Vir Biotechnology - Earnings Call - Q1 2025

Executive Summary

• Q1 2025 revenue was $3.03M and diluted EPS was $(0.88); revenue fell sharply year-over-year due to lapping a $51.7M deferred revenue recognition in Q1 2024 tied to GSK option expiry, while EPS was slightly worse than Wall Street consensus, and revenue missed materially (Consensus: $8.59M revenue, $(0.84) EPS; Actual: $3.03M, $(0.88)).*
• Vir enrolled the first patient in the Phase 3 ECLIPSE-1 registrational program in chronic hepatitis delta (HDV) and reaffirmed cash runway into mid-2027 (~$1.02B cash/investments), positioning for critical catalysts (EASL HBV functional cure data May 9; ECLIPSE-2 initiation; VIR-5525 Phase 1 start).
• Oncology TCE programs continued to dose-escalate: VIR-5818 (HER2) showing 33% confirmed PR in HER2+ CRC at ≥400 µg/kg and durable response >18 months; VIR-5500 (PSMA) with 58% PSA50 responses ≥120 µg/kg, both with favorable CRS profiles; VIR-5525 (EGFR) Phase 1 initiation on track in Q2 2025.
• Guidance: Cash runway maintained into mid-2027; CHB advancement contingent on securing a global partner; management emphasized accelerated regulatory path in HDV (Breakthrough/Fast Track, PRIME/Orphan).

What Went Well and What Went Wrong

• What Went Well

  • “We successfully initiated our ECLIPSE Phase III registrational program with the first patient enrolled in ECLIPSE-1 during the first quarter,” marking a key HDV milestone with breakthrough/fast-track and PRIME/orphan designations.
  • Oncology progress with dose escalation and early signals: VIR-5818 showed 33% confirmed PR in HER2+ CRC and durable response >18 months; VIR-5500 showed 58% PSA50 responses without prophylactic steroids and minimal CRS.
  • Strong balance sheet: approximately $1.02B cash, cash equivalents, and investments; runway into mid-2027, enabling execution through inflection points.

• What Went Wrong

  • Revenue fell to $3.0M from $56.4M in Q1 2024, driven by the absence of the prior-year $51.7M deferred revenue recognition from GSK option expiry; net loss widened to $121.0M (from $65.3M).
  • R&D rose to $118.6M (vs. $100.1M) largely due to a $30.0M expense related to Alnylam and ECLIPSE initiation; SG&A fell to $23.9M but overall operating loss increased on lower revenue.
  • HBV program advancement requires a worldwide development and commercialization partner; until secured, the program is gated, creating execution risk.

Transcript

Operator (participant)

Hello. Welcome to Vir Biotechnology's first quarter 2025 financial results and business 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 presentation, 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.

Rich Lepke (Senior Director of Investor Relations)

Thank you and good afternoon. With me today are Dr. Marianne De Backer, our Chief Executive Officer, Dr. Mark Eisner, our Chief Medical Officer, Jason O'Byrne, our Chief Financial Officer, and Dr. Mika Derynck, 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, Dr. Marianne De Backer.

Please go ahead.

Marianne De Backer (CEO)

Thank you, Rich, and good afternoon, everyone. Thank you for joining us for Vir Biotechnology's first quarter 2025 earnings call. I'm pleased to share our progress and achievements with you today as we continue to execute on our strategic priorities. Before we dive in, I want to express my gratitude for your continued support and interest in our mission of powering the immune system to transform patients' lives. We've had a strong start to 2025 with meaningful progress across our pipeline. Our strategic focus on advancing both our infectious disease and oncology programs continues to position us well for future growth and value creation. I'm pleased to share that we successfully initiated our ECLIPSE Phase 3 registration program with the first patient enrolled in ECLIPSE 1 during the first quarter.

This is a significant milestone in our commitment to develop a potential new standard of care for patients with hepatitis delta virus infection. The ECLIPSE program builds on our SOLSTICE Phase 2 data, which demonstrated impressive virological responses with our combination therapy. Today, I'd also like to provide a refined assessment of the hepatitis delta market opportunity, which reflects the pre-launch work we have initiated in parallel with our Phase 3 trials to better characterize the addressable patient population. Based on our comprehensive market analysis, we estimate that there are approximately 7 million active viremic HDV RNA-positive patients globally. In the U.S., we estimate approximately 61,000 RNA-positive patients. In EU member countries, plus the U.K., we estimate approximately 113,000 RNA-positive patients. Additional geographies beyond these could represent long-term opportunities.

I want to emphasize that these figures specifically focus on RNA-positive patients with active viremic disease who would be candidates for treatment. This distinction is important because we focus specifically on patients with detectable viral replication who face the highest risk of disease progression. We've conducted an extensive evaluation of multiple epidemiological sources and consulted with leading experts in the field to arrive at these estimates. It's important to note that our updated understanding of the market size underscores that hepatitis delta has the characteristics of a rare disease market with significant commercial potential. Let me highlight a few key points. First, this is a disease with severe outcomes. More than 50% of hepatitis delta patients succumb to liver-related death within 10 years of diagnosis, and there are no FDA-approved treatments in the United States.

Second, treatment is managed by a concentrated group of hepatologists and liver specialists, allowing for a focused commercial engagement. Third, the severe clinical outcomes and EMA orphan disease designation support a value-based pricing model similar to other rare disease therapies. Fourth, the high-cost burden of untreated disease progression, including liver transplantation and end-stage liver disease management, provides a compelling economic case for effective treatment. Finally, our market research indicates high physician intent to treat these patients given the lack of effective options. The regulatory designations we've received—breakthrough therapy, fast track in the United States, and prime and orphan drug in the EU—underscore the potential impact of our approach and may help accelerate our development timeline. We are focused on driving enrollment in our ECLIPSE 1 trial and preparing for the ECLIPSE 2 and 3 study initiation.

As we advance our hepatitis delta program, I'm also pleased to report that during the quarter, we reached an agreement with Alnylam whereby they elected not to opt into the profit-sharing arrangement for elebsiran, resulting in a continued milestone and royalty-based structure. This decision provides clarity for our approach to advance our hepatitis delta program and gives us the flexibility to partner the program in Europe and other international markets. The outcome of this agreement was anticipated and factored into our long-term financial planning and was already included in our projected cash runway extending into mid-2027. Jason will provide additional details on the financial aspects of this agreement later in the call. Turning briefly to our hepatitis B program, we are presenting 24-week post-treatment follow-up data from our MARCH Phase 2 study at the upcoming EASL Congress on May 9th.

Specifically, we will be sharing functional cure data from participants who have completed 24 weeks of follow-up after treatment discontinuation. Shifting gears to our oncology portfolio, we continue to make steady progress with the PRO-XTEN dual-masked T-cell engager program. As a reminder, we have worldwide rights to the PRO-XTEN platform in infectious disease and oncology. For VIR-5818, our dual-masked HER2 targeted T-cell engager, we're continuing to dose escalate as monotherapy and in combination with pembrolizumab. Our data presented in January showed a 33% confirmed partial response rate in HER2-positive colorectal cancer patients at doses of 400 micrograms per kilogram and above, with one response lasting over 18 months. We're particularly encouraged by these results in colorectal cancer, where there remains a significant unmet need for effective therapies.

These responses were observed in microsatellite stable tumors, which are typically resistant to immunotherapy, suggesting VIR-5818 could potentially address an important treatment gap for these patients. For VIR-5500, our dual-masked PSMA targeted T-cell engager, we continue to dose escalate given our favorable safety profile and the learnings from VIR-5818. We've evaluated multiple additional dose levels since our last update. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines, with 58% achieving a PSA50 response, all without prophylactic steroids and with minimal cytokine release syndrome. We continue to see strong investigator enthusiasm for this program based on the early signals we've observed. We're also on track to initiate our Phase 1 study for VIR-5525, our dual-masked EGFR targeted T-cell engager this quarter.

This program has the potential to address multiple high-value indications, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and other EGFR-expressing tumors. The Pro-XTEN universal dual-masking approach continues to demonstrate potential advantages in terms of safety profile and dosing flexibility. Beyond our clinical stage programs, we are rapidly advancing several next-generation targets in areas of high unmet medical need. Our antibody discovery and protein engineering capabilities are key to the discovery of new tumor-associated antigen binders to quickly advance new TCE programs. The universal nature of the Pro-XTEN platform allows us to efficiently apply our dual-masking approach. The synergies between antibody discovery capabilities and the Pro-XTEN platform have begun to translate into meaningful progress, with seven targets progressing in preclinical development across a number of solid tumor indications with high unmet need. These research efforts represent important long-term value drivers for our oncology portfolio.

We're also exploring potential collaborations that could further unlock and maximize value from the Pro-XTEN platform. Additionally, leveraging our expertise in infectious disease immunology, we have advanced a broadly neutralizing antibody to development candidate status in our HIV cure program. Looking ahead, our financial position remains strong, with approximately $1 billion in cash, cash equivalents, and investments at the end of the first quarter. This provides us with cash runway extending into mid-2027, giving us the resources to advance our key programs through critical value inflection points. We're maintaining a disciplined approach to capital allocation, focusing our resources on our most promising programs. As we continue to execute on our strategic priorities, we recognize the challenging market environment facing the biotechnology sector as a whole.

In times like these, we believe the most important thing we can do for our shareholders is to remain focused on operational excellence and advancing our pipeline with discipline and purpose. Our strong cash position allows us to weather market volatility. I'm confident that our focused approach to developing potentially transformative medicines for patients with significant unmet needs will make a difference in the lives of patients while driving value creation for our shareholders. With that, I'll now turn the call over to Mark to provide a more detailed update on our clinical development programs.

Mark Eisner (Chief Medical Officer)

Thank you, Marianne. I'm pleased to provide an update on our clinical development programs. We've made significant progress across both our infectious disease and oncology portfolios during the first quarter, and I'll walk you through the key developments.

Let me start with our hepatitis delta program, where we've achieved an important milestone with the initiation of our registrational ECLIPSE Phase 3 program. I'm pleased to report that we enrolled the first patient in ECLIPSE 1 during the first quarter, keeping us on track with our development timeline. ECLIPSE 1 is designed to evaluate our combination therapy in regions where bulevirtide is not available or has limited use, including the United States. The study will enroll 120 participants randomized 2-to-1 to receive either our combination therapy or deferred treatment. The primary endpoint is a composite endpoint of HDV RNA target not detected, meaning that there was no measurable presence of the virus in the blood and ALT normalization at week 48. The key secondary endpoint is HDV RNA target not detected.

We're also preparing for the initiation of ECLIPSE 2, which will evaluate switching to our combination therapy in patients who have not adequately responded to bulevirtide. ECLIPSE 2 will have a 24-week primary endpoint of HDV target not detected. Together, ECLIPSE 1 and 2 are designed to form the backbone of our regulatory submissions in the United States and Europe. This comprehensive approach addresses different patient populations and treatment scenarios, providing a robust evidence package for regulatory review. These studies will include both non-cirrhotic participants and those with compensated cirrhosis. This broad eligibility is important as it reflects the real-world patient population and will provide valuable insights into the treatment effects across different stages of disease.

The regulatory designations we've received, breakthrough therapy and fast track in the United States, and prime and orphan drug in the EU, reflect the significant unmet need and the potential of our approach to address it. These designations may help accelerate our development and review timelines, potentially bringing this important therapy to patients sooner. At the upcoming EASL Congress, we'll be presenting a poster showcasing data from a 24-week subgroup analysis of our SOLSTICE trial, examining the impact of baseline viral parameters and cirrhosis status on responses to our combination therapy. For our hepatitis B program, we'll be presenting 24-week post-treatment follow-up data from our MARCH Phase 2 study at EASL on May 9. This presentation will provide insights into functional cure after treatment discontinuation. As a reminder, advancement of this program into further clinical development is contingent on securing a partner.

Now, I'd like to turn to our oncology portfolio, where we continue to make progress with the Pro-XTEN masked T-cell engager programs. Our dual-masked approach is designed to selectively activate T-cell engagers in the tumor microenvironment, potentially providing a wider therapeutic window than traditional unmasked approaches. Our Pro-XTEN masked TCEs achieve this through the addition of long hydrophilic polypeptide XTEN masks that shield both the CD3 and tumor-associated antigen binding domains by steric hindrance. Importantly, these universal masks are cleaved by proteases found within the tumor microenvironment, enabling selective activation where it's needed most. This technology allows for higher dosing with reduced systemic toxicity, which we believe could translate to improved efficacy and safety profiles. The selective activation in the tumor microenvironment is key to minimizing off-target effects while maximizing anti-tumor activity.

For VIR-5818, our HER2-targeted T-cell engager, we're continuing dose escalation in both monotherapy and in combination with pembrolizumab. As a reminder, our data presented in January showed a 33% confirmed partial response rate in HER2-positive colorectal cancer at doses of 400 micrograms per kilogram and above, with one response lasting over 18 months. This durability is particularly encouraging in this heavily pretreated population. Importantly, as Marianne mentioned, the responses we observed in microsatellite stable colorectal cancer are noteworthy from a mechanistic perspective. These tumors typically have low tumor mutational burden and limited T-cell infiltration, creating significant challenges for immunotherapy approaches. Our data suggest that VIR-5818's ability to redirect T-cells to HER2-expressing tumor cells may provide a way to overcome these immunological barriers.

The durability of response we've seen further supports the potential of this approach in a setting where patients typically experience rapid progression after exhausting standard treatment options. We remain focused on evaluating the potential of this program across multiple HER2-expressing tumor types, as we believe our approach could address significant unmet needs in various solid tumors where HER2 expression plays a role. For VIR-5500, our PSMA-targeted T-cell engager, we're advancing our dose escalation strategy in both weekly and Q3-week dosing regimens. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines, with 58% achieving a PSA50 response, all without prophylactic steroids and with minimal cytokine release syndrome. This favorable safety profile differentiates our approach from other PSMA-targeted therapies in development.

The program continues to evaluate the potential of our Pro-XTEN dual-masked approach in metastatic castration-resistant prostate cancer, a setting with significant unmet need despite recent therapeutic advances. We are particularly encouraged by the potential for Q3-week dosing. With a half-life of 8-10 days for VIR-5500, we believe we can offer a much more convenient dosing schedule. This would be especially important for patients in earlier lines of treatment where quality-of-life considerations become increasingly significant. We've successfully evaluated multiple dose levels since the data we shared in our January 8 event and are continuing with dose escalation. This ongoing dose optimization is critical to identifying the regimen that provides the optimal balance of efficacy and safety.

We believe VIR-5500 has the potential to be a best-in-class treatment option in this area of significant unmet medical need, offering a combination of efficacy, safety, and convenience that could meaningfully improve outcomes for patients with prostate cancer. Building on our progress with our first two TCE programs, we're now expanding our portfolio with our third clinical candidate. We're on track to initiate our Phase 1 study for VIR-5525, our EGFR-targeted T-cell engager, during this quarter. This program has the potential to address multiple high unmet need and high-value indications with EGFR expression, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and other EGFR-expressing tumors. The unmet need in these indications remains substantial despite recent advances, with hundreds of thousands of patients diagnosed annually with EGFR-expressing tumors across these indications.

VIR-5525 has the potential to address the substantial unmet need through a novel modality that harnesses the patient's T-cells to kill EGFR-expressing cancer cells. Our PRO-XTEN dual-masked approach could offer a differentiated safety profile, potentially allowing for more aggressive targeting of EGFR-expressing tumors compared to traditional approaches. The universal nature of the PRO-XTEN platform enables us to leverage our learnings from our earlier T-cell engager programs to optimize study design and dose escalation for VIR-5525. In conclusion, I'm very pleased with the progress we're making across our entire portfolio. The initiation of our ECLIPSE Phase 3 program and continued advancement of our T-cell engager programs demonstrates our commitment to addressing significant unmet medical needs. We remain focused on executing our clinical development plans with scientific rigor and operational excellence, always keeping in mind the patients who could benefit from these potential therapies.

With that, I'll now hand over the call to Jason.

Jason O'Bryne (CFO)

Thank you, Mark. I'm pleased to share our first quarter financial performance and overall financial position. We continue to maintain a strong financial foundation while advancing our key programs, and I'll start with several key financial metrics for this past quarter. R&D expenses for the first quarter of 2025 were $118.6 million, which included $7 million of noncash stock-based compensation expense, compared to $100.1 million for the same period in 2024, which included $13.6 million of stock-based compensation expense. The increase in R&D expenses was primarily driven by a $30 million payment to Alnylam and expenses related to the initiation of the ECLIPSE registrational program. These increases were partially offset by lower R&D expenses associated with past headcount reductions, deprioritized programs, and the closing of our St. Louis, Missouri, and Portland, Oregon sites.

SG&A expenses for the first quarter of 2025 were $23.9 million, which included $7.1 million of stock-based compensation expense, compared to $36.3 million for the same period in 2024, which included $10.2 million of stock-based compensation expense. The decrease was largely due to ongoing cost savings realized through headcount reductions and other initiatives. Combined, our first quarter operating expense of $142.6 million increased modestly by approximately $6 million year-over-year. Net loss for the first quarter of 2025 was $121 million, compared to a net loss of $65.3 million for the same period in 2024. The higher net loss was largely driven by $52 million of revenue in the first quarter of 2024, compared to approximately $3 million of revenue in the first quarter of 2025. Turning to cash, our net cash consumed in the first quarter was $75.6 million, which is in line with our expectations.

We ended the quarter with approximately $1 billion in cash, cash equivalents, and investments. Based on our current operating plan, we continue to project our cash runway extending into mid-2027. This provides us with the resources to advance key programs through planned value inflection points. As Marianne mentioned earlier, Alnylam has elected not to opt into the profit-sharing arrangement for elebsiran. As a result, we recognized $3 million as R&D expense in the first quarter, which was paid in cash to Alnylam in April of this year. This payment reduced potential future development and regulatory milestones that were described in our most recent 10-K from $175 million to $145 million. The amended terms are further described in our first quarter 10-Q. The agreement with Alnylam remains a milestone and royalty-based arrangement. This was our base case outcome and was assumed in our current runway guidance.

Our capital deployment strategy remains focused on our most promising programs, advancing our hepatitis delta ECLIPSE registrational studies, with ECLIPSE 1 continuing to enroll and preparations underway for ECLIPSE 2 and ECLIPSE 3. Continuing dose escalation for our T-cell engager programs, VIR-5818 and VIR-5500. Finally, initiating and advancing the Phase 1 study for VIR-5525. For our hepatitis B program, any further development will be contingent upon securing a development and commercialization partner. We continue to apply financial discipline as we deploy resources toward advancing these key programs to create value and benefit for patients. With that, I'll hand it back to Rich to initiate the Q&A session.

Rich Lepke (Senior Director of Investor Relations)

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.

Operator (participant)

At this time, we will begin conducting our analyst Q&A session. Your first question comes from the line of Gena Wang with Barclays. Please go ahead.

Gena Wang (Managing Director)

Thank you. I have two questions. So maybe the first one regarding the Alnylam decision. Did they see most up-to-date data for both HBV and the HDV? And what was the reason they provided for not updating? And the second question is, you know, thinking about you have so many programs progress so rapidly in the oncology space. When should we see the next update from the programs and which will be likely the venue we will see those data update?

Marianne De Backer (CEO)

Yes, thank you, Gena, for those questions. Maybe I'll start with the last one first. When the next oncology data update will be coming?

The way we think about it for any next data update, what we would be anticipating to share is, first of all, obviously more mature data at higher dose levels beyond what we presented just a couple of months ago in January. We would also want to share comparative data between weekly and every 3-week dosing. We think the latter is especially relevant for our ambition to go into earlier lines. Also, a clearer picture, obviously, on those response relationships, additional insights into the safety profile at higher doses, and of course, also PSA responses. Once we have all that for 5500 and for 5818, we will be sharing it, of course, either through a medical congress or through a more focused investor event. As soon as, you know, we are ready, we will do so. Your second question, Gena, related to Alnylam.

Alnylam made their decision to opt out of the profit-sharing arrangement before our most recent HBV functional cure data was available. As you know, that data is only going to be presented for the first time on Friday at EASL on May 9th. This decision was really based on their own strategic portfolio prioritization.

Gena Wang (Managing Director)

Thank you.

Marianne De Backer (CEO)

Sure.

Operator (participant)

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

Paul Choi (Biotechnology Analyst)

Hi, everyone. Thanks for taking our questions. I want to ask first about EASL, and it looks like you have a late breaker of the doublet in combination with the Virion 200 asset. Just curious, I think that's the first look we'll get at that program.

Just curious sort of what the rationale is behind that new triplet combination strategy there and just sort of how you think about the development plans for that versus your other combinations. My second question is, can you comment maybe in broad strokes on how you're thinking about completing enrollment or completing either the ECLIPSE 1 or ECLIPSE 2 studies? This will be helpful to understand in the context of your cash guidance runway to 2027 since you're just putting in first patient in the first quarter here. Just some context on that timing would be helpful. Thank you very much.

Marianne De Backer (CEO)

Okay, thank you, Paul. Maybe the first question on the Virion combination, Mark, do you want to answer that?

Mark Eisner (Chief Medical Officer)

Yeah, thanks, Paul, for the questions.

I mean, first of all, that's a study conducted by Virion, and you know we did provide access to bulevirtide and elebsiran for that study, but we're not, you know, it's being run by Virion and it's in their portfolio and not ours. I think, you know, the data are interesting in terms of, you know, some of the early responses in terms of surface antigen decline, but you know that's really in their portfolio rather than ours. You're asking a really good question about HDV and our timelines. You know, we did announce first patient dose for ECLIPSE 1, and we have a study estimated completion date of the end of 2026. That means we would be aiming to complete enrollment in that study by the end of this year.

I mean, that's an aggressive target, but we are putting all of our resources behind getting these ECLIPSE trials up and running. For ECLIPSE 2, we haven't provided guidance yet, but I can assure you that, you know, we are laser-focused on getting that study up and running. It's important to note that the ECLIPSE 2 actually has a 24-week endpoint. Even though it's starting dosing a little bit later, you know, it will have a 24 versus 48-week readout. The timing will provide some more guidance, you know, when we're able to do that, but that's an important point to consider.

Paul Choi (Biotechnology Analyst)

Got it. That's helpful color, Mark. Thank you very much.

Operator (participant)

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

Avi Nova (Equity Research Analyst)

Hi, good afternoon. This is Avi Nova on the line for Mike. Thank you for taking our questions.

A competitor of yours recently shared updated data from its TCE PSMA targeting program in metastatic CRPC. I was wondering if you had any updated thoughts on the competitive positioning of the VIR-5500, and do you see a median PFS of around seven and a half months as, I guess, a fair and achievable benchmark for your program? Thanks.

Marianne De Backer (CEO)

Yeah, I can take that question. First of all, we're actually very encouraged about the continued progress for T-cell engagers in general, including the fact that JANX continues to prove proof-of-concept that masking technology actually extends the therapeutic index. While I can't comment directly on how we would be compared, because we are relatively earlier in our dose escalation compared to where they are, we do think that we are quite differentiated in that our PRO-XTEN is a dual mask technology.

It's quite a different masking technology than the other masks that are out there. It's a universal mask. It's the only clinically validated mask in terms of having clinical validation in other platforms such as the drug Altuvia, a hemophilia drug. We do think that we have a really very favorable safety profile. We demonstrated in our January update that we have a very low rate of CRS. We do not use any prophylactic steroids. We know that every other T-cell engager program needs some form of prophylaxis. Despite the lack of use of corticosteroids, we have this very low-grade CRS and also no evidence of significant IL-6 elevation. Despite that, we are seeing some nice, really early activity.

The other big differentiator, which I think is important both for safety and is in the front line, is that we have a longer half-life of eight to 10 days, which enables our Q3 week dosing schedule. We know that for convenience and quality of life in the front line setting for prostate cancer in particular, these types of differentiation is going to be critically important for overall tolerability, a huge unmet need where we think these drugs could potentially offer significant convenience for that.

Avi Nova (Equity Research Analyst)

Okay, great. Thank you.

Operator (participant)

Your next question comes from the line of Eric Joseph with JPMorgan. Please go ahead.

Hi guys, this is Ron on for Eric. I wanted to ask, how does the recent bulevirtide update in 2020 around the potential finite versus long-term chronic treatment with the combination for HDV? Thanks.

Marianne De Backer (CEO)

Sure. Mark, do you want to take that?

Mark Eisner (Chief Medical Officer)

Thanks for the question. Yeah, sure. I think your question is about bulevirtide and their long-term outcome data and their ability to achieve finite treatment. How does that affect our program? Just to remind everybody, I mean, we achieve in our SOLSTICE study very high rates of target not detected or complete viral suppression. We're achieving it in the majority of patients by week 24 and week 36. You know, we're getting to 64% at week 36. That compares to bulevirtide in week 48 of only 12%. We think we can achieve very high rates of viral suppression in terms of long-term suppression. The bulevirtide data that are related to finite treatment are with their higher dose. That's one thing to consider. You know, it's not really something that's in their label right now.

So, you know, we are aiming for a chronic viral suppressive regimen. We think we can suppress the virus in the vast majority of patients. We're also achieving, you know, three log declines in hepatitis B surface antigen, again, just pointing to the potency and the depth and breadth of our viral suppression for delta. We are really excited to be moving into the Phase 3 program.

Operator (participant)

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

Nik Gasic (VP of Biotechnology Equity Research)

Hey, good afternoon. This is Nik Gasic on for Roanna. Thanks for taking our questions. Maybe first on HBV, you know, how should we think about your expectations heading into the 24-week off treatment data for March at EASL? You know, what are you hoping to see from a functional cure standpoint relative to the end of treatment data we got at AASLD?

Maybe, you know, what implications could this new data have for potential partnership discussions in HBV? Thanks.

Mark Eisner (Chief Medical Officer)

Thanks for the question.

Go ahead, sorry.

Marianne De Backer (CEO)

Go ahead, Mark. No, no. Go ahead.

Mark Eisner (Chief Medical Officer)

Yeah, I was just going to say we are looking forward to the presentation of our March data, 24-week off-treatment data this Friday at EASL. This will be the look at our functional cure rates. You know, as you might imagine, we are going into a quiet period because it is, you know, just a very short period between now and then. We do not want to comment extensively except to say that we have been signaled in the past that we are looking for a 20% in the doublet and a 30% functional cure rate in the triplet.

You know, I think, you know, stay tuned and you'll see the full data at EASL in just a couple of days.

Marianne De Backer (CEO)

Yeah, the only thing I would add is that, as we have already mentioned in January, any further development on the HBV program is contingent on securing a worldwide development and commercial experience partner.

Operator (participant)

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

Phil Nadeau (Managing Director)

Good afternoon. Thanks for taking our questions. Two from us. First, on 5500, you mentioned that there have been multiple doses tested since the data in January. We're wondering if you would care to comment on whether those additional doses have continued to suggest a dose response in efficacy in terms of PSA response rate and durability. That's the first question.

Second, on HDV, the RNA positive figures that you gave for the prevalence of the condition, can you clarify, are those overall prevalence or patients diagnosed having positive RNA? If it's not diagnosed, do you have a sense of what the diagnosis rate is? Thanks.

Marianne De Backer (CEO)

Yes, thank you, Phil. Maybe I'll start with your last question on delta prevalence. What we did is we really looked across all available studies, all available reports on delta prevalence. We sort of started out with determining that, you know, based on all the numbers we could get our hands on, there are about 2 million patients in the U.S. that are HBV positive. Again, through a very extensive literature search, talking to KOLs, different sources, we found that on average about, you know, 4.7% of those B patients are delta antibody positive.

Again, then further drilling down, that gives you about 92,000 patients actually in the United States. If you then think about the patients that are actually going to get treated, those are the patients that, you know, are RNA positive, you know, that are actively viremic. Again, based on a lot of sources, we came to the conclusion, as we shared, that about 61,000 patients in the United States would be RNA positive and eligible for treatment for our regimen. That is sort of, you know, the breakdown of how we got to the numbers. Your first question related to 5500 dosing, maybe Mika, you can comment.

Mika Derynck (EVP of Oncology)

Yeah, we have continued the dose escalation both at the Q week and the Q3 week dosing. Really, we are not prepared to make any comments.

You know, we are encouraged with the 5818 data that also showed a nice dose response. We had that one patient who clearly had a dose response within that while he interpatient dose escalated, a colorectal cancer patient who went from 60 micrograms per kg up to 600 micrograms per kg and continued to have a long durability of response lasting over 18 months. It's tight and hopefully we'll be able to say something soon.

Operator (participant)

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

Hey guys, this is Matthew on for Alec here. Thanks for taking our questions. Maybe a couple from us on 5525. We saw recently that the trial design on clin trials for 5525 includes four parts: monotherapy escalation/expansion, and then combos with pembro escalation/expansion.

Would be helpful to have any color on why you chose this design, maybe the ordering of the parts, and whether you would still explore combination options if initial monotherapy data looked good.

Marianne De Backer (CEO)

Yeah, I'm happy to answer that. Thank you for the question. Yes, we're very excited about having our third Pro-XTEN T-cell engager program go into the clinic. We believe we've shown some nice early proof of concept with the prior two molecules. In terms of the trial design, we do know that there's good scientific rationale for combining with a checkpoint inhibitor. What we've seen with prior T-cell engagers is that you can see upregulation of PD-L1 upon treatment with a T-cell engager.

It really makes sense in terms of combining with a checkpoint inhibitor as well with combinations, again, in the context of other T-cell engagers, is that we've seen deeper responses and more durable responses with the combination. Hence, we are considering the combination for the 5525 program as well. As you mentioned, there are four parts. The first part is dose escalation as monotherapy. The second part is to look at specific indications in expansion cohorts as monotherapy. Parts three and four are similar, except in combination, a dose escalation component with pembrolizumab followed by an expansion cohort with a combination at, again, a data-driven decision on which indications that we would pursue.

Operator (participant)

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

Marianne De Backer (CEO)

Hey Patrick, we cannot hear you.

Patrick Trucchio (Biotechnology Analyst)

Oh, sorry. Hi there. Good afternoon.

Just the first question is on the CHB program. I'm wondering if you can tell us, you know, in terms of the functional cure rates that you're looking for, would you be looking for those rates in kind of certain levels of HB surface antigen at baseline? Separately, I'm wondering on the HDV program, do you need data from all the ECLIPSE trials in order to submit for regulatory approval, or how should we think about potential for, you know, accelerated approval? Is that a possibility? Just the last question is, just in terms of partnering or collaborations, how should we think about both the CHB program, but as well any of the Pro-XTEN programs? In particular, as there are seven additional programs in preclinical development. Thanks so much.

Marianne De Backer (CEO)

Yes, thank you Patrick for that question.

Maybe I'll ask Mark first to address your questions on the hepatitis B and delta programs.

Mark Eisner (Chief Medical Officer)

Sure. Thanks for the question. So for the MARCH Phase 2 study in chronic hepatitis B, you know, as we presented at AASLD, we saw the best responses at end of treatment in those patients with surface antigen levels at baseline of less than 1,000. This is very consistent with what others are seeing with different mechanisms of action in the field, that patients with low surface antigen at baseline are responding better than patients who have surface antigens that are very elevated at baseline. We will present the data, both all comers and divided by surface antigen, as we did for the end of treatment data for the functional cure data, you know, in two days. Look forward to that.

For your HDV question, your question was, you know, do we need all three ECLIPSE studies for approval? I do not believe so. I believe we need, you know, ECLIPSE 1 and ECLIPSE 2 as our base case for a filing package that should be sufficient for approval. We would be looking for an accelerated approval based on in ECLIPSE 1, the composite of target not detected ALT normalization, and for ECLIPSE 2, target not detected virologic endpoint. We are, of course, we have breakthrough therapy designation in the U.S., and we have Prime in Europe, as well as orphan in Europe. We are in active dialogue with regulators globally about, you know, the program, how to accelerate the program, and how to get this drug combination to patients as quickly as possible because the unmet need is so high.

Just one other comment about partnering, and I'll turn back to Marianne, is for hepatitis B, as we've said that we are only going to be able to move hepatitis B forward if we have a global development and commercialization partner, whereas for hepatitis delta, we are in full study startup mode for all three ECLIPSE studies, and we are running those studies as Vir Biotechnology on our own.

Marianne De Backer (CEO)

Thank you, Mark. I would just add related to your question on partnering of the preclinical programs, Patrick.

I mean, what is really unique is that, you know, the universal nature of the Pro-XTEN platform allows us to come up very efficiently with new potential therapeutic molecules, right, which are going to be, from a T-cell engager perspective, very well engineered because that's the capability we've had here at Vir for a very long time, and we can now combine it really with that masking capability. The seven preclinical programs that we have started, it will be, you know, we envision a mix of approaches. Some of them will be kept for internal development, you know, a number of select really high priority targets that align well with our strategic focus. Some are open to partnerships, and especially, you know, those where we think there could be complementary expertise elsewhere. It is going to be really a mix of both strategies.

Operator (participant)

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

Joseph Stringer (Senior Analyst)

Hi. Thanks for taking our questions. Just given some of your recent work updating your HDV patient estimates, had a question on HDV diagnosis. Have there been any changes to U.S. guidelines? I suppose, do you anticipate any updates to this in the near term? How big of an impact could this be to the potentially addressable patient population in the U.S.? Thanks.

Marianne De Backer (CEO)

Yeah, thank you for that question. No changes yet to the guidelines for delta diagnosis or reflex testing here in the United States. You know, we do believe that there is a heightened awareness also in the context of, you know, the American Association of Liver Diseases.

We are hopeful that, you know, we will continue to have that conversation, obviously, and that when we have AASLD coming up later in the year, there might be some announcements in that regard. Thus far, no changes on reflex testing. That is, however, very effectively already deployed in Europe. They are, you know, really seeing that if you just base diagnosis on risk factors, etc., you are really not finding the patients. It is really only when patients are tested for hepatitis B and when they are found to be positive, they are automatically tested for delta that you end up identifying many more patients. Mark, anything to add there from your perspective?

Mark Eisner (Chief Medical Officer)

No, I think you captured it very well, Marianne.

Just to state that we do believe that the prevalence of diagnosed HDV or delta is underestimated because of the lack of reflex testing in the United States, it's just, you know, I think once we have our therapy approved and on the market, assuming success, that we would expect with such an effective product that this will drive more diagnosis and more disease prevalence. I think there are other examples of similar cases like this in medicine. To your point, we're still not seeing the reflex testing deployed in the United States at this time.

Operator (participant)

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

Rich Lepke (Senior Director of Investor Relations)

Thank you, Eric. Thank you all for your continued support and for joining us today. We look forward to updating you on our progress in the coming months.

Operator, you may now end the call.