreversible form of dry age-related macular degeneration that leads to progressive vision loss and has a meaningful impact on daily functioning, including reading, driving and recognizing faces. A substantial body of evidence implicates the complement system in GA pathogenesis, including genetic associations, histopathology and preclinical studies validated further by the fact that both approved GA therapies locally inhibit complement. However, despite 2 approved products, there remains significant unmet need in geographic atrophy as these approved therapies have slow lesion growth, but have not prospectively demonstrated preservation or improvement of visual function.

Also, current intravitreal therapies require frequent intravitreal injections and carry meaningful ocular safety risks. Cemdisiran plus pozelimab is being evaluated as a differentiated systemic approach with the goal of delivering meaningful disease modification while potentially avoiding the ocular safety issues associated with the intravitreal administration.

Slide 20 depicts the trial design of the ongoing Phase III SIENNA trial, which is a global randomized, double-mask placebo-controlled study in patients with GA secondary to AMD that will evaluate whether systemic C5 inhibition can deliver a meaningful disease-modifying effect while potentially avoiding ocular safety issues seen with intravitreal approaches. For this study, there will be a total of approximately 975 patients in the trial, which is designed as a seamless 2-cohort program similar to how we structure the Phase III PNH program. While Regeneron has not previously generated clinical data in this indication, we have decided to go straight to a Phase III program given our deep understanding of disease biology and data generated in other complement mediated diseases.

As we have previously stated, cohort A is fully enrolled, and we expect interim data in the fourth quarter of 2026. These results from approximately 225 patient cohorts will guide with a systemic C5 inhibition demonstrates sufficient therapeutic effect in GA, whether monotherapy, is sufficient or combination therapy is required and will inform future trial design parameters. Note, the cohort A is not powered for statistical significance and is not a regulatory readout, but rather it serves as a decision enabling checkpoint.

Systemic C5 inhibition offers a fundamentally different treatment paradigm compared to today's treatment options. Regeneron's approach moves beyond intravitreal only therapy by enabling systemic administration, which may allow treatment of bilateral disease without separate injections in each eye, addressing a key burden of current GA care. Approved GA agents will require every month or every other month intravitreal injections often in both eyes, a systemic subcutaneous option with meaningfully reduced procedural burden for patients and retina specialists, especially for those patients who may be co-treated with anti-VEGF therapies.

In terms of safety, current intravitreal therapies have reported ocular safety events, including occlusive retinal vasculitis, which has caused catastrophic blindness in some patients. A systemic approach is anticipated to reduce localized ocular risk, representing a potentially important safety advantage.

We also have an opportunity to go beyond slowing of lesions growth and prospectively demonstrate a functional benefit. Regeneron's program aims to show greater reduction in GA lesion growth alongside preservation of visual function, raising the bar on meaningful clinical outcomes. Further, today's therapies require frequent in-office administration by retinal specialists. Regeneron's approach introduces the potential for self-administration via subcutaneous dosing, reducing clinic visits and improving patients' quality of life. The C5 program leverages with Regeneron's deep experience with complement inhibition and established ophthalmology presence, positioning us to pursue a differentiated scalable opportunity in a large and growing GA market.

In parallel, Regeneron has also initiated development of an intravitreal pozelimab formulation aimed at longer durability, potential safety advantage from a non-pegylated reagent and potential to coformulate with anti-VEGF therapy, providing strategic flexibility across patient segments.

Now I will turn it over to Umesh, our Global Clinical Head of C5, who will discuss general myasthenia gravis.

Thanks, Andres. First, let me give a bit of background on generalized myasthenia gravis, starting on Slide 23. gMG is a rare chronic autoimmune disease where pathogenic autoantibodies, most commonly against the acetylcholine receptor activate the complement cascade, leading to a formation of the membrane attack complex at the neuromuscular junction. This complement mediate injury disrupts the neuromuscular transmission, damages postsynaptic membrane and ultimately drives the muscle weakness and fatigue that characterize this disease. Importantly, this is not simply an antibody-mediated signaling issue. It is a complement-driven structural injury, which is why inhibiting C5 has proven clinically effective.

Despite advances in treatment, there remains a clear unmet need. Many patients experience incomplete, fluctuating responses waning between doses, safety trade-offs and high treatment burden, particularly with chronic IV or frequent dosing regimens. Our goal with cemdisiran is to address this by delivering sustained targeted C5 inhibition that aligns with gMG biology, providing rapid efficacy, durable disease control and meaningfully reduce treatment burden.

Slide 24 outlines the Phase III NIMBLE trial, which was designed to evaluate cemdisiran and cemdisiran plus pozelimab combination in patients with symptomatic generalized myasthenia gravis. NIMBLE is a randomized, double-blind, placebo-controlled study, enrolling acetylcholine receptor positive patients on stable background therapy who have initiated meningococcal vaccination reflecting real-world clinical practice. This study includes a 24-week placebo-controlled double-blind period, which is the basis for the primary and key secondary efficacy analysis, followed by a 28-week double blind extension and open-label treatment period and then long-term post-treatment follow-up. The primary endpoint is the change from baseline in myasthenia gravis activities of daily living, or MG-ADL total score at week 24 with a key secondary endpoint of change in quantitative myasthenia gravis or QMG total score at week 24. During the 24-week double-blind treatment period, all patients -- all treatments were administered subcutaneously with cemdisiran dosed every 12 weeks, highlighting the convenience of a quarterly regimen.

As shown in the efficacy data presented subsequently, cemdisiran monotherapy met the primary and all key secondary endpoints, demonstrating rapid, deep and durable clinical benefit without weaning across the dosing interval.

Now let's describe the results from this registrational study. With this -- with quarterly subcutaneous dosing, cemdisiran met the primary endpoint delivering a 2.3 point placebo-adjusted improvement in the MG-ADL total score at week 24, which is clinically meaningful and statistically significant. The magnitude of benefit compares favorably to historical C5 inhibitor data, which have generally shown 1.6 to 2.1 placebo-adjusted MG-ADL improvements in their respective pivotal studies at similar time points.

Importantly, efficacy emerge rapidly with clinically meaningful improvements seen as early as week 2 continued to deepen over time and was sustained without any evidence of waning across the full dosing interval. The key secondary endpoint, QMG, was also met with a 2.8 placebo-adjusted improvement, reinforcing the consistency between patient-reported and physician-assessed outcomes. While the combination arm also met the primary and key secondary endpoints, it did not provide additional benefit over cemdisiran monotherapy in gMG, demonstrating that complete complement blockade is not required to achieve robust clinical benefit in gMG.

Taken together, these data suggest that cemdisiran delivers rapid, deep and durable efficacy with markedly reduced treatment burden, positioning it as a best in -- potentially best-in-class C5 targeted therapy for patients with gMG.

Safety also appears to be a differentiating factor for cemdisiran in this indication. Overall, safety profile was favorable and consistent with expectations for the C5 class with no new or unexpected safety signals observed across treatment arms. Cemdisiran monotherapy was generally well tolerated with no serious infections, no meningococcal infections and no treatment discontinuations during the 24-week double-blind period. Rates of adverse events, serious adverse events and severe adverse events were numerically lower with cemdisiran versus placebo and combination therapy, supporting the safety of partial C5 inhibition in gMG.

It is also worth noting that only 1% of patients in the cemdisiran cohort experienced the adverse event of myasthenia gravis compared to 17% of patients randomized to placebo, further reiterating the treatment of effect of cemdisiran in this setting.

Taken together, these data support a differentiated benefit risk profile, pairing strong efficacy with a generally manageable safety profile suitable for chronic use.

Slide 27 summarizes what we believe is a clearly differentiated clinical profile for cemdisiran in generalized myasthenia gravis. From an efficacy standpoint, cemdisiran delivered clinically meaningful improvements within the first 2 weeks with depth of response that compares favorably within the C5 class and remains durable across the full dosing interval. Importantly, that efficacy is sustained without waning, supporting a quarterly dosing regimen that meaningfully reduces treatment burden for patients managing a chronic disease.

From a patient experience perspective, subcutaneous administration and infrequent dosing differentiates cemdisiran from both IV-based C5 inhibitors and more frequent cyclic daily or weekly options.

On safety, through 24 weeks, cemdisiran demonstrated a generally manageable profile with no treatment discontinuations, no serious infections and lower rates of severe adverse events relative to placebo. Taken together, these attributes position cemdisiran as a differentiated potential advanced therapy option, balancing strong clinical performance with convenience that is highly relevant in a real-world gMG management.

This slide highlights how cemdisiran differentiates within the C5 class, specifically, compared cross-trial to Ultomiris, an infused C5 inhibitor. Cemdisiran achieved rapid, deep 2.3-point placebo-adjusted MG-ADL improvement with only 2 subcutaneous injections over a 24-week treatment period. Ultomiris requires 4 infusions over a 26-week treatment period and demonstrated a 1.6-point placebo adjusted MG-ADL improvement. We believe cemdisiran has the potential to offer a best-in-class profile, combining strong sustained efficacy with a substantially reduced treatment burden through convenient, quarterly subcutaneous dosing.

Now compared cross-trial to Vyvgart, the leading FcRn inhibitor, which have grown the advanced therapy market for gMG. We believe cemdisiran can offer a differentiated clinical profile. A key distinction is durability as cemdisiran maintains efficacy throughout the dosing interval without the cyclic waning of efficacy that can be seen with Vyvgart and the other SCR-based approaches.

Unlike Vyvgart, which is dosed cyclically, cemdisiran provides deep and continuous improvement in MG-ADL scores with only 2 injections over 24 weeks. That durability enables quarterly subcutaneous dosing, which meaningfully reduces treatment burden compared with frequent cyclic administration schedules. This is particularly relevant in a chronic disease like gMG where patients require sustained symptom control rather than episodic relief.

And finally, Slide 31 highlights how cemdisiran differentiates relative to the newly approved B-cell depleting agent, particularly in speed of response and durability. From an efficacy standpoint, cemdisiran delivers rapid placebo-adjusted improvements in MG-ADL, with clinically meaningful benefit observed within weeks rather than months. Also, the mechanism matters. By directly targeting complement-mediated damage at the neuromuscular junction, cemdisiran provides symptom control without relying on broad immune cell depletion.

While B-cell depleters may offer a potentially longer dosing interval, that does come with prolonged IV infusions that require premedication and post-infusion monitoring requirements.

In summary, the gMG market is very competitive, and we believe cemdisiran has the potential to offer a differentiated alternative to currently approved advanced therapies with strong efficacy, generally manageable safety and quarterly subcutaneous dosing.

With that, let me turn the call over to Soma, who will now discuss the commercial opportunity.

Thanks, Umesh. We believe our C5 program represents a late-stage multi-indication, multibillion-dollar opportunity, spanning gMG, PNH and GA. Today, these markets combined generate about $9 billion in annual globalized sales and continues to grow rapidly, supported by strong underlying prevalence dynamics. gMG represents the first and largest near-term opportunity with an FDA decision and potential product launch in the fourth quarter of 2026. As Umesh has highlighted, we believe cemdisiran's clinical profile, including quarterly subcutaneous dosing and strong efficacy, has the potential to position it competitively in the rapidly expanding advanced therapy market. PNH represents another potential large commercial opportunity with current annual worldwide sales of around $3 billion.

The cemdisiran and pozelimab combination targets patients who require complete and uninterrupted C5 inhibition, offering a differentiated option versus entrenched standards of care. And then rounding it out, geographic atrophy provides the largest population with over 1 million diagnosed patients in the U.S. alone. Currently approved agents have started to build this space, delivering just over $1 billion in annual worldwide sales today, reflecting the early stages of disease modifying agent adoption.

A systemic approach could differentiate meaningfully here versus chronic intravitreal injections if efficacy can be demonstrated. Two important commercial considerations for our C5 commercial strategy I'd like to highlight. First, Regeneron are solely responsible for development, manufacturing and commercialization for both cemdisiran monotherapy as well as for the combination and pay modest royalties on net sales to Alnylam. Secondly, our commercialization strategy is highly indication-specific, allowing us to optimize value and access [indiscernible]. This allows us to align pricing and access to the underlying disease biology, market size and competitive dynamics.

We believe this C5 franchise presents a long-term growth opportunity for Regeneron given this derisk program, multiple shots on goal and staggered launches.

Now let me focus on the near-term gMG commercial launch and strategy. The gMG market is undergoing a structural shift driven by rapid adoption of advanced therapies as treatment goals move beyond symptom control towards durable disease modification. Advanced therapy penetration is relatively low today at just 15%, but is expected to grow materially closer to 40% over time, creating a multiyear growth category. Both FcRn inhibitors and C5 targeting agents are expected to account for the majority of incremental sales as patients cycle through earlier lines of therapy more quickly.

Despite increasing competition, the market is expanding faster with total U.S. gMG net sales expected to more than double over the next several years to over $12 billion in annual net sales by 2032, supported by newly approved agents, higher treatment rates and longer durations of use. Cemdisiran is expected to enter this market at an inflection point as the first siRNA in gMG offering a differentiated mechanism, quarterly dosing and a profile well aligned with physician and patient preferences for durability and convenience. Importantly, this expansion in the use of advanced therapies broadens the treated population, potentially allowing differentiated agents to succeed without having to displace incumbents.

Our objective with cemdisiran in gMG is very clear. We plan to position cemdisiran as a differentiated and convenient targeted therapy for gMG patients. Cemdisiran represents a first-in-class siRNA approach targeting C5. This will require education to ensure stakeholders understand how this differs mechanistically from antibodies, FcRn inhibitors and B cell depleters. To establish cemdisiran in this market, we look to drive adoption by leading with cemdisiran's potential best-in-class clinical profile highlighted by its efficacy, safety as well as dosing convenience. The Phase III data show rapid, durable symptom improvement with no waning between doses, which clearly differentiates cemdisiran for cyclic or infusion-based therapies.

Just as importantly, quarterly subcutaneous dosing meaningfully reduces treatment burden with potential to improve predictability and adherence for patients living with a chronic neurological disease.

As we move into launch optimization, the focus shifts to maximizing long-term adoption and value. We are actively working to evolve from HCP administered vials to patient self administration, further reducing treatment burden and improving persistence. We also plan to expand beyond the U.S. into key international markets where the combination of strong efficacy and quarterly subcutaneous dosing is also viewed as highly differentiated there. As the use of advanced therapies for gMG expands, self-administration options are introduced, and we expand into additional geographies, cemdisiran is poised for sustained growth.

Now I will turn it back to George for closing comments.

Thanks, Soma. Let me briefly summarize this roundtable discussion. C5 program is not a single asset story, it's a differentiated pipeline and a product opportunity with blockbuster potential. Cemdisiran used either alone or in combination with pozelimab enables different levels of C5 inhibition, depending on how much complement suppression each disease requires. We've shown that partial C5 inhibition is sufficient and optimal in generalized myasthenia gravis while complete uninterrupted blockade is required in diseases like PNH. That flexibility is the core advantage of our siRNA and antibody approach.

Moreover, while our C5 program has achieved clinical validation in its 2 leading indications, we expect to generate proof-of-concept data later this year in geographic atrophy, potentially derisking yet another significant commercial opportunity for complement mediated disease with significant unmet need.

In summary, with near-term pivotal data and planned upcoming launches, we believe the C5 program represents an under-appreciated opportunity for long-term growth, not currently reflected in Regeneron's valuations.

And with that, let me turn it back to Ryan.

Thanks, George. This concludes our prepared remarks. Thank you for your attention. We will now open the call for Q&A. [Operator Instructions] Shannon, can we please go to the first question?

[Operator Instructions] Our first question comes from the line of Evan Seigerman with BMO Capital Markets.

Really appreciate you doing this. So regarding the geographic atrophy opportunity, can you walk me through some of the rationale why you think your approach will be better than the currently available assets? I know that there's limitations and most physicians are not thrilled with those. I'd love to know how you think you can improve on those given that this is a pretty tough indication?

Well, in one case, in terms of being better, our studies are powered to pick up a potential functional benefit, which the other studies did not actually pick up. But our major advantage is going to lie in the setting of both convenience and safety, as we outlined. Right now, patients often suffer from bilateral disease. And as you probably know, treatment often triggers a requirement for anti-VEGF therapy as the patients progress from dry AMD to wet AMD. So the treatment burden is very substantial for many of these patients with bilateral injections targeting complement as well as additional injections for their wet AMD.

What we hope to be doing here is using a subcutaneous systemic treatment approach that will dramatically decrease the treatment burden. It will allow simultaneous bilateral treatment from the systemic approach. And if the patients then require anti-VEGF therapies, those will be the only intravitreal injections they'll need. They won't need to also be continuing their C5 injections.

We also mentioned, of course, that we do have a follow-on intravitreal approach where we're developing a co-formulated form of what we hope to be a long-acting antibody combined with our long-acting anti-VEGF agent, which would be a completely independent way of addressing the profound treatment burden that these patients suffer from, the need to have these simultaneous treatment approaches going. And so these will be 2 important separate distinct opportunities that could dramatically address the biggest problem that these patients suffer from, which is the treatment burden and also obviously, the safety consideration with the occlusive vasculitis that unfortunately is seen with the current intravitreally administered agents, we would expect not to see that obviously, either with our systemic approach or with our dual antibody EYLEA approach.

Our next question comes from the line of Alexandria Hammond with Wolfe Research.

So what does the path forward look like for moving from the subcu administration in the clinic all the way to that self-administration option, such as I'm assuming with an auto-injector -- on-body injector at home without the need of a health care professional?

Soma, would you like to take that?

Sure. Happy to take it. So we believe that the auto-injector will be an important -- self-administration option will be important for patients. However, as we start, we actually think that the currently C5s are given as infusion therapies. And this is going to be a subcu in the office every 3-month administration, which aligns with those schedules that patients visit anyway. Many patients visit anyway. So we've heard that this is not going to be a barrier out of the gate. But ultimately, this was really a launch sequence that was designed to avoid delaying entry while still enabling a convenience step-up post launch.

I'd just add that the timing for the self-administration option is going to be largely dependent on upcoming regulatory interactions, and we'll certainly keep you informed as those evolve over time.

But certainly, having a subcutaneous treatment regimen every 3 months, which as Soma said, is aligned with patients visits to their physicians is a substantial difference compared to the much more regular large volume infusions having to visit often infusion centers and so forth that these patients have or even the weekly infusions that some patients have with some of these therapies. So obviously, we think it's a very differentiated approach that offers, of course, 2 important features. One is dramatic decrease in the treatment burden. Two is potentially best efficacy in class, but also an efficacy that is very rapid and durable and sustained without cyclical variations. So we believe that it offers a very advantageous profile for patients and physicians to consider from the convenience but also from the treatment benefit side.

Our next question comes from the line of Chris Raymond with Raymond James.

Just a question maybe from Slide 10, kind of intriguing the phenomenon you're seeing that the different diseases may require different amounts of complement inhibition. I think that's pretty interesting. Do you have any plans to maybe more systematically study the biology behind this phenomenon? Or do you think you'll maybe just gradually learn what amount of complement inhibition is needed as you run these trials?

We agree. This is a fascinating scientific question. We are honestly interested in trying to understand it. But as you said, the very first step is to just define how much inhibition you need in the various diseases. We have to admit that although we did the study, as shown on this slide, that showed partial inhibition compared to complete inhibition, that partial inhibition was, if anything, at least as good, if not better, was very surprising to us and I think to the entire field. It really opens up a whole new set of questions, which you're highlighting, and I think it's going to be something that we're all going to be very interested in studying. But the implications obviously are huge from the safety perspective.

Obviously, in a disease where patients have risk of breakthrough hemolysis, thrombosis and death and so forth, such as in PNH, you really want to do what's best to prevent those really bad outcomes in those patients. And there, we believe you do need the complete C5 inhibition that the combination affords. But in myasthenia gravis, the opportunity to be actually seeing, if anything, better efficacy with less complete blockade really raises the possibility that these patients will have a much more favorable infectious risk profile. Now we did see it that in the small study when you compare the adverse events, but we're going to do additional follow-up studies to follow up and see whether that really can hold up to further scrutiny. But that would be a huge advance for the field and for patients.

All the other therapies are much more substantially immunosuppressive. We've seen now even with the FcRn therapies that they can be associated with serious reactivation and even fatal infections from EBV. We all know about complete inhibition with C5 leading to meningococcal infections and so forth. So this offers a very important different opportunity from the potential safety perspective. But as you said, it's a fascinating scientific question. We did not predict this -- and it certainly is a question of that we and I think the whole field is now going to be very interested in following up.

Our next question comes from the line of Mohit Bansal with Wells Fargo.

Sorry about that. And I want to double click on the geographic atrophy strategy a little bit. So I mean that systemic administration and whether or not it does cross the blood retina barrier. And then the C5 that goes in, would it have similar or more benefit than the intravitreal C5. So how do you see that? Do you see C5 -- the intravitreal C5 as the bar? Or do you think a benefit in visual acuity would also be -- will also be need to be seen here for you to move forward here?

We're really sorry the reception on your call was not very good, so we couldn't get the whole question. But certainly, it seems as if, by blocking C5 where it is made, there is very little actually almost no evidence that C5 is made anywhere other than the liver. It does not appear to be made in the eye. So blocking it at its site of production, if anything likely be more effective than trying to block it at the very last point in the eye. That said, we think that our major advantage will not necessarily be in further slowing down the progression of the disease. But because we have larger studies planned and ongoing that we will actually be able to show a functional benefit that was not shown in the other programs. But the first hope in our first study is merely to show a very similar rate of slowing of geographic atrophy with the differentiated and potentially better and potentially safer certainly from the local injection safety perspective of the systemic approach. And that should offer, assuming it's a well-tolerated and safe systemic approach, a huge benefit to patients.

Many of these patients are not taking this treatment. There's -- even though there's over 1 million patients in the United States who could be eligible for this treatment, there is very slight penetration into this market probably on the order of 1% or so. Most patients are not taking these therapies, why because they require injections directly into the eye, multiple injections, you then trigger anti-VEGF injections on top of that and the injections themselves can actually cause catastrophic immediate blindness in rare cases because they cause occlusive vasculitis. So the problem is there is a treatment approach that can help these patients. It's just not widely used because of the treatment burden and the safety risk of the intravascular injections. We hope to open up this entire field and all these patients for a much more convenient treatment approach and allow many more of them to undergo an approach that could slow or prevent progression of their geographic atrophy disease.

Our next question comes from the line of Salveen Richter with Goldman Sachs.

This is Elizabeth on for Salveen. We wanted to get your thoughts on targeting C5 specifically in GA and why inhibition at C5 is optimal within the complement cascade for this disease versus going upstream or potentially downstream?

Well, so far, approaches targeting either C3 or C5 have been shown to be similarly effective. There's no evidence to suggest that going higher up would be more effective. Of course, going higher up blocks more of the pathway and has higher risks in terms of infections and so forth associated with it. And so we thought that the C5 approach had the opportunity to have as good efficacy and potentially better safety once again.

Once again, we have in our pipeline other programs to both address other targets, both in the complement pathway, but elsewhere in this entire pathway as well in the upcoming years that we may be able to bring forth as well. But right now, we thought that C5 was the best known and available target from the safety and efficacy perspective and that we had this differentiated approach that could make the treatment much more convenient and hopefully safer for the patients.

Our next question comes from the line of Geoff Meacham with Citi.

This is Nishant on for Geoff. On gMG, given the competitive treatment landscape, at launch, do you expect uptake to be driven more by switching from existing C5 or by new starts that might otherwise have gone to FcRn? How should we think about that mix evolving over time?

Yes. So we're very -- we're excited about what we think this differentiated profile can do and potential best-in-class efficacy, dosing convenience, we think it will position as a very differentiated advanced therapy in the space. But the launch is really expected to capture a mix of switch and new patient starts. And the plan is really to compete for both because we think that there's certainly people who are on certain things, whether they're on infusions, whether they're on these cyclical based therapies and we think they are perfect candidates for switch. But also, there's so many patients coming into this advanced therapy filter that are going to look for new agents that we think there's also a really good opportunity for new patient starts. So we think it's going to be a little bit of both, but not to underestimate the competition, it's a competitive space. It will take time. And so we do expect that as well.

Thanks, Soma. Shannon, we have time for 2 more questions, please.

Our next question comes from the line of William Pickering with Bernstein.

In geographic atrophy, what read-through do you see from the failed Soliris trial, given that it's also a C5 inhibitor? And could you comment on why you initiated the intravitreal pozelimab trial?

This is Andres. So when you look at the complete study, I think it's important to understand that this was an investigator-initiated study relatively small study. I mean this is 30 patients randomized 2:1. And there are a few, I think, points that are important. One is eculizumab, which was used in that particular study was dosed at 900 milligrams, which compared with our approach does not provide full suppression of terminal complement activity. I think that, that is an important point that we should bear in mind. And also the way the study was designed with a very small number of patients looking at a large magnitude of an effect. Now we have a better understanding of what to look for.

And when we are looking at our particular study with a larger number of patients, and I want to remind you that we are planning to do an interim analysis with approximately 250 patients, we are looking for a 20% treatment effect, which is commensurate with what we have observed with IVT infusions. So I think that there were early days when the complete study was performed. And I'm not sure that had the best and enough power to really detect a significant improvement at that point.

Yes. I mean let's just emphasize what Andres said. We are not expecting to get a bigger slowing than the intravitreal agents. We're just expecting to do it in a much more convenient and safer manner. That slowing is about 20%. A 30-patient study was -- had an 80% power to pick up a 75% slowing. So obviously, with 30 patients, you would not have seen a 20% signal. So you have to just ignore that study if like it was not done, plus it was done with an inferior agent. So of course, we would not be taking a study that has no informative value at all into account into our thinking because it literally taught us or the world nothing except maybe it misinformed some people who weren't paying very close attention.

And you asked a question about the IVT formulation. Why are we doing that? I think that one important component is the fact that we recognize that maybe potentially one may need reduction of C5 or complement activity locally. So we understand that, that might be necessary. But I think what is important is our approach. And the approach that we are taking is a co-formulation with anti-VEGF because as you probably know, the -- when you treat with complement, you may actually worsen the situations with the wet AMD and so forth. So that is one important approach. The other is that our antibody will not be pegylated, which has been potentially associated or speculated that pegylation is what induces the complications, the ocular complications with intravitreal administration. So we recognize that we have multiple shots on goal.

Our last question comes from the line of Tyler Van Buren with TD Cowen.

This is Sam on for Tyler from TD Cowen. These roundtables are very helpful. So just 1 question from us on the Phase III PNH pivotal data later this year. What are your expectations for the performance of the control arm? And what does poze-cemdi need to achieve to reach statistical significance on percent change in LDH? And then maybe what does it need to show to be viewed as having best-in-class efficacy?

I think that the data that give us confidence on the outcomes of the study is what we presented during the roundtable. And that is that when you compare with ravulizumab, which is another standard of care -- a considerable standard of care today in the treatment of PNH, a larger proportion of patients that were treated with the combination of pozelimab plus cemdisiran achieved LDH control. Furthermore, a significant larger population of the patients have a normalization of LDH, which we think really represents the level of ongoing intravascular hemolysis. So we feel very comfortable.

Furthermore, when we looked at patients that were not well controlled or never achieved control with ravulizumab in that cohort, okay? There were 5 patients that never achieved control. When they were switched to the combination, our combination, 4 out of those 5 patients were able to achieve control of their LDH. So we feel confident that we have a more profound, sustained uninterrupted inhibition of C5 activity that will lead to better control of intravascular hemolysis.

So I think that, that is the data that encourages us and make us believe that we have a positive study.

And we won't have to wait much longer to get that data, should be coming in the fourth quarter. Thank you, Andres. And thanks to everyone who joined the call today. Unfortunately, that's all the time we've got. Thank you for your interest in Regeneron and our C5 Development Program. Everyone, have a great day, and we can now disconnect.

This concludes today's conference. Thank you for your participation. You may now disconnect.

So we'll kick it off here. Thanks for your patience. So I'm Dave Risinger. It's very much my pleasure to welcome members of the Regeneron management team. So with us is Marion McCourt, who's Executive Vice President of Commercial; and Ryan Crowe, Senior Vice President of Investor Relations and Strategy. So thanks again for being here with us. I thought that maybe I'd turn it over to you to provide some just opening comments about the prospects for the business this year.

Maybe I'll start, and we really truly appreciate the opportunity to be here, Dave. Leerink conference is always something we plan to attend every year and excited to be back. And today, we think we have a thoughtful discussion around the commercial momentum we have in our business as well as the deep, diverse and diversified pipeline and how we're executing all across that as well as kind of our disciplined approach to capital allocation. But before we get to all those topics and before Marion gives kind of an overview, I need to read this forward-looking statement.

So I would like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Marion?

That was double speed that was impressive.

I got out of practice doing it.

I think you've read that before.

Just a few times.

And I'll go a little bit more slowly, but good morning to everybody. And just to give a little bit of an introduction to the year, I'll give that in context of our fourth quarter performance and obviously wanting to continue the strength of our commercialization and the depth of our portfolio. But in fourth quarter, we shared with you our results on EYLEA HD. Certainly strong numbers with $506 million in the quarter. That was 66% year-over-year growth for EYLEA HD. And certainly, in the end of the year, in the November, mid- late November time frame, we had the enhancements to the EYLEA HD label, which were long awaited, but very important for Q4 weekly dosing and also the RVO indication.

Dupixent also a very strong performance, pleased to say through the year and in the fourth quarter, we had in the fourth quarter, specifically $4.9 billion in sales for Dupixent, and that was obviously in our relationship, the alliance with Sanofi, but very strong performance across all indications with Dupixent. And that also was a significant growth in the fourth quarter number, which was up about 32% versus prior year.

And then also over to Libtayo, strong performance, $525 million. That was a year-over-year increase of about 13%, strength not only in our skin indications, but also performance in lung cancer, and we had also recently launched into the adjuvant cutaneous squamous cell carcinoma setting. Other products certainly in our portfolio, but those would be the highlights and certainly the major brands that I'm sure you're interested in, in in-line commercialization as we go into the year.

Excellent. And so for this year, -- could you just talk about the pushes and pulls and what we should be focused on?

Sure. So I absolutely would continue to focus on -- I'll start with our largest brand in Dupixent. Certainly, we have major established indications in the marketplace. But the exciting thing is even our first indication launch with atopic dermatitis is very much underpenetrated in the marketplace. So the category is growing. Competition is coming in, but Dupixent remains the leading product as the KOL community frequently reminds me first and best product in the category.

We continue to lead in asthma as well in new-to-brand scripts and total scripts, also in nasal polyps, Eosinophilic Esophagitis, all major indications for Dupixent performing really well. on an international basis. And then more recently, we've had the launches of COPD for Dupixent performing quite well. CSU has been really important. chronic spontaneous urticaria, I'll remind is a patient population of about 300,000 patients as well in terms of potential. And then more recently to the label enhancement, we've also had the allergic fungal Rhinosinusitis, which is really important for patients with a really significant condition of allergic fungal infection, often resulting in surgeries, but then having to repeat surgeries because, frankly, it's not an effective means of treating that disease, which is chronic in nature.

So great things happening with Dupixent and certainly a lot of excitement for -- I mentioned Libtayo performance and the indications, but we recently also last year, in the last months of the year, launched Lynozyfic -- and that has been an exciting launch, certainly for later line patients in terms of treatment, but early days seeing a lot of very positive uptake in both academic and community setting based on the clinical profile of efficacy, safety profile, lesser hospitalization, which is so important to those patients and their physicians and also the ability to extend their dosing treatment interval more rapidly, also really important for patients being treated with multiple myeloma.

Excellent, excellent. And EYLEA.

So for EYLEA, certainly, the focus of my attention is now the expansion of EYLEA HD. We have some label expansion, hopefully, more to come with prefilled syringe, but certainly strong performance in the last several quarters in terms of being actually the leading product in the anti-VEGF category for innovative brands in terms of growth and certainly a lot more potential for the product EYLEA, I did mention in our most recent earnings call that we obviously had seen a double-digit decline on sequential quarters in EYLEA.

We expect to continue to see that as we go into the first quarter. At the same time, we commented on seeing growth in EYLEA HD. We talked about high single digits in terms of the EYLEA HD unit growth as we go into the first quarter. So again, declines in EYLEA, not only because of growth of EYLEA HD, but also because of obvious biosimilar competition that we have in market. And I'll remind everybody in the second half of the year, our expectation would be to see additional biosimilar competition to EYLEA 2 milligram.

Excellent. And so you mentioned high single-digit unit growth for HD in the first quarter sequentially. But how should we think about net price sequentially?

Well, I think you have to think a little bit more carefully on that because we did share with you that we had some inventory build in the fourth quarter of last year. That's not unusual. We had a similar inventory build on EYLEA HD and EYLEA in the prior year. I think it has to do with patterns of buying at the wholesale level. But certainly, we continue to see robust demand with EYLEA HD, and there has been very positive response to the enhancements of the label of the Q4 weekly dosing. It gives physicians confidence and flexibility prescribing as they want to use the drug. Even though they see with EYLEA HD great durability, there are occasionally patients, and they don't always know which ones that when they see them when they treat the patient, they want to use the shorter dosing interval for at least one or maybe a couple of more treatments.

And then how important is the prefilled syringe commercially meaning is adoption by physicians really constrained by the lack of a prefilled syringe?

So it's important. I would say that from our demonstrated performance, EYLEA HD has been in market now for over 2 years. We launched in August of 2023. We've been -- we're a blockbuster brand. So I'm very proud of the team and what they've been able to accomplish. It's really all about the science and the profile of the brand that allows that. But I'll share, even though we've done well with EYLEA HD, if I look at EYLEA as an example, 95% of use is with the prefilled syringe. So it's important to practices. It hasn't constrained use. It certainly will open use, though in some practices where they may have been more hesitant.

Great. And since we just talked about your commercial presence across different therapeutic areas, -- could you just talk a little bit about -- and maybe this is more of a question for Ryan, but both of you can comment maybe the opportunity to leverage Regeneron's infrastructure through M&A, meaning obviously, the company wants to invest aggressively in R&D going forward. But I would think there's an opportunity to roll in products that leverage where you're already operating in specific therapeutic categories to drive even better financial returns to support that R&D growth in the future.

I'm happy to start, and then I'm sure Ryan will have comments as well. So absolutely, when we built the commercial organization over many years now, starting in ophthalmology and then broadening into immunology, oncology, hematology, rare disease, and having the infrastructure to allow for increment to the portfolio, we did so always with the future of mind of being specialized in therapeutic areas, but being able to expand. I'll give you a quick example of something that already is a byproduct of partnership.

We have cemdisiran coming into the marketplace, fingers crossed with an approval, if not end of the year, early next year for generalized myasthenia gravis. We already are working towards the footprint and the build of a neurology business unit for a product that we brought into the organization. Similarly, as we look to the future of our own science and potentially partnered or M&A, as you asked, types of opportunities, we have the infrastructure in place to be able to do that.

Yes. I think Marion has it right. We certainly have the core infrastructure of the commercial team that can support a number of products. And as you know, Dave, we have a very broad pipeline across many, many therapeutic areas. And as those advance into pivotal stages, the commercial team begins to get built around that. I'd say in terms of bringing in outside opportunities, commercial synergies are unlikely to be the primary motivation there. We have done historically earlier-stage M&A and platform-focused M&A. I think that's probably going to remain how we view the opportunities outside, but not ruling out something bigger and more late stage for sure. I just -- I don't think it would ever be commercial synergy-driven M&A.

Got it. So regarding the Sanofi alliance, can you talk a little bit about the strategic decision-making framework within Regeneron, specifically, whether it makes sense to try to extend the duration of the alliance or not? Any high-level comments would be helpful.

Sure. So as a start, I think that the alliance with Sanofi has been very important for Regeneron, and we're incredibly proud of what we've created. And specifically with Dupixent today, we have 1.4 million patients on Dupixent worldwide. It's been an amazing product, helps so many patients and been obviously really important to both organizations. As we have opportunities to look at strategic endeavors that make sense for both companies, absolutely, that's the right thing to do. I think, Ryan, perhaps you have some more detail on some of the elements of consideration.

Yes. I think Dupixent would not be the product that is today without both Regeneron and Sanofi. And I think it's in the best interest of both companies to maximize all of the progress that we've made together beyond maybe Dupixent. And we have plenty of next wave opportunities within our own pipeline, Sanofi as well and trying to leverage Dupixent to the max, I think, is in both sides' best interest. There are certain assets that we've identified in our preclinical portfolio that also hit the IL-4 receptor alpha.

They're already kind of by default in the collaboration, but there are others that do not and are not currently in the collaboration. Whether that can change is a matter for us and Sanofi to figure out whether, a, it makes sense for both sides; and b, at what terms. So we're certainly interested in pursuing that. We've been great partners over the years, of course, with some disagreements along the way. But overall, a highly successful partnership that I think we should continue to try and maximize.

Excellent. And just remind us about what you had updated the Street on in early January about which candidates are in the alliance, which candidates are out of the alliance. I think there was that one specific slide where you had some of those details.

Yes, that's right, Dave. So it's not really that complicated. In fact, if it hits -- if an antibody or some other drug hits the IL-4 receptor alpha, which is the target of dupilumab, it's in the collaboration. That's a very bright line in the agreement. If it hits really any other target, it is not. So for some of the next-generation assets that we are working on preclinically at the moment, including our long-acting IL-13 antibody, our long-acting IL-4 antibody, our long-acting IL-4 by IL-13 bispecific antibody, none of those are in the Sanofi collaboration. So we are independently working on them.

We have, I'd say, bespoke development plans around each of those assets. IL-13 long-acting will be the first of those opportunities to enter the clinic. We've said that, that would occur in the first half of this year, and that remains on track. So we're looking forward to putting that into a human very soon. And the first indication that we'll be pursuing is in atopic dermatitis. So initially in healthy volunteers, and then we plan to follow an expedited development program to hopefully allow for registration and launch ahead of Dupixent's composition of matter patent expiry, which would be the earliest potential launch of a biosimilar. I think there's some opportunity to maybe extend that exclusivity runway beyond that date, though.

So is that what George referred to as supi-dupi? Or is that a different one?

Supi-dupi, I think George was talking about the long-acting fully human IL-4 receptor alpha antibody. So literally another version of Dupixent that can be dosed at longer intervals. So that is the supi-dupi. And then these other opportunities are kind of adjacent to that, all within the IL-4, IL-13 axis, which we think is truly the underlying driver of all these atopic inflammatory diseases.

Got it. Okay. That's great. And turning back to EYLEA. Could you just talk about sort of the commercial dynamics when a number of additional biosimilars launch later this year? Just how you manage this year ahead of that and next year after that? Obviously, I'm sure you want to convert as many patients as possible to HD. But it'd be just helpful to have you describe sort of your commercial positioning as you're operating it today?

Sure. So I think it's important to understand that when you look at the market today, even for years, there's always been a low-cost alternative with Avastin in the anti-VEGF category. So that's one fact that remains. And certainly, as more biosimilars come into the marketplace, you would expect to see more price competition, things of that sort, where today, the biosimilar use aflibercept 2 milligram has been limited to select practices as opposed to a widespread use in the marketplace. Having said that, your point was spot on, we're very fortunate to have EYLEA HD next-generation product. Retina specialists are a very sophisticated audience, both scientifically and from a business standpoint.

And I think for them, it's really important to be using state-of-the-art care for their patients. The durability of EYLEA HD is very exciting in the market. We know the label enhancements have been important. So the timing is really nice that we're bringing forward EYLEA HD to be all that it can be, hopefully very quickly so that we're in a really strong position to be the product in the marketplace and the innovative branded product in the marketplace that physicians see all the attributes of what's most important to them for the retina patients.

And then you would expect with more biosimilars, potentially more elements of pricing actions and also physicians potentially always having the thought in retina because we inject into the eye, there's always the consideration as new products come into the marketplace, wanting to see them in the real-world setting. It's not possible always to know, and this is true of all products, not just biosimilars, but even branded products, we've seen some products before the market experience fail because of safety, but we've seen others that we thought were going to be highly effective in the marketplace, not succeed because of issues related to safety. So that, too, is something that always will be really important in this category.

Sorry. So thinking about that commercial infrastructure that you have for EYLEA. So could you just talk about leveraging that longer term and maybe also comment on pipeline candidates as well that could fit in?

Yes. So very happy to. And there is a lot, obviously, in our various programs that potentially feed into the ophthalmology business unit for commercialization. So just to maybe mention a few that I've been incredibly impressed with is we have a program for uveitis. We have a glaucoma program. We have a geographic atrophy program. There may be others that we haven't commented on yet that Ryan, you can add to my comment, but really exciting and Regeneron is a long respected company in the retina and ophthalmology community. So we're really excited. And to your point of building out business units, that is an example. And I'll also share with you, I'm never hesitant to build a new business unit as we did for oncology or hematology or as I mentioned, neurology as our science feeds in. But in this particular case, it's a therapeutic area where we have a footprint.

Yes I would just add, we also have an opportunity in thyroid eye disease using a novel target. So a few of these are going to be first-in-human targets that we're excited about. And I think they -- as they move along in clinical development, the commercial team will be preparing.

Excellent. That's great. So maybe we could turn to a couple of other pipeline questions. So could you just talk about fianlimab, -- if you could provide an update. Obviously, the trial has been delayed. We're still awaiting the results. And I know that you've commented before. Obviously, there have been some investor concerns that maybe the pembro arm is performing dramatically better than anticipated. But would love to hear the latest please.

Sure. Certainly been a lot of scrutiny around this study and the readout has been delayed a couple of times, and we're now still on track for a first half readout as we await these final PFS events to come in. We don't believe we've enrolled a population that would result in an outsized pembrolizumab benefit of above and beyond its historical analogs of, call it, 4 to 5 months. Some of the inclusion criteria in some of the trials that have been recently conducted, I think, are slightly different than what we enrolled. And as a result, pembrolizumab perhaps did better in those trials than we would expect it to do here. We don't know how pembrolizumab is doing in our study.

We are totally blinded to the events and where they're occurring. We only know the total number and how they are accruing at the rate in which they're accruing. So we will see. I think you can look at it from 2 different ways. On the negative side, pembrolizumab is doing something miraculous and amazing and it's going to have a much higher-than-anticipated median PFS or you could look at it and say, well, the active arms are actually doing quite well and are approaching the activity that we saw in the early human studies where pooled median PFS across 3 independent cohorts was 24 months.

I'd add that we feel that we've conservatively powered this study and actually have assumed pembrolizumab performs at a median PFS of 7 months, which is roughly 50% better than it has in first-line metastatic melanoma in past studies. And so based on that assumption and our assumption of at least Relatlimab/nivolumab [indiscernible] activity from our combination, we feel comfortable with the powering of the study even if pembro were to outperform its historical analogs.

That's very helpful. And can you talk about with respect to that enrollment, the mix of patients by PD-L1 status?

Sure. We haven't stratified by PD-L1 status. There's no floor. There's no cap in enrollment. We are pursuing patients that are in the real world. So we would expect to enroll a roughly even split between expressers and non-expressers of PD-L1, but those baseline characteristics have not yet been disclosed.

Okay. Very helpful. So you have a new launch to prepare for in [ MG ]. Could you talk a little bit about that and whether there's any possibility of launching earlier than the schedule for the first quarter of '27?

Yes. Well, based on the filing and submission, we had been speaking about early portion of next year, January. There are scenarios where potentially you could move it late this year. We certainly will be launch ready, and we look forward to participating in this marketplace. The product profile is exciting from the standpoint of efficacy, safety, convenience of dosing. There's still a lot of unmet need in myasthenia gravis marketplace. It's about a $5 billion marketplace today. By 2030, it could be up to about $10 billion. A lot of potential, a lot of unmet need, obviously, a highly competitive marketplace as well, but one we're excited in being able to participate in with an approved product.

And I would just add, we do plan to present the full data from the NIMBL study next month at [ AAN ]. So we'll show what the curves on MG-ADL look like. And I think what you'll see is rapid improvements in the activities of daily living and sustained across 6 months with every 3-month dosing, which is very differentiated from the medicines that are approved today for myasthenia gravis.

Yes. And just given the evolution of the MG commercial market, could you just shine some light on exactly where you see the product being positioned and taking share?

I would say that we're looking at a variety of scenarios now based on the profile I mentioned related to efficacy, safety, dosing convenience and then the unmet need of patient population. I think it's early to give you specifics on the strategy because I'd like to have the final label, and there are a number of different opportunities, all very exciting. So I just would request a little patience, stay tuned. And then as with all of our other launches, we've always held back on specific strategy of launch until the timeliness, but delighted to share as we move along and the decisions being made.

Excellent.

I will share that as we've built a number of business units at Regeneron. It's always really been exciting the level of talent that we've had from -- in the industry wanting to join Regeneron. And I can share with you that early days in our build-out of the neurology business unit, we're seeing that again.

Excellent. And so could you talk a little bit about label scenarios?

I think it's early, candidly, Ryan, I'll always defer to you and the IR team of what you've been sharing or what you'd like to share. I would only comment that it relates to the notion of the mechanism of the product, the degree of inhibition, the level of efficacy you see, the -- as Brian was mentioning, the patient experience in terms of their activities of daily living, really important. dosing frequency is always an element of convenience that is important to patients with a chronic disease like this, which is truly debilitating.

As you know, for women, it's usually an earlier age diagnosis, bimodal disease. Men, the diagnosis tends to be a little bit later, more often patients in their 60, 65 and up age range. But all these patient groups having similarities of need in terms of relief of symptoms, products that are convenient to use, safe and allow them to go about their lives. But the specifics, I'm going to wait until we get the label. I appreciate the question, though.

All right. Why don't we pivot to the GA readout that you have ahead? That's clearly a very exciting opportunity, very substantial. Could you just remind us about that and discuss the efficacy bar for success?

Sure. So this is an exciting one for us. And of course, we're doing this a little differently than the currently approved products for GA, where we're approaching this with a systemic administration with both a combination of cemdisiran plus pozelimab, our antibody to C5 as well as cemdisiran monotherapy against placebo. We believe while the actual cause of geographic atrophy is a little ambiguous, the key driver of the disease is complement-mediated inflammation of the correl capillaries along with some genetic and perhaps environmental factors.

And by completely blocking C5, which we've demonstrated in multiple studies with the combination of cemdisiran and pozelimab, we can eliminate circulating C5 with pozelimab and stop the liver from making more with cemdisiran. So in the PNH -- I'm sorry, the gMG study, we saw the combination reduce C5 levels in patients by 99%, at least 99%.

So if you believe that complement drives this disease and you eliminate complement, you should see improvement in lesion growth or deceleration in lesion growth, which is what our interim analysis is going to explore at the half year mark. So it's going to be an early look. It's going to be a subset of patients, but it should give us an indication about whether or not the systemic approach for either the combination or the monotherapy is differentiated from a placebo. So we're looking forward to that. It's going to be towards the end of 2026. And that will inform our future plans for a second study in GA.

Excellent. Well, we're actually out of time. Thanks so much for joining us.

Okay. I think we can get started. Good morning, everyone, and welcome to Miami. Very happy to have Regeneron here with us today to kick off the morning here at the Barclays Global Healthcare Conference.

I'm Ellie Merle, one of the biotech analysts here at Barclays. Very happy to have Marion McCourt here with us, the Head of Commercial; as well as Ryan Crowe, the Head of Investor Relations. Thank you both so much for joining us.

Before we jump into questions, Ryan, I'll pass it to you for some opening remarks.

Thank you, Ellie, and thanks for having us, and welcome to the sell-side coverage of Regeneron. I wanted to start today kind of highlighting your initiation report from last week, which I thought hit on a lot of themes that we'll cover in our chat today. And really underpinning your buy rating was your argument that the stock is fundamentally mispriced on the durable cash flows.

And when you consider our valuation today really only reflecting the cash flows from DUPIXENT, the EYLEA franchise and our cash on hand, if anything in our pipeline works, I would argue we are undervalued. And if a lot of things work in our pipeline, we are significantly undervalued. So I'm sure we'll get to a lot of the themes I'm about to highlight in our chat. I just wanted to go through a couple of areas to frame the discussion.

DUPIXENT momentum, really as a pipeline and a product, is well positioned to continue with growth anticipated across all 9 of its FDA-approved indications, including more recently, the launches of chronic spontaneous urticaria as well as COPD. It has a long runway and a lot of growth to come.

EYLEA HD, now approaching half of the revenues from the EYLEA franchise, and market share is poised to continue to expand with the label enhancements that were put on the FDA label late in 2025 and the hopeful approval next month for the prefilled syringe, which will really round out the profile.

And then you specifically highlighted in your report, LYNOZYFIC, which I think is a very underappreciated asset that's now approved in late-line myeloma, but with a significant commercial opportunity in earlier lines of myeloma as well as in precursor conditions, all of which are currently being evaluated in various clinical studies.

And finally, there's a lot of near-term catalysts that I think we'll talk about today, including Fianlimab plus LIBTAYO in metastatic melanoma, which has a near-term readout sometime in the first half of this year.

And then we have some interesting data coming from our Geographic Atrophy program likely in the second half of this year as well as a pivotal readout in paroxysmal nocturnal hemoglobinuria or PNH from the C5 combination of pozelimab and cemdisiran late this year.

So before we go any further though, I need to read this forward-looking statement disclosure, and we can jump straight into the questions. I'll do this as quickly as I can.

I'd like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise.

New record time.

That was very fast.

Anyway, I think -- I hope I framed the conversation well. Let's get into your questions.

Awesome. Well, starting off with DUPIXENT, what are your expectations for some of the newer launches this year?

Yes. Ellie, I'll jump in, and good morning to everybody. Very nice to be here. So certainly, DUPIXENT has been amazing as we reported to you most recently in our earnings call, last year's sales $17.8 billion, up 32% year-over-year. We have the established indications that are still growing based on patient unmet need like atopic dermatitis, like asthma, certainly been really excited by the recent launches as well.

COPD has been remarkable for patients who had such limited therapeutic choices previously. And then additionally, as Ryan was mentioning, as I go to some of the newer launches, with so many indications, I'll try to give you a quick comment on some of them, but I don't want to miss anybody either.

But certainly CSU, chronic spontaneous urticaria is off to a really strong start. A lot of unmet need for these patients where antihistamine therapy alone just didn't give them the relief from the hives and the itching and the concerns that they had.

Bullous pemphigoid for older patients, an amazing launch in that arena, smaller group of patients, but previously tremendous unmet need. Really the only therapy that was used was chronic steroids, which isn't good for that age group of patients. Worse still, it did not work.

And certainly across all the indications, most recently, we launched for allergic fungal rhinosinusitis, very difficult disease, often results in immune allergic fungal responses requiring surgery, but now with DUPIXENT, a tremendous opportunity for patients. So across geographies, indications, age groups, we continue to see growth and tremendous progress with DUPIXENT.

Great. And COPD as well, I mean, I know it's approved a little bit earlier, but massive indication. Can you talk a little bit about some of the trends that you're seeing there and how we could think about that as contributing to the top line this year?

Sure. So very exciting indication, as I mentioned, tremendous unmet need. But now with some time in the market with COPD, often, it's an older age group of patients. We've made tremendous progress in making sure that pathways are established where necessary eosinophilic levels, biomarkers [Audio Gap], payer coverage is robust.

So there's a lot of enthusiasm with pulmonologists as we brought COPD into the marketplace. Of course, they'd had experience often or their institutions had with DUPIXENT in asthma, so rounding out into COPD patients where there's so much unmet need, has really been amazing.

Each phase of launch has gone on track. Our DUPIXENT organization, I think Regeneron overall, we're a bit of a launch machine, but certainly, each stage of launch has important parameters, goals, execution, delivery performance metrics that we look at, and COPD certainly has been living up to the opportunity it presents for patients and their prescribing physicians.

We've heard stories of patients coming back in for routine visits who had been on oxygen therapy. For anyone who's ever had a loved one on oxygen therapy, you know how incredibly difficult it is even for transport, the patients coming back into the office, being able to be ambulatory, engaging not only in their physician visit, but life generally just makes such a tremendous difference in their care.

Okay. Great. And turning to the atopic dermatitis side of things. There's a lot of compounds in development for atopic dermatitis. Obviously, DUPIXENT was the first. How are you thinking about life cycle management here, what you have in development and sort of the sustainability of the DUPIXENT revenues in light of some of this emerging competition?

Sure. So I'll take it as a 2-step. Maybe I'll cover the market currently, and then Ryan will cover a little bit of the future for us. But one of the things that I hear most frequently at the KOL visits or major meetings like the upcoming American Academy of Dermatology meeting later this month, the KOL community so often repeats one simple phrase to me is that is DUPIXENT is first and best in atopic dermatitis.

And the data, the clinical data, the market experience, the patient experience really does seem to at every turn, establish that dynamic. Other categories that many of us have worked in across our careers, the later compounds sometimes show improvement in differentiation. It's the opposite with DUPIXENT, and it's better that they describe it to me and I repeat it to you, but it's the dual mode of action that you see with DUPIXENT, it's the tremendous market experience, it's the efficacy, it's the relief the patients feel.

So other products coming into the marketplace have actually been important from the standpoint of getting more education to the market, more consumer education, more physician education, and this actually is benefiting DUPIXENT as the product, the patients and their physicians know now and reach for first.

So we'll keep a close eye on competition. Competition always makes you better. But in the case of DUPIXENT, all the aspects of our dosing convenience, mode of action, the fact that we have so many indications and truly is the product that gets at comorbidities across the type 2 cascade is highly differentiating.

It also really matters to physicians and patients that across any of the age groups and indications, you can say that DUPIXENT is approved for children as young as 6 months in atopic dermatitis, 1 year in eosinophilic esophagitis, which is a major indication that I didn't even talk about today. But these characteristics, this market experience, efficacy of the product and safety really make it the first product that physicians and patients turn to.

Yes. So the bar that Dupi has set in the marketplace and in its clinical studies is very high, and we've seen many competitors try and reach that bar and fail to reach it. We have been thinking about life cycle management for DUPIXENT for a number of years, and I think we've built a robust approach to ultimately succeeding DUPIXENT with even better products.

I would highlight a few that we've talked about in recent months that should be entering the clinic either later this year or into 2027, all of which have custom development plans, and we plan to expedite based on our experience, not only in the marketplace, but also in conducting these studies.

So I'll start with the supi-dupi as our Chief Scientific Officer, George Yancopoulos, termed on our last earnings call. This is a long-acting fully human IL-4 receptor alpha antibody that is the exact same target that DUPIXENT currently hits and would have that same dual mechanism of action that Marion mentioned.

That one is part of the Sanofi collaboration by default as it targets the same receptor that's in our agreement, and we are looking forward to hopefully partnering with Sanofi on developing it once it is clinic-ready.

Beyond that, outside of the Sanofi collaboration, I would highlight the lead candidate being a long-acting fully human IL-13 antibody that we'll be entering the clinic within the next couple of months, we've said first half of this year. And we will be looking at the IL-13 antibody in atopic dermatitis initially.

We believe we can reach at minimum every 3-month dosing with this antibody and would hope for even longer intervals with comparable efficacy to DUPIXENT. We think longer intervals are obviously more convenient for patients and would be well received in the marketplace.

Beyond that, we have other long-acting antibodies, including one for the IL-4 ligand, which would be outside of the Sanofi collaboration, as well as a bispecific that would target both IL-4 and IL-13. So a life cycle strategy that is certainly centrally focused on the IL-4/13 axis as we believe that is the fundamental underlying driver of all these atopic diseases, and we look forward to keeping you updated on our progress across this important part of our pipeline.

Great. A lot of exciting programs. So for EYLEA HD, the prefilled syringe approval is expected soon. I guess, what's been the feedback from the retina clinics on the importance of prefilled syringe and operating their workflows? And I guess, how should we think about a potential inflection in the demand curve for EYLEA HD once the prefilled syringe is approved?

Sure. Thanks, Ellie. So I'll reflect a little bit on the recent experience with label enhancements. As you know, it's towards the end of November, where we were able to secure FDA approval for Q4 weekly dosing for EYLEA HD and also the RVO indication.

Also just as a quick reminder, in the last quarter, we reported sales of $506 million, up 66% year-over-year for EYLEA HD. So certainly progress being made. I was really proud of our commercial and medical affairs team on the education and promotion in the marketplace, showing that EYLEA HD was actually the innovative branded product growing more than any other in the anti-VEGF category.

To the question of prefilled syringe, very much look forward to that approval. I do think it will be important. As a point of reference for you, with EYLEA, about 95% of our business is with prefilled syringe. But certainly, I believe we have a very strong profile with EYLEA HD that we're working with right now and working on steadily in the marketplace, and obviously, a very competitive anti-VEGF category.

But EYLEA HD is becoming known as the product with the broadest label in terms of dosing flexibility opportunities and the durability at every turn is bearing out. So the phrase there that I hear most often is EYLEA made better in EYLEA HD. So certainly a lot of work underway and a lot of progress to be made even before we have the prefilled syringe in the marketplace.

And I guess turning to sort of the implications for pricing, both for potentially EYLEA HD as well as EYLEA with the entrance of new biosimilars this year. How should we think about that in terms of the incentives of the practices to say, continue to stock both products and the implications for pricing?

So I think it's a number of factors. One is that the retina community and physicians like to choose the product that they're selecting for their patients. Many of them are highly academically oriented, have participated in clinical trials. And certainly, there are select practices, and it is select, it's not across the market, that have used biosimilars for financial reasons.

That's not the totality of the marketplace, it's something that we're well aware of. But I would think more broadly over time, consider that physicians want to make the selection of product that's best for their patients as they're treating blinding eye disease.

Having said that, we did want to be balanced, and I think I shared with everybody in the last earnings call, when you think of EYLEA, now I'm not talking about EYLEA HD, but EYLEA, we would expect to see declines quarter-over-quarter.

I referenced double-digit types of sequential decline. That in part is because of coming biosimilar or current biosimilar competition, but it's also because we deliberately are making conversions not only of EYLEA, but other patients coming into the anti-VEGF category, naive patients or switch patients over to EYLEA HD.

Great. Pivoting a little bit to the pipeline, you recently had some data in obesity. The question that we get from investors is obesity is a very crowded market. So where do you think Regeneron and your program fits into this?

That's a great question, and I'm pleased to share the information that was relayed via Hansoh, our -- the company from China that we've licensed our GLP/GIP receptor agonist from, a peptide called olatorepatide, which is a mouthful. But the first pivotal data in China was generated and showed that olatorepatide was able to generate 19% weight loss and over 95% of patients were able to achieve at least 5 months -- 5% of their weight reduction.

These are very similar to the in-market and market-leading GLP/GIP agonists that are out there. And I would add, perhaps differentiating about olatorepatide is its tolerability profile, particularly in GI tolerability, where Hansoh reported, on average, under 10% incidence of nausea and under 5% incidence of vomiting, both of which would be about 1/3 of the incidents reported by the market-leading GLP/GIP agonist.

So very excited about this encouraging data from China. Our plan for U.S. development and, I guess, ex-China development, which is where we have our rights in this license, is to begin our Phase III study later this year, initially enrolling patients outside the U.S., and by end of year or perhaps in early 2027, begin enrolling patients into these pivotal studies in the U.S.

In parallel, we are working on co-formulation of alirocumab or Praluent with olatorepatide, which we hope will eventually lead to a product that combines these 2 important products to one that can generate meaningful weight loss while also reducing LDL cholesterol, which is a need by about half of the market today that is currently not being served by in-market products, which only reduce LDLs by low to mid-single digits.

Praluent, on the other hand, has demonstrated in its clinical studies, at least 50% reduction in LDLs, which I think could be very important for many patients from hypercholesterolemia. So we're excited about the opportunity in obesity. We have other ideas around combining olatorepatide with other assets and pipeline opportunities in our pipeline. So look for more to come in terms of our approach in obesity.

Great. Well, turning to LAG-3, which is certainly of a lot of focus in the near term. Maybe for either the first-line metastatic melanoma trial, how are you thinking about what success looks like here from a competitive perspective? And what should we expect to see on OS?

Great questions and ones I wish I could answer today. But unfortunately, the data is still maturing. So we've been running a study in first-line advanced melanoma. We're looking at 2 different doses of Fianlimab, our LAG-3 antibody, in combination with LIBTAYO, our approved PD-1 inhibitor, compared to pembrolizumab or KEYTRUDA.

So we -- the primary endpoint of the study is progression-free survival. And once we reach a certain number of events in this study, we'll be able to read out the data. So we're waiting on events to continue to accrue. And once we reach that magic number, we will lock the database and read out the data.

I think for differentiation, we've seen in the PD-1 class kind of mid-single digit, maybe low single-digit median PFS. We see combinations from Bristol with ipilimumab and nivolumab, hitting around 11 months of median PFS and their LAG-3 -- Bristol's LAG-3 combination has generated around 10 months of median PFS.

So while the study is powered against pembrolizumab, I think cross trial comparisons will be made, and I think they'll be appropriate given the population we're enrolling is very similar to those in other pivotal studies.

For differentiation there, I think low to mid-teens median PFS would put us clearly at the top of the board there and potentially practice changing. In terms of OS, it's highly unlikely that, that data will be mature at the time of the final PFS readout. Hopefully, we'll be able to have some initial trends in overall survival, and there will be interim analysis.

I think there's 4 interim OS analyses built into this clinical protocol before a final OS analysis will be made. So there's opportunity to have a clinically significant or statistically significant, clinically meaningful benefit on OS, where Opdualag has failed to do so in theirs. So that would really be another differentiator that we're hopeful for from this study.

Great. Just in the interest of time, turning to LYNOZYFIC. Maybe starting first with sort of the first line plus opportunity. Marion, I guess, how are you thinking about the size of this opportunity?

Sure. so very exciting launch in hematology with LYNOZYFIC this year, both U.S. and select international markets. Early progress and early read on use has been that the differentiating characteristics of efficacy, potential for less hospitalization for patient on initiation of therapy, getting to extended dosing intervals more quickly, all has been really important. Early use has been positive.

I will just comment, it is a refractory patient population, fourth line plus. So patient population in the U.S. about 3,000 to 4,000 patients. But certainly, we're making a lot of progress with pathways at the institutional level going through the REMS process of education and payer coverage.

So early days, really exciting, and perhaps most important of all, this early experience in later line certainly suggests that with clinical trial readout in earlier lines of therapy, we'll be able to participate more broadly in this $30 billion market, which is really significant and a potential to help a lot more patients.

But we're starting in the late line setting, and certainly we'll work hard there and then be ready to go into earlier line settings with the clinical data readout and approvals.

And yes, I guess how should we think about the cadence of the launch over the course of this year? And then as we pivot to thinking longer term, I mean, can you sort of help quantify a little bit how we should think about the size of the opportunity as you potentially move into the second line plus setting?

As you start moving earlier, and Ryan maybe can help me with some of the specific numbers, I know that the patient population, for example, in the U.S., about doubles as you go from fourth line plus the third line plus. As you go up into second line plus, it's a much bigger patient population.

So we have aspirations to go into the earlier settings as quickly as we have the data readouts and the product profile is suggestive that we really will be able to make a difference for these patients. Ryan may wish to add more.

Yes. I mean I think we've demonstrated best-in-class activity in the late line settings. And as we are generating earlier line data, we're also seeing best-in-class activity in second line and in first line myeloma with very limited combinations.

So we're very excited about LYNOZYFIC as a differentiated BCMA by CD3 antibody. I think we can compete very effectively. And oftentimes in oncology, the data will sell your product, and we're in the process, we think, of generating a very compelling data set for patients.

Great. Well, you guys have a very rich pipeline. Maybe in the last minute or so that we have, Ryan, can you sort of walk us through maybe what you think are the key catalysts for the pipeline over the next 12 to 18 months? And any programs that you think people should be paying more attention to?

Sure. I can walk through a few. We've already talked about LAG-3. That's clearly front of mind for many. I think in the second half of the year, we should have an interim readout for the C5 opportunity in Geographic Atrophy, which is a very meaningful opportunity and then in PNH towards the end of this year.

We also have Factor XI in the process of enrolling patients. And I think even by sometime in the first half of next year, get a readout in the VTE study following post knee replacement. So beginning to read out some pivotal data from Factor XI as early next year. So we're certainly excited about that. That program is huge and has a lot of opportunity.

I think there's also going to be read-throughs that we can make from competitive readouts that should be occurring in the second half of this year. So we'll be looking at those. Additionally, I think the obesity study start will be important for us as a milestone. And then I guess, ultimately, we're going to be looking for those LYNOZYFIC readouts beginning sometime in 2027.

Great. Well, thank you both so much for joining us, and thank you for everyone for joining us in Miami.

Thanks, Ellie. Thanks, everyone.

Thanks, Ellie.

Good morning, everyone. Tyler Van Buren here, senior biotech analyst at TD Cowen. Thank you very much for joining TD Cowen's 46th Annual Healthcare Conference.

For next session or first session of the day, actually, very excited to be hosting a fireside chat with Regeneron. And it's my pleasure to introduce Chris Fenimore, Executive Vice President of Finance and Chief Financial Officer; and Ryan Crowe, Senior Vice President, IR and Strategic Analysis for Regeneron.

Chris and Ryan, it's a privilege to have you here. Thank you very much for joining me.

Thanks, Tyler. I think my shoes have finally dried out from the trudge in through the snow last night, but it's always great to be here at the TD Cowen Conference and looks like a great attendance. So thanks, everyone, for coming.

Chris and I have a very compelling story to tell you today, I think, when you look at Regeneron and all the things we're going to talk about over the next 30 minutes, most of it's besides maybe Dupixent and EYLEA, not reflected in evaluation. We've got clinical programs that we're working very hard on to bring to patients, none of which is really being appreciated, I think. So I'd ask that you listen to the story here today.

And before we get to it, though, I got to read this forward-looking statement. So I'll do that very quickly. I remind you that remarks made today may include forward-looking statements about Regeneron. And each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Tyler, back to you.

Wonderful. So at a high level, I wanted to kick off just with the earnings growth story over the next 2 to 3 years, it's undeniable if you spend enough time in the model, it's pretty objective just modeling the underlying business and things like the Sanofi development balance payoff that's now occurring midyear.

Some are saying could even get to $70, $80 of earnings and 2 to 3 years from now. And if you guys trade at a discount to your historical multiple of 20 times, you're going to get to well over $1,000 per share regardless of the pipeline, which we'll get to.

So maybe you guys could talk about some of the key growth drivers to earnings over the next few years on the top line? And maybe just the details of the Sanofi development balance payoff and the magnitude of that? And then also on the bottom line with respect to your update on earnings margins, expenses and then tax as well.

Sure. Again, thanks for having us, Tyler. So as we look at the top line, there are a number of different levers that will drive the top line going forward. We are obviously with our commercial team laser-focused on converting EYLEA 2 mg over to EYLEA HD as rapidly as possible.

We had our approvals at the end of last year for every 4-week dosing and RVO. If you think about RVO, it's upwards of close to 20% of the market opportunities, so something that we were unable to tap before. It really presents a sizable opportunity for EYLEA HD and for every 4-week dosing, it was something that was very important for reimbursement confidence for the physician community. So getting those 2 behind us is very encouraging for EYLEA HD and then obviously with the prefilled syringe coming next month. That is also something that we'll be reinforcing for the EYLEA and ophthalmology franchise.

As we turn to Dupixent. Dupixent continues to do exceedingly well. If you just look at the fourth quarter and annualize the revenue that was just under $5 billion, obviously, doing very, very well, continue to do well, supported by recent launches and obviously, additional expansions going forward. As you think about the base of the revenue as it continues to grow, we would -- while obviously continuing to support the brand and invest in the brand, expect some sort of margin enhancements as the higher revenue would drop to the bottom line.

And then as you touched on, Tyler, the repayment of the development balance. So we've guided that we expect that to be repaid by the middle of this year. We ended 2025 with approximately $600 million. So just doing it on a run rate basis, on an annualized basis, that's approaching $1.2 billion. So we'll get the benefit of that in the second half of this year and then obviously a benefit in '27 and beyond on a full year basis.

And then beyond Dupixent, we have our oncology franchise and hem/onc franchise, where Libtayo recently with a launch in adjuvant CSCC, which we believe is sort of a blockbuster status onto itself, at least on a global basis. And then Lynozyfic, which is approved in late lines in multiple myeloma, it will be its first full year, so we'll see some growth there as well.

Turning to other things in the pipeline, and I know we'll touch more on that a little bit later, but a filing for myasthenia gravis and then a potential launch potentially as early later this year will be another inflection point. And that's just one of the many things that are in the pipeline that we expect to evolve over the next couple of years. On the expense side, I will say that the way Regeneron manages the business is we make sure we resource our capital allocation priorities.

So first and foremost, that's investment in our internal R&D capabilities. We guided at the midpoint of the range to roughly $6 billion on a non-GAAP basis in R&D expense in 2026. Just a reminder that we have several late-stage Phase III programs that are fairly large. So we will continue to ensure that those are properly resourced and properly funded. With that being said, we're very mindful and cost-conscious in terms of managing our expenses. We recently hired a Chief Digital and Technology Officer as well as a Chief AI officer. So trying to run the operation, obviously, as efficiently as possible and leveraging technology in AI as much as we can as trying to get as much leverage on the expense side.

We gave guidance on the tax rate and also COGS. I think on the tax rate, it's consistent with what we've described in the past, which is from a mid to long term to be kind of in the mid-teens range. What drives that to go lower historically has been stock-based compensation, and that just depends on the timing of when employees exercise their options.

And on the cost of goods sold front, we view that as transient in terms of some investments that we're making in terms of the impact on margins. It will be a multiyear journey as we're investing in various aspects of our manufacturing network in both manufacturing as well as fill/finish capabilities.

Awesome. That was a lot. But we'll try to knock off some commercial questions and then we'll get to the pipeline. And I'll do my best to be efficient. So forgive me for the multipart questions.

But -- so EYLEA HD, a real nice reacceleration and growth last year entering '26 with some momentum. Can you just talk about if you've seen kind of increased uptake following the RVO and every 4-week dosing label expansions, so far, if you're seeing that already? And just, I guess, PFS were high level of confidence we're getting that in Q2 and the latest on charity funding as well.

Sure. So there's a lot in that question. So as you look at the enhancement and we talk about them. It's -- we used to get asked a lot which one is the most important in our response was always they're all important. So what we hear from the physician community is obviously very receptive to having RVO because as you think about it, when they keep product in their refrigerators, in those physician offices, if one of the products doesn't have one of the indications, it's just the way we described it, it was almost a handicap in terms of our commercial team's ability to execute in that area.

So obviously, important, as I said earlier, reimbursement confidence also important and very important to the physician community. In terms of the prefilled syringe, as I said, we're expecting that next month. And people always ask how important is the prefilled syringe. It's very important. I mean there are going to be some practices that just basically don't want to use it just because of the administration that's required in their practices and the overhead involved in that. There are going to be others that it really doesn't matter. But at the end of the day, we know based on our own data that EYLEA 2 mg is upwards of, I think, 95% of utilization is a prefilled syringe. So it's clearly important to the physician community to have the flexibility of having a prefilled syringe.

On the charitable funding side, we announced basically that there was a contribution at the end of last year and the fourth quarter of $60 million. We matched that accordingly based on our matching program. So there was funding available around the beginning of the year of around $120 million. We know historically based on what the need is out there in the community that that's not enough to satisfy all the need that is out there.

We obviously want to see that patients get access to the therapies that their physicians recommend for them that they think is most appropriate, which is why we, again, announced that we are prepared to match in 2026. Up to another $200 million. But we also recognize the reason we put that matching program in place and then reinforce it for 2026 as we can't do it alone, and we need others to participate. From an impact of what we saw in 2025, the data that we see is the number of injections in terms of on the branded side, decreased about 12% year-over-year.

And the number of Avastin injections increased year-over-year. The data that was recently told to me, about 1 million injections increased from '24 to '25. So it clearly has an impact on the ability for patients to get the therapies that they think are and their physicians think are important. So it's meaningful, and we're prepared to obviously fund assuming that others are as well.

Sounds like the potential for a pretty significant reversal if others get their act together. But have you seen anything year-to-date to match? Is there any updates on that front with respect to charitable contributions?

I think it's too early to tell just based on where we are in the year.

Okay. All right. So Dupixent, I mean, a beast of a franchise continues to beat almost every single quarter. The CSU launch has been very impressive as well in addition to [ COPD ], many indications for that product. But maybe I could just touch on maybe IP first, right? That's been a recent topic. What your expectations are for IP and also the ability to extend the Dupixent IP beyond current expectations.

Yes, it's a great question and certainly an amazing commercial story, but we'll start with IP. We have a composition of matter patent for dupilumab that expires in the U.S. in March of 2031. And in Europe March of 2033 and then in Japan in 2034.

So that's sort of your earliest potential timing for biosimilar competition for Dupixent. But that's just one patent of many dozens, in fact, many of which cover the dosing paradigms for each of these indications as well as the formulation, the manufacturing processes that are used to make dupilumab efficiently, all protected into the mid- to late 2030s, and even some patents going into the early 2040s.

And of course, us and Sanofi, our partner on this product are going to be asserting and defending this intellectual property to the greatest extent we can, and hopefully extend beyond that composition of matter date, expiry date. So we have a strategy there, and we're -- but in the background, also working on next-generation products that offer, we hope, a longer dosing paradigm with similar or even better efficacy than Dupixent can offer today. And the first of those efforts is going to be entering the clinic in the first half of this year. So we can probably talk more about that later, but that's sort of the high-level IP view here, and we'll see what -- how this plays out over the coming years.

Yes. It'd actually be great if you just expanded on the life cycle management plans and updates that you provided earlier this year as well as touch on the Sanofi relationship and the ability to potentially leverage that very significant commercial infrastructure with life cycle management programs in the future.