Vir Biotechnology, Inc.

Reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode. After the speaker's remarks, there will be a question and answer session. I will now turn the call over to Rich Lefke, Senior Director, Investor Relations. You may begin, Mr. Lefke.

Thank you, and good afternoon. With me today are Dr. Marianne DeBacker, our Chief Executive Officer, Dr. Mark Eisner, our Chief Medical Officer, Jason O'Byrne, our Chief Financial Officer, and Dr. Mika During, our Executive Vice President of Oncology, who will be available during the Q&A session. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q, and 8-K. I will now turn the call over to our CEO, Marianne DeBacker. Please go ahead.

Good afternoon, everyone, and thank you for joining us for VIEW by Technology's Second Quarter 2025 earnings call. I'm excited to share our progress with you today as we've achieved several important milestones across our pipeline this quarter. The past few months have been remarkably productive with significant advances in both our hepatitis delta and oncology programs. These achievements reflect our team's commitment to our mission of powering the immune system to transform patients' lives, and I'm grateful for both their dedication and your continued interest in our journey. Our key accomplishments this quarter demonstrate our continued momentum across our pipeline. First, we've made significant progress in our Eclipse registration program for hepatitis delta. Following our first quarter milestone of enrolling the first patients in Eclipse 1, we have now recently enrolled the first patients in both Eclipse 2 and Eclipse 3, and all three registrational studies are now actively recruiting patients globally. Second, we've successfully initiated our phase one study for VIEW 5525, our ETSR targeted T cell engager, marking our third clinical stage T cell engager program. And third, we've continued to make progress in our existing T cell engager programs with both VIEW 5818 and VIEW 5500 advancing in their respective phase one studies. We also received IMD clearance to evaluate VIEW 5500 in earlier lines of prostate cancer treatment in combination with androgen receptor pathway inhibitors. Let me now elaborate on our chronic hepatitis delta program, which will present a significant near term commercial opportunity for VIEW bio. The Eclipse registration program is designed to address different patient populations across the treatment continuum, from treatment naive patients to those who have not adequately responded to existing therapies. This comprehensive approach builds on our compelling SOSIS phase two data, which demonstrated impressive biological responses with our combination therapy of tobevibart-class elapsolone. The hepatitis delta opportunity is particularly compelling from a commercial perspective for several reasons. Our comprehensive market analysis indicates approximately 7 million active ceramic HDV RNA positive patients globally, including approximately 61,000 patients in the United States and 113,000 patients in the EU member countries plus the UK. The patient population is geographically concentrated, particularly in the United States, where delta patients are predominantly clusters in major urban centers like New York, Chicago, Los Angeles, and San Francisco. This concentration would allow for an efficient commercial approach with a targeted specialty sales force focused on hepatologists and infectious disease specialists. This disease has severe clinical outcomes, including accelerated progression to cirrhosis and a more than 50% 5.0 mortality rate within 10 years, creating a compelling case for effective intervention. The EMA orphan disease designation and the lack of FDA approved treatments in the US support a value-based pricing model similar to other rare disease therapies. Additionally, the high economic burden of untreated disease progression provides a strong economic rationale for effective treatment, while the regulatory designations we've received may help accelerate our development timeline. As we advance our hepatitis delta program toward potential commercialization, our strategy includes pursuing commercialization partnerships in Europe and other key international markets. Turning to our oncology portfolio, as mentioned, I'm very excited about VIA 5525, our dual-masked EGFR targeted T cell engagers. This program addresses a significant unmet need across multiple solid tumor types where EGFR is expressed. Despite years of development of EGFR targeted therapies, including tyrosine kinase inhibitors and monoclonal antibodies, these approaches have limitations. TKIs are primarily effective only in the subset of patients with specific EGFR mutations, while antibodies like Cytoxymab and Panitumumab face resistance mechanisms and significant toxicities that limit their use. For example, these therapies are not used in tumors with KRAS or BRAS mutations in colorectal cancer and head and neck squamous cell carcinoma, as they typically derive minimal or no benefit from current EGFR targeted treatments, leaving a substantial unmet need. The pro-extent approach fundamentally changes this paradigm. By redirecting T cells to kill tumor cells expressing EGFR, VIA 5525 has the potential to work across a much broader patient population, regardless of their mutational status, including those with KRAS mutations. Because VIA 5525 harnesses the patient's own immune system to target EGFR expressing tumor, we believe the likelihood of developing resistance to treatment that often occurs in these diseases is low. Mark will provide more details on the clinical development plan, but I want to emphasize that VIA 5525 exemplifies how we're leveraging our platform to potentially address major limitations of existing therapies. For VIA 5818, our dual-masked HER2 targeted T cell engager, we have completed the monotherapy dose escalation portion of our study and are now analyzing that data as we continue dose escalation in combination with temporal isomet. For VIA 5500, our dual-masked PSMA targeted T cell engager, we continue our dose escalation study and recently obtained US IND clearance to evaluate the program in earlier lines of prostate cancer. This expansion into first-line metastatic castration-resistant prostate cancer and hormone-sensitive disease in combination with ARPIs represents an important step in exploring VIA 5500's full potential across the prostate cancer treatment continuum. The PRO-X10 universal masking approach continues to demonstrate potential advantages in terms of safety profile and dosing flexibility across our T cell engager portfolio. This platform technology allows us to apply an identical masking approach across multiple targets, accelerating our development timelines for future programs. Beyond our clinical stage programs, we continue to advance multiple preclinical T cell engager candidates targeting various tumor-associated antigens. For these preclinical candidates, we're taking a strategic approach to development, advancing some internally while exploring potential partnerships for others where combining our platform with complementary expertise could maximize value and accelerate development timelines. Our financial position remains strong with approximately $892 million in cash, cash equivalents and investments at the end of the second quarter. This provides us with a cash runway extending into mid-2027, giving us resources to advance our key programs through critical value inflection points. Looking ahead, we're focused on several key priorities. Driving enrollment across all three Eclipse studies to advance our chronic hepatitis delta program towards registration. Advancing our clinical stage T cell engager programs, including exploring fear 5500 potential in early alliance of prostate cancer treatment. And executing on our business development strategies to maximize the value of our assets. With that, I'll now turn the call over to Mark to provide a more detailed update on our clinical development program.

Thank you, Marianne. We've made significant progress across both our infectious disease and oncology portfolios during the second quarter. And I'll walk you through the key developments. I'm excited to report substantial progress in our Eclipse registration program for hepatitis delta. Building on our first quarter milestone of enrolling the first patient in Eclipse one, we have now just recently enrolled the first patients in both Eclipse two and Eclipse three. And all three studies are now actively recruiting patients globally. We remain on track with our overall development timeline with primary completion for Eclipse one expected by December, 2026. Let me now provide details on each study. Eclipse one is designed to evaluate our combination therapy in regions where bleuvertide is not available or has limited use, including the United States. The study will enroll 120 participants, randomized two to one to receive either combination therapy or deferred treatment. The primary endpoint is a composite endpoint of HDV, RNA, target not detected, and ALT normalization at week 48. Eclipse two will enroll approximately 150 patients, randomized two to one, and evaluate switching to our combination therapy in patients who have not adequately responded to bleuvertide. This study addresses an important unmet need for patients who have limited options after bleuvertide treatment. Eclipse two has a 24 week primary endpoint of HDV, RNA, target not detected, which could potentially provide a readout at a similar time point as Eclipse one. Eclipse three is our phase two B study that will enroll approximately 100 patients comparing our combination therapy to bleuvertide and bleuvertide naive patients. This head to head comparison will provide important data to support access and reimbursement discussions. Together, Eclipse one and two are designed to form the backbone of our regulatory submissions in the US and Europe. This comprehensive approach addresses different patient populations and treatment scenarios, providing a robust evidence package for regulatory review and approval. The regulatory designations we've received, including breakthrough therapy and FastTrack in the US, PlusPrime and Orphan Drug in the EU, continue to facilitate productive interactions with regulatory authorities. These designations reflect the significant unmet need in hepatitis delta and the compelling data from our solstice phase two study where our combination regimen demonstrated impressive virologic responses. I'd now like to turn to our oncology portfolio where we've also made important advances this quarter across our T cell engagement programs. As Mary Ann mentioned earlier, I'm pleased to report that we've successfully dosed our first patient in our phase one study for VIR 5525, our EGFR targeted T cell engagement, which has the potential to address several critical limitations of current EGFR targeted therapies. EGFR has been a validated oncology target for many years with multiple approved therapies demonstrating clinical benefit in specific patient populations. However, current approaches face significant challenges. First, TKs like osmirtinib are primarily effective only in the subset of patients with specific EGFR mutations, leaving the majority of EGFR expressing tumors unaddressed. Second, in colorectal cancer, monoclonal antibodies like cetuximab and panetumumab are ineffective in patients with K-RAS mutations, which represent approximately 30 to 45% of cases. Similarly, in non-small cell lung cancer, where 25 to 30% of non-sclameless tumors harbor K-RAS mutations, current EGFR targeted therapies have limited efficacy in this population. Third, K-RAS inhibitors have been important advances in lung and colorectal cancer, but redundancy of the pathway and other resistance mechanisms result in eventual progression. Our VIR 5525 program takes a fundamentally different approach of redirecting the patient's own immune system to eradicate EGFR expressing tumors. The Universal Pro Extend dual mask design allows for selective activation in the tumor microenvironment where proteases can unmask VIR 5525 to unleash a potent T cell engager against EGFR expressing tumors. In normal tissues, where EGFR expression may occur, the masks remain intact and prevent any T cell activation. Preclinically, VIR 5525 has demonstrated potent protease-dependent tumor killing in xenograft models to a similar extent as the unmasked version. Importantly, no cell killing was observed in normal cells, even at very high concentrations in vitro. In safety studies with non-human primates, VIR 5525 showed an approximate 250-fold safety margin compared to the unmasked version with only minimal cytokine release syndrome and IL-6 elevation, substantially less than seen with the unmasked T cell engager in these models. What's particularly encouraging is that VIR 5525 uses the same masking technology as our other two clinical programs, both of which have demonstrated promising safety profiles so far. This consistent performance across multiple targets gives us confidence that VIR 5525 will show a similar safety profile. In contrast to traditional oncology therapies that inhibit signaling through wild-type or mutated EGFR, VIR 5525 is designed to be unmasked specifically in the tumor microenvironment where the unmasked TCE can effectively redirect T cells to kill EGFR-expressing tumors. Through this tumor-specific unmasking mechanism, VIR 5525 has the potential to treat a wide spectrum of tumors, regardless of their underlying mutational status or resistance mechanisms, while sparing normal tissues that express EGFR. With this broad potential in mind, our phase one study is designed to address significant unmet needs across a focused group of tumor types with high EGFR expression. Inosmosis lung cancer of VIR 5525 may benefit patients regardless of their tumor-specific driver mutations, whether they have EGFR mutations, K-RAS mutations, BRAF mutations, or others. Our approach is potentially applicable to both major histological subsets, squamous and non-squamous. This includes tumors with high PDL1 expression, where we can leverage the existing T cell infiltration to enhance tumor killing. We will also be exploring combinations with chlomeralizumab in this phase one study. For colorectal cancer, approximately 80% of tumors express EGFR, yet current antibody therapies like cetuximab and panetumumab are not effective for the 30 to 45% of patients with K-RAS mutations. Our experience with VIR 5818 has shown promising activity in colorectal cancer, demonstrating that T cell engagers using our pro-extend platform can be effective in this disease. In head and neck squamous cell carcinoma, over 90% of HPV negative tumors significantly express EGFR, and these HPV negative cases represent the majority of this cancer type. Despite cetuximab's approval, response rates remain low and resistance develops quickly. The overall prognosis and quality of life for these patients remains poor. Introducing a T cell redirecting therapy like VIR 5525, potentially in combination with chlomeralizumab, could offer a major advance by potentially avoiding the resistance mechanisms that limit current chemotherapy and targeted treatments. In metastatic cutaneous squamous cell carcinoma, approximately 80% of the tumors express EGFR, and advanced disease has limited treatment options beyond checkpoint inhibitors, to which nearly half of patients don't respond. Collectively, these indications represent hundreds of thousands of patients diagnosed annually with EGFR expressing tumors who face significant treatment challenges. Our pro-extend approach is designed to address these limitations through its unique dual masking technology and T cell engaging mechanism. The phase one study designed for 5525 has been optimized to efficiently assess proof of concept and incorporates extensive learnings from our VIR 5818 and VIR 5500 programs, potentially allowing for accelerated dose escalation and more efficient decision-making while prioritizing patient safety. We've designed a focused approach that includes both monotherapy and combination approaches with chlomeralizumab. We believe the combination with chlomeralizumab represents a particularly promising approach. Chlomeralizumab is already approved as first line therapy in non-small cell lung cancer and head and neck cancer, providing a strong foundation for combination and a potential path to earlier lives. T cell engagers like VIR 5525 can potentially convert cold tumors to hot tumors by recruiting T cells to the tumor microenvironment, potentially enhancing the efficacy of checkpoint inhibitors. With this strong scientific rationale, we've designed a robust yet focused clinical development program for VIR 5525 that is now recruiting at multiple sites. Having discussed our newest clinical program, I'd now like to provide updates on our other T cell engager programs. For VIR 5818, our HER2 targeted T cell engager, we have recently completed the monotherapy dose escalation portion of our study and are now analyzing that data as we continue dose escalation in combination with chlomeralizumab. We're taking a comprehensive approach to determine the optimal dose and schedule for advancing this program. We are encouraged by the responses we've seen in HER2 positive colorectal cancer patients, which are particularly noteworthy as these patients typically have limited options after progressing on these standard therapies. This activity in microsatellite stable patients who have traditionally immunotherapy resistant tumors underscores the potential of our pro-extend platform approach. Among these responses, we've observed one colorectal cancer patient who's maintained a durable response for over 18 months as of our January update, further supporting the promise of this approach. For VIR 5500, our PSMA targeted T cell engager, we continue to dose escalate on a two week and two, three week dosing schedule. The program is progressing with no maximum tolerated dose reach yet. The half-life of eight to 10 days supports our two, three week dosing evaluation, which could offer significant convenience advantages for patients. We're excited about the recent USIND clearance to evaluate VIR 5500 in combination with ARPIs in first line metastatic castration resistant prostate cancer patients and patients with hormone sensitive prostate cancer. This expansion into earlier lines of therapy and combination settings represents an important step in exploring the full potential of VIR 5500 across the prostate cancer treatment continuum. We look forward to generating a more comprehensive dataset as we continue to advance this program and remain committed to sharing meaningful updates as our programs progress. As we look to the future, our ProExTen platforms clinical validation across three distinct targets is demonstrating versatility and provides a strong foundation for our pipeline of preclinical candidates. This validation enables us to advance additional T cell engager candidates more efficiently and with greater predictability, whether independently or through strategic partnerships. In conclusion, I'm very pleased with the progress we're making across our entire portfolio. We remain focused on executing our clinical development plans with scientific rigor and operational excellence. With that, I'll now hand the call over to Jason.

Thank you, Mark. I'm pleased to share our second quarter financial performance and overall financial position. R&D expenses for the second quarter of 2025 were $97.5 million, which included $6.9 million of non-cash, stock-based compensation expense. This compares to $105.1 million for the same period in 2024, which included $13.1 million of stock-based compensation expense. The decrease was primarily driven by cost savings from previously announced restructuring initiatives, partially offset by clinical expenses from the initiation of our Eclipse Registrational Program, expenses associated with the progression of our oncology programs, and expenses incurred due to an increase in the fair value of potential future hepatitis delta milestone payments. SG&A expenses for the second quarter of 2025 were $22.3 million, which included $5.5 million of stock-based compensation expense, compared to $30.3 million for the same period in 2024, which included $9.1 million of stock-based compensation expense. The decrease was largely due to ongoing cost savings realized through headcount reductions and other restructuring initiatives. Our second quarter 2025 operating expenses totaled $119.6 million, representing a $42.1 million decrease from the same period in 2024. This -over-year reduction reflects the changes I just noted in R&D and SG&A expenses, plus the absence of $26.3 million in restructuring and impairment charges that were incurred in the second quarter of 2024. Net loss for the second quarter of 2025 was $111 million, compared to a net loss of $138.4 million for the same period in 2024. Turning to cash, our net cash consumed in the second quarter was approximately $127.7 million, which includes $50.5 million in milestone payments related to the first patient dose in Eclipse 1. These amounts were previously expensed in prior quarters. These milestone payments were anticipated and are described in our SEC filings, including the 2024 10K. Excluding these milestone payments, our quarterly net cash consumed was approximately $77.2 million. We ended the second quarter with approximately $892 million in cash, cash equivalents, and investments. Based on our current operating plan, we continued to project our cash runway extending into mid-2027. Our capital deployment strategy remains focused on our most promising programs. First, advancing our hepatitis delta eclipse registrational program. With all three registrational studies, Eclipse 1, 2, and 3, now actively enrolling patients globally, following the recent enrollment of the first patients in Eclipse 2 and Eclipse 3. Second, advancing our T-cell engagement programs in clinical development, including VIIR 5500, VIIR 5818, and the recently initiated VIIR 5525. We maintain strict financial discipline while focusing our resources on programs that can both create shareholder value and address significant unmet patient need. With that, I'll hand it back to Rich to initiate the Q&A session.

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

At this time, we will begin conducting our analyst Q&A session. Our first question comes from the line of Mike Holtz from Morgan Stanley. Please go ahead.

Hey, thanks for sharing your question. It's Avi Novak on the line for Mike. Yeah, so I guess just on HDV, could you perhaps give us a little bit of enrollment update on the Eclipse programs, particularly for Eclipse 1, and then the same question for you, which might be a little bit premature, but I guess as we think about the TAM and HDV, can you tell us about any sort of prep work or thoughts on how to further identify the prevalent patient population?

Thanks. Thank you, Ravi. I'll ask Mark to comment on that.

Yeah, thanks for the question. So yeah, we're really excited that we now have all three Eclipse registrational studies up and running with enrolling patients. Enrollment in Eclipse 1 is going very well. We were not in a position yet to provide more specific updates, but we have said before, we anticipate completing enrollment by the end of this year with a completion date for the primary endpoint of the end of 26. Eclipse 2 and Eclipse 3, we've just gotten up and running, so it's a little premature to make statements about how enrollment is going, but so far we're working really hard, executing really well, really excited about the investigator excitement and responsiveness for these programs. In terms of the work on prevalent HDV, I mean, I think what you're alluding to is, it is a challenge estimating the epidemiology of HDV because particularly in the US, because there's no approved therapy, there's no reflex testing, which is automatic testing in HPV positive patients for Delta. So it's a little bit unclear right now how many patients there may be. I mean, we're estimating about 61,000 who are viremic in the US right now. We suspect that's probably an underestimate. Once we get to the finish line in long-term therapy, which would be very attractive for patients, that there'll be more education, screening, and effort to find patients.

All

right, great. Thank you for taking our questions.

Our next question comes from the line of Jenny Wong from Barclays.

Thank you for taking my questions. I have a two and one is a four eclipse and the other is four five five two five. So regarding eclipse, if I hear correctly, you said that December, 2026 primary completion for eclipse one, is it fair to say that you already enrolled majority of the 120 patients since the study is 48 weeks. My second question is regarding five five two five. I saw your starting dose is only three micrograms per kilogram. Since you expect similar safety profile for five five two five versus the other two targets, why not start at the higher dose? Also, will you test the both, like once weekly dosing and once every dose?

Thank you. Thank you, Gina. It was a little bit difficult to hear you. So please correct us if we haven't fully understood the question. On eclipse one, you were referring to our primary data completion of December, 2026 and enrollment. So maybe Mark, you can comment on that. Yeah, I

would say we're not providing specific updates on enrollment, but recall that enrollment in trials always starts off slower than ramps up as sites are activated and rolling patients. All I can say is we're really pleased with how we're doing and we'll provide an update in the future. So stay tuned for that.

Okay, and then as it related to your question on our EGFR, T-cell engagement 5525. So if I understood you correctly, you were asking why not start at the higher dose given sort of what we have learned from our prior programs. Mika, do you wanna comment on that? Sure,

sure. Yeah, thanks for the question. So we are basically starting at a dose that is sort of standard by regulatory authorities for T-cell engagers, which is using the Mabel dose. And so each molecule has, they're in the same range, but they have their own estimated Mabel dose. And that's, we just have to do our start dose from there. But we do have a lot of confidence that we have the potential for a wide therapeutic index for 5525 in that this is a universal platform in that the masks are identical for 500 and 5818, and as are the protease linkers. And so in terms of you look at the preclinical data for 5500 and 5818, both of those programs have shown really robust potential for a wide therapeutic margin and safety profile. And similar, when we make those comparisons preclinically with 5525, again, we see this very encouraging and promising potential for a wide therapeutic margin looking at safety studies, toxicology studies, and animals and so forth. So we do believe that there is this wide potential for this molecule and we'll be able to accelerate this program much faster given the learnings that we've had from both the two previous HER2 and the MPSMA programs. And as far as testing other dosing regimens, just as standard for the IND studies, we are required to study this initially weekly, but we are certainly, again, our preclinical data does suggest that we would have a potentially good half-life to be able to dose less frequently, Q3 week and particularly later.

Our next question comes from the line of Paul Choi from Goldman Sachs. Please go ahead.

Hi, this is Daniel Ahn for Paul. We're wondering if there are gonna be additional data cuts from the phase two solid study for the HDV program. And we're also wondering for the next data cut for VIR 5500 for TSM-A, are you gonna share PFS-D? Are there gonna be any additional data or radiology-based measurements in addition to PSA biomarkers? Thank you.

So thanks for the question. We do plan to provide an update on the SOLSTAS study, the complete 48-week data by the end of the year. So stay tuned for that. For 5500 next data cut, we haven't provided guidance about exactly when that will be. We do want it to be a very meaningful update. We're currently escalating in Q1, Q2, three weeks, and it's going very, very well. In terms of what specific data we'll present, also we haven't provided guidance there, but we will try to provide clear evidence of dose response, of depth and durability, the PSA responses and other biomarkers and other measures. So we'll provide more detail on what to expect at a later date.

Thank you. Our next question comes from the line of Alex Tranahan from Bank of America. Let's go ahead.

Hey guys, this is Matthew on for Alec. I appreciate you taking our questions. Maybe first one from us on Eclipse. Can you just remind us whether both Eclipse 1 and 2 data is needed for registration in the US? And then maybe on the TCE program, would you expect the next updates for 58, 18, and 5,500 to be sort of the go, no-go point for these studies? Would we expect a final decision on dosing frequency for those programs as

well? Thanks. So thank you for those questions. The first question is around whether we expect to need both Eclipse 1 and Eclipse 2 for the first registrational filing. That is our base case. That said, we have other scenarios that we could consider. If, for example, Eclipse 1 completed much ahead of Eclipse 2, we could consider filing that along with Solstice for an initial approval in the US. That would have to depend on the strength of the data, discussions with regulators, including FDA, having breakthrough therapy designation status in the US and prime in Europe does allow us to have those conversations, but it's gonna depend on the relative speed of enrollment of the trials. And as a reminder, Eclipse 2, although it started a little bit later, has a 24 as opposed to a 48-week primary endpoint. So it could complete around the same time as Eclipse 1, but it's a little early to say for sure. I think your next question was around data updates for the 58, 18 and 5,500 and what to expect there. We haven't made final decision about exactly what those updates will look like, whether they'll be together, whether they'll be separate. For 58, 18, we have said that we are, we've completed monotherapy dose escalation, but we're continuing with escalation with Cumberlyzumab and we're currently analyzing all of the data, PK, PD, efficacy, looking at dose and schedule and making, we'll be making decisions about next steps of development. So we would expect to provide that at an upcoming time. And for 5,500, again, it's a little early to be definitive about what we'll provide, but as I was saying before, we wanna be able to provide a meaningful update where you get a strong sense of depth, durability, dose response, other key pieces of information.

Our next question comes from the line of Phil Nadeau for TD Cowan, please go ahead.

Good afternoon, thanks for taking our questions. Congrats on the progress. First one on Eclipse 2, I believe that you are defining the enrollment criteria for that of patients who are on HEP-Clutex, who don't achieve HDV RNA, less than 500, international units per ML. Can you talk about how you're identifying those patients and how easy you expect it to be to recruit that trial? That's the first question. And then second, just in terms of updated data for 5518 in particular, sounds like the monotherapy dose escalation is completed. Are there any thoughts to releasing that monotherapy data once you're done analyzing it, or will you hold that data to have the combo data as well?

Thanks. Sure, so thanks for your questions. On the first question for Eclipse 2, correct. These are patients who have been on the levertide for at least six months, are still viremic, and they are then eligible, they meet other criteria as well for enrollment. We actually, identification of these patients relatively straightforward, because the investigators all know which of their patients are on levertide. So they can then test them to see what their level of viremia is, and then if they're eligible, they can be enrolled. So identifying those patients is relatively straightforward. And then I think we randomized them, of course, to switch to Bivobartone and Lebseron versus continued levertide with the 24-week primary endpoint HDV target not detected, so virologic endpoint. I think it's a very appealing trial because patients who are still viremic on levertide then will have the opportunity to be tested on our regiment where we've been able to show approximately two thirds of patients are achieving complete viral suppression. For your question about 50.18, what's the next data release look like? Is it gonna be monotherapy or we're gonna hold for combination? Yeah, we really haven't decided. I mean, we're looking at the totality of the data now. We're escalating in combination with Hormerolizumab. That's going very well. So we'll just have to make a decision about what would be the most appropriate update and what would be the most appropriate setting for that update.

Our next question comes from the line of Rhonda Ruiz from Living Fact Partners. Please go ahead.

Yes, hi, this is Maisie, on for Rhonda. Just one on the hepatitis space for muscle. How do you view the evolving competitive landscape in the chronic hepatitis delta space? And then what advantages do you see for your accommodation approach in terms of market positioning?

Sure, so in terms of the competitive landscape, you know, it's a couple of comments. One is, you know, Gilead apparently has or is refiling a bell ever try to have critics for the US. And, you know, we don't know about the timing specifically, but assuming that they would get approved sometime in 2026, we actually think that'd be a big positive for us because having Gilead going out and starting that education of physicians and healthcare providers and promoting testing for HTV would help prepare the way for VIR in our launch. So we would welcome that opportunity. And particularly since we have a drug regimen with our combo of to the left hand where we're achieving high levels of target not detected a week 48, you know, we've shown we expect to have above 60%, you know, with the lever time. So we think we have a very compelling clinical case to make there in terms of the combo approach. You know, I think we're very excited about it because we're suppressing the virus undetectable in the majority of patients. It's clearly better than our monotherapy with to be prepared our antibody. So we think we can beat other monoclonal antibodies as well in terms of viral suppression. We also can suppress hepatitis B surface antigen by three logs, which is multiple logs greater than a monoclonal antibody alone. And recall that you need the HPV surface antigen for the Delta virus to replicate itself. So we're starving the Delta virus of what it needs for its viral life cycle. So I think all in all, we feel like we have a best in disease best in class approach and we're, you know, executing the trials well and we're looking forward to helping as many patients as possible.

Thank you, Mark. I would just add that, you know, as Mark mentioned, we have a profile that really has the potential to set a new standard of care. And obviously, you know, with more entrance centering to the market, it's also really a testament to the unmet need that we are seeing in hepatitis Delta and obviously the commercial opportunity that it represents.

Yeah, and that's great, Marianne, really great comments. And the other point would be that, you know, with a monthly administration, we feel we're gonna have very, very superior convenience to blevertide, which is daily and other competitors are more likely gonna be weekly with an antibody. So we think from a convenience and an insurance point of view, we're feeling very good about where we're landing there.

Our next question comes from the line of Sean McCutcheon from Raymond James, please go ahead.

Hi guys, thanks for the questions. Just a couple on 5500 for us. Can you speak to the patients you've been enrolling since the prior update for 5500? Obviously a lot of focus on the post-PSMA radio ligand setting. Are you prioritizing this patient population and should we anticipate a meaningful look at activity in that patient population at the next update? And then additionally, can you provide your view on the relative importance of less frequent dosing for 5500 and maybe perhaps speak to the biologic rationale for less frequent dosing or dosing holiday as it relates to T cell exhaustion for T cell gators? Thanks.

Yeah, so thanks for that question. So the types of patients that we are currently enrolling in sort of a standard first in human phase one where they must have exhausted all standard of care. Now, having said that, where we are currently open right now is in Australia and in Europe. And in those settings, there aren't as many, there are some, but there aren't as many patients who've had prior radio ligand. So we don't have quite yet a lot of data in that patient setting, but we do plan on opening in the US and we do plan on trying to generate that data in late line setting. But we're also excited about going into the early line setting as well. We've recently, as Mark had mentioned, that opened, have an ID clearance to combine with androgen receptor pathway inhibitors in the front line setting in a very early metastatic hormone sensitive prostate cancer setting as well as a biochemical recurrent setting. And so that early line setting I think will be quite meaningful for something like this with our current toxicity profile. And then that sort of also relates to the less frequent dosing. So we have demonstrated with the HER2 program that we can dose less frequently at Q3 a week and see a similar safety and efficacy profile thus far. We are currently encouraged of what we're seeing. We're now dosing at Q3 a week in the 5,500 program as well. And what we've learned from the HER2 program at least is that we don't see resensitization during that week holiday. So I think this is an important factor in T cell engager space is that most people have to step up dosing. Everybody has to step up dose. And then the reason to get that is to desensitize so that you can get to much higher doses. But then once you get up there, what's really next important is to have a reasonable half-life that allows you to then do less frequent dosing and then you don't have that resensitization. And that's been proven out with the HER2 program. And similarly, efficacy we've seen at the same doses, either Q week or Q3 week efficacy in the HER2 program. So we think that this bodes well for the 55 program. It has a slightly longer half-life than the HER2 program. And then this is gonna be so important in the early line setting where dosing strategies are often for months, if not years, and to have a much less frequent dosing is gonna be a key differentiator for our program.

Our next question comes from the line of Patrick Cucho from HCE Wainwright. Please go ahead.

Thanks, good afternoon. Just a couple of follow-ups from us. Just a clarification question on whether the US regulatory filing could proceed based on Eclipse 1 and solstice or is the base case still for both Eclipse 1 and 2. And then just with Eclipse 3, this is the head of the US regulatory filing -to-head comparison versus bullet-vertein. Can you talk about what you would need to see in that program and is that primarily for the European or ex-US reimbursement and what would you need to see to give confidence in that you can get reimbursement in that program internationally? And then just separately on the pro-extend, I'm just wondering, given this unique opportunity to see the 5525 program and the 5525 program to ensure you capture that population.

Okay, so a couple of quick questions on Delta. The first one has to do with the US regulatory filing and what we expect we need. You're right, we do expect Eclipse 1 and 2 to be the base case for filing. I do think that if they finish in the similar timeframe, which we expect that would be ideal, we would use both of those as the sort of core part of the filing for the US. If for some reason Eclipse 1 were to finish substantially ahead, we could talk to FDA about whether Eclipse 1 and Solstice could comprise the initial filing package and leverage our breakthrough therapy designation in the US and our prime designation in Europe to have those discussions. So those do remain potential options down the road. For Eclipse 3, yes, we're reminded once a -to-head study to be able to write in the lepseran versus belovedrhtide and belovedrhtide is naive patients. And we are looking at a viral biologic endpoint, target not detected, week 48, compared to belovedrhtide. Belovedrhtide is expected to be about 12%. We expect to be north of 60% for our combination. So we are looking for superiority based on the viral biologic endpoint. The primary driver for the study, Russian office study is to enable European payer HTA negotiations around price and access. It will comprise data that will be useful for all of our filings globally on the safety data side. And also a dead data are always helpful, but primarily we are looking at that as a payer and access oriented study.

Yes, I can take on the ProExtend question. So our 5525 phase one study as standard, again, we have to enroll patients who must have exhausted all standard of care. And that includes any KRAS inhibitors that are approved in either lung cancer or any other space. And so we do anticipate that we will be able to enroll these patients. But I think a really very important point is that the T cell Engager, our mass T cell Engager is a different mechanism of action altogether. It is redirecting your immune cells to kill any tumor cells expressing EGFR. And by doing so, it uses it as an address. And so it's regardless of the downstream mutations that are there. So it should work in tumor types that are driven by KRAS, as well as any other mutation, even EGFR mutation, as well as the multitude of other mutations that happen in lung cancer. So I think this is a unique modality that could either go anywhere in the journey of a patient with lung cancer, it potentially could combine with a KRAS inhibitor, again, because of that differential mechanism of action.

Our final question comes from the line of Joseph Stringer from Needham Company, let's go ahead.

Hi, thanks for taking our question. The Eclipse-1 trial has a 12 week deferred treatment period versus 24 weeks for a phase three competitor. So can you remind us the rationale for the 12 weeks here and what's the potential impact on trial success or potential differentiation? Thanks.

Yeah, so a good question. So Eclipse-1 randomizes us to our regimen at the Bivouvard and Lefzeran versus a 12 week deferred treatment period. And the primary endpoint is actually a 48 weeks for our combination versus 12 weeks in the deferred treatment arm. The rationale for that is that Delta virus without any treatment, essentially we expect essentially zero patients to spontaneously clear the Delta virus. So a 12 week deferred treatment arm is really acceptable because it's gonna predict almost perfectly what's gonna happen in week 48. We have agreement from FDA and EMA on that point. 12 weeks is in our mind better than 24 weeks operationally because it's a more appealing design for patients because they don't have a long time to wait if they get randomized to the deferred treatment arm to cross over to the active treatment arm. So we think it's a very patient friendly design from that standpoint. From a probability of success, I would say 12 versus 24 weeks is essentially the same because in neither time period we expect spontaneous Delta conversions to complete suppression in either setting. So I think it's 12 weeks is very patient friendly. I think in terms of probability of success, it's also very attractive.

This concludes the Q&A session of the call. Thank you for participating and I'll turn the call back over to Rich.

Thank you, operator. Thank you all for your continued support and for joining us today. Look forward to updating you on our progress in the coming months. Operator, you may end the call.