Vir Biotechnology Q2 2025 Earnings Call Transcript

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Provided by Quartr
August 6, 2025

Key Takeaways

  • Positive Sentiment: We enrolled first patients in both ECLIPSE 2 and ECLIPSE 3, so all three Phase III registrational studies for hepatitis delta are now recruiting globally, advancing toward registration.
  • Positive Sentiment: We initiated the Phase I study of VERU-5525, our dual-masked EGFR-targeted T cell engager, marking our third clinical-stage T cell engager program addressing solid tumors.
  • Positive Sentiment: Our other T cell engagers, SER-518 and SER-5500, continue to advance in Phase I, and we received IND clearance to evaluate SER-5500 in earlier lines of prostate cancer with AR pathway inhibitors.
  • Positive Sentiment: We ended Q2 with approximately $892 million in cash, extending our runway into mid-2027 to fund key pipeline milestones.
  • Positive Sentiment: Q2 operating expenses fell by $42.1 million year-over-year, and net loss improved to CAD111 million from CAD138.4 million, reflecting cost savings from restructuring.
AI Generated. May Contain Errors.
Earnings Conference Call
Vir Biotechnology Q2 2025
00:00 / 00:00

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Operator

Hello. Welcome to Veer Biotechnologies Second Quarter twenty twenty five 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 speakers' remarks, there will be a question and answer session.

Operator

I will now turn the call over to Rich Leppke, Senior Director, Investor Relations. You may begin, Mr. Leppke.

Richard Lepke
Richard Lepke
Senior Director - IR at Vir Biotechnology

Thank you, and good afternoon. With me today are Doctor. Mary Anne DeBacker, our Chief Executive Officer Doctor. Mark Eisner, our Chief Medical Officer Jason O'Burn, our Chief Financial Officer and Doctor. Mika Derink, our Executive Vice President of Oncology, who will be available during the Q and A session.

Richard Lepke
Richard Lepke
Senior Director - IR at Vir Biotechnology

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 ks, 10 Q and eight ks. I will now turn the call over to our CEO, Mary Anne DeBacker. Please go ahead.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

Good afternoon, everyone, and thank you for joining us for Verbai Technologies second quarter twenty twenty five 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 program. 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.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

First, we've made significant progress in our ECLIPSE registrational program for hepatitis delta. Following our first quarter milestone of enrolling the first patient in ECLIPSE one, we have now recently enrolled the first patients in both ECLIPSE two and ECLIPSE three, and all three registrational studies are now actively recruiting patients globally. Second, we successfully initiated our Phase one study for VER-five 525, 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 SER-five 818 and SER-five 500 advancing in their respective Phase I studies. We also received IND clearance to evaluate SER-five 500 in earlier lines of prostate cancer treatment in combination with androgen receptor pathway inhibitors.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

Let me now elaborate on our chronic hepatitis delta program, which represents a significant near term commercial opportunity for Verbio. 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 two data, which demonstrated impressive biological responses with our combination therapy of tobevibart plus elepso. The hepatitis delta opportunity is particularly compelling from a commercial perspective for several reasons. Our comprehensive market analysis indicates approximately seven million active Thyramic HBV RNA positive patients globally, including approximately sixty one thousand patients in The United States and one hundred and thirteen thousand patients in the EU member countries plus The UK.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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 fifty percent five-zero mortality rate within ten years, creating a compelling case for effective intervention. The EMA orphan disease designation and the lack of FDA approved treatments in The U. S.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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 towards potential commercialization, Our strategy includes pursuing commercialization partnerships in Europe and other key international markets. Turning to our oncology portfolio.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

As mentioned, I'm very excited about VIO-five thousand five hundred twenty five, 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. PKIs are primarily effective only in the subset of patients with specific EGFR mutations, while antibodies like cetuximab and panitumumab, 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.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

The PROACT 10 approach fundamentally changes this paradigm by redirecting T cells to kill tumor cells expressing EGFR, HER-five thousand five hundred twenty five has the potential to work across a much broader patient population regardless of their mutational status, including those with KRAS mutation. Because SER-five thousand five hundred twenty five 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. Marc will provide more details on the clinical development plan, but I want to emphasize that Fiore five thousand five hundred and twenty five exemplifies how we are leveraging our platform to potentially address major limitations of existing therapies. For VER5818, 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 VIO-five thousand five hundred, our dual masked PSMA targeted T cell engager, we continue our dose escalation study and recently obtained U.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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 the 5,500 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.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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. We're combining our platform with complementary expertise, could maximize value and accelerate development timelines. Our financial position remains strong with approximately $892,000,000 in cash, cash equivalents and investments at the end of the second quarter. This provides us with a cash runway extending into mid-twenty twenty seven, giving us resources to advance our key programs through critical value inflection points.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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 VER-five thousand five hundred potential in earlier lines 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 Marc to provide a more detailed update on our clinical development program.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Thank you, Mary Anne. 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 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Let me now provide details on each study. ECLIPSE one is designed to evaluate our combination therapy in regions where blebartide is not available or has limited use, including The United States. The study will enroll 120 participants, randomized two to one, to receive either a combination therapy or deferred treatment. The primary endpoint is a composite endpoint of HDV RNA target not detected and ALT normalization at week forty eight. 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 belaboratide.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

This study addresses an important unmet need for patients who have limited options after belaboratide treatment. ECLIPSE two has a twenty four week primary endpoint of HgvRNA target not detected, which could potentially provide a readout at a similar time point as ECLIPSE one. ECLIPSE three is our Phase IIb study that will enroll approximately 100 patients comparing our combination therapy to blebartide and blebartide 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 U.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Plus PRIME, an 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 II 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 Mary Anne mentioned earlier, I'm pleased to report that we've successfully dosed our first patient in our Phase I study for VERU-five thousand five hundred twenty five, 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

However, current approaches face significant challenges. First, TKAs like osimertinib 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 thirty to forty five percent of cases. Similarly, in non small cell lung cancer, where twenty five to thirty 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Our VER-five 525 program takes a fundamentally different approach of redirecting the patient's own immune system to eradicate EGFR expressing tumors. The Universal Pro Xtend dual mask design allows for selective activation in the tumor microenvironment where proteases can unmask VERU-five 525 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, VERU-five thousand five hundred twenty five 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

In safety studies with nonhuman primates, VERA-five thousand five hundred twenty five showed an approximate two fifty fold safety margin compared to the unmasked version with only minimal cytokine release syndrome in IL-six elevation, substantially less than seen with the unmasked T cell engager in these models. What's particularly encouraging is that VERU-five thousand five hundred twenty five 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 VERU-five thousand five hundred twenty five will show a similar safety profile. In contrast to traditional oncology therapies that inhibit signaling through wild type or mutated EGFR, VER-five thousand five hundred twenty five 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, VR5525 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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. In non small cell lung cancer, VERU-five thousand five hundred twenty five 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

For colorectal cancer, approximately eighty percent of tumors express EGFR, yet current antibody therapies like cetuximab and panitumumab are not effective for the thirty percent to forty five percent of patients with KRAS mutations. Our experience with VR5818 has shown promising activity in colorectal cancer, demonstrating that T cell engagers using our ProExtend platform can be effective in this disease. In head and neck squamous cell carcinoma, over ninety percent 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Introducing a T cell redirecting therapy like VERA-five thousand five hundred twenty five, 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 eighty percent 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 I study design for 5525 has been optimized to efficiently assess proof of concept and incorporates extensive learnings from our VERU-five 818 and VERU-five 500 programs, potentially allowing for accelerated dose escalation and more efficient decision making while prioritizing patient safety.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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 lives. T cell engagers like VERU-five thousand five hundred twenty five 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, REVER-five 525, that is now recruiting at multiple sites.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Having discussed our newest clinical program, I'd now like to provide updates on our other T cell engager programs. For VERU-five thousand eight hundred eighteen, 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Among these responses, we've observed one colorectal cancer patient who has maintained a durable response for over eighteen months as of our January update, further supporting the promise of this approach. For VERU-five thousand five hundred, 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 reached yet. The half life of eight to ten days supports our Q3 week dosing evaluation, which could offer significant convenience advantages for patients. We're excited about the recent U.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

S. IND clearance to evaluate VERU-five thousand five hundred 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 VERA 5,500 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 Pro X10 platform's clinical validation across three distinct targets is demonstrating its versatility and provides a strong foundation for our pipeline of preclinical candidates.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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.

Jason O’Byrne
Jason O’Byrne
EVP & CFO at Vir Biotechnology

Thank you, Mark. I'm pleased to share our second quarter financial performance and overall financial position. R and D expenses for the 2025 were $97,500,000 which included $6,900,000 of non cash stock based compensation expense. This compares to $105,100,000 for same period in 2024, which included $13,100,000 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.

Jason O’Byrne
Jason O’Byrne
EVP & CFO at Vir Biotechnology

SG and A expenses for the 2025 were $22,300,000 which included $5,500,000 of stock based compensation expense compared to $30,300,000 for the same period in 2024, which included $9,100,000 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 twenty twenty five operating expenses totaled $119,600,000 representing a $42,100,000 decrease from the same period in 2024. This year over year reduction reflects the changes I just noted in R and D and SG and A expenses, plus the absence of 26,000,000 in restructuring and impairment charges that were incurred in the 2024. Net loss for the 2025 was CAD111 million compared to a net loss of CAD138.4 million for the same period in 2024.

Jason O’Byrne
Jason O’Byrne
EVP & CFO at Vir Biotechnology

Turning to cash. Our net cash consumed in the second quarter was approximately CAD127.7 million, which includes $50,500,000 in milestone payments related to the first patient dosed in ECLIPSE one. These amounts were previously expensed in prior quarters. These milestone payments were anticipated and are described in our SEC filings, including the twenty twenty four ten ks. Excluding these milestone payments, our quarterly net cash consumed was approximately $77,200,000 We ended the second quarter with approximately $892,000,000 in cash, cash equivalents and investments.

Jason O’Byrne
Jason O’Byrne
EVP & CFO at Vir Biotechnology

Based on our current operating plan, we continue to project our cash runway extending into mid-twenty twenty seven. 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 one, two and three now actively enrolling patients globally following the recent enrollment of the first patients in ECLIPSE two and ECLIPSE three. Second, advancing our T cell engager programs in clinical development including VER-five 500, VER-five thousand eight hundred and eighteen and the recently initiated VER-five thousand five hundred twenty five. We maintain strict financial discipline while focusing our resources on programs that can both create shareholder value and address significant unmet patient need.

Jason O’Byrne
Jason O’Byrne
EVP & CFO at Vir Biotechnology

With that, I'll hand it back to Rich to initiate the Q and A session.

Richard Lepke
Richard Lepke
Senior Director - IR at Vir Biotechnology

Thank you, Jason. This concludes our prepared remarks, and we will now start the Q and 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

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

Avraham Novick
Avraham Novick
Biotech Equity Research Associate at Morgan Stanley

Hey, thanks for taking our question. It's Avi Novik on the line for Mike. Yes, so I guess just on HDV, could you perhaps give us a little bit of enrollment update on the ECLIPSE programs, particularly for ECLIPSE one? And then this 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.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Yes. Thanks for the question. So yes, we're really excited that we now have all three ECLIPSE registrational studies up and running with enrolling patients. Enrollment in ECLIPSE one is going very well. We're not in a position yet to provide more specific updates.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

But we have said before, we anticipate completing enrollment by the end of this year with a completion date for the primary endpoint by the '6. ECLIPSE two and ECLIPSE three, 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 HCV, I think what you're alluding to is it is a challenge estimating the epidemiology of HCV because, 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So it's a little bit unclear right now how many patients there may be. I mean, we're estimating about sixty one thousand who are viremic in The U. S. Right now. We suspect that's probably an underestimate.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Once we get to the finish line and launch our therapy, which would be very attractive for patients, that there'll be more education, screening and effort to find patients.

Avraham Novick
Avraham Novick
Biotech Equity Research Associate at Morgan Stanley

All right. Great. Thank you for taking our questions.

Operator

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

Gena Huidong Wang
Gena Huidong Wang
MD - Biotech Equity Research at Barclays

Thank you for taking my questions. I have two. One is for ECLIPSE and the other is for 05/2025. 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 forty eight weeks? My second question is regarding five thousand five hundred twenty five.

Gena Huidong Wang
Gena Huidong Wang
MD - Biotech Equity Research at Barclays

I saw your starting dose is only three microgram per kilogram. Since you expect similar safety profile for five thousand five hundred twenty five versus the other two targets, why now start at the higher dose? Also, will you test both like once weekly dosing and once every dosing?

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Yes. I would say we're not providing specific updates on enrollment. But recall that the enrollment in trials always starts off slower than 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.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

Okay. And then as it related to your question on our EGFR T cell engager five thousand five hundred and twenty five. So if understood you correctly, you were asking why not start at a higher dose given sort of what we have learned from our prior programs. Mitra, do you want to comment on that?

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

Sure. Sure. Yes. 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 MABL dose.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

And so each molecule has they're in the same range, but they're in they have their own estimated MABLE 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 5,525 in that this is a universal platform in that the masks are identical for five hundred and five thousand eight and eighteen and the as are the protease linkers. And so in terms of you look at the preclinical data for five thousand five hundred and five thousand eight and eighteen, 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 5,525, 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.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

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 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 potentially later.

Operator

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

Analyst

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 HDD program. And we're also wondering for the next data cut for VIR-five thousand five hundred for TSMA, are you going to share PFS data or radiology based measurements in addition to PSA biomarkers? Thank you.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So thanks for the question. We do plan to provide an update on the Solstice study, the complete forty eight 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

We're currently escalating in Q1, Q3 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, of PSA responses and other biomarkers and other measures. So we'll provide more detail on what to expect at a later date.

Analyst

Thank you.

Operator

Our next question comes from the line of Alex Tranehan from Bank of America. Please go ahead.

Matthew Guggenbiller
Matthew Guggenbiller
Equity Research Analyst at Bank of America

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 one and ECLIPSE two data is needed for registration in The U.

Matthew Guggenbiller
Matthew Guggenbiller
Equity Research Analyst at Bank of America

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? Thanks.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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 one completed much ahead of ECLIPSE two, we could consider filing that along with Solstice for an initial approval in The U.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

And as a reminder, ECLIPSE II, although it started a little bit later, has a twenty four as opposed to a forty eight week primary endpoint. So it could complete around the same time as ECLIPSE I, 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, whether they'll be separate. For 05/2018, we have said that we are we've completed monotherapy dose escalation, but we're continuing with escalation with pembrolizumab.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

And we're currently analyzing all of the data, PKPD efficacy, looking at dose and schedule and making we'll be making decisions about next steps of development. We would expect to provide that at an upcoming time. And for May, 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, other key pieces of information.

Operator

Our next question comes from the line of Phil Nadeau for TD Cowen. Please go ahead.

Phil Nadeau
MD - Health Care & Biotechnology Research Analyst at TD Cowen

Good afternoon. Thanks for taking our questions. Congrats on the progress. So first one on ECLIPSE II, I believe that you are defining the enrollment criteria for that of patients who are on Hep Cludex 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?

Phil Nadeau
MD - Health Care & Biotechnology Research Analyst at TD Cowen

That's the first question. And then second, just in terms of updated data for five thousand five hundred eighteen in particular, it 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Sure. So thanks for questions. On the first question for ECLIPSE II, correct. These are patients who have been on veliparatide for at least six months, are still viremic, and they are then eligible, if they meet other criteria as well, for enrollment. Actually, identification of these patients is relatively straightforward because the investigators all know which of their patients are on valvipatide.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So they can then test them to see what their level of viremia is and then if they're eligible they can be enrolled. Identifying those patients is relatively straightforward. Then I think we randomized them, of course, to switch to tibibrovart nelepcerin versus continued blurbotide with the twenty four week primary endpoint of HBV target not detected, so virologic endpoint. I think it's a very appealing trial because patients who are still viremic on blebirtide then will have the opportunity to be tested on our regimen where we've been able to show approximately two thirds of patients are achieving complete viral suppression. For your question about 06/2018, what's the next data release look like?

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Is it going to be monotherapy? Are we going to hold for combination? Yes, we really haven't decided. I mean, we're looking at the totality of the data now. We're escalating in combination with famurilizumab.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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.

Operator

Our next question comes from the line of Rona Ruiz from Leerink Partners. Please go ahead.

Mazahir Alimohamed
Biotech Equity Research at Leerink Partners

Yes. Hi. This is Maisie on for Rona. Just one on the hepatitis space from us. So how do you view the evolving competitive landscape in the chronic hepatitis delta space?

Mazahir Alimohamed
Biotech Equity Research at Leerink Partners

And then what advantages do you see for your combination approach in terms of market positioning?

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Sure. So in terms of the competitive landscape, it's a couple of comments. One is Gilead apparently has or is refiling about Levirtaty to have Cudex 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 would be a big positive for us because having Gilead going out and starting that education of physicians and health care providers and promoting testing for HBV would help prepare the way for Veer and our launch.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So we would welcome that opportunity. And particularly since we have a drug regimen with our combo of teprotumumab, where we're achieving high levels of target not detected at week forty eight, we've shown we expect to have above sixty percent all told. That compares to twelve percent with the lever time. So we think we have a very compelling clinical case to make there. In terms of the combo approach, I think we're very excited about it because we're suppressing the virus to undetectable in the majority of patients.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

It's clearly better than our monotherapy with tivivibart antibody. 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So I think all in all, 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.

Marianne De Backer
Marianne De Backer
CEO & Director at Vir Biotechnology

Thank you, Marc. I would just add that, as Marc mentioned, we have a profile that really has the potential to set a new standard of care. And obviously, with more entrants entering 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Yes. That's great, Maryann, really great comments. And the other point would be that with a monthly administration, we feel we're going have a very, very secure convenience to belabratide, which is daily, and other competitors are more likely going to be weekly with an antibody. So, we think from a convenience and adherence point of view, we're feeling very good about where we're landing there.

Operator

Our next question comes from the line of Sean McCotcheon from Raymond James. Please go ahead.

Sean McCutcheon
Sean McCutcheon
VP - Biotechnology Equity Research at Raymond James Financial

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 5,500? Obviously, lot of focus on the post PSMA radioligand setting.

Sean McCutcheon
Sean McCutcheon
VP - Biotechnology Equity Research at Raymond James Financial

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 five thousand five hundred 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 engagers? Thanks.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

Yes. So thanks for that question. So the types of patients that we are currently enrolling is sort of a standard first in human Phase I 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 radioligands. So we don't have quite yet a lot of data in that patient setting.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

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.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

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 in the 5,500 program as well.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

And what we've learned from the HER2 program at least is that we don't see resensitization during that weak 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 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.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

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.

Operator

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

Patrick Trucchio
MD & Senior Healthcare Analyst - Equity Research at H.C. Wainwright & Co.

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 one and Solstice or is the base case still for both Eclipse one and two? And then just with ECLIPSE three, this is the head to head comparison versus bullavertide.

Patrick Trucchio
MD & Senior Healthcare Analyst - Equity Research at H.C. Wainwright & Co.

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 on the Pro PRO X10, I'm just wondering, given this unique opportunity in KRAS mutant tumors, particularly in CRC and lung, how are you designing the 5525 program to ensure you capture that population?

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

You're right. We do expect ECLIPSE one and two 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, that we would use both of those as the sort of core part of the filing for The U. S. ECLIPSE if for some reason ECLIPSE one were to finish substantially ahead, we could talk to FDA about whether ECLIPSE one and Solstice could comprise the initial filing package and leverage our breakthrough therapy designation in The U.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

S. And our prime designation in Europe to have those discussions. So those do remain potential options down the road. For ECLIPSE III, yes, remind everyone it's a head to head study of tebivarat and levsiran versus belabertib and belabertib naive patients. And we are looking at virologic endpoint target not detected week 48 compared to belabertide.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Belabertide is expected to be about twelve percent. We expect to be north of sixty percent for our combination. So we are looking for superiority based on the virologic endpoint. The primary driver for the study, Rationaleva 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

But primarily, we are looking at that as a payer and access oriented study.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

Yes. I can take on the PRO XTEN question. So our 5,525 Phase I study as standard again, we have to enroll patients who must have exhausted 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.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

But I think a really very important point is that the T cell engager, our masked 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 a multitude of other mutations that happen in lung cancer.

Mika Derynck
Mika Derynck
EVP - Therapeutic Area Head Oncology at Vir Biotechnology

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.

Operator

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

Joseph Stringer
Senior Analyst at Needham & Company

Hi, thanks for taking our question. The ECLIPSE one trial has a twelve week deferred treatment period versus twenty four weeks for a Phase three competitor. So can you remind us the rationale for the twelve weeks here? And what's the potential impact on trial success or potential differentiation? Thanks.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

Yeah. So good question. So ECLIPSE-one randomizes us to our regimen of tebivagar and leosiran versus a twelve week deferred treatment period. And the primary endpoint is actually a forty eight weeks for our combination versus twelve 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.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So a twelve week deferred treatment arm is really acceptable because it's going to predict almost perfectly what's going to happen in week 48. We have agreements from FDA and EMA on that point. Twelve weeks is, in our mind, better than twenty four 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 twelve versus twenty four weeks is essentially the same because in neither time period do we expect spontaneous delta conversions to complete suppression in either setting.

Mark Eisner
Mark Eisner
EVP & Chief Medical Officer at Vir Biotechnology

So I think twelve weeks is very patient friendly. I think in terms of probability of success, it's also very attractive.

Executives
    • Richard Lepke
      Richard Lepke
      Senior Director - IR
    • Marianne De Backer
      Marianne De Backer
      CEO & Director
    • Mark Eisner
      Mark Eisner
      EVP & Chief Medical Officer
    • Jason O’Byrne
      Jason O’Byrne
      EVP & CFO
    • Mika Derynck
      Mika Derynck
      EVP - Therapeutic Area Head Oncology
Analysts
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