VIR

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Transcript Summary

Vir Biotechnology reported a milestone-heavy Q1 2026, headlined by the closing of a $1.7 billion collaboration with Astellas for VIR-5500, a PSMA-targeted T-cell engager. The deal provided an immediate $315 million in capital, extending Vir's cash runway into H2 2028. VIR-5500 Phase I data showed favorable safety and efficacy in late-line prostate cancer, with Phase III planned for 2027. In Hepatitis Delta, Vir's combination therapy (tobevibart and elebsiran) demonstrated 88% viral clearance at 96 weeks. The company is advancing three Phase III ECLIPSE trials, with top-line data from ECLIPSE-1 expected in Q4 2026. Management highlighted their monthly dosing regimen as a key differentiator against daily/weekly competition. Additional platform assets targeting HER2 and EGFR are in early-stage development, with data readouts expected later this year. Financially, the company ended Q1 with $809.3 million in cash, excluding subsequent Astellas and financing proceeds. Vir remains focused on disciplined capital allocation and rapid clinical execution across its oncology and infectious disease portfolios.

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Vir Biotechnology: Cash-Rich Burn Rate vs. Chronic Equity Dilution

Full Earnings Call Transcript — Q1 • 2026-05-07

Operator: Hello, and welcome to Vir Biotechnology First Quarter 2026 Financial Results and Corporate Update Conference Call. As a reminder, this call is being recorded. [Operator Instructions] I will now turn the call over to Kiki Patel, Head of Investor Relations. You may begin, Kiki.
Kiki Patel: Thank you, operator, and welcome, everyone. Earlier today, we issued a press release reporting our first quarter 2026 financial results and corporate update. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration outcomes, future results, performance or achievements to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements include, but are not limited to, statements regarding the potential benefits of our collaboration with Astellas, the therapeutic potential of VIR-5500 and our PRO XM platform, our development plans and time lines, financial terms and milestone payments and our cash runway and capital allocation priorities. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q and 8-K. Joining me on today's call from Vir Biotechnology are Dr. Marianne De Backer, our Chief Executive Officer; and Jason O’Byrne, our Chief Financial Officer. During the first quarter of 2026, the Vir Bio team delivered meaningful advances across our T-cell engager and Hepatitis Delta programs, underscoring our ability to execute towards key clinical and corporate priorities. The agenda for our call today is as follows: First, Marianne will share an update on our recent landmark global strategic collaboration with Astellas and our prostate cancer program. Next, she will provide an update on our Hepatitis Delta program evaluating tobevibart, an investigational neutralizing monoclonal antibody and elebsirin, an investigational small interfering RNA. Then Jason will provide an overview of our first quarter 2026 financial results. And finally, Marianne will close the call, and we'll open the line for Q&A. With that, I'll now turn the call over to Mary Anne.
Marianne De Backer: Thank you, Kiki. Good afternoon, everyone, and thank you for joining us for Vir Biotechnology First Quarter 2026 Earnings Call. Since our last earnings call in February, we have remained highly focused on execution as we advance both our oncology and hepatitis delta programs with speed and focus. I will begin by providing a brief update on the current status of our recent collaboration with Astellas, a deal valued at up to $1.7 billion. In addition, in the U.S., commercial profits will be split 50-50 between the parties with Vir Bio having the option to co-promote alongside Astellas. As a reminder, on February 23, we announced that we entered into a collaboration with Astellas to co-develop and co-commercialize VIR-5500, our PRO-XTEN dual-masked PSMA-targeted T-cell engager. Since then, the transaction successfully closed on April 15, marking an important transition from deal announcement to deal execution. With the deal closed, our joint teams are operational and partnering closely on a shared clinical development plan to enable rapid expansion and accelerate delivery to patients. This collaboration brings together Astellas' global leadership in prostate cancer with our differentiated PRO-XTEN -enabled T-cell engager. We chose to partner with Astellas because of their decade-long track record of successfully co-developing category-defining therapies, including XTANDI, the world's #1 prostate cancer drug. Metastatic castration-resistant prostate cancer, or MCRPC, remains a significant unmet need with a 5-year survival rate of only 30%, underscoring the urgency for new treatment options that can deliver even deeper, more durable disease control and improved quality of life. VIR-5500 is the most advanced dual mask T-cell engager currently under evaluation in prostate cancer. The foundational driver of the Astellas collaboration shaping our development strategy going forward is our Phase I data for VIR-5500. Dr. Johan De Bono shared an update from this study evaluating patients with advanced MCRPC as an oral presentation at ASCO GU in February. Today, I'll highlight key takeaways from the data. For a more comprehensive update from the trial, please refer to our fourth quarter earnings call from February 23. Overall, the VIR-5500 data showed a favorable safety and tolerability profile with no observed dose-limiting toxicities. At the dose levels of 3,000 micrograms per kilogram and above, we saw mostly Grade 1 cytokine release syndrome or CRS, defined as fever only. We did not observe any Grade 3 CRS at this dose, reinforcing the potential of the PRO-XTEN dual masking platform to widen the therapeutic index of our T-cell engagers. We view the absence of high-grade CRS at our go-forward monotherapy dose, together with a lack of mandatory steroid premedication in our protocol as a meaningful differentiator for VIR-5500. We believe that sparing steroids may help preserve T-cell function and reduce treatment complexity for both patients and physicians. Collectively, these attributes support the potential for outpatient administration and could translate into significant clinical and commercial advantages over time. Importantly, this profile may support positioning VIR-5500 in both the pre- as well as post-radioligand therapy or RLT settings, offering flexibility across the treatment continuum and potential use in routine care settings relative to the specialized infrastructure required for RLT administration. Furthermore, the depth of PFA and RECIST responses we observed were particularly encouraging with several patients sustaining responses for up to 27 weeks. Additionally, we saw emerging signs of durability up to 8 and 12 months, respectively, in patient cases with extended follow-up. One of the most compelling aspects of our data is that these deep responses were observed in heavily pretreated patients with advanced poor prognosis disease, including liver metastasis. This is historically the most difficult population to treat and resistant to immunotherapies, underscoring the clinical significance of the activity we are seeing. Additionally, we observed a complete response for a patient who previously relapsed on an actinium-based PSMA directed radioligand. We view these findings as especially meaningful given the historically poor outcomes and limited responsiveness of this patient population to subsequent therapies. Building on these encouraging Phase I dose escalation monotherapy results, we have dosed the first patient in our Phase I dose expansion cohort for VIR-5500 in late-line patients. This milestone represents an important step in further evaluating VIR-5500's best-in-class potential for people living with prostate cancer. In the monotherapy expansion cohorts, we are evaluating Q3 week 800, 2,000, and 3,500 microgram per kilogram step-up dosing. This study will measure safety and efficacy, including PSA responses and objective response rate or ORR of VIR-5500 in patients with MCRPC who are refractory following treatment. These patients will have had exposure to multiple prior lines of therapy, including at least one second-generation androgen receptor pathway inhibitor and taxane regimen. The expansion includes 2 distinct cohorts: patients who are naive to prior RLT and patients who have previously received RLT in any treatment setting. Dose escalation of VIR-5500 in combination with enzalutamide continues in early-line MCRPC patients. We anticipate dosing the first patient in the combination dose expansion cohorts in both early-line MCRPC and metastatic hormone-sensitive prostate cancer over the coming months. Together, these cohorts highlight the potential of VIR-5500 across the prostate cancer continuum, including in the frontline setting. Without the challenges associated with RLTs, such as radioactivity and restricted settings of care, we believe masked T-cell engagers represent the long-term future in this space and that VIR-5500 has the potential to be a best-in-class T-cell engager. We anticipate initiating our registrational Phase III program for VIR-5500 in 2027. These results provide validation of our broader PRO-XTEN platform, unlocking significant opportunities to develop next-generation masked T-cell engagers in other solid tumor types. Turning now to the rest of our clinical stage T-cell engager programs. VIR-5818 is our PRO-XTEN masked HER2-targeted T-cell engager. We view this as a signal finding study given the early stage of development and the basket design where multiple tumor types are evaluated in parallel. We expect to report preliminary response data evaluating VIR-5818 monotherapy and combination therapy with pembrolizumab in the second half of 2026. This update is intended to inform our understanding of dose and help identify which HER2-expressing populations may warrant further study, particularly in areas of high unmet medical need. For VIR-5525, our PRO-XTEN dual-masked EGFR targeted T-cell engager, Phase I study enrollment is progressing as expected. The study design incorporates learnings from VIR-5818 and VIR-5500 to enable efficient dose escalation. We are evaluating both monotherapy and combination with pembrolizumab across multiple EGFR-expressing tumor types, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and cutaneous squamous cell carcinoma. We believe this program has the potential to address significant unmet medical needs in these indications where existing EGFR-targeted approaches have limitations. Turning now to our Hepatitis Delta program. The hepatitis delta community is severely underserved, with approximately 180,000 actively viremic patients across the United States, the U.K., and the EU, based on a composite of high-quality epidemiology sources. In the U.S., the patient population is highly concentrated in major urban centers and can be supported by an efficient commercial approach with a targeted specialty sales organization focused on hepatologists, gastroenterologists and infectious disease specialists. Overall, we expect our tobevibart plus elebsiran combination to have 2 clear advantages in chronic hepatitis delta versus our competitors. The first is that we are seeing potential best-in-class efficacy with a strong safety profile. The second that our regimen is designed with once monthly subcutaneous dosing and the potential for both at-home and in-office administration. For viral infectious diseases, clearing the virus is the key to improving long-term outcomes. KOLs in the chronic hepatitis delta space highlight undetectable virus as measured by target not detected or TND, as the gold standard measure of viral clearance. Achieving undetectable HDV by this measure is the most stringent threshold available and means that the delta virus is completely cleared from the bloodstream. As the delta virus replicates so aggressively, patients need HDV to be completely undetectable for positive clinical outcomes and to avoid rebounds. Peer-reviewed evidence suggests that patients with hepatitis delta who achieve undetectable virus have significantly improved long-term clinical outcomes, including reduced progression to cirrhosis, hepatocellular carcinoma, liver transplantation, and death compared with patients in whom the virus remains detectable. These data support an undetectable virus as a key clinically meaningful goal of antiviral therapy for patients with hepatitis delta. In January, we reported potential best-in-class efficacy in our Phase II SOLSTICE trial in patients with chronic hepatitis delta for a subset of patients at 96 weeks. Evaluated participants receiving the combination therapy of tobevibart and elebsiran showed increased and sustained viral suppression of HDV RNA versus treatment with the antibody alone. The data showed 88% of evaluable participants achieved undetectable virus compared to 46% on tobevibart monotherapy alone. Additionally, we saw a rapid onset of viral suppression, achieving already 41% undetectable virus within 24 weeks. These results underscore the limited efficacy of hepatitis delta treatment with antibody monotherapy alone. In contrast, combining complementary mechanisms of action with tobevibart plus elebsiran raises the rate of undetectable virus to approximately 90%. Importantly, we see similar efficacy in cirrhotic patients, which will be a significant patient cohort at launch due to the delayed diagnosis of most hepatitis delta patients to date. The combination was well tolerated with no grade 3 or higher treatment-related adverse events and discontinuations. The second key differentiator is that tobevibart plus elebsiran will only be administered monthly, consisting of 2 subcutaneous injections to be administered at the same time. As a reminder, competitors' sleep regimens require either daily or weekly injections. For the hepatitis delta patient population, this frequency will be a significant challenge. So, we see monthly dosing as an additional meaningful differentiator for our regimen. Additionally, due to the need for a higher dosing frequency of competitive regimens, tobevibart plus elebsiran may have the potential to be the only product conveniently enabling both self-administration at home and physician administration in the office. This is important because physicians have indicated that up to 20% of hepatitis delta patients might not be able to self-administer. So tobevibart plus elebsiran may be the only treatment available for this group of patients. Our hepatitis delta regimen has already been recognized by multiple global regulators with FDA breakthrough therapy and Fast Track designations as well as EMA Prime and orphan drug designation, underscoring both the unmet need and the strength of the data package. These designations provide ongoing engagement with both agencies and support a high level of confidence in our ability to achieve broad labels for our regimen. We are pleased to share that we will be presenting the complete 96-week SOLSTICE Phase II data in an oral presentation at the upcoming EASL 2026 Annual Meeting in Barcelona on May 29th. We will also be presenting a poster of a 48-week subgroup analysis evaluating the impact of VMI on ALT normalization after successful viral control. As we look ahead to our ongoing registrational program, all 3 of our ECLIPSE studies are on track. ECLIPSE-1 enrollment is complete with approximately 120 participants randomized 2:1 to our combination therapy versus deferred treatment. The primary endpoint is a composite of undetectable virus as measured by HDV RNA target not detected plus ALT normalization at week 48. We expect to report top line data from ECLIPSE-1 in the fourth quarter of this year. ECLIPSE-2 enrollment continues on track across multiple European sites. This study will enroll approximately 150 patients who are being randomized 2:1, evaluating the switch to our combination therapy in patients who have not adequately responded to bulevirtide. The primary endpoint for the trial is undetectable virus as measured by HDV RNA target not detected at week 24. The strong enrollment momentum we are seeing in Europe reflects an important unmet need in patients previously treated with bulevirtide. For ECLIPSE-3, our Phase IIb head-to-head comparison, enrollment is complete with approximately 100 patients randomized 2:1 to our combination therapy versus bulevirtide. The primary endpoint for the trial is undetectable virus as measured by HDV RNA target not detected at week 48. In general, we view Gilead's expected U.S. launch of bulevirtide as a positive for the hepatitis delta market overall and one that helps pave the way for next-generation therapies like ours. Hepatitis delta remains significantly underdiagnosed and undertreated and the introduction of the first approved therapy in the U.S. should meaningfully raise disease awareness, expand screening and establish treatment properties among treating physicians. Complementing this, we have an experienced commercialization partner through our collaboration with Norgine, who holds an exclusive license across Europe, Australia and New Zealand. Norgine's established infrastructure and expertise in specialty pharma and hepatology positions us to maximize the commercial opportunity of our HDV regimen across these geographies. In summary, we have made exceptional progress across our entire clinical portfolio, and we believe these advancements leave us well positioned to deliver on our clinical and corporate objectives. With that, I'll now hand the call over to Jason for our financial update.
Jason O’Byrne: Thank you, Marianne. Before discussing the first quarter financials, I will share the latest news about our Astellas collaboration. We are pleased to report that the VIR-5500 global collaboration and licensing agreement closed on April 15, 2026, following expiration of the HSR waiting period. Upon closing, Vir Biotechnology received a $75 million cash payment, representing Astellas' equity investment. And within 30 days of closing, we will receive a $240 million upfront payment. As a reminder, we are eligible to receive a $20 million manufacturing tech transfer milestone payment in 2027. We will share global development costs, 40% by Vir Bio and 60% by Astellas. We will split U.S. commercial profit loss equally with Astellas, and we are eligible to receive up to an additional $1.37 billion in development, regulatory and ex-U.S. sales milestones, along with tiered double-digit royalties on ex-U.S. net sales. A portion of certain collaboration proceeds will be shared with Sanofi according to the terms of that licensing agreement. Overall, this deal provides immediate capital and significantly reduces our near-term development spend while preserving substantial long-term economic upside. The collaboration with Astellas can maximize the value of VIR-5500 through accelerated clinical development and global reach, potentially benefiting more patients and creating greater value for our shareholders. Shortly after announcing our global collaboration with Astellas and sharing updated Phase I data from the VIR-5500 program, we completed a follow-on equity offering. On February 27, 2026, the offering closed, and we received gross proceeds of approximately $172.5 million before deducting underwriting discounts and commissions and estimated offering expenses. We intend to use the proceeds from the offering to fund our share of the development costs for VIR-5500 to advance the broader T cell engager platform and for working capital and other corporate purposes. Turning now to our balance sheet. We ended the first quarter with approximately $809.3 million in cash, cash equivalents and investments, which includes the aforementioned proceeds from the follow-on offering. Subsequent to quarter end, we closed the Astellas collaboration, and therefore, the $315 million in proceeds from that transaction are not reflected in our March 31, 2026 cash position. Based on our current operating plan and including the net effects of the recent Astellas agreement and capital raise, we expect our cash runway to extend into the second half of 2028, enabling multiple value-creating milestones across our pipeline. Now I will review our first quarter 2026 financial performance and overall financial position. R&D expense for the first quarter of 2026 was $108.9 million, which included $6 million of stock-based compensation expense. This compares to $118.6 million for the same period in 2025, which included $7 million of stock-based compensation expense. The year-over-year decrease was primarily driven by a $30 million payment to Alnylam in the first quarter of 2025, partially offset by hepatitis delta qualification batch manufacturing costs and to a lesser extent, higher clinical expenses in the first quarter of 2026. SG&A expense for the first quarter of 2026 was $23.3 million, which included $6.1 million of stock-based compensation expense compared to $23.9 million for the same period in 2025, which included $7.1 million of stock-based compensation expense. Our first quarter 2026 operating expenses totaled $132.3 million, representing a $10.3 million decrease compared to the same period in 2025. Net loss for the first quarter of 2026 was $125.7 million compared to a net loss of $121 million for the same period last year. Looking ahead, we will continue disciplined allocation of capital, prioritizing investments in those programs with the greatest potential for meaningful patient benefit and value creation. With that, I will now turn it back over to Marianne to close the call.
Marianne De Backer: To close, we are exceptionally well positioned for long-term value creation at this inflection point. Since December 2025, the combination of our collaborations with Norgine and Astellas, together with a successful financing has generated over $0.5 billion in capital, significantly strengthening our balance sheet. With the closing of our global collaboration with Astellas this quarter, we now have an established partner to advance VIR-5500 aggressively across the prostate cancer landscape while maintaining disciplined capital allocation. Overall, the combination of potent antitumor activity and a favorable safety profile underscores VIR-5500's potential as the best-in-class T cells engager for the treatment of prostate cancer. Beyond our clinical programs, we are steadily advancing 7 preclinical T-cell engager assets that utilize the PRO-XTEN platform and broaden our pipeline's optionality, positioning us well to generate the next wave of value creation. At the same time, our hepatitis delta program continues to generate compelling and increasingly differentiated clinical data with multiple near- and mid-term catalysts ahead across our ECLIPSE studies. Taking together with our progress in oncology, this momentum underscores the breadth of our scientific platforms and our ability to execute with focus, urgency and discipline. Looking ahead, our priorities are clear: to deliver rapid, high-quality clinical execution, advance multiple expansion and registrational-enabling studies and deploy capital thoughtfully in ways that maximize long-term value while keeping patients at the center of everything we do. With that, I'll turn the call over to Kiki to begin the Q&A session.
Kiki Patel: Thank you, Marianne. This concludes our prepared remarks, and we will now start the Q&A session. Joining me for the Q&A are Marianne and Jason. Please limit questions to two per person so that we can get to all of our covering analysts. I'll turn it over to you, operator.
Operator: [Operator Instructions] Our first question comes from Paul Choi with Goldman Sachs.
Kyuwon Choi: My first question is on 5818 in the HER2 setting. Can you comment on your level of interest in future development, particularly in HER2-positive breast cancer. It's not listed among the tumor types in your quarterly deck here. And so, I'm just curious, given the number of available therapies for that particular tumor type, sort of what is the criteria from your upcoming data set for potential development in that tumor type? And then I had a follow-up question.
Marianne De Backer: Thank you, Paul, for that question. Yes. So, we will be sharing data on our 5818 programs in the second half of this year, and this will be both for our monotherapy dose escalation and the dose escalation in combination with pembrolizumab. As to future development, we will, at that time, be able to provide a better picture as to what future expansion cohorts could be. Specifically, to your question on breast, I would say that, obviously, the bar is high, but do keep in mind that this drug, for example, like in HER2 has a 1% mortality rate. So, there's certainly still a prospect to come up with better treatments. But again, we will be sharing data second half of the year, and we'll then give further guidance.
Kyuwon Choi: Okay. Great. And with regard to 5500 and your comment on potential development earlier treatment settings, I guess, what would sort of, I guess, the framework for that be and potential timelines? Would you file an IND for that particular population this year or possibly in 2027?
Marianne De Backer: Yes. So just to recall that we already have a dose escalation ongoing for early line 5500 combined with an ARPI. What we are planning to do now together with Astellas, our collaboration partner, is start expansion cohort in the same setting, combination of VIR-5500 with enzalutamide. So that is something that is coming in expected coming months.
Operator: Your next question comes from Roanna Ruiz with Leerink Partners.
Unknown Analyst: This is Michael on for Roanna Ruiz at Leerink Partners. Regarding 5500 late-line MCRPC monotherapy expansion cohort, what would constitute a clear signal as a green light to initiate Phase III in 2027? Are you anchoring on like, PSA50, 90 or RECIST or PFS, something like that?
Marianne De Backer: Yes. So, we started first -- we dosed the first patient in the late-line expansion cohort for VIR-5500 monotherapy. We are going to, in that expansion cohort, explore a little bit more in-depth both pre- and post-radioligand therapy. So that will be additional data that we will be gathering. We only have a limited set of such patients in our initial cohort on which we reported data on February 23. And I would say it's going to really be the totality of the data. Obviously, PSA, RECIST, RPFS, we will have a more full data set to then decide on the next steps. But our goal is pending data, obviously, to start pivotal trials in 2027.
Unknown Analyst: Great. Just one more question. I also had a question about the underlying biology for PRO-XTEN cleavage. How tumor-specific is the protease activation profile across different tumor types? For example, are you seeing differential cleavage kinetic in like prostate versus colorectal or CLC that might affect that therapeutic index?
Marianne De Backer: Yes. One of the founders of the company that was acquired by Sanofi and from which we licensed the technology has been working in this field for over 20 years. And it's fair to say that the protease cleavable linker is really promiscuous linker. There's different families of proteases there to really ensure that you are going to be successful across a broad set of tumor types.
Operator: Your next question comes from Cory Kasimov with Evercore.
Mario Joshua Chazaro Cortes: This is Josh Chazaro on for Cory. Maybe one on hep B. As you approach the pivotal hep B data, wonder what your latest thoughts are on pricing there.
Marianne De Backer: Sure. Thank you, Josh. So, if you look -- first of all, hepatitis delta is an orphan disease. There's a number of anchor points for price that we can point to. The first one, I would say, is to look at the price of bulevirtide in Europe, which varies somewhere between $60,000 and 165,000 gross price. You can also look at the price of bulevirtide in Canada, which was set at, I believe, USD 115,000. And then if you look across your fellow analysts, I see that estimated prices vary somewhere between $150,000 and $250,000. We think that is very adequate for, again, a disease that is very severe, an orphan disease where we would be delivering substantial benefit for patients.
Mario Joshua Chazaro Cortes: And then just one -- another quick one on 5500 here, maybe following up on one of the previous questions, especially in the late-line castrate-resistant setting, is there a minimum durability you're looking for with you and Astellas before you move into a Phase III? Is there a number you guys have in mind or a certain competitive threshold you're looking at?
Marianne De Backer: Yes, not specifically. Again, we will be looking at, obviously, the totality of the data. I didn't hear it very well, but what your question on durability?
Mario Joshua Chazaro Cortes: Correct.
Marianne De Backer: Yes. Yes, I can only point to -- so what we know thus far is that several T-cell engagers have been showing durable responses. Our data set was still a little bit early, but also in our data set, you could already see that we had a number of resisted patients with data post 27 weeks confirmed partial responses. And also, we had a couple of patient cases, one patient that had been on treatment for 8 months. We had another patient that had been on treatment for a year and continuing. So we have sort of case examples of durability. And obviously, we will be looking in our broader data set for durability more consistently across the entire expansion cohort.
Operator: Your next question comes from Alec Stranahan with Bank of America.
Unknown Analyst: This is Matthew on for Alec. Congrats on the progress. I guess 2 for us on competitive landscapes. First for HDV. Just curious your thoughts on this year data that came out recently and whether that sort of changes your thoughts on commercial opportunity or competitive landscape? And then secondly, for EGFR T-cell engagers, competitor of yours recently discontinued development of theirs dual mask. I guess just what gives you confidence that your strategy will pan out where others have failed?
Marianne De Backer: Thanks, Matthew. Yes, on your first question, so as I laid out in the introduction, we -- and generally the key opinion leaders in the field very strongly believe that what really matters in a viral disease is to get rid of the virus. And the way that we measure that is through HDV RNA target multi-tectin. So, if you look at our levels of TMD for our monthly regimen of tobevibart and elebsiran, also 48 weeks, which is our primary endpoint, we achieved about 66%. And we have also shown that it really increases. It's actually increasing from 41% at 24 weeks to 66% at 48 weeks and then to 88% at 96 weeks. So, we saw that significant increase in target multitasking over time for our dual mechanism regimen. We did not see that actually for our monotherapy antibody. We saw it at about 30% TMD at 24 weeks and then sort of plateaued around 50%. It seems that what Mirum is sharing for their monthly therapy, which would be most comparable to our monthly therapy is only 5% target not detected. So that might not be very viable. And then for their weekly regimen, at 300 milligrams, they are showing at 24 weeks, 30% target not detected. So, we believe that from an efficacy perspective, we have a potential superior drug here and potential best-in-class regimen. Also from an ALT perspective, you can now see sort of across the different regimens that are in development that everyone is sort of landing around the 50%. We had 47% at 24 weeks. I think Mirum reported between 40% and 45%. So, ALT normalization seems to be sort of evening out across different regimens. But again, we do believe that it's really the viral efficacy measured by viral elimination and getting to undetectable that really matters. And there, we clearly have superior data. As to your question on EGFR, yes, Janux discontinued their EGFR T-cell engager. I would say the only sort of surprising thing there from our perspective is that they saw muscular skeletal issues that were mentioned as dose-limiting toxicity. That was unexpected and something, of course, that we will watch. But the reason why we strongly believe in the differentiation of our mask T-cell engagers is first, the masking technology is fundamentally different. So, we use steric hindrance. It's the same mask across all of our clinical programs. So, we don't need to redesign a new mask every time for every program. So, we really take learnings from one program to the next. And what we have seen with VIR-5500 is that, that masking technology allows you to dose much higher. And if you can dose higher, obviously, you can get potentially to a better therapeutic index. So, I would say that our masking technology is fundamentally different.
Operator: Your next question comes from the line of Phil Nadeau with TD Cowen.
Philip Nadeau: Two from us. First on 5818, you referenced the dose escalation data in the second half of the year. Can you give us some sense of what will be disclosed at that time, things like number of patients, duration of follow-up measures that you'll talk about, what tumor types will be in the update? That's the first question. And then second, on HDV, your presentation cites about 174,000 patients with HDV in the U.S. and Europe. We're curious how many of those you estimate are diagnosed and under the care of a physician, so could be amenable for therapy shortly after launch.
Marianne De Backer: Thank you, Phil. Yes, on 5818, so we will be sharing data both from our monotherapy dose escalation and also from the dose escalation in combination with pembrolizumab. A number of patients, we will share at a later date. I want to maybe point out that the 5818 trial is very different actually from our 5500 trial in the sense that it's a basket trial. So, we actually have a wide variety of tumor types in that trial. And we have already shown you some initial results, for example, in metastatic colorectal cancer, where we had a 33% confirmed partial response. So, we will be where possible and where we have enough patients in one given tumor type, be sharing you, of course, information on where we use CA to look at responses, tumor shrinkage, et cetera. So, we see it importantly as a signal-seeking trial that will give us information around what indications to potentially go into expansion cohort. And then your question on hepatitis delta. So, from those patients, we estimate that there are about 61,000 actively viremic patients here in the United States. And it's a hugely underdiagnosed disease, as I mentioned earlier. We believe that actually only about 10% to 15% of those patients are diagnosed at this moment in time. We do believe that once a regimen can become available that, that could really change. And the diagnostic testing is also getting better. For example, diagnostic tests for Delta are also relatively affordable. The Medicare reimbursement rate for an antibody test is $17 and for a quantitative RNA test about $43. The only difficulty at this moment in time is that patients often need to go 2 or 3 times to see their physician before all testing is done. The first time for hepatitis B test, the next time for the antibody test and the next time for the RNA test. So, there's a lot of streamlining that can happen. And in Europe, they have already shown that if you do reflex testing, so really when a patient tests positive for hepatitis B immediately proceed to testing for hepatitis delta on the same sample that, that could really increase diagnosis rates substantially. So that is something that if the guidelines get adopted here in the United States, that could drive a lot of difference.
Operator: Your next question comes from Etzer Darout with Barclays.
Unknown Analyst: This is Luke on for Etzer. For HCV, with the ECLIPSE-1 trial reading out in 4Q and then you have ECLIPSE 2 and 3 reading out in 1Q next year, how are you guys thinking about assuming a positive ECLIPSE-1 trial, is that going to be enough to support a BLA filing? Or do you need to wait for 2 and 3 to do that? And then on 5500 with the partnership with Astellas, and the announcement said that they will be responsible for all development activities after Phase I. Just wondering what kind of visibility you'll have into those trials as they enroll.
Marianne De Backer: Sure. I'll start with your last question on collaboration with Astellas. So, it is a global co-development and co-commercialization agreement, and we have quite significant joint governance in the deal. So, we have a joint development committee, of course, the joint steering committee, joint manufacturing committee, joint IP committee, joint finance committee and so on, with equal representation and joint decision-making with some level of escalation to executives, et cetera, pretty standard, I would say, for a 50-50 type of partnership. So, we will remain very intricately involved. We are, of course, running the Phase I trials now. And of course, Astellas are very involved in that as well. So, it doesn't really matter who operationally runs the trial. It's really important that we have pre-aligned on the clinical development plan and the associated budget, and we try to make decision-making, of course, jointly, but also very swiftly. And then your first question on what is required for filing. So, our guidance is that we would need a combination of ECLIPSE and ECLIPSE for filing. So we will have the ECLIPSE -1 data, as you mentioned, the fourth quarter of this year and then the ECLIPSE -2 is coming in the first quarter of next year.
Operator: Your next question comes from Sean McCutcheon with Raymond James.
Sean McCutcheon: Just one quick question from us. So, you've talked a bit to the competitor data in HDV. But maybe could you speak to the specific component of the competitor running an all-comer study with a meaningful proportion of patients with elevated ALT above the 5x the upper limit of normal? And any potential read-through to kind of how you guys are seeing the patient population here?
Marianne De Backer: Yes. So, the estimation is that maybe about 5% of delta patients have an ALT that is above 5x the upper limit of normal. And these kind of very high levels of ALT can have a lot of different reasons. We and KOL strongly believe that the real measure of looking at whether there is damage to the liver is looking at cirrhosis. And that's why we have enrolled more than 50% of patients in our trial that are CPTA-cirrhotic and have shown actually really good results, similar to slightly better in those type of patients.
Operator: Your next question comes from Joseph Stringer with Needham.
Joseph Stringer: 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?
Marianne De Backer: Yes. Thank you for that question. So, ECLIPSE-1, just to remind everyone, is a trial where we compare treatments with our regimen of tobevibart and elebsiran within the first treatment. So, it is almost like placebo-controlled trial, which makes it, of course, very, very likely that we will be successful in that trial. The bar for success is really low. I mean, again, target not effective, for example, for tobevibart, which is in Phase III development, 10 milligram is about 20%. So irrespective of the ALT levels with an endpoint of TND plus ALT, you cannot get more than 20%. And it was 12% for the 2-milligram tobevibart dose. So, the bar for success is not that high. But again, I think we have a combination of best-in-class variable efficacy and then again, ALT normalization that seems to be pretty similar across all regimens.
Operator: Your next question comes from Patrick Trucchio with H.C. Wainwright.
Luis Santos: This is Luis Santos in for Patrick. A follow-up question on the strategy for hep B has to do with where does the at-home self-administration strategy stand from a regulatory and device standpoint. Would you expect to launch to begin with the clinical administration before transitioning to that self-administration? And how -- and the follow-up question would be, by then, bulevirtide is expected to already be accepted in the U.S. How much do you think the at-home administration benefits versus hepcludex or bulevirtide?
Marianne De Backer: Yes. Thank you, Luis. So maybe answering your second question first. So, patients who will be on bulevirtide will have to inject themselves daily, and it's a chronic treatment, right? So really chronically every single day, they will need to inject themselves. And as I just mentioned, for bulevirtide 10 milligrams, the expected level of target effect that you can reach is about 20%. In contrast, what we have is a regimen of a combination of tobevibart and elebsiran, which is a monthly administration also subcutaneously, but with a level of targeted at 48 weeks of 66%. So, the chances of success for patients are much higher and the convenience is also much better. So, I think there will be a real potential desire for patients and physicians to look at such a regimen. In addition, we are running ECLIPSE-2 and ECLIPSE -2 is really looking at bulevirtide failures. So, patients that haven't been achieving adequate control of their virus on bulevirtide and then can switch to our regimen. So, we will also have data to show that, obviously, that makes sense for patients to do. As to your question for at home and at clinic, so the good news is that with our monthly administration subcutaneously, we have a very convenient offering, both for patients who want to do the administration at home. And of course, there's a lot of different ways we can achieve that and also actually for patients who might not be capable to inject themselves at home and where physicians and patients might think they prefer administration in office by physician, this level of once-month administration is really convenient to allow that to happen. So, we will be preparing at launch to have both available, both options at home and in office.
Operator: This concludes today's call. Thank you for attending. You may now disconnect.