Hello, and welcome to Vir Biotechnology's ECLIPSE 1 Pivotal Phase III Top-Line Results and SOLSTICE Finite Treatment Conference Call. As a reminder, this call is being recorded. At this time, all participants are in a listen-only mode. After the speaker's prepared remarks, there will be a question-and-answer session. I will now turn the call over to Kiki Patel, Head of Investor Relations. 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 8-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. We saw robust and consistent viral and biochemical responses regardless of cirrhosis status. At week 48, approximately 85% of patients with compensated cirrhosis achieved undetectable virus, or TND, along with 73% of patients without cirrhosis. This demonstrates that the depth of virologic response was maintained even in patients with more advanced liver disease. Importantly, these results are consistent with the trends we previously observed in SOLSTICE, providing additional confidence in the consistency of treatment effect across disease severity.
Next, let us review the hepatitis B surface antigen findings in greater detail. Hepatitis B surface antigen plays a critical role in the delta virus life cycle and is required for viral replication. elebsiran and tobevibart target complementary components of that life cycle by reducing hepatitis B surface antigen production, neutralizing circulating virus, and blocking viral entry.
We believe this two-pronged approach can drive the deep and sustained hepatitis B surface antigen suppression. As shown on the slide, treatment with elebsiran and tobevibart produced substantial and progressively deeper reductions in surface antigen over time, with approximately 95% of patients achieving levels below 10 IU/mL by week 48. Hepatitis B surface antigen suppression continued to deepen with extended treatment. These findings are consistent with our two-pronged approach to attack the virus and demonstrate its ability to drive sustained viral suppression. With that, let me now turn to the safety and tolerability findings from ECLIPSE 1. We believe the efficacy profile just discussed is supported by a favorable tolerability profile that remains consistent with our experience from our SOLSTICE phase II trial. Notably, all treated patients completed the full 48 weeks of therapy without treatment discontinuations or dose interruptions. Overall, our monthly regimen was well tolerated.
There were no serious adverse events reported in the study, no grade four adverse events, and a single grade three adverse event considered treatment-related, which was a decrease in neutrophil count that resolved in 15 days, and the patient did not interrupt treatment. Flu-like symptoms were among the more common treatment-emergent events. However, these were predominantly associated with the first dose and resolved within 24- 48 hours. No patient discontinued treatment due to adverse events. Taken together, the efficacy and safety results provide a strong foundation as we transition to evaluating durability and long-term outcomes. With that, let us now move to the long-term follow-up data from SOLSTICE. Our phase II SOLSTICE trial provides our longest clinical experience with elebsiran and tobevibart, with nearly two years of treatment experience. As treatment has continued, the responses we observed earlier in the study have continued to deepen and remain durable.
These longer-term data provide valuable context for ECLIPSE 1 and give us greater insight into a potential trajectory of response with continued treatment. With that framework in mind, let's review the latest week 96 efficacy outcomes. The week 96 dataset continues to demonstrate what we believe is one of the defining characteristics of the regimen, viral suppression that is rapid, deep, and durable. Among the 28 patients who remained on treatment through week 96, 100% of patients achieved undetectable virus. Additionally, 53% of all patients achieved ALT normalization at week 96. Taken together, these findings reinforce our confidence in the durability of the antiviral effect and provide an important long-term perspective of what may be achievable with sustained therapy. Next, let's look beyond viral suppression and examine measures of liver health.
Many patients with hepatitis delta have ongoing liver inflammation and injury, which over time can lead to fibrosis and ultimately cirrhosis. The next important question is whether that virologic control can begin to translate into improvement in the underlying liver disease, particularly fibrosis or scarring of the liver. The data through week 96 are encouraging. Among patients with paired liver stiffness assessments, 89% had stable or improved liver stiffness, with particularly notable reductions observed in patients with cirrhosis. Liver stiffness is a non-invasive measure associated with fibrosis, so seeing an impact that is consistent with reduced fibrosis provides an important indication that treatment may be changing the underlying course of the disease. Now we can ask, if treatment can achieve such profound viral suppression and reduction in fibrosis, does treatment need to be chronic? Could patients ultimately stop therapy and maintain viral response off treatment?
The next several slides provide a promising early look at that possibility. In SOLSTICE, patients who maintained undetectable virus for at least 96 weeks were eligible to discontinue treatment and enter a structured follow-up period while remaining on background hepatitis B therapy. This exploratory cohort was designed to begin answering an important question, whether the viral suppression achieved with elebsiran and tobevibart could be sustained after treatment is stopped, supporting the potential for a curative approach. Ten patients had elected to discontinue treatment, including seven patients with cirrhosis. Patients had received therapy for approximately 100- 128 weeks before discontinuation and have now been followed off treatment for approximately 12- 48 weeks as of the data cutoff. All 10 patients are continuing follow-up to later time points. With that context, let's review the initial results.
Although these data are early and exploratory, the findings are highly encouraging and provide an important first indication that finite treatment and ultimately curative potential may be achievable in hepatitis delta. All 10 patients who discontinued treatment have maintained a sustained virologic response through at least 12 weeks of follow-up. Among those who have reached later time points, seven have achieved SVR24 and one has achieved SVR48. Additionally, we have observed no viral rebounds or ALT flares, and ALT levels have remained stable throughout follow-up. We want to be clear that these finite treatment data represent an initial exploratory analysis in a small number of patients with varying durations of follow-up. While the findings provide an important early look at what may be possible, longer follow-up in additional patients will be needed to fully understand the durability of response, the potential for finite treatment, and ultimately curative potential.
Looking ahead, our focus is on advancing our ECLIPSE registrational program toward global regulatory submissions. ECLIPSE 1 has now delivered positive pivotal phase III results, marking an important milestone for our program, and we have significant momentum behind it. ECLIPSE 2 and ECLIPSE 3 are both fully enrolled with top-line data expected in the first quarter of 2027. The ECLIPSE 2 trial is evaluating patients switching from bulevirtide, and ECLIPSE 3 will provide a head-to-head comparison against bulevirtide. We believe the data from ECLIPSE 2 and 3 will become increasingly important as bulevirtide utilization grows. Physicians will need data from randomized controlled trials to guide how they manage patients who do not achieve adequate viral suppression, as well as those who may benefit from an alternative treatment approach.
To our knowledge, no other late-stage chronic hepatitis delta program is expected to include comparable bulevirtide switch and head-to-head data as part of its regulatory package. Data from all three ECLIPSE studies are expected to support a comprehensive global regulatory filing package, including a planned FDA regulatory submission in mid-2027. With that, I'd like to close by summarizing the key takeaways from today's call. As we step back and look across the totality of the data, we believe an exceptionally compelling and consistent profile has emerged for elebsiran and tobevibart. Rapid antiviral activity that deepens with treatment duration, resulting in high rates of undetectable virus. These results were observed across patient subgroups, including patients with compensated cirrhosis, and resulted in reductions in liver stiffness consistent with improvement in fibrosis. Our early exploratory treatment discontinuation data raises the possibility that treatment may not need to be chronic.
All 10 patients evaluated to date have maintained sustained virologic response off treatment. The implications could be profound for this disease. Hepatitis delta is a severe chronic disease with no cure today. If these early findings are confirmed with longer follow-up and in more patients, we believe they could fundamentally redefine what treatment can achieve and ultimately support the curative potential of our combination regimen. At AASLD this weekend, KOLs described elebsiran and tobevibart as potential new standard of care for hepatitis delta. Delivering this potential best-in-disease regimen will unlock the significant commercial opportunity in the hepatitis delta market, both in the U.S., where the prevalent population is approximately 61,000 patients, and ex-U.S., where the population is significantly higher. In closing, today represents an important milestone for Vir Bio and for our hepatitis delta program.
We are incredibly proud of these results and deeply grateful to the patients and their families who have participated in our studies, to our investigators, and to our team members who have worked tirelessly to advance this program. Most importantly, today's data bring us one step closer to potentially transforming hepatitis delta care, from getting a majority of patients to undetectable virus, as seen in ECLIPSE 1 today, to a potential finite treatment, as seen in SOLSTICE. This is an incredibly exciting future and one we are committed to pursuing for patients. With that, I'll now turn the call over to Kiki to begin the question-and-answer session.
Thank you, Marianne. This concludes our prepared remarks, and we will now start the Q&A session. Joining me for the Q&A are Marianne and Aziz Sawaf, our Chief Financial Officer. Please limit questions to two per person so we can get through all of our covering analysts. I'll turn it over to you, operator.
At this time, we will begin conducting our analyst Q&A session. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Cory Kasimov with Evercore ISI. Your line is open. Please go ahead.
Hey, good morning. Thanks for taking my questions, and congrats on these great results. I do have two for you. The first one is, based on your discussions with hepatologists, primarily this weekend at AASLD, and given the overall highly impressive profile that exists for this regimen today, what would keep this from becoming the preferred initial treatment option for an eligible patient? Why wouldn't every patient get this at this point upon approval? Then I have a follow-up.
Okay, thank you, Cory. We've had, of course, Nancy Reau present the ECLIPSE 1 data at AASLD, and this was very excitingly received by hepatologists. You're absolutely right. Given that we can really get every single patient in SOLSTICE who stayed on treatment for 96 weeks to undetectable virus, and we see this very strong data in ECLIPSE, where already after 48 weeks, we get nearly 80% of the patients to undetectable virus. This is really remarkable data, and there's no comparison.
Okay. Then the follow-up is on those lines. What do you believe drove the even deeper, faster and deeper for now, TND than we saw in SOLSTICE in the phase II at this time point? Along those lines, how is a cure defined in HBV?
Yes, thank you. We saw deep responses also in SOLSTICE. We have always seen that our regimen, the combination of elebsiran and tobevibart, has very rapid responses, brings a high percentage of patients over time to undetectable virus. We have seen in SOLSTICE the 66% of patients at 48 weeks that achieved that undetectability. You're right, now we saw nearly 80%. There isn't an obvious reason for the result to be even better than what we saw in SOLSTICE. We have actually a pretty advanced disease patient population in ECLIPSE, so 55% of the patients are cirrhotic. You wouldn't expect such an advanced population to respond so well, but they did.
I think it's really due to the two-pronged approach, where we have the siRNA that dices up all the transcripts, and importantly, the transcript for the HBs surface antigen that delta needs for its life cycle. Then, of course, you have the antibody that neutralizes the virions and prevents from the virus to enter the hepatocytes. So together, these two mechanisms of actions really deliver this exceptional result. Then your question about hepatitis C. In hepatitis C, it was, of course, an evolution. At a certain point in time, they went even to as little as eight weeks of treatment before they discontinued patients. That wasn't the right amount of time for every patient, then they went back to 12 weeks.
But it was an evolution where they started with a very long time and then really cut it back and saw what was possible. We have here kept patients for 96 weeks undetectable before they were eligible to discontinue. As you have seen, the 10 patients at the data cutoff all showed sustained viral response and also really ALT normalization that remained constant.
Got it. That is very helpful. I appreciate you taking the questions.
Sure.
Your next question comes from the line of Phil Nadeau with TD Cowen. Your line is open. Please go ahead.
Good morning. Congratulations on the data. Very impressive. Two questions from us also. First, on target not detected, can you talk about the sensitivity of the assay and how you define TND versus your competitors? There seems to be some question as to whether your definition of TND and theirs is the same. That is the first question. Second, we are intrigued by the potential for the finite duration regimen in curing patients. Can you talk a bit more about your plans to explore that further? Will you do formal trials, or will the SOLSTICE follow-up be most of the data? Thank you.
Yes, thank you, Phil. First, on target not detected. In every single trial among our own trial and those of our competitors, what you are really doing is you get to the lower level of quantification, and at that point in time, you have two outcomes. Either you can still detect the virus in the blood of the patient, or you cannot, and then we call it target not detected. The sensitivity of the assay is slightly different, I would say not meaningful. It is really all about, can you still amplify the virus out of the blood of the patient? If you cannot, that is what determines the target not detected definition. Then finite treatment. We are very, very pleased to see these initial results from the 10 patients in SOLSTICE. Obviously, we are going to continue to follow those patients.
There is an opportunity to look at additional patients in the SOLSTICE trial. Then, as you know, Phil, in our ECLIPSE 2 and ECLIPSE 3 trial, we have built in the possibility for patients to discontinue treatment after a period of time. So, we will also be generating more data in our ECLIPSE trials over time.
That's very helpful. Congratulations again.
Thank you.
Your next question comes from the line of Alec Stranahan with Bank of America. Your line is open. Please go ahead.
Hey. Hey, guys. I want to add my congrats as well. Long time coming on the ECLIPSE readouts here. Great to see the positive data. Two questions. I guess first, in SOLSTICE, ALT normalization stayed fairly flat from week 48 to week 96, while undetectable rates kept rising. I guess, should we expect the same pattern in ECLIPSE 1, or could ALT keep improving with longer treatment? Just looking to ECLIPSE 2 and ECLIPSE 3, I guess for ECLIPSE 2, what should we look for in patients switching from bulevirtide? Will it address the flare risk after discontinuation that is on the black box warning? Thank you.
Yeah. Thanks, Alec. First on your question on ALT normalization. We have, as mentioned before, a relatively high percentage of patients in our trial that are cirrhotic, 55%, compared to significantly lower in some other competitor trials. These patients are known to have more difficulty in normalizing their ALT. I would say that is one thing to take into account. The other is that ALT is just a very nonspecific measure. There is a lot of reasons why ALT can vary, and we see it also in patients that are not getting treated, obviously. Yeah, difficult to predict what will happen. We will, of course, follow the patients further in ECLIPSE. But again, what we hear constantly from physicians that are really treating these patients, it is all about getting rid of the virus.
We have now shown that we can get rid of the virus in 100% of patients in SOLSTICE 2 and 80% after 48 weeks already in ECLIPSE. That is really very, very meaningful, and that is obviously, in the end, going to drive the clinical outcomes. On your question regarding ECLIPSE 2, yeah, so there is a black box warning for bulevirtide if you take patients off treatment, that there is the risk for flares. What we are doing in the ECLIPSE 2 trial is really providing or trying to establish evidence that you can safely switch patients who are on bulevirtide to our regimen. So, we will be taking patients who have not adequately gotten their virus controlled on the bulevirtide regimen and then switch them to ours and then see if we can get to better outcomes.
Thank you. Congrats again.
Your next question comes from the line of Roanna Ruiz with Leerink Partners. Your line is open. Please go ahead.
Hey, guys. This is Frank on for Roanna. Good morning. Congrats on the data. I guess, curious, looking towards the potential commercial launch, do you think with the high rate of TND, you could price at kind of a premium to Hepcludex? Thanks.
Frank, thank you for that question. Clearly, there is a number of differentiators that our regimen has. I mean, first, you have seen the potential best-in-disease efficacy profile. We have that two-pronged approach that really makes it possible, in our minds, to achieve these very high levels of target not detected. Then we have the monthly dosing, and then we are going to show, with our ECLIPSE 2 and ECLIPSE 3 trials, both switch data and head-to-head data with bulevirtide. So, obviously, all of that is going to be very important as we look at access and pricing and reimbursement.
Great. Thanks.
Your next question comes from the line of Sean McCutcheon with Raymond James. Your line is open. Please go ahead.
Hi, guys. Thanks for the question, and congrats on the data. Apologies if this has already been asked. I just hopped on. Can you speak to the performance of the three patients in the study with prior bulevirtide exposure? How long was that exposure? Did the patients have a virologic response? Did you see a superior outcome as relative to bulevirtide in these patients, particularly on TND, where it was not achieved prior? Understanding this is entirely anecdotal, but perhaps a hint at the results of ECLIPSE 2. Thanks.
Yeah. We only have the total data set that we have shared today, so I do not have the specifics on the three prior bulevirtide-exposed patients.
Your next question comes from the line of Patrick Trucchio with H.C. Wainwright. Your line is open. Please go ahead.
Hi, this is Cynthia Garcia for Patrick. Congrats again on the data. We were just wondering, what are the key remaining steps before the planned U.S. submission? Are those mainly the ECLIPSE 2 and 3 analysis and integrated safety work, or is there still manufacturing, stability, or administration? Which of those, if any, could affect the filing timeline?
Thank you, Cynthia. As we have shared, we will have our top-line data for ECLIPSE 2 and ECLIPSE 3 in the first quarter of next year, and that is really what is going to be combined with our ECLIPSE 1 data to generate the filing package, which we have now said we target the filing in mid-2027. We are really very well on track.
Okay. Thanks so much.
Your next question comes from the line of Joseph Stringer with Needham. Your line is open. Please go ahead.
Hi. Good morning. Thanks for taking our questions. Two from us. Just curious if you can comment on what the overall AE rates look like over time. Secondly, can you elaborate a bit more on the single grade three neutrophil decrease signal? Are there any other details or patient-level context on that particular case? Thank you.
Yes. Thank you, Joey. Maybe your second question. Yes, so there was one patient with a decreased neutrophil count, which normalized over a period of 15 days and never discontinued treatment. We actually had two similar types of events in the delayed treatment arm. It is something that we do not really have a reason for. It could be idiopathic. Your other question about AEs over time. As you can see, this is a very well-tolerable drug. There is not a single participant who interrupted drug, not a single discontinuation. The most notable is the flu-like symptoms, which, as I mentioned, is typically only one episode at the very first dose that patients ever achieve, and it is mild, it is transient, it disappears within 24- 48 hours. Next question.
Your next question comes from the line of Etzer Darout with Barclays. Your line is open. Please go ahead.
Great. Thanks for taking the question, and congrats on these data. I'll have one question and then a second one after you answer the first, if that's okay. I guess the first one, given the ECLIPSE 1 results and the accumulating relationship between TND and longer-term outcomes, does this dataset strengthen the regulatory argument for TND alone as the more clinically relevant endpoint rather than a composite with ALT normalization? Then I have a follow-up.
Yeah. Thank you, Etzer. Indeed, in the past, because the regimens were just not powerful enough to drive significant percentages of undetectability or TND, there was always the composite endpoint with ALT normalization. We have, across our ECLIPSE program, different endpoints. ECLIPSE 1 has the combination with ALT, but ECLIPSE 2 and 3 are only TND already. I think that for the FDA, this is, of course, important to see that there is now a regimen that can drive significant number of patients to undetectability, and it might lead to that evolution over time, which you basically already see within the context of our own program.
Great. Thank you. One of the more surprising findings was that TND was numerically higher in cirrhotic patients, 85% versus 73% in non-cirrhotics, while the combined endpoint was essentially identical. Do you have any biological or baseline characteristics explanation for that, and does that increase your confidence that disease severity isn't limiting antiviral efficacy?
Yeah. We do not believe it is necessarily statistically significant. However, what is really important to see is that we can get a significant number of patients, even the patient that have CPT-A, to undetectable virus. That is, of course, incredibly important because that's typically the time at which physicians see patients for the first time. To be able to show that result is very important. As I mentioned, we had a relatively high number of cirrhotic patients in our trial, 55%.
Great. Thank you. Congrats again.
Thank you.
This concludes the Q&A session of the call. I will now turn it back to Kiki Patel to close the call.
Thank you for joining us today and for your continued interest in Vir Biotechnology. We look forward to keeping you updated on our progress. This concludes today's call.