Vir Biotechnology Inc Aktie

Thank you. Hello and welcome to VEER Biotechnology's second quarter 2026 financial results and corporate update conference call. As a reminder, this call is being recorded. At this time, all participants are in a listen-only mode. After the speaker's prepared remarks, there will be a question and answer session. I will now turn the call over to Kiki Patel, Head of Investor Relations. You may begin, Kiki.

Thank you, Operator, and welcome, everyone. Earlier today, we issued a press release reporting our second quarter 2026 financial results and corporate update. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration outcomes, future results, performance, or achievements to differ significantly from those expressed or implied in such forward-looking statements. Forward-looking statements include but are not limited to statements regarding the potential for new therapies to improve awareness, testing, and access to care for the chronic hepatitis delta community, the therapeutic and commercial potential of our CHD program, the therapeutic and commercial potential of VIR 5500, and the other clinical and preclinical assets in our oncology solid tumor program. as well as the ProX10 masking technology, our development plans and timelines, the potential benefits of our collaborations with other companies, including financial terms and milestone payments, and our cash runway and capital allocation priorities. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including our forms 10-K, 10-Q, and 8-K. Joining me on today's call from Vier Biotechnology are Dr.

Marianne DeBacher, our Chief Executive Officer, and Brent Sabatini, our Interim Principal Financial Officer. The agenda for our call today is as follows. First, Mary Ann will provide an update on the meaningful progress we've achieved across our Hepatitis Delta program and outline how we're positioning the program for a successful regulatory submission. Next, she will provide an update on our dual-mass T-cell engager programs utilizing our best-in-class Pro X10 platform. Then Brent will provide a summary of our second quarter 2026 financial results. And finally, Marianne will close the call and will open the line for Q&A.

With that, I'll now turn the call over to Marianne. Thank you, Kiki. Good afternoon, everyone. And thank you for joining us for Vierbouw Technologies' second quarter 2026 earnings call. During the quarter, we continue to execute across our portfolio, demonstrating meaningful progress in both hepatitis delta and oncology, while further strengthening our regulatory and commercial readiness. In the second quarter, we presented compelling data for our hepatitis delta program on the complete a 26-week solstice trial at the ESL Congress in Barcelona. These data generated excitement from leading KOLs across the US and Europe, emphasizing the potential best-in-class profile of our hepatitis delta regimen. Against this backdrop, our focus remained on executing our registrational program.

We are pleased to share that we completed enrollment in Eclipse 2 during the second quarter. With enrollment now complete across all three registrational ECLIPPS studies, we are entering a catalyst-rich period for hepatitis delta, with top-line data expected first from ECLIPPS 1 in the fourth quarter of this year, followed by readouts from ECLIPPS 2 and ECLIPPS 3 in the first quarter of 2026. In parallel, we are rapidly advancing our oncology pipeline and have entered the next phase of development for our ProX10 dual-masked PSMA-targeted T-cell engager VIR5500 in partnership with Astellas. We are accelerating our clinical development plan in prostate cancer. and have started enrolling patients into multiple expansion cohorts, both as monotherapy and combination therapy in parallel. We believe these efforts can inform future registrational development while positioning VIR5500 as a potential best-in-class therapy across the prostate cancer landscape. I'll begin with updates on our Hepatitis Delta program. Patients living with chronic hepatitis delta continue to face significant unmet need.

Importantly, the recent approval of bulevertide marks a major milestone for the hepatitis delta field and serves as a meaningful tailwind for the entry of our regimen. We know from the European experience that the approval of the first hepatitis delta therapy led to a substantial increase in disease awareness, with testing and diagnosis rates reportedly increasing by as much as 5 to 10 fold in certain territories. That experience underscores how therapeutic innovation can catalyze activity across the entire care ecosystem. During independent investor events this quarter involving leading hepatitis delta KOLs from across the US and Europe, experts highlighted the updated AASLD guidelines addressing HDV screening and treatment are expected in the near term. They also emphasize the potential impact of double reflex testing, in which hepatitis B surface antigen positive patients automatically receive HDV antibody testing, and if antibody positive, reflex directly to HDV RNA testing without additional physician order. Taken together, we believe the availability of the first approved therapy in the US, expected updates to AASLD screening and treatment guidelines, and the implementation of double refrex testing have the potential to meaningfully accelerate disease awareness, expand patient identification and diagnosis, and improve the quality of care for patients with ASLD. establish treatment pathways for a disease that has historically been significantly underdiagnosed and undertreated. Against this evolving backdrop, we believe it is important to consider the ultimate goal of therapy. hepatitis delta as with other chronic viral diseases, the objective is not simply viral suppression, but viral clearance.

In conjunction with our easel presentation, we conducted an advisory board with leading hepatitis delta experts from the US and Europe, and a clear theme emerged these discussions. Physicians consistently viewed undetectable virus as the most meaningful measure of disease control and the endpoint most predictive of favorable long-term outcomes, including lower rates of cirrhosis, of hepatocellular carcinoma, liver transplantation, and mortality. Several experts described target not detected, or TND, as the gold standard endpoint in hepatitis delta, with 1KOL emphasizing that the only good virus is a dead virus. Notably, our clinical data package continues to show progress toward this elevated treatment goal. At this year's EASL Congress, we presented complete week 96 results from our Phase II solstice study during an oral presentation. The data show robust rates of undetectable virus with Elapsiran and Tubavibard, reinforcing our confidence in the potential of our dual acting regimen. Overall, the results continue to show durable viral suppression, a favorable safety profile, and increasing rates of undetectable virus over time.

By week 96, 88% of patients in the intention-to-treat analysis receiving Elapseron and Tobevibart achieved undetectable virus, compared with 53% of patients receiving Tobevibart monoclonal antibody therapy alone. The last observation carried forward analysis, 97% of patients receiving the combination achieved undetectable virus at week 96. This underscores the scientific rationale of combining two drugs with complementary mechanisms of action to inhibit both entry of HDV and production of hepatitis B surface antigen. HDV relies on circulating hepatitis B surface antigen to replicate and complete its life cycle. observed rapid and durable reductions in hepatitis B surface antigen with the combination regimen compared with tobevibart antibody monotherapy. By week 96, approximately 90% of patients receiving combination therapy achieved hepatitis B surface antigen levels below 10 IUs per ml, versus only 25% with antibody monotherapy alone. Importantly, the antiviral activity observed with the combination therapy was accompanied by an ALT normalization rate of 53%. These effects were observed in a study population in which approximately 50% of patients had cirrhosis as defined by Child Pew Class A, underscoring the activity of the regimen in patients with more advanced liver disease.

ALT declines remained durable through week 96, further supporting the overall clinical activity of the regimen. Overall, the combination continues to be generally well tolerated. The most common treatment emergent adverse event was flu-like symptoms, which were mild to moderate in severity, transient and resolved after the first dose of treatment. There have been no treatment-related serious adverse event or discontinuations. Taken together, we believe the complete solstice dataset presented at EASL reinforces Elapseron and Tobevibar's best-in-class potential. As one leading hepatologist emphasized in a recent independent investor event, 88% target not detected at week 96 with the VIR combination is the best ever target not detected rate in 50 years of HDV treatment experience. It is something that must be acknowledged.

Looking ahead, given how swiftly we have been able to enroll patients in our ECLIPPS trials, we can now file one of the most comprehensive clinical data packages in CHD, drawing on data from all three ECLIPPS studies. Collectively, Eclipse 1, 2 and 3 are designed to provide evidence across key patient populations, including treatment-naive patients, patients switching from Belavertide, and patients enrolled in a head-to-head comparison against Belavertide. We continue to maintain close engagement regulatory authorities in both the US and Europe, including a formal interaction with the FDA for a Type B CMC meeting in July. Together, we believe these interactions and breadth of evidence positions us well to support broad regulatory submissions globally. As I mentioned earlier, we have completed enrollment in Eclipse II, our Phase III study, evaluating elapserone and tobevibart in patients who have not achieved viral suppression with bulevertide therapy. The Belevertide Switch cohort is an important component of our overall data package because it is designed to provide information on outcomes in patients transitioning from the only approved therapy for CHD. This dataset is relevant given the boxed warning on the current Belavertide label regarding the risk of severe acute exacerbations of hepatitis D and hepatitis B following treatment discontinuation.

To our knowledge, no competing CHD development program is expected to have comparable switch data at launch, which we believe represents a meaningful point of differentiation for the Eclipse program and could further strengthen our overall package. Beyond regulatory execution, we continue to advance our manufacturing and commercial readiness activities. Our commercial strategy is designed to support both at-home administration and healthcare provider administration, providing flexibility for both patients and physicians. Through our ongoing interactions with the FDA under Breakthrough Therapy designation, we are currently conducting human factor studies intended to support at-home administration, we believe could further enhance patient convenience and access. In addition, we are pursuing co-packaging of Elapseron and Tobevibard in the US to help streamline the treatment experience. We believe this could further differentiate the regimen and support adoption. As for manufacturing readiness, we are pleased to report that the drug substance process performance qualification, or PPQ, manufacturing activity is now complete for both Elapsiran and Tobevibart.

Successfully completing drug substance manufacturing represents a major accomplishment for the program. Looking ahead, we are now progressing on the drug product PPQ batches as planned. Furthermore, following the license agreement with Norgene late last year, launch preparation activities are well underway across Europe, Australia and New Zealand. Based on the team in place and collaboration to date, we believe Norgene is well positioned to support a successful launch of Elapseron and Tobevibard in these territories if approved in the EU. Overall, we believe the strength of our efficacy and safety package, coupled with once-monthly subcutaneous dosing and the ability to support both at-home and in-office administration, if approved, could drive strong adoption in the evolving CHD treatment landscape. Even with a new treatment option now available in the US, KOLs continue to highlight limitations, including the burden of daily administration, treatment fatigue, and uncertainty around treatment discontinuation. Given these dynamics, we believe that, if approved, Elapsron and Tobivibart will be well positioned to set a new standard of care in CHD with a differentiated profile that addresses key physician and patient needs.

Turning now to our oncology portfolio, where we are building a differentiated and increasingly robust T-cell engager portfolio, powered by a proprietary ProX10 dual masking platform. We believe this technology represents a meaningful advancement in the field and positions us to develop next generation T-cell engager. engagers across a broad range of cancers. I'll begin with VIR5500, our ProX10 dual-mass PSMA-targeted T-cell engager, which we are advancing in collaboration with Astellas. Following encouraging data at our go-forward dose showing potent anti-tumor activity, favorable early safety data, and no observed dose-limiting toxicities, we are actively enrolling patients across expansion cohorts with the ambition to initiate phase 3 registration trials as as next year. Currently, we have dosed our first patients with VIR5500 across three monotherapy populations, Taxe-naive MCRPC, radioligand therapy naive MCRPC, and radioligand therapy exposed MCRPC. In parallel, we are advancing three combination cohorts. One cohort in Taxe Naive MCRPC evaluating VIR5500 with enzalutamide, which is currently enrolling patients.

The second cohort, Intex-A-Naive MCRPC, evaluating VIR5500 with docetaxel, which will be initiated in the coming months. and the third cohort in metastatic hormone-sensitive prostate cancer, evaluating VIR5500 with darolutamide, which will be initiated in the coming months. We are evaluating step-up dosing at 800, 2,000 and 3,500 micrograms per kilogram, Q3 weekly across both monotherapy and combination therapy cohorts. We believe this development plan builds upon the opportunity to unlock VR5500's potential across the prostate cancer treatment continuing. Together with Astellas, we have launched scale-up efforts and have secured a manufacturing contract to support the VR5500 phase 3 program. Our goal has been to ensure that CMC readiness advances in parallel with clinical development so that manufacturing does not become rate-limiting as the program progresses. Moving to VR5818, our ProX10 dual-masked HER2 targeted T-CEN engager. Dr. 5818 is the first MASS T-cell engager in clinical development for HER2-expressing tumors.

We view the ongoing phase 1 trial as a the signal finding study given the early stage of development and the basket design where multiple tumor types are evaluated in parallel. expect to report updated dose escalation data evaluating VIR5818 monotherapy and combination therapy with pembrolizumab in the second half of 2026. This update is intended to inform the dosing regimen we will take forward and help identify which HER2-expressing populations may warrant further study, particularly in areas of high unmet medical need. In parallel, we are also advancing VIR5525, our ProX10 dual-MAS eGFR targeted T-cell engager. We are continuing dose escalation in the phase 1 study, evaluating VIR5525 as both a monotherapy and a combination with pembrolizumab across multiple EGFR expressing tumor types. The study incorporates learnings from both VIR 5500 and VIR 5818 to support efficient clinical development. The dose escalation is tracking well to plan and we look forward to sharing updates as the program matures. Beyond our three clinical stage T-cell engagers, we have a pipeline of seven preclinical assets underscoring both the breadth and scalability of the platform.

Importantly, the encouraging clinical data generated to date serves as early validation of our platform, reinforcing our confidence in its ability to deliver differentiated profiles across multiple programs. We expect to nominate additional development candidates in 2027, further accelerating the expansion of our pipeline. With that, I'll now hand the call over to Brent for our financial update.

Thank you, Marianne. I am pleased to share that we saw significant improvement in our cash position over the second quarter of 2026. We ended the quarter with approximately $1.01 billion in cash, cash equivalents, and investments, representing an increase of $198.5 million. During the second quarter, the company received payments of $315 million from Astellas, consisting of a $240 million upfront payment and a $75 million equity investment payment. I would like to note that since December 2025, our collaborations with Astellas and Norgene, together with our follow-on expectations, offering have generated more than half a billion dollars in cash, meaningfully strengthening our balance sheet and positioning us to execute across multiple value creating milestones. Based on Based on our current operating plan, we continue to project cash runway into the second half of 2028. Now moving to financial performance. We recognized $238.9 million in license and collaboration revenue during the second quarter of 2026, largely related to the $240 million upfront payment we received from Astellas. R&D expense for the second quarter of 2026 was $135.3 million, which included $5.5 million of stock-based compensation expense and $48 million of expense associated with a milestone payment to Sanofi, representing 20% of the $240 million upfront payment we received from Astellas.

This compares to $97.5 million for the same period in 2025, which included $6.9 million of non-cash stock-based compensation expense. The year-over-year increase was primarily driven by the milestone payment to Sanofi, and to a lesser extent, hepatitis delta qualification manufacturing costs. SG&A expense for the second quarter of 2026 was $30.2 million, which included $6.9 million of stock-based compensation expense. compared to $22.3 million for the same period in 2025, which included $5.5 million of stock-based compensation expense. The increase was primarily due to one-time advisory and legal expenses in connection with the closing of our STELUS agreement in the second quarter of 2026. Net income for the second quarter of 2026 was $80.1 million compared to a net loss of $111.0 million for the same period last year. The same period last year, A significant improvement in net income was primarily driven by the previously mentioned $238.9 million in Estella's license and collaboration revenue recognized this quarter. With that, I'll turn it back over to Mary Ann to close the call.

Thank you, Brent. In summary, I am incredibly proud of the strong execution we have delivered in the first half of the year, highlighted by the deal with Astellas on our lead clinical oncology program and the integration of our teams since the close and enrollment of the Eclipse studies. Looking ahead, we are positioned for a meaningful sequence of upcoming milestones in hepatitis delta, beginning with top line data for eclipse one in the fourth quarter of this year, followed by eclipse two and three in the first quarter of 2027. Based on the totality of data generated to date, including our recent presentation at EASL, we believe the dual acting mechanism of Elapseron and Tobevibard has the potential to define a best-in-class profile in an emerging commercial market. In oncology, our collaboration with Astellas in prostate cancer has enabled a rapid advancement of your 5500 into expansion cohorts, and we are focused on generating the data needed to support our planned transition into registrational trials next year. We believe VIR5500 has the potential to become a foundational therapy in prostate cancer, with broad applicability across both monotherapy and combination treatment settings. Taken together, we believe we are entering a period of sustained value creation, supported by a strong balance sheet and financial discipline, multiple near and mid-term catalysts, and a focused approach to execution. We look forward to updating you on our progress over the coming quarters.

With that, the Q&A session. Thank you, Mary Ann. This concludes our prepared remarks. We will now start the Q&A session. Joining me from the Q&A are Marianne and Brent. Please limit questions to two per person so we can get to all of our covering analysts. I'll turn it over to you, operator.

At this time we will begin conducting our analyst Q&A session. If you would like to ask a question, please press star 1 to raise your hand and to withdraw your question, press star 1 again. We ask that you pick up your handset when asking a question for optimum sound quality and if muted, Locally, remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Paul Choi with Goldman Sachs. Your line is open. Please go ahead.

Hey, thank you. This is Eric for Paul Choi, and thanks for taking the question. The question about, you know, after the initial Eclipse 1 readout, what is the plan and timing for long-term extension data, and will the follow-up assess the durability of TND and whether patients could.

eventually discontinue treatment. Thank you for that question. I thought a second one was coming, but maybe not. Yes, so thanks, Eric. So we have in our trial design for Eclipse 2 and Eclipse 3 incorporated the exploration of the potential for finite treatment. This is not something that is incorporated in our Eclipse 1 trial design where we're really comparing the treatment with elapsed run. and to bevipart versus the deferred treatment. But it is something in our overall Eclipse program that we will be exploring.

Oh, thank you. Your next question comes from the line of Rowana Ruiz with LeRinc Partners.

Your line is now open. Please go ahead. Okay. Hey, everyone. So with the enrollment completed for Eclipse 2, can you talk a bit about what thresholds you're hoping to see on both efficacy and safety from that particular study and how the data on switching from the lever tide could help inform future physician prescribing?.

Yes, thank you, Rana. So Eclipse 2, just for everyone, is the trial where we really are looking at patients that fail on the lever tide and then are switched to our combination regimen of Elapsed Run and to Vivipart. And what we're looking at there as an end result is that we're looking at the patient's condition. point is after 24 weeks really target not detected. So we think that the bar is considered to be low because our target not detected rates compared to Belevertide are significantly higher, as you recall. So that's really the outcome that we will be watching. And maybe just to add that given the black box warning that Beléver-Tide has now for switches or discontinuations of Beléver-Tide, we believe that the Eclipse 2 data will be very, very valuable. And as mentioned in the prepared remarks, we believe that we are the only company that will have that data at the time of launch.

Yes, got it. And as another question for 5818, could you talk about how much you hope to share with the upcoming data set in second half 26, help frame, you know, the potentially number of patients or any other insights that you really hope to share? hoping to think about as you kind of narrow it down on different tumor types for that program.

Sure. So 5818, I heard to study just for everyone's recollection is a basket trial. So it contains a lot of different tumor types. And we have a monotherapy escalation cohort and a combination cohort with pamburizumab. So we will be sharing. those escalation data. We see it as a signal-seeking study, again, given the heterogeneity of the data. Rana is really a good insight into the dose for any potential next steps and then also insight into what exploration, what indications might really be valuable for the program.

Okay, got it. Thanks. Thank you. Your next question comes from the line of Corey Kazimov with Evercore. Your line is open. Please go ahead.

Hi, this is Josh on for Corey. Question for you, Marianne, and I realize this is a difficult question to answer, but we figured it'd be best to ask it here. There's been a significant amount of management turnover this past year. How confident are you that you have the team in place to effectively manage both the two important in the distinct clinical programs? And how do you envision best bolstering the C-suite rings in the coming months? Thank you.

Yes, thank you for that question, Joss. I'm very confident that we have a very strong team in place, as I think is evident from the progress that we are making quarter to quarter. We are looking to bring in a new CMO. And as mentioned before, we are looking there for a very strong profile in medical oncology because beyond Delta, where we are close to having registrational data coming out this quarter and the fourth quarter and then the first quarter next year, the future of our pipeline will nearly entirely be in immuno-oncology. So we're looking for a very strong leader in that field. And for the CFO, yes, we have actually started started interviews last week. And again, you know, we have a roster of, I think, what are very strong candidates to move forward in the process.

Great, thank you. Sure. Your next question comes from the line of Alex Strawnahan with Bank of America. Your line is open. Please go ahead. Hey, guys. Thanks for taking my questions.

one on HCV and one on 5500. So first on HCV, after the Belever Tide approval and pricing here in the US, I guess, how is your thinking around competitive positioning for your combo and pricing change, if at all? And then on 5500, just thinking towards the phase three, starting next year, I guess, how much will the early line data, including the doxotaxel combo, kind of feed into how you design the path forward for Pimple. Thank you.

Yes, thank you for that question. Maybe first on Delta and the impact of blepharotide approval. As mentioned, what is really helpful now is that, you know, there's an increased awareness around the disease. We also know that the blepharotide price has been set at around $283,000, obviously, with Delta being recognized as a rare disease. We believe that we have a potential best-in-class profile. You have seen the phase two data from Solstice at EASL, where we have 88% target not detected at 96 weeks. So very durable data. And even if you use the last observation carried forward analysis, we can... go up to 97%.

So very strong efficacy data combined with monthly dosing and combined with a very, very very good safety and durability profile. So we believe that we have a profile that is significantly differentiated from the lever tight and obviously we will be hoping that that patients will benefit from that that differentiation. For the next question on 5500, yes, so we are very excited that since closing the deal with Astellas in the second quarter, we have been able to bring online now a total of already expansion cohorts, which we are enrolling patients and two others that are in preparation. This is exactly what we had hoped to achieve, real acceleration and being able to do quite a number of explorations in parallel so that we can really determine the full scope of possibility for VR5500. as monotherapy or as combination and the the data that we will be collecting with docetaxel will of course be very uh important for the design of our of our pivotal trials as are of course the data from from our other cohorts we will really be um be led by by what uh what the data will.

tell us. Thank you. Your next question comes from the line of Philip Nadeau with TD Cowan. Your line is open. Please go ahead.

Good afternoon. Thanks for taking our questions. One from us on HDV and one on 5818. On HDV, you mentioned the human factor study. Can you go into a little bit more detail as to how Tobinela are being dosed in the pivotal trials and how you hope to have the commercial formulation do in terms of devices, well as at home versus in the clinic. And then second on 5818, you mentioned this is a signal finding study. Can you give us some sense of what the bar is to moving forward in any individual indication? Do you need to see responses? Is prolonged stable disease enough? Some sense of what you're looking for in the different cohorts. Thank you.

Sure, thank you Phil. So starting with hepatitis delta. So in our ECLIPSE trials the combination of elapseron and tobevibart is being administered in a a hospital setting. And what we are doing with the human factor study is really bridging to human, you know, to in-home administration. We've had, as mentioned, had a type B CMC meeting with the FDA, which has been very, very productive. Basically, what the The dosing is, of course, it's monthly, it's subcutaneous, it's two injections at the same time. So we are looking into co-packaging Elapseron and Tobevibar to make it even more convenient for patients to self administer. And one of the really positive things is that even for who are not in a position to self-administer, I think our monthly dosing is really opening up that possibility for dosing in office or in hospital by a physician or a nurse in an ongoing chronic treatment.

So yes, we are very optimistic about this. the progression we are making in our preparation for our human factor study. Then on 5818, so what signal we are looking for, Phil? Obviously it depends significantly on what kind of indication you're speaking about. As you know, for example, in MCRC where we showed some initial data last year, and especially microsatellite stable MCRC, the bar is extremely low. single digit ORR. So again, depending on what kind of indication you will be looking at, the signal you will be looking for is a little bit different.

That's very helpful. Thank you. Your next question comes from the line of Etzer DeRoute with Barclays. Your line is open. Please go ahead.

Great. Thanks for taking the question. Maybe just curious if you have any analogs or if you've heard any commentary from key opinion leaders on how quickly the new patient ID and diagnosis methods could be adopted by physicians for HDV. And then question on on the expenses in the second quarter, and whether or not you can maybe comment on what you see sort of trends are for the balance of the year across R&D and SG&A. Thank you.

Thank you, sir. I'll ask Brent to first maybe answer your second question. Sure. Thank you, Marianne. Yes, regarding expenses. So we expect, you know, as Marianne said, we finished our PPQDS batches mostly in the first and second quarter. And then we are you know, we are keeping our cash runway into the second half of 2028. So with that, I would say we don't give individually quarter guidance, but, you know, THE BIGGER DS EXPENSES ARE BEHIND US AND WE CONTINUE TO MOVE FORWARD WITH OUR PROGRAMS.

Thank you, Brand. And then to your other question, Edsor. So what we have seen, especially since, again, the lever tide launching a couple of months ago, is that, first of all, we heard and probably you heard it, too, in other independent investor call that some KOLs were mentioning the fact that, you know, testing for COVID. for reflex testing, incorporating that in the guidelines for the US was something that was really getting very acute. I mean, of course, if that happens, that would be a major achievement. We also hear that a number of major sites here in California are already implementing universal reflex reflex testing for Delta now that there is a treatment available. And some are also, we hear from KOL, some are also re-screening all their patients in the HPV registry for hepatitis Delta. So we think that, you know, gradually there's signs that things are going to change. You know, they aren't necessarily pointing. to analogs, but certainly, again, the fact that There is an unmet need.

There's a treatment available now in the market. You can see certain things changing, and that is exactly what we had hoped for. And we hope that, of course, there will be also much more diagnosis and testing happening going forward.

Great. Thank you. Your next question comes from the line of Sean McCutcheon with Raymond James. Your line is open. Please go ahead.

Hi guys, thanks for the questions. Two from us. First, could you maybe go into some of your efforts to expedite the BLA filing once the Eclipse suite of studies is in hand? And then second question, you go into the rationale for starting a darolutamide combo in the hormone-sensitive.

setting as opposed to a combination with Enzo Luttabait. Thank you. Thank you, Sian. So maybe first on efforts to expedite our BLA filing. So we have, you know, of course been very focused on mapping out, you know, the from last patient, last visit to database lock and stop line data to filing what that timing would look like. And we're really looking at that as a matter of hours and days. So we have prepared this quite well. And of course, we are trying to really expedite as much as possible and take out any unnecessary. very downtime in that process. So I would say that we're very well equipped as soon as data come in for Eclipse 1 in the fourth quarter and then Eclipse 2 and 3 in the first quarter of next year to move as quickly as possible.

Then your question, darolutamide. So the rationale for combining VIR5500 with darolutamide is really rooted in what we believe is a complementary mechanism of action. So we think there's synergy with the AR blockade, but we also believe that darolutamide is a complementary mechanism of action. may increase the PSMA target density. And of course, at the same time, if there is a lower disease burden and a more intact immune context, in the case of metastatic hormone-sensitive prostate cancer, we think this might be, in general, a more favorable setting to T-cell engagers.

Your next question comes from the line of Joseph Stringer with Needham. Your line is open. Please go ahead.

Hi, thanks for taking our question. One on HDV, where do you peg the current U.S. HDV diagnosis rate today? And I suppose now that there's an approved therapy plus some momentum toward universal testing in the guidelines, where do you think diagnosis rates could realistically plateau and over what time frame. Thank you.

Hey Joe, thank you for that question. Yes, so diagnosis rates for Delta in the United States are relatively low. I mean, they're around 10 to 15% only. We do believe that it can reach maybe about 25% and maybe even more. more, really depending on the awareness that is going to be created, the ease of testing, of course the reimbursement related to testing practices. So there's still a lot that needs to be put in place, but we think there's a lot of low-hanging fruit to improve diagnosis for Delta.

Your next question comes from the line of Patrick Trucchio with HC Wainwright. Your line is open. Please go ahead.

Hi, it's Arabella for Patrick. Thank you so much for taking the question. I guess given the field in HDV kind of shift towards focusing on TND more. I was wondering if the FDA has shared their view on TND alone versus TND plus alt normalization and then separately for eclipse one, could you comment on the BMI and steotic liver disease distribution and how it compares to solstice? Thank you so much.

Thank you for that question. We are very happy to see that there is this broad recognition that getting rid of the virus, so really looking at target not detected, is the most important endpoint and related to outcomes. As you know, even in our existing Eclipse trials design, Eclipse 2 has an endpoint that is only TND. So I think, again, we obviously do not know the FDA's position on this topic, but I think the fact that they have accepted our endpoints as we have them today, I think is a good parameter. on your second question related to to bmi um so yes our team has done an um an analysis of impact on BMI on the On the data in solstice, we haven't really designed our eclipse trials differently, so there isn't going to be a fundamental difference between BMI, as you saw it in solstice, versus how we have it in eclipse. Thank you.

This concludes the Q&A session of the call. Thank you for participating. You may now disconnect.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Thanks for joining the session with Vir Biotechnology. My name is Alec Stranahan. I cover SMID-cap biotech at Bank of America, and I'm the covering analyst for Vir. And it's my pleasure to introduce Marianne De Backer, Chief Executive Officer of Vir. Marianne, thanks for being here.

Yes, my pleasure. Thank you.

Looking forward to the discussion. I guess just jumping right into it, you've effectively built a 2-engine value story for Vir. You've got the near-term potential from HDV, which we can talk about and the longer-term oncology platform using the PRO-XTEN technology. I guess when you look at how the market is valuing the company today, where do you see the biggest opportunity for re-rating? Is it on HDV approval and launch? Is it on the VIR-5500 progress to registrational studies? Or is it maybe the broader platform as the TCE data matures?

Sure. Yes. Thank you. And thank you, Alec, for hosting us and Bank of America for hosting Vir Biotechnology. So we are very fortunate that at Vir Biotechnology, we have multiple pathways to value creation, as you point out. Obviously, our most advanced program is our delta program, already in registrational trial, initial data are going to read out starting fourth quarter of this year. So obviously, that's an important route to value creation near term.

And then as you mentioned, we have a portfolio of 3 clinical assets, 3 clinical masked T-cell engagers. And just in February, we read out quite promising data for our prostate cancer program. So again, huge opportunity potentially. T-cell engagers have in the solid tumor space been very challenging, faced with a lot of toxicity. And we believe that with our PRO-XTEN platform, we can really address that and come up with T cell engagers that have a unique therapeutic index.

And then thirdly, to your point, we have the platform. And we really think that the PRO-XTEN platform is like an IND machine. And so we have started 7 preclinical programs. Of course, we will not keep them all wholly owned. We are going to partner some of them. But again, that's going to be an important path to the future and more mid- and long-term value creation for the company.

Great. And obviously, we can get into the partnerships that you've already struck for VR-5500. But maybe just before we get there, in terms of capital allocation and prioritization within the pipeline, your cash runway is pretty extensive after the recent raise. I guess, how are you balancing the Phase III ECLIPSE trials, of which you've got three ongoing and the commercial build-out in HDV with maybe the dose expansion and the combination studies across the oncology TCE portfolio?

Sure. So at the end of the first quarter, we had $809 million. And because we entered into a partnership with Astellas, we will have about $315 million coming in. So one important aspect of the funding for the VIR-5500 program is that due to the partnership with Astellas, Astellas will be taking on 60% of the clinical development costs going forward. And that is very important because we really want to fully explore the potential of that asset, and we are doing a number of trials in parallel. And obviously, that's going to be quite funding intensive.

On the other hand, again, our delta trial is in registrational phase. So that is really taking up the bulk of our investment at this moment in time. But you can sort of expect that over time, there will be a shift from investment into our delta program to floating more of that investment into our oncology portfolio.

Okay. Great. Well, maybe we can start with VIR-5500. You recently had an update at ASCO GU, which showed very good efficacy. I think 82% PSA 50, 53% PSA 90, 45% ORR at the go-forward dose. As you move into the expansion cohorts, I guess, which of these metrics, either the depth of the PSA response, the ORR by RECIST or durability or maybe a combination of these sort of stand out and give you the most confidence in moving these to Phase III study?

Yes. So as mentioned, the real crux of being able to come up with a best-in-class T cell engager for solid tumors is to get to a very favorable therapeutic index. If you look at a lot of T cell engagers, again, in that space, you can get to reasonable efficacy, but it's combined with pretty problematic toxicity. So it's really not just looking at efficacy, but it's the combination of efficacy and safety. The data that we showed in February were, of course, quite compelling to your point, very promising PSA data, and it was perfectly concordant with RECIST data with PSMA-PET evaluations -- with RECIST evaluations.

So efficacy, very nice dose response, nice concordant data, but more importantly, it was combined with a very, very nice safety profile. So predominantly say only Grade 1 CRS. And that is really what we would want to see. The expansion cohort has actually already started for late-line mCRPC. We have selected our dose. And the idea there will be at one dose level to explore, obviously, a broader set of patients and then also explore a little bit more than we have done up to now what it looks like in pre-radioligand therapy and post-radioligand therapy patients.

I see. And I guess when you think about the durability of response, I think we have a few case studies that could speak to the long sort of deep response that's possible with 5500. What are these responses and the durability sort of suggests about the mechanism? And any initial thoughts on sort of PFS and what you want to see there?

Yes. So on the durability side, we had a number of case studies, as you pointed out, we had a patient that had been 8 months on study. We had a patient that had been a year on study. And then we had a number of patients where we had RECIST responses that confirmed post 27 weeks. So those were sort of the initial signs of durability. But the data set was still pretty much immature at the time of sharing it back in February.

We will, in our expansion cohort and of course, in our existing cohort continue to look at durability. From our perspective, there's no reason why you wouldn't see durability. There's a number of other T-cell engagers in the prostate cancer space, STEAP1, KLK2 that have shown durability. So there's really no reason why PSMA-targeted T-cell engager would not show durability. And again, we have these early very promising signs. The other thing I would say is that given our technology, our masking technology, which is the same across all our clinical assets in our HER2 program where we use the same masking technology, we had a patient that we showed data on last year that also had been 18 months of treatment.

So we also see that the masking technology across different targets actually allows us to get results and also allows us to show durability. Again, this is still sort of case specific. But as the data mature, we hope to show more. And as to your question on rPFS, again, our data sets in February was a bit early. But in our expansion cohort, it's, of course, absolutely the intent to look at our rPFS and share the data when available.

Okay. Great. And I guess when we think about the patients that respond well or respond less well, I think you had 2 early progressors with PSMA-negative lesions. I guess as you plan combinations with enzalutamide and explore earlier lines of therapy where PSMA expression may be more variable or could maybe be suppressed after Pluvicto, although I'm not sure that's well studied. But how are you thinking about prospectively monitoring antigen loss in your pivotal programs just to make sure that patients are expressing the target?

Yes, you're absolutely right. I mean you have obviously heterogeneity on PSA levels between patients. And then you have actually different levels of PSMA expression depending on which tumor within the patient. So you have intratumor variability. So it is something that we pay a lot of attention to. And our translational biomarker study using PSMA-PET is really looking to look at pretreatment, post-treatment and then again, across patients and intra-patient at potential variations in PSMA levels.

I wanted to say, though, that in our earlier data set from February, we had about 7 patients that had been having PSMA radioligand therapy. And unfortunately, there was only one patient that was already at efficacious dose for which we had the data, but that patient showed incredible responses, PSA99s, very clear T cell infiltration in the lymph nodes. You could see on PSMA PET completely the lesions clearing up after 9 weeks. So it's not the case that if you have a PSMA directed therapy that it isn't possible anymore to use our T cell engager after that. And again, this is something that in our expansion cohort, late line monotherapy, we're going to explore a bit further.

Right. And you're obviously testing post-Pluvicto and also pre-Pluvicto, so?

Correct. Yes. And not just Pluvicto, also other actinium, et cetera, radioligand therapy.

Okay. And you alluded to this, but the CRS profiles look very good. I think 50% of patients were entirely grade 1 to 2 largely early cycle with no need for prophylaxis really. How much of this differentiated CRS profile would you attribute to the dual masked versus maybe patient population or dosing schedule?

Yes. We really believe that it is our masking technology that makes all of the difference. So our masking technology is basically this hydrophilic protein structure that we form around the T cell engager. And we mask both the CD3 binding domain and also the tumor-associated binding domain, so the PSMA binding domain. So the dual masking obviously is important, but the masking technology is really crucial because what the masking allows us to do is really -- again, the whole idea is that through creating this mask around the T cell engager, you can dose the patient.

The mask T-cell engager gets a longer half-life in the case of VIR-5500, 8 to 10 days. It can safely sort of transport into the bloodstream of the patient. It can get to healthy tissues and nothing happens. But when it enters the tumor microenvironment, then the protease cleavable linkers are going to be cleaved -- being cleaved by proteases in the tumor that -- where they are dysregulated, the mask fall off and then the T-cell engager can exert its effect. And when the masks are removed, the half-life is really reduced to only a couple of hours. So that mechanism is really allowing us to dose up quite high, so you get a good efficacy and that you can combine with, again, a really differentiated safety profile because it's really protected outside of the tumor.

And I guess when you think about moving to earlier line patients, is there any reason to think that the CRS profile might be better or worse? Just thinking about tumor debulking sort of the cytokine release itself, how much pent-up cytokine is within the tumors? Any sort of biologic rationale for why a frontline or an earlier line patient might have better or worse CRS?

Yes. So we see in a very refractory patient population already really good results. And I just want to remind you that the patient set for VIR-5500, almost half of the patients had visceral metastasis. 1 in 5 had liver metastasis. So really patients with very bad prognosis. And in that data set, we showed really good efficacy. But what KOLs believe is that if you go to earlier lines, you even might have the possibility to see better efficacy because, obviously, there is a possibility that you have a healthier T cell repository there. And of course, for T cell engagers to be effective, you need good CD8 positive T cells. So we don't have that data yet, but it could be that it actually is going to be looking even more promising.

Okay. And maybe one more question, circling back on a point that you mentioned about the dual mask and the cleavage in the tumor. I think you showed 93% of patients had unmasked drug concentrations that were essentially undetectable in circulation. When you look at patients that have distant metastases, does the cleavage profile change at all across different tumor microenvironments? And I guess, how does that data sort of shape your confidence on expanding into broader, more heterogeneous population?

Yes. So first of all, we have designed our protease cleavable linker such that there is a level of promiscuity. So there's different protease families that can cleave the linker. And it is based on, of course, decades of understanding what proteases are upregulated in tumors. What we know now, and of course, we are learning as we go, but what we know now is that, obviously, we get effective cleavage in the prostate.

We see that we get effective cleavage in the metastatic sites, you have seen evidence of that in the lung, in the lymph nodes, in the liver. So we have a lot of examples now. And also with our HER2 program, we have shown that we saw some effects in metastatic colorectal cancer, in the breast cancer patient. So I think this shows you that it's actually a very versatile platform and that the unmasking actually really does happen across a broad tumor -- set of tumor types.

Okay. Great. And I guess in terms of the dose optimization and sort of your strategy going into the pivotal, what does the expansion cohort data set really need to show to justify a particular go-forward dose? And I guess, given the 8- to 10-day half-life of the mask molecule, are you exploring maybe step-up dosing or other approaches to further flatten the CRS curve?

Yes. So we have selected a go-forward dose for our late-line monotherapy cohort. So we have selected indeed a step-up dosing of 800, 2,000, 3,500. So the way it works is that patients get dosed at 800 micrograms per kilogram, a week later at 2,000 micrograms per kilogram, then a week later at 3,500 micrograms per kilogram. And then actually, the therapy starts with every 3 weeks, 3,500 micrograms per kilogram.

So that is the go-forward dose we have selected for monotherapy. We haven't shared yet the data around the go-forward dose for the combination cohorts. Those cohorts haven't been started up yet, but we will share that data as it becomes available. And we will also be doing some further optimization to satisfy Project Optimus.

Okay. Okay. Great. And maybe looking beyond 5500, obviously, having the Astellas collaboration kind of in your pocket for when you're releasing the data was a stroke of confidence, obviously, for the program. Does the Astellas collaboration kind of represent the ideal partnership archetype for other TCEs such as 5818 or 5525? Or will the partnership maybe vary depending on the tumor type or the stage of derisking in the clinic?

Yes. Whether we keep a program wholly owned or whether we partner and how we partner really depends on the program. And it depends on, okay, what is the unmet need, what other competitive regimens are there already there? How can we really come up with a differentiated offering, what would it take development-wise and what would it cost to get there? So there's a lot of considerations, I would say. So we will really be looking and we are strategically looking at each program, what might be optimal for the program.

For VIR-5500, we think that the deal with Astellas is really optimal because it's a co-development, co-commercialization deal. We retained 50% of the profit in the U.S. This year, as I mentioned, 60% of the development cost going forward. And it allows us to really go faster and grow the pie bigger, faster. So we can now do late line, early line mCRPC and HSPC in parallel much faster than we would have been able to do on our own.

Okay. And I guess when you think about advancing new TCE assets forward in preclinical development and into the clinic, how do you sort of navigate the target -- potential target space? Obviously, it's a very flexible platform. There's a lot of ways you could take it. But do you have a preference to going after well-known targets or in like kind of well-studied indications? Or are you looking for going after something a little bit more novel?

Yes. I mean what we really want is to find an application for our technology that offers something that is really differentiating. And what we can really differentiate on is getting to T cell engagers with a broad therapeutic index, so much safer than any T cell engager that is unmasked or single masked or masked with a different technology.

So what we have been looking at is largely targets where there is a clear biological rationale. So they are not novel, they're not unproven. There's some gradation in biological validation, but there is generally biological validation. But we're just given the targets, it has been difficult to come up with safe molecules. And again, that's where we really can make a difference.

Okay. And maybe on that last point, EGFR has been a difficult space to develop any sort of TCE against masked or unmasked. I guess does your view on partnering or portfolio prioritization change at all following the discontinuation of a competitor's EGFR TCE program?

Not really. So EGFR is certainly a more difficult target. So if you compare it to PSMA, for example, PSMA is, of course, expressed in prostate. It's also expressed in some other tissues, but it's relatively limited. If you look at an EGFR, of course, it's expressed in a lot of tumors, but it's also expressed in a lot of healthy tissues. So the bar for any masking technology is very, very high.

We do believe that we have a very unique masking technology, and we are now putting it to the test in our clinical trials. So -- but yes, we will be continuing our monotherapy and the combination therapy. And then as soon as we have some meaningful data set, we will be sharing it with the public.

Okay. Okay. Great. I want to shift gears now to HDV. This is kind of the other arm of the pipeline. And the focus from investors from my conversations tends to shift back and forth between this and your TCE portfolio. So I do want to give it the time that it deserves. Maybe we can just start on the competitive landscape here. I guess, how do you view the broader competitive landscape? How did bulevirtide or I guess, the recent data from Mirum from the AZURE-1 data, particularly on, I guess, target not detected. How does this sort of shift your thinking around your program and execution or market expectations?

Yes. So obviously, because hepatitis delta is a viral disease, what you really want to get undetectable...

Let me shift gears now.

Really shifting gears -- so you're really trying to get to undetectable and undetectable virus. And the way that undetectable virus is measured is through target not detect, TND. So what we know now is Gilead is one of our competitors in the space. They are going to launch with a daily administration regimen probably very soon. And they get to target not detected rates of around 12% to 20% of 48 weeks.

Then Mirum recently shared their data with their monthly regimen. They had a target not detected rates of 5%. And to just give you a comparison, we also have a monthly regimen and our target not detected rate at the same time point is 41% and it goes to 66% at 48 weeks and actually to 88% at 96 weeks. So I think from a monthly regimen perspective, we're by far efficacy. Mirum has a weekly regimen that has shown about 30% TND at 24 weeks. And again, that compares to 41% for us.

Also on ALT normalization, which is a very aspecific marker, but nevertheless, we see now that competitors are getting normalizations between 40%, 45%. We had [ last week ] of 56%. So I think that we really are seeing the potential for our regimen to be best in class market....

That's great. And maybe the next question sort of around positioning versus -- that was nice. That was a lovely backdrop for that response.

I guess just as we think about bulevirtide in the real world, obviously, this is approved in different geographies. We're thinking maybe it will expand. I guess as the efficacy and convenience contrast becomes clear for your asset versus bulevirtide, I guess, how do you expect prescribing to evolve? Will switching underresponders be common? Or is your primary launch opportunity to sort of bulevirtide in patients?

Yes. So the way that we have designed our trials is we have -- we can show actually how our regimen is doing in bulevirtide-naive patients. And we have our ECLIPSE-1 trial, which is comparing to a deferred treatment. So it's basically an almost placebo-controlled trial. And then we have ECLIPSE-2, where we look at patients that have been on bulevirtide but have not been adequately virologically controlled and that are switched to our regimen.

And then we have a third trial where we compare head-to-head our regimen with bulevirtide. So we will really be equipped by the time that we get to market to obviously be prescribed for naive patients, treatment-naive patients, but also to really capture those patients that come off bulevirtide. Again, bulevirtide is a daily injection. Patients need to inject themselves daily. And as I mentioned, they get to about 12% to 20% undetectable after 48 weeks.

With our regimen, it's monthly, so monthly 2 injections, and we get to 66% undetectable after 48 weeks. It also allows us with a monthly administration to have both at-home administration, so patients can dose themselves every month at home. But for those patients who prefer or unable to inject themselves, they can also have in office or in the hospitalization on a monthly basis. So it's really a very conveniently -- very convenient regimen in that regard that leaves up -- leaves open the option for at home or in office.

Okay. And I guess for those maybe less familiar with HDV, it is a fairly underserved patient group and maybe even underdiagnosed to a certain extent. I guess with Gilead likely to launch bulevirtide in the U.S. How does this -- we talked about the competitive differentiation. I think that will be proven out with ECLIPSE. But how does Gilead sort of building out the initial market kind of benefit you guys once ECLIPSE does read out and you're thinking about the launch next year?

Yes. So first of all, this is great for patients. The disease awareness is going to significantly increase is our estimation. Also, we believe that diagnosis rates will go up once -- at this moment in time, even though it's very easy to diagnose hepatitis delta, it's not happening. There's only 10% to 15% of the patients that are getting diagnosed. And the reason why it's not happening is because there's really nothing available in the U.S. to treat patients. So we believe that once a treatment is on the market, there will be an impetus to test patients. Again, testing is not difficult.

There will be a possibility to do reflex testing. I think the patient journey and treatment pathways will become much clearer. So we think that Gilead launching ahead of us is actually very beneficial, again, for patients and also for us who are then coming with a regimen that is much more convenient and with a much more efficacious profile.

Okay. And obviously, you'll have ECLIPSE-3, which is the head-to-head versus bulevirtide. I think the top line from that is expected in 1Q of next year. You've said in the past that this is probably not required for an NDA. But I guess how critical do you expect this data set will be in sort of your payer conversations? And is there a risk that a strong head-to-head data becomes table stakes rather than upside?

Yes. I mean it's something that you just need to have, right? You need to be able to show what your value proposition is compared to what might be standard of care at that time. So we will have that. And again, given the Phase II data that we have and what we know about bulevirtide, it will not be very difficult to show that added value. But we think it's a very important study to do, and it will be even more important, we believe, in Europe, for example, as a region for pricing and reimbursement negotiations.

Okay. And you mentioned the cash position. It sounds like it's scaling even up to $1 billion currently. How do you see investments in the commercial build-out in HDV? What does that process look like? When do you start that process? And what does it leave for investing in TCE and other parts of the company?

Yes. So we have guided to a cash runway until the second half of [ 2028 ]. We have now a small commercial group. We have a number of medical science liaisons that have already been out for quite some time since last year that have been involved in the studies and are involved in insights generation. So we are really building this up very gradually.

What is important is that Delta is a rare disease. It's an orphan disease. It's -- the patients are geographically quite concentrated in certain metropolitan areas. So it's not like you need this broad swath of sales or MSL people to put -- you have to take a very surgical approach. And that's exactly what we are preparing for.

Okay. A lot of exciting things happening at the company, especially over the next 12 months. So I really want to thank you, Marianne, for the great conversation. Looking forward to the updates. And thanks for bearing with us through the technical difficulties. More than that disruptive, hopefully. And thanks, everyone, for your attention. Thank you.

Thanks. Thank you, Alec.

Hello, and welcome to Vir Biotechnology First Quarter 2026 Financial Results and Corporate Update Conference Call. As a reminder, this call is being recorded. [Operator Instructions] I will now turn the call over to Kiki Patel, Head of Investor Relations. You may begin, Kiki.

Thank you, operator, and welcome, everyone. Earlier today, we issued a press release reporting our first quarter 2026 financial results and corporate update.

Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration outcomes, future results, performance or achievements to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements include, but are not limited to, statements regarding the potential benefits of our collaboration with Astellas, the therapeutic potential of VIR-5500 and our PRO XM platform, our development plans and time lines, financial terms and milestone payments and our cash runway and capital allocation priorities. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q and 8-K.

Joining me on today's call from Vir Biotechnology are Dr. Marianne De Backer, our Chief Executive Officer; and Jason O’Byrne, our Chief Financial Officer. During the first quarter of 2026, the Vir Bio team delivered meaningful advances across our T-cell engager and Hepatitis Delta programs, underscoring our ability to execute towards key clinical and corporate priorities.

The agenda for our call today is as follows: First, Marianne will share an update on our recent landmark global strategic collaboration with Astellas and our prostate cancer program. Next, she will provide an update on our Hepatitis Delta program evaluating tobevibart, an investigational neutralizing monoclonal antibody and elebsirin, an investigational small interfering RNA. Then Jason will provide an overview of our first quarter 2026 financial results. And finally, Marianne will close the call, and we'll open the line for Q&A.

With that, I'll now turn the call over to Mary Anne.

Thank you, Kiki. Good afternoon, everyone, and thank you for joining us for Vir Biotechnology First Quarter 2026 Earnings Call. Since our last earnings call in February, we have remained highly focused on execution as we advance both our oncology and hepatitis delta programs with speed and focus. I will begin by providing a brief update on the current status of our recent collaboration with Astellas, a deal valued at up to $1.7 billion. In addition, in the U.S., commercial profits will be split 50-50 between the parties with Vir Bio having the option to co-promote alongside Astellas.

As a reminder, on February 23, we announced that we entered into a collaboration with Astellas to co-develop and co-commercialize VIR-5500, our PRO-XTEN dual-masked PSMA-targeted T-cell engager. Since then, the transaction successfully closed on April 15, marking an important transition from deal announcement to deal execution. With the deal closed, our joint teams are operational and partnering closely on a shared clinical development plan to enable rapid expansion and accelerate delivery to patients. This collaboration brings together Astellas' global leadership in prostate cancer with our differentiated PRO-XTEN -enabled T-cell engager. We chose to partner with Astellas because of their decade-long track record of successfully co-developing category-defining therapies, including XTANDI, the world's #1 prostate cancer drug.

Metastatic castration-resistant prostate cancer, or MCRPC, remains a significant unmet need with a 5-year survival rate of only 30%, underscoring the urgency for new treatment options that can deliver even deeper, more durable disease control and improved quality of life. VIR-5500 is the most advanced dual mask T-cell engager currently under evaluation in prostate cancer. The foundational driver of the Astellas collaboration shaping our development strategy going forward is our Phase I data for VIR-5500. Dr. Johan De Bono shared an update from this study evaluating patients with advanced MCRPC as an oral presentation at ASCO GU in February.

Today, I'll highlight key takeaways from the data. For a more comprehensive update from the trial, please refer to our fourth quarter earnings call from February 23. Overall, the VIR-5500 data showed a favorable safety and tolerability profile with no observed dose-limiting toxicities. At the dose levels of 3,000 micrograms per kilogram and above, we saw mostly Grade 1 cytokine release syndrome or CRS, defined as fever only. We did not observe any Grade 3 CRS at this dose, reinforcing the potential of the PRO-XTEN dual masking platform to widen the therapeutic index of our T-cell engagers. We view the absence of high-grade CRS at our go-forward monotherapy dose, together with a lack of mandatory steroid premedication in our protocol as a meaningful differentiator for VIR-5500. We believe that sparing steroids may help preserve T-cell function and reduce treatment complexity for both patients and physicians.

Collectively, these attributes support the potential for outpatient administration and could translate into significant clinical and commercial advantages over time. Importantly, this profile may support positioning VIR-5500 in both the pre- as well as post-radioligand therapy or RLT settings, offering flexibility across the treatment continuum and potential use in routine care settings relative to the specialized infrastructure required for RLT administration. Furthermore, the depth of PFA and RECIST responses we observed were particularly encouraging with several patients sustaining responses for up to 27 weeks. Additionally, we saw emerging signs of durability up to 8 and 12 months, respectively, in patient cases with extended follow-up.

One of the most compelling aspects of our data is that these deep responses were observed in heavily pretreated patients with advanced poor prognosis disease, including liver metastasis. This is historically the most difficult population to treat and resistant to immunotherapies, underscoring the clinical significance of the activity we are seeing. Additionally, we observed a complete response for a patient who previously relapsed on an actinium-based PSMA directed radioligand. We view these findings as especially meaningful given the historically poor outcomes and limited responsiveness of this patient population to subsequent therapies.

Building on these encouraging Phase I dose escalation monotherapy results, we have dosed the first patient in our Phase I dose expansion cohort for VIR-5500 in late-line patients. This milestone represents an important step in further evaluating VIR-5500's best-in-class potential for people living with prostate cancer. In the monotherapy expansion cohorts, we are evaluating Q3 week 800, 2,000, and 3,500 microgram per kilogram step-up dosing. This study will measure safety and efficacy, including PSA responses and objective response rate or ORR of VIR-5500 in patients with MCRPC who are refractory following treatment. These patients will have had exposure to multiple prior lines of therapy, including at least one second-generation androgen receptor pathway inhibitor and taxane regimen.

The expansion includes 2 distinct cohorts: patients who are naive to prior RLT and patients who have previously received RLT in any treatment setting. Dose escalation of VIR-5500 in combination with enzalutamide continues in early-line MCRPC patients. We anticipate dosing the first patient in the combination dose expansion cohorts in both early-line MCRPC and metastatic hormone-sensitive prostate cancer over the coming months. Together, these cohorts highlight the potential of VIR-5500 across the prostate cancer continuum, including in the frontline setting. Without the challenges associated with RLTs, such as radioactivity and restricted settings of care, we believe masked T-cell engagers represent the long-term future in this space and that VIR-5500 has the potential to be a best-in-class T-cell engager. We anticipate initiating our registrational Phase III program for VIR-5500 in 2027. These results provide validation of our broader PRO-XTEN platform, unlocking significant opportunities to develop next-generation masked T-cell engagers in other solid tumor types.

Turning now to the rest of our clinical stage T-cell engager programs. VIR-5818 is our PRO-XTEN masked HER2-targeted T-cell engager. We view this as a signal finding study given the early stage of development and the basket design where multiple tumor types are evaluated in parallel. We expect to report preliminary response data evaluating VIR-5818 monotherapy and combination therapy with pembrolizumab in the second half of 2026. This update is intended to inform our understanding of dose and help identify which HER2-expressing populations may warrant further study, particularly in areas of high unmet medical need.

For VIR-5525, our PRO-XTEN dual-masked EGFR targeted T-cell engager, Phase I study enrollment is progressing as expected. The study design incorporates learnings from VIR-5818 and VIR-5500 to enable efficient dose escalation. We are evaluating both monotherapy and combination with pembrolizumab across multiple EGFR-expressing tumor types, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and cutaneous squamous cell carcinoma. We believe this program has the potential to address significant unmet medical needs in these indications where existing EGFR-targeted approaches have limitations.

Turning now to our Hepatitis Delta program. The hepatitis delta community is severely underserved, with approximately 180,000 actively viremic patients across the United States, the U.K., and the EU, based on a composite of high-quality epidemiology sources. In the U.S., the patient population is highly concentrated in major urban centers and can be supported by an efficient commercial approach with a targeted specialty sales organization focused on hepatologists, gastroenterologists and infectious disease specialists. Overall, we expect our tobevibart plus elebsiran combination to have 2 clear advantages in chronic hepatitis delta versus our competitors. The first is that we are seeing potential best-in-class efficacy with a strong safety profile. The second that our regimen is designed with once monthly subcutaneous dosing and the potential for both at-home and in-office administration.

For viral infectious diseases, clearing the virus is the key to improving long-term outcomes. KOLs in the chronic hepatitis delta space highlight undetectable virus as measured by target not detected or TND, as the gold standard measure of viral clearance. Achieving undetectable HDV by this measure is the most stringent threshold available and means that the delta virus is completely cleared from the bloodstream. As the delta virus replicates so aggressively, patients need HDV to be completely undetectable for positive clinical outcomes and to avoid rebounds. Peer-reviewed evidence suggests that patients with hepatitis delta who achieve undetectable virus have significantly improved long-term clinical outcomes, including reduced progression to cirrhosis, hepatocellular carcinoma, liver transplantation, and death compared with patients in whom the virus remains detectable. These data support an undetectable virus as a key clinically meaningful goal of antiviral therapy for patients with hepatitis delta.

In January, we reported potential best-in-class efficacy in our Phase II SOLSTICE trial in patients with chronic hepatitis delta for a subset of patients at 96 weeks. Evaluated participants receiving the combination therapy of tobevibart and elebsiran showed increased and sustained viral suppression of HDV RNA versus treatment with the antibody alone. The data showed 88% of evaluable participants achieved undetectable virus compared to 46% on tobevibart monotherapy alone. Additionally, we saw a rapid onset of viral suppression, achieving already 41% undetectable virus within 24 weeks. These results underscore the limited efficacy of hepatitis delta treatment with antibody monotherapy alone. In contrast, combining complementary mechanisms of action with tobevibart plus elebsiran raises the rate of undetectable virus to approximately 90%.

Importantly, we see similar efficacy in cirrhotic patients, which will be a significant patient cohort at launch due to the delayed diagnosis of most hepatitis delta patients to date. The combination was well tolerated with no grade 3 or higher treatment-related adverse events and discontinuations.

The second key differentiator is that tobevibart plus elebsiran will only be administered monthly, consisting of 2 subcutaneous injections to be administered at the same time. As a reminder, competitors' sleep regimens require either daily or weekly injections. For the hepatitis delta patient population, this frequency will be a significant challenge. So, we see monthly dosing as an additional meaningful differentiator for our regimen. Additionally, due to the need for a higher dosing frequency of competitive regimens, tobevibart plus elebsiran may have the potential to be the only product conveniently enabling both self-administration at home and physician administration in the office. This is important because physicians have indicated that up to 20% of hepatitis delta patients might not be able to self-administer. So tobevibart plus elebsiran may be the only treatment available for this group of patients.

Our hepatitis delta regimen has already been recognized by multiple global regulators with FDA breakthrough therapy and Fast Track designations as well as EMA Prime and orphan drug designation, underscoring both the unmet need and the strength of the data package. These designations provide ongoing engagement with both agencies and support a high level of confidence in our ability to achieve broad labels for our regimen.

We are pleased to share that we will be presenting the complete 96-week SOLSTICE Phase II data in an oral presentation at the upcoming EASL 2026 Annual Meeting in Barcelona on May 29th. We will also be presenting a poster of a 48-week subgroup analysis evaluating the impact of VMI on ALT normalization after successful viral control.

As we look ahead to our ongoing registrational program, all 3 of our ECLIPSE studies are on track. ECLIPSE-1 enrollment is complete with approximately 120 participants randomized 2:1 to our combination therapy versus deferred treatment. The primary endpoint is a composite of undetectable virus as measured by HDV RNA target not detected plus ALT normalization at week 48. We expect to report top line data from ECLIPSE-1 in the fourth quarter of this year. ECLIPSE-2 enrollment continues on track across multiple European sites. This study will enroll approximately 150 patients who are being randomized 2:1, evaluating the switch to our combination therapy in patients who have not adequately responded to bulevirtide. The primary endpoint for the trial is undetectable virus as measured by HDV RNA target not detected at week 24. The strong enrollment momentum we are seeing in Europe reflects an important unmet need in patients previously treated with bulevirtide.

For ECLIPSE-3, our Phase IIb head-to-head comparison, enrollment is complete with approximately 100 patients randomized 2:1 to our combination therapy versus bulevirtide. The primary endpoint for the trial is undetectable virus as measured by HDV RNA target not detected at week 48. In general, we view Gilead's expected U.S. launch of bulevirtide as a positive for the hepatitis delta market overall and one that helps pave the way for next-generation therapies like ours. Hepatitis delta remains significantly underdiagnosed and undertreated and the introduction of the first approved therapy in the U.S. should meaningfully raise disease awareness, expand screening and establish treatment properties among treating physicians.

Complementing this, we have an experienced commercialization partner through our collaboration with Norgine, who holds an exclusive license across Europe, Australia and New Zealand. Norgine's established infrastructure and expertise in specialty pharma and hepatology positions us to maximize the commercial opportunity of our HDV regimen across these geographies.

In summary, we have made exceptional progress across our entire clinical portfolio, and we believe these advancements leave us well positioned to deliver on our clinical and corporate objectives.

With that, I'll now hand the call over to Jason for our financial update.

Thank you, Marianne. Before discussing the first quarter financials, I will share the latest news about our Astellas collaboration. We are pleased to report that the VIR-5500 global collaboration and licensing agreement closed on April 15, 2026, following expiration of the HSR waiting period. Upon closing, Vir Biotechnology received a $75 million cash payment, representing Astellas' equity investment. And within 30 days of closing, we will receive a $240 million upfront payment. As a reminder, we are eligible to receive a $20 million manufacturing tech transfer milestone payment in 2027. We will share global development costs, 40% by Vir Bio and 60% by Astellas. We will split U.S. commercial profit loss equally with Astellas, and we are eligible to receive up to an additional $1.37 billion in development, regulatory and ex-U.S. sales milestones, along with tiered double-digit royalties on ex-U.S. net sales.

A portion of certain collaboration proceeds will be shared with Sanofi according to the terms of that licensing agreement. Overall, this deal provides immediate capital and significantly reduces our near-term development spend while preserving substantial long-term economic upside. The collaboration with Astellas can maximize the value of VIR-5500 through accelerated clinical development and global reach, potentially benefiting more patients and creating greater value for our shareholders. Shortly after announcing our global collaboration with Astellas and sharing updated Phase I data from the VIR-5500 program, we completed a follow-on equity offering. On February 27, 2026, the offering closed, and we received gross proceeds of approximately $172.5 million before deducting underwriting discounts and commissions and estimated offering expenses. We intend to use the proceeds from the offering to fund our share of the development costs for VIR-5500 to advance the broader T cell engager platform and for working capital and other corporate purposes.

Turning now to our balance sheet. We ended the first quarter with approximately $809.3 million in cash, cash equivalents and investments, which includes the aforementioned proceeds from the follow-on offering. Subsequent to quarter end, we closed the Astellas collaboration, and therefore, the $315 million in proceeds from that transaction are not reflected in our March 31, 2026 cash position. Based on our current operating plan and including the net effects of the recent Astellas agreement and capital raise, we expect our cash runway to extend into the second half of 2028, enabling multiple value-creating milestones across our pipeline.

Now I will review our first quarter 2026 financial performance and overall financial position. R&D expense for the first quarter of 2026 was $108.9 million, which included $6 million of stock-based compensation expense. This compares to $118.6 million for the same period in 2025, which included $7 million of stock-based compensation expense. The year-over-year decrease was primarily driven by a $30 million payment to Alnylam in the first quarter of 2025, partially offset by hepatitis delta qualification batch manufacturing costs and to a lesser extent, higher clinical expenses in the first quarter of 2026. SG&A expense for the first quarter of 2026 was $23.3 million, which included $6.1 million of stock-based compensation expense compared to $23.9 million for the same period in 2025, which included $7.1 million of stock-based compensation expense. Our first quarter 2026 operating expenses totaled $132.3 million, representing a $10.3 million decrease compared to the same period in 2025. Net loss for the first quarter of 2026 was $125.7 million compared to a net loss of $121 million for the same period last year.

Looking ahead, we will continue disciplined allocation of capital, prioritizing investments in those programs with the greatest potential for meaningful patient benefit and value creation.

With that, I will now turn it back over to Marianne to close the call.

To close, we are exceptionally well positioned for long-term value creation at this inflection point. Since December 2025, the combination of our collaborations with Norgine and Astellas, together with a successful financing has generated over $0.5 billion in capital, significantly strengthening our balance sheet.

With the closing of our global collaboration with Astellas this quarter, we now have an established partner to advance VIR-5500 aggressively across the prostate cancer landscape while maintaining disciplined capital allocation. Overall, the combination of potent antitumor activity and a favorable safety profile underscores VIR-5500's potential as the best-in-class T cells engager for the treatment of prostate cancer. Beyond our clinical programs, we are steadily advancing 7 preclinical T-cell engager assets that utilize the PRO-XTEN platform and broaden our pipeline's optionality, positioning us well to generate the next wave of value creation.

At the same time, our hepatitis delta program continues to generate compelling and increasingly differentiated clinical data with multiple near- and mid-term catalysts ahead across our ECLIPSE studies. Taking together with our progress in oncology, this momentum underscores the breadth of our scientific platforms and our ability to execute with focus, urgency and discipline.

Looking ahead, our priorities are clear: to deliver rapid, high-quality clinical execution, advance multiple expansion and registrational-enabling studies and deploy capital thoughtfully in ways that maximize long-term value while keeping patients at the center of everything we do.

With that, I'll turn the call over to Kiki to begin the Q&A session.

Thank you, Marianne. This concludes our prepared remarks, and we will now start the Q&A session. Joining me for the Q&A are Marianne and Jason. Please limit questions to two per person so that we can get to all of our covering analysts. I'll turn it over to you, operator.

[Operator Instructions] Our first question comes from Paul Choi with Goldman Sachs.

My first question is on 5818 in the HER2 setting. Can you comment on your level of interest in future development, particularly in HER2-positive breast cancer. It's not listed among the tumor types in your quarterly deck here. And so, I'm just curious, given the number of available therapies for that particular tumor type, sort of what is the criteria from your upcoming data set for potential development in that tumor type? And then I had a follow-up question.

Thank you, Paul, for that question. Yes. So, we will be sharing data on our 5818 programs in the second half of this year, and this will be both for our monotherapy dose escalation and the dose escalation in combination with pembrolizumab. As to future development, we will, at that time, be able to provide a better picture as to what future expansion cohorts could be. Specifically, to your question on breast, I would say that, obviously, the bar is high, but do keep in mind that this drug, for example, like in HER2 has a 1% mortality rate. So, there's certainly still a prospect to come up with better treatments. But again, we will be sharing data second half of the year, and we'll then give further guidance.

Okay. Great. And with regard to 5500 and your comment on potential development earlier treatment settings, I guess, what would sort of, I guess, the framework for that be and potential timelines? Would you file an IND for that particular population this year or possibly in 2027?

Yes. So just to recall that we already have a dose escalation ongoing for early line 5500 combined with an ARPI. What we are planning to do now together with Astellas, our collaboration partner, is start expansion cohort in the same setting, combination of VIR-5500 with enzalutamide. So that is something that is coming in expected coming months.

Your next question comes from Roanna Ruiz with Leerink Partners.

This is Michael on for Roanna Ruiz at Leerink Partners. Regarding 5500 late-line MCRPC monotherapy expansion cohort, what would constitute a clear signal as a green light to initiate Phase III in 2027? Are you anchoring on like, PSA50, 90 or RECIST or PFS, something like that?

Yes. So, we started first -- we dosed the first patient in the late-line expansion cohort for VIR-5500 monotherapy. We are going to, in that expansion cohort, explore a little bit more in-depth both pre- and post-radioligand therapy. So that will be additional data that we will be gathering. We only have a limited set of such patients in our initial cohort on which we reported data on February 23. And I would say it's going to really be the totality of the data. Obviously, PSA, RECIST, RPFS, we will have a more full data set to then decide on the next steps. But our goal is pending data, obviously, to start pivotal trials in 2027.

Great. Just one more question. I also had a question about the underlying biology for PRO-XTEN cleavage. How tumor-specific is the protease activation profile across different tumor types? For example, are you seeing differential cleavage kinetic in like prostate versus colorectal or CLC that might affect that therapeutic index?

Yes. One of the founders of the company that was acquired by Sanofi and from which we licensed the technology has been working in this field for over 20 years. And it's fair to say that the protease cleavable linker is really promiscuous linker. There's different families of proteases there to really ensure that you are going to be successful across a broad set of tumor types.

Your next question comes from Cory Kasimov with Evercore.

This is Josh Chazaro on for Cory. Maybe one on hep B. As you approach the pivotal hep B data, wonder what your latest thoughts are on pricing there.

Sure. Thank you, Josh. So, if you look -- first of all, hepatitis delta is an orphan disease. There's a number of anchor points for price that we can point to. The first one, I would say, is to look at the price of bulevirtide in Europe, which varies somewhere between $60,000 and 165,000 gross price. You can also look at the price of bulevirtide in Canada, which was set at, I believe, USD 115,000. And then if you look across your fellow analysts, I see that estimated prices vary somewhere between $150,000 and $250,000. We think that is very adequate for, again, a disease that is very severe, an orphan disease where we would be delivering substantial benefit for patients.

And then just one -- another quick one on 5500 here, maybe following up on one of the previous questions, especially in the late-line castrate-resistant setting, is there a minimum durability you're looking for with you and Astellas before you move into a Phase III? Is there a number you guys have in mind or a certain competitive threshold you're looking at?

Yes, not specifically. Again, we will be looking at, obviously, the totality of the data. I didn't hear it very well, but what your question on durability?

Correct.

Yes. Yes, I can only point to -- so what we know thus far is that several T-cell engagers have been showing durable responses. Our data set was still a little bit early, but also in our data set, you could already see that we had a number of resisted patients with data post 27 weeks confirmed partial responses. And also, we had a couple of patient cases, one patient that had been on treatment for 8 months. We had another patient that had been on treatment for a year and continuing. So we have sort of case examples of durability. And obviously, we will be looking in our broader data set for durability more consistently across the entire expansion cohort.

Your next question comes from Alec Stranahan with Bank of America.

This is Matthew on for Alec. Congrats on the progress. I guess 2 for us on competitive landscapes. First for HDV. Just curious your thoughts on this year data that came out recently and whether that sort of changes your thoughts on commercial opportunity or competitive landscape? And then secondly, for EGFR T-cell engagers, competitor of yours recently discontinued development of theirs dual mask. I guess just what gives you confidence that your strategy will pan out where others have failed?

Thanks, Matthew. Yes, on your first question, so as I laid out in the introduction, we -- and generally the key opinion leaders in the field very strongly believe that what really matters in a viral disease is to get rid of the virus. And the way that we measure that is through HDV RNA target multi-tectin. So, if you look at our levels of TMD for our monthly regimen of tobevibart and elebsiran, also 48 weeks, which is our primary endpoint, we achieved about 66%. And we have also shown that it really increases. It's actually increasing from 41% at 24 weeks to 66% at 48 weeks and then to 88% at 96 weeks. So, we saw that significant increase in target multitasking over time for our dual mechanism regimen.

We did not see that actually for our monotherapy antibody. We saw it at about 30% TMD at 24 weeks and then sort of plateaued around 50%. It seems that what Mirum is sharing for their monthly therapy, which would be most comparable to our monthly therapy is only 5% target not detected. So that might not be very viable. And then for their weekly regimen, at 300 milligrams, they are showing at 24 weeks, 30% target not detected. So, we believe that from an efficacy perspective, we have a potential superior drug here and potential best-in-class regimen.

Also from an ALT perspective, you can now see sort of across the different regimens that are in development that everyone is sort of landing around the 50%. We had 47% at 24 weeks. I think Mirum reported between 40% and 45%. So, ALT normalization seems to be sort of evening out across different regimens. But again, we do believe that it's really the viral efficacy measured by viral elimination and getting to undetectable that really matters. And there, we clearly have superior data.

As to your question on EGFR, yes, Janux discontinued their EGFR T-cell engager. I would say the only sort of surprising thing there from our perspective is that they saw muscular skeletal issues that were mentioned as dose-limiting toxicity. That was unexpected and something, of course, that we will watch. But the reason why we strongly believe in the differentiation of our mask T-cell engagers is first, the masking technology is fundamentally different. So, we use steric hindrance. It's the same mask across all of our clinical programs. So, we don't need to redesign a new mask every time for every program. So, we really take learnings from one program to the next. And what we have seen with VIR-5500 is that, that masking technology allows you to dose much higher. And if you can dose higher, obviously, you can get potentially to a better therapeutic index. So, I would say that our masking technology is fundamentally different.

Your next question comes from the line of Phil Nadeau with TD Cowen.

Two from us. First on 5818, you referenced the dose escalation data in the second half of the year. Can you give us some sense of what will be disclosed at that time, things like number of patients, duration of follow-up measures that you'll talk about, what tumor types will be in the update? That's the first question. And then second, on HDV, your presentation cites about 174,000 patients with HDV in the U.S. and Europe. We're curious how many of those you estimate are diagnosed and under the care of a physician, so could be amenable for therapy shortly after launch.

Thank you, Phil. Yes, on 5818, so we will be sharing data both from our monotherapy dose escalation and also from the dose escalation in combination with pembrolizumab. A number of patients, we will share at a later date. I want to maybe point out that the 5818 trial is very different actually from our 5500 trial in the sense that it's a basket trial. So, we actually have a wide variety of tumor types in that trial. And we have already shown you some initial results, for example, in metastatic colorectal cancer, where we had a 33% confirmed partial response. So, we will be where possible and where we have enough patients in one given tumor type, be sharing you, of course, information on where we use CA to look at responses, tumor shrinkage, et cetera. So, we see it importantly as a signal-seeking trial that will give us information around what indications to potentially go into expansion cohort.

And then your question on hepatitis delta. So, from those patients, we estimate that there are about 61,000 actively viremic patients here in the United States. And it's a hugely underdiagnosed disease, as I mentioned earlier. We believe that actually only about 10% to 15% of those patients are diagnosed at this moment in time. We do believe that once a regimen can become available that, that could really change. And the diagnostic testing is also getting better. For example, diagnostic tests for Delta are also relatively affordable. The Medicare reimbursement rate for an antibody test is $17 and for a quantitative RNA test about $43.

The only difficulty at this moment in time is that patients often need to go 2 or 3 times to see their physician before all testing is done. The first time for hepatitis B test, the next time for the antibody test and the next time for the RNA test. So, there's a lot of streamlining that can happen. And in Europe, they have already shown that if you do reflex testing, so really when a patient tests positive for hepatitis B immediately proceed to testing for hepatitis delta on the same sample that, that could really increase diagnosis rates substantially. So that is something that if the guidelines get adopted here in the United States, that could drive a lot of difference.

Your next question comes from Etzer Darout with Barclays.

This is Luke on for Etzer. For HCV, with the ECLIPSE-1 trial reading out in 4Q and then you have ECLIPSE 2 and 3 reading out in 1Q next year, how are you guys thinking about assuming a positive ECLIPSE-1 trial, is that going to be enough to support a BLA filing? Or do you need to wait for 2 and 3 to do that? And then on 5500 with the partnership with Astellas, and the announcement said that they will be responsible for all development activities after Phase I. Just wondering what kind of visibility you'll have into those trials as they enroll.

Sure. I'll start with your last question on collaboration with Astellas. So, it is a global co-development and co-commercialization agreement, and we have quite significant joint governance in the deal. So, we have a joint development committee, of course, the joint steering committee, joint manufacturing committee, joint IP committee, joint finance committee and so on, with equal representation and joint decision-making with some level of escalation to executives, et cetera, pretty standard, I would say, for a 50-50 type of partnership. So, we will remain very intricately involved. We are, of course, running the Phase I trials now. And of course, Astellas are very involved in that as well. So, it doesn't really matter who operationally runs the trial. It's really important that we have pre-aligned on the clinical development plan and the associated budget, and we try to make decision-making, of course, jointly, but also very swiftly.

And then your first question on what is required for filing. So, our guidance is that we would need a combination of ECLIPSE and ECLIPSE for filing. So we will have the ECLIPSE -1 data, as you mentioned, the fourth quarter of this year and then the ECLIPSE -2 is coming in the first quarter of next year.

Your next question comes from Sean McCutcheon with Raymond James.

Just one quick question from us. So, you've talked a bit to the competitor data in HDV. But maybe could you speak to the specific component of the competitor running an all-comer study with a meaningful proportion of patients with elevated ALT above the 5x the upper limit of normal? And any potential read-through to kind of how you guys are seeing the patient population here?

Yes. So, the estimation is that maybe about 5% of delta patients have an ALT that is above 5x the upper limit of normal. And these kind of very high levels of ALT can have a lot of different reasons. We and KOL strongly believe that the real measure of looking at whether there is damage to the liver is looking at cirrhosis. And that's why we have enrolled more than 50% of patients in our trial that are CPTA-cirrhotic and have shown actually really good results, similar to slightly better in those type of patients.

Your next question comes from Joseph Stringer with Needham.

For the Phase III ECLIPSE-1 trial in HDV, what's your current thinking on the bar for success, on the response rates on the 48-week primary composite endpoint? Would replicating the 38% or so response rates that you saw in Phase II set you up for success here?

Yes. Thank you for that question. So, ECLIPSE-1, just to remind everyone, is a trial where we compare treatments with our regimen of tobevibart and elebsiran within the first treatment. So, it is almost like placebo-controlled trial, which makes it, of course, very, very likely that we will be successful in that trial. The bar for success is really low. I mean, again, target not effective, for example, for tobevibart, which is in Phase III development, 10 milligram is about 20%. So irrespective of the ALT levels with an endpoint of TND plus ALT, you cannot get more than 20%. And it was 12% for the 2-milligram tobevibart dose. So, the bar for success is not that high. But again, I think we have a combination of best-in-class variable efficacy and then again, ALT normalization that seems to be pretty similar across all regimens.

Your next question comes from Patrick Trucchio with H.C. Wainwright.

This is Luis Santos in for Patrick. A follow-up question on the strategy for hep B has to do with where does the at-home self-administration strategy stand from a regulatory and device standpoint. Would you expect to launch to begin with the clinical administration before transitioning to that self-administration? And how -- and the follow-up question would be, by then, bulevirtide is expected to already be accepted in the U.S. How much do you think the at-home administration benefits versus hepcludex or bulevirtide?

Yes. Thank you, Luis. So maybe answering your second question first. So, patients who will be on bulevirtide will have to inject themselves daily, and it's a chronic treatment, right? So really chronically every single day, they will need to inject themselves. And as I just mentioned, for bulevirtide 10 milligrams, the expected level of target effect that you can reach is about 20%. In contrast, what we have is a regimen of a combination of tobevibart and elebsiran, which is a monthly administration also subcutaneously, but with a level of targeted at 48 weeks of 66%. So, the chances of success for patients are much higher and the convenience is also much better. So, I think there will be a real potential desire for patients and physicians to look at such a regimen.

In addition, we are running ECLIPSE-2 and ECLIPSE -2 is really looking at bulevirtide failures. So, patients that haven't been achieving adequate control of their virus on bulevirtide and then can switch to our regimen. So, we will also have data to show that, obviously, that makes sense for patients to do.

As to your question for at home and at clinic, so the good news is that with our monthly administration subcutaneously, we have a very convenient offering, both for patients who want to do the administration at home. And of course, there's a lot of different ways we can achieve that and also actually for patients who might not be capable to inject themselves at home and where physicians and patients might think they prefer administration in office by physician, this level of once-month administration is really convenient to allow that to happen. So, we will be preparing at launch to have both available, both options at home and in office.

This concludes today's call. Thank you for attending. You may now disconnect.

Good afternoon, and welcome to Vir Biotechnology's conference call to discuss the company's VIR-5500 Strategic Collaboration with Astellas and Positive Phase I Data, and 2025 financial results. As a reminder, this conference call is being recorded. [Operator Instructions] I will now turn the call over to Kiki Patel, Head of Investor Relations. You may begin, Kiki.

Thank you, operator, and welcome, everyone. Earlier today, we issued 3 press releases, including a joint release with Astellas, announcing a strategic collaboration with our PSMA-targeted T-cell engager, VIR-5500, a second release reporting the Phase I VIR-5500 data that will be presented at ASCO-GU, and a third release reporting our fourth quarter and year-end earnings.

Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration outcomes, future results, performance or achievements to differ significantly from those expressed or implied in such forward-looking statements.

Forward-looking statements include, but are not limited to, statements regarding the potential benefits of our collaboration with Astellas, that the closing of the Astellas collaboration is subject to the expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, the therapeutic potential of VIR-5500, our PRO-XTEN platform, our development plans and time lines, financial terms and milestone payments, and our cash runway and capital allocation priorities. These risks and uncertainties associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including our Forms 10-K, 10-Q and 8-K.

Joining me on today's call from Vir Biotechnology are Dr. Marianne De Backer, our Chief Executive Officer; Dr. Mark Eisner, our Chief Medical Officer; and Jason O'Byrne, our Chief Financial Officer. Additionally, Dr. Johann de Bono from the Institute of Cancer Research in the U.K. is joining us for our prepared remarks to provide a clinical and investigator perspective.

Let me briefly outline today's agenda. Marianne will start by sharing the high-level overview of the strategic collaboration with Astellas and discuss how VIR-5500 has the potential to be a best-in-class T cell engager to address the significant unmet need in metastatic castration-resistant prostate cancer or mCRPC. Mark will then review the Phase I clinical data for VIR-5500, and he'll invite Dr. de Bono to walk through illustrative case examples. Mark will then summarize the broader data set and outline next steps for the program. Jason will cover the financial terms of the collaboration and provide an update on our 2025 financial results. And finally, Marianne will close the call, and we'll open the line for Q&A.

With that, I'll now turn the call over to Marianne.

Thank you, Kiki. Good afternoon, everyone. Today marks a pivotal moment for Vir Biotechnology as we announced a landmark strategic collaboration with Astellas to advance the global development and commercialization of VIR-5500, our PRO-XTEN, dual masked PSMA-targeting T cell engager for prostate cancer. VIR-5500 is our most advanced immuno-oncology asset. And today, we are sharing new Phase I data that will be further presented by Dr. de Bono at ASCO-GU this Thursday, February 26. Together, we believe these milestones position VIR-5500 for rapid advancement and allow us to move forward with both urgency and discipline.

The collaboration we've announced with Astellas combines their deep global experience in prostate cancer with our differentiated T cell engager powered by the PRO-XTEN masking technology. Structurally, the collaboration is designed to accelerate the development of VIR-5500 across both earlier and later lines of prostate cancer, unlocking a significant market opportunity while meaningfully derisking our pipeline of cancer immunotherapies more broadly.

Importantly, the new Phase I data that we are sharing today show a compelling emerging safety and efficacy profile. While still early, these data increase our confidence that VIR-5500 has the potential to be a best-in-class T cell engager for the treatment of prostate cancer.

And finally, today's update is also an important validation for the broader PRO-XTEN platform approach, which we believe can unlock opportunities to develop next-generation T-cell engagers in solid tumors.

To understand the significance of this opportunity, it's important to consider the current landscape in prostate cancer. Prostate cancer remains a significant global health burden, representing the most common diagnosed cancer among men with 1 in 8 men being diagnosed in their lifetime. Despite significant progress in treatment, the 5-year survival for patients with mCRPC is only 30% with an estimated 100,000 mCRPC patients in the U.S. and Europe.

Across the prostate cancer continuum, there is a substantial and growing unmet need for novel solutions, capable of improving long-term disease control as well as quality of life. T-cell engagers, which activate the human body's own immune cells in situ to fight cancer have transformed outcomes in several hematologic malignancies, and there are multiple products on the market today.

In solid tumors, however, use has been limited by toxicity challenges, including of tumor activation and cytokine release syndrome. We believe VIR-5500 powered by the PRO-XTEN technology has the potential to address these challenges. The PRO-XTEN platform leverages a universal dual masking approach, which consists of a T-cell engager that simultaneously targets both the tumor antigen, shown here in blue, and CD3 on T cells shown here in orange, and the PRO-XTEN masks in gray, which shield the T-cell engager through a unique steric hindrance mechanism.

As you can see on the left side of the slide, the large hydrophilic polypeptide XTEN masks surround and sterically hinder the CD3 and tumor-associated antigen binding sites. Upon reaching the tumor microenvironment, proteases cleave the linkers, here shown in pink, unmasking the active molecule precisely where it's needed. And once unmasked, the molecule combined both tumor cells and T cells, promoting targeted cancer cell killing.

In healthy tissue, the XTEN mask remain intact, dramatically reducing interactions with normal cells and minimizing systemic T-cell activation and subsequent cytokine release. The dual masking approach is designed to reduce toxicity, enabling higher dosing and a wider therapeutic window. Additionally, the XTEN mask themselves provide an extended half-life of the molecule supporting optimization of dosing schedules for patients. And as you'll see later in this call, this hypothesis is translated directly into our VIR-5500 Phase I clinical study results. In the trial, VIR-5500 affirmed early signals of a favorable safety and efficacy profile. Treatment with VIR-5500 also showed a dose-dependent antitumor activity as measured by PSA declines, radiographic RECIST responses as well as PSMA-PET responses.

Now let me turn to the collaboration with Astellas and why we believe they are the partner of choice for VIR-5500. First, Astellas is the market leader in prostate cancer. XTANDI remains the #1 therapy globally in this space, having treated more than 1.5 million men worldwide. This commercial success demonstrates the deep experience in bringing important prostate cancer therapies to patients at scale.

Second, Astellas has repeatedly proven its abilities to successfully co-develop blockbuster medicines with biotech partners. The examples on this slide highlight Astellas' ability to work collaboratively and successfully to translate innovation into market-leading therapies. Third, Astellas brings strong internal global clinical development and life cycle management capabilities, operating across roughly 70 countries. XTANDI has benefited from robust life cycle management, enabling multiple label expansions into earlier lines of prostate cancer. This ability to continually generate data, expand indications and maximize long-term asset value is a key differentiator and an important capability as we think about the future development opportunities.

Here is a snapshot of the deal terms that we announced with Astellas today, whereby Vir Bio and Astellas will co-develop and co-commercialize VIR-5500 for the treatment of prostate cancer. The financial impact of these terms is substantial. The total potential in combined upfront and milestone payments is $1.7 billion. In addition, in the U.S., commercial profits will be split 50-50 between the parties with Vir Bio having the option to co-promote alongside Astellas. And outside of the U.S., Astellas obtains exclusive commercial rights for VIR-5500, while Vir Bio is entitled to receive sales milestones and tiered double-digit royalties on ex-U.S. net sales. Global development costs will be shared between the parties with Vir Bio contributing 40% and Astellas 60%. Overall, this deal provides immediate capital and significantly reduces our near-term development spend while preserving substantial long-term economic upside. The collaboration can maximize the potential of VIR-5500 through accelerated clinical development and global reach, thereby creating value and benefiting more patients.

I'll now turn to Mark to walk you through the compelling VIR-5500 Phase I data that forms the foundation of this collaboration.

Thank you, Marianne, and good afternoon, everyone. I'm pleased to walk you through the latest Phase I data for VIR-5500, which have been accepted for an oral presentation at the ASCO-GU conference taking place later this week. This is the only dual mask T-cell engager under evaluation in prostate cancer, and the emerging signals we are seeing reflect the potential of the PRO-XTEN masking platform to unlock the promise of TCEs for the treatment of solid tumors. As of the January 9, 2026, cutoff, we enrolled 58 patients with advanced metastatic castration-resistant prostate cancer in weekly and every 3-week monotherapy dosing regimens. Importantly, all dose escalation cohorts have cleared the dose-limiting toxicity period.

Our dose escalation strategy leveraged insights from our broader TCE platform, enabling us to advance efficiently from very low initial flat doses to step-up dosing with the highest Q3 week maintenance dose of 4,000 micrograms per kilogram. Throughout this escalation, prophylactic steroids or IL-6 blockade were not required and was only explored in 3 patients at the highest 4,000-microgram cohort.

Based on the emerging data for VIR-5500, our development focus is now centered on doses at or above 3,000 micrograms per kilogram given once every 3 weeks. These dose levels are where we are seeing the clearest clinical signals.

Here, we see the baseline characteristics for patients enrolled in the study. Participants were heavily pretreated with a median of 4 prior lines of therapy and some receiving up to 7. 95% had received prior taxane chemotherapy. These are patients with extensive disease burden, 93% presented with bone metastases, 45% of visceral involvement and 18% of liver metastases. Liver metastases are associated with rapid disease progression and poor response to existing treatment modalities. Approximately half of the study population was RECIST evaluable at baseline, enabling assessment of radiographic responses alongside PSA and biomarker responses.

This slide summarizes the emerging compelling efficacy and safety signals across the study. Overall, the VIR-5500 data show a favorable safety and tolerability profile with no observed dose-limiting toxicities. Cytokine release syndrome events were limited and predominantly low grade, representing fever only. Importantly, we did not observe Grade 3 CRS events at the dose levels of 3,000 micrograms per kilogram and above, reinforcing the potential of the PRO-XTEN dual masking platform to widen the therapeutic index of our T-cell engagers. We observed a clear dose response relationship for efficacy.

At Q3 week doses at or above 3,000 micrograms per kilogram, the data showed deep and consistent PSA declines. In 11 RECIST evaluable patients at these dose levels, 5 experienced objective responses, 4 of these responders achieved confirmed responses with 1 pending follow-up confirmation. We're also seeing emerging evidence of durability with several patients maintaining PSA and radiographic responses with continued therapy up to 27 weeks, though many in the higher dose cohorts remain early in their treatment course.

Finally, the depth of PSA declines is particularly encouraging. 82% of patients achieved PSA50, more than half achieved PSA90, and nearly 1/3 reached PSA99. These are meaningful results for late-line metastatic castration-resistant prostate cancer patients, especially patients with visceral disease and liver metastases who represent the poorest prognosis population.

To bring these data to life at the individual patient level, I'd now like to invite Dr. Johann de Bono to share his clinical perspective and discuss the real-world implications that illustrate the depth of responses we're seeing. Dr. de Bono is a world-leading physician in prostate cancer research with fundamentally changed how the disease is treated. It supported development of many breakthrough therapies, including abiraterone, cabazitaxel, enzalutamide, and olaparib. Dr. de Bono?

Thank you, Mark. The 5 case studies I'm going to share with you, many of whom are my patients, demonstrate multiple, impressive, biochemical and radiology responses to this dual masked T cell engager, VIR-5500 in sufferers from metastatic and heavily pretreated prostate cancer. I serve these men in my clinics and have witnessed their experiences and symptomatic improvements on this agent. In advanced metastatic prostate cancer, many subjects experienced significant pain, especially bone pain.

VIR-5500 resulted in pain disappearing following treatment in many patients as their disease regressed. Reduction in such pain is incredibly important to these men that we serve. Critically, I believe that the data from this trial show that the dual masking approach works at minimizing cytokine release syndrome, also known as CRS. We are reporting multiple amazing responses with little clinically significant CRS. In fact, circulating interleukin-6 levels remain low and relatively unchanged following treatment with VIR-5500 across these patients, with usually only grade 1 fever being observed, which is really quite remarkable and different to many other T-cell engagers we have studied that have resulted in cytokine release syndrome with hemodynamic instability requiring patient admission, vasopressors and treatment with oxygen, et cetera, for respiratory compromise.

In addition to this absence of requirement for prophylactic steroids or tocilizumab in this trial, very few subjects have required treatment with steroids after receiving this drug, VIR-5500. And this is really quite important since steroids are immunosuppressive and can limit immunotherapy with T cell engagers antitumor activity. So this dual masking by limiting CRS has major advantages.

Now let's go through these 5 cases in turn. Case study 1 demonstrates complete resolution of multiple, approximately 14, liver metastasis after 9 weeks of therapy with a 99% PSA fall, really very impressive. This was a 63-year-old man who had received most standards of care treatments, including taxanes, olaparib, the PARP inhibitor and abiraterone. This man had a substantial disease burden, many liver metastasis, diffuse bone disease, poor prognosis disease seen on the PSMA PETs imaging as shown on the left side of the slide. This gentleman received VIR-5500 at 800, 1,500 and 3,000 micrograms per kilogram, step dosing regimen dosed every 3 weeks. And he had a stunning response with complete resolution of all the liver lesions and near complete resolution of the bone disease, as you can see in these images. The patient achieved a partial radiographic response with a 62% reduction in the sum of the longest diameters and the 99%, as I said, PSA decline and importantly, marked improvement in his tumor pain.

Now what's really noteworthy here is that liver metastasis are often resistant to therapy associated with poor prognosis, including resistant to hormonal therapies and often other therapies, too. And in my practice, these patients are very hard to treat and seeing such remarkable responses in late-stage heavily treated prostate cancer is really quite amazing, really, unprecedented maybe even.

In the next slide, case study 2, we see here another significant RECIST response in multiple large liver metastasis again in a 75-year-old man with large bulky disease in the liver. As seen on the CT imaging on the left, with 3 course of treatment with VIR-5500 monotherapy, resulting in major shrinkage of liver lesions by 50% measurements being shown here on the slide. This patient had a 94% PSA fall as well as partial response radiologically and remain on treatment after 10 courses. Again, such responses in liver lesions is particularly impressive with a single-agent T cell engager and underscores the broad potential of this agent monotherapy to really impact outcome from this challenging disease.

Let's move now to the next case, case study 3. This 70-year-old man had a durable RECIST, PSMA PET and PSA90 response lasting more than 8 months. He had peritoneal and abdominal wall lesions, as can be seen on the scan and essentially had complete resolution of these lesions on PSMA PET scan with a complete metabolic response. And as I said, a PSA fall of more than 90%, maintaining an excellent quality of life while on therapy.

Let's now turn to the fourth case. This is a gentleman who is a farmer, who have been off work because of his symptoms. What's been amazing is that he had resolution of his pain and he was able to go back to work. That's very powerful. The 63-year-old man with diffuse lesions in the bone and lymph nodes with prior exposure to multiple prior lines of therapy, including an actinium-based PSMA radiopharmaceutical, had a complete radiographic response by week 9, accompanied by a 99% PSA fall, as you can see on the right in the slide here, with PSA resolution to nearly undetectable levels, as you can see down to 0.05 ng/mL.

Now let's turn to the matched tumor biopsy data from the same patient on the left, which we believe is compelling evidence for VIR-5500's mechanism of action and potential. The Duplex PSMA/CD3 IHC for these biopsies at baseline on the left and post treatment on the right show what this drug induces. You see on the left extremely dense PSMA-positive tumor architecture and no meaningful T cell infiltration. At week 5, you now start seeing a major increase in T cell abundance and a significant eradication of PSMA-positive tumor cells. This overall illustrates the ability of PRO-XTEN masked T cell engagers to engage the immune system to drive an antitumor immune response.

Let's now turn to the last subject. Here we see a complete response with 3 weekly 1,000 microgram per kilogram with approximately 12 months of durability in response. This is a 77-year-old man with more than 20 bone lesions and lymph node involvement, who actually received a lower dose of VIR-5500 with step dosing of 300, 600 and 1,000 micrograms per kilogram, given every 3 weeks after the step dosing. This patient, as I said, had a complete radiographic response by week 9 with resolution, as you can see on the scans of his bone lesions and his PSA becoming undetectable. He experienced clinical benefit with diminished pain and actually, in fact, is regularly going to the gym while on drug. And here, we start seeing durability really even with lower doses of drug.

So overall, I've shown you 5 very impressive case studies from the trial overall, showing the potential for impressive and durable disease control in many patients with this dual masked T cell engager. I will now pass back to Mark to review the results of the trial overall. Thank you so much for your attention.

Thank you, Dr. de Bono. Your clinical perspective on these patients treated with VIR-5500 is invaluable as we continue to advance this program.

Turning back to the full study population. The safety profile of VIR-5500 remains favorable. The table on the left displays treatment-emergent adverse events for all patients treated with weekly and every Q3-week dosing. The emerging safety profile supports a wide therapeutic index. We've seen no dose-limiting toxicities to date with grade 3 or higher treatment-related adverse events in only 12% of patients. Most of these are laboratory abnormalities.

We had only 2 patients discontinue treatment due to an adverse event. The first patient experienced spinal cord compression that was due to his underlying disease and not attributable to VIR-5500, and the second patient due to treatment-related blurred vision. The bottom half of the table on the left displays treatment-related adverse events at the highest doses of more than 3,000 micrograms per kilogram Q3 week.

As you can see, the AEs were mostly grade 1 and 2. The grade 3 and higher events are listed at the bottom, but primarily consist of neutropenia and tumor flare, which are indicative of immune-mediated engagement. We observed 2 events of treatment-related blurred vision with unclear pathophysiology and nonspecific MRI findings that improved toward baseline visual acuity. Overall, limited CRS was observed in high-dose cohorts of 3,000 microgram per kilogram and higher.

The bar graph on the right shows cases of CRS by dosing cohort. As you can see, all cases were low grade, either Grade 1 or 2 with no Grade 3 CRS. The Grade 1 events were only fever, treatable with antipyretics. We did not require prophylactic steroids or anti-IL-6 therapy overall. In the highest dose cohort of 4,000 microgram per kilogram, we did evaluate pre-dose steroids in cycle 1.

This slide highlights the strength of the dose response relationship across the doses tested. The waterfall plot illustrates all patients who had an evaluable PSA. Each bar represents an individual patient with the dose cohorts indicated at the bottom and CRS shown by the green and white colored markers. Across the entire dose range, increasing doses generated deeper and more consistent PSA declines. At doses of 3,000 micrograms per kilogram and above, PSA responses were rapid, pronounced and durable with responses confirming at subsequent time points. CRS severity remained low grade at the higher doses with no Grade 3 CRS observed.

This slide presents PSA data for patients treated at or above 3,000 micrograms per kilogram in the Q3-weekly regimen. Responses were observed early with some patients demonstrating deep declines as rapidly as cycle 1, day 8. What's striking here is the depth and consistency of the PSA responses displayed in the table on the right. Additionally, radiographic RECIST responses were concordant with PSA responses in evaluable patients. In other words, patients with the deepest PSA responses, PSA90 and PSA99 often had confirmed RECIST responses, supporting clinically relevant antitumor activity.

This is an exploratory analysis evaluating the concordance of PSMA PET total tumor volume as assessed by RECIP criteria with PSA declines and RECIST responses. RECIP is an imaging-based response framework developed specifically for PSMA PET scans in prostate cancer. RECIP can detect treatment effects earlier because it tracks PSMA-avid tumor volume, not just anatomical size changes. This is especially useful in prostate cancer where PSMA levels reflect tumor activity. Higher doses of VIR-5500 significantly reduced PSMA-avid tumor volume. These reductions correlated with both PSA responses and RECIST responses, providing further evidence of the drug's targeted activity against PSMA expressing tumors.

This slide presents radiographic response data for the 11 RECIST evaluable patients treated at our highest Q3 week dose cohorts of 3,000 micrograms per kilogram or above, showing best changes from baseline in some of longest diameters. We're seeing a 45% objective response rate or ORR, which includes 4 patients with confirmed responses and 1 patient who is awaiting a confirmatory scan. We are seeing a 64% disease control rate. Patients with partial RECIST responses are also showing deep PSA declines with PSA90s. It's worth noting that we're seeing these deep RECIST responses in patients with challenging disease characteristics, including those with liver metastasis.

What you're looking at on this slide is a spider plot illustrating the change of RECIST SLD or sum of the longest diameters over time at the 3,000 microgram per kilogram or higher Q3 week dosing level. We're starting to observe RECIST responses that persist over time and are concordant with deep and sustained PSA responses. The higher dose cohorts are continuing to mature.

This swimmer plot gives us a longitudinal view of durability. Here, we're also looking at patients treated at 3,000 micrograms per kilogram or higher Q3 week. In this graphic, you'll see markers indicating PSA50 and PSA90 responders, RECIST responses and grade 1 or 2 CRS events. Each bar represents 1 individual patient. And importantly, we have multiple patients staying on treatment for at least 6 months. Patients achieving deeper responses, both PSA and RECIST are also the ones remaining on therapy longer. As shown, CRS is largely limited to Grade 1 and 2 early cycles, after which it falls off, allowing patients to continue on therapy with good tolerability.

This slide presents VIR-5500's early clinical profile with other clinical stage T cell engagers currently in development for the treatment of prostate cancer. While cross-trial comparisons have inherent limitations and are not head-to-head studies, in the table, we compared VIR-5500 against each program's recommended or go-forward dose. Based on the early numbers, VIR-5500 is exhibiting a highly active profile with deep PSA responses and markedly lower rates of high-grade CRS and treatment-related AEs despite the majority of patients not receiving prophylactic steroids. Importantly, our every 3-week dosing schedule for VIR-5500 may enable administration in the outpatient setting, representing a potential advantage in treatment convenience and broader clinical adoption.

Overall, the combination of potent antitumor activity and favorable safety profile underscores VIR-5500's potential as a best-in-class T cell engager for the treatment of prostate cancer. The totality of the data we've shown you today has enabled us to select a preliminary dose to take forward in the late-line mCRPC expansion cohorts. Importantly, we do not plan to use prophylactic steroids or anti-IL-6 agents with this dose.

With Q-week and Q3-week dose escalation complete, our program is now positioned to transition into expansion cohorts. Our initial focus areas include late-line mCRPC monotherapy, first-line mCRPC in combination and metastatic hormone-sensitive prostate cancer in combination. We expect to initiate these dose expansion cohorts in the second quarter of 2026.

We plan to continue dose optimization in parallel to address the goals set out by the FDA Oncology Center of Excellence's Project Optimus and support advancement into Phase III development in 2027. These next steps reflect our confidence in VIR-5500's clinical profile and the strength of the collaboration with Astellas, which enables broad and accelerated development across all disease stages.

Now I will turn the call over to Jason.

Thank you, Mark. Let me first summarize the economic structure of the Astellas collaboration. In the U.S., we will co-develop and co-commercialize VIR-5500 under a 50-50 profit sharing arrangement with Vir Bio retaining the option to co-promote alongside Astellas. Outside the U.S., Astellas will hold exclusive commercial rights and Vir Bio will receive milestones and tiered double-digit royalties on net sales. Global clinical development costs are shared 40% by Vir Bio and 60% by Astellas. Expenses related to U.S. specific studies will be shared by Vir Bio and Astellas 50-50, while Astellas will cover 100% of any expenses related to ex U.S. specific studies. We will receive combined upfront and near-term payments of $335 million, excluding certain payments to Sanofi. That amount includes a $315 million upfront, comprised of $240 million in cash and $75 million as equity investment. The $75 million equity investment is priced at $10.36 per share, a 50% premium to Vir Bio's 30-day volume weighted average price as of February 17, 2026. Further, we are entitled to a $20 million manufacturing tech transfer milestone expected by mid-2027.

The collaboration includes up to an additional $1.37 billion in development, regulatory and ex-U.S. commercial milestones. The total potential in combined upfront and milestone payments, excluding certain payments due to third parties, is $1.7 billion. Closing of the Astellas collaboration is subject to the expiration or termination of the applicable Hart-Scott-Rodino Act waiting period. We are pleased with the terms of the agreement and see Astellas as the partner of choice in prostate cancer. The agreement offers a capital-efficient structure that derisks our development spend while potentially expanding the number of patients who may have access to VIR-5500.

Moving now to our year-end results. We are pleased to report that our multiyear focus on financial discipline and prioritization has led to continued improvements in performance. Let me highlight a few key financial metrics for 2025 compared to 2024. R&D expenses for 2025 were $456 million compared to $507 million in 2024, a $51 million or 10% reduction. SG&A expenses decreased to $92 million in 2025 from $119 million in the prior year. This represents a 23% decrease in SG&A spend compared to 2024. This net reduction was primarily achieved through previously announced cost-saving initiatives. Our net loss for 2025 was $438 million compared to $522 million in 2024.

Turning to cash. Our 2025 net change in cash and investments was approximately $314 million. This amount includes a $64.3 million initial cost reimbursement payment received from Norgine in December. We're starting 2026 with a strong financial position of approximately $782 million in cash, cash equivalents and investments, not including the upfront cash and equity we will receive through the Astellas collaboration. Based on our current operating plan and including the net effects of the Norgine and Astellas agreements, we anticipate cash runway extending into the second quarter of 2028, enabling multiple value-creating milestones across our pipeline.

I will now turn the call back to Marianne to provide the closing remarks.

Thank you, Jason. Today's announcements mark major progress towards our goal of building a world-class cancer immunotherapy program, the vision we set out for our company just 18 months ago. We believe the data we have shared today for VIR-5500 validates the potential of the PRO-XTEN platform, enabling more rapid advancement of our pipeline of differentiated T cell engagers, and positioning Vir Bio to be a leader in immuno-oncology.

We have a lot to look forward to across our pipeline. Our HER2 and EGFR programs use the same dual masking architecture and benefit from shared learnings. We plan to share Phase I dose escalation data from our HER2 program in the second half of this year. The PRO-XTEN's platform plug-and-play design also lets us rapidly engineer new masked T-cell engagers for high-value solid tumor targets, creating a sustainable pipeline of differentiated therapies. We have thus far developed 7 preclinical programs and will progress to development candidate selection by early 2027.

As we conclude today's presentation, I want to return to what fuels everything we do at Vir Bio, transforming patients' lives, especially people living with devastating diseases who are vastly underserved by current treatment options. The partnership with Astellas will not only allow for swift advancement of VIR-5500, but also positions us well for more rapid pipeline expansion. All this gives us further flexibility to consider how we develop our pipeline assets and continue to unlock earlier value for patients and our shareholders alike.

And importantly, by combining Vir Bio's potential best-in-class T cell engager with Astellas' global capabilities, we will bring complementary strengths to one of the biggest unmet needs in oncology. Together, we can move faster and maximize the potential impact of VIR-5500 for people living with prostate cancer.

I would like to close by sincerely thanking the patients, their families and the investigators who have supported the development of this program. With that, I'll turn the call back over to Kiki to begin the Q&A session.

Thank you, Marianne. This concludes our prepared remarks, and we will now start the Q&A section. Joining me for the Q&A are Marianne, Mark and Jason. Please limit questions to 2 per person so we can get through all of our covering analysts. I'll now turn it over to you, operator.

[Operator Instructions] Your first question comes from the line of Paul Choi with Goldman Sachs.

Congratulations on the data as well as the deal. Two questions for us, please. First, either for Marianne or Mark. Can you maybe comment on the range of PSA responses you've seen by prior line of therapies, particularly with regard to prior radiotherapy. Any details there would be helpful, both on the PSA50s and PSA90s.

And my second question is, how do you think your data today potentially reflects on the probability of success for your other T-cell engager programs? And just what is your level of confidence that we can make a reasonable inference of higher probabilities of success for your other programs?

Thank you, Paul. Really appreciate it. I'll start with answering your second question and then turn it over to Mark. So we really believe that the data we have showed you today validates our dual masking steric hindrance approach, so really the PRO-XTEN masking. You've seen that the lower systemic immune activation is reflected in limited CRS toxicity, very low incidence of high-grade treatment-related AEs and very limited number of PSMA target-related AEs, again, all very low grade. Also, you saw that we can reach now a wider therapeutic window. So we are able because of the mask to dose higher and less frequently. So we have actually selected a preference for every 3-week dosing. And then thirdly, you have seen that there's great concordance between PSA responses, RECIST responses, PSMA PET responses, which all show great on-tumor engagement. So we think this all bodes really well for our other programs. Of course, every program is unique, but we have, I think, really here shown a validation for the technology.

As to your question of range of PSA responses, especially with patients that have been exposed to prior radioligand therapy, Mark, can you...

Sure. Yes. Very good question, Paul. So first of all, we have a very heavily pretreated population with a median of 4 prior lines of therapy. The vast majority of patients have received taxanes. So we -- and we do think we have very strong PSA responses, particularly as we get into the 3,000 microgram per kilogram doses and above.

I'd direct you to Case # 4, the one that was presented by Dr. de Bono. This patient had received radioligand treatment, an actinium conjugated agent, PSMA-targeted agent. That patient had a PSA99 response and a complete response in the target lesions. And that patient also had evidence of -- in the lymph node of PSMA decline in terms of expression and T cell abundance in the lymph node 5 weeks after treatment. So we don't have a lot of data yet in the post-RLT setting. We are continuing to look at those patients, of course. But at least in this one patient post-RLT, very, very promising results in this individual.

In terms of other prior lines of therapy, it's difficult to say because the patients were just generally very heavily pretreated. So we haven't been able to disambiguate any specific effects of prior line of treatment on PSA responses, but they do appear to be strong across the board, particularly when we get to the higher doses.

Yes. I mean the only thing I would add is we have 2 patients that were exposed prior to the steep TCE, so we have annotated those on the slides, if you would want to go and have a look.

Your next question comes from the line of Cory Kasimov with Evercore ISI.

This is Josh Chazaro on for Cory. Congrats on all the progress. And clearly, you guys have been busy executing here. And question here is, can you give us a little bit more color on what the next steps are before you and Astellas move to Phase III? And are there plans for you and Astellas to explore additional dosing schemes beyond the Q3 week?

Yes. Thank you for that question. Is it Josh? Yes, Josh, thank you for the question. Mark, do you want to take that?

Absolutely. So yes, we're very excited about the partnership with Astellas, and we're also very excited about the next steps of the program. So we do plan to get into -- we've selected a go-forward dose. We plan to get into expansion cohorts in Q2, very shortly in this year. We will be having late-line mCRPC, which is the population here as a monotherapy. We'll have a combination with enzalutamide in the early line taxane-naive setting. And we also will be doing some dose optimization in parallel to satisfy the goals of the Project Optimus to satisfy the FDA's requirements there. So we will be working with Astellas. And I should also mention the combination of metastatic hormone-sensitive prostate cancer and expansion cohort. So taken together with the expansion cohorts, with the dose optimization work, we expect to get into Phase III in 2027 and to be well positioned now.

Yes. This was exactly why we were so excited about entering into the partnership with Astellas. It allows us to accelerate the clinical development and also really broaden the potential and expanding the trials to reach more patients.

Your next question comes from the line of Roanna Ruiz with Leerink Partners.

So 2 questions from me. On the Astellas collaboration, I'm just curious, how are you thinking about unlocking resources for investing into the broader PRO-XTEN platform and thinking about other solid tumor indications? And what sort of calculus will you do in terms of thinking about prioritizing certain programs over accelerating others?

And my second question with the larger cohort of patients evaluated on VIR-5500, how does this evolve your thinking about where VIR-5500 could be positioned within the sort of treatment paradigm in terms of line of therapy, combination versus monotherapy and thinking of the future?

Yes. Thank you, Roanna. Yes, as it relates to resourcing, obviously, teaming up with a world-class player in the prostate cancer field and Astellas has entirely internal development capabilities, that will help us tremendously in again, accelerating the VIR-5500 program. From a finance perspective, also it allows us to divert certain expenses to other programs and potentially accelerate those as well. So we think that the collaboration certainly has a lot of benefits beyond just for VIR-5500 alone. As to where to position VIR-5500, do you want to...

Sure, absolutely. So yes, so we are very excited about the progress we've made so far and the data that we've presented to you today. And we plan to really be able to address a broad range of patients with metastatic prostate cancer, including late-line mCRPC and a monotherapy. And these are the data we presented you today, a more early line mCRPC in combination. And as you recall, we've been dose escalating in combination with enzalutamide in the frontline taxane-naive setting already, and that's going well. And then in addition, in metastatic hormone-sensitive prostate cancer in combination. So we really are very excited to continue to progress the program. And these are certainly 3 high unmet need populations within the metastatic prostate cancer setting that we think we can address.

Your next question comes from the line of Mike Ulz with Morgan Stanley.

Congratulations on the data and the deal as well. Maybe just one on VIR-5500 and durability. I guess, maybe just talk about your level of confidence there that some of this very strong early data that you're seeing can be sustained over a longer term.

Yes, absolutely. So we are very encouraged by the RECIST responses that we've seen, particularly those that have occurred up to 27 weeks and the fact that we're able to confirm RECIST responses in patients. We're also seeing a concordance of RECIST responses with PSMA PET responses and deep PSA responses, which we also think is further evidence of the efficacy we can achieve. Also the case studies that Dr. de Bono presented to illustrate patients with up to 1 year of durability, which represents the potential, I think, of VIR-5500. So taken together, we're really pleased with the emerging evidence of durability in the program.

Yes. Makes sense. And maybe just one more question for me. Obviously, you're presenting the data at ASCO-GU later this week. Just curious if the data you shared with us today is the same that will be presented at the meeting? Or are there any additional updates or data points we should be looking out for?

Yes. The oral presentation at ASCO-GU this Thursday by Dr. de Bono, I mean, these oral presentations are rather short. So there won't be additional data, but it will be a subset of this data.

Your next question comes from the line of Phil Nadeau with TD Cowen.

Congratulations on the data and the Astellas collaboration. Two from us. First, in terms of the go-forward dose, could you give us more information on what that dose is? And I guess, in particular, was there a dose response in those doses above 3,000 microgram per kilogram Q3W? Or how did you identify that go-forward dose? And then second, just a clarifying question. It sounds like there's no Grade 3 CRS in doses above 3,000. Was there any below? It didn't seem to be from one of the slides, but we just want to make sure we saw that correctly.

Thanks for the question. So in terms of the go-forward dose, we've done a lot of work on that, integrating safety, the efficacy, PSA, PSMA PET, RECIST responses and so forth. And we have selected a go-forward dose. As you can appreciate, we have now a partner Astellas, which we're thrilled to have on board. And so we're not going to be communicating the exact dose today because that's something that involves both of us in the partnership. But I can tell you, we'll be in the 3,000, 3,500 maintenance dose range.

In terms of dose response above -- at or above 3,000, I mean, you can see clearly, we showed you all the data for all the doses tested for PSA responses. I think you can see there's a compelling dose response across all of those doses. Once we get above 3,000, there still is some dose response, but primarily, we're in a range where we're seeing very, very strong efficacy and a very strong therapeutic index. So we feel confident that we've identified a go-forward dose that really optimizes the therapeutic index moving forward.

In terms of Grade 3 CRS above 3,000 mg per kilo in the go-forward dose range, we've seen no Grade 3 CRS. We did observe one Grade 3 CRS in an earlier dose cohort in a low-dose patient who had intra-patient dose escalation and had one episode of Grade 3 CRS that recovered rapidly and the patient did very well.

Your next question comes from the line of Etzer Darout with Barclays.

Congrats on this data set. Really nice to see. Just one question I had on the go-forward dose. Just wondering if in the combination study that you've initiated if new patients would be enrolled at these effective doses of greater than 300 micrograms per kilogram. And then also, is there an opportunity with this data in hand to maybe convert to a flat dose versus a weight-based dose in these patients and whether you see this as a potential opportunity moving forward for the molecule?

Yes. Thanks. Good question. So in terms of the go-forward dose in combination with enzalutamide, I mean, we anticipate that the dose should be consistent in the 2 populations. We are doing a -- we're almost complete with the dose escalation in combo with enzalutamide frontline mCRPC, just to confirm that there's no issues there, but we do anticipate should be very similar or the same. In terms of flat dose, right now, we do not have plans for a flat dose. I mean it would be possible in theory, but we're still using the microgram per kilogram dose.

Your next question comes from the line of Joseph Stringer with Needham & Company.

Just a follow-up on the deal with Astellas for VIR-5500. What might this mean for the rest of the oncology pipeline? Is there an opportunity for some of these programs to be stand-alone for Vir? Or do you see the long-term strategy here to seek partners or to partner these programs? And then a question for Dr. de Bono, just based on these updated data, what are the read-throughs in your outlook? And where do you see potential for VIR-5500 in earlier lines of mCRPC therapy?

Thank you, Joey. Yes. So the Astellas deal, again, was a very strategic choice based on the fact that first of all, the unmet need in prostate cancer is incredibly high. The landscape is evolving very quickly. We thought that time to market is most important. So we really were looking for a global partner with scale and with aligned incentives that would help us accelerate the program. And also, as I mentioned earlier, really allow us to really grow the pie, so to speak, and see how much value -- how much more value could we bring to a broader subset of patients. And that's everything that Astellas collaboration really delivers while we can retain a significant portion of the value through the 50-50 profit split, the milestones and the ex U.S. royalties and so on.

For the rest of our pipeline, we are going to be very strategic and thoughtful in a similar vein. A lot depends again on the competitive landscape on the size of the commercial opportunity and the indications about the financial need to bring these indications forward. So we will be making very thoughtful choices on what to partner, how to partner, what to keep for ourselves 100%. Also just to remind you that we have 7 preclinical masked T cell engagers. And for sure, on the preclinical programs, this is just too much for us to move forward on our own. We will certainly be looking for partners there. And because of the plug-and-play nature of the platform, again, it allows us to move actually pretty quickly in preclinical research. So you will be seeing that we will be looking for partners in some of those areas.

Your second question was related to read-through. Okay. Dr. de Bono is not available here during the Q&A. But Mark, do you want to take that?

Sure. So your question was about the potential in earlier lines of metastatic prostate cancer. So yes, we definitely believe there is potential there. We are planning first-line taxane naive metastatic castration-resistant prostate cancer as an expansion cohort in addition to metastatic hormone-sensitive prostate cancer. So we are really looking across the metastatic prostate cancer landscape to help these patients who really need better treatments.

Your next question comes from the line of Patrick Trucchio with H.C. Wainwright.

Congrats on the data and the deal. I guess just a follow-up on the Astellas deal with Vir having an option in the U.S. to co-promote, what would that look like? And at what point in the development process would you be able to exercise that option?

Okay. Thank you, Patrick. Yes, so we have an option to co-promote alongside Astellas in the U.S. And up to a year before the start of our pivotal trials, we will be able to make that decision.

Great. And then if I could, just a follow-up question for Dr. de Bono. I'm just wondering, just based on the data that you've seen so far, how confident are you that this treatment could potentially move into frontline? And what would you need to see in order to give you that confidence?

Thank you, Patrick. So unfortunately, Dr. de Bono is -- [ given time ] so it's not available for this Q&A. He will be at the ASCO-GU this Thursday. But maybe, Mark, do you want to...

Yes. So yes, I encourage everybody who can to attend this talk or to understand his perspective there. But for sure, we see potential across the metastatic prostate cancer landscape. We have generated, we think, compelling early data in the late-line mCRPC setting. We're currently enrolling patients in dose escalation in the frontline taxane naive mCRPC setting. We would anticipate based on what we've seen to date that we should have an effective drug in that population potentially. They do have lower disease burden overall, and we think our mass TCE approach should work, and we will be generating those data. And as I mentioned before, we are also going to be looking at the metastatic hormone-sensitive prostate cancer setting as well. So that gives you kind of an idea of where we're heading.

Your next question comes from the line of Sean McCutcheon with Raymond James.

Congrats on the strong data. A couple from us. Given the seeming lack of strong dose response on CRS and lack of DLTs, how are you thinking about the limit on the higher end of the range of dose escalation, whether that's saturating on enzymatic activity or otherwise? And second question, how are you guys thinking about the partnership with Astellas and optionality for combining VIR-5500 with other ARPIs beyond enzalutamide?

Thank you, Sean. I will take your second question. Obviously, in partnership with Astellas, we will be determining our future combination strategy, which, of course, could be broader than just the ARPIs, but that will be something that we will need to inform you about at a later time point. Your first question -- what's related to the dose...

Yes. So you're asking about dose response for CRS and efficacy and what's the limit of the dose on the high end. So a couple of points there. I mean our whole goal has been to maximize and optimize the therapeutic window to get the best possible safety with the minimum possible adverse events and CRS. So we've taken a careful look across the data set on all the efficacy parameters and safety parameters, including PSA, including RECIST, PSMA PET, all the safety events, CRS, et cetera. And we think we've gotten to a range in the 3,000 to 3,500 maintenance dose, and we have a specific dose there, which we can communicated in combination with our partner at a later date where we think we really optimize the therapeutic index and can move forward into expansion cohorts in Q2 of this year.

Your next question comes from the line of Alec Stranahan with Bank of America.

Congrats on the really clean update here. Maybe first, just following up on an earlier question regarding durability. I'd be interested to hear your thoughts on how we could correlate PSA declines with -- as maybe a leading indicator for what we could expect on PFS with longer follow-up and when you think you might be in the position to update the markets with that data?

And then second, in the 6 patients with the evaluable PSA but not RECIST, assuming these will feed into the overall PFS analysis, could you maybe talk about why we weren't -- those weren't available at baseline and what your prediction might have been in terms of response, given many of them have fairly deep PSA declines, maybe on disease control rate or something else?

So your first question has to do with durability and how do we think PSA declines will track with PFS, right? So in general, I would say that the deeper PSA declines, particularly PSA90s and PSA99s are associated with more durable responses. And we are very encouraged to see that we have some very deep PSA declines, PSA90s and PSA99s. In terms of radiographic PFS, I mean, you're correct, we did not present those data at this update because as you can see, the data, particularly for the high-dose cohorts is still evolving and the patients are still maturing over time. So those data really aren't available yet. And in terms of exactly when we'll present further data, I think that we'll just have to give guidance on that at a subsequent time point.

Could you clarify -- I wasn't quite sure I got the second question. Was that why were not some patients not PSA evaluable? Or what was the question?

Well, I think there was 6 patients that had a PSA like, out of the 17, 6 were not evaluable for RECIST. I guess, what was sort of the -- you couldn't get the scans at baseline. Was that kind of the driver there? And then I guess, what would you sort of expect in terms of PFS for those patients?

Yes. No, thanks for clarifying. I appreciate it. So yes, so in the 3,000 or above, we had 22 patients in the cohort. We had 17 patients who were PSA evaluable. Two of those patients are just early at the time of the clinical cutoff. So we will get those subsequent PSA values, they weren't part of the data set. So 2 out of 5 are early, then there's a coming. 3 out of the 5 discontinued early. So we will not have -- they won't be PSA valuable. And that's very typical for prostate cancer trials in the late-line setting. So these patients are quite sick with a very heavy disease burden. We have 11 patients who are RECIST evaluable. And among those, we had 5 responses, 4 were confirmed and 1 is still waiting for the next confirmatory scan between week 9 and week 18. So that one is coming in time.

This concludes the call. Thank you for participating.

Good afternoon, everyone. My name is Mary Liu, and I'm one of the associates on the healthcare investment banking team at JPMorgan. It's my pleasure to introduce our next presentation from Vir Biotechnology. I'm joined by the company's CEO, Marianne De Backer, who will give a presentation on the business followed by a Q&A session. Marianne, thank you very much for being here. And with that, I will turn it over to you.

Okay. Good afternoon, everyone, and thank you, Mary. Thank you, JPMorgan, for the opportunity to present Vir Biotechnology to you today and the swift progress that we are making across our pipeline in infectious disease and in oncology. The presentation includes forward-looking statements. So I refer you to our website where we have a notice regarding legal disclaimers and regulatory filings. Our mission at Vir Biotechnology is really all about harnessing the power of the human immune system to fight disease. And that could be an infectious disease or it could be cancer.

So we have a deep understanding of immunology since really our inception as a company. And what we are doing is enabling really innovative solutions to be developed across a series of very serious diseases. Our path is such that we sorry, our path is such that we are aiming to really deliver only transformational therapies and for unmet needs that are very, very serious. So we are aiming our powerful R&D engine that I will be talking about a little bit to changing not just some of the devastating diseases in infectious disease, but also trying to really aim to change the face of cancer treatment. Our strategy at Vir Biotechnology is really based on 3 pillars. The first is we believe we have a really compelling and superior Phase III candidate for chronic hepatitis delta.

So we see this as a significant opportunity for our company, both as a commercial opportunity in the U.S. and in other key regions. And our registrational program for hepatitis delta is well underway in setting the stage for a potential regulatory review already next year in 2027. So we expect this program to be a really major driver of near-term sustainability for the company.

Our second pillar is we are progressing a clinical stage lineup of dual-masked T-cell engagers. And this is aimed at solid tumors where patients currently have few options. And we believe that these programs could bring important new breakthroughs and add value over the next few years. In fact, we'll be sharing updated safety and efficacy data on VIR-5500, our PSMA targeting T-cell engager already in the first quarter of 2026. So a little bit more about that in just a moment.

Third, we are really putting our discovery engine to work and are developing a series of potential best-in-class preclinical pipeline of T-cell engagers and cancer immunotherapies. And that can really fuel the company's value in the long term. Underpinning these 3 pillars is our strategic approach to partnering. So we believe that if we selectively partner certain drug candidates that, that can really allow us as a company to maximize our resources and again, unlock more value of the pipeline. And we believe that collaborations also in certain areas can allow us to potentially move faster, but also to reach more patients. And then finally, importantly, we have the capital to advance our key programs across key value inflection points, and we can accomplish this in the next few quarters and years.

Next, I will be talking about our addressable market. So as I mentioned in the beginning, our clinical programs really address serious and hard-to-treat diseases that all are in need for new solutions. The numbers we're showing here reflect addressable patient populations in just the key territories. Starting on the left side with hepatitis delta, you can see that chronic hepatitis delta cases are rising likely because of increased awareness and also early diagnosis improving. And we estimate about 174,000 patients that are actively vireamic, again, in the key markets of Europe and United States.

Moving from the left to right here on the slide and then also switching to oncology for the PSMA-expressing tumors, castration-resistant prostate cancer represents about 100,000 patients. And our Phase I program potentially also allows us to pursue hormone-sensitive prostate cancer. If that were the case, then again, the addressable patient population increases to about 160,000 patients. Then moving to HER2. So HER2, we are really focused there on predominantly urothelial and colorectal cancers, where the estimated addressable population is about 38,000 patients.

And finally, on the right, for EGFR expressing tumors, our third clinical stage asset in the clinic. There we are really focused on non-small lung cancer, head and neck and colorectal cancers. And that is really a very significant addressable population of around 770,000 patients. So again, we're really focused on high unmet need of very serious diseases. I will start with focusing on our lead program now in hepatitis delta. We've just shared actually new data from our Phase II SOLSTIS trial study this week, and we put out a press release to highlight that. And our ECLIPSE program, again, our registrational program for hepatitis delta is well underway.

Maybe again, briefly talking about delta. It's a devastating liver disease. Options for treatment are limited. There is no treatment available for hepatitis delta currently in the United States. More than 50% of the people once they are diagnosed with hepatitis delta really progress to liver-related death within a period of 10 years. And a lot of them suffer actually from liver-related failure sooner. So they're also about 3x more likely to develop liver cancer compared to patients that are just infected with hepatitis B virus alone. Globally, there are about 7 million people living with this disease. And we believe this is a big opportunity for us to step up as leaders in this space and make a difference in this area.

Our combination regimen of tobevibart, which is a monoclonal antibody and elebsiran and siRNA is emerging as potentially best-in-class for hepatitis delta. It basically uses a two-pronged approach, 2 complementary mechanisms to fight the same virus, and it makes -- and that really allows it to stand out versus the rest. As mentioned before, hepatitis delta can really only exist if there's already hepatitis B. And tobevibart is a specialized antibody that really latches on to the hepatitis B surface antigen to prevent the entry of the delta virus into hepatocytes and neutralize the delta variants.

Elebsiran on the other side, as I mentioned, is an siRNA molecule that basically allows to limit the production of HBV surface antigen. And the regimen sort of dual and complementary mechanism of action is quite unique and allows us to really come up with a differentiated approach. The key differentiators for our combination regimen are the deep and increasing rates of undetectable HBV RNA over time. I'll be talking about that a little bit more, also monthly dosing and a very favorable safety profile.

Right now, our combination therapy is being tested both in a Phase II SOLSTIS trial as well as in our Phase III ECLIPSE clinical trials. In November, we shared impressive 48-week results at a major liver conference and published them as well in the New England Journal of Medicine. So this week, we provided updated data, positive updated 72-week data for all 65 patients in the Phase II trial, plus data for a subset of patients, 48 people, who've reached 96 weeks of treatment, showing ongoing improvements in patients getting our combination therapy versus those on monotherapy. And in this study, we are evaluating patients that are without and with cirrhosis and that got either, again, our combination therapy once a month or tobevibart alone, the antibody monotherapy twice a month.

So if you take away one data slide from today's presentation, this is the one. Hepatitis delta is a viral disease. It's caused by a small virus hepatitis delta. And it's all really for this disease about inhibiting viral replication. That's really key to improving clinical -- so a most stringent measure of suppression of viral replication is what we call HBV target not detected, which means that you can no longer amplify the virus -- PCR amplify the virus from the patient's blood.

So here, you see time points, 72 weeks and 96 weeks new data of our combination regimen where you can see that at 96 weeks, we achieved 88% of the patient's target not detected. So that is really unprecedented. And you see that for the monotherapy with an antibody alone, we achieved around 46%. So it really shows that a two-pronged approach of using a monoclonal antibody combined with an siRNA and really attacking the virus from 2 different directions allows you to reach these incredible antiviral efficacy results. Another important measure to look at is HBs antigen levels.

So the delta virus is actually a defective virus, and it depends on the hepatitis B virus surface antigen to replicate. And so lowering this antigen is critical to controlling the delta virus. That's why our combination therapy results are actually so impressive. As you can see here, about 90% of the patients on the combination regimen reached very low levels of HBV surface antigen that were less than 10 IUs per ml very quickly actually already after 24 weeks of treatment and stay really at that level over up until 96 weeks of treatment. You can see that the same is not true for an antibody monotherapy treatment. There, you can only reach about 20% of the patients that get this deep reduction of HBs antigen levels. And this is a really important consideration, again, for potentially in the future finite therapy and improvements in long-term clinical outcomes for patients.

So in summary, as you can see, the SOLSTIS results to date are extremely promising. They demonstrated that the monthly tobevibart plus electron combo could represent the best-in-class therapy for hepatitis delta. We're seeing clear and very substantial improvements in the combination therapy arm over time versus treatment with an antibody monotherapy alone. And in addition to the very high rates of delta RNA target not detected and reductions in serum HBV that I discussed, the combination therapy also demonstrated similar ALT normalization levels between cohorts at 48 weeks versus 17 weeks and all the way through 96 weeks.

Now the combination of tobevibart and elebsiran also continues to be very well tolerated with no grade 3 or higher treatment-related adverse events and treatment-related adverse events in general were very mild, moderate and transient. So we plan to submit the full 96-week data set at a future medical meeting. Now turning our attention to our registrational program. Patient enrollment has been very strong. We have actually completed enrollment already for ECLIPSE-1 and ECLIPSE-3, which sort of speaks to the real need for new treatments in this space. And we anticipate initial top line data already in the fourth quarter of this year with additional top line data for ECLIPSE-2 and ECLIPSE-3 in the first quarter of 2027.

We are also in discussions with the regulators to see if there's a potential faster path to market. And again, the results for our combination therapy that we have shown to date will be very helpful in that regard. Importantly also is that we have begun to unlock the value of our hepatitis delta program through a commercial license agreement with Norgine that we announced last month. Norgine is a top specialty pharmaceutical company in Europe. The transaction included an upfront of EUR 550 million in milestone payments.

And as you can see here, healthy royalties on sales. Norgine is also covering about 1/4 of our ECLIPSE program costs going forward. Importantly, we've retained all commercialization rights for the regimen in the U.S. and other markets outside of the Greater China territory, which we see as a big area of future growth. And this collaboration should really help us to roll out tobevibart and elebsiran faster in Europe, Australia and New Zealand. And we believe Norgine is actually the perfect partner to help us reach more patients faster in these territories.

Norgine has a lot of experience in the hepatology space, also a lot of experience in the rare disease space. So they were really an excellent strategic fit for this regimen. Now switching gears, let us turn our focus to our second strategic pillar and a unique portfolio of our T-cell engagers for cancer immunotherapy, where despite recent advances, there are many solid tumor indications where patients are vastly underserved and clinical outcomes do remain poor. We have an opportunity, we believe, with our platform and our assets to become a leader in cancer immunotherapy.

Very briefly about T-cell engagers in general. So you probably know T-cell engagers are a very powerful modality, and they basically turn the body's own T-cells into cancer fighters, and they've already shown major promise. There's 10 T-cell engagers already in the market, mostly for blood cancers. And while this modality holds tremendous potential, the broad applicability really in solid tumors has been held back by toxicity and especially the appearance of cytokine release syndrome and off-tumor activation in healthy tissue.

So our universal PRO-XTEN masking platform really addresses those shortcomings. It enables T-cell engagers to act as Trojan horses by shielding them and in effect, keeping them inactive while they are circulating in the patient's blood or they are in the patient's healthy tissue until they reach the tumor microenvironment. And the PRO X1 platform has been clinically validated via its use in an FDA-approved blockbuster drug, Altuviiio for the treatment of hemophilia A.

So we use a universal -- we use the same universal masks and CD3 binding domain across all of our programs. So if you look at our clinical programs, you look at our preclinical programs, this is really a plug-and-play platform, and we have observed the same high level of protection across all our programs. So this provides us confidence that the expanded therapeutics that we are aiming for and what we see with masking translates really from one program to another. This is really about a platform technology that we really can very broadly and that can be translated across programs. With the PRO-XTEN platform, our T-cell engagers are designed to maximize the therapeutic index by reducing dose-limiting toxicity and extending the drug half-life.

Very briefly about our platform. So the power of the Pro-XTEN platform really lies in the dual masking approach that binds the tumor on the one side and the T cell on the other side as depicted here in blue on the one hand and orange on the other. And this spaghetti-like shields that you see here serve as a steric hindrance and is made up of large hydrophilic polypeptides that elegantly mask the T-cell engagers. And again, they are shielding both the CD3 binding domain as the tumor-associated antigen binding domain and they only get cleaved off, the mas only get cleaved off once the masked T-cell engager reaches the tumor microenvironment. This is really the key differentiating factor. If you think about an unmasked T-cell engager, a single mask T-cell engager, this really allows again to have our T-cell engagers be very safe in the patient's blood in healthy tissues, but really only exerts its tumor killing effect in the tumor microenvironment.

Now switching to our programs. We have 3 programs that are using this platform in Phase I, and we have been working very rapidly to advance these. VR-5500 on the left side is the only dual masked PSMA-targeted T-cell engager in development. VIR-5500 is currently being evaluated in a Phase I study as both a monotherapy and in combination with androgen receptor pathway inhibitors in patients with metastatic castration-resistant prostate cancer. VR-5500 has demonstrated very favorable efficacy and favorable safety profile. We shared initial data at the onset of last year, and we showed low rates and low grades of cytokine release syndrome, even in the absence of prophylactic steroids. So the next steps in this program are to continue Q3 week monotherapy, dose escalation in mCRPC and also in first-line taxane naive mCRPC combination with XTANDI. So those trials are actively ongoing.

Our second target here in the middle is VIR-5818. It's the only masked HER2-targeted T-cell engager in development. It's being evaluated again as a monotherapy, but also in combination with KEYTRUDA in patients with advanced solid tumors. Earlier last year, we demonstrated with 5881, a 33% response and 100% biomarker response in Phase I dose escalation in metastatic colorectal cancer. And we've also observed at the time and shared with you 50% tumor shrinkage sort of across the board of a basket of HER2 tumors. These early signals of efficacy were accompanied by a very safety -- a very favorable safety profile, and we are continuing dose escalation in combination with KEYTRUDA, and we'll be evaluating next steps for dose expansion with this program.

And then finally, our third target, VIR-5525. It's a PRO-XTEN masked EGFR targeted T-cell engager. This has really the potential, as mentioned earlier, to unlock multiple high-value indications like non-small cell lung, head and neck and colorectal cancers. Phase I dose escalation study evaluating 5525 started in July of last year for monotherapy, and we're also now studying it in combination with KEYTRUDA, which kicked off in the third quarter of 2025. Very briefly, again, about FIR-5500. So we -- last year, we presented the initial data, the initial Phase I data showing, as mentioned, promising early signs of efficacy as well as safety. And the Phase I trial is looking at mCRPC patients who have exhausted really all other lines of therapies. These are very severe patients.

The images you see here on the right represent one case study that we shared with you before of a patient with a very high burden of disease, where a whole body MRI and PSMA PET scan showed very widespread and homogeneous changes indicating tumor cell death, exactly what we would like to see with our mechanism. And you saw this already by week 9. So that patient reported significant improvements in pain symptoms, and we saw rapid PSA declines, highlighting deep biochemical and physical responses to VIR-5500. In the broader data set at that time, we had 12 patients and all patients in the Phase I study experienced a measurable PSA decline, and we saw for all of them a very favorable safety profile.

These were early data, but they were very promising and especially for the heavily pretreated patients, as I mentioned, being evaluated in our trials. These were all still very low doses at the time. So the favorable CRS profile that we saw at that time really reflected very well our intent of our dual masking platform. Looking ahead, though, we will provide updated data from VIR-5500 at the upcoming ASCO GU here in San Francisco in February. And for the upcoming VIR-5500 update, we plan to present a really substantive data set on our monotherapy dose escalation trial.

So we will be sharing with you both weekly and Q3 weekly dosing in late-line monotherapy dose escalation. We will be sharing all our detailed safety data, including CRS, the treatment-related adverse events. When we shared the data initially at the beginning of last year, we were very -- we were still very early on, and we couldn't really show you dose response relationship. We will now be sharing much more information related to that. We will be sharing RECIST evaluations were evaluable and potential confirmations of RECIST over time. We will be sharing PSA responses with you, PSA 50, PSA 90s, longitudinal views of the PSA responses. So our data set in February is promising to be a very complete data set.

We will also be discussing with you next steps for the program. related to dose selection and planning for expansion cohorts in late-line mCRPC. Now switching to our third strategic pillar, diving a little deeper there. Vir Bio's discovery engine is truly exceptional. We have really combined antibody -- the ability to come up with unique antibody therapeutics and protein engineering with our PRO Xtend masking technology. And we really believe that sets us apart to build a very promising pipeline going forward.

So our discovery pipeline is really fueling the next generation of powerful medicines that we hope to bring to patients. So one, we have, as I mentioned, what we believe is world-class protein engineering capability, and that has been shown by -- we have 2 therapeutics that were discovered by scientists at Vir Bio that have gone all the way to market, Ebenga addressing Ebola infection and vud addressing COVID infection. And that capability for protein engineering has now become extremely handy as we are coming up with new T-cell engagers. Secondly, we have an antibody -- an AI engine that we are using for antibody and T-cell engager optimization.

And I have been really impressed by how quickly that leads us to new starting points for antibody and T-cell engager therapeutics. And then thirdly, we have, as I mentioned, our Pro X10 universal plug-and-play masking technology, which allows us to really go very, very quickly because we do not need to redesign the masking -- the mask for each molecule. We can really use exact same PRO X10 mask across all our preclinical programs. We are also building on our learnings and our legacy in infectious disease to deliver the next generation of cancer immunotherapies.

And again, the focus really is delivering superior therapeutic indices. It's these distinct capabilities altogether that have enabled us to develop a very powerful pipeline. As you can see here, it's a very differentiated pipeline. We believe our programs, both in infectious disease and in oncology will have a substantive impact on patients, and we have a pipeline that can deliver both in the near term with delta and also in the mid- to long term with our T-cell engager portfolio. In addition to the clinical programs that we have been discussing, we also have a burgeoning pipeline of 7 preclinical mass T-cell engagers.

And these are across a range of solid tumors across lung, colorectal and bladder. And we have opted there to really look for targets that are biologically derisked, but again, where T-cell engagers have not really been able to reach its potential because of potential toxicity and where our masking technology can really offer that clear differentiation.

These are our upcoming key milestones for this year and next year. So for hepatitis delta, we're well on track to report top line data, initial top line data for all 3 Phase III ECLIPSE studies starting in the fourth quarter of this year and then continuing in the first quarter of 2027. We will work, as I mentioned in the beginning, with regulators to rapidly file for marketing authorization with the goal of being prepared for commercial launch in the U.S. as soon as possible. For VR-5500, we look forward to reporting our Phase I data this quarter in February. For VIR-5518, we anticipate that we already have our full monotherapy data set, and we are still dose escalating in our combination with pembro.

So we estimate that we will have the full data set ready in the second half of this year. And for VIR-5525, we will provide information once we are a little bit further along in our dose escalation. So entering 2026, we are at a very important point for Vir Biotechnologies maturation as we execute on the vision and execute on our clinical stage pipeline.

Our hepatitis delta program, we really believe, is on a path to change the course of this debilitating disease and represent a significant revenue opportunity for us that we have started to begin to capitalize on through our ex-U.S. partnering strategy. And our pipeline of 3 clinical stage masked T-cell engager will offer value creation opportunities for the company as the data matures. Also, as mentioned, we believe that our Vir Bio drug discovery engine offers a lot of value -- a lot of potential for future value creation. We have worked also really hard to extend our cash runway. So we have now a cash runway into the fourth quarter of 2026 -- '27, and that is through both doing a strategic collaboration with Norgine, but also through disciplined resource deployment.

We expect that this runway until, again, the fourth quarter of 2027 will see us through major clinical inflection points, including preparation for the commercial launch of our hepatitis delta program. So by rapidly advancing on all of these priorities, we are developing opportunities to really transform clinical outcomes for patients and creating significant value for all of our stakeholders. Thank you very much, and I'm really looking forward to doing the Q&A, answering any questions you might have. Thank you.

Great. Thanks very much. We will open the floor to questions.

So on the [indiscernible] stage, I have 2 question, the first is, which is the PSA reading [indiscernible] and then the second question if you want me to do it, [indiscernible] And then do you guys have a ...

Right. So first question was related to what do we think matters most PSA 50s vs PSA 90s? We're still learning a lot in the T-cell engager space. There's certainly some trend to seeing that PSA 90 is better correlate with durability over time, but time will tell. Also, obviously, PSA responses are not recognized as a regulatory endpoint as a reason for that, right? So if it was a perfect sort of biomarker, that would be the case.

So I think we're still learning a lot, but obviously, it's a very easy to measure biomarker, and it does tell you a lot. And in combination with all the other things you're measuring, you're looking at RECIST, et cetera, it gives you a good perspective on whether you have a drug or not. Your second question was related to whether we are using prophylactic steroids. Is that correct?

Or managing CRS...

Or managing, right. Yes. So I can only speak to the to where we were when we last presented data at that moment in time, we did not use any prophylactic steroids, not any prophylactic IL-6. There was an opportunity for physicians when they saw CRS to potentially manage it in the way that they saw fit, but it wasn't really part of our protocol.

So as your mask engager data coming out, are you seeing any hint of immunogenicity there?

Sorry, could you repeat that question?

Are you seeing any hint of immunogenicity on your -- the mask engager as the Phase I data started coming...

Yes, I cannot really comment on the data that we will be sharing. So I can only refer to the data that we shared before where you could see that the CRS profile was very, very manageable. And also, we didn't see any elevations of immunomarkers.

I was asking immunogenicity, not CRS.

Okay. Yes, we haven't really -- we don't really have that data yet.

Maria, nice to meet you here. I want to know does Vir has other investment of BV planning in the HBV function cure here at current stage?

So we have a very full plate, as you can see from our clinical pipeline. So we are not looking to bring in any additional opportunities in hepatitis B. So we are really focused on our -- obviously, our registrational program for delta, getting that to patients as quickly as possible and then progressing our immuno-oncology portfolio.

As Vir continues to progress its programs from clinical to full deployment, what has been more challenging to scale than you initially thought, the science, the manufacturing capability or the partnerships that are necessary to sort of have an impact at a population level?

Yes. So I must say that we had expected that bringing together the capabilities that were already at Vir in, again, coming up with really unique T-cell engagers, antibody therapeutics and masking would be synergistic. I must say I've been pleasantly surprised how fast that has integrated and how quickly we are actually building a pipeline of preclinical assets. So there, actually, the whole point is that we cannot progress. We can create a lot of value from our platform, but we cannot progress those on our own because we really have to focus our cash on our late-stage programs. So there, we're really looking to partner. That is going to be very important.

Certainly, scaling and manufacturing is always a topic. And luckily, we have inherited clinical stage assets that -- and we have not just inherited the assets, but also the people that have been with the assets from the onset and have deep CMC and manufacturing expertise related to it. So that has been -- when we took over these assets from Sanofi, we brought over about 50 people. And I don't think the scaling and the speed would have been possible if we hadn't done that.

So we have the people who know the platform. We have the people who have been with the assets in the clinic from the beginning. We have the people who have the deep CMC and manufacturing capability. And so that has really helped. But certainly, there has been a lot of focus on the manufacturing piece because, again, once we have success, there's going to be a significant need to scale.

Some competitors have put out what I think the market would call disappointing data in the past. What do you think are the key shortcomings that are addressed by 5500 relative to what we've seen with some of the other TCs, [ NAC ] TCs specifically?

Yes. So what is really unique about VIR-5500 and again, any asset that we would have that is using our Pro-XTEN platform is that it's dual masked. And so we believe that the dual masking really allows us to reach a better therapeutic index. So better efficacy associated with more acceptable safety. That's really the whole aim of our platform.

And we believe that, again, non-masked T-cell engagers such as the KLK2 shows great safety with high levels of steroids, but not so great efficacy data perhaps. And then you have unmasked T-cell engagers such as the [ STEEP ] where you see maybe great efficacy data, but associated with quite a bit of toxicity. So we really believe there's an opportunity to come up with a T-cell engager for prostate cancer where you can have a most optimized therapeutic index.

I have a follow-up question to that, if that's okay. Where do you think VIR-5500 could best fit into the mCRPC treatment paradigm?

Yes. Of course, everything will be data-driven, but we are, of course, investigating it in late-line metastatic mCRPC. We are also investigating it in combination with enzalutamide first line in taxane-naive patients. And as I mentioned earlier, our Phase I also allows us to potentially explore the asset in hormone-sensitive prostate cancer patients. So we really don't want to sort of pigeonhole us in any given area at this moment in time. It will be guided by the data. And we also realize that the speed is of the essence actually in this space.

In February, most of the patients have already -- In the updated data in February, will most of the patients already have seen a taxane? Or will you have any taxane naive patients?

Yes. So our monotherapy trial in late-line patients, again, these are very heavily pretreated patients. They have mostly exhausted all prior lines of therapy. So most of them have seen -- most of all have seen taxanes.

Great. Well, thank you so much again, Marianne.

My pleasure. Thank you.

Thanks, everyone, for joining.

Hello, and welcome to Vir Biotechnology's Third Quarter 2025 Financial Results and Corporate Update Call. As a reminder, this conference call is being recorded. [Operator Instructions]

I will now turn the call over to Jason O'Byrne, Chief Financial Officer. Please go ahead.

Thank you, and good afternoon. With me today are Dr. Marianne De Backer, our Chief Executive Officer; and Dr. Mark Eisner, our Chief Medical Officer.

Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q and 8-K.

I will now turn the call over to our CEO, Marianne De Backer. Please go ahead.

Good afternoon, everyone, and thank you for joining us for Vir Biotechnology's third quarter 2025 earnings call.

Today's call will highlight the significant progress we've made and our clear path forward as an organization. We'll provide guidance on our VIR-5500 program time line, discuss the upcoming SOLSTICE data presentation and highlight how our clinical execution this quarter positions us for the significant value-creating opportunities ahead. The third quarter has been marked by important achievements across both our hepatitis delta and T-cell engager programs that demonstrate our ability to execute on critical milestones. Our team remains committed to powering the immune system to transform patients' lives. And today, we'll outline how our recent accomplishments set the stage for what we believe will be a pivotal period for Vir Bio.

I will now highlight the key accomplishments from this quarter that demonstrate this accelerating momentum. First, we completed enrollment in ECLIPSE 1, our first registrational Phase III study for hepatitis delta. Second, we're excited to provide guidance that we plan to share a comprehensive data update for VIR-5500, our PRO-XTEN masked PSMA-targeted T-cell engager in the first quarter of 2026. And third, we dosed the first patient in our first-line metastatic castration-resistant prostate cancer combination study with androgen receptor pathway inhibitors. Collectively, these achievements represent an acceleration in our development trajectory and provide clear line of sight to multiple value-creating catalysts ahead. We're executing with precision while advancing towards multiple important data readouts and regulatory milestones.

I will now provide more detail on our hepatitis delta program, where we've made exceptional progress this quarter. The completion of ECLIPSE 1 enrollment represents a pivotal step towards bringing our differentiated combination regimen to patients with hepatitis delta in United States and beyond. This achievement accomplished ahead of our internal projections reflects both strong investigator confidence and the substantial unmet medical need in this devastating disease. With ECLIPSE 1 enrollment complete, we now expect primary completion in the fourth quarter of 2026, with top line data for all 3 ECLIPSE studies expected by the first quarter of 2027. This accelerated time line positions us well for regulatory submissions and demonstrates our operational excellence in executing registrational studies.

ECLIPSE 2 continues to enroll well across European sites and remains on track. Together, ECLIPSE 1 and ECLIPSE 2 are designed to form the backbone of our regulatory filing package. ECLIPSE 3, our Phase IIb head-to-head comparison against bulevirtide is progressing ahead of schedule with strong enrollment momentum and will provide valuable comparative data to support access and reimbursement discussions, particularly in European markets. The hepatitis delta market represents a compelling commercial opportunity with approximately 61,000 RNA-positive patients in the United States and 113,000 in EU markets. The patient population's geographic concentration, particularly in major U.S. urban centers, supports an efficient commercial approach with a target specialty sales organization focused on hepatologists and infectious disease specialists.

Looking ahead to this month, we are preparing to present the complete 48-week SOLSTICE data set at AASLD on November 9. This presentation will provide important insights into the safety and efficacy profile of our combination regimen and is expected to provide supportive data that reinforces confidence in our registrational program.

Turning to our oncology portfolio. We are excited to provide guidance that we plan to share a data update for VIR-5500, our PSMA-targeted T-cell engager in the first quarter of 2026. We've made substantial progress in our dose escalation across both weekly and every 3-week schedules, and this data set is expected to provide important insights into the program's potential. We are enthusiastic about this program and the differentiated PRO-XTEN dual-masking approach. As I mentioned, we recently dosed the first patient in our first-line metastatic castration-resistant prostate cancer combination study with ARPIs, a first step towards addressing a significant unmet need for patients in earlier treatment lines.

For VIR-5818, our PRO-XTEN masked HER2-targeted T-cell engager, we are continuing dose escalation in combination with pembrolizumab, which is actively enrolling. For VIR-5525, our PRO-XTEN masked EGFR-targeted T-cell engager, our program continues to advance with enrollment in our Phase I study progressing as expected. We are leveraging the extensive learnings from both VIR-5818 and VIR-5500 to enable efficient development and accelerate decision-making.

The clinical experience we are gaining across 3 distinct targets, PSMA, HER2 and EGFR is building evidence for the versatility of the PRO-XTEN universal masking platform. This emerging clinical validation gives us confidence as we advance our preclinical pipeline of additional T-cell engager candidates targeting various tumor-associated antigens, whether through internal development or strategic partnerships that leverage our platform technology.

Finally, we ended the third quarter with approximately $810.7 million in cash, cash equivalents and investments. Based on our current operating plan, we continue to project our cash runway extending into mid-2027. This strong financial foundation enables us to advance our registrational hepatitis delta program and our oncology pipeline with confidence.

With that, I'll now turn the call over to Mark to provide a more detailed update on our clinical development programs.

Thank you, Marianne. I'm pleased to provide detailed updates on our clinical development programs. Starting with our hepatitis delta program, ECLIPSE 1 enrollment was successfully completed with approximately 120 participants randomized 2:1 to our combination therapy versus deferred treatment. This achievement was accomplished approximately 2 months ahead of our aggressive internal enrollment assumptions, demonstrating exceptional execution by our study teams and reflecting the significant unmet medical need in this patient population. The strength of our enrollment reflects multiple factors.

First, the robust SOLSTICE Phase II study results, second, strong engagement with our clinical investigator community, third, the absence of FDA-approved treatments for hepatitis delta in the United States and limited options globally, and fourth, the urgent need for more effective and convenient therapies for this devastating disease. Study team engagement throughout startup led to accelerated country and site activation, allowing us to complete study enrollment faster than originally projected. This was further reinforced by consistent enrollment momentum across regions with investigators actively identifying and referring patients.

ECLIPSE 2 continues with enrollment progressing well across multiple European sites, demonstrating similar investigator enthusiasm and patient need. The study will enroll approximately 150 patients randomized 2:1, evaluating the switch to our combination therapy in patients who have not adequately responded to bulevirtide with a 24-week primary endpoint of HDV RNA target not detected. The strong enrollment momentum we're seeing reflects an important unmet need for inadequate bulevirtide responders, and we expect primary completion by year-end 2026 with top line data expected in the first quarter of 2027. ECLIPSE 3, our Phase IIb head-to-head comparison is progressing ahead of schedule with strong enrollment momentum. This study will enroll approximately 100 patients comparing our combination therapy to bulevirtide in treatment-naive patients and based on the strength of enrollment we're seeing is tracking toward a similar completion time line as ECLIPSE 1 and 2. ECLIPSE 3 enrollment has progressed ahead of our projections, and this study will provide critical comparative data for access and reimbursement discussions with top line data expected in the first quarter of 2027 alongside the other ECLIPSE studies.

Regarding our upcoming AASLD presentation, the complete SOLSTICE 48-week data set for the combination regimen of tobevibart and elebsiran represents an important clinical milestone. This additional follow-up provides important safety and efficacy insights and builds on our previously reported compelling Phase II results that demonstrated 64% of patients achieving HDV RNA target not detected at week 36 with our monthly combination regimen.

Turning to our oncology programs. We continue to advance our PRO-XTEN masked T-cell engager portfolio across multiple targets. For VIR-5500, our masked PSMA-targeted T-cell engager, dose escalation is advancing in both weekly and every 3-week schedules. We have not reached a maximum tolerated dose and escalation continues as planned. The half-life of 8 to 10 days potentially supports our every 3-week dosing evaluation with the potential for even longer dosing intervals. As Marianne mentioned, we achieved an important milestone this quarter with the first patient dosed in our first-line metastatic castration-resistant prostate cancer combination study with androgen receptor pathway inhibitors.

This earlier line expansion offers the potential to address significant unmet need for patients earlier in their treatment journey. We're planning for a comprehensive data update in the first quarter of 2026 with a meaningful data set across dose levels in late-line patients. We expect this will include safety assessments and efficacy measures, including PSA responses and kinetics, imaging and RECIST evaluations. The program is designed to leverage the potential advantages of the PRO-XTEN platform, including a favorable safety profile and extended half-life. Our approach seeks to maximize the therapeutic index of solid tumor T-cell engagers through selective tumor activation while minimizing systemic activity.

For VIR-5818, our HER2-targeted T-cell engager, combination dose escalation with pembrolizumab is actively enrolling and progressing according to plan. For VIR-5525, our EGFR-targeted T-cell engager, Phase I study enrollment is also progressing as expected. The study design incorporates learnings from VIR-5818 and VIR-5500 to enable efficient dose escalation. We are evaluating both monotherapy and combination with pembrolizumab across multiple EGFR-expressing tumor types. As we've discussed on our second quarter call, we believe this program has the potential to address significant unmet need for patients across multiple solid tumor types where current EGFR-targeted approaches have important limitations.

We also continue to advance multiple preclinical T-cell engager candidates targeting various tumor-associated antigens. The clinical experience from our current programs is informing the development of these preclinical candidates, and we're taking a strategic approach that combines internal advancement with potential partnership opportunities to accelerate development and advance a broader pipeline that addresses unmet need across multiple cancer types. We've made exceptional progress across our entire clinical portfolio during the third quarter.

ECLIPSE 1 enrollment completion provides a clear path to pivotal data in early 2027 for all 3 ECLIPSE studies. Our upcoming VIR-5500 data update will provide important insights into our oncology pipeline's potential and our platform leaves us well positioned to efficiently advance multiple future candidates.

With that, I'll now hand the call over to Jason for a financial update.

Thank you, Mark. I am pleased to share our third quarter financial performance and overall financial position. R&D expense for the third quarter of 2025 was $151.5 million, which included $5.5 million of noncash stock-based compensation and a $75 million milestone payment triggered by first-in-human dosing of VIR-5525. This compares to $195.2 million for the same period in 2024, which included $8.9 million of stock-based compensation and a $102.8 million upfront payment made to Sanofi at the closing of our exclusive worldwide license agreement.

The year-over-year decrease was primarily driven by lower license expense and cost savings from previously announced restructuring initiatives, partially offset by increased clinical development expenses associated with our hepatitis delta and oncology programs. SG&A expense for the third quarter of 2025 was $22.2 million, which included $5.8 million of stock-based compensation expense compared to $25.7 million for the same period in 2024, which included $7.8 million of stock-based compensation expense.

The decrease was largely due to efficiencies and cost savings from previously announced restructuring initiatives. Our third quarter 2025 operating expenses totaled $173.7 million, representing a $46.2 million decrease from the same period in 2024. Net loss for the third quarter of 2025 was $163.1 million compared to a net loss of $213.7 million for the same period last year.

Turning to cash. Our net change in cash and investments in the third quarter was approximately $81.4 million. During the third quarter, we also made certain cash payments from restricted cash, including a $75 million payment to former Amunix shareholders. As described earlier, this payment was triggered by dosing the first patient in our VIR-5525 study and was fully anticipated, having been held in escrow as restricted cash since we signed the Sanofi agreement last year. As a reminder, restricted cash is excluded from our reported balances of cash, cash equivalents and investments.

As such, disbursements from restricted cash accounts do not affect our projected cash runway. We ended the third quarter with approximately $810.7 million in cash, cash equivalents and investments. Based on our current operating plan, we continue to project our cash runway extending into mid-2027. Our capital deployment strategy remains focused on our most promising programs. We are advancing our hepatitis delta ECLIPSE registrational program while also advancing our T-cell engager programs, including VIR-5500, VIR-5818 and VIR-5525. We continue to deploy capital strategically, prioritizing investments in programs with the greatest potential for both meaningful patient impact and value creation while also advancing business development opportunities that can further optimize our resource allocation.

This concludes our prepared remarks. We will now initiate the Q&A session. Please limit questions to 2 per person so that we can get to all of our covering analysts. I'll turn it over to you, operator.

[Operator Instructions] Our first question will come from the line of Gena Wang with Barclays.

This is Kun Wang on behalf of Gena Wang from Barclays. We have 2 questions. First one for the PSMA, the [ GenX ] actually setting a higher bar for the PSA 50. However, the durability doesn't seem good. So how do you think the PSMA could show actual differentiation of your asset? And then we know the KOLs we spoke to actually focus on durability of the PSA control and more importantly, durability, the durable tumor response. The second question actually for the HDV. For the Phase III readout, what's your clinical bar as the key differentiation?

Yes. Thank you for those questions. So maybe on PSMA, I will just start by saying that we're really excited to provide the guidance and share a comprehensive data update for our lead asset, VIR-5500 in the first quarter of 2026. And of course, at that point, we will have a really meaningful data set across multiple dose levels, obviously, in the late-line patient setting. We will have data on both weekly and every 3-week dosing. And there will be certainly sufficient patient numbers to provide robust insights. Maybe I'll ask Mark to add anything.

Sure. Thanks, Marianne. Well, we do think we have a differentiated approach with the PRO-XTEN platform and in particular for VIR-5500 PSMA. I'll comment on the fact that we use a steric hindrance mechanism for masking both the CD3 and the PSMA side of the molecule. We have a dual-masking approach, which is unique in the masked PSMA space. It's a clinically validated approach. There's a product on the market called ALTUVIIIO that uses the PRO-XTEN masks. So we know it's safe in that setting. And we think we can get to a really exceptional therapeutic index, which would include both depth and durability of PSA response.

But stay tuned for our Q1 update. Your other question is about HDV and the ECLIPSE program and what we think the bar is, particularly for ECLIPSE 1. Just to remind people, we showed in the SOLSTICE trial, 64% viral suppression target not detected at week 36, that was at week 36 that we presented back -- before, and we are going to be presenting the complete 48-week SOLSTICE Phase II data at AASLD very shortly. In terms of the bar, we think the combination of our tobevibart and elebsiran have exceptional ability to suppress HDV viral RNA and achieve target not detected. We can hit HB surface antigen down by 3 logs. So I'm not going to give you a specific number today, but we are expecting to have a very exceptional efficacy in terms of the virologic outcomes that I mentioned.

Our next question will come from the line of Mike Ulz with Morgan Stanley.

This is Rohit on for Mike. In terms of the VIR-5500 data, will that be presented at a conference in early January? Or do you think later in the quarter? And then secondly, is there anything you can point to that we should focus on, on the upcoming presentations at AASLD?

So -- sure. So the first question is about the update and exactly the timing in quarter 1 and the setting for quarter 1. We haven't provided that guidance exactly what month for what it will be in the setting. It could be a company event. It could be an academic conference. That's to be announced at a subsequent time. In terms of the focus for AASLD and the SOLSTICE, we will be showing the complete 48-week data for tobevibart and elebsiran and tobevibart monotherapy arms. So this will provide a complete update for target not detected for HB surface antigen, safety. So you'll get a complete picture there, which I think will be a meaningful update from what we've shown before.

Our next question will come from the line of Paul Choi with Goldman Sachs.

My first is on VIR-5500 as well. Can you please clarify if your planned update in the first quarter of next year will be just the monotherapy patients? Or will you have any data with regard to the combination group that are being tested with ARPIs? And my second question is on hep D. Gilead announced that they're filing bulevirtide but at a 10-milligram dose versus the 2-milligram dose that is currently approved in Europe. Can you comment on how you think that might change the landscape here in the U.S. as you progress with your program? And also any potential regulatory implications, if any, if you think there are any there?

Thank you. Yes. Thank you, Paul. Maybe just on your first question. As you know, we only recently started the first-line mCRPC combination study with ARPIs. So that data will not be part of the first quarter 2026 update. And then on bulevirtide, Mark, do you want to take that?

Yes. So your question, Paul, is about the Gilead announcement that they expect approval in H2 2026 and your question specifically about the 10-milligram dose. I mean we actually think it's a very net positive for Vir Bio that Gilead will launch bulevirtide ahead of us. We think that they will help to drive disease awareness. We think that they will help to focus on testing, HDV testing, which would make -- prepare the landscape for our launch. We don't see the 10-milligram or 2-milligram. We see those similarly. I mean we still think our regimen of tobevibart and elebsiran can achieve really, really strong virologic suppression compared to bulevirtide with either dose.

In terms of regulatory implications, we feel very confident that our program is designed to secure regulatory approval with ECLIPSE 1 and ECLIPSE 2 as being the core of the regulatory package and ECLIPSE 3 is providing really strong head-to-head information, which will bolster the value proposition for patients and in particular, for payers in the EU.

Our next question will come from the line of Cory Kasimov with Evercore ISI.

This is Josh Chazaro on for Cory Kasimov. Based off your PK and PD modeling data, are you surprised that you have not reached the maximum tolerated dose for VIR-5500? And can you share on whether you have seen any Grade 3 CRS events?

So are we surprised that we have not reached the maximum tolerated dose? Well, we've been going through dose escalation systematically, and that's been going very well. And I'm not really prepared to share any further details about dose escalation or results today. So stay tuned for our event in quarter 1 next year. And regarding more updated information on safety, again, we will be discussing that in quarter 1 next year at our data release.

Our next question will come from the line of Alec Stranahan with Bank of America.

This is [ Matthew ] on for Alec. In terms of the 48-week HDV data, can you maybe speak to how meaningful this data is for physician education ahead of a potential launch? And any reason to think that there would be a significant change from week 36 to 48?

So a great question. I do think that the data will be meaningful for educating physicians, clinicians and others who are interested in HDV about what our regimen can deliver at week 48. In terms of what we expect to show you, I mean, I would just say it's not going to be a long time. So stay tuned for our presentation, but we've been seeing deepening of responses over time to date. So we're excited to have the presentation and look forward to sharing it with you.

Our next question will come from the line of Ellen Horste with TD Cowen.

Just to drill down a little bit more on the TCE update. Can you talk a little bit more about how you're prioritizing the 3 TCE programs? Is there a world where you take all 3 of them forward? Or are you imagining that this will be a no-go/go decision for all 3 such that you only move forward with the best data? And maybe talk about the endpoints that you think are most important for that no-go/go decision, whether it's response rate or durability, safety, et cetera?

Thank you, Ellen. I'll start by saying our capital allocation priorities, as we have said, are really based on progressing our registrational study for hepatitis delta and then certainly accelerating as much as we can, our VIR-5500 prostate cancer program. Our other T-cell engager programs, I mean, obviously, are gated based on data as is typical. And as we have also shared before, we have a number of preclinical programs that have garnered a lot of external interest. So we're also looking at potential business development opportunities across our pipeline.

Our next question will come from the line of Sean McCutcheon with Raymond James.

So how are you thinking about the optimal setting for the TCE program in prostate cancer? We got the results from PSM addition, albeit a tepid reaction [ at U.S. ], but a lot more patients going to be PSMA radioligand exposed in the coming years. I know you've started the pre-taxane cohort that's up and running. But should we expect some proof-of-concept results post PSMA radioligand from your next update with more U.S. patients enrolled?

Sure. So in terms of what to exactly expect in terms of the patient population for our update, just as a reminder, we are currently doing dose escalation in both mono -- in both [ q week ] and [ q3 week ] in the third-line plus mCRPC setting. That would include post-RLT patients as a population. We also started, as Marianne said, the frontline taxane-naive, although we won't have that data for the update. In terms of where we're ultimately going to position this asset in terms of the patient population, I mean, we are interrogating the full gamut and intend to the patient populations from late-line to earlier line to hormone sensitive. So we will -- this will ultimately be a data-driven decision by how we ultimately position the molecule. But just to get back to the update in Q1, that will be the later-line patients that were the Part 1 or are Part 1 of the Phase I program.

Our next question will come from the line of Joseph Stringer with Needham & Company.

You've shown that your HDV combo therapy can reduce the hep B surface antigen level over time. I guess how well does this data resonate with KOLs and physicians? Is this something that you believe could be beneficial and potentially differentiator given the long-term chronic treatment paradigm for HDV? Or is it not nearly as important as, say, ALT and virological response?

Thanks for the question. I mean, firstly, I would state that the most important objective of our program with tobevibart and elebsiran is to suppress the virus to target not detected in a large proportion of patients because we know that suppressing delta virus to TND will translate into better outcomes for patients in terms of progression of the underlying liver disease. But I do think that the fact that we can reduce hepatitis B surface antigen levels by about 3 logs is important and does resonate with KOLs because as you recall, the surface antigen is critically important for the viral life cycle of delta. It needs the surface antigen to form its own viral code. So the fact that we are starving the delta virus of the surface antigen is another mechanism by which we suppress the virus with our combination regimen. So we do think that is important and differentiating.

Our next question will come from the line of Patrick Trucchio with H.C. Wainwright.

Just a follow-up question on HDV. First, just in terms of the addressable patients in the U.S. that you believe the combination of tobevibart and elebsiran could be relevant for at the time of launch. I'm wondering if that would include the 61,000 patients estimated in the U.S. who are viremic with HDV? Or is there a subgroup of patients who would be best for treatment at the time of launch? And separately, just sort of what efforts are ongoing to identify these patients? I mean, I appreciate that ECLIPSE 1 enrolled 2 months ahead of schedule. So just curious if -- particularly as bulevirtide maybe gets approved, if there's just going to be more awareness and how you'll actually go about discovering those patients? And ultimately, how many patients do you think you can reach at the time of launch?

Yes. So excellent question. So in terms of the HDV addressable population and launch, I mean, we're estimating approximately 60,000 patients in the U.S. who are viremic with HDV. We really think we can -- our regimen -- the patients will be eligible for a regimen [ broadly ] because we can treat patients effectively with high viral loads or lower viral loads. We can treat patients with compensated cirrhosis or non-cirrhotic. So we expect to be able to treat a very broad population of patients who are viremic with HDV. So we don't feel that, that will be constrained to any kind of subgroup at all.

We feel like it will be a broad population. In terms of the -- how are we approaching the launch? Well, first of all, I would note that -- I agree with you that the [ first ] enrollment of ECLIPSE 1 really speaks to the high unmet medical need for a regimen that like tobevibart and elebsiran that can meaningfully address the delta virus patient, the patients with HDV and their viremia and the liver disease that follows. We also think that Gilead launching bulevirtide ahead of us, like I said before, would be a real advantage because it will drive disease awareness, drive testing and those things. We are in active discussions with KOLs, with advocacy groups, diagnostic companies, et cetera, about the best way forward to make -- to driving awareness ourselves.

And back to an earlier question in terms of what will be the impact of our SOLSTICE presentation at AASLD this year, I mean I think it's going to be very significant because this is the first time we'll present the 48-week complete data for the combination, which really undergirds our ECLIPSE program and provides further confidence, I think, in what we're trying to achieve with ECLIPSE, which is really high rates of target not detected, HBV surface antigen suppression and really hopefully driving good outcomes for patients.

Yes. And Patrick, as you know, I mean, both from an efficacy perspective and also from a patient convenience perspective, our regimen being monthly dosing, that is a very big differentiator.

This concludes the Q&A session of the call. Thank you for participating. I will now turn the call back over to Marianne.

Thank you, operator, and thank you all for joining us today. We look forward to updating you on our progress in the coming months. Operator, you may end the call.

This concludes our call today. Thank you for joining. You may now disconnect.

All right. Good afternoon, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Ulz, one of the biotech analysts here. And it's my pleasure to introduce the team from Vir Biotechnologies, including Marianne De Backer, CEO; as well as Mark Eisner, CMO.

But before we get started, I just need to read a quick disclaimer for important disclosures. Please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative. With that, Marianne and Mark, thanks for joining us today. And maybe I'll hand it over to you, Marianne, to make some introductory comments for people that might not be familiar with your story.

Yes. Thank you, Mike. Thank you for hosting us today. So yes, for people not as familiar with Vir Biotechnology, we are a company that is at a clinical stage immunology-focused company. What we really try to do is harness the power of the immune system to address certain diseases in infectious diseases and in cancer.

And we have 4 clinical stage programs. Our hepatitis delta program is in registrational trials. We announced earlier this year that actually each of the 3 trials within the [ ECLIPSE ] program have -- are now enrolling patients. That is going really well. And that registrational program is really built on very strong data from our FLI Phase II trial where we could show that when treating patients with hepatitis delta infection after 36 weeks, already 64% of the patients in their blood, the delta virus could no longer be detected.

So very, very great efficacy, very promising for obviously, a registrational trial. Our other 3 programs in the clinic are earlier stage. The Phase I T cell engager programs. It's a portfolio that we acquired from Sanofi last year. And the T cell engagers are very specific in the sense that they are masked. So as you know, T-cell engagers, especially in the field of solid tumors have been hampered by often a problematic toxicity profile.

And our masked T cell engagers, and we showed data earlier this year in January for our HER2 program and our PSMA program showed really promising efficacy combined with a great safety profile. And that's really what we are aiming to achieve with those programs. Beyond that, we have a very powerful platform that is actually combining our ability to come up with great antibody therapeutics or T cell engagers and combining it with masking.

And so we acquired the rights to that PRO-XTEN masking platform from Sanofi for the entire field of oncology and infectious disease. And then finally, just to say we're very well capitalized. At the end of the second quarter, we had $892 million in cash, and we have a projected cash runway until mid-2027.

Great. Thanks for that introduction. And maybe we can start with the T cell engager platform, and you mentioned you acquired the program from Sanofi. So maybe just remind us of the rationale behind that deal and kind of how that deal came to fruition.

Sure. Yes. So we brought in that deal about a year ago. I think it's going to be exactly a year ago, actually today or tomorrow. And the whole idea was Vir has always been a company that is -- that was very strong in understanding how the immune system fights disease. And of course, its history was mostly focused on fighting infections.

But we were really looking for a platform and ideally clinical stage assets that would build on that strength of, again, harnessing the power of the immune system to fight disease. And those 3 clinical stage T cell engagers that we acquired from Sanofi, we thought looked incredibly promising. And as I mentioned, the platform is highly differentiating, and we have the rights for the entire field of oncology and infectious diseases.

We paid $100 million upfront to acquire the entire portfolio and platform. And we also had the very unique opportunity to bring over 50 employees, 5-0, who were prior [ Aminix ] employees. And so people who were deeply familiar with the platform, who had been working on developing the programs, who have been working on how to manufacturing these mass B-cell engagers. So we really not just got the assets and the platform, but sort of all the expertise that is really needed to be successful came on board.

And I must say now a year later, the transition could not have been more swift and smooth. I mean everything has been transitioned over from Sanofi to us. We have taken on sponsorship and everything just was executed in a very, very efficient way.

Great. And maybe you can talk a little bit about just the PRO-XTEN platform. Just give us a quick background there, how it's differentiated maybe from some of the competitors out there.

Yes. I'll start, and Mark, please chime in. So the PRO-XTEN platform is unique in the sense that it really use steric hindrance as a way to shield the binding side. So if you look at your T cell engagers, you have your CD3 side binding the T cell and then you have your [ PSMA ] or HER2 EGFR that you're binding the tumor-associated antigen. And what we do is really mask both sides of the molecule, both the CD3 binding site and the tumor-associated antigen binding site with an X10 mask, which is basically a hydrophilic polypeptide.

And it's forming a sort of balloon around the T cell engager. And we have engineered it such that it can be cleaved off in a certain environment. So we have protein cleaved on linkers. So basically, what happens is that this mask molecule can enter into the bloodstream of the patient, nothing much happens until it really reaches the tumor microenvironment where the proteases that are active in the tumor are going to cleave off the masks. And at that moment in time, the molecule is going to get activated.

The great thing about this masking is also that the [ X10 ] mask extends the half-life. So we have half-lifes of our molecules for the HER2 program, 5 to 6 days for our PSMA program, 8 to 10 days, which is, of course, very beneficial. And as soon as the masks are cleaved off, the half-life is very short. And so any potential toxicity can be avoided. So I think it's a very unique way to mask molecules. It's not based on affinity-based mask. It's really stero hindrance. The great thing about the platform is that it's a plug and play.

So we do not, every time that we want to mask T cell engager, have to come up with a whole new way of masking. We can just take exactly the same X1 with the same [indiscernible] linkers and apply these to the different molecules. So we have that same mask on our HER2 program, PSMA program and our EGFR program that we just dosed the first patient in July. And we're also working on preclinical programs that, again, can really deploy that same mechanism.

The whole idea about the masking is, of course, to be able to achieve a very good therapeutic index. So because you are shielding the binding and you avoid masking in healthy tissue, you can -- you have the opportunity to really push the dose and combine great efficacy with ideally a great safety profile.

And finally, the mask itself, the [ Xtend ] mask has been -- is being used actually in a molecule that is already on the market, [ Saltuvio]. So from that perspective, the mask itself has been highly derisked, which is, of course, a big benefit for us in clinical development.

A lot of advantages to the platform. I guess, maybe drilling down a little bit into the dual mask versus maybe a single mask and what's the difference there? How does that manifest in the study, for example?

Sure. So I think it's important because if you take our PSMA molecule, for example, PSMA is actually expressed pretty widely in normal tissue, albeit at very low expression levels. So by masking the CD3 part of the molecule, as Marianne said, and the PSMA part, it really protects the molecule in the normal circulation in the normal tissue. And it's only when it gets into the tumor microenvironment that the proteases cleave off the linkers, release the masks and it can form an immune synapse between the tumor cell, the T cell and kill the tumor cells.

So I think it's really very important for the therapeutic index that we're able to achieve. And I think with the PSMA program and the HER2 program now together proof points and validation for the platform, which is why we're excited to get into the clinic in our EGFR program, and we're excited about our next-generation targets in research as well.

Maybe you can talk about some of the data you've generated so far with the PSMA program itsER50.

You shared some Phase I data earlier this year. So Marianne referred to it a little bit earlier, very promising. Maybe you can give us some details there

Sure. So yes, so back in January, we presented data on the program, both the HER2 and the PSMA program. and what we showed is that although we were a very early stages of dose escalation in patients with very late-line metastatic castration-resistant prostate cancer, the median number of prior lines of therapy with 4 to 5, so very heavily pretreated patients.

But despite that, we were able to show PSA declines, even all the patients specifically in 12 patients who are receiving therapeutically relevant doses of 120 mgs per kilo or higher and [ PSA50 ] responses and 58% and 1 out of 12 by 8% of PSA 90. So impressive responses given that we're early in dose escalation. So we're very pleased about that.

There was 1 patient in particular that are -- one of our investigators, Professor [ DeBono] presented that how the [ PSA 90 ] response that was sustained for at least 12 weeks at our time, [indiscernible] ability as well. And the safety was very favorable. I mean 25-ish percent of cytokine release in [indiscernible]. So very tolerable.

[indiscernible] the fact we weren't using any steroid during [indiscernible], very low incidence of grade 3 or higher treatment-related adverse events. So showing a very promising therapeutic index, very promising benefit risk, giving us confidence to go subsequently to really push the dose scaling in both [ Q ] week and Q3 week, which as Marianne alluded to, because of the half-life of 8 to 10 days, we are able to interrogate Q3 redosing too.

So we're in the process of dose escalation. It's going very well, and we're really looking forward to continuing to generate those data.

How much you can talk about just the doses you tested initially and then maybe just how you're thinking about escalation and maybe how high you go?

So at the time of our last presentation, we had gone up to 1,000 micrograms per kilogram. We were imminently going into 2,000 likes per [ Turo]. We're not really talking yet about what specific doses have followed out, but it's been multiple months since then, and we're continuing to make really good progress on the dose escalation.

And I guess the question that you're getting the most, I guess, when do we get the next update? Or how do you think about that?

Yes. So it's important to understand that those escalation is still ongoing. So we haven't achieved any [ MTD]. There is no DLT, obviously. So we're still in those escalation with [ Mark ] as we evaluating reply in Q3 dosing. So we -- again, we would have an opportunity to put partial data out there. Ideally, I think we put a meaningful package out there where we have determined what the bot is going to be for the next step program.

We are still sort of debating that, and we haven't excluded sharing data still this year. At the same time, we are not waiting for that to play out. We are actually quite imminently going to dose in the first line cohort for a combination that we have 5,500 with an ARPI.

And that's in the pretax in the [indiscernible]. So -- and that will be at a dose that is in an efficacious range. So we are sort of not letting that exploration in earlier lines being determined by sort of determining our final on the current [indiscernible].

When you think about dose escalating in terms of how high you would like to go, do you want to hit an MTD and you start to see some tolerability, then you start adding some sorts [indiscernible]?

If we get with the dose escalation cohorts when we have a complete or we have adequate data on each cohort, the patients minimum. And not -- it's a lot of clinical judgment involved. It's not necessarily the case to reach MTD or drug limiting toxicities. I mean that certainly would be any reason why one might discontinue going higher, but we're really looking to characterize the therapeutic index, find a dose that can get to deep and durable responses with acceptable safety.

So there's a lot of clinical judgment that goes into that. And we're very privileged to work with world-class investigators, along with our team to help have those discussions and make those decisions to benefit our patients.

Since we're talking about timing, you also have the [ HER2 ] program. You also shared initial data in January and you continue to dose escalate. Should we think about those updates on those programs are probably at different times? Or would you try and sort of share them together?

Yes. So the first update that we provided in January was sort of our PSMA program on our [ HER2 ] program. At the same time, it was the first time post again doing the deal with Sanofi that we were sharing the data. Going forward, that doesn't necessarily need to be the case, right? We want to put data out there when it makes sense for each of the programs individually.

For the HER2 program, we have completed monotherapy escalation, but we're still in full dose escalation in the combination with [ Tango]. So we don't have that full data set at this moment in time.

Maybe you can give us a little flavor of the initial sort of Phase I data and what you saw there and what was citing there?

All right. So [indiscernible] our HER2-targeted program what we presented, it's a basket trial design. So there's a number of different HER2-positive tumor types. And we had a 50% overall number of patients who reach tumor shrinkage.

I think what was particularly exciting in the metastatic colorectal cancer cohort of 6 patients. We had 2 or 32% achieved a partial response, which is really quite impressive for early-stage data, given how heavily pretreated these patients were and how limited their other treatment options are. We had 1 patient who actually maintained a response for more than 18 months.

And what's also interesting about that patient is they started on a low dose of 60 mgs per kilo, and we -- the investigator escalated the dose all the way up to 600 over a number of months. And the tumor shrinkage initially declined and was maintained by the intrapatient dose escalation, so showing a dose response relationship within that patient. So I think that was really impressive. Again, the safety was quite good.

I mean, the cytokine release syndrome grade 1, grade 2, limited a number of grade 3 treatment-related adverse events. So again, favorable profile to move forward. And we've continued to escalate the dose in monotherapy, and now we're done escalating in monotherapy Q1 and Q3 week. We're continuing to dose escalate in combination with females to test the hypothesis is, whether a checkpoint inhibitor can affect the safety and efficacy of our molecule.

And we're in the monotherapy setting, we're currently doing an extensive evaluation of our data exposure response, dose response, looking to define what the go-forward dose can be for an expansion cohort and also what expansion cohort we would choose. I mean colorectal, I mentioned as appealing because we've generated significant data there, but this is a significant ongoing internal discussion that we're having.

Maybe we can shift to [ 5.525]. That's your EGFR. I think you just initiated the Phase I study that you mentioned earlier. Maybe just talk about the design there.

Sure. Yes, it's a basket trial design, and it's including patients who have high EGFR-expressing tumors such as non-small cell lung cancer, head and neck metastatic colorectal and also systemic severe cutaneous in cancer as well, cell carcinoma as well. It's a dose escalation design. It's a bone design like the other ones.

I think what's really important to note is that we -- we're leveraging our learnings from the platform and the other 2 programs and are going to be able to -- we anticipate being able to escalate into therapeutically relevant doses very quickly. So I think that's going to be important. And trying to get to some safety and efficacy readouts that will be relevant as soon as possible. So I think a really exciting program.

These are diseases with high unmet medical need, they're common tumor types where I think we can potentially make a difference. Maybe one other thing to note is that as opposed to TKIs or other antibodies targeting eGFR, our molecules used eGFR as an address. So we're basically able to target these tumors regardless of any mutational status in the EGFR or downstream mutations in KRAS or BRAF, those really don't matter.

We're just targeting tumors express EGFR in bringing the T cell engaged into the tumor in the microenvironment. So I think we're excited about that prospect. And then just lastly, because of Marianne mentioned some of the unique properties of our platform with the steroid indent mechanism, the cleavable linkers and half-life extenders we think that we have a really compelling proposition in the EGFR space. And we're really looking forward to generating those data.

And then just in terms of the data and disclosing it, what's sort of the thought process there? Is it something similar to where you've been with the other programs? And you gave sort of an early update and then a later update or how should we think about that?

Yes, it's likely going to be the case. Again, it's a little bit early, of course, because we just [indiscernible]. But yes, that is probably a good way to think about it.

Just in terms of indications for the EGFR program, are there any specific ones you're sort of prioritizing over others at this point?

Yes. I mean I think we've designed the study to focus on tumors that are, by nature, high EGFR-expressing tumors. So I think we -- it's a basket design. So we'll test the hypothesis that our molecule can have relevant terminal responses in those tumors. I think there's a lot of biomarker work that we have planned to further drill down on that. But since it's such early days, it's hard to get more specific.

I mean we have selected in contrast to the HER2 trial for indications as not mentioned. And so I think for now that sort of the focus of the tone.

Maybe you can switch to hepatitis delta, and you shared some data previously from a Phase II study. So maybe you can talk a little bit about why that data is so positive?

Yes. I think just to take a moment about some mechanism of action. So tobevibart is our monoclonal antibody against surfacing engine. So it blocks the entry of delta virus that had surface antigen on its viral envelope into the podocyte. It also optimizes the viral code engages in immune response. [indiscernible] is sRNA that knocks down all of the HBV viral transcripts, including that for surface antigen, which is necessary for Delta to form is viral envelope.

So we're tackling the virus via 2 distinct mechanisms of action. What we presented so far is through week 36, we last presented this at ASLD last year, where we were having very good antiviral responses in the mid-40% range, 80% in the rollover cohort at week 60. So -- and this is target not detected or complete suppression of the virus. So very, very compelling end of viral responses. We're going to present the 48-week complete data set at SLD this year in November.

So I think that will continue to reinforce the very, very deep and profound viral efficacy that we're seeing. We're also knocking down hepatitis B surface antigen production by 3 logs, which I think it's highly significant because we're essentially starving the delta virus of what it needs to form a viral envelope. So I think that's very therapeutically important data.

It's really very well tolerated. We do have some flu-like symptoms that are seen in patients, but generally with the first dose, very tolerable and really very low incidence of other treatment-related adverse events. So again, really looking forward to presenting those data, the [indiscernible] data.

You showed the promising data, I guess, next question is what this market opportunity look like? How do you address it?

Yes. So it's a rare disease. It's estimated at about 60,000 stations here in the United States. There's no treatment on the market for patients that get [ diet delta]. In Europe, there's about double that kind of patient population and they are just 1 drop on the market deliver tied. So what we have shown, as Mark mentioned, is that already after 36 weeks of treatment, we see 64% of target not detected.

So we do the virus disappeared no longer being detectable in the bloodstream. You know, blevatide has shown 12% after 48 weeks. So we think that from an efficacy perspective, we do have a superior regimen and also our regimen for the combination of tobevibart and elebsiran is a monthly regimen, which is, of course, for patients highly convenient in contrast to [indiscernible], which is it's a daily injection.

I think there's quite a bit of work that needs to be done, especially in the United States for diagnosing the disease. I think the good news is that we are really learning from what is happening in Europe. So in Europe, so you cannot have delta infection unless you have hepatitis B infection. It's a co-infection. And in Europe, patients that get diagnosed with hepatitis B gets more and more reflex testing.

So they automatically get tested also for halides data. So a lot of key opinion leaders, importance in this space are really working very hard to get the guidelines also adjusted in the United States. This, of course, already the CDC guideline to get tested for hepatitis B and if we could get that reflex testing into the guidelines in the United States that will be a big step forward. The testing for Delta itself is really not complicated. It's an antibody test. It's just a matter of getting patients diagnosed. And of course, because there is no treatment available to patients here today, there is no incentive.

There's no impetus to get any 1 dose, right? So we really hope to turn that around by bringing a resto the market that is actually very efficacious and also continuing [indiscernible].

Maybe you can talk about just your Phase III program. You've got all 3 studies now up and running. Maybe just walk us through those.

Sure. And yes, Marianne, thanks for correcting [indiscernible] 64% is the right number weeks, and we really expect to be able to reach complete viral suppression in the majority of patients over time. The [ ECLIPSE ] program is divided into 3 studies, the global studies and each have slightly different names. So [ ECLIPSE 1 ] is a randomized trial of [indiscernible] versus a deferred treatment period, which will show what our regimen can do compared to control of no treatment at all. And then those patients on the deferred arm will switch over after 12 weeks to our combination regimen.

This is a really important trial because in North America and other countries where [indiscernible] is either not approved or not easily accessible or available. This trial will provide very clear evidence about what our regimen can do in terms of suppressing the virus and achieving the composite endpoint of ALT normalization and target now detected.

The [indiscernible] 2 is addressing the specific question of [indiscernible] patients who are still -- sorry, as Marianne said, even after 48 weeks the majority of patients continue to be viremic with levertide. So we're randomizing those patients to either switch to our combination regimen or continue on [indiscernible] for 24 weeks with an endpoint of target not detected.

So we'll be able to show in a switch study population, what our drug regimen can do in terms of suppressing the viral replication much, much further, much deeper. And then finally, [ ECLIPSE 3], which is a study that's designed primarily for payer access and pricing considerations ex U.S. It's a head-to-head study of [indiscernible] compared to bleed with the endpoint of target not detecting to 48 weeks.

So there, we aim to show superiority of our combination regimen versus blovirtide 48-week period. It's important to note that [ ECLIPSE and CLSI ] are the core part of our registrational package for filing in U.S. and [ ECLIPS-3 ] will generate really critical data that will also support the value proposition, particularly for pricing access considerations.

Yes. And enrollment is going really, really well. And for ECLIPSE 1, our primary completion date is at the end of 2026, and for Eclipse 2, I mean, maybe important to mention that, that has a 24-week endpoint. So there's a possibility that could sort of flood out at a similar time.

Yes. We're really happy with how well it's enrolling. And I think -- it reflects the engagement of our investigators, the strength of the science behind this regimen and the unmet need around the world for a regimen.

Okay. Great. And maybe I can ask the last year, just a couple of sort of macro questions that are topical that we've been asking all the companies at the conference. So maybe 2 different questions. I'll start with the first. So with China's rise in biotech innovation, how are you thinking about your competitive position here and will this influence your R&D strategy?

Yes. So obviously, it is critically so that we see that China is not just very quickly copying a lot of the innovation maybe that gets published out of U.S. and elsewhere, but also making innovations beyond that, right? So I think that switch from China being maybe more doing 2 signs to really becoming an innovator has been very clear. I think you see it in many shapes and forms, a lot of the deals that large farmer is entering into. I think it's 30% to 40% now are with Chinese biotechs, you see also VCs fishing more in the Chinese pond, so to speak.

And then you know that some investigator-initiated trials in China, I mean they can be done in a way that is certainly much faster and also cheaper. So -- and obviously, the China government has been significantly investing in this area for a long time. It has been a top priority from a government perspective. So I think you see all that dynamic developing and certainly biotech in China is getting very strong.

So I think it's really important, again, for ourselves to stay ahead of the game. I think we are in a field with [ MOS T ] cell engagers that is the tip of the spear of innovation. And we have important plug-and-play platform, strongly IP protected that we can continue, of course, also to innovate. And I think that's what is really important is that you continue to innovate on your innovation so that you can really stay ahead of competition, not just in China, but of course, generally solid.

Makes sense. Maybe we can move to the second question. How are you currently leveraging AI or thinking about AI's future disruption potential in the field?

Yes, I'll start, and Mark, please chime in. So we have consistently using AI for quite some time now in the design of new antibody therapeutics and also T-cell engagers. So the same way that you're using your large language models, we are using cost protein models to come up Initially, we isolate antibody therapeutics out of either human subject or animal models. And then for further optimization, it can be affinity, potency, developability, whatever it might be. We use a selection of a number of different AI models combined with our internal data set to come up with just data molecule.

And again, that has been pretty amazing to see. I mean I do believe that we have some of the best protein engineers in the world, there's just new proposals that the AI models come up with that our team would not necessarily come up with. And again, it's not just you asked the AI model to come up with a proposal.

It's still a process where you get proposals of what an optimized sequence would look like, then you -- you have to do still your wet experiment, test them and feed it back into the system. And you go through a number of these continuous improvement leads to come up with really powerful molecules. So that is where we have seen an impressive impact on our drug discovery efforts already. Other areas where we're using AIs, everything that is related with competitive intelligence, obviously. And then in our regulatory filings, we may be marketing.

Yes. No. I mean we're using it and evaluating it as a way to write regulatory documents that are required. I think it's well suited assimilating data and at least writing a good first draft of documents like that. We have an internal chat bot that we use for searching and decision-making and things of that nature. We're using it for accelerating statistical programming, things of that nature. I mean, we're really evaluating it in multiple different fronts from a clinical development perspective. And we have a kind of concerted effort across the company to really see where we can apply the most efficiently.

Yes. And it's not a stand-alone same, right? It's sort of incorporated in all those activities that we do.

Okay. Great. Looks like we're out of time. So when we end it there. Thanks so much, Marianne and Mark. Really appreciate your time today.

Appreciate it. Thank you.