Vir Biotechnology, Inc.

Thank you, and good afternoon. With me today are Dr. Marianne DeBacher, our Chief Executive Officer, Dr. Mark Eisner, our Chief Medical Officer, Jason O'Byrne, our Chief Financial Officer, and Dr. Mika Durink, 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 risk 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 DeBacher. Please go ahead.

Thank you, Rich, and good afternoon, everyone. Thank you for joining us for Vier 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 as well for future growth and value creation. I'm pleased to share that we successfully initiated our Eclipse phase three registrational program with the first patient enrolled in Eclipse one 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 two data, which demonstrated impressive biological responses with our combination therapy. Today, I'd also like to provide our refined assessment of the hepatitis delta market opportunity which reflects the prelaunch work we have initiated in parallel with our phase three 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 United States, we estimate approximately 61,000 RNA positive patients. In EU member countries, plus the UK, we estimate approximately 113,000 RNA-positive patients. And 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 deaths within 10 years of diagnosis, and there are no FDA-approved treatments in the United States. 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. And 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 I trial and preparing for the ECLIPSE II and III 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 in to the profit-sharing arrangement for elapseron, 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 II 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 ProX10 dual-mask T-cell engager program. As a reminder, we have worldwide rights to the ProX10 platform in infectious disease and oncology. For VR5818, 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 VIR5818 could potentially address an important treatment gap for these patients. For VIR5500, our dual-masked PSMA-targeted T-cell engager, we continue to dose escalate, given our favorable safety profile and the learnings from VIR5818. 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 decline, with 58% achieving a PSA 50 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 one study for VIR5525, 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 ProX10 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. And the universal nature of the ProX10 platform allows us to efficiently apply our dual masking approach. The synergies between antibody discovery capabilities and the ProX10 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 ProX10 platform. Additionally, leveraging our expertise in infectious disease immunology, we have advanced a broadly neutralizing antibody 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 infection 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. a strong cash position allows us to weather market volatility. I'm confident that our focused approach to developing potentially transformative medicine 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 program.

Thank you, Mary Ann. 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 three 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 Bolivar Tide is not available or has limited use, including the United States. The study will enroll 120 participants, randomized two to one, to receive either our combination therapy or deferred treatment. The primary endpoint is a composite endpoint of HDV RNA target not detected, 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 bulevertide. 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 two study at Eazl on May 9th. 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 ProX10 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 ProX10 masked TCEs achieve this through the addition of long hydrophilic polypeptide X10 masks that shield both the CD3 and tumor-associated antigen binding domains by hysteric 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 VIRA5818, 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 suggests that VIRA5818'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 VR5500, 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-extend 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 to 10 days for VR5500, 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 8th event and are continuing with dose escalation. This ongoing dose optimization is critical to identifying a 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 one study, Revere 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 remain substantial despite recent advances, with hundreds of thousands of patients diagnosed annually with EGFR-expressing tumors across these indications. Vera 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-extend dual mast 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 ProExtend platform enables us to leverage our learnings from our earlier T-cell engager programs to optimize study design and dose escalation for VERA 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.