Vir Biotechnology Status update

You may begin, Kiki. Thank you, operator, and good morning, everyone.

Yesterday, we issued a press release announcing positive top-line results from our ECLIPSE 1 pivotal Phase III trial evaluating our potential best-in-disease combination regimen of elebsiran and tobevibart for the treatment of people living with chronic hepatitis delta. We also issued a second press release highlighting expanded week 96 results from our Phase II SOLSTICE trial. During today's conference call, Marianne will walk you through the data, beginning with the ECLIPSE 1 top-line results, followed by the expanded Phase II SOLSTICE dataset and our exploratory analysis of finite treatment. Next, she will share our next steps, including our regulatory path forward, and then we'll open the line for Q&A. Before we begin, I would like to remind everyone that today's remarks and slides include forward-looking statements under applicable securities laws.

Forward-looking statements include, but are not limited to, statements regarding the therapeutic and commercial potential of our hepatitis delta program, our development and regulatory plans, and related timelines, and as otherwise described in the legal disclaimers accompanying our public presentations. These forward-looking statements involve substantial risks and uncertainties, which are described in our reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q, and eight-K, and could cause our future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. Joining me on today's call is Dr. Marianne De Backer, our President and Chief Executive Officer.

Thank you, Kiki. I'm incredibly proud of the results I'll be sharing with you today and could not be more excited about what we are seeing across the ECLIPSE and SOLSTICE programs. This is a transformational moment for our program and could change what people living with hepatitis delta can expect from treatments. The data have exceeded our expectations and point to three clear conclusions. First, ECLIPSE 1, our first pivotal Phase III study of the program, met its primary and key secondary endpoints, demonstrating robust antiviral activity. 100% of patients achieved a virologic response at week 24, with 79% of patients achieving undetectable virus, defined as HDV RNA target not detected, or TND, at week 48. This is a remarkable virologic response, demonstrating the rapid and deep antiviral activity of the combination. We also observed a favorable safety profile consistent with what we've observed in our Phase II trial.

Second, our expanded phase II SOLSTICE data show that responses are not simply maintained, they continue to deepen over time, with 100% of patients who remained on combination treatment through week 96 achieving undetectable virus. Third, and perhaps most exciting, we now have a glimpse of what may be possible for elebsiran and tobevibart as a finite treatment. In an exploratory analysis of the first 10 patients who discontinued treatment after prolonged viral suppression during the SOLSTICE trial, we observed sustained viral response ranging from 12-48 weeks as of the data cutoff. Our message today is simple. We believe these data support the potential for elebsiran and tobevibart to deliver a best-in-disease profile, and importantly, open the door to something that has not been possible for the majority of patients with hepatitis delta today, the potential for curative treatment.

If sustained off-treatment viral control can ultimately be confirmed, we believe it has the potential to fundamentally change the paradigm from managing a lifelong chronic infection to a disease that could potentially be cured. Despite recent advances, hepatitis delta remains one of the most serious and rapidly progressive forms of chronic viral hepatitis. Patients living with this disease face substantially increased risk of cirrhosis, liver failure, hepatocellular carcinoma, and liver-related mortality. Disease progression can occur surprisingly quickly, and many patients experience clinically meaningful deterioration within the few years of diagnosis. What makes this particularly challenging is that these patients often develop complications at younger ages and at a faster pace than what physicians may typically observe with hepatitis B alone. As we engage with hepatologists around the world, we continue to hear a consistent message.

Physicians are looking for therapies that deliver sustained viral suppression while reducing the treatment burden for patients through less frequent dosing. I'll now take you through the results of our pivotal phase III ECLIPSE 1 study. Let's begin with what fundamentally sets our regimen apart, a two-pronged approach designed to inhibit the viral life cycle and ultimately drive sustained viral suppression. This may not be possible with a single agent focused simply on viral control, and it's why we believe our regimen has the potential to deliver a best-in-disease profile in hepatitis delta. Elebsiran is an siRNA designed to reduce the production of hepatitis B surface antigen, which is critical to the delta virus life cycle. Tobevibart is a monoclonal antibody that neutralizes circulating hepatitis delta and hepatitis B virions and inhibits viral entry into hepatocytes.

The combination is administered subcutaneously once every four weeks, with the flexibility for administration at home or in a physician's office, providing a potentially more convenient treatment approach for patients. Moving to the ECLIPSE 1 study design. This was a global, randomized phase III study evaluating the combination of elebsiran and tobevibart in a broad and diverse population of people living with hepatitis delta across multiple countries and included patients with advanced disease. A total of 124 patients were randomized 2:1 to receive the combination or delayed treatment. Patients in the active treatment arm received elebsiran and tobevibart every four weeks. Patients in the delayed treatment arm remained untreated for the first 12 weeks, providing a randomized control period, and then crossed over to receive our combination regimen. One of the important features of ECLIPSE 1 is the rigorous efficacy endpoint that reflect a demanding measure of treatment success.

This sets ECLIPSE 1 apart from other late-stage studies in hepatitis delta. Rather than measuring virologic response based on a reduction in HDV RNA from baseline, the primary endpoint of ECLIPSE 1 required patients to achieve both undetectable virus, defined as HDV RNA target not detected, or TND, plus ALT normalization. This was assessed at week 48 for the combination arm compared with week 12 for the delayed treatment arm. The key secondary endpoint evaluated undetectable virus, or TND, alone. Undetectable virus has been associated with lower rates of progression to cirrhosis, liver cancer, and death. This is why hepatologists increasingly view achieving undetectable virus as an important next frontier in hepatitis delta care, with the potential for deeper disease control and meaningful clinical benefit for patients.

As you'll see over the next several slides, ECLIPSE 1 not only met this high bar, but delivered remarkably consistent results across efficacy endpoints in both cirrhotic and non-cirrhotic patients. Let's now turn to the characteristics of the patients enrolled in ECLIPSE 1. Looking at the baseline demographics and disease characteristics, we believe the enrolled population reflects a meaningful cross-section of patients commonly encountered in hepatology practice. Baseline characteristics were generally balanced between the treatment and delayed treatment arms. Approximately 55% of patients had compensated cirrhosis at enrollment, which is notable because these patients represent a more advanced disease population and are often among the most difficult to treat. With that foundation established, let's move to the primary efficacy results. We are very pleased to report that the study achieved its primary and all other study endpoints at week 48, delivering what we believe is a highly compelling efficacy profile.

Starting with the primary endpoint of achieving undetectable virus as measured by HDV RNA TND together with ALT normalization. Patients receiving elebsiran and tobevibart had a 44% response rate at week 48, compared with 0% in the delayed treatment arm at week 12. We believe this is a meaningful endpoint because it combines profound viral suppression with improvement in ALT. The study also met its key secondary endpoint. It treated patients achieving undetectable virus at a 79% rate at week 48, compared with 0% in the delayed treatment arm at week 12. We believe the HDV RNA TND results are among the most meaningful observations in the dataset. Every treated patient achieved a virologic response defined as either HDV RNA TND or at least a two-log reduction in HDV RNA.

We also observed ALT normalization in 53% of patients and hepatitis B surface antigen levels below 10 IU/mL in approximately 95% of treated patients. Taken together, the consistency across efficacy measures is also striking. Whether evaluating TND or undetectable virus, ALT normalization, hepatitis B surface antigen suppression, or viral load reductions, all point in the same direction, demonstrating both the depth and breadth of response achieved with our two-pronged approach to attack the virus. We believe these data support the potential for elebsiran and tobevibart to become a best-in-disease treatment option. Let's now look at how these responses evolved over time. One of the most encouraging aspects of the ECLIPSE 1 dataset is both the rapid onset and progressive nature of the response. The majority of patients achieved a virologic response as early as week four, with responses continuing to deepen throughout the treatment period.

Undetectable virus, or TND rates, increased steadily over time, reaching nearly 80% by week 48, with no evidence of an early plateau. This is similar to what we saw in SOLSTICE, where ultimately all patients who remained on treatment reached undetectable virus. ALT normalization followed a similar trajectory, with progressively more patients achieving biochemical improvement through week 48, including patients with compensated cirrhosis, where ALT has traditionally been more difficult to normalize. Next, we will examine efficacy in one of the most clinically important subgroups, patients with compensated cirrhosis. Hepatologists and treating physicians frequently ask whether efficacy can be maintained in patients with more advanced liver disease, because that is the time they typically see these patients. As mentioned earlier, approximately 55% of patients in ECLIPSE 1 had compensated cirrhosis at baseline, providing an important opportunity to evaluate the treatment effect in a population at particularly high risk of disease progression.