Hello. Welcome to Veer Biotechnology's second quarter 2025 financial results and corporate update call. As a 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 Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke.

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 DeRink, 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 VirBiTechnology'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 Registrational Program for Hepatitis Delta. Following our first quarter milestone of enrolling the first patients in Eclipse I, we have now recently enrolled the first patients in both Eclipse II and Eclipse III, and all three registrational studies are now actively recruiting patients globally. Second, we've successfully initiated our Phase I study for VIR 5525, our EGFR 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 VIR 5818 and VIR 5500 advancing in their respective Phase I studies. We also received IND clearance to evaluate VIR-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 represents a significant near-term commercial opportunity for VIR-bio. The Eclipse registrational 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 solstice phase 2 data which demonstrated impressive biological responses with our combination therapy of tobevibart plus elapserone the hepatitis delta opportunity is particularly compelling from a commercial perspective for several reasons. Our comprehensive market analysis indicates approximately 7 million active viramic 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 U.S. 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 chips in Europe and other key international markets. Turning to our oncology portfolio, as mentioned, I'm very excited about VO5525, our dual-masked EGFR-targeted T-cell engager. 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 cetoximab and panitumamab face resistance mechanisms and significant toxicities that limit their use. For example, these therapies are not used in tumors with KRAS or BRAF 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-extend approach fundamentally changes this paradigm. By redirecting T cells to kill tumor cells expressing EGFR, peer 5525 has the potential to work across a much broader patient population, regardless of their mutational status, including those with KRAS mutations. Because peer 5525 harnesses the patient's own immune system to target EGFR-expressing tumors, 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 VIR 5525 exemplifies how we're leveraging our platform to potentially address major limitations of existing therapies. For VIR 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 pembrolizumab. For VIR 5500, our dual-masked PSMA-targeted T-cell engager, we continue our dose escalation study and recently obtained U.S. 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 ARPI represents an important step in exploring near 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 VIR 5500's potential in early alliance of prostate cancer treatment. and executing on our business development strategies to maximize the value of our efforts. 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 registrational program for hepatitis delta. Building on our first quarter milestone of enrolling the first patient in Eclipse I, we have now just recently enrolled the first patients in both Eclipse II and Eclipse III, and all three studies are now actively recruiting patients globally. We remain on track with our overall development timeline with primary completion for Eclipse I expected by December 2026. Let me now provide details on each study. Eclipse I is designed to evaluate our combination therapy in regions where bulvertide is not available or has limited use, including the United States. The study will enroll 120 participants, randomized two to one, to receive either our 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 II will enroll approximately 150 patients, randomized two to one, and evaluate switching to our combination therapy in patients who have not adequately responded to Bilevertide. This study addresses an important unmet need for patients who have limited options after Bilevertide treatment. Eclipse 2 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 1. Eclipse 3 is our Phase 2B study that will enroll approximately 100 patients comparing our combination therapy to blubber-tide and blubber-tide-naive patients. This head-to-head comparison will provide important data to support access and reimbursement discussions. Together, Eclipse 1 and 2 are designed to form the backbone of our regulatory submissions in the U.S. 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 fast-track in the U.S., plus prime 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 2 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 engager programs. As Marianne mentioned earlier, I'm pleased to report that we've successfully dosed our first patient in our Phase I study for VIR5525, our EGFR-targeted T-cell engager, 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, TKAs like osomertinib 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 panitumumab are ineffective in patients with KRAS mutations, which represent approximately 30 to 45 percent of cases. Similarly, in non-small cell lung cancer, where 25 to 30 percent of non-squamous tumors harbor KRAS mutations, current EGFR-targeted therapies have limited efficacy in this population. Third, KRAS inhibitors have been important advances in lung and colorectal cancer, but redundancy of the pathway and other resistance mechanisms result in eventual progression. Our VIR5525 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 Vera5525 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. Pre-clinically, Vera5525 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, Vera5525 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 VIR5525 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 VIR5525 will show a similar safety profile. In contrast to traditional oncology therapies that inhibit signaling through wild-type or mutated EGFR, VIR5525 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 I study is designed to address significant unmet needs across a focused group of tumor types with high EGFR expression. In non-small cell lung cancer, VIR5525 may benefit patients regardless of their tumor's specific driver mutations, whether they have EGFR mutations, KRAS mutations, BRAF mutations, or others. Our approach is potentially applicable to both major histological subsets, squamous and non-squamous. This includes tumors with high PD-L1 expression, where we can leverage the existing T-cell infiltration to enhance tumor killing. We will also be exploring combinations with pembrolizumab in this Phase I study. For colorectal cancer, approximately 80% of tumors express EGFR, yet current antibody therapies like cetuximab and penitumumab are not effective for the 30% to 45% of patients with K-RAS mutations. Our experience with VR5818 has shown promising activity in colorectal cancer, demonstrating that T-cell engagers using our ProXDEN 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 Avira 5525, potentially in combination with pembrolizumab, could offer a major advance by potentially avoiding the resistance mechanisms that limit current chemotherapy and targeted treatments. Metastatic cutaneous squamous cell carcinoma, approximately 80% of the tumors express EGFR and advanced disease as 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 I 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 pembrolizumab. We believe the combination with pembrolizumab represents a particularly promising approach. Pembrolizumab 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 lines. T-cell engagers like GEAR5525 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, Revere 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 VIR5818, 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 pembrolizumab. 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 ProExDen 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 Q-week and Q-3-week dosing schedule. The program is progressing with no maximum tolerated dose reached yet. The half-life of 8 to 10 days supports our Q3-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 VIR5500 across the prostate cancer treatment continuum. We look forward to generating a more comprehensive data set 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 ProExcend platform's clinical validation across three distinct targets is demonstrating its 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 sgna expenses for the second quarter of 2025 were 22.3 million dollars which included 5.5 million dollars of stock-based compensation expense compared to 30.3 million dollars for the same period in 2024 which included 9.1 million dollars 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 year-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. Four. 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 first patient dosed in Eclipse I. These amounts were previously expensed in prior quarters. These milestone payments were anticipated and are described in our SEC filings, including the 2024-10 . 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 continue 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 engager programs in clinical development, including VIR 5500, VIR 5818, and the recently initiated VIR 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 Ols from Morgan Stanley. Please go ahead.

Hey, thanks for sharing your question. It's Avi Novick 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 I. And then this might be a little bit premature, but, you know, I guess as we think about the TAM and HDV, can you tell us about any sort of prep work or thoughts on, you know, 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 some 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. You know, 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 U.S., because there's no approved therapy, there's no reflex testing, which is automatic testing in HBV-positive patients for Delta. So it's a little bit unclear right now, you know, how many patients there may be. I mean, we're estimating about 61,000 who are viremic in the U.S. right now. We suspect that's probably an underestimate once we get to the finish line and launch our therapy, which would be, you know, 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 for Eclipse and the other is 45525. So regarding Eclipse, if I hear correctly, you said that December 2026 primary completion for Eclipse 1. Is it fair to say that you already enrolled the majority of the 120 patients since the study is 48 weeks? My second question is regarding 5525. I saw your starting dose is only 3 microgram per kilogram. Since you expect similar safety profile for 5525 versus the other two targets and why now start at the higher dose? Also, will you test the both like a once-weekly dosing and a once-heavy dosing?

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 1, 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 and then ramps up as sites are activated enrolling 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 engages 55-25, so if I understood you correctly, you were asking why not start at a higher dose given sort of what we have learned from our prior programs? Mika, do you want to comment on that? Sure, sure.

Yeah, no, 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 MAPL dose. And so each molecule has, you know, they're in the same range, but they're in the same, you know, they have their own estimated Mabel dose. And that's, that's, you know, 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, 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, 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 PSMA 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 potentially later.

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

Hi, this is Daniel on for Paul. We're wondering if there are going to be additional data cuts from the Phase II SOLID study for the HDV program. And we're also wondering for the next data cut for VIR 5500 for TSMA, are you going to share PFS 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 SOLSTIS 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, Q3 weeks, and it's going very, very well. In terms of what specific data will 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 Alex. 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 U.S.? And then maybe on the TCE program, would you expect the next updates for 5818 and 5500 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?

So thank you for those questions. The first question is around whether we expect to need both Eclipse I and Eclipse II for the first registrational filing. That is our base case. That said, we have other scenarios that we could consider. If, for example, Eclipse I completed much ahead of Eclipse II, we could consider filing that along with Solstice for an initial approval in the U.S., that would have to depend on the strength of the data, discussions with regulators, including FDA. Having breakthrough therapy designation status in the U.S. and prime in Europe does allow us to have those conversations, but it's going to 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 5818 and 5500 and what to expect there. We haven't made final decision about exactly what those updates will look like, whether they'll be together or whether they'll be separate. For 5818, we have said that we have completed monotherapy dose escalation, but we're continuing with escalation with pembrolizumab, and we're currently analyzing all of the data, PK, PD, efficacy, looking at dose and schedule, and 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 want to be able to provide a meaningful update where you get a strong sense of depth, durability, dose response, you know, other key pieces of information.

Our next question comes from the line of Phil Nadeau for D.D. Cohen. Please go ahead.

Good afternoon. Thanks for taking our questions. Congrats on progress. First one on Eclipse 2. I believe that you are defining the enrollment criteria for that of patients who are on hep glutex who don't achieve HDV RNA less than 500 international units per ml. Can you talk about 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 questions. On the first question for Eclipse II, correct. These are patients who have been on Bilevertide for at least six months, are still viremic, and they are then eligible, you know, they meet other criteria as well for enrollment. We actually, identification of these patients is relatively straightforward because the investigators all know which of their patients are on Bilevertide. So, it's, you know, they can then test them to see what their level of viremia is, and then if they're eligible, they can be enrolled. So, I mean, identifying those patients is relatively straightforward. And then I think, you know, we randomized them, of course, to switch to bivobard and ellipseran versus continued blubber type with the 24-week primary endpoint of HDV target not detected, so virologic endpoint. I think it's a very appealing trial because, you know, patients who are still viremic on blubber tide, you know, then we'll have the opportunity to be tested on our regimen where we've been able to show, you know, approximately two-thirds of patients are achieving complete viral suppression. For your question about 5518, what's the next data release look like? Is it going to be, you know, monotherapy or, you know, holes per 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 cumbrolizumab. 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 Roana Ruiz from Leering Partners. Please go ahead.

Yes, hi. This is Mazian for Roana. Just one on the hepatitis space from us. So 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 that will ever try to have Cludex for the US. And 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 VR in our launch. So we would welcome that. opportunity, and particularly since, you know, we have a drug regimen with our combo of where we're achieving, you know, high levels of target not detected at week 48, you know, and we've shown, we expect to have above 60%, you know, all told that compared to 12% with levertine. 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 to undetectable in the majority of patients. It's clearly better than our monotherapy with tibivobard or 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 HB the 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 executing the trials well, and we're looking forward to helping as many patients as possible.

Thank you, Mark. I would just add that, 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, that's great, Marianne, really great comments. And the other point would be that, you know, with the monthly administration, we feel we're going to have a very, very superior convenience to Belvertide, which is daily, and other competitors are more likely going to be weekly within antibodies. So, we think from a convenience and adherence 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.

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 these alligators.

Yeah, so thank you for that question. So the types of patients that we are currently enrolling is 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 radial ligands. So we don't have quite yet a lot of data in that patient setting. But we do plan on opening in the U.S., 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 IND clearance to combine with androgen receptor pathway inhibitors in the frontline 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 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 week the 5500 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 the T-cell engager space is that most people have to step up dosing. Everybody has to step up dose. And 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 going to 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 going to be a key differentiator for our program.

Our next question comes from the line of Patrick Crucho from H.C. Wainwright. Please go ahead.

Good afternoon. Just a couple of follow-ups from us. Just a clarification question on whether the U.S. 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-to-head comparison versus Bolivar Tide. Can you talk about, you know, what you would need to see in that program? And is that primarily, you know, for the European or ex-US reimbursement? And what would you need to see to give confidence in that, you know, in that you can get reimbursement in that program internationally. And then just separately on the pro extent, I'm just wondering, you know, given this unique opportunity in KRS mutant tumors, particularly in CRC and lung, how are you designing 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 U.S. 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 a 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 U.S. If for some reason Eclipse 1 were to finish substantially ahead, we could talk to FDA about whether Eclipse I and Solstice could comprise the initial filing package and leverage our breakthrough therapy designation in the U.S. and by a prime designation in Europe to have those discussions. So those do remain potential options down the road. For Eclipse III, yes, as I remind everyone, it's a head-to-head study of Tibivirat and Lepsiran versus as a beloved type and beloved type naive patients. And we are looking at a virologic endpoint target not detected week 48 compared to beloved type. You know, beloved type is expected to be about 12%. You know, we expect to be north of 60% for our combination. So, you know, we are looking for superiority based on the virologic endpoint. The primary driver for the study of rationale for the 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 head-to-head data are always helpful, but primarily we are looking at that as a payer and access oriented study.

Yes, I can take on the pro-extend question. And so our 5-5-2-5 phase one study as standard, again, we have to enroll patients who must have exhausted all standard 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 The very important point is that the T-cell engager, our mass T-cell engager is a different mechanism of action all together. It is, you know, redirecting your immune cells to kill any tumor cells expressing EGFR. And by doing so, it uses it as an address. And so, 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 an EGFR mutation, as well as a 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 And because of that differential mechanism of that.

Our final question comes from the line of Joseph Stringer from Needham Company. Please go ahead.

Hi, thanks for taking our question. The Eclipse I trial has a 12-week deferred treatment period versus 24 weeks for a Phase III 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 of the bifibar and the left seran 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. 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 going to predict almost perfectly what's going to happen in week 48. You know, 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 do we expect spontaneous delta conversions to complete suppression in either setting. So I think it's 12 weeks is very patient-friendly. It's, you know, I think in terms of quality 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.