VIR

Hello, and welcome to Vir Biotechnology's first 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 presentation, 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. 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-XTEN platform, our development plans and timelines, 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 Biotechnology 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 elebsiran, an investigational small interfering RNA.

Jason will provide an overview of our first quarter 2026 financial results. Finally, Mary-Ann will close the call and will open the line for Q&A. With that, I'll now turn the call over to Mary-Ann.

Thank you, Kiki. Good afternoon, everyone, and thank you for joining us for Vir Biotechnology's 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 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 23rd, 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. 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 number 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 masked 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. Johann de Bono shared an update from this study evaluating patients with advanced mCRPC as an all 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 23rd. 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 pre-medication 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 PSA 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 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 a first patient in our phase I dose expansion cohorts 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, 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 1 second-generation androgen receptor pathway inhibitor and 1 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 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 ProXtend 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 ProXtend 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-mast 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 need 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 U.S., U.K., and 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 two 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 virus remains detectable. These data support 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. We saw 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' lead 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 office.

This is important because physicians have indicated that up to 20% of hepatitis delta patients might not be able to self-administer. 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 BMI 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 to 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 to 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 to 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 Sciences' expected U.S. launch of bulevirtide as a positive for the hepatitis delta market overall, one that helps pave the way for next generation therapies like ours. Hepatitis delta remains significantly underdiagnosed and undertreated, the introduction of the 1st approved therapy in the U.S. should meaningfully raise disease awareness, expand screening, and establish treatment pathways 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, 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 15th, 2026, following expiration of the HSR waiting period. Upon closing, Vir Biotechnology received a $75 million cash payment representing Astellas' equity investment. 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 27th, 2026, the offering closed. 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 equivalents and investments, which includes the aforementioned proceeds from the follow-on offering. Subsequent to quarter end, we closed the Astellas collaboration. Therefore, the $315 million in proceeds from that transaction are not reflected in our March 31st, 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. 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.

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 Mary-Anne to close the call.

To close, we are exceptionally well-positioned for long-term value creation at this inflection point. Since December twenty twenty-five, the combination of our collaborations with Norgine and Astellas, together with a successful financing, has generated over a half of a billion dollars 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 a best-in-class T-cell engager for the treatment of prostate cancer. Beyond our clinical programs, we are steadily advancing seven preclinical T-cell engager assets that utilize the PRO-XTEN platform and broaden our pipeline's optionality, positioning us well to generate a 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 midterm catalysts ahead across our ECLIPSE studies. Taken 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, Mary-Anne. This concludes our prepared remarks, and we will now start the Q&A session. Joining me for the Q&A are Mary-Anne and Jason. 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.

Thank you. We will now begin the question-and-answer session. If you would like to ask a question please press star one to raise your hand. To withdraw your question please press star one again. We ask that you to pick your handset up when asking a question to allow for optimum sound quality. If you are muted locally please remember to unmute your device. Please standby while we compile the Q&A roster. Our first question comes from Paul Choi with Goldman Sachs. Your line is open. Please go ahead.

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

Thank you, Paul, for that question. We will be sharing data on our VIR-5818 program 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, you know, 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. There's certainly still, you know, a prospect to come up with better treatments. Again, we will be sharing data second half of the year, and we'll then give a further guide.

Okay, great. Thank you for that. With regard to VIR-5500 and your comment on, you know, potential development, earlier treatment settings, I guess, you know, 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. Just to recall that we already have a dose escalation ongoing for early-line VIR-5500 combined with an ARPI. What we are planning to do now together with Astellas, our collaboration partner, is start expansion cohort in that same setting, combination of VIR-5500 with enzalutamide. That is something that is coming in the expected coming months.

Okay. Got it. Thank you for the clarification.

Your next question comes from Roanna Ruiz with Leerink Partners. Your line is open. Please go ahead.

Hi. This is Michael on for Roanna Ruiz at Leerink Partners. Thank you for taking our question. Regarding VIR-5500, late line mCRPC monotherapy expansion cohort, what would constitute a clear signal as a green light to initiate a phase III in 2027? Are you anchoring on like PSA 50, 90 or RECIST or PFS, something like that?

Yes. 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. That will be additional data that we will be gathering. We only had a limited set of such patients in our initial cohort on which we reported data on February 23rd. I would say it's going to really be the totality of the data. Obviously, PSA, RECIST, our PFS. You know, we will have a more full data set to then decide on the next steps. Our goal is, pending data obviously to start pivotal trials in 2027.

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

Yes. You know, 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. It's fair to say that the protease cleavable linker is really a promiscuous linker. There's different families of proteases there to really ensure that you are, you know, going to be successful across a broad set of tumor types.

Okay, great. Thank you so much.

Sure.

Your next question comes from Cory Kasimov with Evercore. Your line is open. Please go ahead.

Hey, this is Josh Schimmer on for Cory Kasimov. Thanks for taking our question. Maybe one on HDV. As you approach the pivotal HDV data, wonder what your latest thoughts are on pricing there?

Sure. Thank you, Josh Schimmer. 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, you know, 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, $115,000 U.S. dollars. If you look across your, you know, 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, and, you know, an orphan disease where we would be delivering substantial benefit for patients.

Got it. Thank you. Just another quick one on VIR-5500 here, maybe following up on one of the previous questions. Especially in the late line mCRPC 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?

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

Correct.

Yes. Yeah, I can only point to what we know thus far is that, you know, several T-cell engagers have been showing durable responses. Our data set was still a little bit early, also in our data set, you could already see that we had a number of resistant developed patients with data post 27 weeks confirmed partial responses. 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 1 year and continuing. We have, sort of, you know, case examples of durability, and obviously we will be looking in our broader data set for, you know, durability more consistency across the entire expansion cohort.

Got it. Thank you.

Sure.

Your next question comes from Alec Stranahan with Bank of America. Your line is open. Please go ahead.

Hey, guys. This is Matthew on for Alec Stranahan. Thanks for taking our questions and congrats on the progress. I guess two for us on competitive landscapes. First for HDV, just curious your thoughts on Mirum Pharmaceuticals' ZSR data that came out recently, and whether that sort of changes your thoughts on commercial opportunity or competitive landscape. Secondly, for EGFR T-cell engagers, competitor of yours recently, you know, discontinued development of their JANX008. I guess just what gives you confidence that your strategy will pan out where others have failed? Thanks.

Thanks for Matthew. Yes. On your first question, as I laid out in the introduction, we and, you know, 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. The way that you measure that is through HDV RNA target not detected. If you look at our levels of TND for our monthly regimen of tobevibart and elebsiran, after 48 weeks, which is our primary endpoint, we achieve about 66%. We have also shown that, you know, it really increases. It's actually increasing from 41% at 24 weeks to 66% at 48 weeks and then to 88% at 96 weeks. We saw that, you know, significant increase in target not detected over time for our dual mechanism regimen.

We did not see that actually for our monotherapy antibody. We saw, you know, it at about 30% TND 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, you know, might not be very viable. For their weekly regimen, at 300 milligrams, they are showing at 24 weeks, 30% target not detected. We believe that from, you know, a viral 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, you know, the 50%.

We had 47% at 24 weeks. I think Mirum reported between 40% and 45%. ALT normalization seems to be sort of evening out across different regimens. 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, Janux discontinued their EGFR T-cell engager. I would say the only sort of surprising thing there from our perspective is that they saw musculoskeletal issues that were mentioned as dose-limiting toxicity. That was unexpected, and something, of course, that we will watch. The reason why we strongly believe in the differentiation of our MAST T-cell engagers is first, the masking technology is fundamentally different. We use stereokindrants.

It's the same PRO-XTEN mask across all of our clinical programs. We don't need to, you know, redesign a new mask every time for every program. We really take learnings from one program to the next. What we have seen with VIR-5500 is that that masking technology allows you to dose much higher. If you can dose higher, obviously you can get potentially to a better therapeutic index. I would say that our masking technology is fundamentally different.

Your next question comes from the line of Philip Nadeau with TD Cowen. Your line is open. Please go ahead.

Good afternoon. Thanks for taking our questions. 2 from us. First on VIR-5818, you referenced the dose escalation date 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 first question. 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 amendable for therapy, shortly after launch? Thanks.

Thank you, Phil. Yes, on VIR-5818, 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, you know, we will share at a later date. I want to maybe point out that the VIR-5818 trial is very different actually from our VIR-5500 trial in the sense that it's a basket trial, we actually have a wide variety of tumor types in that trial. We have already shown you some initial results, you know, for example, in metastatic colorectal cancer where we had a 33% confirmed partial response.

We will be, where possible and where we have enough patients in 1 given tumor type, be sharing you, of course, information on, you know, where we use CA to look at responses, tumor shrinkage, et cetera. We see it, though, importantly as a signal-seeking trial that will give us information around what indications to potentially go into expansion cohorts with. Your question on hepatitis delta. From those patients, we estimate that there are about 61,000 actively viremic patients here in the U.S., and it's a hugely underdiagnosed disease, as I mentioned earlier. We believe that actually only about 10%-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 now are also relatively affordable. The Medicare reimbursement rates 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 two or three times to see their physician before all testing is done. You know, the first time for a hepatitis B test, the next time for the antibody test, and the next time for the RNA test. There's a lot of streamlining that can happen.

In Europe, they have already shown that if you do reflex testing, so really, you know, when a patient tests positive for hepatitis B, immediately proceed to testing for hepatitis delta on the same sample, that could really increase diagnosis rates substantially. That is something that if the guidelines get adapted here in the U.S., that could drive a lot of difference.

That's very helpful. Thanks for taking our questions.

Your next question comes from Etzer Darout with Barclays. Your line is open. Please go ahead.

Hi, this is . Thanks for taking our question. For HDV, with the ECLIPSE 1 trial reading out in 4Q and then you have ECLIPSE 2 and 3 reading out in 1Q next year, you know, how are you guys thinking about it 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? On VIR-5500 with the partnership with Astellas, in the announcement said that they will be responsible for all development activities after phase I. Just wondering what kind of visibility you'll have, you know, into those trials as they enroll.

Sure. I'll start with your last question on collaboration with Astellas. It is a global co-development and co-commercialization agreement, and we have quite significant joint governance in the deal. We have a joint development committee, of course, a 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, you know, standard, I would say, for a 50-50 type of partnership. We will remain very intricately involved. We are of course, running the phase I trials now, and of course, Astellas is very involved in that as well. No, 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. Your first question on what is required for filing. Our guidance is that we would need a combination of ECLIPSE 1 and ECLIPSE 2 for filing. We will have ECLIPSE 1 data, as you mentioned, fourth quarter of this year, and then ECLIPSE 2 is coming in the first quarter of next year.

Okay. Thanks.

Your next question comes from Sean McCutcheon with Raymond James. Your line is open. Please go ahead.

Hi, guys. Just one quick question from us. 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 5 times the upper limit of normal, and any potential read-through to kind of how you guys are seeing the patient population here? Thanks.

The estimation is that maybe about 5% of delta patients have an ALT that is above 5x the upper limit of normal. You know, these kind of very high levels of ALT can have a lot of different reasons. We and K-rel strongly believe that the real measure of looking at whether there is damage to the liver is looking at cirrhosis, that's why we have involved more than 60% of patients in our trial that are Child-Pugh A 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. Your line is open. Please go ahead.

Hi. Thanks for taking our questions. 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, for that question. ECLIPSE 1, just to remind everyone, is a trial where we compare treatments with our regimen of tobevibart and elebsiran with a deferred treatment. It is almost like a placebo-controlled trial, which makes it, of course, very likely that you're gonna be successful in that trial. The bar for success is really low. I mean, again, target not detected, for example, for with the bulevirtide, which is in phase III development, 10 milligram is about 20%. You know, 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 bulevirtide dose. The bar for success is not that high.

Again, I think we have a combination of best-in-class viral efficacy and then again, ALT normalization that seems to be pretty, you know, similar across all the regimens.

Your next question comes from Patrick Trucchio with H.C. Wainwright. Your line is open. Please go ahead.

Hi, everyone. This is Luis Santos in for Patrick. Thank you for taking our questions. A follow-up question on the strategy for HDV 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? 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? Thank you so much.

Yeah. Thank you, Luis. Maybe answering your second question first. Patients who will be on bulevirtide will have to inject themselves daily. It's a chronic treatment, right? Really chronically, every single day, they will need to inject themselves. As I just mentioned, for bulevirtide 10 milligrams, the expected level of target not detected 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 target not detected at 48 weeks of 66%. The chances of success for patients are much higher and convenience is also much better.

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. We will also have data to show that obviously makes sense for patients to do. As to your question for at home and at clinic, 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 a physician, this level of once a month administration is really convenient to allow that to happen. 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.