Amgen Aktie

Good morning. Thank you for joining us. It's my pleasure to introduce the Amgen team. With us, we have Peter Griffith, Chief Financial Officer; Murdo Gordon, Head of Global Commercial Operations; Andrew Martin, Head of U.S. Business Operations; and Casey Capparelli, Head of Investor Relations. With that, I'm going to turn it over to you, Peter, for some opening remarks.

Great. Thank you, Salveen. Good morning, everyone. And Salveen, congratulations on that Knicks win last night. I understand you're now one of the top Knicks fans around. Good. Well, we will be too today when we're with you. So it's great to be here. We appreciate your interest in Amgen. I wanted to share a few thoughts before we get into the Q&A session.

So I think most importantly, we believe there are lots of ways to win for Amgen, especially for patients. We're pleased with our strong first quarter performance, which reinforces our view that 2026 is a springboard year for Amgen. It's a year in which we expect our rapidly growing products to offset the impact of increased competition for the denosumab franchise, and we saw that dynamic play out in the first quarter.

Revenue increased 6% year-over-year. Non-GAAP earnings per share were up 5% year-over-year, demonstrating the disciplined financial management that has long been a hallmark of Amgen. We had 16 products, delivered double-digit or better sales growth; and 17 products now annualizing at more than $1 billion in product sales based on first quarter results.

Importantly, our six key growth drivers, Repatha, EVENITY, TEZSPIRE, our innovative oncology portfolio, our rare disease portfolio and our biosimilars portfolio represents -- represented about 70% of product sales in the first quarter and grew 24% as a group year-over-year. We expect those growth drivers to continue supporting our performance through the end of the decade.

Within oncology, IMDELLTRA now annualizing at more than $1 billion in sales and continues to establish itself as an important treatment option in small cell lung cancer. Within rare disease, UPLIZNA continues to build momentum across NMOSD, IgG4-related disease and generalized Myasthenia Gravis.

We're very encouraged by the progress we're seeing across these franchises. So let's turn to the pipeline then. Confidence continues to build in MariTide as a potential new paradigm for the treatment of obesity, type 2 diabetes and obesity-related conditions.

We're executing across the enterprise from clinical development to manufacturing as we advance MariTide's broad Phase III program and continue to build and optimize manufacturing capacity ahead of launch.

Our manufacturing preparations continue to progress well, and we believe MariTide has the potential to play a very important role across weight loss inductions, long-term weight maintenance and patients transitioning from weekly GLP-1 injections and therapies, with the potential for as few as 4 to 6 injections per year based on our extended dosing.

Our approach reflects how obesity care may evolve. Patients need effective weight loss, but they also need practical and durable maintenance options. And again, that extended dosing should help meet patients with those unmet needs.

Beyond MariTide, we have a robust Phase III pipeline, including olpasiran for the reduction of cardiovascular risk in patients with elevated Lp(a), dazodalibep in Sjogren's disease and xaluritamig in late-stage prostate cancer also exploring and investigating xaluritamig in earlier-stage prostate cancer.

We're investigating, as I said, xaluritamig in earlier stages of prostate cancer. In addition, we continue to pursue new indications for several approved products, including UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy, TEZSPIRE COPD in eosinophilic esophagitis and IMDELLTRA in early-stage small cell lung cancer.

So Salveen, let me just take a couple of moments to provide some additional context around the tax dispute and litigation. We believe some of the framing since our first quarter call overstates the potential cash impact. First, we firmly believe the IRS' proposed adjustments are without merit and our tax reserves are appropriate. We haven't changed that position in the last 4 years.

We will continue to vigorously defend our position as we have throughout this dispute with the Internal Revenue Service. Our position has been consistent, as I said, for many years and reflects the substantial value capabilities, investments, risks and contributions of our Puerto Rico operations.

Puerto Rico is 220 acres or so, 1.7 million square feet and 2,500 colleagues, many of them have technical degrees. It's a very, very important flagship operation manufacturing for us.

So then moving on to 2010 through 2015, a headline numbers from the IRS, they don't translate directly into cash exposure. As we've said before, the proposed amounts include $2 billion in penalties that we believe are wholly unwarranted. We believe the IRS calculations contain approximately $2 billion in errors.

And in addition, any potential payment would be reduced by up to $3.1 billion in repatriation taxes that have been previously accrued and paid. The last payment was actually last year of about $1.85 billion on repatriation taxes and also reduced by $1.9 billion in cash deposits that we've already made with the IRS.

So even if [Audio Gap] the 2010 through 2015, which we don't believe [Audio Gap] proposed adjustment from the IRS and the potential incremental cash impact to Amgen.

For 2016 through '22, those years involve a different tax framework following U.S. tax reform, different tax rates beginning January 1, 2018 forward, lower differences. And in particular, any extrapolation that starts with the 2010 through 2015 year would need to account for the calculation areas that I previously mentioned as well as that different -- those different tax rates and the repatriation tax payments already made.

So having -- let's get all that out of the way. Overall, we're executing against the plan we laid out for 2026. First quarter demonstrates that progress. Key growth drivers performing really well. We've got Murdo and Andrew with us today. I hope you'll explore that.

And that Phase III pipeline continues to advance 3 new Phase III programs with MariTide, a couple of extension or maintenance studies plus the SWITCH study that we've announced, and we're maintaining that rigorous financial discipline that we always do. Lots of ways to win with Amgen. We're very excited about the opportunities ahead for patients and for shareholders.

With that, over to you. Thank you for allowing me to share a few thoughts.

Thanks, Peter. One of the key investor debates for Amgen continues to center around the degree to which the company can offset the losses of exclusivity over the coming years. So walk us through at a high level, the degree to which you believe that Amgen can execute on this front and continue to drive top line growth with the current portfolio and pipeline.

Well, listen, let me flip it to Murdo and Andrew here real quickly. I'd just say somebody asked us earlier this morning about what we said a number of years ago about the long-term growth prospects. And boy, we've hit those hard.

And Repatha continues to be a fantastic franchise. I'm sure you'll [Audio Gap] that exist in primary and secondary prevention with Repatha, with EVENITY and the bone franchise and how well that's doing, with our BiTE portfolio. Thank goodness for the bike portfolio in small cell lung cancer patients in [ IMDELLTRA ]. We're going to go earlier on the IMDELLTRA.

We think lower tumor burden early lends itself exceptionally well to the bispecific T-cell engagers. So that's why we're promptly getting into xaluritamig and investigating that. and investing behind that. So there's lots of ways to win with Amgen. It's growing really, really well.

And look, the first quarter it's the evidence. And look, we've got to continue to execute at Amgen, and we talk about execution excellence all the time, Salveen, up 6% on the top, up 5% non-GAAP earnings per share in the first quarter. We expect to -- and we will work really, really hard to earn that throughout 2026 and going forward.

But let me turn it over to Murdo and Andrew because we're fortunate to have them with us today. I would just add that Andrew mentioned he's headed down to Puerto Rico because he hasn't had a chance to see those operations yet.

And I forgot to mention on Puerto Rico. I think we announced another $300 million going in there this year in investments. Last year, I think we announced about $650 million more going in down there. And so Andrew and I had a chance to catch up, and I was just sharing with them. I've been down there a number of times. It's just a great experience to go down and see the commitment of our colleagues down there, 2,500 plus to creating medicines for people around the world. So Murdo, Andrew, please.

I think you framed it well, Peter. We've got a nice story brewing at Amgen, given that we have a set of prioritized growth drivers, 3 large products with Repatha, EVENITY, TEZSPIRE by our innovative oncology portfolio, our rare disease portfolio and of course, our biosimilars.

So that story of breadth and that focus on those durable growth drivers gives us a real opportunity to sustain the loss of exclusivities that we will face currently with denosumab and Otezla in Europe, which a lot of people forget, we lost exclusivity there.

That business of growth drivers accounts for about 70% of our revenues in Q1 and is growing at 24% year-over-year. So that durable portfolio of growth drivers will allow us to continue to grow through losses of exclusivity through our long range. So that's a nice place to be. And given the number of catalysts for additional growth in that set of growth drivers, we're in good shape.

But Andrew, as you see your business, what are you excited about there?

I'm excited about Repatha, IMDELLTRA, PAVBLU and TEZSPIRE for me or the principal areas of excitement and largely is a byproduct of the enormity of headroom available to us in each of those categories.

If you start with Repatha, there's 100 million or more people globally with elevated LDL, about 50 million of those sit here in the U.S. Approximately 1/5 of those have their LDL today at levels expected as a result of the new ACC and AH guidelines.

PCSK9 have only penetrated about 10% or slightly less than that of that population. So it makes clear the enormity of the opportunity in front of us. And in fact, the momentum that we've created, we are confident, is durable and will sustain through the end of the decade for Repatha.

Same story for IMDELLTRA. We've clearly solidified ourselves as the standard of care in second-line treatment for small cell lung cancer. We frequently hear from oncologists that the durability of response and overall survival rate demonstrated in DeLLphi-304 have completely transformed the way oncologists think about the treatment of small cell lung cancer.

The NCCN guidelines and excellence in execution in the fields have allowed us to open up more than 1,800 sites of care across the country. Notably, half of those or more than half of those are in the community setting, which means we're bringing access to IMDELLTRA closer to the patients and where they sit.

And last, I'll touch on EVENITY. EVENITY is an incredible growth story in a massively undertreated and underpenetrated category of osteoporosis. More than 2 million women in this country have been diagnosed with postmenopausal osteoporosis that are either at very high risk of fracture or high risk of fracture and penetration of the anabolics into that cohort is less than 10%.

So again, another reflection of the significant headroom we have and why we're so confident in our ability to grow through the loss of exclusivity for denosumab.

Peter, you just spoke to the tax situation that's playing out with the IRS here. But you've also noted that the 2010 to 2015 tax [ court ] decision is expected no earlier than the second half of this year. Walk us through the scenarios that could play out when that outcome does come?

Well, I think, Salveen, on that, I would just say we've consistently said that we have confidence in our reserves. We have -- and we have all along. We have confidence in our position, especially after the tax court case itself, which ran from November of '24 to January '25.

By the way, it's not unusual that tax court, it's a different court system that it takes a long time to get a decision because if we do the math, it might be around 2 years before we get a decision, give or take. Think it's important to think about that.

But all along, we've said we continue to have strong confidence where we're at, both in our reserves and all the merit of what we have litigated with the IRS. So we're going to stay right there. We look at our reserves every quarter, we think about those. Our reserves include everything in them. We calculate both.

And the reserves are for everything in the company, not just for the tax case with the IRS. They're for all jurisdictions, all tax issues and so forth. We're very, very thoughtful about that. We're very confident in the tax leadership of the company and spent a lot of time on that. So that's really where we sit on it.

And people ask, "Well, gee, does it perhaps preclude you from thinking about transactions as it somehow affect what we might call our dry powder, so to speak?" I would just remind all our colleagues that in December 22, when we announced Horizon, that case was underway. And we've worked through it with the bondholders.

We had a $24 billion issuance of investment-grade debt, which at the time, I believe, was about the ninth largest issuance ever. And so we had no issues there. We don't expect any. We've got plenty of powder to do what we need to do. So we're going to vigorously defend this.

On the capital allocation strategy here, so how are you prioritizing internal investments such as R&D and manufacturing scale up versus business development opportunities and return to shareholders?

Thank you. So the #1 capital allocation priority to Amgen is to get to the best innovation, whether it's internal or external. And so we're agnostic. We understand we don't have a monopoly on the greatest innovation in the world. We also understand that our shareholders expect us to go out and find it.

And if we do find it, we're looking for, are we the best buyer? Are we the best license? Are we the best collaborator? Are we are the best partner? In other words, when we model that up, what does Amgen specifically bring to that, that's accretive and additive.

And number two, cash-on-cash returns in excess of what we're going to in excess of our hurdle rate. And number three, do we have research in there? Do we have science in the area that's proven? We've found over the years that when we compare where we have science and where we have research to where we execute on transactions broadly defined, we actually perform better and we get better returns.

And then finally, is it something we can integrate quickly? Because being a student of M&A in the capital markets, there's no question the data says faster the integration, the higher the return. And look at Horizon, that's what happened. We got after that quickly. That was a world-class integration by the entire enterprise at Amgen, and the results speak for themselves. And we are so happy to be in rare disease today when we went into it in a big way in December '22.

So I would just say, internal is fantastic. I mean we are working hard on the BiTEs. They're going really, really well. We'll continue to invest in MariTide. That is an internal asset. It's -- we're backing that up. We've got -- we'll have 9 Phase IIIs on that coming up here as we -- I guess we're underway.

3 more after that.

With 3 more after that. So we're going to get to a dozen. I said to Jay Bradner, I said, "Jay, you need 1 more. We'll have a Baker's dozen, but we're going to invest behind that." So capital allocation.

Let me tell you, this company is doing a great job. Rigorous financial discipline, 45% to 46% operating margin guide this year, and we'll be up to 12 Phase IIIs on MariTide. We've got Phase III going on Olpasiran. I think we got about 7,200 patients in there. And then we got [ xaluritamig ] going full speed in Phase III for pre-taxane and post-taxane.

So we've got a lot going on companies exhibiting strong rigorous financial discipline to reallocate back up and innovation. And after that, in our capital allocation hierarchy, if I go down one more notch, we're investing in the business, $2.6 billion guide in CapEx this year. And that's -- we need the capacity to hit the volume requirements that Murdo and Andrew are creating through the opportunities they're getting as they get medicines to these patients.

So we'll continue to vigorously fund that. Last year, we put some money behind UPLIZNA to the -- a couple of those new launches. So we're excited. We've got capital to allocate. We're going to do it prudently, thoughtfully and in a disciplined manner. But the capital allocation hierarchy is not going to change.

And just given that you are at pre-Horizon debt levels here, how willing or interested are you in doing a similar size transaction? And what are the therapeutic areas of focus right now for the company?

Well, let me -- I'll comment on size, but I think it's a great question for me to tend over to Murdo. He and I and Jay and [ Raj ] and I'll work really closely together with BD, but he's got -- he's more articulate than I am on the specific areas and he's deep into them.

In terms of size, look, we our aperture is always open. It was open when Horizon showed up. We had thought about rare and Horizon well over a year before it showed up. We didn't know that it would become actionable, it became actionable, and we were ready to go. And we were able to execute and get it done.

So we're always ready to do whatever we need to do. But again, we go to that capital allocation hierarchy, is that a company with innovation that we're excited about. It might be really small, we won't go out and spend the time and invest in that, might turn into a great opportunity. If it's of a different size and small, medium, large; we're agnostic on size, agnostic on structure.

And we'll do what we need to do to -- if it's going to hit those 4 criteria I talked about for BD, we'll take a good look at it. And if it benefits our patients and our shareholders, we'll get after it. So -- but Murdo should talk a little bit about where we're thinking in terms of the therapeutic areas and different opportunities there, too.

Yes. I think Peter has covered it really well. We look at areas of complementarity, whether that be in our research and development capabilities or in our commercial capabilities.

So if you look at the presence that we had in autoimmune from larger disease areas, translated really well into rare disease when we looked at the Horizon transaction. And as Peter said, we have a really well honed process to integrate new organizations into Amgen and retain the talent as best we can when we do that.

[Audio Gap] As you look forward, [Audio Gap] strength here, we have a very nice growth plan now with the integration of a rare disease business with the products that Andrew mentioned and with our biosimilars portfolio, we can look at a long horizon at earlier opportunities, we can look at mid-stage or even late-stage development assets.

But we're not looking to plug a big hole in revenues anywhere. We've got a nice growth story from the in-line portfolio and the mature late-phase pipeline that we have.

So we're looking in all therapeutic areas. We continue to see oncology, obesity, cardiovascular metabolic, rare disease, rare autoimmune; all as really exciting areas for us. And we do look at everything. I mean we have a large aperture when we look outside the company. So we have an opinion on whatever may transact and whether or not we want to jump in.

Great. Murdo, jumping into the commercial portfolio here. UPLIZNA significantly outperformed in 1Q, driven by the launches in IgG4-mediated diseases in Myasthenia Gravis. Can you highlight how you're thinking about the key launch dynamics to date and the trajectory in both of these indications on the forward?

Yes. No, I'm glad you think it's outperforming. It's always interesting that's in the eye of the beholder. But no, internally, we were excited about this asset when we did the acquisition. And obviously, with positive data in IgG4, I mean, overwhelmingly positive data in IgG4-related disease and then very strong data in the MINT trial in gMG. We see we have a differentiated product in both of those indications.

So strong foundation NMOSD, that continues to provide growth. IgG4-related disease, we're creating the market as we're satisfying it with the only FDA-approved agent there. That's hard when you're doing both, when there's no kind of existing big market where you have a relatively new ICD-10 diagnostic code and you're creating awareness and you're fulfilling that awareness. So that's harder than going into gMG, where there's an established market with incumbent products.

Now the growth outlook for IgG4 is very strong. There's large headroom there. The numbers on [ epidemiology ] are a little fuzzy, but let's say, between 30,000 and 40,000 patients that are eligible for treatment with UPLIZNA. And it's a horrible disease. It goes undiagnosed, physicians often are unaware as to what it is they're looking at. So we're helping with diagnosis and awareness. We're helping patients activate, and that will be a good source of durable growth for the product.

gMG, a little quicker, right? So we're seeing a good source of business coming in from bio-naive patients as well as SWITCH patients. And the SWITCH patients are coming from multiple places, not just one specific product or product category. So very good launch so far.

We did, as Peter mentioned, expand the field resources in both medical and commercial to be ready in advance of the gMG approval. And that's helped, I think, as well being ready. And we're looking at further investments to help activate more patients who are looking for improvements in their activities of daily living despite being on treatment. And we're helping build awareness of the convenience of UPLIZNA and its durable efficacy. But really exciting and a lot of headroom for growth still there.

How do you think the competitive dynamics will evolve with the entry of Regeneron C5?

Yes. I think the experience in complement inhibition in general has been mixed. We are sourcing business from the existing complement inhibitors, and we'll see what the Regeneron profile brings.

But I think given that we're highly differentiated in our mechanism and very convenient in how we [Audio Gap] I really don't see that as a direct competitive threat for us. I think there's so much bio naive and SWITCH patient sourcing that we're doing that we should be able to grow through that.

I should say, we're also in the clinic into additional indications with AIH and CIDP. Peter mentioned in his opening remarks. So we're excited about how that profile, that highly differentiated and convenient profile of UPLIZNA can help patients with those conditions as well.

2027 looks to be a big year for Amgen with regard to cardiometabolic and MariTide, and obesity being one of them. Given the Phase III program, the broad Phase III program is underway, including SWITCH and [ maintenance ] studies, how is your team preparing to launch in this highly dynamic and competitive market? And what do you see as the most important aspects of the commercial strategy?

Yes. Look, we are planning on going to market to establish ourselves as a leader in that category. We have continued to expand, and I'll ask Andrew to comment in a moment here, but we've continued to expand our cardiology and primary care presence for Repatha. We will grow that even further, given the momentum that we're seeing with Repatha in primary care.

We also just presented some data at the ADA on a subgroup analysis from Vesalius-CV for diabetes patients and being able to reduce their risk of an event. So we've got very nice overlap there. That helps, but we'll expand even beyond that for MariTide. So we're already expanding our medical effort. And we will be ready well in advance of those Phase III data coming out for the medical team and then obviously in advance of the FDA approval.

I think it serves us well to have people in territory ready to go well in advance of when the approvals occur. So we're planning on being very competitive in that market with a highly differentiated profile. That's really the thing that we started this journey with, was anticipating in the time frame for when we would launch, there would be a very busy, very competitive market, and that's played out. We've seen that just with a number of new original data presentations at the ADA.

But nothing seems to compare to the differentiated profile that we've got. And so what we said years ago when we started the early Phase I and Phase II clinical trials on MariTide, that differentiation has held up. And so we're in really good shape there.

Differentiated product, the scale of Amgen to be able to go to market, the foundation of Repatha and cardiovascular, I think we've got a really good approach to the opportunity that MariTide represents.

And as we look to all past around data next year as well, Novartis has pointed to about a 13% to 15% MACE benefit from pelacarsen is meaningful for LP(a) control. In the context of just that commercial outlook here, how do you think about what would ultimately drive uptake for a drug of that profile, but also your drug as you look to -- we've seen deeper knockdown?

Yes. Look, I like what we've done in our clinical program. We showed in Phase II that we've got a very potent reducer of Lp(a), 95% to 100% reduction in Lp(a). So if the hypothesis can be validated, olpasiran is the drug that can validate it, given its ability to lower Lp(a). Our patient inclusion criteria, we chose a slightly higher cut point than others did in their clinical trials. So again, slightly higher risk population if the Lp(a) hypothesis bears fruit.

And I like our chances to be able to deliver a strong hazard ratio at the end of that trial. So if pelacarsen reads out favorable, I like that we'll be able to positively differentiate beyond what they show.

And that -- you have to look at the cluster of cardiovascular risk factors here. Physicians are looking to do more and more for their patients. And Lp(a) gets a mention that in the guidelines, it is moderately lowered by Repatha and PCSK9s, but not really.

And so if we are trying to further reduce cardiovascular risk, this genetically defined biomarker needs a specific [Audio Gap] again, no faster [Audio Gap] looks like potentially.

You also have Phase III data in Sjogren's coming by year-end. How are you thinking about the likelihood of success here and the size of the opportunity?

Sjogren's has been a difficult disease area, kind of intractable for a lot of different mechanisms. So I like the purposeful design of dazodalibep. Obviously, the Phase II data look interesting. Horrible disease. Hopefully, in Phase III, we're able to demonstrate efficacy and safety in that category.

But it's a large underserved area where a lot of off-label medicines are used with nominal efficacy and some safety baggage. So very attractive for us. And we've got this -- we were talking about before, we've got the rheumatology capabilities, both in the research, medical and commercial arena. So it fits very well with our portfolio.

And a last question for you, Peter. You raised 2026 guidance on the 1Q call. How would you -- what would you highlight here as potential upside or downside drivers for the 2026 range that we should monitor?

Well, let's go back to those six key growth drivers. So things are going really, really well. with those. So I always like to start with those Repatha, TEZSPIRE, innovative onc, rare disease portfolios, biosimilar portfolio.

But I would say, as we think about the company and what happens in 2026, Salveen, the breadth of the company in the market is strong, 17 products annualizing at $1 billion or more. There's 16 products with double-digit growth or greater, both of those over the prior year's quarter.

And I would just say there's a lot of ways to win there. And our commercial group is working with our operations to make sure we get those to patients in every possible way we can. And so that's strong.

But I would also say we've got this -- in '26, it's important [Audio Gap] we want to win in the pipeline. So it's this disciplined data generation that Dr. Bradner has been talking about for this year. We're working really hard on that. We're going to demonstrate execution excellence in that and make sure we're after that and make the progress we want to make this year in that pipeline also.

So the breadth of the end-market portfolio and how well that's doing the depth of the pipeline and what's going on over there, I think it makes 2026 a year that will be great for patients and strong for our shareholders. And then going out towards the end of the decade and beyond, that strong end-market portfolio, those six key growth drivers, 70% of product sales in the first quarter 24% growth as a group and then going forward, the pipeline will continue to deliver on that.

And we've talked about that, and you've covered Maridebart cafraglutide also known as AMG 133 or as all of you know it, MariTide. And so we're excited about the opportunities that, that will bring and we'll continue to invest behind that.

But Amgen is a great story of rigorous financial discipline, coupled with a very clear capital allocation hierarchy. And at the end of that hierarchy, every time we talk about it, we're going to talk about innovation, the best innovation, whether it's internal or external, and we're working hard at that. And we think we'll continue to be in a position to create value for patients, shareholders and also for our staff.

Just one other question I wanted to touch on. So you've guided to relatively stable operating margins of about 45% to 46% this year as you invest in the late-stage pipeline. How should we think about the evolution of margins as you look to the end of the decade? Could you see expansion back to prior levels?

Well, we don't give long-term operating margin guidance. But in terms of how do we think about the discipline around that, that rigorous financial this one, remember for many years, and that's what you're referring to, beginning in 2013, '14 or '15, I wasn't around then, but we upped our game and took the operating margin up around 50%.

I always said when I came into the seat late '19, I said, if there are opportunities to achieve cash-on-cash returns in excess of our hurdle rates for our shareholders that made sense, we would flex that margin.

And in the last couple of years, thank goodness, we've had the opportunity to do that because that results in -- as Casey mentioned, we're going to have 12 Phase II trials in MariTide at the end of the year. We've got a pass around and moving along with 7,200 patients. We've got value Xaluritamig in Phase [ III ]. We've got the ability to invest behind that.

And we think those are fantastic opportunities. And when we have an opportunity to invest behind what's out in the market right now behind UPLIZNA and make sure that's getting delivered to the patients that should and EVENITY and invest behind that and make sure that's getting to the underpenetrated market that Andrew and Murdo referred to and same with Repatha. I mean, boy, we had an old saying years ago, "Boy, back your winners". And that is such a great medicine for patients with such a great data set.

So that's really how we think about op margin, Salveen, but it's important to us. We understand there's expectations of Amgen to be a top performer in the operating margin percentage, and we're going to continue that. And we're using all the tech and data and AI we possibly can, just like everybody else is.

We have high expectations of ourselves. And we've got a CEO that has high expectations of us and what's going to happen there. And we're excited about that and the challenge that represents.

So we'll continue to be efficient, we'll continue to be effective, and we'll continue to make sure that we produce an operating margin that our shareholders think makes sense in light of the opportunities to invest and in light of the opportunities to exhibit strong financial discipline.

With that, thank you so much. Really appreciate the time.

Thank you, Salveen. Thank you, Goldman Sachs.

Good morning, everyone. I hope you're doing well. Really pleased to see a packed room and really that goes for right now and also just the entire conference. My name is Akash Tewari. I head our pharma and biotech efforts here at Jefferies on the research side. And we have Amgen on the panel today. So really excited to have a discussion.

I'll hand it off, maybe, to Peter for opening remarks, and we'll get going.

Great. Thank you, Akash. Good morning, everyone. Great to see you. We are glad to be here. I'm not used to holding the mic. All right. So we're just -- we're really glad to be here with you. We appreciate your interest in Amgen and a couple of thoughts for you here before we get going into the Q&A.

We believe there are lots of ways to win for Amgen, especially for patients. We're pleased with the strong first quarter performance, which reinforces 2026 as a springboard year for Amgen. This is a year which we expect our rapidly growing products to offset the impact of the loss of expirations on our denosumab franchise and the increased competition there that will occur throughout this year. In the first quarter, we did exactly that. Revenue was up 6% year-over-year and non-GAAP earnings per share was up 5% year-over-year, demonstrating the disciplined financial management that is historic for Amgen. 16 products delivering double-digit or better sales growth. 17 products annualizing at $1 billion or more based on those first quarter product sales.

So as we've been saying for quite a long time, breadth and depth across our portfolio. Importantly, our 6 key growth drivers, Repatha, EVENITY, TEZSPIRE, the innovative oncology portfolio, the rare disease portfolio and the biosimilars portfolio made up 70% of the product sales in the first quarter, and that group grew 24% year-over-year. We expect those to continue to drive us through the end of the decade.

I would suggest in that, that inside the innovative oncology portfolio, we have IMDELLTRA now annualizing at over $1 billion, a medicine for treating small cell lung cancer, and I'm sure we'll talk about that a little bit. Inside of the rare disease portfolio, we have UPLIZNA, which is treating NMOSD, neuromyelitis optica spectrum disorder. It's good for the CFO, isn't it? Not bad. And also IgG4, which it was approved to treat, I believe, last May and then a year ago, May, and then also GMG, generalized myasthenia gravis approved in December, I believe. And so we're very excited about UPLIZNA. So the growth drivers are doing very, very well.

Turning to the pipeline. Confidence continues to build in MariTide as a new paradigm for the treatment of obesity, type II diabetes and obesity-related conditions. We're executing effectively across the enterprise in the pipeline from clinical development to manufacturing. And as part of that, we're advancing MariTide's broad Phase III program and build and optimizing our manufacturing capacity ahead of that launch. And I've had an opportunity to visit all of the sites a number of times and our great manufacturing capacity, our world-class manufacturing capacity is coming along really well. We expect MariTide to be really important for weight loss induction, long-term weight maintenance, patients switching from weekly GLP-1 therapies to MariTide with the potential for as few as 4 to 6 injections per year. Our approach reflects how obesity care may evolve. Patients need effective initial weight loss, but they need practical, durable maintenance options.

And beyond MariTide, we have a robust Phase III pipeline, including olpasiran, which is for the reduction -- being investigated for the reduction of CV risk in patients with elevated Lp(a). I would note Narimon is a cardiologist in charge of our development. So I'm sure we'll want to visit olpasiran here as important as that will be. Dazodalibep being investigated for Sjogren's disease, xaluritamig being investigated for late-stage prostate cancer, another bispecific T cell engager. We're also investigating xaluritamig in earlier stages of prostate cancer.

In addition, we're pursuing new indications for several of our approved products, including UPLIZNA, which I mentioned previously, in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy or CIPD, TEZSPIRE in COPD and eosinophilic esophagitis and IMDELLTRA, again, in early-stage small cell lung cancer.

Now Akash, I know you have a KOL or key opinion leader call, I think scheduled tomorrow on the...

On the tax case, yes, that's right.

And so I just wanted to mention on the tax front since there have been some questions around that since our first quarter call. Two related matters with the same core issue, value attribution. The IRS is arguing that our Puerto Rico operation should be treated as if it were essentially a limited-value contract manufacturer. We strongly disagree with that position, and we have since they've adopted it. We've got 2,500-plus colleagues who are United States citizens at our flagship facility there in Puerto Rico, the majority with technical degrees. It's a very complex operations.

Remember, there are 2 tax periods in question now, 2010 through 2015 and then 2016 through 2018. 2010 through 2015, that tax court matter is not new. It's been around for a number of years. There have been no changes in our position on the status of that case. It's been fully tried and litigated. The tax court stopped hearing that case in January '25. We don't expect a decision from the judge any earlier than the second half of 2026.

Now as fully expected in the ordinary course of the IRS audit process, we received a notice of proposed adjustment, or NOPA, as I call it, for similar transfer pricing issues for that 2016 to 2018 period. It's just an early step in what we would expect to be a multiyear process. It's not a final determination. And importantly, our commitment to Puerto Rico continues to grow. Since our first quarter call, we announced -- you may have seen an additional $300 million investment into Puerto Rico on top of the $650 million that we've announced also in the past year or so. Puerto Rico is a core part of our operations, our manufacturing network, flagship facility, advanced manufacturing capabilities for biologics, deep expertise all the way around. So we disagree strongly with any characterization of those as our operations there is limited value contract manufacturing. So we continue to believe the IRS claims are without merit and our reserves are appropriate as we have all along.

Just closing, we are executing against the plan we laid out for 2026. The first quarter demonstrated the strength, the breadth, the depth of the business, 6 key growth drivers are performing, Phase III pipeline moving along, and we're maintaining our rigorous financial discipline on behalf of our shareholders as we're investing for the long term. Lots of ways to win, Akash. I just wanted to share those comments. Thank you.

No, I appreciate that. That's excellent. And the last panel I just hosted was an AI panel. So I'll give a brief question on this, Peter, to you. And it's -- I think we often hear about AI for drug discovery but we had Albert from Pfizer and he's saying, look, right now, for large organizations, it's about how we operate our cost basis much more efficiently, and that's going to be the first wave of changes.

So really, here's the question. China is making drug discovery cheaper. The cost of making drugs has gone down. Commercial organizations are becoming more efficient. And yet, when I look at my model, I'll criticize myself or really the Street widely, we are not modeling these businesses, including yours, being a step order more efficient when we think about the margin structure, right? We still have the 20% to 25% on R&D. We still have the 20% to 25% on SG&A. And then we have the corporate costs, which can often be very substantial. Are we making a fundamental mistake here? And we are going to see enormous improvements in operating structure with companies like yours in the not-too-distant future.

Thank you. It's a very important question. We are fully committed to technology, artificial intelligence, data. And I would suggest we're fully committed to it across the enterprise. And I will invite Narimon in a moment to discuss ways in which we are using it and applying it in our research and our development functions. But I have said all along, Akash, that in research and development, becoming very, very proficient if you're one of the leading biopharmaceutical companies, which we are, we better be good at it, and we better be on it and working it as effectively, efficiently as we can.

As you go across the enterprise, if I -- if you would allow me before I turn over to Narimon, manufacturing, we opened Amgen, Ohio, which is a finished drug plant a couple of years ago, finished drug processing plant. And that is our most technologically advanced plant. So roughly speaking, we have maybe 50% or 60% of the headcount we would have had in a plant before that. And by the way, the labor is fabulous in Ohio. We're super pleased with it. We're actually opening another plant there. It's under construction, AOH 2 right next door.

We call it a Butterfly plant, just to open the wing up. The technology, the AI there is fantastic. We have -- it's either 7 or 8 automated ground vehicles. Nobody drives forklifts anymore. They're automated, no injuries. They don't go on break. They haven't been getting sick. They get recharged and plug themselves in when they've got time to do it. We then move over to the commercial operations, and we're using it very effectively there. We use it -- Kave, I'd invite Kave after Narimon speaks to talk briefly about it. I know we're taking some time, but this is important.

And Akash, I would suggest we're -- I've guided to on behalf of Amgen, a 45% to 46% operating margin this year. Look, as part of that, we have to start and are incorporating some AI to become more efficient. We -- I would suggest AI is going from the individual and functional use cases across companies, including ours, to enterprise use cases. And we're after that. We are pursuing it vigorously. We think it's really important. And we realize, too, that it's going to cost more. When Google does an $80 billion equity offering, somebody is going to be paying for the cost of all this compute at some point. We're all beginning to, and we're going to be thoughtful about that. So we feel it's incumbent upon us to get those returns for our shareholders and most importantly, to use it to get innovative medicines to patients better, cheaper and faster.

So with that, Narimon, maybe a sentence or 2. I know we're taking some time, but this is so important.

Yes. No, thank you, Peter. And thank you, Akash, for the question. As Peter mentioned a moment ago, we're using artificial intelligence, starting with the very beginning of the R and all the way through the end of the D in R&D. This gets into helping us develop new insights, improving our speed, cost and quality of the work that we do in R&D, all of which are very important.

To give you a sense of some examples of that in terms of insights, think about the data that we have had through our work at Amgen deCode and looking at multi-omic data. We're looking at human genomic data, proteomic data, pulling all that information together and coming up with new targets to interdict upon developing new medications. That is now going to be accelerated and assisted with AI, new insights. We also use this technology to help speed up our late antibody optimization efforts in developing the therapeutics, right? We've seen improvements in speed of up to 50% on that angle in developing the therapeutics to then take into the clinic for clinical testing. Once we make our way into clinical studies, we've applied artificial intelligence in helping us select the sites tailored to the population of patients that we're recruiting.

And at times, we've seen a threefold increase in the speed of recruitment on the basis of picking the right sites that are tailored again to the right drug for the right trial. And once you're finished with the clinical studies, there's, of course, another R, and that is regulatory and filing, and we found that artificial intelligence has enormous potential in ingesting all of this data that we've generated over the life cycle of a medicine and putting it in the form of a draft document that will be ready to submit to a regulatory authority for review. So you can see through all of those steps, you get new insights. It helps with the speed, obviously, the quality of the work that we do goes up, and that will ultimately help us reduce cost.

Kave?

Yes. From the commercial standpoint, to build on what Narimon and Peter shared, we're really focused on the use of the technology to speed up the access and use of our medicines around the world. So we've got 3 big areas where we're focused on AI right now. First, remove the friction from getting access to our medicines, both in the U.S. and abroad, going along with the regulatory comment that Narimon made, it's great if we can get the medicine approved faster. We also need to get it paid for faster. And so using the AI to speed up the filing of our reimbursement applications, the quality of those reimbursement applications. But in the U.S., access to medicine in terms of understanding where you are in the insurance scheme, co-pay, prior authorization, patient support. So that's one big pillar, and that's going to show up in the revenue side more than the cost side overall.

Second area is in patient identification, which is really important in rare disease. We've built some really great capabilities of identifying where patients are so that we can interact with the physician around the time that patient is seen. We're using the AI to speed up and enhance those capabilities, which allows the effectiveness of our promotion to go even higher in those areas.

And then third, we know that physicians are using AI to change their own behavior. So making sure that our content and messages are showing up in those workflows in the AI of their choice is helping us identify and get patients on to therapy faster. So Akash, when you think from the commercial perspective, we're going after the efficiencies, but those efficiencies are being reinvested to drive the top line faster more than the cost line down at a differential rate.

I think that's an important point to note. And I think you'll hear that pretty consistently. It's more about top line growth rather than just outright cost cuts. Maybe going into the clinical side, and we'll start with Lp(a). And it's -- to me, you look at the genetic data, it's clearly a predictive marker. But LDL-C is such a rare kind of biomarker in cardiovascular disease because seemingly, the more that it goes down, it continues to have a benefit I always worry for Lp(a), there might be more of a threshold dynamic where you get to a certain range and you can kind of get into a range where it's not really impacting your cardiovascular risk. So there's more threshold dynamic rather than a marginal dynamic. We've seen headlines from Novartis and others in the field that these trials all tend to go longer and longer.

I'd love to get your take about these trials going longer than expected, the difficulties in terms of modeling kind of event rates in a modern cardiovascular population. And should we interpret the fact that these studies are going longer negatively or not?

Thank you for the question. It's a really good question. Let me start by reminding us that we've had over 50 to 60 years of the benefit of looking at LDL, understanding LDL biology and the science. And thank goodness, we're finally getting to the point and concept that lower is better, lowest is best, right? And with Repatha, I think we have developed a very compelling evidence base, a mountain of evidence, if you will, that shows that, that is, in fact, the case.

Now one of the important lessons from that half century of understanding LDL science and LDL biology is that it is the totality of LDL cholesterol burden reduction that is important for patients. So think of it this way. If you have a patient who has had a very high LDL cholesterol, carrying a large load for a very long period of time, that person is at high risk for having atherosclerotic cardiovascular disease, a heart attack, right? And what you want to do for that patient and the science has borne this out and reduce it to a very simple equation from the CTTC data is you want to remove as much aggregate LDL cholesterol burden from that patient for as long as possible, right?

If you look at the math, the equation is for every 38 milligram per deciliter reduced LDL cholesterol, you have a 22% reduction in relative risk for major adverse cardiovascular events. That's the reduction of LDL cholesterol. And it's what makes a PCSK9 therapy like Repatha so powerful, right? Start earlier, take it longer, reduce the LDL to as low as possible. That's where the puck is headed for LDL biology.

How do we apply that to Lp(a)? Your question, all right? Well, Lp(a) and LDL have a lot in common. If you look at the particle structure, they look quite similar for the exception of a covalently bounded more atherogenic and thrombotic protein, the L(a) of Lp(a), okay? And the way that we've approached studying Lp(a) is we want to start with the patients that have the highest burden of disease, highest burden of Lp(a) that are at risk and have shown that they have had untoward cardiovascular events, specifically coronary events, and we want to be able to follow those patients for a longer period of time. And that is exactly how our study has been designed, high Lp(a) threshold, more than 200. We have an incredibly effective medicine with Olpasiran that can reduce that Lp(a) by more than 95%. In some cohorts from our Phase II, we reduced it by 100%, right? And you want to have this type of therapy for those patients that carry such an enormous Lp(a) burden for a long period of time and have already suffered the consequences of poorly controlled cardiovascular risk. So that is the basis of the outcome study that we have designed.

And as you said, Akash, the human genetic data, Mother Nature's experiment, the human epidemiology, all the anecdotes that we're seeing in the field, all point towards this being a very important dimension of residual cardiovascular risk. Once you address LDL cholesterol, you absolutely have to address your Lp(a) and 20% of us in this room, unfortunately, have a high Lp(a). And I really hope that all of us have at least taken efforts to measure it because we have taken so long to understand what LDL values are for ourselves, and that is simply not acceptable, simply not acceptable in today's age with the technology that we have.

So what do we make of the slower event rates? Should we be discouraged? Absolutely not. In fact, what we've seen over time is if you go back to the '80s to the '90s to the 2000s, the event rates for accruing cardiovascular events have slowly gone down in the population, right, of clinical studies. Why is that? Well, we demand them to be on better medicines for one, right? You want to see patients on PCSK9 inhibitors in a cardiovascular outcome study, so you can understand what value your therapy brings forward on top of LDL reduction.

And so that's one reason for it, all right? There are a number of other reasons that could include highly efficacious mechanism with Lp(a) reduction because when you're looking at event rates in a study, you don't know which arm is having the event rate reduced. You're looking at an aggregate value. And so if you have a very effective therapeutic, the aggregate value of the event rate accrual is going to be lower. That is just going to be the simple math out of that.

So I don't really take any negative signs or concern out of the event rate that's coming out of these studies. I think it's a natural outcome that we expect to see from better care and potentially very effective medications being brought into the clinical trial arena. And I remain very enthusiastic about the mechanism, and I'm looking forward to see what the Novartis study will tell us.

It's a very clear answer, and I really do appreciate it. Hitting on MariTide, and really, I think there's an interesting scientific question because your team has talked about an antibody is different than a peptide in terms of how you can sensitize the receptor. I think Jay talked about it marinating the receptor in an interesting way. I wanted to think about that phenomenon versus like you look at Novo, you look at Lilly. I mean these are companies that are more sophisticated than anyone in terms of running these trials because they have the experience.

And I remember going to ADA 2 years ago when the Amycretin data came out, and it's like 50% vomiting on all their amcretin arms. And they're moving forward to Phase III. And even with orfoglipron, the issue of geographic variability came up pretty predominantly because your diet can really impact your nausea rates. So when I look at for your drug and MariTide, really provocative data that you showed with a different kind of titration regimen, but that was 140 patients in sites in Texas. Now we have to extrapolate that phenomenon to a worldwide perspective. And that's really -- I think the question a lot of investors have is, when you think about geographic variability and just the complexities of running these obesity studies, which is seemingly getting harder, not easier because the adoption has gone up, how do you think about that phenomenon relative to also that really provocative data you've shown that perhaps an antibody has a different type of, I guess, desensitization that maybe a peptide won't, right? How should we think about that?

Yes. Thank you. Again, a great and insightful question on your part, Akash. Let's start with some basics. There are over 1 billion people in the world that suffer from this disease that we call obesity, well over 1 billion, right? And that number is not coming down. And we look at the tremendous success we've seen from the newest therapeutics entering the field, and we see that the usage is about point or 2% or less of the addressable population, okay? So there are a lot of people that have yet to even be touched by a medicine that can treat their obesity, and they really need this medicine. So as we think about the whole space of opportunity, there is still almost all of the opportunity that still resides out in the market for patients that need a treatment for obesity.

So the opportunity is remaining very large. It's true that the scientific bar has gotten up, right, has raised from 5 years ago. But the opportunity remains very large, and there absolutely are going to be segments of the population, which I think you're getting to that are going to benefit more or choose one therapy over the other. MariTide has a very competitive and compelling profile from all the data that we have accrued thus far, Phase I, Phase II and our very encouraging experience in Phase III, right?

We have what we believe is a very compelling and competitive efficacy as well as tolerability profile. And more and more people need to understand that these medicines for chronic long-term conditions need to be taken for a long period of time, right? You benefit from medicines, including medicines that reduce LDL cholesterol by taking them for a long period of time. It reduces your burden of disease over your lifetime. That's how you appreciate the benefit, not just on weight, but all the comorbidities that are chronic comorbidities like heart disease, liver disease, diabetes from them. So why is this important? It's important because you have to think about what are the attributes of your medicine and intervention that enable a patient to take it for a longer period of time, right?

So when you talk about a medicine going from being administered daily, which was back in the day of the first GLP-1s daily to then weekly, that was a big innovation. That was helpful. It's going to be very helpful for people to go from weekly to monthly, potentially every 2 months and potentially every 3 months, right? And these are the questions that we are interrogating with MariTide. We start with monthly. We've recently announced 2 studies that are going to look at maintenance beyond the initial phase of treatment that will look at every 8-week and every quarter administration. You mentioned the SWITCH study, where we're taking patients that are starting on their weekly medications.

And again, we're going to help them understand and the world understand what happens for patients when they take those weeklies and decide, you know what, I want to go to every 2-month or every 3-month administration. This will help with a large segment of the population, irrespective of the geography in which they reside. These are compelling basic needs of patients around the globe. And obesity, like many other diseases that we may end up talking about over the course of the day, is a condition where patients will need more options, not less options.

By the way, I will interpret your answer this way, and I think it's quite important. The sense I get, and I think it's a fair point, which is we're so obsessed with these kind of contrived 68-week studies with titration profiles that no one actually adopts in the real world. And your point is when you look at maintenance data, when you look at switch data when patients are already on a background GLP-1, there's tons of data that can show the drug is very tolerable to switch.

So that in and of itself is an opportunity. So it sounds like we don't know the answer to this question, we'll get in the clinical trial, but we're thinking about this the wrong way is maybe the right way...

Absolutely. You're absolutely right. And think about this. Half the people today of those 2% that have access to these medicines stop taking the medicine before a year is up. That's not great for those patients. And so we absolutely have to address the need of those people.

Understood. Kave, this is a transition to maybe when you think about launching MariTide and the commercial opportunity, it's interesting. There's just seemingly this obsession with this race to the bottom on price. And I always feel like whether you're Novo, Lilly or Amgen, you're thinking about a portfolio approach, you're thinking about sequencing patients on multiple therapies, but also the entry point might be $150 at a low dose. But by the time MariTide is getting on the market, you have potentially millions of patients who are GLP-1 experienced who are now in the insurance market, right? And one of the things that I think stands out about your development program is you're running the outcome studies. You're running -- you're getting clinical data as well.

So when you think about MariTide in the U.S., should we think about it not we're thinking about coming in at direct-to-consumer $150 to compete with oral Wegovy. But no, it's going to be patients who have already failed a GLP-1 often an oral or Wegovy. And now they are going to be in the traditional insurance system. Is that the right approach to think about in the United States? And then when you think about ex-U.S. launching an injectable medication, but it's a huge market, how do you launch an injectable product well in the rest-of-the-world market, forget even just EU-5?

You covered a lot of ground there, Akash. So let me just say, I think that, first, having a great partner like Narimon to really work through these issues in advance in development really helps us from a launch perspective. We think we've got the data that's going to, over time, show that it's easy to start on MariTide. It's easy to stay on MariTide. It's easy to sustain that weight loss on MariTide. And we're going to be ready for a number of different kind of segments of that market, whether that's patient-directed market, and insured market, to your point, throughout.

So one of Amgen's strengths has always been the tight intersection with access through our development plans and our commercialization plans. And so understanding the data and the economic drivers of a payer versus a patient is something that we are building that evidence base of so that depending on how the market evolves over the next few years, and it will evolve quite a bit, we're ready for that market. I would say thus far, what we've seen from a pricing standpoint is in line with our expectations of what we thought would happen.

And we are seeing in this market, which is different than a lot of pharmaceutical markets that the price reductions are coming with demand lifts overall, and that's directed primarily by that patient-driven segment. But irrespective of where the patient is, we want to have a solution for them and the development plan is helping us do that for the United States, but also for outside the United States, where some markets will be more patient-driven and some will be more reimbursement.

And just to hit on that, in line with your expectations, actually, that isn't totally dissimilar to, I think, how Lilly would describe it. But there is this sense, I think, with the established players now that we are maybe out until the end of the decade to, at least in the United States, a level of pricing stability. We'll have mid-single-digit declines but they seem quite confident that price of a cup of coffee, you've kind of reached that price point that there is a ton of inherent demand just to have. And really, the work is going to be on insurance access and just negotiating those contracts. Is that maybe the view Amgen has Because, again, MariTide is -- you're going to be thinking about that commercial market pretty shortly.

Yes. I think that's a scenario that's out there, Akash. We're ready for a lot of different scenarios, and we're really looking to see how they play out in the market in advance of our launch. But I think we're going to be ready for those scenarios once we get to market.

Understood. I'm going to sneak in one more question on IMDELLTRA. And it's really about the opportunity in maintenance. And it's funny, a lot of people focus on KEYTRUDA and lung, but I think a lot of the money they make is in a maintenance setting. I don't think that's well appreciated. Would it surprise investors if the maintenance opportunity in IMDELLTRA could actually be bigger than the frontline traditional opportunity there?

Yes. I'm just back from ASCO. I can tell you that the physician community is extremely excited about IMDELLTRA in both the frontline and in the maintenance setting overall, and we're excited to be releasing additional data over time that shows that durability of response getting to long-term survival overall, Akash. I would say that data will still mature to inform the field, but I can tell you my interactions, the field is quite excited about the maintenance use of IMDELLTRA.

Understood. Thank you so much. I really do appreciate it.

It's wonderful. Thank you, Akash.

Thank you, Jefferies. Thank you all.

I'm Tazeen Ahmad. I'm one of the senior biotech analysts here at the bank. It's my pleasure to have our next presenting company, Amgen. Sitting up on stage, our several members from the Amgen team. Thanks in advance for making the trip over from California. We really appreciate it.

So we have Peter Griffith, who is Executive Vice President and CFO; we have Jay Bradner, who's Executive President of Research and Development; and then we, of course, have Casey Capparelli, who is Vice President, Investor Relations. Gentlemen, thank you for making the trip again.

Thank you for having us.

Okay. So maybe we could do a quick overview of the company and some important comments that you -- or statements that you need to make before we go into more detail. So I'll turn it over to Peter for that.

Great. Tazeen, thank you. Good morning, everyone. I would just add, coming over to Las Vegas is there's traffic coming over. But in today's world, there's a lot less going back. So we'll take advantage of that. So thank you for having us. We are glad to be here.

I've got a few prepared remarks I just want to run through and cover before we go to Q&A. We believe, first of all, there are a lot of ways for us to win. And look forward to the discussion around that, and especially winning for patients. We're pleased with the strong first quarter performance, which reinforces 2026 as a springboard year for Amgen. This is a year in which we expect the rapidly growing products we have to offset the impact of the patent expirations and increased competition.

In the first quarter, we did exactly that. Revenue was up 6% year-over-year. Product sales were up 4% year-over-year. Non-GAAP earnings per share was up 5% year-over-year, strong financial discipline exercised by the company. We've got significant breadth and depth across the portfolio. 16 products delivered double-digit or better sales growth in the first quarter year-over-year. 17 products annualizing at $1 billion or more in the first quarter based on first quarter sales. Importantly, our six key growth drivers, Repatha, EVENITY, TEZSPIRE, an then our innovative oncology, rare disease and biosimilar portfolios accounted for nearly 70% of our product sales in the first quarter, and they grew at 24%. An aggregate rate of 24% growth on those six growth driver categories in the first quarter.

Repatha, EVENITY, TEZSPIRE, each hold leadership positions in underpenetrated disease areas where there are millions of patients yet to be treated. These medicines all grew at 20% or more in the quarter and are well positioned for continued growth this year and through the decade. Our rare disease portfolio grew 25% year-over-year, and we see significant opportunities ahead as we scale those therapies in this category by reaching additional patients, expanding into new indications and launching into new geographies. UPLIZNA exemplifies this opportunity. It's experiencing continued growth across multiple B cell-mediated autoimmune diseases. Pretty good for CFO, Jay.

Pretty good.

Pretty good. In innovative Oncology, our portfolio grew 2% year-over-year, driven by our bispecific T-cell engager portfolio or BiTE medicines which are expanding what is possible for patients across multiple cancers. We remain particularly encouraged by IMDELLTRA, which is rapidly becoming a standard of care in late line small cell lung cancer.

Our biosimilars portfolio remains strong, driven by sales of PAVBLU this year. It's generated sales in excess of $14 billion cumulatively since we launched them in 2018. The portfolio is an important contributor to our growth is well positioned as the next wave of biosimilar candidates advances through Phase III development.

Let's turn to the pipeline. Our confidence continues to build in Meritide as a differentiated treatment for obesity type-2 diabetes and obesity-related conditions. We're executing effectively across the enterprise from clinical development to manufacturing as we advance Meritide's broad Phase III program and build and optimize our manufacturing capacity ahead of launch. We expect Meritide to be important for weight loss induction, long-term weight maintenance and for patients switching from weekly GLP-1 therapies to Meritide with the potential for as few as four or six injections per year. Our approach reflects how obesity care may evolve. Patients need effective initial weight loss and practical durable maintenance options.

Beyond Meritide, we see strong potential across a number of other programs in late-stage development, including Oplisiran, our Lp(a) lowering medicine in Phase III development, Dazodalibep in Phase III for Sjögren’s disease and Zaludirimig, which is in Phase III for late-stage prostate cancer. On the tax front, there are two related matters with the same core issue. Value attribution. The IRS is arguing that our Puerto Rico operation should be treated as if they were essentially a limited value contract manufacturer. We strongly disagree with that position.

We've got 2,500-plus colleagues who are United States citizens there, the majority with technical degrees. It's a very complex operation. There are two tax periods in question. 2010 through 2015 and 2016 through 2018. The 2010 through 2015 tax court matter is not new. There have been no changes in our position on the status of that case. It's been fully tried and litigated. We remain highly confident in the case we presented at trial, and we continue to expect a decision no earlier than the second half of 2026.

As expected in the ordinary course of the IRS audit process, we received a draft notice of proposed adjustment, what I call a NOPA in April for similar transfer pricing issues for the 2016 to 2018 period. It's just an early step in what we would expect to be a multiyear process. It's not a final determination. And importantly, our comment to Puerto Rico continues to grow. Since our first quarter call, we announced an additional $300 million in investment building on the previously announced $650 million in our Puerto Rico facility, Puerto Rico is a core part of Amgen's United States manufacturing network with advanced manufacturing capabilities for biologics, deep expertise all the way around. We strongly disagree with any characterization of these operations as limited value contract manufacturing, and we continue to believe the IRS claims are without merit and our reserves are appropriate.

So now let me close. We're executing against the plan we laid out for 2026. The first quarter demonstrated the strength and breadth of the business, the growth drivers are performing. The pipeline is advancing, and we're maintaining financial discipline while investing for the long term. We believe there are a lot of ways to win for patients at Amgen and for shareholders and staff.

Over to you, Tazeen, for Q&A.

Okay. Perfect. Peter. I think you just discussed everything that I wanted to say.

We're so glad about that.

No, there's plenty to talk about. You're a big company with many exciting things going on. So one of the things that I wanted to spend a couple of minutes on was Repatha, which has been outperforming now, and it looks like the pace of outperformance is increasing. So I wanted to get your thoughts about where the demand is coming from? And why do you think like the interest in this particular asset at this time has increased with physicians and patients.

Well, I think -- first of all, I'll invite Casey and Jay to jump in. Repatha is, first of all, it's such an important medicine and what we hope is a developing cardiometabolic armamentarium for patients that Amgen is working on when we look at the rest of the pipeline. But Repatha itself increased 34% year-over-year to over $900 million in the first quarter, about $900 million.

Strong volume growth, increasing urgency to treat patients across both secondary prevention and high-risk primary prevention. Strong prescribing momentum, new brand -- new to brand prescriptions. This is the one that I wanted to make sure I shared with you, Tazeen, increasing roughly 45% year-over-year in the first quarter. Supported by both cardiology in the primary care setting.

So VESALIUS-CV, the recent guideline updates, they're simply reinforcing earlier identification and treatment of high-risk patients. particularly in primary prevention, where the majority of patients are treated. Access and affordability, they are no longer gating factors. Repatha is on virtually every major U.S. formulary. Most patients are paying less than $50 a month. Amgen now provides another avenue for patients to access Repatha and then the underpenetrated thesis is so important, approximately 100 million patients globally still not -- still not at an LDL-C goal and PCSK9 inhibitors are still way underpenetrated. So we see a long runway for growth. We expect Repatha to continue to grow through the end of the decade, as I mentioned, and we put it as our number one growth driver for the company.

Where do you think peak sales could be just based on the pace that it's at?

We don't give peak sales, but I would just refer you to that underpenetrated population. When we think about 100 million patients out there, and there'll be heterogeneous treatments. I know there's potential oral treatments and so forth. But we're so confident in Repatha. We're confident in the data. The data is so strong for Repatha and so compelling. And so we're going to continue to work as hard as we possibly can to help all those patients in those underpenetrated areas get their LDL-C down to the recommended levels.

And is your sales force rightsized for the expectations that you have for growth over the next several years? Or do you think that you could make tweaks to that?

Our commercial group, they -- is my colleague who plays hockey says. Our commercial group skate to where the puck is going to be. Because the head of commercial, Murdo, also a massive hockey fan too. So we love that saying from Wayne Gretzky. And so they're skating to where the puck is. They're always dynamically reallocating our resources to make sure they meet the needs of the prescribers and the patients to make sure we deliver that medicine around the world at the right time to the right patients.

The group has overcome so many barriers. And I think that it's an incredible and special group of people that care a lot about market access, which is so vital to a medicine and secondary now primary prevention to really reach patients around the world. There are very few barriers now to receiving Repatha. I still sit with cardiologists, they don't understand that. It has been 8 years since we had guidelines. Now we have solid guidelines. They may not go far enough, but they're solid and improving and call out PCSK9 monoclonal antibodies by name.

There's a radical decrease in the number of step-through requirements virtually no prior authorizations to reach the majority of patients. And now with Amgen now, patients can access Repatha quite independently and with a very favorable access price. And so this group has done an incredible amount of work in the journey of Repatha to be prepared for this moment where with primary prevention data and the string of manuscripts that will come from that VESALIUS-CV study awareness and the demand for Repatha is rising.

Okay. Maybe one more question on commercial and then we'll go to pipeline. You guys have had a good early launch to UPLIZNA and gMG. You entered a crowded space, one that's expected to become more crowded. So maybe for Jay, as you think about FcRns, as you think about the potential of Regeneron to launch its C5 into the space late this year into early next and other mechanisms that are earlier stage, -- what's giving you the confidence that the UPLIZNA approach is the right one for gMG? And you've talked now many times on calls about how you expect this could become the first-line drug of choice among patients over time.

I would say that the short answer is efficacy, which is very, very strong, and though it's hard to do cross-trial comparisons, the efficacy is better. Second is durability that we observed engendered response rates really improving through the course of the first calendar year therapy. I'd say third is convenience. Patients don't want to experienced their disease, they also don't want to be reminded of their disease treating themselves.

This medicine is given every 6 months after the loading dose, which is quite remarkable. And then fourth is it targets the actual causal biology. Myasthenia gravis is fundamentally driven by autoreactive antibodies produced by a group of cells, B-cells and pre B-cells. And UPLIZNA targeting CD19 works to deplete exactly those cells, a broader group of cells than, say, a CD20 monoclonal antibody that has a limited utility here. And so I think that these four really important features. I mean, any one of them could be strong enough to compel a physician to prescribe.

But all four of these, including the fact that to date, the medicine has been rather well tolerated. That's big for these patients. And so I think we're not surprised, but we're delighted to see the increased uptake and interest in utility of UPLIZNA. And after neuromyelitis optica spectrum disorder after IgG4-related disease, after generalized myasthenia gravis, the pattern that we're observing is that diseases driven by autoreactive antibodies should respond to UPLIZNA. And if you look at that list in chatGPT or your favorite medical textbook like Harrison's, that's a long list of diseases that we're prioritizing and sequentially, just line them up and knock them down. And the next two for UPLIZNA will be autoimmune hepatitis in CIDP.

Okay. So let's stick to gMG for 1 more minute. Where are you seeing the early patient pickups coming from? Are they switch patients? And what are they switching from? And what percent of the usage right now is in treatment-naive.

Thanks. I'll leave it to Casey to discuss the specifics, but we are seeing uptake in both biologically experienced and biologically naive patients.

Yes. And it's roughly a 50-50 split between those two groups at this point. Tazeen, it's a little bit early to be characterizing exactly what therapies individuals are switching to. But as you can imagine, with other therapies that are on a more treated on a more frequent basis, every time they're in the physician's office, there's an opportunity to switch to UPLIZNA as well. And patients are looking for exactly the attributes that Jay described.

Okay. And then on the one that you're pursuing, one of the two that you're pursuing next CIDP, one that's been dominated by FcRn. You also have IVIG as an indicated usage drug. How are you thinking about the dynamics of that market versus what you're seeing so far with gMG?

I'd say more similar than different. I mean the medicine has to work there, but it targets, again, the underlying biology. It meets the patient where they're at with a convenient dosing schema. I should hope that if active, the durability would be another strong feature given the pharmacodynamic suppression of CD19 positive B cells is so durable with this afucosylated monoclonal antibody. So I would say provided strong efficacy, which is really the anchor of why this medicine is so desirable in myasthenia gravis, generalized myasthenia gravis. I think in CIDP, it stands to be very much the same story.

When should we expect to see data on that?

We haven't as yet indicated when that study will read out..

Yes, we'll be starting those two Phase III studies later this year.

Okay. And are those the extent of indications that you want to pursue for UPLIZNA? Or are there others behind it?

No, there are additional indications for UPLIZNA. And I would also share that because we've been in CD19 for so long, and you must know we have an FDA-approved and broadly utilized standard of care frontline acute lymphoblastic leukemia, CD19 called blinatumomab, BLINCYTO for its leukemia use case and intravenous continuous infusion that in our fridges and in our labs, we have a number of molecules targeting this target and this pathway and have built a whole program around B-cell depletion, leveraging CD19. Some of those diseases will track very nicely to an UPLIZNA use case and others will use a pipeline agent. But I would expect to see proof of concept, if not additional data in lupus with and without nephritis and other disease states.

Okay. All right. So now let's move on to some of your pipeline assets. Let's start with Meritide. So there seems to be a bifurcated reaction to this drug. It's either this is great. It's going to be a market share leader in the obesity space or there's not enough data right now for us to kind of know where it's going to land. What is the real differentiation? You've got a mechanism GLP, but it's going to be dosed less frequently. How is that going to compare to a multitude of other companies that might hope to launch around the same time as you guys would. So maybe help the market better understand this drug. Mechanistically, why do you think it could have some advantages over just being another GLP on the market?

Thank you. Well, I would start by saying that Meritide is a very special molecule, and it's not that complicated. It's a GLP antagonist antibody with GLP-1 agonist peptides that has dramatic efficacy on weight loss is extremely well tolerated at target doses that benefits from dose escalation just like all the other ones and it's given less frequently. So I don't think we should overcomplicate it. It's very simple. If GLP-1 peptides were twice a day, they'd be less exciting than every week. And if a mechanism that if a medicine that exploits this mechanism can be given monthly or as Peter shared, maybe every 8 weeks, where we've already shown and presented data demonstrating real efficacy, maybe every 12 weeks, as we've indicated, we've some maintenance data that gives us conviction there, and we continue to study every 8 and every 12 weeks in prospective and now Phase III trials.

I wouldn't overcomplicate it. It's a very active increasing based weight loss medicine that is just given less frequently. And that's very special. The antibody core affords an opportunity for patients not to inject themselves every single week. And as we continue to see in real-world evidence, weekly injectables are challenging for patients to stay on. And if half of patients are stopping the use of these medicines at 6 months or 12 months, are the patients getting what they need, the protection for these serious diseases are the payers getting what they deserve for providing access to these medicines. And so the features of Meritide could improve patient persistence and for chronic diseases, that really, really matters. But I wouldn't overcomplicate it, an incretin-based medicine that is given less frequently.

As said by CFO.

Simple as it gets.

Tazeen, think 52, 12, 6, 4, which one of those do you want if you're getting poked?

Yes, it's a fair point. When I got my flu shot, I didn't ask if it could be weekly. And so let's see how the data appears when we read out these Phase III studies, but we are very confident in the profile of this medicine, the design of these trials. Their execution has gone very, very well. And I wouldn't overcomplicate it.

Okay. Now what about the tolerability profile? I think there's been some questions about it. You're looking at various titrations [ cavada ] anything you could share on that front?

Yes. I'd break tolerability into two conversations. One is tolerability at target dose. It's extremely well tolerated at target dose. You could be on 350 milligrams of this, you could get it every single month. And as we've shown with the Manhattan plots from Phase II, the drug is just innocuous, just very well tolerated by patients. And the reason for this is it's an antibody core. So you're just kind of marinating in it. It's just smooth exposure.

When you do a pill or a weekly injectable, there's a spike, a medicine is absorbed and then it's metabolized, absorbed and then it's metabolized. And the part of the brain that experiences nausea and vomiting is called the area postrema and the hypothalamus and it responds to these jolts. And so if we see, let's say, the data from oral GLP-1s as presented to date and you look at their Manhattan plots, which is how symptoms are tracked over time, there's just a scattering persistence of nausea and vomiting. I think some data was even disclosed today about switching from injectables to orals. And there was real associated almost 19% nausea, significant vomiting moving to more frequent dosing.

Meritide a target dose is just smooth exposure and a smooth experience. upfront treatment. Here, Meritide is more similar than different to other injectables, that to get a GLP-1 medicine on board you need to start low and go slow with dose titration. And we've learned, as every other company has prosecuting this mechanism, that no dose escalation is worse at 1 step, that 2-step is better than 1 step -- and as we shared on our earnings call that 3-step is unsurprisingly better than 2 steps ploy 3-step dose escalation in our Phase III studies and have real confidence that the upfront experience with Meritide will be competitive and on treatment experience will be extraordinary.

Okay. And let's talk about the opportunity for it to be used in the maintenance setting.

Yes. None of these diseases go away after 52 or 72 weeks, which is how we're studying these medicines in clinical investigation. And in this room in rooms like it, those numbers matter, and we're going to deliver great numbers. But in clinical practice, these physicians are seeing patients, and these patients are experiencing these diseases for a whole lifetime. And so how patients can remain on therapy and derive durable benefit for their whole lifetime because we're not curing obesity with these medicines. But we are effectively treating it.

We are effectively treating associated diabetes and many other related conditions. We and others have become very interested for what happens after the primary endpoint. And through long-term extensions and now dedicated Phase III clinical investigation, we intend to characterize the benefits of Meritide when used for an additional year after a year of treatment or beyond.

And there, we believe that one might even require less Meritide than the acute and treatment phase because the long-lasting antibody has long-lasting effects. And so we've seen data in Phase II clinical investigation in our Part 2 extension that every 8-week and even every 12-week dosing can maintain lost weight. And the field of obesity is not surprised by this because they've talked about this metabolic set point for a long, long time, and these medicines are reducing that set point and then keeping the weight off.

We now want to follow up on this strong signal in two ways. One is could maintenance Meritide be less frequent than treatment Meritide. And second, if we can switch from Meritide to a less frequent Meritide, could we get people off weekly injectables to a much more convenient maintenance Meritide? And so we announced in our earnings call that we are initiating clinical investigation on a maintenance as well as on a switching to Meritide experience that will feature less frequent dosing. This is very important to translate efficacy which is what you see on a clinical trial to effectiveness, how well medicines can work in the real world.

Okay. How long do you expect this maintenance study that you announced to last?

Well, we have, I think, reported on clinicaltrials.gov, the length of the maintenance studies, and they'll be about a calendar year.

Okay. And in terms of pace of enrollment, do you think that this is going to be quickly enrolled?

The long-term extensions are invitations to patients who've been on the Phase III clinical trial to continue. And there, we expect real followership, really strong participation because when we did our Phase II clinical study and we offered patients to complete on to a maintenance, I think we had more than 90% conversion. Is that right, Casey?

That's correct.

Yes, more than 90% participation. So you get an e-mail or your doctor or clinician asks you, could you be interested to keep taking this medicine for a year and more than 90% signed up for that, which is people voting with their feet and their thumbs. So we're expecting very strong participation. And in fact, all of our clinical studies of Meritide have enrolled ahead of expectations. These are a strong set of clinical trials.

Okay. So we'll stay tuned on updates from these studies as we go forward. Let's maybe take a minute to talk about a couple of other pipeline assets and indications. I wanted to maybe spend a little bit of time on Lp(a) because you've got a competitor that's going to have data coming, I think, later this year, for which nearly everyone expects there to be a read-through for Amgen. So rather than me talking to investors about what the right read-through should be, I thought I would ask you, Jay, what is the right read-through to be thinking about when we see the Novartis data released for Lp(a) later this year?

No, I know that medicine well, and I'm following that research very closely as our -- as is this community. I would say that the read-through from the Novartis readout midyear will be sort of directional, but not absolute as to what to expect from our OCEAN(a) study that is forecast to read out later. It's a event-driven study. And the reason for that is that, number one, we're both testing a really strong hypothesis with very effective medicines.

Lp(a), a genetically defined risk factor for atherosclerotic cardiovascular disease. Each Lp(a) particle is 6x more atherogenic pound for pound, than an LDL-C particle. And look at all that we know about LDL-C and its reduction in its management. experiments of nature have shown that a gradient that as Lp(a) ramps up in our blood streams, a risk for heart disease ramps up in parallel. And so both of these companies are testing the same hypothesis. I like our chances.

Our medicine is quite a bit more potent than the Novartis medicine. If that medicine, pelacarsen reduces Lp(a) 70% to 75%, our medicine olpasiran flatlines Lp(a) more than 95% could matter. Second is our study has a slightly different endpoint. Novartis uses a 4-point MACE endpoint, major adverse cardiovascular events. We're using a 3-point endpoint. We didn't see from an epidemiologic standpoint, quite as much weight around stroke. And so we've thought to consolidate all of our alpha around the endpoints that we think will really move the needle for patients. And in that regard, Novartis is a good company with a good molecule, asking a good question. And so we're very interested to see the outcome, but the guidance, we think, would be -- for us would be directional.

Okay. And when the data does come out, does that allow you to make any changes if you need to? Would you think you would want to?

I think a late-stage protocol amendment would not be our preferred path forward. We are very confident in the design of this trial.

It's an event-driven study. So I think some folks had expected maybe it could come out later this year, but now you think expectations are sometime into next year. When would you have a better sense of guiding towards a data readout?

We -- there's a monitoring committee that's tracking these events. We're performing this study in collaboration with the leading global cardiovascular group. We and they have executed through the development of Repatha cardiovascular outcome trials in a very expert way. We are forecasting the event rate is not going to read out this year, and we'll have more to say about the readout as the aperture narrows on the target date, which is a certain number of events.

Okay. And maybe last question really quickly. How big do you think this opportunity is?

One in five humans is born with an elevated Lp(a). And we are studying secondary prevention first. But should that be positive, as for LDL-C, I would have a hard time explaining scientifically why that mechanism wouldn't work in primary prevention, which is a much bigger number of people. So it's a big opportunity.

Would you put it on the same level as LDL like statins and those types of drugs are bigger?

It feels like that. It feels like that. But Casey, what would you say?

I'd say it will be dependent upon the Phase III data.

Of course. And I guess if you needed to build a sales force for that, what kind of investment would you need?

I would say, and it's a good point. If you think about Repatha and what Peter described in terms of our cardiometabolic foundation that we built, very strong cardiology presence, very strong primary care presence. You can layer in olpasiran on top of that. And then also think about Meritide and the various metabolic diseases that we're studying with Meritide, but also fit right in. So we feel like we have the potential to have a very strong cardiometabolic presence in general, especially if you -- if we're successful with Meritide and with olpasiran on top of what we built with Repatha.

You actually bring up a good point. What type of overlap would there be in physicians prescribing Repatha and those who might prescribe it for Lp(a)?

It would be a high degree of overlap. Lipid management clinics are now measuring Lp(a) and the current guidelines from the AHA, one thing they got just absolutely right was recommending that patients know their Lp(a) number as all of us in this room should because even without effective medicines that we hope to have in the near term, knowing you have an elevated genetically defined risk that you can't eat better and it goes away, stop smoking it goes and go away, even Repatha doesn't make it go away, you approach your life a little bit differently perhaps.

Maybe you do an extra 15 minutes on the treadmill every morning. And so I think knowing about Lp(a) is very important. And in that way, the community is activated. Lp(a) measurement is in the guidelines, and that leads to the question, okay, so what can we do about it?

Okay. With that, we're out of time. Thanks, gentlemen, for joining me today. Thanks, everyone, for listening..

Thank you, Tazeen, and thank you, BofA.

My name is Julianne, and I will be your conference facilitator today for the Amgen Q1 2026 Earnings Conference Call. [Operator Instructions]

I would now like to introduce Casey Capparelli, Vice President of Investor Relations. Mr. Capparelli, you may now begin.

Thank you, Julianne. Good afternoon, everyone, and welcome to our first quarter of 2026 earnings call. Bob Bradway will lead the call today and be followed by a broader review of our performance by Murdo Gordon, Jay Bradner and Peter Griffith.

Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially.

Over to you, Bob.

Okay. Good afternoon, and thank you for joining us. We had a strong first quarter and are well positioned to achieve our objectives for the year. Recall, we previously described 2026 as a springboard year for Amgen, a year in which we expect our rapidly growing products to offset the financial impact of patent expirations and increased competition while our next generation of molecules progress through the R&D pipeline, setting the stage for sustained long-term growth.

As you can see from our progress thus far, we're on track to achieve these objectives. With steady execution through the rest of the year, we expect, once again, to demonstrate that we can grow through a period of patent expiration and deliver attractive performance for our shareholders with a strong portfolio of innovative medicines and biosimilars that meet the needs of patients with serious diseases.

As you listen to Murdo's presentation in a moment, the momentum of our 6 key growth drivers. Together, they generated 70% of our sales in the quarter and grew in aggregate by 24%. That strong performance sets us up well for the year and well beyond.

Turning to the pipeline. Our focus this year is on disciplined data generation and execution across a number of important Phase III programs, which again, we expect will drive attractive long-term growth for Amgen. Our confidence in MariTide as a differentiated treatment for obesity, type 2 diabetes and obesity related conditions, continues to build. We're executing effectively across the company, building the capabilities we need to bring this medicine to market.

As Jay will discuss in a moment, we're disclosing additional Phase III studies of MariTide, one of which will evaluate switching from the weekly injectables to MariTide on an every 8 or 12 week schedule. In other words, we'll evaluate switching from medicines which are injected 52 times a year to one which can be injected as few as 4 or 6 times a year. In addition, we'll evaluate weight maintenance for MariTide on a schedule of 4 or 6 injections a year as well. We expect there will be a great deal of interest in these data.

Beyond MariTide, we see strong potential across a number of other programs in late-stage development, including Olpasiran and other innovative programs in Phase III. We've talked about the excitement we feel about the convergence of technology and biology including the application of artificial intelligence across the company. Here, too, we're making great progress. And there's no question we're in a period of tremendous change, and we're encouraged by the progress we're making in embedding new capabilities.

We're doing this across the company, and we took steps early on to have Dave lead these efforts, and we're grateful to -- accomplishments leading activities across the company. I'll have more to say about Dave at the end of the call, but before we turn to Murdo, let me just thank my Amgen colleagues around the world for their dedication to our mission to serve patients and the quality of their work again this year.

Murdo, over to you.

Thanks, Bob. As mentioned in the first quarter of 2026, 16 products achieved double-digit or better sales growth and 17 products are now annualizing at sales of $1 billion or more. Overall, we delivered 4% growth in product sales, driven by a diversified portfolio of fast-growing products that continues to outpace the impact of losses of exclusivity. The evolution of our business is now well underway with our 6 key growth drivers, which include Repatha, EVENITY and TEZSPIRE, 3 innovative medicines, delivering significant clinical benefit for large populations of undertreated patients, also included our rare disease, innovative oncology and biosimilars portfolios. Collectively, these growth drivers delivered 24% year-over-year sales growth and generated $5.6 billion in sales in the first quarter, representing almost 70% of total product sales.

Starting with General Medicine. Repatha delivered $876 million of first quarter sales, up 34% year-over-year. Growth was driven by increased urgency to treat patients in both secondary prevention and high-risk primary prevention, where intensive LDL-C lowering with Repatha significantly reduces major cardiovascular events. The ACCHA updated their dyslipidemia guidelines now reinforcing earlier risk identification, lower LDL-C level and targets and earlier uses of therapy like Repatha. These guidelines do not yet reflect the practice-changing Vesalius CV data, leaving a clear opportunity to further evolve clinical guidelines and quality measures. We expect these additional changes will further encourage cardiologists and primary care physicians to manage LDL-C levels below 50 milligrams per deciliter alongside lifestyle modification to reduce cardiovascular risk in both primary and secondary prevention.

Position to our landmark VESALIUS-CV study has been strong with sustained increases in new-to-brand prescribing across cardiology and primary care, particularly in support of high-risk primary prevention patients with diabetes. At the recent ACC meeting, the VESALIUS-CV subgroup analysis in patients with diabetes and without known significant atherosclerosis was presented and simultaneously published in Jan. These data further reinforce the consistent and significant benefit of Repatha, delivering a 31% reduction in cardiovascular events.

A trend in lowering mortality rates was also observed. The body of evidence is now very clear, treating patients earlier with Repatha can lower cardiovascular events. In the U.S., Amgen now is further strengthening access to Repatha by offering a simplified cash pay option to patients. We're seeing encouraging patient interest in this direct access model, which now also includes Enbrel, Otezla, and AMJEVITA.

Repatha is now the only PCSK9 inhibitor with positive outcomes data in both high-risk primary and secondary prevention patients. These data, along with Repatha's broad access, create an imperative to close the treatment gap for millions of patients for whom Repatha can help reduce heart attacks and strokes and potentially save lives.

EVENITY sales increased 27% in the first quarter to $562 million. U.S. sales grew 35% year-on-year, and EVENITY maintains leadership of the U.S. bond builder market with a 65% market share. To date, approximately 320,000 U.S. patients have been treated with EVENITY, supported by increased investment and an expanded field force. However, the unmet need remains significant, with more than 90% of the 2 million women have very high fracture risk remaining untreated, presenting a clear opportunity to expand the market and drive additional EVENITY growth and impact. In Japan, EVENITY has been prescribed to more than 900,000 patients since launch. And it leads the bone builder category with over 55% market share. We see a positive reaction to the treatment guideline updates by the Japan Osteoporosis Society, which further improves EVENITY's positioning and potential.

Moving to inflammation. Test buyer sales grew 20% year-over-year, reaching $343 million in the first quarter, driven by robust patient demand and solid execution across both pulmonology and allergy specialties, partially offset by a burn in channel inventory. TEZSPIRE remains well positioned to reach more patients in the U.S., given its differentiated TSLP that targets multiple inflammatory pathways driving severe uncontrolled asthma, including in those patients with coexisting chronic rhinosinusitis with nasal polyps. This new indication is gaining traction and helping expand TEZSPIRE's reach across a broader patient population.

PROLIA and XGEVA combined delivered $1.1 billion in sales in the first quarter, a decrease of 32% year-over-year. Erosion of exclusivity remains in line with our expectations, and we anticipate accelerated sales erosion over the remainder of 2026 driven by increased competition from multiple biosimilars.

Our rare disease portfolio grew 25% year-over-year to $1.2 billion. The plasma sales increased 188% year-over-year to $262 million in the first quarter, reflecting growing demand across all 3 approved indications. We're encouraged by the pace of growth and the potential that it plasma has to help patients living with rare autoimmune conditions with significant unmet need. uptake in gMG has been strong across both by naive and switch patients, supported by broad access for most covered patients without requiring a step through another approved biologic. Given this momentum, we see a meaningful opportunity for to become the first-line and first switch choice for appropriate patients living with gMG.

Momentum in IgG4-related disease continues with UPLIZNA adoption led by rheumatologists and increased prescribing by GI specialists and neurologists. In NMOSD, UPLIZNA continues to maintain its leadership as the most prescribed FDA-approved therapy in the U.S.

TEPEZZA sales grew 29% in the first quarter to $490 million. In the U.S., more than 25,000 patients have been treated since launch, with growing interest from both new and returning prescribers, increased prescribing from endocrinologists and a broadening specialist base. We see rising awareness of moderate thyroid eye disease in the U.S. This positions TEPEZZA for growth, supported by its best-in-class efficacy, well-established safety profile, industry-leading patient services and broad payer coverage.

We're also encouraged by the positive Phase III data for the on-body injector, which demonstrated comparable efficacy to IV TEPEZZA and supports a clear path to subcutaneous administration without compromising clinical benefit. This convenient dosing option will enable TEPEZZA administration at additional sites of care and expand access for more patients in the future. Following our launch in Japan in 2025, we expect additional global launches of TEPEZZA in 2026 and beyond.

TAVNEOS sales were $119 million in the first quarter, up 32% year-over-year driven by strong volume growth. Since its launch in 2021, more than 8,000 patients have been treated with TAVNEOS, and Jay will comment on recent regulatory events in just a few months.

Our innovative oncology portfolio, which consists of BLINCYTO, IMDELLTRA, Vectibix, KYPROLIS, LUMAKRAS and Nplate grew 25% year-over-year, generating $1.8 billion of sales in the first quarter. IMDELLTRA delivered $258 million in first quarter sales, driven by deep clinical conviction and continued adoption across care settings. More than 1,800 U.S. sites now administered IMDELLTRA with a majority of doses delivered in the community setting. This progress has been supported by the combined efforts of our commercial, medical and access teams to remove operational barriers that physicians encounter in practice, helping expand patient access to treatment.

IMDELLTRA has become the standard of care in second-line small cell -- an aggressive disease with poor survival outcomes and few effective options to extend life.

BLINCYTO sales were $415 million in the quarter, increasing 12% year-over-year, driven by broad prescribing across both academic and community settings. BLINCYTO is widely recognized as the standard of care in combination with multi-agent chemotherapy for patients with Philadelphia chromosome-negative B-cell ALL.

Our biosimilar portfolio delivered 14% year-over-year growth, generating $835 million in sales in the first quarter. PAVBLU, our biosimilar delivered $280 million in first quarter sales. Adoption continues to expand among retina specialists who appreciate PAVBLU's ready-to-use prefilled syringe, and Amgen's track record of manufacturing biologics and delivering reliable supply.

Since our first product approvals in 2018, our biosimilars have generated more than $14 billion in cumulative sales, contributing meaningful growth while expanding patient access to high-quality, lower-cost biologics.

Our first quarter results reflect both the strength of our key growth drivers and the commitment of our commercial, medical and policy colleagues globally to improving the lives of patients facing serious diseases, and we remain focused on extending the reach of our medicines to even more patients in 2026.

And now I'll hand it over to Jay.

Thank you, Murdo, and good afternoon, everyone. Let me begin with MariTide, a new paradigm in the management of obesity, obesity-related conditions in type 2 diabetes. The unique antibody peptide conjugate design of MariTide delivers a potential for strong efficacy with monthly or less frequent dosing and favorable tolerability to improve long-term treatment. With existing obesity medicines, treatment burden and dosing frequency remain barriers to long-term persistence on therapy. For individuals with chronic conditions, sustained treatment is often required to realize the full health benefit of therapy. MariTide's unique properties, particularly its potential for monthly or less frequent dosing may help reduce treatment burden and improve persistence on treatment over time.

Towards this objective, we are excited to announce two new Phase III studies that focus on longer-term maintenance therapy with MariTide. We have initiated 2 long-term extensions of our ongoing Phase III chronic management studies to evaluate MariTide maintenance for durable weight loss. Participants who completed 72 weeks of treatment in the parent trial will enter a 48-week extension treatment period, where they will receive a monthly every 8-week or quarterly dose of MariTide. To date, our clinical trials have studied MariTide in the initial management of obesity and overweight. We recognize that many patients may wish to switch to MariTide from weekly injectables. Today, we announced the initiation of another new Phase III study that will evaluate switching from weekly injectable GLP-1 therapies to MariTide, following dose escalating to a convenient every 8-week or quarterly dosing schedule. Combined with our ongoing pivotal chronic weight management Phase III trials, the MariTide program will inform physicians on how to start a new patient on MariTide and how to switch to a more convenient, less frequent dosing.

Previously, we described the benefit of dose escalation for improving initial tolerability with MariTide. We observed marked improvements in GI symptoms progressing from 1-step to 2-step dose escalation. Our accumulating experience with 3-step dose escalation is quite positive. For example, we recently completed one of our standard Phase I physiology study preparation for potential regulatory filings that utilize 3-step dose escalation. As anticipated, 3-step dose escalation further decrease the rates of nausea and vomiting as compared to prior experience with 2-step dose escalation.

We believe that 3-step dose escalation and less frequent dosing are effective and well tolerated because of the unique antibody backbone of MariTide. The long-lived stability of an antibody creates a gentle and smooth step-wise increase in sustained drug exposure. Stable drug levels avoid the frequent peaks and troughs of daily orals and weekly injectables that may contribute to intolerability.

We remain confident and excited by MariTide and are focused on delivering high-quality clinical data to support future regulatory filings. The studies are enrolling well, indicating strong physician and patient interest in MariTide. MariTide is emerging as a new paradigm for patients with obesity, diabetes and related conditions as a well-tolerated first monthly or less frequently administered medicine.

Turning from one major public health challenge to another. We continue to build on the landmark findings from Repatha in the prevention of neovascular events. In March, a new prespecified subgroup analysis from the Phase III VESALIUS-CV trial was presented at the American College of Cardiology and simultaneously published in the Journal of the American Medical Association. In this subset of high-risk patients with diabetes and without known significant atherosclerosis, Repatha demonstrated a significant 31% reduction in major adverse cardiovascular events, including heart attack.

Repatha also demonstrated a nominal 32% reduction in the risk of cardiovascular death and a nominal 24% reduction in all-cause death. Taken together with the VESALIUS-CV data presented last fall, these findings reinforce the breadth and magnitude of benefit from Repatha in the primary prevention of cardiovascular disease. We look forward to sharing additional insights and analysis from VESALIUS with the scientific community, notably at the upcoming American Diabetes Association Annual Meeting.

Olpasiran, our potentially best-in-class small interfering RNA medicine that delivers greater than 95% reduction in Lp(a) with a quarterly dosing schedule continues to progress in Phase III clinical investigation for secondary prevention of cardiovascular events. We have recently initiated the Oceana CCDA study that evaluates the effective Olpasiran on the burden of non-calcified plaque in coronary arteries as measured by coronary CTN geography.

Attention to Lp(a) in medical practice is rising, reflected by the recently updated ACC/AHA lipid guidelines that now recommend broader Lp(a) testing.

Moving to rare disease, we continue to build strong momentum across our portfolio. For UPLIZNA, we recently received European Commission approval for generalized myasthenia gravis. Supported by a strong biological rationale, we expect to initiate 2 pivotal Phase III studies of UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy by the second half of this year. We are also advancing TEPEZZA, where we recently reported positive Phase III top line data for subcutaneous administration via an on-body injector. These data demonstrated robust efficacy in patients with thyroid eye disease consistent with intravenous administration alongside a favorable safety profile.

Subcutaneous administration of TEPEZZA represents an important step forward in improving convenience and expanding treatment options for patients with thyroid eye disease. Dazodalibep, our first-in-class CD40 ligand targeting fusion protein continues to progress with 2 Phase III studies in Sjögren's disease now fully enrolled. These studies address both systemic and symptomatic disease, and both are expected to complete later this year.

As publicly disclosed, the FDA proposed to withdraw the approval of TAVNEOS. We continue to believe that TAVNEOS is an important medicine for patients with ANCA-associated vasculitis, a rare and life-threatening disease with limited treatment options. We are confident in the benefit risk profile of this medicine and expect to engage further with the FDA on this topic.

Turning to oncology. Our bispecific T cell engager or BiTE platform continues to deliver meaningful impact for patients with advanced cancer. IMDELLTRA is emerging as a standard of care in line extensive stage small cell lung cancer, delivering an unprecedented survival benefit in a disease that has seen very little innovation for decades.

As we work to advance IMDELLTRA into earlier lines of therapy, we are encouraged by the apparent improvement in median overall survival in the first-line maintenance setting to 25.3 months observed in the Phase Ib DeLLphi-303 study. Frontline maintenance with IMDELLTRA is now being evaluated in the ongoing Phase III DeLLphi-305 study.

Xaluritamig, our first-in-class STEAP1 targeting bispecific T cell engager is advancing rapidly with two ongoing Phase III studies in metastatic, castration-resistant prostate cancer. Multiple ongoing Phase Ib studies are underway, where we've taken a deliberate and differentiated approach towards earlier stages of disease to maximize long-term patient benefit.

First, in biochemical recurrence, where patients experience a rising PSA without clinically evident disease, we are evaluating xaluritamig's monotherapy without androgen-deprivation therapy. Second, we are advancing into metastatic hormone-sensitive prostate cancer, where we are evaluating xaluritamig on top of standard of care hormonal therapy with the goal of developing a more effective regimen without chemotherapy.

One last but important note about our oncology portfolio. Following a comprehensive review, we've taken the decision to discontinue development of AMG 193, our MTA cooperative PRMT5 inhibitor.

Over the last several years, amidst the rapid advances in artificial intelligence, we've taken a principled approach to reconsidering and augmenting drug discovery and therapeutic development at the intersection of powerful AI models develop both externally and internally with Amgen Research and insight-rich proprietary data sets, we are beginning to see meaningful tangible advances across Amgen R&D. Integrated multi-omics data resources at Amgen to Code Genetics identify new targets for therapeutic consideration, in particular with the noncoding regions of the human genome study to population scale.

Anti-body lead optimization has accelerated by 50% from contributions, both to lead discovery and lead optimization. In clinical development, we have designed and implemented a proprietary site selection model that improves clinical trial enrollment with a significant and in some cases, up to threefold improvement in enrollment rates. Leveraging large language models and agentic AI for regulatory filing preparation, we are seeing early promising results in data ingestion, integration and document drafting. These are early innings. But we are captivated by the potential for AI and data science to deliver measurable impact in value in R&D and across the enterprise, as Peter will highlight in a few moments.

With the retirement of our and beloved colleague, David Reese, I'm excited to lead the AI and data transformation across our business at the enterprise level, working in partnership with our leadership, staff and collaborators. Let me close by saying that we are encouraged by the progress we've made in the first quarter with a continued focus on disciplined data generation across the portfolio with a robust pipeline and meaningful breadth and depth across 4 therapeutic areas, we are well positioned to deliver continued innovation for patients with long sustained value.

I want to thank my colleagues across Amgen for their continued focus on patients and their commitment to advancing innovative medicines for serious diseases.

I'll now turn it over to Peter for the financial update.

Thank you, Jay. We are pleased with our strongest quarter performance, executing through a full quarter of the patent expirations and losses of exclusivity. Our non-GAAP operating margin was 45%. We continue to invest in advancing our pipeline with non-GAAP R&D spending increasing 16% year-over-year in the first quarter. This reflects increased spending on our late-stage pipeline, including continued investments in MariTide, IMDELLTRA and Olpasiran. Our non-GAAP cost of sales as a percentage of product sales was 19.5%, driven by higher profit share and royalty expenses and changes in our sales mix. We expect these factors will continue to negatively impact the cost of sales in future quarters. We further expect second quarter operating margin to be in line with the first quarter operating margin.

Our non-GAAP OI&E resulted in $480 million of expense for the quarter including a gain of about $90 million from retiring debt through open market repurchases. Our non-GAAP tax rate decreased 1 percentage point year-over-year to 13.6%, primarily due to net favorable items in the current year period, partially offset by the change in earnings mix. We generated $1.5 billion in free cash flow in the first quarter, reflecting continued momentum across the business.

We spent $700 million in the first quarter on capital expenditures, driven by investments across our U.S. manufacturing sites, including Ohio, North Carolina and Puerto Rico. We continue to expect capital expenditures of approximately $2.6 billion in 2026, reflecting significant investment in our business to scale manufacturing capacity for volume growth. including for MariTide launch. We see technology and artificial intelligence and increasingly important tools to help Amgen operate with greater speed, productivity and scale across the enterprise.

Beyond what Jay described, we are also seeing tangible benefits in other parts of the business. In AI-enabled automation, it has reduced production line clearance time at one of our manufacturing sites, from approximately 30 minutes to about 2 minutes per batch run. We are also seeing promising results as our colleagues across Amgen use AI to enhance productivity.

In addition, we returned capital to shareholders through competitive dividend payments of $2.52 per share, representing a 6% increase compared to the first quarter of 2025. Let's turn to the outlook for the business for the remainder of 2026. As we said last quarter, we expect 2026 to be a springboard year for future growth. Our strong first quarter performance reinforces that outlook, and we're raising our 2026 guidance ranges for both revenue and non-GAAP earnings per share.

We expect 2026 total revenues in the range of $37.1 billion to $38.5 billion and non-GAAP earnings per share to be between $21.70 and $23.10. These ranges reflect our confidence that the emerging growth drivers will more than offset the outgoing legacy brands. Note, our guidance does not include any potential business development transactions that may occur throughout the remainder of the year.

Let me highlight a few updates to our outlook for the remainder of the year. For the full year, we now expect other revenue to be in the range of $1.7 billion, $1.8 billion, we now anticipate non-GAAP OI&E to be in the range of $2.2 billion to $2.3 billion of expense in 2026. We now expect a non-GAAP tax rate in the range of 15.0% to 16.5%. And let me remind you of prior items that have not changed. We continue to expect -- the full year non-GAAP operating margin as a percentage of product sales to be roughly 45% to 46%. This reflects our commitment to investing in the best innovation as we continue to rapidly advance the MariTide Phase III program and additional key late-stage assets. We expect share repurchases not to exceed $3 billion.

Finally, in regard to our ongoing tax litigation, the tax court litigation covering tax years 2010 and through 2015 remains ongoing. And while we expect a decision no earlier than the second half of 2026, we remain confident in the case we presented at trial. We are currently under audit by the IRS for the 2016 to 2018 tax years. In April 2026, we received a draft notice of proposed adjustment, or NOPA, from the IRS for 2016 to 2018, asserting significant adjustments primarily related to the allocation of profits between the United States and Puerto Rico.

The approach taken by the IRS is similar in nature to our 2010 to 2015 dispute with the IRS currently pending in tax court. If sustained in full, the adjustments set forth in the draft, NOVA could have a material impact on our financial statements. We disagree with the draft NOPA and have informed the IRS audit team that its draft calculation methodology is inconsistent with the positions asserted by the IRS and the tax court, which positions were more favorable to Amgen than the draft calculation methodology taken by the IRS audit team.

We firmly believe that the IRS positions are without merit, and we also believe that our tax reserves are appropriate. We intend to continue to vigorously defend our position just as we have throughout our entire dispute with the IRS. We remain focused on delivering sustained long-term growth and creating value for patients, staff and shareholders by doing what we said we would do, executing on our growth drivers, advancing innovation in areas of high unmet medical need and maintaining rigorous financial discipline. I'm grateful to work with all of our colleagues worldwide in our mission to serve patients.

This concludes our financial update. I will now hand it over to Bob for Q&A.

Thank you, Peter. Julianne, why don't we open up the lines for questions. I know it's been a long day for many of our callers. So let's jump straight in and try to get to everybody. So as many questions as we can. Try to limit you to 1 question each, please. But let's get started, Julianne. .

[Operator Instructions] Our first question comes from Yaron Werber from TD Cowen.

Great. Maybe, Jay, unsurprisingly first question on the MariTide switch studies. Can you give us a little bit of a sense? Are you switching sort of one-to-one-to-one to monthly, every 2 months and every 3 months? And are you looking at superiority or noninferiority and sort of what's the noninferiority sort of margin?

Yes, Yaron. Thank you for the interest. As I just shared, people naturally very interested to know what will it take to switch from a weekly injectable to a medicine potentially quite a bit more convenient and quite active. And so the SWITCH study is designed to provide that experience. There will be 300 subjects on study with obesity or overweight. There will be a run-in on weekly semaglutide or tuzepatide, and then they'll switch to MariTide. As I said, every 8 week or a quarterly basis. The primary endpoint of this trial will be a change from baseline body weight after 52 weeks of MariTide treatment. We look forward to these results.

Our next question comes from Salveen Richter from Goldman Sachs.

Could you just comment on the MariTide switching study and why it only evaluates the every 2 months and 3 months or not every 1 month? And then as you think about the profile today and how significant do you expect the maintenance opportunity to be for MariTide?

Why don't I start with the question around the design of the SWITCH study, Murdo, and then you can talk about the opportunity thereafter. We have a lot of experience with monthly MariTide in this program, which is featured in to date, all of the enrolling Phase III programs. And we've had a really good experience in the maintenance setting in our Phase II Part II. In that regard, the long-term extensions that we've just described where we switched from MariTide to MariTide give us a chance to explore less frequent dosing after effective dosing and comparably in the SWITCH study, we're focusing that trial on the learnings of going from weekly to in every 8 weeks and every 12 week treatment regimen, which can make MariTide quite attractive to patients is successful. Murdo?

Yes. Thanks, Jay. Thanks, Salveen. Obviously, the goal here for weight loss is to lose weight and then sustain it over multiple years, so that you can get the full medical benefit of the treatment. And given that we are coming later into this market, and there will be many, many patients already on other weekly treatments, we thought it would be helpful to prescribers to clinicians and patients to understand how to convert, how to switch from those weekly agents to, as Jay mentioned, a more convenient regimen like MariTide.

Importantly, it will also be necessary to describe once you reach your weight loss goal on monthly MariTide, how you would want to modified that dose interval either to QA week or to Q12 week for even more convenience. And so -- we've taken the opportunity, given the timing of our launch and order of entry to fully describe how to start patients on MariTide then how to switch from other treatments that patients may be on and they may be dissatisfied with.

Our next question comes from Luca Issi from RBC Capital Markets.

This is on for Luca. I have a question for IMDELLTRA. IMDELLTRA clearly done very well so far in second-line setting. Can you tell us more about what for IMDELLTRA, not only in terms of the opportunity you get when you move to the fronter lines, but also now with IMDELLTRA part of the real-time clinical trial pilot program. Could you help us understand the process? Is the idea basically FDA will look at your data scientists together as the is going and for indications with no healthy volunteers, you essentially can go straight from first in human to approval without posing for safety or end of phase reviews? And curious what made FDA take IMDELLTRA as the pilot program?

Well, let me please start, Luca. Thank you for the question. IMDELLTRA is really emerged as the standard of care for patients with second-line small cell lung cancer because as I mentioned moments ago, the unprecedented efficacy afforded by IMDELLTRA just the most important endpoint, overall survival. As for so many medicines in advanced cancer, medicines that work in later stages of the disease, tend to confer even more clinical benefit when they've moved to earlier lines of therapy and earlier stages of lower disease burden, especially when they're used in combination. And so we are advancing IMDELLTRA quite actively and aggressively into frontline induction as well as frontline induction and maintenance. The maintenance experience with IMDELLTRA and the frontline experience will be an extensive stage small cell lung cancer, and these studies are rapidly progressing. Further, we have the DeLLphi-306 study, which studies tarlatinab versus placebo after chemotherapy and radiation in frontline limited-stage small cell lung cancer. We're so hopeful for these trials and just cannot wait to read them out.

As you've described, we have had a chance to collaborate with Commissioner McCary and members of the FDA on imagining what a clinical study might look like in the real-world prospective practice. And we have a very fine design coming together with the FDA that will give us a chance to characterize IMDELLTRA in a clinical trial setting, but in the real world, leveraging things like electronic health records and real-time data capture as opposed to the way the clinical trials are conducted today. This could be a very important experiment for us and for others because so many clinical trials initiated don't complete. Enrollment is very challenging, managing data and packaging it and submitting it to regulators is quite a bit big book of work. And if there's a way to do this in more real time, we would all benefit from having this learning. So we're looking forward to working with them on that.

Yes. Thanks, Jay. The other thing that I would add here is we've seen very good progress in where patients are treated for their small cell lung cancer with IMDELLTRA. And we've seen really good uptake in the U.S. in community oncology. We've seen a very good launch in Japan. We expect to be launching in the second line indication across multiple markets this year. And then as Jay said, we have a nice randomized clinical program reading out through the balance of this year into next to further expand the use of this product. IMDELLTRA seems to have very durable survival as we've seen in our Phase I data. And importantly, in these innovative trial designs that the FDA is in discussion on, this will further help physicians, primarily those in community settings and regional hospitals or in community oncology practices, better care for their patients closer to their homes, which is a really exciting opportunity.

Our next question comes from Michael Yee from UBS.

Maybe a question on Olpasiran. Obviously, you guys have a well-designed study and potentially superior drug. I'm wondering if you think that background therapies such as GLP-1 or PCSK9, either would impact your trial design or your competitor trial design, and how you think about that impacting the overall results of what we might see from a competitor.

Jay, why don't you answer that?

Yes. Thank you for the question. And we see it the same way. The OCEAN(a) study is a very well-designed study, a randomized controlled trial of almost 7,300 patients with over 200 and the medicine Olpasiran with best-in-class performance characteristics as you cite, 95% reduction in Lp(a) with every 12-week dosing. So we're really looking forward to reading out this event-driven trial.

We have built this study around a very high-risk group of patients. Elevations in LP(a) are genetically defined. And as such, 1 in 5 individuals will have elevated Lp(a). Unfortunately, to your question, you can't take a GLP-1 medicine or a statin or even Repatha and meaningfully reduce levels of Lp(a). This independent risk factor maps to a very atherogenic and inflammatory characteristic of the LPA containing particle, which is actually 6x more inflammatory atherogenic than the LDL-C containing particle, which, of course, we and others have shown to be a dramatically an importantly modifiable risk factor.

And though we observed improvements in the standard of care for patients with cardiovascular disease, and we contribute to that with Repatha. We're very confident in the study as defined, which focuses on a high risk, high leverage elevated LP(a) population treated with direct and targeted therapy to Lp(a) itself.

Our next question comes from Terence Flynn from Morgan Stanley.

Great. Bob, I was just wondering, we've seen pretty active M&A year thus far in the sector. just as you think about Amgen's needs, potential size of opportunity, how are you thinking about the BD and M&A landscape right now, given your current needs, but also your stronger balance sheet?

Yes. I think, Terence, I would not sure I'd use the word needs the way you have in your question, but we're very active in business development, as we always have been looking for innovation that we think we can add value to. So that remains the case. I think the areas where we're interested are very clear to you and to our investors. And we'll continue to see if there are things that again, that line up in a way that we can take over programs and still add value to our shareholders.

Our next question comes from Geoff Meacham from Citi.

Great. Murdo, Repatha has been consistently strong, but I want to get some perspective from you on penetration into primary prevention? And where could it go? And as you look to the Olpasiran data, how do you think primary prevention looks as a key market within the LP(a) segment?

Thanks for the question, Geoff. We're really excited about what's happening in primary care. As you'll recall, we expanded promotion and coverage of our primary care sales team at the beginning of last year. We expanded our medical teams in anticipation, of course, of some of the news flow that we've seen new data from the VESALIUS-CV trial that we presented last November at the AHA meeting. And then as Jay mentioned, the subsequent sub-study in diabetes patients without atherosclerosis, also showing significant benefit with a 31% reduction in 3-point -- 31% reduction in 4-point So we have a clear opportunity to help these patients who are in the care of the primary care physician. The average diabetes patient without documented atherosclerosis is someone who's not being referred to a cardiologist. And so since the change in our label, which occurred actually just prior to the VESALIUS trial being presented. We've been out there talking to primary care physicians. We've seen really, really good uptake.

In the quarter, we had strong overall growth in Repatha globally. But if you look at new-to-brand prescription evolution in the U.S., we were up 44% in the quarter, and that's being driven by increased depth of prescribing by cardiologists, and increased breadth of prescribing by primary care physicians. So very strong foundation, very pleased with the momentum, but we still have a huge opportunity ahead of us in primary prevention promotion of Repatha, the only PCSK9 with that data generation now.

So real opportunity for us. Now when we look at Lp(a), the one thing I will say that helps us is the new treatment guidelines that came out from the They have recommended that everyone who is at risk of cardiovascular disease be tested. As you know, this is a genetically determined level. So you really only need to do the test once. It's affordable. It's accessible. And so that bodes well for having some population of patients who will know their Lp(a) level. And I do think that primary care physicians will play a significant role in treating those patients in lowering their Lp(a) levels with hopefully a product like Olpasiran should the data bear out.

Our next question comes from David Risinger from Leerink Partners.

So my question is for Murdo, please. So congrats on the launch of Amgen Now, I think that occurred last fall. Could you provide some quantification on the uptake of Repatha by cash pay patients? And I don't know if it's meaningful enough yet, but possibly the current mix of sales between cash pay and covered given the strong ramp of Amgen Now? And then is Amgen considering leaning into offering Repatha as a cash pay product ex U.S.?

Thanks for the question, David. We've been pleased with the overall response to the Amgen Now offering. As you'll recall, Repatha is offered at a $239 a month price point. And we are seeing cash paying patients interested in pursuing Repatha. Now at the same time, however, it's important to note, we've opened up access substantially for Repatha. And so many patients now can access Repatha without much friction and their physician can simply attest that the patient meets the criteria for the indication of the product. So I wouldn't expect the cash paying component of patients going through Amgen Now to be substantial.

We are in the kind of the 8,000, 9,000 patient range of patients moving through the Amgen Now program, and we continue to see more and more interest there. So it's been a success. But as a percentage of total Repatha, as you'll know, it's relatively small.

Our next question comes from Matt Phipps from William Blair.

I was wondering on some of the blinatumomab updates. First off, you noted in the press release that enrollment has stopped in the SLE trial. Can you give us any updates on that status. And it also looks like you're pausing enrollment of the subcu administration and ALL, any additional reasoning for that pause?

Sure. Thanks, Matt, and happy to take the question. Blinatumomab is proving to be an important component of standard of care for adults and children with relapse and refractory B-cell leukemia. And its current instantiation is delivered by intravenous continuous infusion. We have studied and characterized subcutaneous, we administered blinatumomab in the past. And there is a chance with this medicine for even higher remission rates, as we have previously shown at the EHA presentation, we observed 89%, 92% remission rates with manageable safety in adults with relapsed and refractory BALL. And so we're very encouraged by the efficacy seen with subcutaneous blend and are moving subcutaneous blend or earlier lines as you shared. We have a potential registration-enabling Phase II initiated in adults and adolescents. We have a Phase Ib/II study of subcu as well initiated in pediatric patients there with relapsed and refractory and MRD-positive B-cell ALL.

As you noted, we have paused some of these studies for enrollment. BiTEs are known to have inflammatory side effects. We prioritize patient safety, especially in the conduct of clinical investigation and observing a handful of inflammatory reactions were -- at this moment, collecting some patient data and having a dialogue with the FDA, we expect to be able to open these studies back for enrollment shortly.

Our next question comes from Chris Schott from JPMorgan.

I just want to come back to MariTide, sounds like some encouraging earlier stage data on the titration. Are you able to provide any more color on what levels of vomiting and duration of vomiting you're seeing with the 3-step titration from some of these earlier studies, if you can't provide specific numbers, just maybe directionally where that's shaking out versus Olavi or is outbound?

Yes, Chris, thanks. The level of nausea and vomiting observed with 3-step dose escalation is lower than we've seen before. Dose escalation works for GLP-1 agonism based therapy that is known. In our experience, 1-step improved GI tolerability significantly. 2-step, improved it further. And today, we share the unsurprising by accumulating data that provide clinical confirmation that 3-step dose escalation further improves GI tolerability. Now we await efficacy and tolerability data from the ongoing Phase III studies, but we're quite encouraged by what we've seen.

Jay, on the question on duration, you may help him understand what we see -- help Chris understand what we see and how it's different from what we're observing from the weekly and dailies -- in terms of the side effect...

Side effect profile. Yes. Before we started this research, we didn't know with a long-acting medicine like Maritime that can be delivered monthly or every 8 weeks or every 12 weeks, enjoy durable efficacy owing to high time on target. This antibody backbone leads to very smooth and stable exposure over long period of time engaging GLP-1 receptors and gift receptors in the brain and peripheral tissues. With that durable efficacy be associated when there was a side effect with a long-term side effect and that we don't see. When we do observe nausea and vomiting, it tends to be quite short in its duration over the course of one or several days, no different than the weekly GLP-1s. But different than the weekly GLP-1 and different than oral GLP-1s that are short half-life medicines, this trough-to-peak spike that's experienced every time these medicines are taken, we believe can be associated with intolerable side effects in the GI and otherwise. And this can be avoided with a steady, stable, long-acting medicine like MariTide. We see this target dosing of MariTide by Manhattan plot, versus what's reported in the field with more frequent dosing. And so in the fullness of time, this could prove to be a very important attribute, keeping patients on the medicine for the length of time that they have these diseases, which is for many of them, a lifetime.

Our next question comes from Akash Tewari from Jefferies.

For DAZO Phase III Sjögren's program, you're making interesting bets splitting it up into systemic and symptomatic patients. What kind of drove that decision? And which one of those trials are you even more confident will work? And can you go over any of the biological difference between DAZO and then the Novartis CD40, but also Sanofi CD40L which both ended up discontinuing their programs?

Akash, I love your questions because they invite a mechanistic characterization of these molecules, but I'll try to keep this brief, though it will be hard for me. We observed in Phase II very strong activity of dasodalibeb, which as you comment, is a CD40 ligand FC fusion protein, targeting protein. And the performance against the STI score in Sjögren Syndrome is quite a unique situation. It has proven very hard to develop effective medicines in Sjögren's disease. But seeing movement in the STI score that made us very motivated to follow this up in Phase III clinical investigation. The presentation of this heterogeneous disease can be quite different clinically. And so we thought to segregate in order to have clear clinical outcomes in these clinical trials into 2 Phase III studies, patients with what we'll call systemic disease but then also very sick, a separate study of moderate to high symptomatic disease, but they are with low systemic disease activity. In the case of these 2 populations might be considered differently to observe meaningful differences attributable to those biological, those clinical presentations. These studies have completed enrollment and completion of both studies is expected in the second half of this year.

Dazodalibep is a product of a long sought after drug discovery campaign, honestly in the field of immunology. cD40, CD40-ligand signaling is fundamental to T cell B-cell co-stimulation, CD40 ligands on T cells, CD40 on many, many different kinds of cells. And that makes this molecule very different than CFC 533 from Novartis. What is true of Sjögren's disease, whether or not it's systemic or symptomatic is that T and B cell activation is the primary driver. This isn't a dry gland disease. It's enriched with inflammatory cells. And so we believe the CD40 ligand is the right lever to press on as it will impact all downstream signaling by targeting the upstream CD40 ligand on T cells. So we look forward to reading out these studies. One with the SDI score, another with the DAS score appropriate for a symptomatic study in the second half of this year.

Julianne, let's take one last question, and then I'll have a couple of remarks and we'll be finished.

Our last question today will come from Louise Chen from Scotiabank.

I just wanted to ask you, if you get MariTide approved, what are you playing for here? Do you want to be the #3 player behind Noble Lilly? Or are you assuming a higher position than that with your product?

Louise, that's a tempting question to consider a softball pitch over the middle of the plate here at the end of the day. But Murdo, do you want to offer any quick thoughts for Louise, and then we'll wrap up.

Well, I think we're going to be the best monthly or less frequently prescribed agent, Louise. But no, no sincerity. This is a highly differentiated product. I think the opportunity is substantial to come into a market with something -- there really is a new paradigm-changing opportunity for a massive category. And our focus is going to be on helping as many patients as possible in that category, whether they are de novo patients who have yet to attempt a weight loss treatment and they'll be new to MariTide or whether they're on another therapy and they're not achieving the results they like or they're not enjoying the frequency of injections or they're having side effects and they want to try another treatment. And we will, across the business -- across the company, we will be ready to go into that market and compete effectively with all of the other companies that are already there.

I know some of our competitors have risen to the beta of that question, Louise, but we'll resist and wait instead until we have the data in hand. And as you know, we're working diligently to try to generate the necessary data to register this molecule. And as Murdo said, help as many patients as possible. There are very many who need differentiated therapy like this, and we're looking forward to having the data so that we can appropriately talk to them.

But before we wrap up, I just wanted to -- as I mentioned earlier in my remarks, I just wanted to take a moment. And acknowledge that Dave Reese will be retiring from Amgen at the end of the second quarter, and I wanted to thank him publicly for his contributions to Amgen over the past 20 years. As a long-standing leader and former Head of R&D, Dave's legacy here, as you all know, includes a generation of innovative medicines.

What you may not be as familiar with is that Dave has been a persuasive champion for change and new technologies at Amgen. And recognizing long ahead of many others, the growing importance of AI and what he called the Hinge moment, Dave both raised his hand to be Amgen's first Chief Technology Officer, and helped attract Jay Bradner to be his successor as Head of R&D. So we're thrilled, excited about the progress that we made in artificial intelligence and data under Dave's leadership as well as the other businesses that Dave has had responsibility for. And again, we're grateful that Jay will build on what is a very solid foundation following Dave's retirement at the end of the second quarter.

Dave is both a close colleague and friend to many of us, and we will all miss him and wish him well and what we're sure will be a very active retirement. So Dave, on behalf of all of Amgen, thank you. And let me thank all of you for joining our call as well. Thank you.

This concludes our Amgen Q1 2026 Earnings Conference Call. You may now disconnect.

We're ready to get started. On behalf of Leerink Partners, I wanted to welcome you all to the session with Amgen. So very much my pleasure to welcome Peter Griffith, the company's CFO. And actually, in between Jasper and Peter is Casey, who runs IR. Jasper Van Grunsven, is that how you pronounce your last name?

It's very good.

My apologies. I got Jasper right, at least. So he runs rare disease for Amgen. So I thought we'd have Peter kick it off with some opening comments.

Dave, thank you, and good morning, everyone. We're so glad to be here as we always are here in South Beach. I have a few prepared thoughts that I'd like to share. So we exited 2025 with strong momentum across the portfolio. 13 products delivered double-digit growth, 14 exceeded $1 billion in annual sales and 18 delivered record performance. That breadth supported double-digit growth in both revenue and earnings per share in 2025.

The momentum is underpinned by our 6 key growth drivers: Repatha, EVENITY, TEZSPIRE and rare disease, innovative oncology and the biosimilars portfolios. Repatha, EVENITY and TEZSPIRE all grew over 30% year-over-year in 2025 and delivered record sales with each representing a multibillion-dollar global franchise. These medicines address large unmet needs where there are millions of patients yet to be treated and represent growth drivers not just for 2026, but for the rest of the decade.

Our rare disease portfolio delivered $5 billion in 2025 sales, up 14% year-over-year, driven by reaching new patients, geographic expansion and launching new indications. UPLIZNA is a great example of this, growing 73% in 2025, supported by the IgG4-related disease launch. We expect continued growth in 2026 as that launch progresses and we build on the recent generalized myasthenia gravis approval and launch. We also plan to initiate additional Phase III studies of UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy later this year.

Our innovative oncology growth is being driven by our bispecific T-cell engager or our BiTE platform. IMDELLTRA, our DLL3 targeting BiTE has rapidly become the standard of care in second-line or later small cell lung cancer. With 3 Phase III studies in its early-stage small cell lung cancer underway, IMDELLTRA has the potential to reach many additional patients. We're also progressing xaluritamig, our first-in-class STEAP1 bispecific T-cell engager, with 2 ongoing Phase III studies in metastatic castrate-resistant prostate cancer. And we're also actively evaluating opportunities to expand xaluritamig into earlier lines of prostate cancer.

Our biosimilars portfolio generated $13 billion -- excuse me, it's accumulated cumulatively about $13 billion in sales. And in 2025, it generated $3 billion of product sales, growing 37% year-over-year. The momentum here is in part due to the strong uptake of PAVBLU, our biosimilar to EYLEA. Future growth is going to be driven by our biosimilar candidates to OPDIVO, KEYTRUDA and OCREVUS, which are all currently in Phase III development.

Let's turn to the pipeline. 2026 is going to be a year of disciplined data generation across multiple Phase II and Phase III programs that support long-term growth. We remain confident in MariTide's potential as a differentiated treatment for obesity, type 2 diabetes and obesity-related conditions. In a field featuring dozens of potential daily oral and weekly injectable medicines, MariTide stands alone as the only therapy in late-stage development to offer the paradigm-changing prospect of strong efficacy and favorable tolerability at monthly, every other month or even quarterly dosing.

The fully enrolled OCEAN(a)-Outcomes study of olpasiran, our potentially best-in-class small interfering RNA medicine targeting Lp(a) continues to progress. This is an event-driven study, and the aggregate endpoint accrual rate remains lower than initial predictions. While we recently pushed out our estimated completion date, our conviction in olpasiran remains very strong based on the genetic and epidemiologic evidence that has established elevated Lp(a) as an independent risk factor to heart disease.

Finally, we're advancing dazodalibep, our CD40 ligand targeting biotherapeutic with 2 Phase III studies in Sjogren's disease now fully enrolled and study completion expected in the second half of 2026.

Turning to a few financial updates. We see strong momentum in the business for the full year. However, in terms of quarterly phasing, historically, Q1 is lighter for us relative to subsequent quarters, and we expect that to be the case this year as well.

Let me remind everyone of a few points from our recent earnings call on the outlook for the first quarter. As we typically see with the United States insurance cycle, we expect a seasonal Q1 headwind from benefit plan changes, reverifications and higher patient co-pays. We also expect Otezla and Enbrel to follow their historical pattern of lower sales in the first quarter relative to subsequent quarters. I'd also add that as of January, Otezla now faces European generic entry. And for reference, European sales of Otezla were USD 282 million in 2025.

We continue to expect accelerated erosion in 2026 for Prolia and XGEVA, including in the first quarter because of a full year of biosimilar competition. Additionally, we saw approximately $250 million of inventory build in the fourth quarter of 2025 that could potentially impact first quarter sales. And consistent with lower Q1 product sales, we expect first quarter non-GAAP operating margin to be the lowest of the year and roughly consistent with the fourth quarter of 2025, which was approximately 43%. I also provided some commentary on the full year outlook on our recent earnings call, and I'd encourage you to reference the Q4 transcript for my full remarks.

And in closing, as we enter 2026 with strong commercial momentum across our diversified set of 6 key growth drivers and a Phase III pipeline that spans 4 therapeutic areas with meaningful depth and breadth, we're well positioned to deliver sustained long-term growth.

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

Excellent. Well, thank you very much for that, Peter. Would love to have you talk a little bit about opportunities for growth beyond 2026 and what you think the investment community may be underappreciating?

Thanks. Great question, Dave, and I'll invite Casey and Jasper to hop in when they'd like to. They certainly have plenty to add here.

I would recap those 6 key growth drivers. I always think about those, and they're doing so well. So Repatha, we can talk about the VESALIUS study and the Outcomes data there. We can get deep into that. Jasper actually worked Repatha for a number of years and did a great job getting it going, about -- starting about 5 years ago, he was involved in that. EVENITY, what a great medicine, went through $2 billion last year, and there's so many -- that's such an underpenetrated market. postmenopausal women. This is a great medicine for that. And certainly, TEZSPIRE, getting through $1 billion last year, severe uncontrolled asthma. I would also add on that, I can't resist mentioning the chronic obstructive pulmonary disease study underway, Phase III. And that's, I think, the third leading killer of humans on the planet. So that's super important.

I think about the rare disease portfolio, too, Dave. And I just think about those medicines. I look at UPLIZNA and it's just doing so well, and Casey and Jasper can talk about even some of the additional studies beyond the successful gMG approval into the autoimmune area that we're thinking about with inebilizumab, that's close enough, which is the molecule itself for UPLIZNA. And so a lot going on there. We like to think about that.

I would say when you get to innovative oncology, I just have to pause for a moment and IMDELLTRA. This is a bispecific T-cell engager addressing a horrible disease, small cell lung cancer, where survival rates have been very challenging. This medicine has had a very rapid uptake. It's on our -- it's the first medicine to address a common solid tumor, and it's done it really well. I think we launched that in about May of '24, and it's been very successful. And that one, I certainly would hope over the long run, really continues to do well for patients with this very, very serious disease.

And then biosimilars. So through $3 billion last year, a strong year, certainly, PAVBLU was a contributor to that. But going forward, thinking about our molecules relative to KEYTRUDA and OPDIVO and OCREVUS that I talked about, that's strong, too.

So we've got the 6 key growth drivers. We've got a strong Phase III pipeline. So we're busy. We're investing. And of course, we'll talk about MariTide. We know we'll do that. As CFO, I'd just remind you, we've got 6 Phase III studies underway, and I'm glad we do, and they're important. But that certainly is a significant investment our shareholders are making in that -- what we expect to be a really, really important medicine in the battle against obesity disease and all the related indications and type 2 diabetes.

So I think there's a lot. It's the breadth and depth. It's the 18, the 14, the 13. So certainly, the 14 products that generated greater than $1 billion last year. And so we're just really 18 record, 13 double digits. Did I get that right? So it's kind of -- that's how I think about it, Dave, breadth and depth, driving innovation at speed and scale. That's what the company is doing. And we're busy. And we see this year as a super important year of execution excellence. We've got a great portfolio. We're fortunate to have a great pipeline and myself and our colleagues are focused on sustainability of that growth rate over the long term. Do you fellows have anything you want to add?

I'd love for maybe Casey to talk a little bit about MariTide. So you had mentioned monthly, every other month or quarterly dosing. But could you just provide a little bit more color, Casey, on how you get there? I think the first Phase IIIs just have monthly dosing that are reporting out early next year. So maybe if you could share some insights on how we should think about the potential for different dosing in the future.

Yes, sure. Happy to do so. Yes. So to set the context, Dave MariTide, as Peter said, has 6 global Phase III studies underway. We anticipate additional Phase III studies coming online this year in type 2 diabetes. The 2 that are most advanced are our 2 chronic weight management studies. That's where we're looking at monthly dosing over the course of 72 weeks. There's a short 3-step dose escalation period to initiate those studies. But think about that as driving patients towards their weight loss goal over the first 72 weeks with monthly dosing. Then with MariTide, and we established this through Part 2 of our Phase II chronic weight management study, we observed that with lower monthly dosing or with quarterly dosing, we were able to maintain weight loss that was achieved over the first 52 weeks for a subsequent 52 weeks.

And so we feel like there's many options once the patient is at their weight loss goal with MariTide to stay on lower monthly dose to potentially move to every 8-week dosing to potentially move to quarterly dosing to maintain the weight that they lost. And interestingly, particularly with the quarterly dosing in that second 52-week period, we saw MariTide was very well tolerated in the quarterly dosing. That was a question that we thought was important to answer since it was such a long time between doses, you could imagine tolerability kind of coming back to almost a treatment-naive situation, and that wasn't the case. We saw a very well-tolerated molecule. And that's been consistent with MariTide where it is once you're at target dose of MariTide, it's a very well-tolerated medicine. And obviously, we're quite encouraged by the data we've seen thus far and are investing heavily behind it, as Peter had indicated.

Excellent. That's great. So maybe we could pivot to UPLIZNA, Jasper. Would love to hear you talk about the long-term potential, including which indication is your favorite, i.e., might be the biggest percentage of the pie longer term?

That's an interesting question. Let me start with where Peter left off. Like if you think about Amgen's growth portfolio, like look at those numbers, I'm very excited about that. If you look at 18 products with record sales, 13 products with double-digit growth, that breadth is very exciting. If you bring that to the rare disease portfolio, we see similar numbers across all our franchises in rare disease. And UPLIZNA is a unique example in that. And UPLIZNA in last year grew 73%. And I always have to remember -- remind people of that 73% is driven by our base indication, which is NMOSD, which where we saw very good new patient growth, very strong adherence, which is important. And so it's driven by NMO and, let's say, 8 months of the IgG4-RD launch, which is a very exciting new indication, a very big unmet need, like we're the first FDA-approved therapy in that indication. And UPLIZNA has a fantastic profile there. I can talk about that a little later.

But what we see is very good strong uptake there. So we have over 500 active prescribers there in that indication, and that's breadth of prescribing. You expect rheumatologists to prescribe. We see GI specialists prescribe. But even beyond that, we start to see prescribing. So we feel very good about that. So that's our 73% growth last year is NMO full year, 8 months of IgG4. And then as Peter said, we have the gMG approval December last year, which basically means a launch this year. And that uptake has been very exciting as well.

gMG, of course, it's a busy area. But I always say it's a busy area with competition, but there's still a very big unmet need. And people don't often see that. But if you look at the existing therapies, patients cycle through them relatively quickly. Like I think more than 50% of patients only stays on a therapy less than 12 months. So that tells you there's still a significant unmet need. And when we talk to physicians and patients, they talk about unmet need in a way, hey, we need a durable therapy that doesn't have additional flash between dosing. And that's exactly what UPLIZNA offers in our opinion. And we see since launch, and it's very early, we see very good uptake, and we're particularly excited by the breadth of uptake. So we see both bio-naive patients, probably 50% of our new patients are bio-naive and 50% come from switch.

So if you put that together, we expect continued strong growth. It's honestly very difficult to say which of those indications would be biggest. I think all of them will significantly contribute to UPLIZNA and the rare disease portfolio. And then, of course, as we deeply believe in upstream CD19-directed B-cell depletion has a very good mode of action in autoimmune disease, we also have these other indications that Peter mentioned. So we think UPLIZNA is set for a very, very strong future growth.

Excellent. That's great. And so in gMG, obviously, it is crowded and will become more crowded. Could you talk about UPLIZNA's competitive positioning and just how you see its adoption?

Yes. So I just explained already that we still see that as a big unmet need. I explained that. And I just also explained what our insights were around what physicians and patients want. And what UPLIZNA offers, if you think about CD19-directed B-cell depletion, what we offer is we offer that very strong durable efficacy. That's one. Second, we have a very known and well-tolerated safety profile. And three, we have, in maintenance, twice-a-year dosing. And then we have a pretty broad set of sub indications in gMG as well.

So if you put that together, I think we have an extremely competitive profile. If you compare it with existing competition as well as future competition, I think we are very competitive if you just put that together. And that's what we see because we get patients uptake in bio-naive and we get patients uptake in switch.

Excellent. Excellent. So why don't we turn to TEPEZZA. So the company has a forthcoming subcutaneous version. Could you just discuss that product profile and how quickly you might be able to convert the market from IV?

Yes. So If you look at thyroid eye disease, it's good to know that we also feel there -- and again, it's the story that Peter said as well for many of our indications, but the penetration, so the unmet need is big. So the penetration is still only single digit. And that's mostly in the area of the chronic or low clinical activities score disease patients. So that's important to know. If you then think about the subcu formulation, we feel that subcu is a more patient-friendly sort of convenient formulation that specifically will help unlock in that chronic patient population, so we think it will significantly help. Of course, we have to wait until our Phase III read out before we can comment more on what the actual profile will be and how we will launch that subcu formulation. But we feel it will significantly help in unlocking that chronic patient population.

Excellent.

And Jasper, is it also fair to say that, Dave, we envision IV continuing, IV TEPEZZA continuing, but also bringing online a subcutaneous administration, which will help us, as Jasper was saying, to reach additional patients, particularly in that low clinical activity score setting.

Excellent. So why don't we turn to dazodalibep, if I'm pronouncing that correctly? So...

The CFO way to describe it is daz. You're beyond that, Dave. I just say daz.

Yes, that makes a lot of sense. Keep it simple. So it's clearly an important pipeline opportunity. If you could just share your thoughts on it and news flow ahead.

Yes. So dazodalibep, let's call it daz, indeed, is absolutely a very exciting asset for Amgen. And it starts like in rare disease, it starts with the unmet need. And we know in Sjogren's disease, there is very significant unmet need. We currently have around 350,000 patients diagnosed in the U.S. And if you look at the subset of patients or the subset of patients in that 350,000 diagnosed, we basically have 2 big groups. One is the 30% to 40% systemic disease groups, 30%, 40% of those patients has systemic disease. But another 60% to 80% of patients have some overlap between those groups, obviously, 60% to 80% of patients has only symptomatic disease.

But if you talk to physicians and patients, the unmet need there when it comes to dryness, fatigue, pain is very, very significant. And we've seen in our Phase II data that we show initial efficacy in both of those indications. So we feel we feel that looking forward to our Phase III trial that we have potentially a good profile there. And we're very excited about the unmet need is significant there.

Excellent. Excellent. And so you said the timing was second half.

Mm-hmm.

Excellent. Okay. Great. And just so that we understand sort of based upon your prior data, regarding adverse events, what are your expectations for antidrug antibodies and the risk of thromboembolic events?

Yes. Let me jump in on that one, Dave. So daz is a CD40 ligand targeting fusion protein. And it's specifically designed and engineered to avoid some of what we saw previously with other monoclonal antibodies that were targeting the CD40 ligand or CD40 pathway where there was platelet aggregation, thromboembolic events. And so in our Phase II study, we saw a favorable safety profile. It provided us the confidence to advance into Phase III. Obviously, in larger number of patients, we'll continue to watch the full safety profile of daz. But the way that we've engineered the molecule hopefully will allow us to avoid some of what others have seen with monoclonal antibodies targeting the same pathway, and we're optimistic for what Phase III can bring. But obviously, the data will inform us in terms of the potential of the molecule and its safety profile.

Excellent. That's great. And then why don't we just pivot back to MariTide, just given how important that product can be for the company. There's been a lot of changes in the market recently, obviously, greater pricing pressure. Lilly has had declared earlier this year that it's much more of a consumer market than they originally expected. And I guess would love to hear about -- if we think about the market being in 2 segments, commercial coverage and consumer. I would love to hear your plans for the consumer market. And then on the commercial side, we get questions about how Amgen will compete with the rebate wall from Lilly and Novo given their current dominance in obesity.

Yes. So let me start and then Peter and Jasper, feel to add on. So it starts with the evidence base that we're generating with MariTide. So 6 global Phase III studies underway, 2 in chronic weight management, 2 in obstructive sleep apnea, 1 in heart failure, 1 in ASCVD, both Outcomes studies and then obviously in type 2 diabetes as well. So we are working to establish a very comprehensive evidence base for MariTide. And we feel that's important both to characterize the molecule, but also to characterize the potential of reaching a number of different patients with obesity or obesity-related conditions.

That plays into how you think about entering the market. I would say, details to be determined in terms of our exact approach to the market, but we're watching carefully. We're well aware of the consumer element of this and thinking through how we can best position MariTide with respect to all of the different aspects of the obesity market and which, as you know, Dave, are rapidly evolving, and we feel a little bit advantaged to be watching how things play out as we think strategically about how to ultimately bring MariTide to market.

Maybe just for a minute. Casey, talk a little bit about the adherence because we think MariTide is characterized and the data turns out the way that we hope it does, that perhaps it's able to help patients and their adherence, given the adherence on the weeklies is not as strong probably as we would hope.

Yes, it's a good point. It's really why does monthly dosing matter in a way. And we see that there is -- that currently treatment burden and dosing frequency continue to be barriers to long-term persistence on therapy. I mean we feel like with a monthly or to maintain weight, a less frequently dosed molecule, we have a real opportunity to improve adherence, improve the patient experience.

And why does that matter? To your point, Peter, that matters because in order for patients individuals living with obesity-related conditions to experience the long-term benefit of that medicine, they have to remain on the medicine to achieve those health benefits, to improve their diabetes, to improve their cardiovascular outcomes, to improve their sleep apnea. These are chronic conditions need to be treated chronically. And we feel like a medicine with MariTide with its dosing frequency and long-term tolerability at favorable tolerability at target dose really helps to fit what we see is an emerging unmet need in the space.

Maybe just one add on and Jasper, I'll turn it to you then, is when you think about Amgen's history, Dave, with Repatha, with Prolia, the ability to generate delivery of important medicines to areas with significant unmet medical need, millions of patients. We have that history. It's not a perfect analog, but it's our commitment to trying to get these medicines that have huge impact where there is a significant unmet need to get them to those patients.

So we've built our capacity for that. We're building our capacity for that. We've got to guide out this year, $2.6 billion in CapEx. We're working hard on yield management. We're working hard on the science and manufacturing. We're working hard on making sure the devices are just right for doing this. So we're focused on that. The company has been focused on it for a long time. So Jasper, you've been trying to say something?

No, no, but it's like your question was on the commercial launch. And I think, Casey, Peter, you said it very nicely. If the profile of MariTide shapes up the way it does in Phase III, I think we have a very competitive profile. I just want to reiterate what you said, Peter, is like the commercial capability that we built in cardiovascular and cardiometabolic where we have like a track record over 10 years, getting Repatha to a very successful brand, I think, it's a very important base that we launched MariTide of, which is pretty unique if you look at all the competitors developing in obesity. Of course, we have formidable competitors with Lilly and Novo, but I think Amgen with this cardiometabolic franchise and footprint is really -- will be very competitive commercially as well.

Excellent. Well, we are actually about to run out of time, but I had one more question for Peter. So obviously, you have a strong balance sheet, a lot of flexibility. But how do you see the current M&A environment, meaning there are a lot of companies that are looking for attractive targets. And so it'd just be helpful for -- it would be helpful to get your perspective on that current environment and opportunities or challenges for Amgen in executing in that environment.

Sure. Just to level set and calibrate, we were able last year by the end of the third quarter to get back to the balance sheet that we committed to when we announced the Horizon deal in December of 2022. And Jasper and the team in rare disease did a great job integrating that and making it all work so well.

So let's just start with that and then just say as we take that -- the strong balance sheet and we think about M&A, in terms of inorganic activity, mergers and acquisitions, licensing, collaborations, partnerships, Dave, which we're structurally agnostic. We're always in the market. We're always looking, but we always stick to our principles. So our capital allocation hierarchy, number one is the best innovation, either internally or externally. And so we're committed to finding the best innovation.

Now let's get to your point, which is, can you get it at somewhat of an effective value for shareholders? Well, our first principle is are we the best buyer, collaborator, licensor, partner, which simply means when it's in our hands, can we add to it? Are we accretive to that? Can we model it a little bit better than everybody else in a realistic way. Number two, cash-on-cash returns. We always stick to that. Number three, do we have research in the area. If we've got research in an area, we think we do a lot better with any one of those structural inorganic opportunities. And fourth, can we integrate promptly? We think returns are generated by promptly integrating acquisitions and these other types of partnerships and licensing and collaborations.

But acquisitions in particular, and we showed that with Horizon. We were able to achieve accretion in the first full year. We achieved our pretax cost synergies of more than $500 million a little bit early. And as I said, we were able to strengthen that balance sheet early. So moving quickly, that fourth thought in our minds. So we always prosecute these. We want to have an opinion on everything, too. We think it's super important at Amgen that we see what's out there and what's available. And if it becomes transactable and it makes sense, we'll certainly participate, but we'll stick to our rigorous discipline in terms of how we look at these opportunities.

Excellent. Well, that's great. Right. To wrap up, thanks so much for being here. Appreciate it.

Thank you, Dave. Thanks for the invite.

Thanks for having us.

Thank you.

Good afternoon, everybody, and thank you once again for joining us for the 46th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the next fireside chat with Amgen. With us today, returning from a hiatus from IR in an expanded role is Justin Claeys, Senior Vice President of Finance. To his right, really for the first time with us is Kave Niksefat, who is SVP of Global Marketing and Access. And to his right, needs no introduction, Casey Capparelli the new Head of IR and our guru on everything, Amgen. So gentlemen, thanks so much. Let me turn it over to you maybe for some opening remarks, and then we'll go into Q&A.

Yes. Thank you, and thank you, Yaron, again, for having us back at Cowen. We're glad to be here. So a few prepared remarks for us to open, and we'd like to share before moving over to Q&A. We exited 2025 with strong momentum across the portfolio, 13 products delivered double-digit growth, 14 exceeded $1 billion in annual sales and 18 delivered record performance. That breadth supported double-digit growth in both revenue and earnings per share in 2025. The momentum is underpinned by our 6 key growth drivers, Repatha, EVENITY, TEZSPIRE and our rare disease, innovative oncology and biosimilars portfolios. Repatha, EVENITY and TEZSPIRE all grew at over 30% year-over-year in 2025 and delivered record sales with each representing a multibillion-dollar global franchise. These medicines address large unmet needs where there are millions of patients yet to be treated and represent growth drivers not just for 2026, but for the rest of the decade.

Our rare disease portfolio delivered $5 billion in 2025 sales, up 14% year-over-year, driven by reaching new patients, geographic expansion and launching new indications. UPLIZNA is a great example of this, growing 73% in 2025, supported by the IgG4-related disease launch. We expect continued growth in 2026 as the launch progresses and we build on the recent generalized Myasthenia Gravis approval and launch. We also plan to initiate additional Phase III studies of UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy later this year.

Our innovative oncology growth is being driven by our bispecific T-cell engager platform or BiTE. IMDELLTRA, our DLL3 targeting BiTE has rapidly become the standard of care in second-line or later small cell lung cancer with 3 Phase III studies in early stage small cell lung cancer underway. IMDELLTRA has the potential to reach many additional patients. We are also progressing xaluritamig, our first-in-class STEAP1 bispecific T cell engager with 2 ongoing Phase III studies in metastatic castrate-resistant prostate cancer, and we are actively evaluating opportunities to expand xaluritamig into earlier lines of prostate cancer.

Our biosimilars portfolio generated $3 billion in 2025 sales, growing 37% year-over-year. Momentum here is in part due to strong uptake of [indiscernible] our biosimilar to EYLEA. Future growth will be driven by our biosimilar candidates to OPDIVO, KEYTRUDA and OCREVUS, which are all currently in Phase III development. Turning to the pipeline. 2026 will be a year of disciplined data generation across multiple Phase II and Phase III programs that support long-term growth. We remain confident in MariTide's potential as a differentiated treatment for obesity, type 2 diabetes and obesity-related conditions. In a field featuring dozens of potential daily oral and weekly injectable medicines, MariTide stands alone as the only therapy in late-stage development to offer the paradigm-changing prospect of strong efficacy and favorable tolerability at monthly, every other month or even quarterly dosing.

The fully enrolled OCEAN(a)-Outcome study of olpasiran, our potentially best-in-class small interfering RNA medicine targeting Lp(a) continues to progress. This is an event-driven study and the aggregate endpoint accrual rate remains lower than initial predictions. While we recently pushed out our estimated completion date, our conviction in olpasiran remains strong based on the genetic and epidemiologic evidence that has established elevated Lp(a) as an independent risk factor for heart disease. Finally, we are also advancing dazodalibep, our CD40 ligand targeting biotherapeutic with 2 Phase III studies in Sjogren's disease now fully enrolled and study completion expected in the second half of 2026. I'll now turn it over to Justin for a few financial updates.

Great. Thank you, Kave. And Yaron, it's great to see you again. Great to be back and join the conference. As Kave mentioned, we see strong momentum in the business in 2026. Given that we're now into March, I did want to remind everyone of some points on our quarterly phasing. Historically, Q1 is lighter for us relative to subsequent quarters. I'll highlight a few points on this from our recent earnings call where we gave some commentary on the outlook for the first quarter. As we typically see with the U.S. insurance cycle, we expect a seasonal first quarter headwind from benefit plan changes, reverifications and higher patient co-pays.

We also expect Otezla and Enbrel to follow their historical pattern of lower sales in the first quarter relative to subsequent quarters. I would also add that as of January, Otezla now faces European generic entry. For reference, European sales of Otezla were $282 million in 2025. We continue to expect accelerated erosion in 2026 for Prolia and XGEVA, including the first quarter because of a full year of biosimilar competition. Additionally, we saw approximately $250 million of inventory build in the fourth quarter of 2025 that could potentially impact first quarter sales.

And consistent with lower Q1 sales, we expect first quarter non-GAAP operating margin to be the lowest of the year and roughly consistent with the fourth quarter of 2025, which, as a reminder, was approximately 43%. Peter provided commentary on the full year outlook on our recent earnings call, and I'd encourage you to reference the fourth quarter transcript for his full remarks on that. In closing, we entered 2026 with strong commercial momentum across our diversified set of 6 key growth drivers and a Phase III pipeline that spans 4 therapeutic areas with meaningful breadth and depth. We're well positioned to deliver sustained long-term growth. Yaron, over to you for Q&A.

Great. Thank you so much. That was good to know. I think news about the Otezla generic as well. Okay, maybe, Kave, to you, first question since we have you on market access, which is critical. So Amgen has done very well financially and continue to -- pricing has been variable across assets, and you obviously have both rare, to oncology, to mass market. What's the secret sauce? What's Amgen's secret sauce on Access and negotiations and formulary placement?

Yes. I think from my perspective, Amgen has experience and access across a wide number of therapeutic areas. We're in 4 therapeutic areas now. We've got experience and access in over 100 markets around the world. We build in access as part of our strategies from early on in our pipeline to make sure we're generating the evidence that we believe makes our products competitive not just from a physician choice standpoint, but from a payer choice standpoint and evidence that helps us justify the economic value that our medicines bring going forward. I think that integrated approach from molecule inception all the way to on market and LOE has allowed us to perform very well from an access perspective, making sure that our medicines that we invent are accessible to patients at prices that are affordable to the health care system.

And is it -- it's how you negotiate access on an annual basis or how you negotiate access even on a portfolio basis? What sets you apart?

Yes. So again, I think access negotiations in general happen at a product level within a category versus the other therapeutic options that are there. And again, I think that body of evidence that we create either through clinical trials, the real world that we're able to bring the fact that we're forthright in thinking about access allows us to navigate those potential headwinds as a forethought rather than afterthought, Yaron?

Repatha, I think, is really -- has been one of the examples, right? I think Access was tough. There was 2 different SKUs. One of them was pulled and then Access has really improved dramatically plus the data continues to get enhanced. Obviously, the latest data is primary prevention. Technically, that was on the label already. But now you have Amgen 1 (sic) [AmgenNow ] at a monthly price of $239. How important is Amgen 1 (sic) [ AmgenNow ] ? Or is it just another vehicle, but overall, it's really the rest of the channels are going to be really the most important?

Yes. Thanks, Yaron. And we've named our program AmgenNow, not Amgen 1, but that's okay. We know there's a lot of these that are coming up. Let me talk a little bit about Repatha, and I'll build in the AmgenNow answer there, if you don't mind. I think Repatha is a great example of how Amgen's Access skills have come to really unlock a really critical medicine in the U.S. and around the world. There's over 100 million individuals around the world with elevated LDL despite the fact that they're on standard of care therapy.

Only about 5% of them today are on a PCSK9. As the market leader, most of those 5% are on Repatha. By opening up Access, we think we can continue to penetrate that very large population that is underserved today. And by bringing the changes that we've done in the U.S., for example, Repatha is now listed as a preferred therapy on virtually every formulary regardless of whether it's Medicare or commercial. Average co-pay is down to less than $50 a month. The over half of Medicare patients no longer need a prior authorization to get the medicine. And we've now got great data with primary prevention, 36% reduction in first heart attack, 25% reduction in MACE, 20% reduction in all-cause mortality that with that good access environment is allowing us to scale.

Now despite that great Access environment, we know that some patients remain uninsured or are in high deductible health plans or are on one of the limited number of plans that are still making it challenging to get Repatha. And that's where Amgen now comes in. It's a direct-to-patient offering, $239 a month, in line with the lowest price around the world for Repatha. And we introduced that program in October. So we've been on the market now for about 5 months. We've been very pleased with the uptake thus far. We've got over 5,000 patients in the U.S. using Amgen now to get their Repatha. And we see that as an additional channel, Yaron, that goes beyond the very well-covered insurance channel to make sure that any patient who wants Repatha, whose physician wants them to have Repatha is able to get and afford Repatha in the U.S.

There is increased competition. Leqvio is now waiting for its outcomes. It's Q6 months. I think the access there has been improving. And there's going to be a couple of orals, one a little bit more differentiated from the other, one is from Merck, the other one is from Astra. Any thoughts about how does that work in a competitive dynamic? And again, we're aware that the other 3 don't have outcomes yet.

Yes. So let's just start. If we look back at cardiometabolic markets, the history of them, we would say that, first and foremost, the goal here of us, and we think the goal of the field is to improve penetration into that 95% that is not yet on therapy rather than just fight over the relatively small patient population that has access to therapy today -- is on therapy today. When we look overall -- these additional entrants, we expect will grow the overall penetration of the market at a rate that's faster than share is consumed by them.

And so we think that, that increased share of voice will increase focus on LDL and increase treatment rates overall. In terms of the competitive dynamic, as you've said, we're really proud to have 2 outcome studies, both primary prevention and secondary prevention. These add to the mountain of data that's been created on Repatha. We've done over 30 clinical trials ourselves. There's hundreds of clinical trials that have been run with Repatha. We think that, that primary prevention data, which is unique to Repatha is a huge differentiator and allows us to continue to hold our competitive position as new competitors enter.

Can we maybe move to Tezi? So Tezi posted $1.5 billion to Amgen. The accounting is a little complicated, as everybody knows, because of the AstraZeneca relationship. It obviously sold more than that globally. That was up 52% year-over-year. And now CRS with nasal polyps was approved in October. For Dupi, CRS is now more than $1 billion in that brand. Where -- do you have any sense what percentage of new patients is Tezi getting and maybe overall share in asthma right now?

Yes. Yaron, I don't have those numbers off the top of my head. What I would say is that Tezi is the one molecule in the severe asthma class that can be used irrespective of eosinophilic or allergic status overall. It's the one medicine that can be used for all patients with severe asthma. That's been a differentiating factor for us.

It's been very competitive across the different phenotypes of patients that the other competitors are targeting overall. When we look at polyps, polyps is a really important indication. One, it's highly comorbid with severe asthma. And so it helps us continue to penetrate and win additional share of the asthma patients that also happen to have nasal polyps. It's also representative of a highly eosinophilic disease. And so with the great data that we showed with its high efficacy to prevent surgery, we think it helps us in both of those populations and further penetrate the market.

Okay. And then UPLIZNA launch, I think since its launch, more than 500 unique prescribers have written it for IgG4. The market right now based on claims is thought to be around 35,000, so not small at all. The feedback from clinicians, data looks really good. There was one question about what does it sequence relative to Rituxan because Rituxan is obviously a lot cheaper. And now you just got gMG approval, too. So maybe we'll start with IgG4. Do you have a sense how is it being used? And is there a large patient population that is now getting tapped? Or is it mostly for new patients?

Yes. So as you said, Yaron, we see the market the same way. We see about 35,000 patients diagnosed with IgG4 disease as of right now. This designation of IgG4-related disease is only about 10 to 15 years old, coding for it in the U.S. is only 2 years. So we do expect that, that could -- that number could evolve over time as additional treatments are used in the field.

As you've said, to date, we've had about 500 unique prescribers prescribe UPLIZNA. This is a very diverse disease that is viewed by a diverse set of physicians. And we see this as a patient finding and physician activating game -- ground game, which we've done quite well with TAVNEOS, for example. In terms of where it's being used, we see it used at all lines of therapy right now. We're seeing it as a first-line therapy. We're seeing Rituxan-experienced patients come in. This is an area where UPLIZNA is the first and only approved medicine for IgG4 with an 83% reduction, if I'm remembering my number correct, reduction in overall flares. And so we are seeing the community respond very positively to the disease, and we think uptake will continue across activating additional prescribers and finding additional patients.

And then for myasthenia gravis, any sense where the drug is going to get used?

Yes. So we got approved for myasthenia gravis in December. And so we've been now on the market for about 2.5 months overall. MG has about 80,000 to 100,000 patients. Competitive field, obviously, other biologics in the market already. Launch to date, about 50% of our prescriptions are coming from bio-naive patients, about 50% are coming from bio-experienced patients. We think the market is reacting to what we saw in ADVANCE, which was this was a market that was interested in a reliable therapy that had durability, efficacy and convenient extended dosing. And with UPLIZNA being twice a year after an initial induction dose of -- induction 2 doses, we think we've met that bar.

And so we're seeing uptake across the board, Yaron. I'd highlight as well that specifically in the bioexperienced market, given the frequency by which other therapies are offered, it's offering us a number of opportunities to play for switch. And that frequency is giving us additional shots on goal as patients progress and need to come back for reevaluation and retreatment.

Does it make sense to run a SWITCH study to help inform how to use the drug?

Yes. I think we remain interested in a number of things on UPLIZNA, Yaron. We're not going to announce a SWITCH study today, but we do know that, that is an area of interest. And like I said, the community is already appears to be switching without that study.

We've done a fair amount of work with physicians, and they are interested in using it broadly. 6 out of 10 right now are going on Vyvgart right away. And so the feedback -- the one challenge with UPLIZNA and their fans of the durability is that it's slower action. And so not all patients would qualify. Does -- how do you think that's going to ultimately fit into where you really get stable in terms of traction?

Yes. I think time will tell on the market exactly how that plays out. Look, physicians right now are excited to be getting experience with this medicine. We're excited to bring another option overall to patients around. And in due course, we'll see exactly how it plays out across the marketplace.

Let me actually zoom out. And when we talked about access overall, I neglected to ask about Europe because sadly, Europe is not as big a part of the market these days. Is -- are things stable in Europe now? Are they getting -- continuing to get more challenging? And are they -- are you beginning to see that they are willing to pay a little bit more for medicines?

Yes. I think last year was a bit of a wake-up call across the ex-U.S. markets around where the U.S. sits within the drug innovation ecosystem and how some of their systems have progressed. I'd say we're in constant discussions with governments around the world, making sure that they understand what the world looks like in a post most favored nation setting overall and advocating just like we've been advocating before that Europe, in particular, should recognize the value of medicines that we bring. We're seeing some governments start to react and start to think differently. We're seeing some that are not. But there's definitely -- the challenges remain in terms of access across Europe, and we're looking forward to engaging on those.

With PAVBLU was off to a really strong launch, but it's probably not going to remain the only biosimilar. It's a question of when the next ones will come, whether it's starting next year. As much as the launch has gone well, I think it's got less than a 10% share right now, roughly in the U.S. What is it going to take to really expand it further?

Yes. So we're really pleased with PAVBLU thus far. We -- last year, we think we did $700 million of total sales as the only biosimilar on the market.

I was thinking, by the way, of all anti-VEGF and bispecifics, not just EYLEA.

Yes. And overall, Yaron, I think the way we see this market continuing to evolve primarily based off new biosimilars entering, which, as you've said, we're expecting from what we've seen externally to occur at some point this year. Until that comes, we continue to be the only biosimilar on the market and compete with the innovator.

And is that this year in the U.S. or mostly ex U.S.?

I think time will tell you, Yaron. There's a lot of factors that affect how and when biosimilars enter, and I think we'll just have to watch how that landscape evolves.

Yes. Any -- maybe from a payer perspective also or a marketing perspective for MariTide, pricing in general has continued to come down. The Access has gotten more resolved, and now it's really about differentiation. As you think about MariTide maybe for maintenance, what do you think you need to show in any sense, how do you weave that into a clinical program?

Yes. So maybe I'll just start by saying that we're obviously aware of the pricing changes that have been underway. The price has evolved in line with our expectations. We continue to be very excited about MariTide. We think we have a differentiated asset, especially whether it's monthly or less frequent dosing. And as you got to see in Ohio, we're proud of the manufacturing capabilities that we have and think that those will give us the ability to continue to compete as price evolves.

In terms of the maintenance setting, it's obviously something that we're quite excited about. We provided some update earlier this year on our phase -- our Phase II, Part 2 data, which tested less frequent dosing. It's obviously a competitive market. In due course, we'll have an update with how we plan on using that data and how we plan on approaching the market from a maintenance standpoint in light of pricing and competitive dynamics.

As it relates to MariTide, I had 2 questions. One is by the time you get on the market, which I'm assuming is 3 to 4 years from now, how do you see the competitive dynamics having changed, assuming the only 2 other products on the -- other 2 companies are Lilly and Novo with expanded product lines? And how important do you think it is to be able to have approvals not for obesity or weight loss, but from an insurance standpoint to have approvals for the 7 chronic conditions that obesity is related to that result in a reduction of morbidity, mortality and cost.

Maybe we'll just restate the question for those on; the webcast.

Please go ahead.

Yes. I mean just to summarize. So I think the first question was how would we plan on competing given that there are folks on the market today, and we would be coming later. Just to clarify, we haven't commented on launch time lines. So we'll let you make your own assertions there. And I think the second part of the question we caught.

Yes. So -- and the second part of the question was, how do you plan on competing against other companies that have multiple offerings. So...

And do you think that it's important to have approvals not for obesity or weight. I don't personally don't care about the 16% or 19% weight loss or 22%. I think that the insurers are more interested in the docs in the 7 chronic conditions that obesity is related to where you can have a significant reduction in morbidity, mortality and cost.

Yes. So let me address that then in 2 parts. One, we're excited to be bringing a differentiated molecule to the marketplace. And we think that differentiation earns us a seat at the competitive table with what we're bringing, really focusing on efficacy that is in the mid-20s on weight loss and big impact on cardiometabolic parameters, including HbA1c, a tolerable medicine that we're looking to improve the initiation protocol with 3-step dose escalation and then finally, monthly or less frequent dosing.

In terms of the obesity-related conditions, that's an area we're very interested in. As we shared earlier, we are on 6 Phase III clinical trials, and then we were also looking to add type 2 diabetes. But our clinical trials for the related conditions are ASCVD, heart failure and sleep apnea. And then we believe that the whole suite of evidence will be important, not just for payers, but to compete in the class.

Maybe a question again, Kave, while we have you on Sjogren's. It's an area we've done a lot of work on. Technically, it's not an orphan market. But once you look at the patient population being RFRO positive, moderate to severe, naturally becomes an orphan market. Can a market like that, and you're looking at both systemic and symptomatic and you're the only company right now, and that's critical because 60%, 70% of patients are actually symptomatic. So everybody else is going for the smaller segment, albeit obviously important. Can it support premium pricing?

Yes. So Yaron, let me give you how we see the market, which I think might be just slightly different than as you see it, but we see about 350,000 patients that are RO or RF positive diagnosed. And we see this as a serious but also highly heterogeneous disease. Given that heterogeneity, we see room for multiple therapies in this market. And we think some will go in the first line, some will go in second or later line, some will go for the whole population, some will go for smaller populations.

And obviously, we'll have different value propositions depending on exactly where they sequence overall. So we see a lot of different routes to make this a viable marketplace. As you shared, we are studying in both the systemic and symptomatic populations separately. The systemic population, we see that as roughly 30% to 40% of the market. And then the symptomatic population, we see that as 60% to 85% of the market. Now that doesn't add to 100%. That's because some of these patients are both systemic and highly symptomatic overall. But we decided to run 2 different Phase III trials to cover the waterfront to understand the effect this medicine can have on both those populations.

The reality is when we talk to physicians, for the most part, they tell me, first, it's a Sjogren's patient. And you kind of have to really dig under to see how they're subclassifying between those 2 population types. We thought -- given the data we saw in Phase II, we'd study the entire population. So when they see a moderate to severe Sjogren's patient, they can hopefully, depending on the data, pull for dazodalibep. So it's an opportunity we're excited about. We've been excited about since the time of the Horizon acquisition, where we got this molecule. And both of those studies read out at the end of the year. And based off the readouts of those studies, we'll understand exactly what our path to market is. And really, are we positioning for a broad population or a smaller orphan subset population?

To your point, the symptomatology is fairly variable, anything from dry eye to fatigue to some arthralgia, -- it could be a lot more systemic and has a real tissue involvement. So that's why I'm trying to -- for me, it's a little hard to try to figure out the price -- if you look at some of the other companies working in this space, Sjogren's is probably going to be an add-on indication, and they're deep, deep in orphan pricing. I guess Novartis will be first, and we'll have to see how they price. But by virtue of the competition, it looks like they're going orphan, and that's maybe that's the opportunity. But the question is it severe enough?

Yes. I think, again, time will tell based off that Phase III data exactly where this product gets positioned and the size of the population that addresses to the opening point you made, I think this is an area where we will wait for the data and follow the data before making any commercial decisions.

Yes. Maybe finally, just a broad question. In general, pricing for biologics is going down. I'm talking about mass market and volumes are going up a lot. So to your point, Repatha $239 x 12, it's about $,3000 -- just under $3,000 a year. MariTide and obesity drugs now are anywhere between $300 and $400, $500 a month. And they require a lot of injections and a lot of injectors. So I guess my question with Amgen, I mean, you're making drugs that are costing $150, $200, $300 and making drugs that cost $3,000. How do you work on the margins?

Yes. Thanks, Yaron. I would start by saying that this evolution is exactly what we've expected. We certainly, I think, for years now, have seen that U.S. prices -- prices in the U.S. and around the world would face pressure over time. And our strategy has been volume-driven growth. So you're right to kind of square that circle, what you need is a manufacturing footprint and a capability where you can keep your cost structure under control and manage that. So that's something we've been doing for years.

If you look at Prolia and denosumab, I mean, that's a primary care medicine where we've been able to earn a very nice return. And I think credit to the manufacturing and the operations team, what they're very focused on year after year is driving more productivity and efficiency gains. And so that's definitely part of the game plan.

When Amgen launched the new sort of high-yield perfusion and high-yield manufacturing, does it normally go into all products or certain products get that and some of the other ones don't.

It's really product by product, kind of case by case.

But is it -- maybe final question, fair to assume that Amgen is making money in every drug?

I don't -- I mean we don't disclose the gross margin by product, but I think if you look at our overall results, I think they speak for themselves.

Well, team, thank you so much. Good to see you. We appreciate it.

All right. Welcome to the afternoon sessions of Citi's Virtual Oncology Leadership Summit. My name is Geoff Meacham. I'm the Senior Biopharma Analyst here at Citi and Jarwei Fang from my team with me as well. We're thrilled today to have Jean-Charles Soria from Amgen, who is the Senior VP, Global Development in Oncology. We did this session last year, a lot of really good meat on the bone. We also have Casey Capparelli from the IR team. So guys, welcome. Thanks for joining us.

Thank you so much for the invitation

Yes. So I guess, Jean-Charles, we'll just kick it off with kind of the high-level questions on Amgen's kind of oncology approach. Maybe just talk through kind of as you see then the top priorities within oncology for Amgen on the R&D side, maybe what are the bigger opportunities? Are you guys good with the technologies you have in place. And now it's just a matter of moving the products through clinical development at a high level? Just wanted to get some perspective from you.

Yes. Thank you for that question, Geoffrey. Well, we have a framework that allow us to see how oncology or investments we'll be delivering. We believe that we are committing to bringing differentiated and transformative therapies. We don't want marginal benefit. That's one of the big rules. So there's one rule that we want to steal, to play both in hard-to-treat solid tumors as well as selected hematological malignancies. The third one is that we have at least two clear pillars in our modalities, one being the T-cell engagers and the other one being the precision therapies with our small molecules.

I would say on the T-cell engager front, we have invested for decades, and we are the only company with T-cell engager approved, both in hematological malignancy and solid tumor, and there is more to come there. The frontier of bringing T-cell engagers in frequent solid tumors is a very important one for us. On the small molecule front, we are strong chemistry -- teams have been able to get to very tough targets such as KRAS or PRMT5. That being said, we are also looking at diversifying our modalities, among which we believe ADCs as can play a role.

But we're very selective in where do we choose to play because it needs to be leveraging our own strengths and we're a biologics company with good chemistry understanding that makes, for instance, choosing other modalities, not the ideal fit for us. So that's the global framework.

Yes. Yes. And it's interesting, Amgen is one of the companies that can really add value along the entire way of the value chain. I think going back to the deCODE data, right, on the discovery side straight through to technology using BiTE and other platforms, I think that's somewhat unique. I mean, there's not necessarily a need to to do a deal to bring in new technologies, nothing that you guys don't already have, in-house, in a dramatic way, right?

Yes. Thank you for that comment, Geoffrey. I think resilience is an underrated virtue in pharma, like we have stick with T-cell engagers for a very, very long time. It's a little bit North Face or the Annapurna to bring them to solid tumors without HLA restriction and in frequent ones. We are very glad for the patients that are on IMDELLTRA is bringing transformative benefits in small cell lung cancer. And we are very hopeful to see xaluritamig potentially doing that in prostate cancer, a tumor type where immunotherapy is basically totally inactive. But we monitor the external environment, and we are convinced we don't have the monopoly of the best science, but we will do selective investments where we see it's complementary to our priorities, to our own pipeline, and it's truly transformational.

Yes. Well, you mentioned IMDELLTRA. So let's get into the market of product portfolio, and that's a good place to start. So full approval, extensive stage small cell lung cancer, but many other tumor types that it could go into. Maybe just help us with kind of the commercial backdrop here. How do you see kind of the next 12 to 18 months roll out on a geographic basis? And maybe help us with -- remind us of the other data sets to come that could further expand the label for this exciting medicine.

Yes, Geoff, why don't I jump in on the -- just the commercial aspects and then Jean-Charles, I'll turn it to you to highlight maybe just reflections that you've heard clinically from the approved indication, which is second line or later small cell lung cancer, but also maybe a few words on the development program.

So as I mentioned, Geoff, approved in second line or later small cell lung cancer that's full approval received last year in 2025. And in addition, NCCN guidelines have been updated to reflect IMDELLTRA's benefit in that setting. And so we feel like we have a lot of momentum commercially in reaching patients with IMDELLTRA, in fact, over 1,600 sites in the U.S. now administer IMDELLTRA, and the majority of our doses are provided in the community setting. That was an open question that we had, our ability to really reach patients that are treated with small cell lung cancer in the community setting.

And based upon what we've learned from BLINCYTO, we've really been able to do that in a fairly rapid fashion with IMDELLTRA. We have approval in Japan, pending approvals in other geographies based upon the Phase III study that generated full approval in the U.S. I mean, we're excited about the potential to continue to reach patients with this second line or later setting in the currently approved indication. But there's a lot more going on with IMDELLTRA even beyond the current approved settings. And Jean-Charles, maybe I'll turn it to you to talk a little bit more about that.

Yes. Thank you, Casey, for that context setting. We fit IMDELLTRA, we saw such a compelling activity on the basis of the Phase I, II that we launched multiple Phase III trials. And we have, on top of the already disclosed positive second-line Phase III trial, three other ongoing Phase III trials. One in the first-line metastatic setting in the maintenance setting, that's Trial 305, which is fully enrolled. We have another first-line metastatic trial, which is Trial 312 that is enrolling. And we -- that gives IMDELLTRA combination with chemo and PD-L1 upfront.

And then we have another Phase III trial ongoing in limited stage small cell lung cancer. So we really want to bring the value of this modality to the whole spectrum of the disease.

Just given the modality of this with being a DLL3. Jean-Charles, maybe help us with kind of the -- any other tumor types that you think could be suited here? I know obviously, the -- mostly the focus is on small cell lung cancer, but are there reasonable opportunities looking broadly across the lung or other tumor types?

Yes, certainly, Geoff. Thank you for that. Beyond I expand on other tumor types, we are also doing a lot of efforts to make this more convenient and friendly for the patients and health care providers. We are testing BLINCYTO subcutaneously that will alleviate a lot of the pressure on the beds. We are doing alternative testing, so not only Q2 weeks, but also Q3, Q4 weeks, those trials are ongoing, we are prospectively testing whether the monitoring can be reduced to shorter timeframes like 6 to 8 hours or even shorter. All of these will facilitate the uptake of this therapy in community-based hospitals and beyond.

But your question more specifically is, are there other tumor types in which these DLL3 T-cell engager could potentially play. And the answer is yes, we have reported data on the activity of our T-cell engager in neuroendocrine prostate cancer and that's a different type of neuroendocrine tumor versus small cell lung cancer. That's neuroendocrine differentiation on the therapeutic pressure. It happens when you have people with prostate cancer that had multiple lines of therapies and then you have a transformations to a standard endocrine form at the same way you can have EGFR mutant adenocarcinoma, the lung that develops small cell lung cancer transformation on the therapeutic pressure. Those are areas where potentially this asset could be developed.

Right. Okay. That makes sense. And then moving down the pipeline to, I would say, more recently marketed products like LUMAKRAS. Same thing there in terms of expanding the opportunity beyond lung into colon cancer. I know you guys have done some work on this over the past couple of years. Maybe give us a status update of where the Phase IIIs are going? I know you are still enrolling first-line lung in colorectal, but are there any other kind of line extensions that make you more excited as you look at LUMAKRAS as a brand that's still growing and impactful to Amgen.

Thank you for the question. LUMAKRAS is currently available in both second-line non-small lung cancer and third-line colorectal cancer in combination with our on Vectibix. Longer-term growth of LUMAKRAS will probably be driven by -- it's moving into earlier lines. So let's discuss lung and then colorectal. In non-small cell lung cancer, we have seen that the combination of LUMAKRAS with chemotherapy did led to durable responses with a very good manageable safety profile. And this was notably in treatment-naive patients with KRAS G12C mutation. So this is why we launched the CodeBreaK 202 Phase III trial that is testing the combination of chemotherapy with LUMAKRAS versus chemotherapy and pembrolizumab, that in KRAS G12C patients who are PD-L1 negative.

For the colorectal tumor types, the triple combination of LUMAKRAS, Vectibix and FOLFIRI, show very compelling objective response rate of around 55% with the disease control rate north of the 90%. And the responses were observed, regardless of the number of prior lines of therapy including progression [indiscernible]. And this is why we launched a first-line colorectal cancer that is currently enrolling and hopefully, will bring this therapy into that earlier line setting.

Okay. That's helpful. I think Jarwei from the team had a couple, we wanted to stick with marketed products with BLINCYTO, but then obviously, that has a pretty deep pipeline behind it. Jarwei, go ahead.

Yes, definitely, on BLINCYTO, you have a number of Phase III studies that are currently enrolling. One of which is, I believe, it's the Golden Gate Study for older patients with leukemia. I guess just thinking about the opportunity and also just the bar for efficacy that you need to see there, how do you think that represents the -- another leg of growth for BLINCYTO going forward?

Thanks for that question, Jarwei. I would say what we have come to realize with BLINCYTO is that as we move this asset to earlier lines of therapy, we see higher efficacy, better tolerability, and that's an important trend. And in fact, it's a blueprint that we are using for the development of IMDELLTRA, referring specifically to the Golden Gate Phase III study. This is in older adult patients, mostly 55 years and above with newly diagnostic B-ALL. And that is an indication where we have chemotherapy sparing regimens that are very important for those patients who have less tolerability. So that will bring a new perspective for BLINCYTO. We're also advancing subcutaneous blinatumomab who has the potential to improve convenience tolerability and efficacy.

And we believe this is going to be very important also for this asset. We have had Phase Ib data suggesting better efficacy at CIV. And we have other trials that are going to be -- we exploring this in a more registrational manner.

And so for the subcutaneous formulation of BLINCYTO, do you expect certain indications or certain age groups to see faster uptake? Or could you see a scenario where subcutaneous formulation kind of supplants the current route of administration, fully?

Well, we will be driven by the data, correct? And what the data told us in a very limited Phase Ib setting was that this potentially will bring more convenience and even higher activity. But you imagine the efferent number of trials, it took for BLINCYTO to be validated in later lines relapsed/refractory earlier. Now the first-line setting, you will need to do that movement for subcu at the same time. So let's see how the initial readouts pan out. But yes, that could be potentially a framework, Casey, anything to add on that?

No, I think you covered it. I would just quickly mention, Jarwei, I know we're focused on oncology, but we're also exploring blinatumomab in the space of autoimmune disease where B-cell depletion has been shown to be important in a variety of autoimmune settings. We have a couple of Phase II studies underway exploring blinatumomab, both in the SLE with and without nephritis setting as well as in refractory rheumatoid arthritis. And so potential to even move beyond oncology with the B-cell depleter like BLINCYTO.

I would like to add, Jarwei, that it makes complete sense mechanistically, correct? Because CD19 is B-cell antigen and B-cells produce antibodies. And if you suffer an autoimmune disease because you have auto antibodies, depleting the B-cells that produce those autoantibodies is rationalisticy very logical those -- the pad that Casey has highlighted for our own BLINCYTO in that setting. .

Got you. Makes sense. And maybe just one more, shifting back to IMDELLTRA real quick since we talked about BLINCYTO and the subcu formulation. Ease of access for patients and also reducing bed burden is definitely top of mind for community centers. Could we see later on as IMDELLTRA becomes more mature in its product cycle, that subcu might one day be explored as well? Or do you have to see BLINCYTO data first as a gating factor for the BiTE program, for BiTE platform rather?

Yes. Thank you. Well, in fact, we are exploring IMDELLTRA in a subcu Phase Ib trial that is ongoing because we are completely cognition of the barriers of patients being treated in community base hospital need to overcome and not competing for the beds, being able to provide subcu, being able to do Q4 dosing versus Q2 dosing or being able to have less of a follow-up after administration are some of the levers. We are very actively trying to pull through with prospective data and therefore, making IMDELLTRA more available.

Makes sense. And I think, Geoff, I think you have a few questions on prostate. Maybe we can move to that.

Yes, yes. Let's switch gears, Jean-Charles to xaluritamig, which is a super exciting product in prostate and Ewing Sarcoma, but there's a lot of investments you guys have made in prostate. Maybe just at a high level, talk through how you think the differentiation could play out. That's obviously a pretty crowded market, but so far, you've had some pretty compelling kind of mid-stage data. Maybe what makes you exciting as you turn the card -- prepare to turn the card over on larger-scale Phase IIIs and then move to market. .

Yes. Thank you for that question. What is really exciting for us with xaluritamig in prostate cancer is that it levers a mechanism of action that has currently no approval. There are no PD-1s, PD-L1 or CTLA-4s approved in prostate cancer. Patients with that disease are very well aware of that and really would like to see an immune-related asset that could bring sustained responses, that's number one.

And the second one is that we have seen very clear signs of efficacy, both in PSA 19 and PSA 50 but more importantly, in objective response rate for this asset. And therefore, we are going to do many things -- we are doing many things in our Phase III trials to differentiate ourselves in a very competitive landscape, as you rightly highlighted. First, we want to lead with the gold standard of survival evidence, especially versus highly active chemotherapy comparators.

We are designing our pivotal programs to generate overall survival in both the post-taxane and the pre-taxane setting, that's a bold bar in prospect cancer, but we are confident and we really want to make sure that we are having the right comparators with the right endpoint.

The second element is for us to speak to market. We have prioritized monotherapy development in the post-taxane setting because that's an area with very high unmet medical need, and we want to reach the patients very, very quickly. The third element I would say is we want to be differentiated in terms of practicability, meaning we don't need a biomarker gate and our breadth of addressable patients is extremely broad in the prostate cancer space. We don't need enrichment through PSMA or through PET or through a mutation or anything else. That's another element.

And finally, the chemo-free regimen for the pre-taxane setting is another pillar of differentiation. We are positioning ourselves as a potential non-chemotherapy option with survival advantage versus chemotherapy that's both twice because you're putting OS as an endpoint because you want to show that you can beat chemo without being combined with chemo. So those elements are very, very clear. And we believe in this combination, in that setting.

Finally, we want to remove a lot of the friction that comes from implementing a new modality with a new mechanism exception and new tolerability challenges for the clinicians. So as we are enrolling on our Phase II trials, we are working very much hand in hand with investigators to clarify the type of adverse events and how do we learn and moderate them and what is the optimal management of this therapy. Prostate cancer is a world where you have multiple players, whether it is Urology, the Nuclear Medicine doctors or Medical Oncologies. Those would be the key differentiator drivers.

Yes. Yes. I wanted to ask you on a couple of the comments as a follow-on to your response. When you think about prostate overall, it's a lot of different markets. And so I was wondering if there is a way to maybe take advantage of some of the differentiation. Would there be a regulatory incentive, for example, to maybe pursue accelerated approval for post-taxane just given the unmet need or chemo or hormone-free doing a head-to-head. Could you take advantage of faster regulatory pathways through that. I'm just trying to think of ways to maximize the novelty from a clinical development perspective with regard to the mechanism.

Thank you for that. We haven't shared any details of any of our statistical analysis. So I'm not going to reveal anything here. But I would reply to your question by saying that we are so convinced of the importance of this therapy that we are bringing in and this is completely under -- regarded by many investors to earlier lines. We are -- we have 3 ongoing Phase Ibs, one in the neoadjuvant setting. So before surgery. We have one in biochemical recurrence. And we have one in hormone-sensitive prostate cancer.

So we already changed the narrative. We are now waiting for our Phase IIIs to read out positive in castration-resistant prostate cancer, post-hormonal therapy, post-taxane. We are already testing it in the Phase Ib sitting in the earlier sites of prostate cancer. So we hope that we'll generate data that will help us then move to that setting in a registrational trial.

I mean, Geoff, I want -- just to build on what Jean-Charles is saying. One of the things that provides us confidence to do, as Jean-Charles described, is what we've observed with both BLINCYTO as well as IMDELLTRA. And that is when you move the T-cell engager earlier in the treatment paradigm into settings of lower tumor burden you really see impressive inflections in survival. And we saw that with BLINCYTO, we're seeing evidence of that with IMDELLTRA and that furthers our hypothesis and the rationale to pursue xaluritamig in the early stages of prostate cancer as well. We'll have to see what the data teach us, but that underpins some of the thinking that Jean-Charles just described.

Okay. That's helpful. Thanks, Casey.

Makes sense. And maybe just sticking on xaluritamig for a little bit longer. We often get questions on prostate cancer, but Ewing sarcoma is certainly one that isn't really brought up very often. And given you have a Phase Ib study and a pretty broad population going on in relapsed/refractory. Maybe tell us a little bit more about xaluritamig's opportunity there and why STEAP1 would be a good target for that type of indication. Jean-Charles, I think you're on mute.

I am on mute, thank you for letting me know. So in drug development, we always navigate this tension of what can we do for rare indications, but when you have an asset like xaluritamig, where the development plan in a common indication is there and its clearing is compelling. Going to Ewing sarcoma is something that was justified by the biology of the disease, the extremely high levels of expression of the target. And the true unmet need because if you fail the frontline therapy in Ewing sarcoma, and this is both for young adults and pediatric cases. It's not a good prognosis.

So we are very excited to bring this innovation in that setting and the trial is open and we are eager to see what it will bring. But the biology makes sense, the unmet need is there, and it's a rare disease, but we can justify doing it because we have already made an investment in the common tumor type.

Jean-Charles, let's switch gears to maybe the earlier to mid-stage pipeline. So AMG 193 in development for mTAT solid tumors. Talk a little bit about kind of what insights at Amgen has gained here given this -- the mechanism. I think it does showcase kind of Amgen's more discovery kind of angle here to bring a unique asset like this. But talk about the next -- what tumor types do you think is -- could this work for the best, based on the data that you have today, I know you have Phase Is in lung, but maybe lead us down to the path of where the science could go in terms of other tumor types.

Yes. Thank you. Thank you for that. We presented our data at ESMO presidential session and show activity across multiple tumor types, that we have focused the development more on long and gastrointestinal solid tumors. In lung cancer, we have a Phase Ib combining AMG 193 with different standards of care to see the combinability, that's an important one. In lung, we also are doing the randomized dose optimization to define what will be the recommended dose for registrational trials. And that one is ongoing. And it makes sense because it's a very big tumor type where the prevalence is significant. I mean, not significant at least good enough that you have enough patients.

And we are also combining AMG 193 with other standards of care in the setting of gastrointestinal tumors. And we -- I would just refer also to a trial in which we are combining AMG 193. We did the revolution medicine RAS inhibitor in pancreatic cancer. This is to tell you, we are following the science and the biology and combining with what makes sense as the standards of care in different tumor types or standards of care to be common in the case of tarlatamab.

Jean-Charles, are there lessons to be learned in the case of the mechanism here from resistance. In other words, can you find other dual mechanisms as you try to think about a combination sphere that could help mitigate the risk of that and maybe maximize the antigen activity.

That's a very good question. In fact, the biology of PRMT5 inhibition in the setting of the pent-up deletion is a new one, is a new frontier. We had the first generation inhibitors that were not really active, that had a lot of hemtoxicity, but squeezed inhibitors that are MTA-comparative are a new reality. And -- what we are discovering is that the biology of how the tumor response to that therapeutic pressure is pretty unique. We have not only objective response rates, but we have stable disease that become, with time, objective responses. That's not common in oncology to have that transformation. So it's an area where further investment in our understanding of science is yet needed and more to come as we unfold the results.

Yes. Yes. And I guess just as a follow-on to that, when you look at the tools that Amgen has in place, I mentioned the deCODE. Also the utilization of more AI driven. Talk a little bit about how that -- how technology has played a bigger role in maybe discovery, but also just trying to maximize the earlier Phase I data that you get that can maybe derisk a drug or give you a window into maybe other tumor types?

Yes, that's a very good question. We completely recognize how important the pace of change through technology and AI and machine learning is changing the world, the world of biology, the word of drug development, the world as a whole. And at Amgen, we are literally leveraging these tools from targeting identification and molecule design and generation of target antibodies to translational insights and better understanding our own clinical data. The tools will help us enhance our ability to analyze complex data sets.

You need to understand the complexity of putting those data sets in X5 is beyond human understanding, when you have very rich omics and radiomics and clinical data points. That's an area where patent recognition will be expedited through AI. Our goal is not just speed, it's also precision in improving the quality of our hypothesis and how we prioritize things and how we execute. You can imagine, for instance, how important it is to have an AI protocol uttering tool that will help you get protocols that are sharper with zero consistencies where we'll integrate amendments in an easier manner. Those are obvious ways.

With you AI has an amplifier of human expertise. These technologies really augment with our science and our drug developers, can generate in terms of creativity, in terms of experience, in terms of analysis. But we need to maintain extremely high standards. We are a regulated environment. So this needs to be done within defined guardrails. We are embedding AI and advanced analytics in most of our research engines, we are already seeing a shortening of the timelines as well as enhanced decision-making. And I'm very optimistic of what this will bring. It's accelerating quarter-by-quarter. It's getting better and better.

So maybe sticking onto the AI theme. Given the potential of your BiTE platform, how are you leveraging AI and maybe looking at other targets that you could look at, maybe your research into what other solid or liquid tumors that you maybe could target. Maybe give us a sense of the types of work you're doing to expand that platform and just make it even more fulsome than what we've already seen.

Yes. Thank you for the question. Obviously, creating new white space for T-cell engagers, but other modalities too, is extremely important, correct. We suffer in our industry from sometimes all going against the same targets. We were quite unique with DLL3 T-cell engager. There are many other modalities. So creative white space is very important. And it comes frequently through the very unique conversions of biology, technology and compute power. And I will give you a very clear example. We announced a deal with a company called DISCO Pharmaceuticals because they were ahead of us on understanding the surfaceome.

So the surfaceome is the reality of expression at the surface of a cancer cell of the different proteins, but people have a very simplistic view of how they are expressed. In fact, they create communities, they cluster together in certain ways. They have different densities. There are many new technological tools and AI tools that have helped tremendously accelerate the understanding of who is clustering with who and in which proportions that all of a sudden gives you a white space for new targets that would be dependent on the coexpression of an existing target. You can choose to say, what I want to know, who's the best and closest partner of DLL3 in proximity in a surface cancer cell.

Well, we announced a deal with DISCO Pharmaceuticals because they found a very interesting target in small-cell lung cancer. And that's an example of bringing in a very concrete way what the advancement of biology computing and technology can't.

Just as a follow-up to that, Jean-Charles, I know on bema, you guys aren't pursuing the gastric indication, but is FGF still an interesting target to you guys? Is there -- are there ways to go back to the drawing board using something like AI to maybe find some lessons learned here to try to redeploy into other tumor types. Just want to get your perspective on that.

Yes, sure. Casey, you want to start?

Happy to start. So for bemarituzumab, Geoff, as you mentioned, we've decided not to pursue regulatory submission in frontline gastric cancer. We're currently determining what the best next steps are for that program, and I think we'll have more to say beyond that. Jean-Charles, anything that you would add there in terms of...

Yes. We follow the science. So we need to understand what happened in the Phase III trials. So we are looking at elements from the biology that will explain some of the results, and we will share more down the line. But we follow the science train, not only for developing of assets, but also for analyzing some of the outcomes.

Okay. That's helpful. I guess in conjunction with use of AI and biomarkers. Just help us with kind of how much emphasis does Amgen have on things like novel biomarkers, diagnostics, things of that nature. I wasn't sure if there is an approach to embed more kind of discovery or bells and whistles, if you will, in a Phase I on more novel mechanism drugs like IMDELLTRA, like xaluritamig, that could help you down the road, right, more maximize treatment effect and minimize tolerability?

It's a great question. Thank you. We have a precision medicine department that serves all the therapeutic areas that is trying to bring that value. The value of better predicting what's the best biomarker package of an asset that will enter Phase I. Do we have molecular predictors of efficacy, but also the reverse translation of when you see an extreme responder or you see emergence of resistance, what is driving that? So we really believe in the value of that and we are investing. There are many frontiers, correct, in oncology, one of them being the availability of some of these markers in the blood versus the tissue.

The tissue is the issue very frequently in oncology. Everyone wants the tissue and people get very small biopsies. So that's a frontier where we have interest, and we hope to advance radiomics and combining radiomics with our old omics from deCODE and combining that with additional single cell analysis or clinical data to create if you want a more comprehensive multidimensional data set of clinical points is another one where we are investing.

Yes. And just the last question, just along those lines Jean-Charles. With regard to, say, cell and gene therapy, are you -- that hasn't historically been a major focus from Amgen, but is that a sort of modality or technology that I think, overtime, Amgen could develop? Or are you pretty comfortable with the bispecific and T-cell engager and pDC. You have a lot of tools right now in the tool chest. So I guess that's the question. Do you add more? Or do you maximize kind of working out?

Thank you for that question. Our pillars on T-cell engagers and small molecules are not meant to be exclusive. So we will invest where it makes sense and leverage our strengths. I mean ADCs is one area which could make sense because we are a very strong biologics company and have good chemistry. But on the cell therapy front, that's a completely different modality and quite competitive. I mean, it's around T-cel engagers, correct. We are happy to see our T-cell engagers bringing benefit for solid tumor patients. We have not seen cell therapy deliver that in solid tumor patients. So cell therapy with other complexities in terms of the production, the availability, the cost. So we are very pragmatic. We follow the data points. And that is the answer I will give it to you. We will follow the science, but be very selective. Amgen is very disciplined in what it does. So we are not spreading and making beds everywhere. We are selectively making certain beds.

Makes sense. Okay. With that, we're out of time. So Jean-Charles, thank you so much, Casey, as well. I appreciate the input guys. Super helpful conversation.

Thank you for inviting us.

Yes. Thank you for having us today. Good to see both of you.

You too.

All right, everyone. Good afternoon. This is David Amsellem from the Piper Sandler Biopharma Research team and a happy almost Friday to everyone listening in. So in the next 25 minutes, we're going to be speaking with Amgen and lots to talk about when it comes to immunology and inflammation. We're delighted to have CMO, Paul Burton. We also have from the IR team or the Head of the IR team Casey Capparelli as well. Thanks, gentlemen, for joining us.

So I know there's a lot to talk about. And last week, there were some new developments in terms of new clinical trial initiations and also new data. So I'm admittedly going to bounce around. But one product I wanted to start with, Paul, if you don't mind, is UPLIZNA. So obviously, you had the label expansions last year. But you did discuss last week plans to initiate Phase III studies in autoimmune hepatitis and also chronic inflammatory demyelinating polyneuropathy later this year. So I guess a high-level question here. You got a B-cell depleter in UPLIZNA. So maybe talk about your rationale here for moving ahead with these 2 clinical settings and help us better understand the rationale for B-cell depletion in both of these clinical settings.

Great. David, look, thanks for having us. I think as a company, we have strong experience in B-cell depletion. We have BLINCYTO which has had data from a number of centers, looking at patients with RA as well as systemic sclerosis, showing clinical improvement there. And we also have a master Phase II protocol actually enrolling patients both with SLE or rheumatoid arthritis, looking at both UPLIZNA and BLINCYTO. And so UPLIZNA is a remarkable medicine, 6-monthly dosing, excellent safety profile. And both autoimmune hepatitis, AIH and CIDP are conditions where pathogenic B cells seem to play a central role, probably through autoantibody production, but immune disregulation as well. And so UPLIZNA being a B-cell depleter targeting CD19 is interesting because it's able to really target a broad spectrum of B-cells, pre B-cells, mature B cells and then plasmablasts.

And we think it's this breadth of its activity that is able to bring about diverse range of improvement in disease driving autoantibody conditions. So AIH is characterized by liver inflammation and that can cause progressive scarring and loss of liver function, CIDP, disabling immune-driven neuropathy that damages peripheral nerves, myelin. And both of these diseases have quite a lot of similarities with IgG4-related disease as well as generalized myasthenia gravis, where UPLIZNA because of its B-cell depletion activity has been able to show durable and really quite profound clinical benefit. So it's really this scientific basis where we've had proven effectiveness of UPLIZNA that makes us think that AIH and CIDP are really important unmet medical needs where UPLIZNA could play very strongly. And so that's why we're interested now in tackling those diseases.

And then one more quick question before I kind of move on to other parts of the I&I portfolio in terms of just how you think about the sizing of these to populations? Just help us better understand how you think about that, particularly relative to gMG and IgG4-related disease. And I mentioned IgG4-related disease because our understanding of the population is it looks to be a good bit bigger than what we thought it might be. So I'm kind of asking a similar question about these 2 populations and how are you thinking about that?

Yes. I think IgG4-related disease is interesting. When you have an impact for medicine, I think physicians are more likely to diagnose and to treat. And so that's important. For CIDP, we think the pool in the U.S. is around 35,000 patients. So that would be the prevalent pool with maybe about 7,000 to 10,000 incident new cases diagnosed a year. AIH is probably larger than that, but it's difficult to get an absolute number on it. But that just gives you a kind of a ballpark sense of where we are.

Okay. All right. That's helpful. So let's talk about Daxdilimab. So you announced -- or the team announced last week, positive results in -- Phase II discoid lupus, so just wanted to take a step back here. So Daxdilimab, I think it was acquired by the Horizon transaction, if I'm not mistaken. It did fail a Phase II study in SLE. Obviously, it worked in particularly challenging cutaneous manifestation with lupus. So I guess with that in mind are -- as you think about a product like this a plasmacytoid dendritic cell depleter, are these kind of cells more prominent in cutaneous manifestation of lupus? Or maybe put differently, can you talk to the mechanistic rationale behind the success in discoid/cutaneous lupus, but the failure in SLE.

Yes. So as you very rightly say, David, Daxdilimab is a first-in-class molecule that targets something called immunoglobulin like transcript 7 protein or ILT7. And it seems that, that is involved in driving plasmacytoid dendritic cell function and in turn interferon production. So Daxdilimab is essentially a plasmacytoid dendritic cell depleting agent, just like we've talked a little bit about in a different setting with UPLIZNA, which obviously goes after B sales. So SLE is an autoimmune disease. It tends to affect the skin, joints, kidney, the nervous system as well with autoantibody production and often you get complement depletion.

Discoid lupus is a skin manifestation. So it's similar to lupus, but it has SLE, but it has a different underlying pathology. It's driven, as I said and you said as well by plasmacytoid dendritic cells, interferon production in the skin, which leads to this dermatitis. And so we think because of that biology and the pathology that Daxdilimab would be a good potential therapy for discoid lupus. And in fact, as you say, we did do a Phase II study of Daxdilimab in those patients with discoid lupus. It met the primary endpoint, which was really a reduction in disease severity index at week 24. And it also met the key secondary endpoint, which was looking at investigator-assessed global assessment of disease activity.

We also have a smaller study, a Phase II study in just 12 patients with dermatomyositis where it also showed clinical benefit. So while, it didn't show the efficacy that we were hoping for, as you say, in SLE, we think that this positive Phase II in discoid lupus, coupled with the biology, coupled with the pathophysiology in that disease makes us feel confident that we can take this molecule into that setting and hopefully provide some clinical benefit there in these patients with discoid lupus. So we're excited about that.

Is the plan to move right to Phase III? And do you evaluate discoid lupus specifically? Or do you look at a broader population with cutaneous manifestations of lupus?

It's a great question. And I would say we're still thinking about exactly that we want to be very thoughtful. This is a difficult disease with few treatment options. We think we have a very attractive asset here. So I think we probably need a little bit more time just to continue to look at the data and plan the Phase III and then we'll share those plans in due course.

Okay. And then looking at Daxdilimab more broadly, can you just talk generally about other autoimmune disease settings where you think a product with this mechanism could play a role? And maybe just I'll ask bluntly, are you thinking about other potential indications for Daxdilimab regarding its development?

Yes, certainly, we'll be very methodical and very thoughtful in that anywhere where plasmacytoid dendritic cells, interferon production may have a role. We'll obviously think about but we're going through that whole process now. So I think we need just a little bit more time, and I will be able to comment more on that.

Okay. And then I wanted to spend a little bit of time on dazodalibep, which your CD40-directed treatment. So I believe the enrollment in your pivotal is wrapped up. Before we talk about Sjogren's, which I think is a really interesting space, can you talk to the underlying mechanistic rationale here?

Yes, absolutely. So for dazodalibep, the CD40, CD40 ligand axis, there's a common theme here, I think, David, in many of the diseases we've talked about, the CD40, CD40 ligand axis really drives B-cell activation cytokine production. And there is good evidence that it's active in Sjogren's syndrome. And so dazodalibep is a fusion protein that inhibits CD40 ligand. And by blocking this pathway, we think that we can interrupt the upstream immune activation that contributes not only to autoantibody production, but then in turn as well the downstream inflammatory cascade that you see in Sjogren's disease or Sjogren's syndrome. We think that mechanistically, dazodalibep is well suited to Sjogren's disease because it's heterogeneous and there's frequently immune activation across all of these different disease manifestations in that syndrome.

Okay. So I know you're running the 2 Phase IIIs, one is moderate-to-severe systemic disease activity. The other is a different population...

High symptomatic burden.

High symptomatic burden, it's low systemic disease activity. They're very different populations. So I guess what -- there's 2 questions I have here. One is how are these 2 different groups managed? And I guess, secondly, how could the drug be beneficial in both of these groups given its mechanism of action.

I think the answer to the first part, today, Sjogren syndrome is really managed symptomatically. So you have good oral care, tear replacement, analgesia for the pain. And sometimes, you can use glucocorticoids and steroids. So there's really not a good definitive treatment for it. We did publish the results in 2024 of our Phase II study, which also looked at these 2 groups independently within that study. And we were able to see an improvement in disease activity index as well as patient-reported outcome. And so that gives us confidence that going in now to this Phase III study that enrolls those 2 groups of patients.

But if the medicine behaves as it did in Phase II, we would hope to see a successful clinical outcome there. I think what we know about the disease is that CD40, CD40 ligand axis is active across both of those types of manifestations of Sjogren's. So I think you can have one therapy that is able to attack that underlying pathophysiological mechanism and bring about clinical improvement, albeit in 2 different subsets of the disease.

Is there a path to approval in 1 of the 2 subgroups or maybe put differently, do you have to have success in both studies to be in a position to file?

I think we would have to wait and see -- wait and look at the data and see how compelling it is. Again, we were successful in the Phase II in both groups and so we'll be hopeful that we'll be there as well.

Okay. And then on the competitive landscape or potential competitive landscape because there's a lot of white space here. But what are your thoughts on the FcRn directed treatment nipocalimab in Sjogren's and how you think as dazo stacks up versus that agent?

Just to remind everyone, we're hoping to have results from our Phase III study in the second half of this year. And I think, honestly David, we'll have to wait, it's just around the corner, really to see that and then how it compares. I would say that we are the first therapy to demonstrate efficacy in Phase II in both of those groups that you mentioned and that we're now studying them definitively in Phase III.

Okay. Okay. So let's -- let's talk about TEZSPIRE and all things, TSLP, lots going on. So I wanted to start with the label expansion for TEZSPIRE in chronic rhinosinusitis with nasal polyps. So this is a little bit of a commercial question and a little bit of a science question, which is how you see the product fitting into a treatment landscape relative to IL-4, IL-13 directed treatment and also the IL-5, I mean, I guess -- or maybe asked differently from a mechanistic perspective, how do you see the fit and also how TEZSPIRE could have an advantage in the nasal polyp indication?

Yes. Okay. So CRS with nasal polyps is a heterogeneous inflammatory disease. It often coexists with asthma, other respiratory conditions as well. And as you say, most therapies target the single or double downstream Th2 cytokines, IL-4, 5, 13. But those therapies do not address the upstream drivers like TSLP, which is involved in epithelial dysfunction and immune activation. And I think we've talked about this in the past. What's so exciting about TEZSPIRE is that it attacks TSLP right at the top of the inflammatory cascade. And so that gives it a differential profile. So upstream therapy can take out multiple inflammatory pathway. It's not only cytokine production downstream but also these diseases are often mediated through inflammatory cells, particularly eosinophils being recruited and activated.

So if you can control TSLP, you really can control both of those different pathways. And I think that mechanism we've seen has given strong adoption and confidence in some of the prescribers. In the -- just to remind everybody as well in that Phase III WAYPOINT study that underpinned the approval of TEZSPIRE in CRS with nasal polyps were able to show statistically significant clinically meaningful reduction in nasal polyp severity. Almost complete elimination of the need for surgery and a big reduction in the use of steroids versus placebo. So I'd say in summary, we think we're well positioned to reach more patients due to the differentiated mechanism, upstream mechanism of action. It's broadly applicable across multiple different patient phenotypes and that's widely appreciated by prescribers today rather than a single downstream pathway.

And one thing we hear a lot about is the extent to which is coexisting, a lot of coexisting asthma and nasal polyps. So -- is it your view that having nasal polyps in the label is something that actually can enable you to reach more asthma patients with TEZSPIRE?

Yes, it is. I mean we think that about the coexistence of chronic rhinositis and severe asthma is probably about 20%. So the overlap is large and really highlights a significant overlap between the 2 diseases, underlying pathophysiology that is both cytokine as well as [ eosinophilically ] driven and really supports the clinical value of TEZSPIRE in these 2 indications.

And then just touching a little bit more on asthma. What are your thoughts on the implications of the availability of an ultra long-acting biologic? I mean we have the -- we have now once or twice a year, depemokimab, that product recently is approved. I know it's mechanically different, but how do you see that impacting TEZSPIRE, if at all?

I mean I think these new agents, I think, are going to have to demonstrate safety, durability and meaningful clinical benefit. And so until we see those data I think it's difficult to comment on that. Our focus really is on execution. We have approved indications where the medicine is really showing excellent benefit, and we have other indications in development. I think what I can say is that with low penetration in severe asthma and the recent approval now for CRS with nasal polyps plus these additional Phase III studies we have underway, COPD, esenophilic esophagitis, we think that TEZSPIRE really has great potential to be a durable growth driver well beyond 2026 into a very large population of patients.

So let's talk about EoE. I know that study is not far away from reading out. But I had a couple of questions here, maybe we can tackle in the 5 minutes we have left. One is just talk to the nature of the unmet need and specifically biologic penetration here. And I guess where I'm going with the question is, we've got DUPIXENT available. We -- but there's a lot of corticosteroid management, of course, so just trying to get a better sense of how you're framing the unmet need, the underlying opportunity, particularly given the TSLP mechanism here?

Yes. So for eosinophilic esophagitis, we have not formally characterized the epidemiology of the disease. But when you look at the literature, here in the U.S., some databases would say that has a prevalence of about 1 in 700 people. I think it does represent an important and a high unmet medical need. The therapy today is proton pump inhibitors, surveillance maybe still reduce as well. So there's not a clear definitive therapy for the disease. And I think the fact that it is clearly a [ eosinophilically ] driven. And effectiveness and efficacy that TEZSPIRE has shown in those types of diseases that we've just talked about, it's very exciting.

And so as you say, the Phase III study is enrolled and we hope to have data being available in the second half of this year as well. I think in terms of comparisons, again, I'd be hesitant until we see the data to really make comparisons with other agents. But the data really are just around the corner second half of this year, and then I think we'll be able to define its profile and compare it to other therapies.

One quick follow-up here just in terms of data. And I know it's may be a hard question to answer, but one of the endpoints, co-primary endpoint, one piece of that is the dysphagia symptom questionnaire. So help us contextualize what kind of improvement here would be considered clinically significant. I mean I think the other endpoint is eosinophil count. So -- but I'm just trying to better understand on the DSQ, how you think about what would be clinically significant.

Yes. Well, look, again, I think we'll have to see the results of this study. And then I think we're going to have to talk to regulators. We talk to physicians and groups who are here in the U.S. and around the world. And I think it's oftentimes with these patient-reported outcome physician assessments, it's a discussion on the totality of data, the two endpoints together and really what do they see as the important difference there.

Okay. I wanted to just ask a general question about TEZSPIRE and just TSLP directed treatments and your plans beyond the core or what I call the core of asthma, nasal polyps, COPD and EoE, I mean, those are certainly, those are big populations in the aggregate, but are you thinking even more expansively about your TSLP franchise and other indications?

I would say we agree with you. I think they're big populations, the medicines being shown to really provide profound clinical benefit. I think for us now, it's about execution to build in those populations. As I said, we're still building penetration, and we have a lot of headroom. So we're not pursuing other indications for TEZSPIRE at this time. We do have AMG 104, which is an inhaled TSLP antibody fragment, and that may also have utility. We've tested that in Phase II. So we like TSLP as a target. We clearly have a great medicine for it. We want to execute there and then think about perhaps the inhaled agent as well.

Yes. So in the minute we have left, I wanted to ask about the inhaled agents. I know the enrollment in the Phase II is complete, so potentially another readout this year. But my question here is sort of 2 parts. One is your thoughts regarding the challenges of adequately delivering a biologic into the airways into the lungs. And then how you think you overcome those challenges? And then I guess the second question is, if you have data that you like and you want to move forward, maybe jumping ahead where does an inhalable TSLP fit in within the asthma armamentarium?

So look, I think mechanism of delivery, it's proven with other agents. We've conducted the Phase I. It was a small Phase I, it was like 104 patients in the first part and the second part of it, it's 77. It did show effectiveness, efficacy there, consistent with what we've seen with TEZSPIRE. So I think that's encouraging as well. We think that for more severe asthma inhaled corticosteroids, beta agonists are clearly sort of foundational therapy. But then something that, again, can attack right at the top of that inflammatory cascade, taking out cells as well as cytokine mediators could really have an important role in managing asthma and delivering a therapeutic right to the site of insult being converted into injury through TSLP production. So the Phase II is expected to complete in the first half of this year and so we'll have more data soon, and we'll be excited to share with.

And then just real quick, do you think it's potentially the 104 could be another option ahead of injected biologics. I mean is that one way to think about it?

Yes. I think it is. We'll obviously have to see the data. Think about it with experts, but yes, it certainly has the potential for that.

Okay. Well, I wish we had more time, but this has been great. Thanks so much, Paul. Thanks, Casey, and thanks to everyone listening in. But yes, this is an exciting year ahead in terms of readout. So more to come. But yes, thanks again, and really appreciate your time and wrap things up.

Thanks, David.

Thanks David.

My name is Julianne, and I will be your conference facilitator today for the Amgen Q4 2025 Earnings Conference Call. [Operator Instructions] I would now like to introduce Casey Capparelli, Vice President of Investor Relations. Mr. Capparelli, you may now begin.

Thank you, Julianne. Good afternoon, everyone, and welcome to our fourth quarter 2025 earnings call. Bob Bradway will lead the call today and be followed by a broader review of our performance by Jay Bradner; Murdo Gordon; and Peter Griffith. Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompanied this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially.

Over to you, Bob.

Okay. Thank you, Casey, and good afternoon, everyone. Thank you for joining us today. Today, we'll cover full year results for 2025 and provide a preview of what to expect from us in 2026.

Amgen delivered strong operational performance across the board in 2025. And you can see that in the breadth of our business. Note that 14 of our products achieved blockbuster status with sales of $1 billion or more, 13 products delivered double-digit sales growth and 18 products achieved record results for us. The strength of that broad portfolio enabled us to post double-digit growth in revenues and earnings per share for 2025.

Looking to 2026, I would highlight 6 areas of momentum. Three of these, Repatha, EVENITY and TEZSPIRE all grew by more than 30% year-over-year in 2025. These medicines have a few important things in common. First, their highly effective, innovative therapies that address important public health needs. Second, their leading products in their fields. And third, while each of these products represents a multibillion-dollar global franchise already, they address areas of large unmet medical need, where there are millions of patients yet to be treated. In this sense, they represent growth drivers not just for 2026, but for the rest of the decade.

In rare disease, our portfolio generated more than $5 billion in sales in 2025. Here, too, many of our medicines are early in their life cycle and positioned as leaders in their respective categories. Growth has been fueled by reaching new patients, expanding into additional geographies and launching new indications. We see further opportunity ahead as we scale these therapies. UPLIZNA exemplifies this growth opportunity with approvals in IgG4-related disease and generalized myasthenia gravis in 2025.

Our innovative oncology portfolio grew at 11% year-over-year in 2025 driven by our BiTE or bispecific T-cell engager medicines. We're particularly excited about IMDELLTRA which has rapidly become the standard of care in patients with second line or later small cell lung cancer, supported by unprecedented survival benefits.

We're an industry leader in biosimilars. Our biosimilars portfolio has contributed more than $13 billion in sales since the launch of our first medicine there in 2018. With $3 billion in 2025 sales, this business is an important contributor to our organization and poised for growth with the next wave of biosimilar launches. You can appreciate the depth of our business through the lens of our research and development activities. 2026 will be a year of disciplined data generation from a number of exciting Phase II and Phase III programs that will pave the way for long-term growth at Amgen.

Our confidence continues to build in MariTide as a differentiated treatment for obesity, type 2 diabetes and obesity-related conditions. In a field featuring dozens of potential daily oral and weekly injectable medicines, MariTide stands alone as the only therapy in late-stage development to offer the paradigm-changing prospect of strong efficacy and favorable tolerability at monthly, every other month or even quarterly dosing. In addition to MariTide, we remain excited about olpasiran and what it might represent for patients with elevated Lp(a) a heritable risk factor for cardiovascular disease. We see olpasiran as an opportunity to build on our leading positions in cardiometabolic disease.

It shouldn't be lost on any of us that Repatha, olpasiran and MariTide together would represent a very compelling set of cardiometabolic medicines to expand our leadership in the treatment of serious chronic diseases well into the next decade. Beyond the pipeline, there's a great deal of enthusiasm about the convergence of technology and life science. And based on what we're seeing at Amgen, we believe that enthusiasm for convergent innovation is well placed and will have significant impact on how we discover, develop and commercialize medicines.

As always, I thank my Amgen colleagues around the world for supporting our mission to serve patients. And with that, let me turn it over to Jay for an update in R&D.

Thank you, Bob, and good afternoon, everyone. Fourth quarter capped off a year of strong disciplined execution across R&D. Throughout 2025, we advanced multiple late-stage programs, delivered 5 key regulatory approvals and strengthen the evidence base supporting our marketed medicines. Taken together, these contributions demonstrate real scientific rigor and illustrate the breadth of opportunity ahead.

Let me begin with MariTide, which continues to develop a meaningful and very encouraging ways. The MARITIME Phase III program is rapidly advancing with strong enthusiasm from investigators and participants. Both of our Phase III chronic weight management studies are fully enrolled and our ASCVD and heart failure outcome studies are progressing well. In parallel, we continue to expand the clinical landscape of MariTide across obesity-related conditions. As we began enrollment of our 2 Phase III sleep apnea studies In adults with and without positive airway pressure therapy. Altogether, we now have 6 global Phase III studies underway with MariTide collectively designed to deliver a comprehensive evidence base.

In addition, as we shared last month, we've completed part 2 of the MariTide Phase II chronic weight management study. We also completed the first 24 weeks of the Phase II type 2 diabetes study that enrolled participants with and without obesity. Results from these 2 studies further increase our confidence the MariTide can represent a new paradigm in obesity, type 2 diabetes and other obesity-related conditions. We believe MariTide has the potential to expand what's possible for patients. Availing an opportunity for monthly or less frequent dosing. MariTide's strong efficacy, infrequent dosing and excellent tolerability to target dose has the potential to further enhance the patient experience and therefore, treatment persistence, a major unmet need in the field.

Beyond obesity and general medicine, the fourth quarter brought a landmark contribution to cardiovascular health for Repatha. In November, full results from the Phase III VESALIUS-CV trial were presented at the American Heart Association Scientific session and simultaneously published in the New England Journal of Medicine. This study enrolled more than 12,000 patients without a prior heart attack or stroke, testing the impact of Repatha for LDL-C lowering when added to optimize lipid therapy, namely statins, with a median follow-up of approximately 4.5 years.

In VESALIUS CV, Repatha demonstrated a 25% relative risk reduction in the composite of coronary heart disease death, heart attack or ischemic stroke and delivered a 36% reduction in heart attack with no new safety signals observed. These data clearly demonstrate that intensive LDL-C lowering with Repatha can meaningfully reduce the risk of a first cardiovascular event. Reinforcing its role across the full continuum of cardiovascular risk.

Turning to olpasiran, our potentially best-in-class small interfering RNA medicine targeting Lp(a) the fully enrolled OCEAN A outcome study continues to progress. As previously discussed, this is an event-driven study, and the aggregate endpoint accrual rate remains lower than initial predictions. As the study matures, we will update on the date for primary analysis as appropriate. Our conviction in olpasiran to reduce cardiovascular risk conferred strong grounded in compelling genetic and epidemiologic evidence that establish elevated Lp(a) as an independent risk factor for heart disease.

Moving to rare disease. The fourth quarter was highlighted by important regulatory momentum for UPLIZNA. In November, the European Commission approved UPLIZNA for the treatment of adults with active IgG4-related disease. And in December, the FDA approved UPLIZNA for the treatment of generalized myasthenia gravis in adult to our anti-acetylcholine receptor or antimusc antibody positive. These approvals built on strong Phase III data, demonstrating durable efficacy, a steroid-sparing benefit with every 6-month dosing. This research further extends the impact of CD19-directed B-cell depletion across serious autoimmune diseases.

More broadly in B cell depletion, where we have a number of proof-of-concept studies underway, we expect to initiate 2 pivotal studies this year. The first is for patients with autoimmune hepatitis, a serious disease characterized by persistent liver inflammation that can lead to progressive scarring, loss of liver function and ultimately, liver failure. The second that is chronic inflammatory demyelinating polyneuropathy, or CIDP, a disabling immune-mediated neuropathy that damages peripheral nerve bilan resulting in worsening strength, worsening sensation, and for many patients, substantial impairment in daily activity.

With UPLIZNA, we are targeting these diseases at their root cause by depleting pathologic B cells that drive disease through secreted autoantibodies. Given the strong efficacy of UPLIZNA in other settings, we're excited about the potential to bring a meaningful new option to patients with these 2 devastating conditions.

We are also advancing dazodalibep our CD40 ligand targeting biotherapeutic with both Phase III studies in [indiscernible] disease now fully enrolled and study completion expected in the second half of 2026. We're pleased today to announce positive Phase II data with daxdilumab, a first-in-class plasmacytoid dendritic cell depleting monoclonal antibody targeting ILT7, for the immunoglobulin-like transcript Devin protein. This study in patients with primary discoid lupus arosomatosis met both primary and key secondary endpoints with an attractive safety profile.

Encouraged by these data, we are working to advance daxtilimab to the next phase of development in this setting. In inflammation, the TEZSPIRE Phase III program continues to advance with ongoing studies in chronic obstructive pulmonary disease and eosinophilic esophagitis, where we expect study completion in the second half of this year.

We recently announced the decision to terminate the rocatinlimab development and commercialization collaboration with [indiscernible] with significant breadth and depth across all 4 therapeutic areas, we took a portfolio decision to focus resources on other late-stage programs. Rocatinlimab will return to our partners at [indiscernible] who will assume full ownership of the program.

Turning to oncology. In November, the FDA granted full approval to IMDELLTRA for the treatment of adult patients with extensive stage small cell lung cancer with disease progression on or after platinum-based chemotherapy. This approval represents a meaningful advancement for patients facing a disease that has seen very little innovation for decades. To extend the impact of IMDELLTRA, we are presently advancing this medicine as combination therapy in front-line extensive-stage small cell where we observed unprecedented survival in early phase clinical trials.

Further, we are also advancing IMDELLTRA with an ongoing Phase III study of limited-stage small cell lung cancer. It's joy to see IMDELLTRA, like BLINCYTO, becoming a standard of care in the management of advanced cancer. Our first-in-class [indiscernible] directed bispecific T cell engager zalaritomig, continues to advance through Phase III development in prostate cancer.

Beyond prostate cancer, we have recently initiated a Phase Ib study in relapsed or refractory in sarcoma, a rare malignancy with high STEAP1 expression and patients in an urgent need for targeted therapy. Across IMDELLTRA, BLINCYTO and Zalaritomic, we continue to see meaningful long-term impact from our bispecific T cell engager platform. We remain committed to bringing transformative and innovative therapies like these to patients with cancer.

To close out oncology, given the previously announced results from FORTITUDE 101 and FORTITUDE 102, we have decided not to pursue regulatory approval for bemarituzumab, our FGFR2b targeting monoclonal antibody in first-line gastric cancer. The overall efficacy did not meet our expectations. We observed an emerging signal of punitive survival benefit in a subset of biomarker to find patients. We expect to share these findings with the scientific community in the future.

As with rocatinlimab, we took a portfolio decision to focus resources on our other late-stage programs. Across biosimilars, both ABP 206 and ABP 234 biosimilar candidates to OPDIVO and KEYTRUDA, respectively, have completed enrollment in each of their comparative clinical studies supporting continued progress of the next wave of our biosimilar portfolio.

Before closing, as described in our press release, we are engaged in an ongoing dialogue with the FDA regarding Tamio our medicine for the treatment of a rare and severe disease, ANCA-associated vasculitis. We will update you on those discussions as necessary.

Now let me finish by saying that 2025 was a year of consistent execution, real scientific progress and disciplined decision-making. We expect 2026 to bring another year of strong execution disciplined data generation and new scientific advances as we continue to progress our robust pipeline.

I want to thank our colleagues across Amgen for their continued focus on patients, and their commitment to advancing innovative medicines for serious diseases. With a broad and deep pipeline, we are well positioned to deliver sustained long-term growth.

I'll now turn it over to Murdo for the commercial update.

Thanks very much, Jay. In 2025, we delivered 10% sales growth with 13 products achieving double-digit or better performance. 14 products exceeded $1 billion in annual sales and 18 products achieved record sales. These results underscore the strength and growth potential of our portfolio and demonstrate the disciplined execution of our teams serving patients globally.

Starting with General Medicine, Repatha sales grew 36% year-over-year in 2025, surpassing $3 billion. This performance was driven by growing urgency to treat patients in both secondary and primary prevention. Today, more than 100 million people around the world still need effective LDL-cholesterol lowering. And Repatha remains the first and only PCSK9 inhibitor with outcomes data for patients in both high-risk primary and secondary prevention. As Jay mentioned, the landmark VESALIUS CV trial showed a reduction in the risk of first major cardiovascular events by 25% in high-risk patients. These data strengthen Repatha's position as the most evidence-backed therapy in the PCSK9 class and support this critical role in earlier and more intensive LDL cholesterol management.

Given these results and our leadership in this category, we believe there's now a clear opportunity to update clinical guidelines and quality measures. We expect these changes will encourage cardiologists and primary care physicians to manage LDL cholesterol more proactively alongside lifestyle modification and reduced cardiovascular risk in both primary and secondary prevention.

In the U.S., we continue to improve patient access to Repatha with broad formulary coverage and the launch of Amgen Now, our new direct-to-patient program. Amgen now offers a simplified lower cost cash pay option for patients to access Repatha. Following a successful launch, we've announced plans to expand this program to additional medicines and we're excited to make our therapies available through Trump Rx, helping improve affordability for Americans. EVENITY sales increased 34% in 2025, reaching $2.1 billion in sales. EVENITY remains the only treatment that simultaneously builds new bone and reduces bone resorption, a dual mechanism that has proven to rapidly reduce fracture risk in the postmenopausal women.

In the U.S., EVENITY sales grew 41%, driven by higher volumes from both established and new prescribers. EVENITY leads the bone builder segment with over 60% market share and is now growing faster than the category overall. To date, approximately 300,000 U.S. patients have been treated with EVENITY with a 33% increase of new patients in just 1 year. Increased investment has helped accelerate this growth, which we expect to continue. Despite strong progress, nearly 90% of the 2 million women at very high risk of fracture remain untreated, presenting a clear opportunity for EVENITY to drive growth and impact.

Prolia delivered $4.4 billion in sales in 2025, an increase of 1% year-over-year. In 2026, we expect accelerated sales erosion driven by increased competition as multiple biosimilars have launched globally. Our rare disease portfolio grew 14% year-over-year to nearly $5.2 billion and 19% in the quarter. With strong performance across the portfolio. [indiscernible] sales increased 73% year-over-year to $655 million, reflecting growing patient demand across all 3 approved indications. In December, UPLIZNA received FDA approval for the treatment of generalized myasthenia gravis, marking an important milestone for patients with this chronic debilitating disease. Hourly physician response has been strong across both bio-naive and switch patients. Prescribers have noted the benefits of a business upstream B-cell mechanism, targeting the root cause of the disease and it's also has demonstrated safety profile and the convenience of its twice yearly dosing.

Uptake of UPLIZNA for use in IgG4-related disease continues to grow since the launch in the U.S., nearly 500 specialists, including rheumatologists, gastroenterologists, among others, have prescribed UPLIZNA. In addition to the more recent launches, UPLIZNA continues to lead in NMOSD and remains the most prescribed FDA-approved therapy in the U.S. for this condition, supported by consistent new patient growth and strong adherence across treatment cycles.

TEPEZZA grew 3% to $1.9 billion in 2025 driven by higher net selling price. Over 25,000 patients have received treatment since launch in the U.S. with growing interest from both new and returning prescribers. We continue to see increased prescribing by endocrinologists and a broadening base of specialists. In Japan, approximately 1,200 patients have been treated since launch, reflecting growing awareness of the burden of thyroid eye disease among both patients and prescribers. We plan to launch TEPEZZA in additional markets in 2026, expanding access to this important therapy globally.

TAVNEOS sales were $459 million in 2025, an increase of 62% year-over-year driven by strong volume growth. More than 7,000 patients with ANCA-associated vasculitis have now been treated with TAVNEOS with over 4,000 health care professionals prescribing the therapy since its launch in 2021. We an associated vasculitis is a serious, potentially life-threatening disease that can cause significant organ damage is not well controlled and has limited therapeutic options. We remain confident that apneas is an important and effective medicine based on clinical data, real-world evidence and its favorable benefit risk profile.

In inflammation, TEZSPIRE sales grew 52% year-over-year to nearly $1.5 billion for the full year. TEZSPIRE is well positioned to reach more patients in the United States due to its differentiated TSLP mechanism that targets multiple inflammatory pathways driving severe uncontrolled asthma, including in those with coexisting chronic rhinositis with nate rhinosinusitis with nasal [indiscernible]. TEZSPIRE substantially reduced the need for surgery in this population, reinforcing its value in eosinophilic disease. TEZSPIRE is now the leading therapy for new-to-brand patients amongst allergists in severe uncontrolled asthma, fueled by strong prescriber confidence and continued expansion across respiratory specialties.

Otezla sales increased 7% year-over-year to nearly $2.3 billion for 2026. We expect sales erosion driven by unfavorable pricing in the U.S. and generic launches, particularly in the EU. Our innovative oncology portfolio, which includes BLINCYTO and Delta, Lumicras, Vectibix, KYPROLIS, Nplate and XGEVA grew 11% year-over-year, generating $8.7 billion in full year sales.

IMDELLTRA delivered $627 million of full year sales, fueled by strong clinical conviction and rapid adoption across care settings. Over 1,600 U.S. sites now administer IMDELLTRA with the majority of doses provided in the community setting. IMDELLTRA was granted full FDA approval in the fourth quarter, supported by compelling data from the Phase III [indiscernible] trial. NCCN guidelines also recognized IMDELLTRA as the highest recommended therapy and it has become the standard of care in the second-line setting, reinforcing its leadership position in small cell lung cancer.

BLINCYTO grew 28% year-over-year to over $1.5 billion in full year sales, driven by broad prescribing across both academic and community segments. Blincyto is widely recognized as the standard of care in combination with multi-agent chemotherapy for patients with Philadelphia chromosome-negative B-cell ALL. Our biosimilar portfolio delivered another strong year with sales increasing 37% to $3 billion.

Our expanding biosimilar portfolio provides meaningful top line growth, durable cash flow and broad patient access to high-quality cost savings for biologic medicines. PAVBLU, a biosimilar to EYLEA continues to gain momentum, reaching $700 million in sales in 2025. Adoption continues to build among retina specialists who value the products ready to use prefilled syringe format and the reliability of Amgen's manufacturing and supply chain. We delivered strong results in 2025 with continued momentum across our priority growth brands, and we look forward to serving even more patients with Amgen products in 2026.

Now I'd like to hand it over to Peter.

Thank you, Murdo. We're pleased with our execution and performance in the fourth quarter and for the full year 2025, and we remain on track with our long-term objectives. The financial results are shown on Slides 34 to 36 of the slide deck. Murdo has covered our strong revenue growth across the portfolio. For the full year, we delivered a non-GAAP operating margin of 46%. We continue to invest in advancing our pipeline with non-GAAP R&D spending increased 22% year-over-year for the full year to a record $7.2 billion. This reflects increased spending on an unprecedented number of opportunities in our late-stage pipeline, including continued investments in MariTide, olpasiran, [indiscernible] and rare disease. In addition, we closed several business development transactions in the third and fourth quarters, resulting in roughly $300 million in incremental R&D spending.

Full year non-GAAP other income and expense was $2.1 billion. We continued to strengthen our balance sheet with $6 billion of debt retired in 2025. Our non-GAAP tax rate increased 1.4 percentage points year-over-year to 15.9% for the full year, primarily due to changes in earnings mix. We generated $8.1 billion in free cash flow for the full year, reflecting operational momentum across the business and rigorous management of working capital, all while continuing to invest in innovation. We're leveraging AI across the value chain to accelerate therapeutic discovery and late-stage development, optimize manufacturing and improve customer engagement allowing us to drive productivity at speed and scale.

We executed capital expenditures of $2.2 billion in 2025. Our capital expenditures reflect significant investments across the United States including Ohio, North Carolina, Puerto Rico, Rhode Island and California to support continued volume growth in our commercial brands and to prepare for pipeline product launches, including Maritime. In addition, we returned capital to shareholders through competitive dividend payments of $2.38 per share in the fourth quarter, representing a 6% increase compared to 2024.

Let's turn to the 2026 outlook on Slide 37. We expect our 2026 total revenues in the range of $37.0 billion to $38.4 billion, and non-GAAP earnings per share between $21.60 to $23. Our revenue range reflects continuing strong performance from our 6 key growth drivers. Repatha, EVENITY, TEZSPIRE, our rare disease, innovative oncology and biosimilars portfolios, positioning 2026 as a springboard year for future growth. We expect this growth in 2026 to more than offset anticipated declines from increased denosumab biosimilar competition, price declines for certain other products in 2026 and continued increases in 340B program utilization.

As you model the first quarter of 2026, consistent with historical trends tied to the annual United States health insurance cycle, we expect a seasonal headwind to sales, driven by benefits land changes, insurance reverifications and higher patient co-pay obligations. We also expect Otezla and Enbrel to follow their historical pattern of lower sales in the first quarter relative to subsequent quarters and expect additional impact from denosumab biosimilar competition in Q1. Additionally, note that we saw roughly $250 million of inventory build in the fourth quarter of 2025 that could potentially impact first quarter sales. For total company revenues, we expect lower mid-single-digit year-over-year growth in the first quarter.

For the full year, we expect other revenue in the range of $1.6 billion to $1.8 billion reflecting our commitment to investing in the best innovation while also driving execution excellence, efficiency and prioritization across the organization, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 45% to 46%. This guidance does not include any potential business development transactions that may occur throughout the year. We expect non-GAAP R&D expense to grow low single digits excluding the roughly $300 million of business development transactions in 2025.

We continue to execute 6 global Phase III clinical trials for MariTide, advance additional late-stage assets, and invest in the best innovation while maintaining disciplined resource allocation. In line with lower product sales in the first quarter, we expect Q1 non-GAAP operating margin to be the lowest of the year and roughly the same as Q4 of 2025. We anticipate non-GAAP other income and expense to be about $2.3 billion to $2.4 billion in 2026. We expect a non-GAAP tax rate of 16% to 17.5%. We expect share repurchases not to exceed $3 billion in 2026. We expect capital expenditures of about $2.6 billion in 2026. This is consistent with our capital allocation priority to invest in our business and scale manufacturing capacity for volume growth, including preparing for MariTide launch. We remain focused on delivering sustained long-term growth and creating value for patients and shareholders by doing what we said we would do, advancing innovation in areas of high unmet medical need and maintaining rigorous financial discipline.

I'm grateful to work with all of our colleagues worldwide to serving patients. This concludes the financial update. And now I'll hand it back to Bob for Q&A.

Okay. Thank you, Peter. And as I hope you all appreciate it now. I think we ended '25 with our track record intact for having delivered against the objectives that we set for you at the beginning of the year. We're determined to do the same now in 2026. So we're entering the year with momentum, excited about what we see ahead.

Let's open up the call to questions, Julian. We'd be happy to entertain any of our callers now.

[Operator Instructions] Our first question comes from Michael Yee from UBS Financial.

It looks like guidance is growth for the year despite the biosimilars. Obviously, obesity is top of mind for everybody, and you've disclosed some information on MariTide recently. I was wondering and curious to ask your view of the portfolio overall in obesity given that for like today are disclosing combinations with monthly or monthly and then combinations and how you see this playing out given you're focused on MariTide, but not so for about the rest of the portfolio there.

Okay. Thank you, Michael. We'll take a stab at answering your questions. Connection wasn't great, but I think we got most of what you were trying to ask, Jay, do you want to kick off?

Yes, I'd be happy to. Thanks, Michael. The Amgen's really made for this moment, developing MariTide across so many different indications, a leading cardiovascular company, also a leading respiratory disease company, and there are so many opportunities there for MariTide. We've been in obesity, as you know, a long while all the way back to the left in days and enjoyed stable discovery leadership team since that time. Internally, we have another clinical stage asset, called AMG 513. We have yet to disclose the mechanism of that medicine is progressing in Phase I clinical investigation. And preclinically, we have a rather exciting set of rising programs that are both increasing base as well as nonincrease in base, both injectable as well as oral medicines. And the aperture is always open for innovation on the outside.

I think you should expect us to be competing broadly in the field, Michael.

Our next question comes from Yaron Werber from TD Cowen.

I have a question actually about dazodalibep for primary Sjogren�s Syndrome. It looks like both studies are now fully enrolled, and you're saying completion in the second half, the only company with both the systemic and the symptomatic study in Phase III based on the Phase IIs, would -- should we expect the data this year? And do you want to give us any color on the reliability of the Phase II into the Phase III, just given it's a tough condition.

Thanks, Yaron, and thanks for noticing about dazodalibep. This is a very exciting medicine in the portfolio. This is a CD40 ligand targeting biotherapeutic and the CD40 pathway has long been postulated to be driving the inflammatory cascade in Sjogren's Syndrome. The challenge is only that the biology is somewhat ambiguous. And so we take a really nice and incisive approach with dazodalibep disease. As you noted, the 2 Phase IIIs that we have opened in Sjogren's syndrome will be in moderate to severe symptomatic activity. That's our population on as well as in patients with a very high symptom burden. That's population 2. Sjogren's has been very challenging for drug development, but here we find this hypothesis is quite compelling.

The second study has already completed enrollment of patients. This is the MariTide in the burden group with low systemic disease activity. and we expect completion of the trials later this year, and we'll inform later about our plans to communicate this information. As for reading through the reliability of Phase II into Phase III, there have been historic challenges here. but the performance against this SDI score, which is the clinically utilized as well as regulatory paradigm for approval was 1 of the first medicine ever to improve an STI score in that disease space. So we're confident going into Phase III, I can't wait to look at the results.

Our next question comes from David Amsellem from Piper Sandler.

So I had a couple of line-related questions. Can you talk about the extent to which the underlying IgG4-related disease population is larger than what literature has suggested historically and what that means for the underlying opportunity? And then secondly, I know it's early in gMG, but just -- can you talk about how the product is being used to date? And what kind of role do you think it's going to have in the -- in an admittedly more crowded treatment armamentarium?

Yes. Let's -- don't we tackle this in 2 parts. Jay, if you take the first part and then maybe, Murdo, you can jump in on the second.

There is, in medicine, an experience where the availability of a targeted therapy a really effective therapy can actually increase the incidence of a disease through awareness of the disease, why take a diagnosis unless you have reason to intervene effectively. And that may, in the fullness of time, be the case here, limiting a precise description of the epidemiology, even over the last 5 to 10 years is the lack of really coherent registry data as well as appropriate coding that would allow such an analysis from electronic medical record data. And so I think it's a good question. I think it's a moving object, and we'll have better precision on that in the few years to come.

Murdo, what are your in things? I think that's a very clear description, Jay. I think the availability of the ICD-10 coding as you alluded to, is really about a 3-year presence in the market. Right now, we estimate the diagnosed population to be in the neighborhood of 35,000 and that could grow. As you outlined, there are mentions in the literature of higher numbers. However, we're obviously focused on those that are already diagnosed already in care, and we're trying to build that awareness that you spoke of. Again, so far so good. UPLIZNA is doing extremely well in its uptake in IgG4-related diseases. We see a nice breadth of prescribing across a number of different specialties that see these patients because of the end organ involvement in the inflammatory condition. And we'll continue to make sure that we do our part to improve that awareness, improve that diagnosis.

These patients undergo a very complicated patient journey in that this disease can mascara as many other things. But so far so good, and we're happy to be able to help these patients finally get a treatment, the only 1 FDA approved that can help with their symptoms and obviously, the long-term health outcomes particularly for their target organs.

Just on UPLIZNA and GMG, we're very pleased with the initial uptake. As you said, David, it's very early in the launch. But what we're pleased about, and I mentioned this in my opening remarks, is that roughly half of the patients who are being treated are bio-naive patients and the other half coming from switches from other therapies. As we've said before, this is a large but still quite dissatisfied category where the current treatments have limitations whether that be dosing inconvenience, whether that be duration of efficacy and perhaps some waning efficacy in this category. And so far, what we've seen is a very strong interest in UPLIZNA for its mechanism as well as for the convenience that it represents for patients. So so far, so good, excited about UPLIZNA overall in the broader rare disease portfolio.

Our next question comes from Salveen Richter from Goldman Sachs.

Just a follow-up here on UPLIZNA. Walk us through what's giving you confidence here and moving forward with a Phase III study in CIDP and the opportunity in that indication. And if you could also just separately touch on Repatha and how you're thinking about potential impact from the launch of Merck's oral PCSK9 and how you're adapting your commercial strategy there?

With 2 ends of the spectrum there from the very rare to the very common. So let's do -- Jay, you do the first question, and then Murdo, you can take the second.

Thanks, Salveen. We are, as Murdo shared, very bullish about UPLIZNA. Specifically this unique mechanism of action that targets and depletes the CD19 pathologic B-cell These, as you surely know, CB19, the B cell compartment is evident on mature B cells like CD20 targeted by rituximab and other medicines of that type, but also the pre B cell, the more naive B cell, the cell that expands and elaborates many of these auto antibodies. And so now seeing efficacy of UPLIZNA in so many immunoglobulin related disorders, like IgG4-related disease, like myasthenia gravis, the chance to bring it to additional autoantibody-mediated immune conditions, it's just a great chance to help patients with these severe diseases.

In some cases, there are signals from CD20 that we intend to follow up with a broader, more active and hopefully much more convenient UPLIZNA. Autoimmune hepatitis, which I mentioned earlier, is associated with autoantibodies you see ANA, you see anti smooth muscle, you see anti actin, you see anti LC1. And the same is true, though, to a lower proportion with CIDP as well, where maybe 5% to 10% of patients will have autoantibodies to what are called a pair of nodal proteins of 155 and CMTM1, I could go on for a long time. And so this biology being driven by the compartment that UPLIZNA targets makes for a really great chance to extend the benefits of targeting B cells in both of these conditions. Murdo?

Yes. Just the size of the opportunity here is interesting. Roughly the prevalent pool in the U.S. is estimated to be about 35,000 patients, maybe 7,000 to 10,000 incident new diagnosed cases per year in the U.S. So hopefully, we can develop this drug and offer some benefit for these patients. which is yet another steroid intensive condition, and we believe that we can do better than that. So let's hope for that best outcome in those clinical trials. On Repatha, I alluded to what our strategy is in my opening remarks. We are excited by the landmark data that were revealed at the American Heart Association last year in November where we can now clearly promote Repatha for the prevention of first heart attack or first stroke in a high-risk patient population and/or a high-risk primary prevention population.

And so that is our focus right now, and we are the only PCSK9 that has both secondary and primary prevention data in our label the Vesalius data are being met very positively by both cardiologists and primary care physicians, in particular, for the primary care physician for the diabetes patients that were enrolled in the trial who did very well -- so we are focused on making sure there's high awareness of these data. Repatha enjoys great access, broadly preferred on national template formularies by PBMs and health plans around the country and around the world. And of course, we know that there is an immense amount of trust now in the profile by prescribers. And for the millions of patients that have received treatment and are taking Repatha, there's strong acceptance that every 2-week injection to lower cholesterol to the 45 milligrams per deciliter target dose that was achieved in the Repatha arm in VESALIUS so that patients can reduce their cardiovascular risk.

So we've got a lot to talk about. We've maintained all along that there is a lot of room in this market for other therapies to come in, but they will not have the data package and profile that Repatha has established, and we'll continue to remind prescribers and others about that. Thank you.

Okay. Let's go to the next question.

Our next question comes from Mohit Bansal from Wells Fargo.

Congrats on the growth progress here. Maybe like just again, the question on PCSK9 and Repatha at this point. So Murdo, can you please remind us what percentage of your prescriptions are coming from primary care at this point. And with the VESALIUS data, like how do you see the primary care segment of the market evolving over time?

Yes. Thanks, Mohit. I put a number out before the VESALIUS data promotion started where roughly 40% of our prescriptions were coming from patients who were considered primary prevention patients who have not yet had an event where physicians were looking to lower those patients LDL-cholesterol. I would imagine that, that will increase and grow over time. What we are seeing is equal interest, quite frankly, from cardiologists who are excited by the VESALIUS data and the consistency of both the primary endpoint, the secondary endpoint, the MI subgroup, quite frankly, the overall incidence of death in the trial was also something that attracted attention from specialists.

So the cardiology group has seen this as an affirmation of what they were already doing and being aggressive in treating LDL cholesterol. And primary care physicians, as I mentioned, are much more intent and aligned to adding Repatha the optimized statin therapy that most patients are on. As for how much, we don't give product-specific guidance, but hopefully, you can tell, I am extremely excited about the momentum that we have on Repatha right now. I'm really pleased with the execution of our teams around the world. We've made incremental investments in advance of the opportunity of promoting the VESALIUS data, and I expect that momentum to continue.

Our next question comes from Louise Chen from Scotiabank.

I wanted to ask you about TEPEZZA and your thoughts on another potential competitor coming to market. And then also where you stand with AMG 732 for Ted.

Okay. Great. Maybe again, we could do this in 2 chunks. Jay, do you want to talk about the clinical piece and then Murdo talked about the commercial piece.

Thanks, Louise. TEPEZZA is proving to be just a very important medicine for the management of thyroid eye disease. We have established a very strong evidence base in both the high clinical exclusivity score lower clinical activity score, patient populations and are quite proud of this data generation and also the apparent impact that it's having on patients being treated today. We have an ongoing subcutaneous Phase III clinical study in moderate to severe active TED fully enrolled, as we had shared, and we expect to complete this study in the second half of this year. So we have a really terrific medicine that's increasingly a standard of care that's helping a lot of patients and a strong data set that it sits on top of.

Before handing off to Murdo. I'll just quickly comment on AMG 732. Thank you for noticing. This is an IGF-1R targeting monoclonal antibody, also achieves subcutaneous administration. Phase II studies enrolling initially studied to moderate to severe and active TED, and we'll have more to say on that in the future. Murdo?

Yes. Thanks, Jay. As Jay mentioned, we're expanding our treatment for patients with thyroid eye disease into the lower clinical activity score patient population, who tends to be managed by different specialists than the higher clinical activity score patients. We have historically been able to drive very strong penetration with ocular plastic surgeons and general ophthalmologists. We are expanding our prescribing base to include endocrinologists. We made investments. The beginning of last year, and those investments are starting to return now by an increased base of endocrinologists prescribing. So that's in the U.S., and we expect that we'll continue to broaden or treatment of the low clinical activity score patients while maintaining our share of the higher clinical activity score patients. But also our international launches. Our launch in Japan has gone extremely well. We're seeing nice uptake there. We're seeing a very well-received product for higher clinical activities for patients, and we're in the process of launching in multiple markets around the world as we speak. So overall, TEPEZZA will be a good growth driver for us this year.

Our next question comes from Terence Flynn from Morgan Stanley.

I had one on the MariTide Phase III program. Appreciate all the details today, but just was wondering if you have any update in terms of how to think about the design of the type 2 diabetes CVOT trial, particularly the control arm, as I know that's something that you guys were debating here post the -- seeing some of the data from some of the competitors, but just wondering how you're thinking about control arm in that setting.

Sure. Jay, do you want to...

Sure. I'm happy to share, Terence. We're just thrilled by the opportunity to develop MariTide for patients with type 2 diabetes. And this is really where we see a potential paradigm shift in the management of that disease. In my medical training, we practice with insulin and insufficient orals and titrating dosing. And here, we have a medicine that can be dosed monthly. We've seen efficacy in chronic rate management by monthly. We've recently described maintenance approach using quarterly dosing. This is just the new paradigm in the management of diabetes. We've shared the major insights at JPMorgan from the Phase II type 2 diabetes study, which is ongoing. There are additional parts to this trial. It's importantly given us an experience with low BMI patients and also seeing A1c across the dose range. And so the robust findings of this trial position us very well to start to pursue Phase III clinical investigation. The specific design of these studies, control arms and the patients recruited will be a subject for a future engagement.

Our next question comes from Chris Schott from JPMorgan.

Just another MariTide question and just on the topic of less frequent than monthly dosing. It certainly seems like there could be a trade-off here where even more infrequent dosing would obviously be a huge benefit even if it was associated with a bit less weight loss. I guess so as you think about just pushing the program beyond monthly, what profile do you think you'd need to see for that to have a role in the market? Are there minimum efficacy bars you're looking at? And just in general, what is your confidence about the ability to push this beyond monthly?

Okay. That's an interesting question. Murdo, do you want to take a shot at what we think we see in the marketplace and why we believe MariTide has the potential to address what is emerging as a very large unmet need in the field.

Yes, I'll make a few comments here, Bob. Thanks for the opportunity. I think it's pretty clear as we look at the market as it exists today, that there's dissatisfaction with the weekly GLP-1s. And I think you can actually see that in a fairly dramatic way with the advent of oral sema and how rapidly it's been taken up in the market. That tells you that clearly, patients and prescribers are looking for other opportunities. Now what I like is the opportunity that we have to deliver -- what has been mentioned a couple of times in this call as a paradigm-changing therapy. And that's the ability to come into a weekly market bring a monthly therapy that can achieve similar weight loss in a very well-tolerated regimen. And then for those patients who achieve their weight goal for them to convert to every 8 weeks or every 12-week dosing regimen to maintain that weight and/or the metabolic benefits of their therapy. And I think that's a pretty compelling offering. I think that we're targeting that kind of profile, and we'll have multiple ways of generating data to that effect.

Chris, maybe we have Jay just address the piece as well. Go ahead.

Yes, Chris, thanks for the question. If you don't mind, I'm going to reject part of the premise of your question. This idea of less frequent dosing being an absolute trade-off for efficacy. We're not certain that we will see that. Having observed the large majority of patients maintaining weight on low dose and on quarterly dosing. In the field of obesity, they call this a defended fat mass and the capacity to avoid weight regain is a sign that the reset of body weight has been achieved. We have seen with all medicines to date, dose-ranging effects on weight loss. And here, we might expect to see schedule ranging effects on weight loss that would be individualized for patients. And so I wouldn't necessarily assume that we'll see a big trade-off with less frequent dosing of maritime.

Our next question comes from Umer Raffat from Evercore ISI.

I'm really, really lost today. I'm trying to figure out what happened all of a sudden why did FDA decide to ask you to pull the [ ChemoCentryx ] drug? Was there some litigation or some correspondent -- like what prompted it in the first place? And then if I dig in a little more specifically, they're saying that 9 patients need to be readjudicated. Is that referring to the primary endpoint on week 26 remission or the week 52 sustained remission I asked because the week 26 endpoint was not inferior anyway. So even if you re-adjudicate those, it's still not inferior. So I'm just really lost today.

Okay. Well, Jay, you've addressed the question. You may want to just start at the high auto to remind people what TAVNEOS is say a few words about the disease that it addresses. It's obviously a very small product in our portfolio relative to the other things we have going on. But it may be a medicine that's less familiar to most of our colors.

Yes, sure. Thanks, Umer. And just by way of background then. ANCA-associated vasculitis is a group of very serious, rare and destructive inflammatory illnesses that targets blood vessels and can, therefore, damage via organs like kidney, lung, skin, nerves, even heart. On the prior treatment paradigm for TAVNEOS was quite toxic, cyclophosphamide chemotherapy with azafioprine and rituximab, accompanied by long-term steroid use and chronic use of steroids proved very common, but also very challenging, hypoglycemia, lipodystrophy, bone health, mood disorders, immune suppression and then enter TAVNEOS. This is an oral complement Factor Xa receptor blocker, and so it blocks complement-mediated destruction.

We acquired TAVNEOS from ChemoCentryx in 2022 after we've been on the market for a year. Based on approval for the ADVOCATE Phase III study that you referenced as published in the New England Journal. This established the efficacy of TAVNEOS over prednisone steroid tapering for sustained remission out to 52 weeks when it was added to induction therapy with at that time, standard of care, rituximab and cyclophosphamide. As we shared, the FDA requested a voluntary withdrawal in January 16 we were surprised by this, there were concerns raised by the process followed by ChemoCentryx to re-adjudicate primary endpoint results for 9 of the 331 patients. And we're in discussions with FDA, and we'll answer questions as we talk with them.

Our next question comes from Alex Hammond from Wolfe Research.

So you did a strong quarter with Hale. I guess, how do you kind of expect to maintain this leadership position when other manufacturers launch their biosimilars in the second half of the year. I guess essentially, can you kind of help level site growth expectations for this year?

Well, obviously, we're not giving guidance on an individual product, Alexandria. But Murdo, go ahead and talk a little bit about the strong performance that we've observed so far with our biosimilar [indiscernible].

Yes. I think what we've been able to do thus far is establish good inroads with the largest national retina specialist networks. And I think what I would say is they tend to want to pick a product that they know allows them to manage their patients effectively. We think we've got a great device that helps them do that. We obviously are competing effectively against the innovator. And given that we have a lot of biosimilar experience, we'll compete effectively when others enter the market whenever that may be.

Okay. We'll take 1 last question as we're right up against the bottom of the 30-minute mark here or the hour. So why don't we take 1 last question? And then as always, Casey and his team will be around to answer questions if we didn't get to you on this call. Julian, last question.

Our last question will come from Courtney Breen from Bernstein.

I am going to bounce you back to MariTide. And just as we think about maintenance and that kind of less frequent dosing opportunity, can you describe how you might think about the role of this product in the market? Is it only post MariTide white loss? Or how should we be thinking about kind of that switching opportunity and the type of data that you might demonstrate for that positioning over time.

I can imagine there's probably a lot of interest in that. Murdo, do you want to share any thoughts at this point?

Well, thanks, Courtney. Obviously, we think we've got -- as has been said now many times, and I'll repeat it again, a product that changes the paradigm of weight loss diabetes, ASCVD, heart failure management. And we see it as both an effective product to start patients on to get to wait goal and also for patients who receive the medical benefit of their treatment need to be on these therapies for multiple years. This opportunity for MariTide profile to deliver a convenient, well-tolerated efficacious regimen that could be monthly, could be every 8 weeks and could be quarterly. We think that's really exciting. And then, of course, as you hinted that, there may be patients out there on other therapies that want to switch to something as convenient and as well tolerated as MariTide. So -- the answer is all of the above.

Okay. So again, thank you all for your interest. I appreciate you joining our call. Just reiterate if we didn't get to you, please reach out directly to Casey and his team. In the meanwhile, I hope we've left you confident about the momentum that we're carrying into 2026. And again, I would just reiterate that we're excited about the year that we have in prospect here. A year, which, as Peter has described, we view as a springboard to the future growth here at Amgen. So excited about the hand that we have and look forward to sharing with you during the course of the year. Thank you.

This concludes our Amgen Q4 2025 Earnings Conference Call. You may now disconnect.

So good afternoon, everybody. I'm Chris Schott from JPMorgan. And it's my pleasure to be introducing Amgen today. From the company, we have Chairman and CEO, Bob Bradway. Bob, Happy New Year, and thanks for joining us today.

Looking forward to the presentation. We're going to do a presentation on stage, and we'll do a breakout to a Q&A session after that. So, over to you, Bob.

Okay. Very good. Thank you, Chris, and good afternoon, everyone. It's wonderful to see you here and a pleasure to kick off 2026 with all of you. And we're excited about 2026 at Amgen. We're see this as a springboard year for us with quite a lot of exciting in particular clinical data being generated at Amgen in 2026.

So let me jump straight in. You're familiar with the elements of our safe harbor. But just briefly, for those of you who perhaps don't know Amgen as well as some others, let me just point out that we are active in the 4 general therapeutic areas that you see represented here, and in particular, focused on addressing the diseases, where the unmet medical need remains high, such as those that you see on this slide.

And we address these diseases with first-in-class, best-in-class innovative medicines like those shown on this slide as well as our branded biosimilars. And off the back of these products over the course of the last decade, we've delivered very consistent revenue and earnings growth, as you see reflected on this slide.

And we've done that with a number of high potential products delivering growth throughout this period as -- as well as products that are in areas that remain underpenetrated, creating significant ongoing opportunity for growth. So while growing the top line, we've also, I think, established our reputation for rigorous operating and financial discipline, enabling us to deliver earnings growth, as you can see here, well in excess of revenue growth.

Now before turning to 2026, I just thought I might spend a moment to summarize for you where we were, how we performed in 2025. And I thought I might start by reminding you of what we said at this time last year and then pointing out what we did during the course of the year. So a year ago, we told you, you should expect us to deliver attractive financial performance and over the course of the year through the 9 months that we've reported already in 2025, we grew revenues by 10%, paced by the 14 blockbuster products that we feature at Amgen today.

We delivered 14% earnings per share growth. So we said we would deliver financial growth, and that's exactly what we did. We also said that we would expect to generate regulatory approvals across a number of different programs. And again, that's exactly what we did in 2025 with 5 successful FDA approvals.

We said that we were enthusiastic about the prospects for MariTide and would rapidly enter into Phase III clinical development with that program. And we have indeed initiated 6 Phase III programs for MariTide over the course of the past year.

Repatha is a core growth driver for us, addressing as it does, the largest contributor to public health problems on the planet. In particular cardiovascular disease and we said we were excited to demonstrate the benefit of Repatha in primary prevention, which is precisely what we did with the Vesalius data in 2025 demonstrating, for example, the 36% reduction in the risk of a heart attack for those who had never had a previous heart attack.

So really impressive ongoing performance clinically for Repatha. Biosimilars has been a feature of Amgen's business since 2018, and we said that you should expect growth of that franchise in 2025, and we reported 42% year-over-year sales growth for that part of our business through the first 9 months.

And then finally, we said that we would expect off the back of our very strong cash flow generation to strengthen the balance sheet and once more, that's just what we did in 2025, paying down more than $6 billion in debt.

Our outlook for 2026 is colored by our excitement and belief in the 6 growth drivers that you see on this slide, in particular, the 3 products, Repatha, EVENITY and TEZSPIRE each of which, again, still underpenetrated medicines that are innovative therapies that provide a very large clinical benefit for patients that are suffering from the challenging diseases reflected there with heart disease, for Repatha, osteoporosis and bone health disorders for EVENITY and of course, severe asthma for TEZSPIRE.

In addition to those 3 products, we have 3 portfolios that offer attractive growth in '26 and through the end of the decade. Our rare disease business, our innovative oncology business and our biosimilars business, and I'll talk a little bit about each of those in just a moment. But before I do, I wanted to just spend a few more moments with our on Repatha, EVENITY and TEZSPIRE.

Again, Repatha is a product that's performing very well. It was annualizing at about $3 billion at the end of the third quarter. It was growing as you see on the slide, 33% over the course of the year and is a product, which now especially after the sharing of the data from the Vesalius trial is well positioned to grow through the end of the decade.

There are more than 100 million people around the world who are at risk of heart attack or another major adverse cardiac event because of the fact that their LDL levels are too high. And the penetration thus far of that body of patients has been in single percentage digits. So there's considerable opportunity for us to improve public health by reaching more and more patients, who are at risk of heart attack or stroke with Repatha.

EVENITY, again, continued its track record of strong growth, up by more than 30%. And of course, this is a therapy which has proven to be very effective in women, who are at high risk of an osteoporotic fracture. And there are 2 million such women in the United States. And again, the penetration of this population of patients also remains relatively limited.

So considerable opportunity for us to grow EVENITY by reaching more and more of those women, who are at risk of a life-changing fracture that could be prevented with a therapy like EVENITY. And then TEZSPIRE, another attractive product, innovative, first-in-class, only in class medicine that addresses the needs of patients that have severe or uncontrolled asthma.

In addition, to what we've seen in asthma, we demonstrated in a Phase III clinical trial, very, very compelling results for patients that suffer from chronic rhinosinusitis with nasal polyps. And so that adds another important opportunity and gives us further encouragement about the prospects that we might see from the study that's underway in COPD and another study as well that's underway in eosinophilic esophagitis.

So TEZSPIRE is performing very well and has all the hallmarks of a medicine that will go on and make a big difference for many, many patients in a number of different important diseases, where the unmet medical needs remain very high. Now alongside these brands, we have a very important franchise in rare disease and our rare disease portfolio approached $5 billion last year and is a business that was, again, growing very attractively during the course of the year.

These products are still at an early stage of their life cycle. And I think that is most clearly illustrated by UPLIZNA, which was the leading brand for the treatment of Neuromyelitis Optica Spectrum Disorder at the start of the year. And during the course of the year, we gained approvals for 2 other autoimmune conditions, 1 known as IgG4 related disease and the other, of course, is in myasthenia gravis.

And we're very encouraged by the early uptake from prescribers and patients for UPLIZNA in IgG4 and also very optimistic about what this medicine can represent for patients that are suffering from generalized myasthenia gravis. So that's a good example of how we expect to be able to grow our rare disease franchise by expanding into new indications with efficacious biologics like UPLIZNA.

Innovation, of course, is a hallmark of our rare disease business, but it's also a hallmark of our oncology business. And in oncology, in particular, the innovation associated with Amgen, which is our bispecific T-cell engaging franchise had a very strong year in 2025 and encourages us about the outlook for 2026 and the decade beyond.

I would, of course, highlight in that regard IMDELLTRA, which is a medicine for small cell lung cancer, a bispecific T-cell engaging medicine for small cell lung cancer. And in small cell lung cancer, IMDELLTRA very quickly established itself as a standard of care in second line or later therapies.

And we are in clinical development now seeking to move IMDELLTRA into earlier lines of therapy and very encouraged about the Phase I data that we've seen in those settings and very encouraged about what this medicine might represent for small cell lung cancer patients, who went decades without any real meaningful innovation on their behalf.

Of course, BLINCYTO is the medicine that inspired us to have such confidence in IMDELLTRA. And BLINCYTO is, of course, the standard of care in first-line B-cell acute lymphoblastic leukemia, where we've demonstrated spectacular benefit for patients, including those whose disease was refractory -- refractory and recurrent -- so that's the standard on which we have based our other T-cell engaging therapies and we, for example, are very encouraged about the early data that we see in prostate cancer with a medicine that we call Zaluridamig, which is the first and only of its kind, addressing a target that is prevalent on prostate cancer patients known as STEAP1. So that's a program that's in Phase III -- II Phase III trials now. And again, we're excited to see what we might be able to do on behalf of patients with that new approach.

I want to shift gears to our biosimilar portfolio. And again, here, I would point out that in addition to noting that our business grew 42% last year in this area. It may be lost on some of you that this franchise now, which we first entered in 2018 has contributed about $13 billion of revenues for us overall.

So $3 billion annualized through the first 9 months of 2025 and an aggregate $13 billion contribution to Amgen, since we entered that area. And I think, again, it nicely illustrates our skill at providing complex biologics across a large number of patients globally.

On the next slide, I just simply included on 1 page the summary of the products that give us reason to believe that 2026 and the rest of the decade will be years of exciting growth for Amgen. And again, I think the characteristic of that growth for us will be medicines that have a large effect size where the unmet medical need remains very, very significant.

Now shifting away from our in-line brands to our pipeline. I would point out here as well that we're very excited about the deep and broad pipeline that we have, and we believe that the pipeline of Phase III programs, which are shown here, will pace the next wave of growth for Amgen. You can see, of course, that we're very active in general medicine with -- 2 medicines that are attracting a great deal of interest in 2026.

1 is Olpasiran, which is directed against Lp(a), which, again, we all believe to be a residual risk factor in cardiovascular disease, and we're excited to be able to see data there in the future on that franchise and from that Phase III trial. And then, of course, MariTide, which is our differentiated approach to obesity, diabetes and obesity-related conditions.

In inflammation and rare disease, we would expect to continue building on our established platforms and the way I described a moment ago with TEZSPIRE and UPLIZNA. We have enjoyed decades of leadership in inflammation and increasingly now in rare disease, and we're excited about the prospects there. And of course, as I've briefly already discussed, we expect some exciting results from our clinical data in oncology as well in 2026.

With respect to MariTide, let me just point out that our confidence continues to build in MariTide and our belief that MariTide can represent a new paradigm in the treatment of obesity, type 2 diabetes and obesity-related conditions is high, and that confidence is underscored by our belief that we compare strong efficacy with the potential for monthly or even less frequent dosing.

And that approach offers a clear path to long-term maintenance. And we think that, that will offer a very compelling combination for patients, prescribers and payers. And so again, we believe that we have a differentiated approach, and that conviction is the catalyst behind our rapidly enrolling 6 Phase III studies.

I should point out that in addition to those 6 Phase III studies, we expect as well that we will soon begin a Phase III program in type 2 diabetes. Now I think as we're all increasingly aware, the today's injectable in treatment therapies have set a high efficacy bar. But the real world experience, I think, reinforces challenges.

In particular, we continue to see meaningful treatment discontinuation and I think what that discontinuation highlights is some of the disadvantages of the dosing frequency and treatment burden that exists with existing medicines. And in an area like this where persistence is everything because, of course, it's sustained treatment that drives sustained outcomes, we think MariTide is really well suited to the challenge.

So I would also point out that our newest Phase II data strengthens our belief in the story in 2 particular ways. First, in chronic weight management. We've seen that lower monthly dosing or even quarterly dosing can maintain weight loss and do that while sustaining the cardiometabolic benefits that we saw in the Part 1 of the Phase II data.

And I would also point out that in the second year of treatment, we observed that nausea and vomiting rates were very low indeed, supporting our conviction that this is a medicine that will have a favorable maintenance profile.

In type 2 diabetes, we're particularly excited. And again, our data here support our conviction that this medicine, MariTide has the potential to be an efficacious monthly treatment which has been a long-standing goal for the field in type 2 diabetes. So again, stepping back, we think MariTide has the potential to expand what's possible, particularly as it relates to durability and treatment convenience over the long term.

I'll include some data here, I won't go through these slides, but again, I would simply reiterate that we believe that this medicine has the potential to be the first of its kind, which is a monthly treatment for patients with type 2 diabetes, and that's based on the data that we've seen that leads us to believe we can achieve robust and meaningful reduction in both HbA1c and weight with monthly MariTide based on, again, the first 24 weeks of that Phase II study.

The safety and tolerability in this setting of patients, again, is very consistent with what we've observed in general for the GLP-1 class. And we were really encouraged by the favorable improvement in cardiometabolic parameters for these patients. And then in chronic weight management, again, I would simply underscore that -- we have reason to believe there are many ways to win, when it comes to maintenance therapy with MariTide through either lower dosing or less frequent dosing and in particular, quarterly dosing, which we studied in that Phase II trial.

Moving off the pipeline to other areas of focus for us at Amgen. I would point out that we continue to be very excited about where we see opportunity to innovate and in particular, where we see opportunity to incorporate technology and artificial intelligence in ways that are enabling us to do our business better day in and day out. And we're finding that across all of the platforms of our company.

When it comes to capital allocation, capital allocation at Amgen is something we think about proactively, not reactively. Our focus is on investing in innovation, internal and external innovation, also investing in manufacturing, which we consider to be a source of competitive advantage at Amgen. We have throughout our history, invested in manufacturing in order to be able to reliably safely supply complex large molecules to patients all around the world, and we will continue to do that in line with our, kind of, stated and announced capacity expansion plans.

And then we have, again, the benefit of a strong balance sheet and strong cash flows to enable us to invest in both our most attractive internal and external innovation, and we will continue to do that. I thought I might just highlight 2 recent early-stage deals that might have escaped your attention.

I highlight these in the case of dark blue, because it's an example of something that we expect to see more of. This is a greater technology, in this case, applied to cancer target. But -- you've heard us talk through the years about our conviction that the field of what we call inducible proximity platforms is opening a number of new opportunities for us, and this is an example of that from a business development transaction that we undertook a few weeks ago.

And then I also wanted to highlight Disco, it too is an early-stage collaboration, but noteworthy because, again, we have made a commitment with our bispecific T-cell engaging to identifying cell surface antigens of relevance to that approach to treating disease, and we're excited about the collaboration with Disco for what it represents in that regard.

So to sum up, as we enter 2026, again, we're excited to find ourselves with multiple high potential products that we think are still an attractive early stage in their life cycle. We enjoy a leadership position in a number of important disease areas, where the unmet medical need remains very high. We've demonstrated our ability to grow consistently through time, including through patent exploration, which as many of you know, is not something that's common.

In fact, it's very rare in our industry. We've done it before, and we expect to do it again. And again, we've achieved that on the back of the strong innovative products that we have, the timely biosimilars and, of course, the rigorous operating and financial discipline that we've developed at the company. So we're excited about 2026 and the outlook for the long term, and I'd be happy to answer any questions you might have.

Chris, you can bring that presentation down? Or do I need to click.

Yes, they'll throw it down. So yes...

We'll leave. I'll give you a second to come over here.

Thank you. Excellent. Well, maybe we'll -- I'll let you settle in there for a second. We'll kick off the conversation with obesity, probably no surprises there. Can you just help us set the stage initially in terms of your latest thinking around the broader obesity market and how that's going to evolve over time as we think about things like price, cash pay versus reimbursed business and just as you think about where Amgen is going to end up fitting into that landscape as it evolves?

Well, I think, again, what we see is that the medicines are working. They're working in ways that perhaps were not expected. They're working in ways that the patients, prescribers and payers can see. And so the good news is what we're witnessing globally is that medicines that make a big difference for patients that are struggling with diseases like obesity and have a very attractive, bright future. And we expect to be part of that bright future.

So whether it's through cash pay or whether it's through reimbursed product offerings or a combination of both. We think that this is an area that makes sense for us as a company and, importantly, makes sense for society. I think that, again, the data here will become compellingly clear over time that preventing and treating disease like obesity and the related conditions and maintaining control over type 2 diabetes in the way that we think can be done with a medicine like MariTide is in society's interest.

I think we can prevent and forestall a lot of the kind of chronic disease, which today is a cause of such difficulty for the health care systems in the United States and all around the world. So it's an exciting time, Chris, for us. And I hope for the field.

Yes. Great. Touching based on the Part 2 data that you highlighted today. Maybe first, any additional color you can provide on tolerability. It sounds like...

As I said, these the medicine, as we hoped and expected would be very well tolerated in the second year, and that's what we observed. So we have seen that when patients reach the target dose, the medicine performs very well and patients don't seem to have the kind of disruptions that perhaps the weeklies are causing them.

So we also know and we expect to continue to see that lower doses and that stepping through lower doses to target dose improves tolerability. And so again, we'll seek to demonstrate that in Phase III clinical development.

Great. And maybe a similar question on the weight maintenance data, as you think about the different arms. So you think about monthly versus quarterly any just directional color? Were those similar levels of weight loss or?

Well, again, we'll get into the details when we have the Phase III data. But what I would say is that the Phase II chronic weight management data that we have, which were designed -- the part 2 of the study was designed to be qualitative in nature to be informative to help us think through the Phase III development program. I would say that the data, again, underscore our reason for having confidence -- high confidence in this medicine both in an induction setting.

So getting patients to lose a meaningful amount of weight, but then also in maintaining that weight loss. And so the way I would characterize it, Chris, is we think there are many ways for patients to win with MariTide in many ways from lower dosing to less frequent dosing. And again, I think it was broadly understood that we would look at the quarter -- question of quarterly and we did look at the question of quarterly dosing, and we think that's going to be 1 of the many ways that patients might be able to win with MariTide.

And based on this data, should we expect any changes or additions to that Phase III program? Or is this largely consistent?

No. It's largely consistent with what we had expected. I confirm for you that we are moving forward in type 2 diabetes with again, what will be the first of its kind, a monthly or less frequent treatment for patients with type 2 diabetes. So we're very excited about that. And I think you should expect that we will continue to look for ways to differentiate and to identify patients that will benefit from a medicine with the kind of durability profile and tolerability -- long-term tolerability profile that we expect from MariTide.

On that type 2 diabetes opportunity, the monthly is unique. Just how do you think about approaching that market where maybe the GLP-1s are a little bit more entrenched and established versus obesity. Is that -- is that a more challenging market to go after, just given the state of development or...

Well, I think the good news with type 2 diabetes is that the clinical community is alert to the importance of treating these patients and preventing them from going on to develop the long-term complications of chronic type 2 diabetes. And I think again, the good news is the clinicians and the patients and the payers have for some time been hoping for a longer-acting medicine than those which are available.

And based on what we've seen, we think we have that longer acting alternative now for patients. So I think those who want to manage their disease with something other than a weekly injection. Those who want to manage it, for example, with a monthly or less frequent injection will, for the first time ever have that option available to them.

So we're excited, again, to get those Phase III data and then to let prescribers and patients and payers see the data and figure out for which patients and in what settings this represents an improvement over what's available today.

Great. Maybe 1 last one. You've kicked off a number of Phase III programs. Just talk about how quickly these have enrolled and how we think about that implies for...

Well, again, I think that's a subjective question, but subjectively, we're excited by how rapidly they've enrolled. So we had expectations for what we might be able to do. And what I would say is we're on track with what our ambitious expectations were for enrollment. And again, I think that gives us confidence that the physicians, who are enrolling patients in this see the ongoing unmet medical need and see the potential attractions of MariTide.

Great. I know there's been a lot of focus on MariTide and it's highlighted here. The rest of the pipeline -- what are you most excited about? Because I know it's a growing number of assets that are in late-stage development. But if you were to highlight a couple of what were the ones...

Well, again, I think the way to perhaps think about it is in the general categories that I referred to. So we have in general medicine in addition to MariTide, Olpasiran. That's a medicine that reduces by 95% to 100%. The thing that is considered the residual risk factor in cardiovascular disease. So for those who perhaps aren't as familiar with it, the notion is that 1 in 5 people are at high risk of heart disease and in particular, heart attack because they have high levels of what's called Lp(a).

And Lp(a) is not something you can modify with exercise or diet. Unfortunately, it's a genetic attribute and other therapies don't meaningfully move that needle. So we have 1 that lowers it 95% to 100% is dosed quarterly. And we think if it demonstrates that it can meaningfully reduce cardiac events, that's going to be a very, very important development for the field.

So we're excited about that. And Obviously, when you look at the other 3 areas, in inflam, as I mentioned a moment ago, we're building on the established presence that we have in that field. And Olpasiran is represents an example of what we're looking to do. So Olpasiran is our medicine that deletes immune cells that are a cause of autoimmune disease, and we now have approval in 3 different disease areas, and we will continue to look for other disease areas, where we think that by depleting these so-called B cells, we can help prevent patients from suffering the long-term consequences of their autoimmune disorders. So a lot to be excited about there.

Obviously, TEZSPIRE has performed beautifully. Every clinical study of TEZSPIRE has reflected the potential of that anti-inflammatory medicine, again, first-in-class unique medicine. So I know clinicians and patients are excited to see the COPD data they looked good in Phase II, but we need to see in Phase III, whether we can achieve what we did in an earlier trial.

And then, of course, Sinopec esophagitis. So there's an awful lot to get your arms around. And again, just in Phase III alone at Amgen, we have quite a bit going on. I think if you're a cancer specialist, you're probably watching with great interest to see what we can do with early-stage patients with small cell lung cancer. I think, again, that will be a great day for the industry and certainly a great day for Amgen and for patients, if we're able to show that in early lines of therapy, we can prevent this what has most often been a death sentence from being that.

So again, it was possible with BLINCYTO in acute lymphoblastic leukemia. We'd love to see that repeated in small cell lung cancer and even in prostate cancer. But I think that in terms of the next big chunk of data, small cell lung cancer is probably the area, where we'll have data most quickly.

Great. Can I go back to Lp(a). We looked at Repatha. It took a few years. We've obviously got a ton of momentum going -- should I think about Lp(a) being a market that will take some -- also some time to develop? Or is this 1 that just because of the characteristics and lack of alternatives could evolve a lot faster?

Well, I think it's one that certainly needs to develop a lot faster for the benefit of those patients that have this risk. If you think about atherosclerotic cardiovascular disease, it really wasn't until a medicine like Repatha, which was able to so profoundly lower the LDL that became possible to talk about meaningfully preventing first events in the way that we did with Repatha where, again, we showed a 36% reduction in first heart attack by taking patients that were otherwise considered to be on an optimized therapy of statins plus other agents.

Even for those patients, we could reduce by 36% the risk of heart attack. And so that gave and gives, I think, people to hope that maybe we can take those diseases, which are the leading killers of people on the planet and begin to relegate them to some other status. Like maybe this is no longer needs to be the disease we all fear the way many of us grew up fearing it. But the residual piece of that is, we believe, is Lp(a). So if -- if that residual piece falls in a clinical trial that's able to demonstrate, we can prevent events by lowering this LP(a), there clearly will be a bolus of patients, who know that because of the family history and other events that they may have had prematurely that they are at risk. And I would hope that they won't delay in going on treatment.

So we'll have to see, Chris. Let's look at the data. Let's see how loudly the data speak the case for the medicine. But there's no question there will be a lot of attention paid when those data become available.

Excellent. Latest in terms of when we'll see that? Any updates there?

Well, this is an event-based trial. So we're tracking events and we'll see, it's unlikely to be this year, but sometime next year, we should know. And in the meanwhile, we'll continue to execute that trial and do our very best to make sure that we gather all the information needed so that when we have the prescribed number of events in hand, we can see what the answer is.

And maybe a final 1 on this, just differentiation for Olpasiran versus competition. How are you thinking about that?

Well, again, we think we have the most efficacious agent, 95% to 100% reduction of Lp(a). So if reducing Lp(a) in adulthood is sufficient to prevent cardiac events, we should see it. And we think we have a convenient dosing regimen with quarterly dosing. So -- we think it's a medicine that's really well suited to the patient population that's at risk of this disease. And we think the -- again, the medicine is really well suited to answer the clinical question, which is can you reduce events by reducing LP(a)?

Great. On the end market portfolio, there's a couple of quick questions there. First, EVENITY. What's allowed for this really rapid ramp and uptick of that drug? And I kind of think of this as like a slower growth category. This is obviously top in the case here...

I think I would perhaps point out a few things. First, EVENITY is the most potent bone-building agent ever studied in the clinic. So this is a medicine that's used for women who are at a very high risk of osteoporotic fracture. Of course, the fastest-growing segment of our population are women that are postmenopausal and therefore, at high risk of osteoporotic fractures. So we have a demographic wave, which is leading to there being more and more women that are at risk of these osteoporotic fractures.

And again, we have a medicine that has demonstrated itself to be very, very effective in preventing those catastrophic fractures. I say catastrophic, I think it's sometimes lost on us in society that north of 25% of the women, who fall and fracture a hip in the postmenopausal after menopause, die within the 12 months after that event. And so especially for those women, who could have avoided such a fracture by protecting their skeleton with a medicine like EVENITY, there's an urgency to treat.

So the good news is the medicine has demonstrated its safety and efficacy profile. And I think the market is speaking, the market finds that to be an attractive safety and efficacy profile.

On UPLIZNA, can you talk a little bit about the new indications and how you're thinking about kind of those developing as we think about the next year or 2?

Yes. So again, UPLIZNA is a medicine that deletes a subset of immune cells that cause autoimmune diseases. That's the basis of its first approval, which is in NMOSD, which is, again, a very debilitating autoimmune disorder, where UPLIZNA is the leading biologic prescribed for the treatment of that disease. It was approved last year for, again, IgG4-related disease, which is, again, a really devastating disorder in which the cells of the immune system attack organs in the body, creating flares and long-term chronic conditions that can be really devastating for patients.

So -- it's a disease that didn't get its diagnostic code until 2023. So it's not all that well known in the physician and clinical community. Fortunately, the patient groups are increasingly well organized and well informed, and we're working hard with them to try to educate prescribers and physicians what to look for.

And I think 1 of the things we have observed is we're surprised by the range of physicians who are seeing these patients. And so on the 1 hand, that's a challenge for us because we need to educate perhaps a broader range of physicians than if it were the case that it was a simple specialty that's seeing these patients. But I think, again, it illustrates the opportunity, which is that there may be more patients that are suffering from this disorder than we thought.

So we want to do our level best to help educate the clinical community and again, those patients. So that if they have this condition, they can benefit from UPLIZNA, which profoundly reduces the risk of a flare. And then in December, the FDA approved UPLIZNA, again for generalized myasthenia gravis. And I think there are a couple of things that are notable in that disease first, the therapy works across both classes of gMG patients.

So there are some medicines that only work for 1 of the groups of patients that suffer from myasthenia gravis. We have the benefit of working across the full spectrum of those patients. We have a very convenient dosing regimen for those patients. And the clinical data suggests a deep and durable and even perhaps deepening response over time. So this is an area, again, where we expect both to benefit from the churn that occurs in this community clinically, but also expect to be prescribed for a number of patients who are encountering therapy for the first time.

So UPLIZNA is again, proving to be a very attractive medicine in the way that we thought it would be when we acquired it now several years ago. And I think it's a medicine that plays really well to the strengths of Amgen, which are particularly in the area of large molecule biologics and unraveling novel biology like that, which we're doing with UPLIZNA.

Excellent. I think we're out of time. So Bob, I really appreciate the comment.

Thank you -- thank you much.

Appreciate it.

Thank you all.

Citi - 2025 Global Healthcare Conference. So my name is Geoff Meacham. I'm the senior biopharma analyst. I have Jarwei Fang with me from my team as well. So we're thrilled to have Amgen with us today. We have a couple of folks here. We have Peter Griffith, EVP and CFO. We have Kave Niksefat, Senior VP, Global Marketing and Access; and then Casey Capparelli from the IR team. So guys, welcome. Thanks for joining us.

Thank you, Geoff. Thanks for having us.

So I guess, Peter, we'll start off with you just with respect to the trends this year. You've had some standouts. It doesn't look like the denosumab headwinds were as bad as people originally thought. It looks like Repatha is still growing very nicely. So how do you kind of look at the momentum going into '26 on the back of these trends sort of extrapolatable to '26.

Good. Thank you, Geoff. Great to be here. And I would introduce our colleague Omari Wise, our Treasurers in the audience, too. So we brought the full team, here for Citi.

And maybe what I'll do is I'll answer a little bit of that question and then flip it over to Kave. And then Casey's got a quick add on R&D, just to kind of kick things off a little bit, if we could, would be fantastic.

Look, we've got good momentum in the business. So to answer your question, 10% revenue growth through the first 9 months of the year, and that is inclusive of 11% product sales growth, driven by 14% volume growth. What I would also add is in the third quarter, we had 12% revenue growth, driven by 14% volume growth also. My point being is the volume growth is very strong, and that's been our strategy since about 2019 when prices started declining in the industry, net prices and we adopted a really a volume-driven growth strategy. So that's going well this year. It means more patients are getting more medicine.

We continue to invest in innovation and science at Amgen and our capital allocation hierarchy enabling longer, healthier lives. And we also have a strong long-term growth outlook that's driven by the four therapeutic areas and the breadth and the depth in those four therapeutic areas.

So we think we've got a strong foundation and good momentum this year. Geoff, as you point out, we're encouraged by momentum in the business. We're encouraged by momentum in the pipeline. We feel great about that. And Casey can explain a little bit more about that. But so far, so good, strong debt paydown on the debt we took down in connection with the Horizon acquisition. We're delighted to be in rare disease, Kave will fill you in on that.

Our capital allocation hierarchy that I mentioned before, continues to be strong. And we spend where we should. And this year, Geoff, in addition to a strong performance on the top line, we're investing in the business. So 31% up year-over-year in the third quarter in non-GAAP research and development. We had roughly $200 million of business development in that third quarter. So without that, we're about 19% up, still a strong allocation of capital innovation. Our guide for the year in non-GAAP R&D you're familiar with is in the mid-20 percentages. So we continue to do what we want to do, which is work on innovation. And having said that, Kave, I'll flip it over to you for maybe a drive by on the in-market portfolio, which is doing so well.

Yes. Thanks, Peter. As Peter mentioned, we've got six major growth drivers that we have in hand. The first three address major public health concerns. So starting with Repatha, we've had 30% year-over-year growth over the first 9 months of the year, and we have recently shared the VESALIUS-CV primary prevention data in hand that will drive our continued growth going forward.

There's over 100 million patients in the world that have uncontrolled LDL-C. Penetration rates of PCSK9 therapy remain quite low, which offers plenty of opportunity for future growth.

Moving on to EVENITY. It also had 30% growth year-over-year with particular strength in the U.S. and Japan. In the U.S., we've got a 60% share of the bone builder market with EVENITY. But over 90% of the 2 million women who are at very high risk of fracture still are untreated today, again, leaving ample room for growth going forward.

Finally, TEZSPIRE grew 50% year-over-year in 2025, and we've now achieved $1 billion of sales within the U.S. within this year in severe asthma. We recently got approval for chronic rhinosinusitis with nasal polyps and have ongoing Phase III trials in COPD and eosinophilic esophagitis, which will continue to add to the growth story.

Moving on to our fourth growth driver, rare disease. We're now annualizing at close to $5 billion a year and grew 12% year-over-year. This is a very young portfolio of four products UPLIZNA, TEPEZZA, KRYSTEXXA and TAVNEOS. UPLIZNA has grown 50% year-over-year on the back of a strong launch in IgG4-related disease and continued strength in NMOSD. And we've got an upcoming PDUFA date on December 14 in generalized Myasthenia Gravis, which we expect will continue to drive the growth of UPLIZNA going forward.

Innovative oncology has grown 11% year-over-year on the back of our bispecific T-cell engagers, BLINCYTO and IMDELLTRA. IMDELLTRA has now become the standard of care in second-line small cell lung cancer, with over 1,400 sites of care, both in the academic and community setting, now leveraging the product in the United States. We've got ongoing Phase III trials to extend IMDELLTRA's impact to earlier lines of therapy. And then finally, our biosimilar portfolio grew 40% year-over-year is now annualizing at roughly $3 billion.

Since its inception in 2018, the biosimilar portfolio has produced $13 billion of cumulative revenues. PAVBLU in particular, continues to gain traction as the only approved biosimilar to EYLEA. So with that, those are our six major growth drivers in the in-line portfolio, I'll turn it over to Casey for a drive by on the pipeline.

Yes. Perfect. Thanks, Kave. And just one clarification on TEZSPIRE 50% growth year-over-year through the third quarter?

Correct.

Shifting gears though to the pipeline. So Repatha. Kave mentioned the VESALIUS Phase III study, and that's an outcome study in high-risk patients without -- who have yet to have a cardiovascular event. Repatha when added to optimized lipid-lowering therapy, reduce the risk of cardiovascular events in this population by 25% and reduce the risk of heart attack by 36%. And really remarkable results that we're quite well received by the field, and we think provide a lot of momentum for Repatha going into the primary care setting.

If we shift gears to MariTide, MariTide is rapidly advancing in Phase III. We have six global Phase III studies underway, two in chronic weight management that are both fully enrolled. Additional studies in cardiovascular disease, heart failure and obstructive sleep apnea are also progressing very well.

Turning to Part 2 of the Phase II study as well as the Type 2 diabetes Phase II study for MariTide, we're working through the data for both of those studies and expect to provide an update in the new year.

If we stick in general medicine, but move to another product, olpasiran, that's Lp(a) targeting siRNA molecule also in Phase III development. We continue to have strong conviction behind olpasiran in and its potential to reduce cardiovascular risk by reducing Lp(a) another way to further reduce the risk of cardiovascular disease in those individuals that have elevated Lp(a).

As Kave mentioned in IMDELLTRA, advancing in Phase III studies. We presented some very impressive data earlier this year, demonstrating almost a doubling of survival relative to existing standard of care through Phase Ib studies in frontline and also in the frontline maintenance setting of small cell lung cancer. So really impressive data there. We have ongoing Phase III studies in those settings that we're really hopeful will demonstrate a benefit for patients.

And then lastly, to round out our bispecific T-cell engagers that are continuing clinical development. We have xaluritamig, which is in Phase III in prostate cancer. Two studies ongoing and enrolling well as well as additional Phase I studies underway where we're exploring xaluritamig in earlier stages of prostate cancer, similar to how we've approached IMDELLTRA going late stage first and then looking to advance the program into earlier-stage settings. So with that, Geoff, we'll turn it back to you.

Yes. Perfect. That's a great background, guys. Thank you. I guess we'll have a couple of commercial questions and some pipeline questions, but maybe we'll still keep it a bit higher level. Peter, from a policy perspective. I know some companies have announced the agreements with the administration on manufacturing and all the MFN kind of stuff. Where is Amgen as of now with respect to that? Talk a little bit about capital allocation priorities with regard to kind of internal versus external too in that context?

Good. Let me cover the capital allocation internal and external, Geoff and how we're contextualizing that and then I'll turn it over to Kave, who's been on point for us for a lot of the activities in Washington, D.C.

And so when we think about capital allocation internally and externally, you're all familiar with Amgen in the sense that our #1 capital allocation priority is innovation, the best innovation, whether it's internal or external. So in the environment we're in, Geoff, and we think about the tailwinds of demographics and so forth going forward. Innovation is more important than ever. The world needs more innovation, not less. So we're continuing to put our #1 allocation to that.

I mentioned research and development and how we are allocating that this year, mid-20 percentages year-over-year to R&D. We did say at the end of the third quarter, that while we had a bit of a step change in R&D from '24 to '25, because MariTide six global studies, as Casey referred to, are up and running, we wanted to make sure everybody understood we don't expect the same type of step change going forward because that's a big number. So we've got xaluritamig. We've got olpasiran. We've got MariTide Phase III, if you go back to -- we wrapped up VESALIUS and Repatha and studies in rocatinlimab and benralizumab and so forth. So that's -- we still have an increase in R&D or we're thinking about continuing to allocation rather is a better way to say it into R&D in an important way in '26.

And externally, it's a great question. We had roughly $200 million in some business development activities in the third quarter. We think it's a great opportunity and a great time to make sure we're on alert, which we always are. We've always got a wide aperture in terms of business development, structurally agnostic as to what we do, size, we're agnostic. And so we'll continue to keep that open and see what's out there. We have kept it open actually even during the period after we acquired Horizon. We've just got high standards now. And so we're careful about where we allocate capital.

And so that's how we're thinking about capital allocation internally and externally. I would just say internally, too, it goes without saying we've got a capital expenditure guide of $2.2 billion to $2.3 billion this year that we're locking down and finishing up. We've made some announcements. I think is as you've noted, in North Carolina, Ohio and continuing to build on to those facilities to make sure that we have a network capacity that's optimized. And certainly, for all of our products with 14% volume growth we need to. And so we allocate capital to that. And of course, that includes thinking ahead over the coverage of the earth to MariTide and that coming along. So that's capital allocation, Kave. Maybe it'd be great to get an update on how we're thinking about the activities in Washington and so forth.

Yes. So Geoff, just as we have in prior administrations, we're engaging heavily with this administration. We're obviously in receipt of the President's letter. From July, we've seen the deal announcements that have been made by other companies along with the generous demo. I would say, overall, we've had positive relations with this government going back to the first administration where we announced the 60% list price reduction on Repatha, the first time around. Following the Tax Cuts and Jobs Act, we've invested over $40 billion of capital in both manufacturing and R&D in the U.S. and have largely a U.S.-based manufacturing network today. And of course, a few months ago, we announced the introduction of Amgen Now, our direct-to-consumer program, the first offering of Repatha at $2.39 a month, lowest price in the developed world overall. .

What we're continuing to engage and have productive conversations, nothing to announce at this point other than we continue to have these productive discussions and appreciate the President's goals of trying to increase affordability for patients out of pocket in the U.S. and making sure that foreign nations are paying their fair share for the innovation that we bring.

Let me follow that up, Kave, with the recent announcement on GLP-1 as of a month ago. So you guys have, I think, what, eight Phase III, eight or nine Phase IIIs for MariTide in the obesity diabetes space. So how does sort of the pricing volume assumptions in that, does that inform kind of your long-term investments in MariTide as you look forward.

Super quick clarification. I think we're six, the three at this point that have been announced. It's a great question, Geoff. I'd say that Amgen has a long history of being able to navigate the pricing and in the U.S. and highly competitive categories going back to inflammation and our original product there, ENBREL. I'd say, overall, we have expected pricing to evolve in the marketplace that would go along with additional demand generation and what's been spelled out from the administration and the current companies thus far is in line with our expectations going forward. And so we remain very confident and very excited about the MariTide opportunity and look to continue to expand the market, which while large today continues to be underpenetrated with a new monthly or less frequent option.

And maybe earlier, you highlighted some of the growth drivers that are in the portfolio path EVENITY being a few of them. And obviously, with Amgen Now highlighting a direct-to-consumer access for Repatha, maybe just thinking about how do you see that evolving with MariTide potentially coming into play as well? Is that going to become more of an important driver for you guys going forward? Or is the current form of increased access or innovative access models pretty set for the time being?

Yes. I think, look, it's premature at this point to talk about access models for MariTide, especially in such a competitive environment. But I do think Repatha offers a good Amgen blueprint for how we can access large populations from an access driven growth perspective. We've got coverage on nearly 100% of formularies at this point. 95% of Medicare patients pay a low fixed co-pay for the product, generally $50 or less, less than $2 a day. And then in the commercial market, we've got 50% of patients that no longer face a prior authorization for Repatha and, of course, continues to be very affordable with our co-pay card $15 a month.

The addition of the direct-to-patient option opens up access for those folks that are not insured or for specifically patients who cannot get access to Repatha in their insurance construct for their intended use. For instance, primary prevention or primary hyperlipidemia and open that channel up in a meaningful way. It also gives us experience for direct-to-patient options in the future, would we expand that to other products.

So I believe this will be an important attribute going forward. Obviously, in the existing obesity space, it is a very important attribute. Having said that, we still believe that patients with these serious diseases should be covered by their insurance and should be able to access these medicines within the co-pay constructs that are available in their insurance marketplace.

Can I just follow that up, Kave. So Amgen Now, some companies have rolled out more of a consumer portal, if you will. And I wasn't sure if the timing of the Amgen Now is sort of in kind of in response to maybe the industry doing more of a consumer-facing or if it was more related to, say, let's preload the market MariTide and then maybe other products going forward? Or maybe it's probably a combination of both.

Yes. I'd say it's a combination of all of the other Geoff. I think we had long been contemplating a direct-to-patient option for Repatha knowing that some patients still could not access the product through their insurance or directly. The way we've implemented this is primarily with partners such as GoodRx to make sure that it was available at the local pharmacy rather than direct from a portal. But I think there's an experience set there that will benefit us on multiple products going forward.

That makes sense. And then maybe I know we'll talk more about commercial later, but I just wanted to touch real quick on biosimilar headwinds and offsets. I mean, for Q3, the erosion for denosumab really wasn't quite as bad as many anticipated. So maybe just give us a sense of how expectations should be said looking forward, and then also just as offsets to the erosion, you kind of touched upon assets from the Horizon portfolio and with the upcoming PDUFA for UPLIZNA coming up as well. How will that further lever up UPLIZNA's momentum and help offset the erosion on the P&L.

Yes. So let's start with denosumab. So we had biosimilar entry in the U.S. earlier this year. At this point, we've got four biosimilars that have entered the U.S. market for Prolia and XGEVA. And progression of the competitive dynamics to date have pretty much been exactly in line with how we expected. And a reminder, that expectation was built on our experience of being in the biosimilar marketplace either defending against biosimilars or launching biosimilars ourselves for the last 10 years. .

Looking forward, we expect the competitive intensity to increase as additional competitors enter the market. And therefore, we would expect that Prolia and XGEVA revenues will decline as that competitive intensity increases.

Having said that, as we've shared before, we expect different erosion curves for XGEVA versus Prolia. That's because XGEVA operates in the oncology space, which is highly consolidated and has a lot of experience with biosimilars. There's analogs available, both from Amgen and others in that space. Prolia, on the other hand, is administered by a large variety of HCPs, many of whom do not have large consolidated practices or biosimilars experience with biosimilars previously.

In addition, I'd like to remind everyone, we also have EVENITY in the bone space. EVENITY grew 30% year-over-year last year. And differentiated from Prolia, EVENITY build bone, Prolia maintains the bone that is built. Therefore, the products are complementary. We continue to promote EVENITY to the bone marketplace, including all of the HCPs that are in bone health. And as part of that, we also continue to support Prolia with those physicians. And so we expect those erosion curves to look different going forward, but obviously, more intensive competition increase.

Now to offset that, we would look to all six of the growth drivers I discussed earlier. So Repatha, EVENITY, TEZSPIRE continue to grow going forward in those underpenetrated markets. Rare disease continues to grow, especially for UPLIZNA with increased use in IgG4, which has only been on the market now for about 6 to 8 months and myasthenia gravis going forward. in addition to innovative oncology led by IMDELLTRA and BLINCYTO and then finally, our biosimilar portfolio. So we see all of those continuing to grow to give us a good springboard for 2026 and beyond.

Can I just ask maybe on the rare disease success with Horizon, right? So you guys historically have not been in rare disease. And so -- but you've done a number of deals, CHEMOCENTRYX is another one. that really has grown your portfolio in quite a dramatic way. Would you think about like BD or sort of strategies for external growth where does rare stack up kind of in the priority? Do you feel like you have more commercial capacity to add more assets? There are just a lot -- it's a ton more and rarer than there are in other but they're sort of niche or kind of verticals?

Right? I think that's a great question, Geoff. We -- as I said earlier, BD, we keep the aperture open I think you make a really good point is -- we are really glad we're in rare. I think Amgen was made for rare. We have a lot of the rare diseases. They're autoimmune-related and Amgen has just terrific research in that area. I think Kave, correct me if I'm wrong, I think technically BLINCYTO was a rare drug at one point. Correct.

And I think one of the first couple of drugs at Amgen many, many decades ago was filed as a rare I don't want to say which one, EPO or NEUPO. But long story short, we talked a lot about getting into rare. So going forward, we -- there's opportunities there to interrogate we're very interested in. We think it's worked out really, really well. We're so happy with our colleagues that came over from the Horizon team. Thank you. And so we're very pleased with that. And we'll continue to keep that aperture wide open and rare.

As you know, there's -- in the earlier stage companies, not just in rare but a little more widely, there's quite there's quite a bit available right now. There's opportunities for companies like Amgen to go and we're structurally agnostic, licensing, collaborations, partnerships, acquisitions, all of the above. So we're always thinking about that. We'll continue to think about that.

Kave, are those products easier to manage from a market access reimbursement perspective, fewer competitors, but sometimes like it's a much higher price point.

Yes. I would say, in general, in the U.S., rare disease has got lower levels of management than broader diseases overall outside the U.S. There are some incentives available from a market access perspective that can bring those forward. But look, we've built some really nice capabilities for go-to-market on rare disease. And to Peter's point, we're quite confident those capabilities can be applied to additional diseases going forward.

Okay. So I know we have a lot of questions, but it's important to touch upon some of the pipeline stuff that you guys have cooking. And maybe, Casey, I wanted to come back to a point you made earlier, which was on Mirati's Phase II Part 2. Expectations previously were for data in year-end '25. And as you mentioned, we can expect that now in 2026. Just wanted to get a sense of maybe what led to the timing change? And then maybe you'll help remind us what can we expect from the data? And what might you present in.

Sure. So to take the timing question. As I said in my remarks, we're working through the data for both the type 2 diabetes study as well as Part 2 of the Phase II study with MariTide and we'll expect an update in the new year, really nothing more to say beyond that. With respect to Part 2 of the Phase II study, it's principally a maintenance study. And the reason for that is severalfold. One, following Part I or 52 weeks of treatment individuals that had lost 15% or more of their body weight, we're eligible to continue into Part 2. Rough over 90% of individuals offered that opportunity decided to move forward and participate, which we feel is a good vote confidence for wanting to receive a second year of MariTide treatment.

All of those individuals were then rerandomized based upon where they were in Part I of the study into new arms of Part 2. And that includes both individuals with and without type 2 diabetes that participated in Part I. So you get a little bit of a mixed population and then you have obviously, a subset of the individuals in Part I that moved into Part 2.

Because of that, the study is more descriptive in nature. It wasn't designed to drive comparisons of weight loss between the various arms of the study. it will certainly teach us more about MariTide. It will teach us more about what happens after 52 weeks of MariTide treatment if you move to a lower monthly dose or if you move to a quarterly dose if you stop MariTide treatment and move to placebo, but those findings will help to inform our planning. But as I said, weren't designed necessarily to provide a lot of exquisite detail trying to differentiate between those various arms.

Casey, I just ask a quick follow-up on that. So the dosing and strategy in Part 2 is fully captured in the ongoing Phase III, so right?

So the ongoing Phase IIIs are what I would call initial treatment with MariTide. So were you go through a 3-step dose escalation to a target dose and then you receive MariTide out through 72 weeks. The difference with Part 2 is it will help us to think about MariTide in the maintenance setting. So after you've lost in this case, in Part 2, 15% or more of your weight -- is there an opportunity to maintain that weight loss with MariTide and it will inform how we think about other aspects of Mirati's profile in addition to what the ongoing Phase IIIs are exploring.

And as you get the full data from Part 2 and you have a better idea of the maintenance opportunity. Do you think then you'll -- will that be the tipping point? So okay, let's go after more indications maybe outside of obesity diabetes in terms of the number of trials?

Yes. I would say we're constantly watching the field. I mean it's remarkable the number of obesity-related co-morbid diseases. And so we're in heart failure. We're pursuing obstructive sleep apnea, looking at an outcome study in cardiovascular disease. We'll see where the field and where data that we generate leads us and I would say more to come there. If we see an opportunity to invest and meaningfully benefit patients with MariTide we'll look to do that.

And maybe just to expand on some of the opportunities beyond obesity. You mentioned some comorbidities. But there is a presentation at CTAD that will come later today, and I think a lot of the community is going to be focused a lot on and that's in Alzheimer's disease. And given MariTide potential for long-term dosing potential, could there be an opportunity for MariTide being investigated in Alzheimer's disease?

Yes, Jarwei, it's a good question. It's I'd come back to what I said before. We'll watch how the field evolves. And if we do see an opportunity to benefit patients with MariTide outside of where we're currently focused, we'll think about whether to pursue that opportunity or not. It's early days in obesity-related clinical research. And I think we and the field will learn a lot more in the coming years, and we'll look to make the right moves if the opportunity presents itself.

Sorry, maybe just on a clarification point. I'd imagine that the label that you guys would pursue for MariTide would be for chronic weight management. And that may be a specific label for weight maintenance might not be necessary. However, knowing that would a dedicated weight management study for a Phase III, would that be needed in order to fully elucidate data using the dosing levels in the Phase III?

It's a good question. It's something that we're obviously talking about internally will be informed by ongoing work that we're doing with MariTide and more to come there.

Moving down the pipeline, and there's a ton there. So that's a good place to be. So on olpasiran, I know you guys have -- you don't have meaningful large-scale Phase III data for a few more years. But obviously, the Novartis data point we're going to get on Lp(a) in 1Q. Does that inform again your -- the pace of investment or the addition of newer trials for Lp(a)? Or are you guys sort of set the stage and then we'll see what happens in 1Q, but I mean I wasn't sure if Amgen is going to react or I don't think Lilly is either, but based on the initial cut of the Novartis data.

I think we and the field will be interested in seeing data from the first Phase III study with driving reduction of Lp(a). There's some differences between Amgen's molecule and others. We have a molecule that reduces LP(a) levels, roughly 95% to 100%. We have a molecule that is dosed every 12 weeks on a quarterly basis. We also have a Phase III study that enrolled a higher-risk population than some other trials with its Lp(a) cutoff. So we'll be watching eagerly. But I think we'll also be considering olpasiran attributes as we think about data that others may generate.

Well-powered study with 7,300 patients.

Yes. Casey, we really appreciate you going to some of the -- highlighting some of the differences between the trial that you guys are running in Novartis. One of the major differences in our view is the difference in the MACE endpoints, right, where you guys are targeting MACE 3 versus Novartis MACE 4. So Casey, for you, maybe just help remind investors what that means for level of success or confidence you guys have. And then Kave, for you, given the long-term -- the extended dosing potential of olpasiran, what does that mean for market access and perhaps adoption in that front?

Yes, maybe just the context. So the endpoint of our Phase III secondary prevention study is a make does not include stroke as one of the endpoints. The reason for that is when we reviewed epidemiology data of where Lp(a) drives the most significant amount of risk. Stroke came out lower and therefore, we've focused our study on those endpoints where we feel Lp(a) will be driving the greatest risk. We'll have to see how that plays out, obviously, in Phase III. So more to come there, but we're stewards of the data and really look to let the data help us understand where to focus our efforts.

Yes. And so for olpasiran to the point, we do believe we have a highly differentiated molecule with again, Lp(a) knockdown of 95% to 100% that will differentiate it from some of the competition the quarterly self-administered dose, we think, will be a meaningful increase in convenience to patients. And so the combination of what we expect to be the greater efficacy and the greater level of convenience we believe, gives us a very competitive profile going into launch.

Great. And then -- so maybe looking into other areas in your pipeline. Inflammation that you mentioned that test buyer is doing fantastically well. But then also you have rocatinlimab in atopic dermatitis. And so maybe just, give a sense of how are you envisioning positioning of all of these inflammatory assets across type 2 and non-type 2 biology and how can these data help inform optimizing trial designs.

Yes. So let's start with TEZSPIRE. So TEZSPIRE targets TSLP. TSLP is very high in the immune cascade. And we showed in the asthma trials that, that enables us to treat all different archetypes of patients irrespective of eosinophilic levels or allergic levels of their asthma overall, the first and only product to be able to hit all six individual patient segments that are there ongoing studies in COPD and EoE and recent approval in nasal polyps. So we see a long runway for TEZSPIRE, had the pleasure of launching the product in 2021. And the product is performing fantastically in the marketplace with great adoption among allergists and pulmonologists and we're really seeing the polyps data being an additional catalyst for growth.

In terms of rocatinlimab, we now have all eight Phase III trials in hand. We're evaluating the totality of that data in a very competitive atopic dermatitis market. and we'll have further discussions and announcements regarding filing plans in due course.

Kave, I wanted to ask you on switching products. So IMDELLTRA, help us with kind of what you're seeing in the real world and the launch in small cell lung cancer. It's been a pretty good trajectory, but I want to get kind of the drivers and the durability of that, and then we get maybe into some economics of the asset.

Sure. So we've had a really strong launch for IMDELLTRA, both in the U.S. and as we mentioned earlier in the year, Japan now as well. Going -- coming online in the U.S., 1,400 sites of care are now online and using the product as we look going forward with the new NCCN guidance to makes it the most preferred second-line therapy out there really comes down to blocking and tackling to activate additional sites in order to access the additional second-line patients that are out there, while continuing to expand through clinical trials into earlier lines of therapy where we have larger patient populations and would expect a longer duration of therapy in those earlier lines. So very positive launch thus far, continued data that we see, we see inflections with every new data readout that we put out.

And remind us of the timing of the first line and the next kind of data cards to kind of turn over?

Yes. So Casey...

Yes, those are event-driven trials, Geoff. So the -- one of our studies, DeLLphi-305 is fully enrolled, and we're watching event rates, and then we have others that are continuing to enroll patients. as I was mentioning, both of those two of our Phase III studies are in extensive stage small cell lung cancer in the frontline setting, one in frontline maintenance in combination with the PD-1, one in a true frontline setting in combination with the PD-L1 and chemotherapy. And we're excited about both of those based upon some of the really positive Phase Ib data that we presented this past fall at WCLC and ESMO. So we think it bodes well for those Phase III trials. But we're obviously monitoring event rates, and we'll have more to say when we anticipate data from those studies in due course.

And maybe a reminder, those Phase Ib trials when they read out both roughly double overall survival versus standard of care that's documented in the marketplace.

Right. So you have built in interim analyses on these? Or are they just straight...

Yes. We're just watching event rates at this point in time. So I would say more to come there. .

And just the last one on that, just when you think about the revenue sharing component on that, does that sort of change how you invest in the product beyond these two first-line studies. Do you look at this as just sort of as a small cell franchise? Or is there a mechanism proof that you can move beyond that?

I would say from an investment perspective, we're exploring IMDELLTRA fully in small cell lung cancer. The two studies that I mentioned in extensive stage, we have a the study in limited stage small cell lung cancer, a Phase III study that's also underway. And we're thinking about is the utility in other tumors that express DLL3, in addition to small cell lung cancer. So we're quite confident in the asset for the reasons that you heard from all of us and look forward to generating more data.

I would just add, Geoff, that IMDELLTRA, as Kave said, is life changing for these patients with small cell lung cancer, just a devastating disease. So this is exactly -- Amgen is made for these moments. We want to back that up with the capital to explore what we can do to help patients in all aspects of that disease. That's a really important medicine to patients. So it's an important medicine to Amgen.

Awesome. Guys, thank you very much. Appreciate the time.

Thank you.