Atea Pharmaceuticals Inc Aktie

Great. Hello, everyone. I'm Max Skor, Biotech Analyst with Morgan Stanley. And before we get started, for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. I'm very happy to welcome the Atea team. Maybe we go through. We have a few people on the stage, J.P.?

Sure. Good morning. Jean-Pierre Sommadossi, Founder, Chairman, and CEO.

Hello. I'm Janet Hammond. I'm Chief Development Officer.

I'm John Vavricka, Head of Commercial Operations.

And I'm Arantxa Horga. I'm the Chief Medical Officer.

So first, I would like to thank Morgan Stanley for the kind invitation. I appreciate the opportunity to give an update today of our programs. As you know, we recently disclosed a successful first Phase III trial for our treatment against hepatitis C, with achieving the FDA-agreed primary endpoint on our SVR12, and we are very, obviously, very excited to have non-inferiority statistical significance with the current standard of care with Epclusa. We believe that we have a best-in-class regimen with short duration. What's important, obviously, in that Phase III, which was performed in North America, predominantly in the U.S. Let's not forget that we were comparing an 8-week treatment against a 12-week treatment for Epclusa in non-cirrhotic patients, which represented about 90% of the patients in the U.S., and we performed very well from an efficacy and safety standpoint.

We look forward to our ex-U.S. trial, C-FORWARD. We are releasing data very early in Q1 next year. We are fully enrolled. Almost all patients actually have achieved now week 12, which is when they have completed the full treatment. And this second trial will allow us to support the first trial, but also to expand the robustness of the number of patients with genotype 1b, mostly in Western Europe, genotype 3, 4, 5, and 6, which are the rare genotypes and label is essential today as no one is doing genotyping before treatment.

We have also a second program. We are very excited with hepatitis E. We have just -- we're in the process to complete the single ascending dose. We like the PK. We see the drug exposure and the safety so far. We will complete the multiple ascending dose for the end of the year, and we will be in the proof of concept next year for hepatitis E. So next year will be a very important year because that will be when we anticipate in Q2, very likely June, the filing of our regimen for hepatitis C with the FDA. So again, thank you for allowing us to share those updates. And then the team, Janet, John, and Arantxa can go into details on the questions.

That's great. Thank you very much. A lot of exciting things happening at Atea. Maybe we just start with the C-FORWARD results. Would the team like to highlight the top-line results, key takeaways, any secondary endpoints or safety commentary?

Arantxa?

So the C-BEYOND trial, our U.S. trial, we recently have data released from it. And we were very excited to see very robust efficacy with rates in 94%, 95% with only an 8-week regimen as compared to the standard of care, which was a 12-week regimen. And this is with the attributes of what people are expecting today in the hepatitis C landscape. So that's a short treatment duration, low probability of drug-drug interactions, no food effects, and we saw a good tolerability profile, so that's what people are looking for today.

In terms of C-FORWARD, Max, the trial is very well positioned to be a confirmatory trial of what we saw in C-BEYOND. And it's a trial that, as J.P. said, is running ex-U.S. in multiple countries, over 17 countries, and it has a broad global population, and also genetic -- viral genetic diversity with different genotypes, as J.P. mentioned. So we think that that is going to be a confirmatory trial that is very likely to reproduce the excellent results that we saw in C-BEYOND for 2 reasons. One is the trial design is closely aligned to C-BEYOND, so basically they have the same primary endpoint, they have a very aligned statistical analysis plan, the same power assumptions. So this makes it very likely to reproduce what we saw in C-BEYOND.

But also, the strength of C-FORWARD is that we are going to be seeing the primary endpoint in 2 populations like we see in C-BEYOND. In the population which is the mITT population, so that's everybody that received 1 dose, and that's the FDA preference, and we met the primary endpoint there. But also in the per-protocol population, which is the population that is a subset, that is the population that adheres to the regimen and to the protocol, and that was the preference of the EMEA (sic) [ EMA ]. And so we think that in that way, because we met both in C-BEYOND, we're going to -- we have a lot of confidence that we're going to be seeing the same results in C-FORWARD.

Okay, so strong efficacy, clean safety profile, maybe if we can just drill down a bit more on C-FORWARD. So it includes a broader geographic and genotype mix than C-BEYOND, which you've noted. How could these population differences affect the results?

So we see that as a strength. I think C-FORWARD gives us a population that gives us additional strength for the program. One is because of the genetic diversity of the virus. So we'll see multiple genotypes. And we already have experience in vitro that we are pan-genotypic. We can treat all genotypes the same. But further, we also saw pan-genotypic efficacy in our Phase II trial where we treated 275 patients, which is quite a lot for a Phase II trial, spread across genotypes and included genotype 3, which is the hardest-to-treat genotype, and there we had efficacy rates of about -- of 100% if you took the population that was compliant with the drug. And so C-FORWARD is enriched for genotype 3. And we -- that should translate into very strong efficacy as well. So that's the -- from the viral perspective.

From the population perspective, C-FORWARD is a more manageable population from the clinical trial perspective. They are more likely to come back to follow up, less likely to have early treatment discontinuations as compared to the United States. We had to do, obviously, a C-BEYOND, a clinical trial in the United States because that's a big medical need, but the population in C-BEYOND in the United States had a lot of issues and challenges. For example, over more than half of them had a history of IV drug use. They had a history of, or they had actually concomitant medication use. 90% of them have -- 89% of them have concomitant medication use. They have psychiatric disorders. They -- over 10% of them didn't come back or had early discontinuation rates for a variety of reasons, sometimes incarceration, sometimes they just didn't come back for follow-up.

So that was a very challenging population for us to do a very rigorous test in the United States. But C-FORWARD has a population that is easier in that sense, with less of those challenges. So that should decrease the noise, the statistical noise in the trial. And if the data has less variability, because you don't have all that noise. So that should really be able to help us highlighting our unique profile.

Okay. That's great. So I'll press a little bit on this, but what would C-FORWARD need to show for the combined analysis to support a compelling superiority claim rather than confirming noninferiority?

That's a great question. I think that we power these trials for noninferiority, but I want to remind you, noninferiority, so the efficacy is matched with Epclusa, but we do it in 8 weeks. And in order to power for noninferiority, we needed almost 1,000 patients per trial, which is pretty big for a Phase III program. And so if you -- and the cure rates are around 95% -- 94%, 95%. So to demonstrate statistical superiority above 95% cure, you will need thousands of patients, and that is really not realistic in a Phase III program. And so our goal is really not so much to demonstrate incremental superiority -- efficacy superiority, but to have a superior profile overall with this, as you mentioned, lower risk for drug-drug interactions, which is very important for physicians, no food effect, and short regimen, which is very important for patients because they really have a hard time even making it to 8 weeks, much worse to 12. And so when you put all that together, that's the strength of the program because it leads to a simple, practical regimen that physicians can prescribe.

Great. So looking forward, based on or assuming that C-FORWARD is successful, you move on to submission. Can we talk a bit about the label and, as you noted, the differentiating factors from the 2 approved therapies? What really resonates with physicians?

Janet?

So from a regulatory perspective, as J.P. mentioned, we're aiming to file the NDA mid-next year, and we're already actively preparing for that regulatory submission with drafting documents, drafting the label, and discussing things with physicians. And I think what we've heard distinctly from everybody has been that a short treatment regimen is the most important factor for achieving cure in patients. And this is what they're looking for above all else. But what is also important is a low potential for drug-drug interactions, and we have that also. The other factors which are important are that the regimen should be pan-genotypic. We don't have a protease inhibitor which helps, and the regimen obviously needs to be safe and well-tolerated. And all of that we are able to demonstrate.

And so we're in the process of actively working out how to draft a narrative for the regulatory submissions, assuming C-FORWARD is positive, which will highlight that and provide simple prescribing information for physicians.

And we can -- just to add that we are preparing, as you know, Max, we will need just to complete the package for the EMA. It's closely similar, but actually they request some additional environmental and other packages that we are preparing, and we anticipate to file for the -- with the EMA end of 2027, so it's about 6 months after we will have filed with the FDA.

Okay. Could we talk about potential label scenarios? How should we be framing expectations?

Janet.

So I think our expectations are that the label should reflect that the regimen is an 8-week regimen for non-cirrhotic patients, 12 weeks for patients with cirrhosis. There are minimal drug-drug interactions. The safety and tolerability are generally excellent. And we are looking for a pan-genotypic regimen. And I think the label should reflect towards that.

Okay, and then moving on, I know I'm not going to press you on a price, but how are we thinking about pricing this this regimen.

John.

So, right now, we haven't released anything on pricing, but we plan to be competitive within the pricing regimen, closely matching to what the 2 competitors currently are.

Okay. But I think a question for myself is just understanding the broader markets. Can you speak to the market research that you're doing internally, what you're hearing from KOLs, and how that's evolving over time?

Sure. So we've done initial market research directly with the highest prescribers in the U.S. based off of our Phase II data. What they have told us is that when they looked at the profile that Janet and Arantxa so eloquently described, that they showed great preference. As a matter of fact, over 80% said they would be interested in writing it, and the fact that the majority of their patients, they would like to prescribe it to. When you start to ask them why, what they begin to address is the exact profile, to have something that's very potent, less likely to cause drug-drug interactions, and to be the shortest possible course of therapy.

So from that perspective, that's how we're looking at the market. I just want to point out that when we start looking at our launch strategy, it really is grounded in the fact that we are looking at the diagnosed and treated patient population. In other words, historically, the number of patients that have been treated. However, we believe that with this profile, we really have the opportunity to address a lot of those patients who are diagnosed but do not seek treatment. And it kind of ties into what physicians are doing themselves. What are they doing to get more patients treated? Because it is a problem, and that's when they're coming up with their test and treat model of care. Simply put, a patient is diagnosed and treated at the same time.

To provide some historical perspective, a typical patient was diagnosed and might not receive treatment for months. And it kind of explains why you may have 160,000 new patients each year diagnosed, but only half of them are being treated. So if you do this new test and treat model, what most KOLs will tell you is that they can try to get more of those patients treated. The one thing that may have been holding them back in the past is the profile of what's currently available. You really do need a drug where the physicians feel comfortable prescribing, not likely to see DDIs, and also something really convenient for a patient to take. And so we're really confident that as the U.S. moves towards the test and treat model, our drug will really have the best profile for that.

And could you talk about the incidence population or the prevalence population, both in the United States and then Europe?

Well, so for the U.S., what I can tell you is just some general numbers. It's estimated that you have roughly 4 million people that are infected in the United States. That number continues to grow. It's estimated, as I said, around 160,000 new chronic infections each year, with only half of them being treated. So the number continues to grow. It is becoming even more of a growing health concern, because eventually a large percentage of those patients will go on to develop hepatocellular carcinoma if they're not treated. So hence, the interest in the government to start to take a look at that, the interest in physicians to try to treat more of those diagnosed patients.

And how should we think about the cirrhotic versus non-cirrhotic patients?

Well, I'll let my colleagues talk about that, but from a commercial perspective, by far the majority in the United States is -- they're a typical average type patient, and they're not cirrhotic patients.

I think that what I'd like to add also is, and that's why the C-FORWARD will be very important. As you probably know, Max, compensated cirrhosis genotype 3 are the most difficult patients to treat. And we are excited with our regimen. We are also evaluating patients with resistant mutation. So this type of patient will tell us if we are doing -- probably, there is no sufficient power -- sorry about that, to look for superiority. But we'll have a pretty good idea how we compete in terms of those cirrhotic GT3 against Epclusa. And Mavyret physicians don't like to put compensated patients on Mavyret for many reasons, in terms of the presence of protease inhibitors. So we believe that that also will be one of the major advantage of our regimen.

And when could we get an update around that?

That -- when we'll have the C-FORWARD data, very likely we can disclose that C-FORWARD, almost 50% of the C-FORWARD patients are genotype 3, and with a lot of cirrhotic genotype 3.

That's helpful. And maybe if you can just walk us through, specifically in the United States, where are these patients located? Are they concentrated at specific treatment centers? How should we think about the rollout and ultimately I'm asking about a potential sales force.

You want to do? John

So we're fortunate coming to market. Being third to market has -- would have its advantages. One is we know where the current prescribers are. We know, for instance, that you have less than 8,000 physicians write 80% of the market. We know geographically where they're distributed. We know for instance, for the highest writers, what patients are they seeing? Is it Medicare? Is it Medicaid? Is it commercial? Which commercial plans? So there's an over -- a wealth of data in which you can mine.

And as we begin to launch, we know at least from the perspective of the numbers, that we will be able to be very competitive with a sales force of around 100, including managers, MSLs to cover that concentration. And we've been working with IQVIA to actually begin to size the sales force for all of that coverage. We'll choose the exact locations based off of how we choose to penetrate and where we get our market share from. But that will be done closer to launch, but we've already laid the groundwork for what we need to do.

And can you just discuss the competitive landscape in regards to the 2 regimens that are approved? How are sales going there? And how do you expect to, I would say, take market share?

Well, the product is over $1 billion in the U.S. and you have some fluctuations up and down within the quarters. It's interesting, you have an 8-week regimen, you have a 12-week regimen, they roughly have 50-50 share, market share. The 2 companies historically have played very well together when it comes to that. Historically, when you go back and you look at specialty care products and you look at what does a third entrant come in generally do, it's very different than traditional form of hypertension and other types of retail products. They usually generally equalize around 1/3 to 35% coming in.

We have noticed, for instance, that a lot of the, I would say, the competitor activity has moderated now as they move on and promote other assets. Again, it strengthens our position at a company of our size with a relatively small sales force, can compete with share of voice. It also tells us that we were able to get that share of voice in a very efficient manner. So those are kind of the dynamics that exist today. And I also want to go back to the fact that as the market will move to a test and treat, our profile is best suited for that type, both from a physician's willingness to prescribe and from a patient's convenience to take it.

Can you go a bit deeper into that test and treat model and how that differs from the current dynamic?

Yes, so as I said, traditionally it's been that a patient is diagnosed, it may be months before they actually get treatment. They're doing a lot to minimize that. They're not requiring genotyping anymore, different scans are not required. But still, it's multiple visits to get those patients back. When you talk to most KOLs, that is what they say explains the doctor only getting, you're only treating 50% of those that are diagnosed. So with the test and treat, it is relatively straightforward, where these centers are able to diagnose them and to treat them on the spot.

And they feel that you will get many more of those patients treated that have been diagnosed. It's a fact that both Congress and the White House are spending considerable resources now to try to fine-tune what would a test and treat model look like if it was ever broadcast out. I don't think it's imminent this year or next year, but I think within the 5 years, you're likely to see some sort of federal initiative to address this ongoing problem. And what they're at least appearing to both right now, both sides are looking at a test and treat model.

And in regards to potential strategic partners. What are your plans for ex-U.S.?

So we will partner with ex-U.S. Whether we'll be a sole partner or we'll be multiple partners, we have already interested parties. The only major market where we are not going to file with regulatory authority in Japan, but we have some interest there in terms of partnership [ with ] this company. We have 2 other interested parties already. We plan to await the C-FORWARD. We want to have the full package filed with the FDA as well to allow us to be in a position of strength for negotiation and to have strictly a commercial deal as a partnership as we anticipate, as I've said, that we will file in the major territories, EMA, Switzerland, UK, Canada. And so we look forward to have a significant, I would say, return on ex-U.S. territories as well.

Okay. That's helpful. And then over the next 6 to 12 months, we've talked about the C-FORWARD readout, but should we expect additional updates at medical meetings? How should we think about that?

Well, absolutely. We are preparing some abstract for CROI. Actually, we will share data on animal model with hepatitis E. We are very excited about that program. We think we have a winner. We like what we see in the Phase I in terms of drug exposure and safety. We are going to go into multiple ascending dose now, end of the year will be completed and going to proof of concept. Obviously, the brunt will be the -- our hepatitis C program. We felt that we want to have the 2 Phase III completed to allow us to hopefully publish in the top journal, the 2 Phase III at the same time. And in the same time, to go to major scientific meetings beginning of 2027.

Okay. You jumped the gun on me there. I was going to ask about hepatitis E, if you can introduce this opportunity. That would be great.

Sure. So I'm going to let Janet after to discuss our Phase I and what we foresee for proof of concept. This is a first-in-class. It's a candidate that we have discovered internally. It is, I think, with the number of organ transplants increasing constantly in the U.S. and Europe, about 3% of those immunosuppressed individuals are at risk of hepatitis E, that if infected, they can develop cirrhosis within 3 to 5 years. We have only ribavirin. Ribavirin is an old antiviral drug that has a major toxicity, as you know. It's used basically all the time when you don't have anything else. And so we believe that this can be another blockbuster. Obviously, orphan designation, interesting pricing when we see what companies are charging for hepatitis delta, for example, where here you have a patient population with a lifelong -- threatening actually infectious disease. So we are very excited. Janet, you can share where we stand in terms of the Phase I, what we have done so far, and what we foresee to go to proof of concept as well.

So we are currently in Phase I in healthy volunteers looking at single and multiple ascending doses, and really this study I think is the threshold for us taking the program forward. And what we're seeing so far is very pleasing safety and tolerability. And also, what we're looking for are sustained pharmacokinetic exposures, which allow for a practical dosing regimen that achieve levels that are adequate against hepatitis E, from what we've seen from the preclinical models. And to date, that's what we're seeing. And we look forward to taking the program forward, but obviously, the disciplined approach in terms of prioritizing high value activities as we prioritize the HCV launch coming up, too.

Great. And maybe if we can just touch on the current financial position, how are you thinking about cash runway, et cetera?

Look. We have -- end of June, we had almost $220 million on our balance sheet. We have sufficient runway until the end of '27, early '28. We are going to be opportunistic, as I said. We definitely will have a partnership with ex-U.S., where we'll have a significant upfront as well. And we will be opportunistic. And so we want to make sure that we'll have a solid balance sheet for the launch in mid-2028. And based on our forecast, we will be very rapidly profitable here. We have -- I think we shared before, a low cost of goods with the deal we have, the licensing deal with Merck. We basically have a pretty high margin on our regimen. So we feel pretty good where we are from a cash balance standpoint.

Okay. Before I move on to a couple macro questions, what are you just hoping investors take away from this discussion today? You have a lot of exciting things happening, a positive Phase III, a second one coming soon. Anything else that I missed?

No, I think, look, it's always, to me, exciting to have new drugs on board. We have seen, I think, the best view -- feedback we can get from both patients that were involved in our clinical trials and investigators, DSMB is that we enrolled over 1,000 patients per trial in 8 months. That tells you that there is a major appetite for a new regimen. The other 2, okay, they cure a patient, which is great. But it's astounding that 10 years ago, we had 2.5 million infected individuals in the United States. We have 4 million today. So something is not working here. So that's why we believe that our regimen is going to expand the patient population that we are going to be able to cure and avoid, I could tell, an explosion of hepatocellular carcinoma in the United States in the next 5 to 10 years. So that's what's exciting to us. And the second program is exciting to us as well. And look, we can never predict, but we think that we have tremendously de-risked our programs, and so we look forward to launch those 2 products as soon as possible to all the patients and investigators.

Okay, then 1 macro question, if you don't mind. Given the rise of, I would say, China innovation, the competitive dynamic, how is it changing your competitive positioning or maybe your R&D or BD strategy?

Yeah, look, it's interesting that we have not seen anything in the field of anti-infective, antiviral from China. We are working actually extensively with some Chinese colleagues actually and a colleague expressing, enzyme targeting. For example, the hepatitis C polymerase has not been cloned and expressed until now. We need to have the molecular mechanism there. So we have been always working in tandem with a Chinese research organization and labs. But from an innovation standpoint, we have not seen much in our field, to be honest with you.

That's very helpful. Well, I think with that we'll close up. Thank you very much, Atea team. Great seeing everyone.

Again, thank you so much. Thank you.

Thank you. Good afternoon everyone and welcome to the Atea Pharmaceuticals second quarter 2026 financial results and business update conference call. At this time all participants are in a listen-only mode. Following the formal remarks we will open the call up for your questions. I would now like to turn the call over Jonay Barnes, Senior Vice President of Investor Relations and Corporate Communications at Attea Pharmaceuticals. Ms. Barnes, please proceed.

Thank you, operator. Good afternoon, everyone, and welcome to ATAEA Pharmaceutical's second quarter, twenty twenty six financial results and business update conference call. Earlier today, we issued a press release, which outlined the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the investor section of our website. at ir.ateafarma.com. With me from Atea are our Chief Executive Officer and Founder Dr. Jean-Pierre Samadossi, Chief Development Officer Dr. Janet Hammond, Chief Commercial Officer John Vavrica, Chief Medical Officer Dr. Arantxa Horga, Chief Financial Officer and Executive Vice President legal, Andrea Corcoran, who will be available for the Q&A portion of today's call.

Before we begin the call, and as outlined on slide two, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Security. Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on today's call. With that, I'll now turn the call over to Jean-Pierre.

Thank you, Jonay. Good afternoon, everyone, and thank you for joining us. I will begin on slide three. The positive top line results from C-Beyond, our phase three trial evaluating the combination of BAM and Rizosvir for the treatment of hepatitis C in North America represent a significant milestone for Atea and for the millions of people living with hepatitis C we need a shorter, simpler path to cure. We were very pleased that C.B. Young met both his primary and secondary endpoints with bam-rusosver demonstrating statistical non-inferiority to abclusa, the current standard of care. Importantly, this was the first success phase three trial in the global head-to-head HCV program. achieved in the real world patient population that was polymedicated, Psychiatrically complex, substance abuse affected, adherence challenge. These results reinforce the need for a best-in-class profile designed for the broad and complex hepatitis C population clinicians treat today.

The Ransom will review in detail the results of the trial. See for our second phase three trial. being conducted outside North America, is fully enrolled with more than 880 patients, and we remain on track to report top-line results in early Q1, 2027. We believe that the C4WAT dataset will provide important confirmatory efficacy data across a broader range of genotypes, and strengthen the pen-genotypic regulatory package for Ben-Muzazril. In July, we also initiated our first in human phase one clinical trial of AT587, our potential first in class direct acting antiviral for chronic hepatitis E, a serious disease with no approved treatment. therapy today. This milestone reflects the continued advancement of our all-direct acting antiviral pipeline. We remain in the solid financial position with $219.5 million in cash and money. marketable securities as of June 30th, 2026, with our cash runway anticipated through 2027. I will now hand the call over to Arantza, our chief medical officer, to review our phase three program.

Thank you, Jean-Pierre. Good afternoon, everyone. Moving to slide five, See Beyond was a randomized active control non-inferiority trial against the phosphovir-belbatavir marketed as Eclusa, a standard of care regimen. The trial involved patients with chronic HCV, at approximately 120 clinical sites in the U.S. and Canada, including patients co-infected with HIV and patients across the HCV genotypes that predominate in North America. Patients without cirrhosis received benrucesvir for 8 weeks or softvel for 12 weeks. Patients with compensated cirrhosis received 12 weeks of treatment with either regimen. On slide 6, let's now review the C. b. young endpoints and patient populations. The primary efficacy endpoint is SBR or CURE at week 24, assessing the modified intent to treat or MITT population, which was agreed upon with the FDA.

This population includes all patients who received at least one dose of the regimen, including those who discontinued early, were not compliant, or were lost to follow-up. The trial is powered at 90% with a 5% non-inferiority margin. CBIOM is the anchor trial for the USMDA submission. Moving to slide seven, you can see that the baseline characteristics of the patients in C-Beyond were very well balanced across the two arms, including age, sex, BMI, race and ethnicity, status, viral load, and HIV co-infection. On slide eight, see beyond and world the HCV population clinicians are treating in North America today. which looks meaningfully different from the population studied a decade ago. In our trial, more than half of the patients reported injection drug use as the root of HCV transmission. Approximately 89% were taking concomitant medications, two-thirds had a psychiatry disorder, and over 10% prematurely discontinued treatment were lost to follow-up or were not adherent to the protocol.

Current standard of care regimens have challenges where it matters most. moderate proteins inhibitor containing regimen carries DDI limitations that restrict or complicate use in many of these patients while ECLUSAR requires 12 weeks of treatment. In our market research, only 6% of 157 high-prescribing U.S. physicians reported no unmet need, with physicians continuing to cite key priorities such as shorter duration, high efficacy, and fewer contraindications. Let's now review the Phase III results on slide 9. In the primary endpoint MITT population, Bem-Russevier achieved a 93.9% SBR rate compared with 94.8% for soft VEL at week 24, encompassing SBR 12, the accepted definition of cure for HCV. This result met the primary endpoint of statistical non-inferiority within the pre-specified 5% margin. Roots Severe deliver cure rates comparable to the standard of care while offering an 8-week regimen for non-cirrhotic patients compared to 12 weeks for soft bell. On slide 10, in the non-cirrhotic MITT population, BEM-RUSSOSVIR exceeds a 93.5% SVR rate with eight weeks of treatment, compared with 94.6% for SOFVEL with 12 weeks of treatment. in patients with compensated cirrhosis, both arms achieved a 95.4% FVR rate with 12 weeks of treatment. populations are not powered for statistical analysis.

On slide 11 is the the safety summary. Overall adverse events were comparable between the two treatment arms. Most treatment emergency events were mild to moderate and balanced between treatment arms. There were no serious adverse events due to the study drugs and while there were no deaths in the Ben Rousseff arm, three deaths in the South Bell arm were observed, but not related to the study drug. Similarly, there were no early treatment discontinuations related to the study drugs. Moving to slide 12, real-world adherence and discontinuation of treatment with loss to follow-up remains a major barrier in HCV treatment today and helps explain why current SDR rates with approved therapies can fall below the rates reported 10 years ago in the original pivotal studies. Indeed, as you can see in more recent studies, the intent to treat SBR rates fall below the rates reflected in labels established a decade ago, including rates as low as 74% among people who injected drugs with rates consistently in the low 90s.

Glide 13 summarizes the top-line results for C-Beyond. The trial met its primary and secondary endpoint with Benrules SBR demonstrating consistent SBR rates regardless of cirrhosis status and robust performance across genotypes. biological failure rates were low and comparable across treatment arms. Benzalurusvir was generally safe and well-tolerated with a safety profile comparable to soft-belly. On slide 14 is the patient populations and analysis for C-Forward, our second phase 3 trial, being conducted outside of North America to enable a broad pangenotypic label. It is fully enrolled and enriched for genotypes 1B, 3, 4, 5, and 6. using the same non-inferiority methodology and the same powering assumptions. Together, the two Phase III studies will form a comprehensive global data package for regulators worldwide. I will now hand the call over to Janet, our Chief Development Officer.

Thank you, Arantja. Good afternoon, everyone. Moving on to slide 16. M. rususvira is a next generation, pangenotypic, one-stady, six-dose regimen. C-phosphovir is the most potent nucleotide we are aware of, being approximately tenfold more active than C-phosphovir in vitro. And RuSYSVIR is a picomolar potency pan-genotypic NS5A inhibitor. Together, they have been administered to thousands of individuals with generally favorable of the intolerability. Compared to hepcluthor and Mavrit, remrosesvir is the only regimen positioned to offer the full combination of short eight-week duration for non-cirrhotic patients, protease inhibitor-free composition, low potential for drug-drug interactions, and no food effects. That combination is what defines a potential best-in-class profile.

On slide 17, the drug-drug interaction profile is a key differentiator for BEM-resilient. Roughly 80 to 90% of hepatitis C patients in the United States take concomitant medications and prescribers strongly prefer therapies that are simple to prescribe across the classes of oral contraceptives, protease inhibitors and integrase inhibitor HIV regimens, statins, immunosuppressants, digoxin, and proton pump inhibitors and other acid-reducing therapies, BEM-Rusazere is expected to be broadly compatible where competitors carry contraindications or require dose modifications. fewer drug interactions, strychnine fewer specialist referrals, fewer treatment delays, and more patients actually starting and completing therapy. Today's treatment challenge is less about efficacy and more about treatment duration, adherence, drug-drug interactions and access. Based on the potential profile of Benruzizir, we believe our regimen is well positioned to address these barriers and expand the number of patients successfully treated. I'll now turn the call over to John Vavrica, our Chief Commercial Officer.

Thank you, Janet. Let's move on to slide 19. I want to address what we believe is a widely misunderstood dynamic in the HCD market. Wall Street often looks at revenue trends for approved HCD therapies and concludes that this is a declining market. However, the prevalence and treatment data tell a different story. Early diagnosed patients with HCD infections continue to outpace patients treated annually, and that gap is widening. In 2025, only around 50% of those new infected patients were treated. The result is a growing HCD-infected population moving towards 4 million people in the United States. which is an expanding addressable market.

The test and treat model of care is emerging as a reality and will serve as a critical lever to close the gap of untreated patients. It will enable seamless rapid diagnosis and treatment initiation at the same point of care visit, reduce barriers for prescribing, and drastically reduce patient attrition even before treatment begins. This model has broad bipartisan support and is gaining momentum as a pathway towards HCV eradication in the United States. I do believe our regimen's profile is optimal for this model of care. Let's move on to slide 20. Current HCD market dynamics create a clear opportunity for Benmore Xeor. Short duration regimens continue to gain share and prescribing is increasingly driven by polypharmacy and comorbidities.

New infections keep outpacing treatment and there is a decrease in commercial efforts by competitors. Each of these trends plays directly to the strengths of BMR-ZR. We believe a potential best-in-class profile can expand treatment eligibility and improve treatment completion for patients whose medications, comorbidities, and life circumstances have historically limited access and adherence. In addition, there is market growth potential with a simplified therapy and a focused commercialization. Moving on to slide 21, on-market research supports strong uptake of Ben-Marzir. Among high volume DAA prescribers, 76% said they would be extremely likely to prescribe Ben-Marzir. And the research predicts roughly half of both non-cirrhotic and compensated cirrhotic patients would receive Ben-Marzir relative relative to Occlusa and MaviRed.

On slide 22, we believe Benoit's ER is uniquely positioned to capture untreated patients and grow the market, not simply to compete for existing share. Currently, only about half of diagnosed patients in the U.S. are treated annually, leaving roughly 75,000 untreated new infections last year on top of the already large prevalent pool of patients. In 2025, U.S. net sales were $1.3 billion, representing 50% of the global net sales of $2.6 billion. With its differentiated profile, BAM-RZR is uniquely positioned to expand the market, potentially up to $2.5 billion annually in the United States. Slide 23. Taken together, we see peak annual U.S. net revenue potential in excess of 700 million. That's anchored on a widening gap between infections and cures, up to 4 million infected, and the increasing number of untreated people in the United States as a total addressable market. The pricing is expected to be in line with existing branded VA regimens.

In closing, on slide 24, we continue to advance our commercial readiness activities across all key areas. The HCV prescriber base is highly concentrated with approximately 7,800 physicians writing roughly 80% of all DAA prescriptions in the U.S., We can reach the vast majority of this market with a focused specialty sales force of approximately 75 to 100, including sales representatives, sales managers, and medical science liaisons. All components and processes for large scale manufacturing are in place. Commercial launch supply is already underway with low cost of goods relative to the expected net price. And our four week dosing blister card packaging supports patient convenience and adherence. We believe these factors position us for a short time to profitability following a launch. I'll now turn the call back to Janet. that to review the hepatitis E program.

Thank you, John.

And slide 26. In July, we initiated our first in human phase one clinical trial of AT587. The study is being conducted in healthy volunteers with the primary objectives of evaluating safety, tolerability, and pharmacokinetics. It is a randomized double-blind placebo control design with sequential dose escalation and an embedded food effect assessment. The study includes both single ascending and multiple ascending dose phases. providing flexibility to refine dose levels as data emerge, and with dose progression informed by real-time safety and PK review. We have recently completed the first cohort and are moving forward to the next cohort. Hepatitis E has no approved therapy, so this is a potential first in class opportunity that provides a meaningful pipeline program beyond hepatitis C. to turn the call over now to Andrea Corcoran as Chief Financial Officer to discuss the TAIRS financials.

Thanks, Janet. As Joneigh mentioned in her introductory remarks, earlier today we issued a press release containing our financial results for the second quarter of 2026. The Statement of Operations and Balance Sheet can be found on slides 28 and 29. We are pleased to report that our cash and investments balance was $219.5 million at June 30, 2026. The funds we expended in the second quarter were principally directed to the advancement of our HCV Phase III clinical trials, See Beyond and See Forward, and to a lesser extent to the completion of clinical trial startup activities for the first in human study of AT587, which Janet just described is our product candidate for the treatment of HEV. As we have noted recently, milestone events in each program have been realized with the announcement of positive top line results in CPONs, the completion of patient enrollment in C4WRDS, and the initiation of the first in human clinical study of AT527. In the first six months of 2026, our R&D expenses increased compared to the prior year. principally driven by higher external spend related to the HCV phase III program and incremental HEV preclinical and clinical trial startup activities. The incremental expenses were partially offset by lower internal expenses, primarily due to decreases in stock-based compensation and payroll-related costs.

With respect to G&A, there was a decrease in the first six months of 2026 compared to the prior year due principally to lower salaries and lower wages as well as lower stock-based compensation. During the second half of 2026, we intend to maintain our rigorous financial discipline while remaining laser focused on execution and value creating advancement of our HCV and HEV product candidates. As we complete C-Forward, prepare to submit our regulatory filings and engage in pre-launch activities to support substantial majority of our spending will remain focused on the advancement of our Hepatitis C program. With the resources in hand at the end of June, we expect to realize these value-creating milestones for both programs and we project our cash runway to extend through 2027.

I'll now hand the call back to Jean-Pierre for closing remarks. Thank you, Andrea. In closing, on slide 30, I would like our milestones are clear and all near term. We completed patient enrollment for C4 in June and top-line results are expected in early Q1 2027. Pending positive results from C4, our NDA submission is anticipated in the second quarter of 2027. In parallel,.

Ladies and gentlemen, please remain on the line. We are experiencing a technical difficulty. Once again, please remain on the line. a technical difficulty. © transcript Emily Beynon © BF-WATCH TV 2021 Thank you. JP, you may continue.

I was disconnected. So in parallel, our hepatitis E program is progressing very well and advancing toward proof of concept in 2027. We believe that BAM uses potential best in class profile, including high efficacy, short treatment duration, and long-term care. a low risk of drug-drug interactions, and not for the fact position us to meaningfully contribute to the goal of HCV eradication in the US and globally. Based on our projection, we expect a short time to profitability after the anticipated mid-2028 launch. We look forward to keeping you updated on our progress. And with that, I will now turn the call back over to the operator.

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to to pick up your handset before pressing the star keys. One moment, please, while we poll for questions. Our first question comes from Andy Shea with William Blair.

Please go ahead.

Great. Thanks for taking our questions and congratulations on the big milestone for the company. So my first question has to do with... I think JP, you mentioned about the new mechanism of action. I'm curious, with the assembly disruption mechanism, how do you get that into the label that's number one number two It has to do with the test and treat model. I think Johnny mentioned about that. He also mentioned about the one month blister pack. Based on some of the conversations with KOL, they really like to see kind of test and treat model.

On top of that, you basically give all the drugs in one setting. And I'm just wondering what steps do you have to take to really reach that goal? Thank you so much.

Okay. First, Andy, thanks for your scientific knowledge. And we have not released yet all the data. And we continue to build upon this new MOA. And we anticipate to share with the FDA early next year when we'll have the full dataset. So it's a little bit early for me to discuss about it, but obviously we will present at scientific meetings and share with the FDA with the impact that we believe that this supplemental important MOA for them and totally unique. John.

John, you want to address the second question of Andy? Sure. Thanks, Andy. Yes, test and treat is what the KOLs are looking to, what they do believe will actually increase the number of patients that are treated. And you are correct that the way that they would like to practice it is the patient is diagnosed and then immediately treated. just like the other products that are out there. So we will have both bottles and for these blister packs. And similar to the other products, you would have to like the, you know, give two blister packs out if that's what the patient required or two bottles out. Very similar to what you have going on today. The reason for the blister packs was it was just identified as a more convenient way for the ACV patients, and we're trying to do everything we can to make them take their medication and be more compliant.

It's just a matter of the quantity that you'll give them at that time. Does that answer your question, Andy?.

Yes, so I guess the question also has to do with kind of refilling requirements. So after the first month, based on payers or other stakeholders. Basically, how do you eliminate that step to get a refill?.

So, I don't have that answer for you today. What I can tell you is that in talking with physicians who do practice test and treat within their respective states, the payers for those respective states have allowed them to give the appropriate amount without a refill to those patients. And that would be specific to the programs. So you are correct, where it is existing, they do give them to everyone. Would every physician be able to provide test and treat today? That's part of the challenges and the mechanisms that will have to be worked out. But I can tell you in talking to these physicians who have implemented the test and treat and have provided the treatment at that visit, they do see great promise and great success. The one thing that they were very excited about for our profile is that it really would be the best profile to use in the test and treat because of the potential lack of drug-drug interactions and not have to worry about what a patient is either taking now or will be taking, and it will offer the shortest course of therapy.

Great. Thanks so much. Our next question comes from Jonathan Miller with Evercore ISI. Please go ahead.

Hello, this is Yuan Yuan for John. Thanks for taking my question and congrats again on the FICS-3 data. So I'd like to touch on the AASLD simplified treatment algorithm. So can you walk us through the process and timeline to get the treatment included in the guideline and what evidence do you think will be most important for the panel to see from the C-Beyond and C-Forward results to include them in the treatment algorithm. Thank you.

Lorenza, you want to address that? Sure. I think what they are looking for is best-in-class profile. So this is what we are offering here. It's the eight-week for the majority of the patients. And once they see these results, and we obviously get a label and an approval, I think I think that it will not be difficult with this profile to get it into treatment algorithms. and, you know, have it prescribed by physicians. We're hearing really excellent feedback from our PIs.

Okay, thank you. I just want to add one point, is that for both the North American trial and the C4, so in 17 countries, it's absolutely remarkable that we were able to fully enroll. about 900 patients in less than eight months. So with 120 clinical sites with a high demand. And we could see at the end that the demand was going exponentially and we had actually to unfortunately stop because we could not go beyond much more in terms of the number of targeted patients. But there was really a high demand for for this clinical trial in both North America, the U.S., as well as in these 17 countries.

Next question please. Thank you. Our next question comes from Maxwell Score with Morgan Stanley. Please go ahead.

Great. Thank you very much for taking my question and congrats on the update. Regarding the non-inferiority, which also cleared on the per protocol secondary in CBEYOND, which is the C-forwards primary endpoint for the EMA, how much does that lift your confidence going into the early 1Q27 and readout. Also, how comparable do you expect the baseline characteristics to be across the two studies given C-Forward's different geographies and genotype mix? And finally, if I can ask just one more, maybe elaborate a bit more on the pricing reforms, the Medicare Part D and 340B, and how they're related.

reshaping the competitive landscape? Thank you. Great question. Arantza, you want to tackle? We are going to basically report that at scientific meeting, but we do not worry. always worry, but we do not worry on the protocol. As you have seen, it's quite a bit of discontinuation, but we have sufficient power. So why don't you chime in as well and address the difference of patients, which actually, it is substantial. Arvind, can you go ahead? Yes, I think,.

Max, I mean, it's a great question. So for the C4 word, We are more likely to see genotypes, obviously, that are not in the United States. So the United States predominantly is 1A. Ex-U.S., we're going to be seeing more of the 1Bs. And then some of the rare genotypes that we made an extraordinary effort to get, genotypes which are not common in the United States. And so it will differ in terms of genotypes, but I want to remind you that a lot of these genotypes we already treated in Phase II where we had genotype III in particular excellent results. In terms of the population, we think we'll see probably less transmission through the IV drug use, you know, that kind of population that we also saw in the Phase II, because globally there is still quite a lot of transmission through things like dental procedures, transplants, even blood transfusions.

And the population ex-US in general tends to report less frequently adverse events. They tend to be less lost to follow up. They tend to be a little more compliant with the protocol. So if anything, we think we're going to be seeing a more adherent population. and maybe even a little bit closer to what we saw in the Phase 2, where we had already excellent results. I think that was your main question for me. There was another one, though. Yes. I'm sorry, but do I think for John? Yes.

Sure. So, Max, I think your question was on pricing reform and the various, you know, generous and other legislative 340Bs reshaping the landscape. And you are correct. And it depends on, you know, what segment that you're more heavily weighted in. And currently, the two products, whether it's Maverette or Abclusa, have different percentages of their business from Medicaid or Medicare. And those changes have already started to take to effect. So, for instance, having a higher percentage of Medicare patients, the Inflation Reduction Act has had an effect on that. In the past, manufacturers weren't responsible for a percentage of the total prescription cost there, and that is happening. now. As far as the other things you mentioned like generous and so forth, which is, you know, MSN type pricing and its effect on Medicaid.

It could affect the Medicaid discounts that are currently being offered. But there's something interesting, Max, and that is when you start looking at the pricing differential between the US, for instance, and a lot of these generous or mainly EU countries or Western countries, the pricing isn't as dramatically different from the U.S. as other types of pharmaceutical products. And we were kind of shocked at that. So the impact will not be as dramatic as some people think. The other thing to bear in mind is that some manufacturers are already cutting direct deals with individual state Medicaid agencies beyond the statutory discounts to be provided. And so from that standpoint, the difference between the extra rebates that they're already providing and what the generous or the extra rebates for MFN might be, which could theoretically be smaller. But that's what we know now.

The other last thing you mentioned was 340B. I think the proposed legislative or the administrative changes that are happening for 340B, I think will be favorable to the manufacturers in the sense that, you know, if the current thinking goes through, instead of providing an outright discounted price, that it would be handled through a rebate mechanism, thus allowing the manufacturers to make sure that they're not getting double counted on both Medicaid and 340B. But so we'll have to stay tuned to see what happens with that.

Thank you very much. Max, I want to go back just to make sure that there is no misunderstanding here. On the C4, the purple core is the primary endpoint for the EMA. But for the FDA, the MITT is the primary endpoint. primary endpoint. Okay, so please be aware that the MITT has the CBN for C4, the primary endpoint for the FDA will be the MITT. So essentially we will have two primary endpoints in the C4s. I hope that just to make sure that- Very helpful. Thank you for clarifying. I appreciate it.

Thanks. Okay. Very good. Thank you, Max. And any other questions? So thank you all for joining our second quarter conference call, and thank you for your continued support.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Ladies and gentlemen, thank you for standing by. Welcome to Atea Pharmaceuticals First Quarter 2026 Earnings Conference Call. [Operator Instructions] I will now turn it over to the Atea's management team. Please go ahead.

Hi. Thank you, operator. Good afternoon, everyone, and welcome to Atea Pharmaceuticals' First Quarter 2026 Financial Results and Business Update Conference Call. Earlier today, we issued a press release, which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by visiting the Investors section of our website at ir.ateapharma.com.

With me today from Atea are our Chief Executive Officer and Founder, Dr. Jean-Pierre Sommadossi; Chief Development Officer, Dr. Janet Hammond; Chief Commercial Officer, John Vavricka; Chief Medical Officer, Dr. Arantxa Horga; and Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, who will all be available for the Q&A portion of today's call.

Before we begin the call, and as outlined on Slide 2, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on today's call.

With that, I'll now turn the call over to Jean-Pierre.

Thank you, Jonae. Good afternoon, everyone, and thank you for joining us. I will begin on Slide 3. With 2 pivotal Phase III top line readouts for our global Phase III HCV program ahead of us, 2026 will be a catalyst-rich year for Atea. We remain on track and are very encouraged by the substantial progress our team continues to achieve. We completed patient enrollment for C-BEYOND, our North American trial late last year with over 880 patients who are representative of the genotypes and demographics in North America.

For C-FORWARD our ex North America trial, I'm pleased to share today that we have completed enrollment for 95% of the cirrhotic and non-cirrhotic patients and anticipate to complete enrollment next month as scheduled. Currently, enrollment is only open to the less prevalent genotypes such as 4, 5 and 6, which will allow us to support a broad label. This set up 2 important Phase III milestones. We expect top line data from C-BEYOND in midyear, as we have reported before and top line data from C-FORWARD around year-end.

Late last year, we expanded our antiviral hepatitis pipeline to address a major unmet medical need for immunocompromised patients living with chronic hepatitis C infection, a liver disease for which there is currently no approved therapy. If left untreated in this at-risk population, it can rapidly progress to cirrhosis within only 3 to 5 years. We have completed CTA-enabling studies for AT-587, our lead product candidate, and we anticipate to initiate a first-in-human study midyear. Initial results were presented in February at CROI 2026 and additional data will be presented at EASL later this month to support AT-587 as a potential first-in-class inhibitor against hepatitis E infection.

I will review this exciting program and our clinical plan for a first-in-human study later in this presentation. Importantly, with $256 million of cash, cash equivalents and marketable securities as of March 31, 2026, we are in a strong financial position to execute and complete our Phase III HCV program and advance our new HEV development program. We anticipate our cash runway remaining through 2027.

With that, I will now turn the call over to Janet to review the profile of our regimen.

Thanks, Jean-Pierre. On Slide 5, we are conducting the first active controlled Phase III global program for hepatitis C, comparing our regimen against the current standard of care, sofosbuvir and velpatasvir, which is marketed as Epclusa. The data generated to date for the regimen of bemnifosbuvir and ruzasvir support a differentiated potentially best-in-class profile, combining high efficacy, short treatment duration with a low risk for drug-drug interactions, dosing convenience and no food effect.

We continue to add to our data set and recent results demonstrate a low risk for drug-drug interactions with proton pump inhibitors, which are taken by an estimated at least 35% of hepatitis C patients. We've also confirmed the absence of interaction with HMG-CoA reductase inhibitors or statins, another important and commonly prescribed class of medications.

In closing, I'm also pleased to share that we will be presenting additional results at EASL later this month that supports the potential for a best-in-class profile for our regimen. I'm going to hand the call over now to Arantxa to review our Phase III program for the treatment of hepatitis C. Arantxa?

Thank you, Janet. Moving ahead to Slide 7. As a reminder, C-BEYOND enrolled patients in the U.S. and Canada and C-FORWARD is enrolling patients in 17 countries outside of North America. Combined, we expect to enroll more than 1,760 patients in our Phase III program. Both trials are open label, randomized 1:1 against the active comparator and stratified by cirrhosis status and genotype, including patients co-infected with HIV. In patients with cirrhosis, treatment duration is 8 weeks with bemnifosbuvir and 12 weeks with the standard of care. Patients with compensated cirrhosis received 12 weeks of treatment with either regimen. The primary endpoint for both studies is sustained viral response or cure 24 weeks after treatment initiation.

Slide 8 shows that the geographic footprint of our global Phase III program was comprised of approximately 120 clinical sites in the U.S. and Canada for C-BEYOND and another 120 clinical sites in 17 countries outside of North America for C-FORWARD. We completed patient enrollment of our C-BEYOND trial in December with more than 880 patients, and we anticipate top line results midyear. C-FORWARD has a broader global geographic and genotypic footprint, and we expect to complete enrollment midyear and to report top line results around year-end.

As J.P. mentioned earlier, we are pleased to share that for C-FORWARD, we have completed enrollment of 95% of the trial in cirrhotic and non-cirrhotic patients. Enrollment is only open to the less frequent genotypes such as 4, 5 and 6, which will support a broad label. Enrollment of C-FORWARD remains on track to be completed by midyear.

On Slide 9, let's review the Phase III endpoints, patient population and data analyses for our global Phase III program. In C-BEYOND, the primary endpoint will be analyzed in a modified intent-to-treat or mITT population as preferred by the U.S. FDA. The analysis will include patients that have been randomized and dosed regardless of drug adherence or lost to follow-up. The statistical analysis will be based on an imputation model with success or failure depending on PCR value, whether negative or not prior to patient treatment discontinuation.

A key secondary endpoint will be the SVR rate in the per-protocol population. In C-FORWARD, the per-protocol population will be analyzed as the primary endpoint as preserved by the EMA, and the SVR rate will only include patients who are at least 80% adherent as measured by pill count and have an SVR assessment at week 24. A key secondary endpoint will be the SVR rate in the mITT population. The same method for assessing noninferiority will be conducted in both Phase III studies and in both patient populations. The Phase III studies are powered 90% with 5% noninferiority margin with expected rates above 95% in a modified intent to treat or mITT population.

Using these 2 approaches in our post-hoc analyses of the Phase II results, the SVR rate was 95% in [indiscernible] and 98% in the per-protocol population.

I will now hand the call over to John Vavricka, our Chief Commercial Officer. John?

Thank you, Arantxa. I'll begin on Slide 11. HCV remains a significant global health care crisis with an increasing incidence of infections despite the availability of direct-acting antivirals for the past decade. Currently in the U.S., out of the reported 160,000 new chronic infections, only approximately 85,000 patients are treated annually. In the U.S., it's estimated that up to 4 million people are infected with HCV. The unrelenting high rate of new chronic HCV infections, which continues to outpace the number of patients being treated, underscores the need for a new differentiated and optimized therapy.

Most countries worldwide, including the U.S., are not on track to achieve the World Health Organization's goal of HCV elimination by 2030. In fact, current estimates suggest we may not even achieve this goal by 2050. HCV is also a leading driver of liver-related morbidity in the U.S., including progression to cirrhosis and liver cancer, reinforcing the importance of expanding diagnosis and treatment.

Moving to Slide 12. The U.S. HCV market remains substantial with approximately $1.3 billion in annual net sales, about 50% of the roughly $2.6 billion global market, reflecting the size of the opportunity. In our discussions with health care providers, we consistently hear that a point-of-care test and treat approach where testing, diagnosis and treatment initiation occur in a single setting can significantly reduce delays in care and minimize patient drop-off before treatment begins. This model has broad support, including from the CDC and is gaining momentum through bipartisan efforts to achieve HCV elimination in the U.S. Key opinion leaders believe it can be an important lever to help increase the number of patients treated and support HCV elimination efforts, and they continue to emphasize the need for therapy designed to integrate smoothly into this care pathway.

Let's turn to Slide 13. This slide summarizes the U.S. HCV payer mix and expected access dynamics. Medicaid represents just over half of DAA volume with Medicare and commercial plans accounting for the balance. On the right, payer research shows a favorable outlook for parity access at parity net pricing across all 3 segments with meaningful concentrations of Medicare, Medicaid and commercial payers indicating they would be very likely to add another option. Overall, these data support our view that BEM/RZR could achieve broad formulary inclusion subject to regulatory approval.

Slide 14. This slide highlights the competitive positions for the U.S. HCV market today. You can see that Epclusa and Mavyret drive value from different payer mixes inclusive skewing more heavily towards Medicare by Mavyret is concentrated in Medicaid.

Let's move to Slide 15. Using our Phase II results, IQVIA conducted an independent quantitative market research study with 153 U.S. high prescribers. These physicians indicated that they would likely prescribe BEM/RZR regimen to approximately half of their patients, and the results were similar for all patients regardless of their cirrhosis state.

On Slide 8, based on the U.S. HCV market dynamics, we believe we can be well positioned for a capital-efficient commercial launch. The prescriber base is highly concentrated, roughly 7,800 physicians write about 80% of all DAA prescriptions, but we can reach the vast majority of the market with a specialty sales force of approximately 75, including sales representatives, sales management and medical science liaisons. With no other candidates in late-stage clinical development, BEM/RZR enters the market primarily served by only 2 regimens.

On the supply side, all components and processes for large-scale manufacturing are in place and the commercial launch supply production is already underway with low cost of goods relative to expected net pricing. The 4-week dosing blister card packaging supports patient convenience and adherence. Taken together, we believe the concentrated prescriber base, focused commercial infrastructure and favorable manufacturing economics position us for a short time of profitability following NDA approval.

I will now hand the call back to Jean-Pierre to review the HEV program.

Thank you, John. Let's move to Slide 18. Hepatitis E virus or HEV is an acute and a chronic liver disease. In developing countries, genotypes 1 and 2 are most prevalent and the virus is transmitted primarily through contaminated water, leading to epidemics of acute self-limiting viral hepatitis. In developed countries and mostly U.S. and Europe, genotype 3 is the most prevalent and is primarily transmitted through contaminated food such as undercooked meat. This genotype can cause chronic hepatitis in immunocompromised patients, which can progress to cirrhosis within a short time of 3 to 5 years. And as you may know, this is far more aggressive than what's occurred with hepatitis C or hepatitis B where it takes 15 to 20 years or even longer.

Moving to Slide 19. In recent years, with the increasing number of patients who are immunocompromised, including solid organ transplant recipients, hematopoietic stem cell transplant recipients as well as patients with hematologic malignancies such as multiple myeloma, there have been a growing incidence of chronic hepatitis C infection in U.S. and Europe. Currently, the standard of care include reducing immunosuppression and/or off-label ribavirin administration, which both present challenges, leading to a real opportunity for an effective direct antiviral drug.

On Slide 20, each year in U.S. and Europe, 3% of approximately 450,000 patients who have this underlying medical condition are at risk to develop chronic hepatitis C. The unmet need for this patient population potentially represent a market opportunity between $750 million to $1 billion each year.

On Slide 21, this slide highlights the preclinical data for AT-587 as a potential first-in-class direct-acting antiviral for chronic hepatitis E. In the genotype 3 replicant in vitro model, AT-587 demonstrates the greatest potency. And importantly, this antiviral activity has also been confirmed in primary human hepatocytes, the target organ for hepatitis E replications. vitro data also indicate low potential for drug-drug interaction, which is important for this immunocompromised patient who, for some take lifelong therapies.

On Slide 22, to date, AT-587 has a clean in vitro and in vivo safety profile, CTA-enabling GLP toxicology and safety pharmacology studies are completed, allowing us to advance to Phase I studies and positioning this product candidate as a first-in-class direct acting antiviral for chronic hepatitis E infections.

On Slide 23, [ the emerging ] PK data in nonhuman primates and through modeling, we can predict that plasma exposure in humans will exceed the in vitro EC50 against hepatitis E replication in vitro across the internal administration at pharmacologically relevant dosing.

On Slide 24, this slide outlines a synopsis of our first in-human study for AT-587. The study will be conducted in healthy volunteer with the primary objective of evaluating safety, tolerability and pharmacokinetics. It's a randomized, double-blind, placebo-controlled design with sequential dose escalation and an embedded food effect assessment. We have incorporated standard sentinel dosing and gated escalation with dose progression informed by real-time safety and PK review. The study includes both single ascending and multiple ascending dose phases, providing flexibility to refine dose levels as data emerge.

I will now turn the call over to Andrea to discuss Atea financials.

Thank you, Jean-Pierre. As Janet mentioned in her introductory remarks, earlier today, we issued a press release containing our financial results for the first quarter 2026. The statement of operations and balance sheet are on Slides 26 and 27. We are pleased to report that our cash and investments were $256 million at March 31, 2026. The funds expended in the first quarter were principally directed to the advancement of our HCV program, evaluating the combination regimen of bemnifosbuvir and ruzasvir and to the advancement of -- and completion of the CTA-enabling studies and manufacture of clinical trial material of AT-587, our product candidate for the treatment of HEV.

For R&D expenses, quarter-over-quarter, there was an increase in 2026 compared to 2025. The net increase in '26 was principally driven by an increase in external spend related to our HCV Phase III clinical development and HEV preclinical development, offset by lower internal expenses, primarily related to a decrease in stock-based compensation and lower payroll and payroll-related expenses.

For G&A, quarter-over-quarter expenses decreased. The net decrease was primarily related to lower salaries and wages, lower stock-based compensation expense and lower professional fees. In 2026, we intend to maintain our rigorous financial discipline while remaining laser-focused on execution and value-creating advancement of our HCV and HEV product candidates.

As we complete our Phase III trials, prepare to submit our regulatory filings and engage in prelaunch activities, including the manufacturing of commercial launch supply. A substantial majority of our spending in 2026 will remain focused on the advancement of our hepatitis C program. With the resources in hand at the end of March, we expect to realize value-creating milestones for both our hepatitis C and our hepatitis E programs, and we project our cash runway to extend through 2027.

I'll now hand the call back to Jean-Pierre for closing remarks.

Thank you, Andrea. In closing, 2026 is set to be a pivotal and value-creating year for Atea. We remain on track to deliver top line Phase III results from C-BEYOND in mid-2026, followed by top line Phase III results from C-FORWARD around end of the year. We believe the target profile of our regimen, high efficacy, short treatment duration, a low risk of drug-drug interaction and convenient dosing with no food effect position us to meaningfully address the needs of today patients and prescribers.

We believe our regimen fits seamlessly within the test-and-treat model of care, which has the potential to expand the number of patients treated and accelerate progress toward the goal of HCV medication in the United States and globally. Our HEV program is a strategic expansion of our antiviral pipeline aimed at addressing a major unmet need for highly vulnerable patient population with no approved treatment options today. We anticipate initiating our first in-human study midyear, followed by the initiation of a proof-of-concept study around year-end.

With that, I will turn the call back over to the operator.

[Operator Instructions] Our first question is from Jonathan Miller with Evercore.

Looking forward to the upcoming data. Let's start with that. I guess to what extent -- or what should we expect from the top line announcements for C-BEYOND and then later in the year for C-FORWARD? What sorts of data should we expect in a top line press release versus what would be withheld for later publication at a medical meeting or in a peer-reviewed setting, so, a.

And then second, when we think about commercial launch cadence and potential there, assuming the Phase IIIs bear out the differentiated product profile that you guys have been telling us about for a while, to what extent is commercial adoption going to be gated by contracting or by lumpy elements of getting your regimen in place in a program or a test-to-treat initiative that might have requirements on the drug that chooses.

Thank you, Jon. Okay. I will address the first question. The first question, we will release as data with the C-BEYOND, the primary endpoint and the key secondary efficacy endpoint. So the SVR at week 24 after initiation of treatment in the modified intent-to-treat population as well as the SVR at week 24 in the per protocol population. John, you want to address the second part of the question?

Sure. So Jon, thank you for the question. So currently, our launch preparation are currently underway, and that includes the analysis and evaluation of the marketplace and understanding currently where the business segments are coming from, where likely future growth coming from and also looking at where we will focus our activities.

And that would be including across the 3 segments from a commercial perspective of payers in terms of who we want to target and what their formulary status is right now and all those associated time lines as well as preparations for Medicaid and Medicare areas. And the activities we will pull -- start executing them upon the data of our Phase III trials.

And part of the question that you asked in terms of understanding what those time lines are and so forth, we will be evaluating all of that as we put into our penetration segments for the market.

Our next question is from Maxwell Skor with Morgan Stanley.

This is Selena on for Max. With your market research based on Phase II results, what could you see in the Phase III that you would expect to impact prescriber or payer response?

Arantxa do you want to address that question?

Go ahead.

Yes. So with your market research being primarily focused on like the Phase II results, what could you see in the Phase III results that you think might impact the prescriber payer response?

So I think we see things along the same trends that we saw in Phase II, which is great efficacy with low potential for drug-drug interaction, no food effect, et cetera. So data consistent with Phase II, which is what we see -- always see in infectious diseases, the Phase II data translates very well into Phase III. I don't know if John wants to add something to this.

No, I think I'm fine. Obviously, we used the Phase II data, and that data was very well received. And the only thing I'll tell you is that the payers and others are also very much interested in having a head-to-head trial because it's the first time. And it was something that's very intriguing and important to them as well. And it plays into the previous question about being ready for launch readiness. And one of those factors when you talk to the payers also is the head-to-head trial is very helpful to them.

Our next question comes from Andy Hsieh with William Blair.

First one, it has to do with C-BEYOND. So looking at the modified intent-to-treat population analysis plan, I think you basically calculated SVR12 of 95% based on the Phase II study. Looking across the landscape, I believe Gilead published some of the noncompliant SVR12 rates before, and it's in the low 90s depending on the trials that you're looking at. So I'm curious about your thinking in terms of a superiority claim based on that delta. So just maybe commenting on the powering and sample size to see what level of confidence you have to achieve that milestone.

Second question has to do with 587. You mentioned about the first-in-human study and the design. I guess, 2 parts. One is for this first-in-human study, what is the treatment duration that you intend to test? And then I guess, in the real-world setting, what do you expect the treatment duration to be?

Andy, it's a great question. First, look, our goal is to have our regimen delivered to patients and prescriber and with the attributes that we have and we continue to demonstrate through clinical trials and nonclinical studies as well or clinical pharmacology studies as well. And so our goal is a noninferiority trial, as you know, within 5% margin.

When we talk about the real world, including a true intent-to-treat, you're right, it's around 90% or closer. If we take the same value in our Phase II, we were about the same as a true intent-to-treat, as you know.

So look, let's see -- we don't want to speculate what it's going to be. We are going to actually evaluate -- we think we have sufficient power definitely for the noninferiority target. And we'll see the superiority probably with the 2 trials because that we will increase even the power when we combine the trial. And there is actually an analysis that it is planned and that has been shared with the FDA combining this 2 study and evaluated for potential superiority.

For the AT-587, it's a good question. First and then Phase I is going to be a 7-day as standard Phase I as we did with other indications. For the treatment duration, we foresee that we will start the proof of concept, which we believe we should be able to initiate by year-end with a 12 weeks treatment duration. We are the chronic tox -- toxicology studies ongoing right now, and we will have [ p-ANCAs ] 3 months sometimes in the fall. So definitely on time to open a CTA on the proof of concept. We will start very likely based on the Phase I data that we will generate probably as you have seen from the -- from what we predicted, 600-milligram is a potential dose, QD or BID, we'll see. And that would be at 12 weeks.

Now we will upfront to continue this chronic toxicology studies up to 6 months in rat and 9 months in monkey because potentially, we'll see if we don't see a high SVR rate with 12 weeks, we can potentially move to 24 weeks. Treatment duration is not an issue in this patient population. As you know, they take lifelong treatment against organ rejection. So compliance should be very good. And we have seen so far, safety from a preclinical standpoint have been good. And we can have quite the flexibility in the Phase I, as I have just indicated, related to a QD or BID regimen, whether 12 weeks or 24 weeks.

We have reached the end of the question-and-answer session. I would like to turn the call back now to Jean-Pierre Sommadossi for closing remarks.

Thank you all for joining our first quarter 2026 earnings conference call, and thank you for your continued support.

Thank you. This concludes today's conference. You may disconnect your lines at this time. Have a wonderful day.

Good afternoon, everyone, and welcome to the Atea Pharmaceuticals Fourth Quarter 2025 Financial Results and Business Update Conference Call. [Operator Instructions]

I would now like to turn the call over to Jonae Barnes, Senior Vice President of Investor Relations and Corporate Communications at Atea Pharmaceuticals. Ms. Barnes, please proceed.

Great. Thank you, operator. Good afternoon, everyone, and welcome to Atea Pharmaceuticals Fourth Quarter and Full Year 2025 Financial Results and Business Update Conference Call. Earlier today, we issued a press release, which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the Investors section of our website at ir.ateapharma.com.

With me today from Atea are Chief Executive Officer and Founder; Dr. Jean-Pierre Sommadossi; Chief Development Officer, Dr. Janet Hammond; Chief Commercial Officer, John Vavricka; Chief Medical Officer; Dr. Arantxa Horga; and Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, who will be available for the Q&A portion of today's call.

Before we begin the call and as outlined on Slide 2, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on today's call.

With that, I'll now turn the call over to Jean-Pierre.

Thank you, Jonae. Good afternoon, everyone, and thank you for joining us. I will begin on Slide 3. I am pleased to report that we have made substantial clinical progress in the last year, advancing our global Phase III program evaluating the regimen of bemnifosbuvir and ruzasvir for the treatment of HCV infections. Due to the rigorous execution of our 2 pivotal Phase III trial, C-BEYOND and C-FORWARD, we expect top line readout this year for both [indiscernible].

We also presented several datasets, reinforcing the potential best-in-class profile of our regimen at the EASL Congress in 2025 and the liver meeting 2025, the Annual Meeting of ASLD. Janet will discuss highlights from these presentations. We convened two panel discussions with key opinion leaders that underscore the need for a new optimized HCV regimen to address treatment paradigm shifts including the test and treat model of care and how our regimen is uniquely positioned to address the current needs of patients and prescribers and expand the market in the U.S.

In November, we announced the expansion of our anti-viral [indiscernible] pipeline to address a major unmet medical need for immunocompromised patients living with chronic hepatitis E infection, the liver disease for which there is currently no approved therapy available. If left untreated, it can rapidly progress to cirrhosis within 3 to 5 years. In vitro and in vivo results presented last month at [indiscernible] 2026 and at the JPMorgan Healthcare Conference in January support our lead product candidate, AT-587 as a potential first-in-class inhibitor against HEV infection. I will review this exciting program letter in the presentation.

Moving to Slide 4. I'm pleased to report that our global Phase III HCV program is on track. In December, we completed enrollment for our North American trials, C-BEYOND, with over 880 patients, and we expect to complete enrollment in C-FORWARD, which are outside of North America, by midyear. We anticipate top line results for C-BEYOND [indiscernible] and for C-FORWARD by year-end. Following our selection of AT-587 as the lead product candidate in our HEV program, we initiated IND and CTA-enabling studies and anticipate initiated -- initiating a first-in-human study midyear.

Importantly, with $301.8 million of cash, cash equivalents and marketable securities as of December 31, 2025, we are in the strong financial position to execute and complete our Phase III HCV program and advance our new HEV development program. We anticipate our cash runway would extend to 2027.

With that, I will now turn the call over to Janet to review the profile of our regimen.

Thanks, Jean-Pierre. Moving to Slide 6. Hepatitis C remains a significant global health care crisis with an increasing incidence of infections despite the availability of direct acting [indiscernible] for the past decade. Currently, in the United States, out of the reported 160,000 new chronic infections, only 85,000 patients are treated annually. In 2015, there were approximately 2.5 million people infected in the United States. Today, that number has nearly doubled to approximately $4 million, the unrelenting high rate of new chronic hepatitis C infections, which continues to outpace the number of patients being treated, underscores the need for a new differentiated and optimized therapy.

In the map shown on the right, you can see that most countries worldwide, including the United States are not on track to achieve the World Health Organization's goal of the elimination of hepatitis C by 2030. In fact, current estimates suggest we may not even achieve this goal by 2050. Let's not forget that hepatitis C is the primary cause of liver cancer in the United States. The incidence of which is projected to increase by over 50% within the next 5 years from approximately 850,000 cases in 2025 to 1.4 million people.

On Slide 7. We're conducting the first global head-to-head active controlled Phase III trials in our program for hepatitis C, comparing our regimen against the current standard of to [indiscernible], which are marketed as [indiscernible]. Results support our regimen as a potential best-in-class treatment option for patients infected with HCV with a differentiated profile featuring a highly potent combination with a short treatment duration, low risk for drug-drug interactions and convenience with no food effect. We continue to build out our data set and recent results demonstrated a low risk for drug-drug interactions with [ proton pump ] inhibitors, which are taken by an estimated 35% of hepatitis C infected patients.

Moving to Slide 8. We've presented several datasets supporting the potential best-in-class profile of the regimen of bemnifosbuvir and ruzasvir last year at the EASL Congress and then at the liver meeting. Results from the Phase II study in 275 patients demonstrated the 8-week regimen of bemnifosbuvir achieved 98% SVR12 in the protocol treatment [indiscernible] population and a 95% SVR12 in the efficacy evaluable population.

Additional results demonstrated that the regimen has a high barrier to resistance. The regimen has a low risk for drug-drug interactions, including with proton pump inhibitors, H2 blockers and also standard HIV therapy. There is no need for dose adjustment of bemnifosbuvir in patients with hepatic or renal impairment. The regimen can be taken with or without food.

In addition, recently generated data show that in addition to inhibiting HCV RNA [indiscernible] through train termination, bemnifosbuvir also inhibits assembly and secretion of new hepatitis [indiscernible] further extending its high antiviral potency.

With that, I'll now turn the call over to [ Arantxa ] to provide an update on our Phase III program for hepatitisC.

Thank you, Janet. On Slide 10, C-BEYOND enrolled patients in the U.S. and Canada and C-FORWARD is enrolling patients in 17 countries outside of North America. Combined, we expect to enroll more than 1,760 patients in our Phase III program. Both trials are open-label, randomized 1:1 against the active comparator and stratified by cirrhosis status, genotype and including patients co-infected with HIV.

In patients without cirrhosis, treatment duration is 8 weeks with bemnifosbuvir and ruzasvir and 12 weeks with the standard of care. Patients with compensated cirrhosis received 12 weeks of treatment with either regimen. The primary endpoint for both studies is sustained viral response or cure 24 weeks after treatment initiation.

Slide 11 shows the geographic footprint of our global Phase III program with approximately 120 clinical sites in the U.S. and Canada for C-BEYOND and another 120 clinical sites in 17 countries outside of North America for C-FORWARD. As JP mentioned earlier, C-BEYOND patient enrollment was completed in December with more than 880 patients and we anticipate top line results midyear. C-FORWARD has a broader global geographic and genotypic footprint and we expect to complete enrollment midyear and to report top line results by year-end.

On Slide 12, let's review the Phase III endpoints, patient population and data analysis for our global Phase III program. In C-BEYOND, the primary endpoint will be analyzed in a modified intent to treat population as preferred by the U.S. FDA. The analysis will include patients that have been randomized and dosed regardless of drug adherence or loss to follow up. The statistical analysis will be based on an imputation model with success or failure depending on PCR value, whether negative or not, prior to patient treatment discontinuation. A key secondary endpoint will include the SVR rate of the protocol population.

In C-BEYOND, the protocol population will be analyzed as the primary endpoint as preferred by the EMA. And the SVR rate will only include patients who are at least 80% adherent as measured by pill count and half an SVR assessment at week 24. A key secondary endpoint will include the SVR rate for a modified intent-to-treat population.

The same method for assessing noninferiority will be conducted in both Phase III studies in both patient populations. The Phase III studies are powered 90% and with 5% noninferiority margin with expected rates approximating 95% in an MITT population. Using these 2 approaches in a post hoc analysis of the Phase II results, the SVR rate was 95% in an MITT population and 98% in the per protocol population.

I will now hand the call over to John Vavricka, our Chief Commercial Officer. John?

Thank you, [ Arantxa ]. Moving on to Slide 14. As discussed earlier in the call, the rate of newly reported HCV infections in the U.S. is outpacing treatment out of approximately 160,000 new HCV infections only 85,000 patients are treated annually for a total of approximately $1.3 billion in net sales in the U.S. We have consistently heard from health care providers that the test and treat model care which allows for HCV testing, diagnosis and treatment at the point of care, can reduce the barriers to prompt initiation of therapy that exists today. The test and treat model of care has gained broad support including by the CDC and continues to gain momentum through recent bipartisan efforts to advance HCV elimination in the U.S.

Key opinion leaders also asserted can play a critical role in HCV elimination efforts, and agree that a treatment optimized or seamlessly with this model is still needed.

On Slide 15. While we are advancing our global Phase III trials, we are also preparing for a commercial product launch. Our commercial package will include a blister card for convenience and adherence with a simple 4-week dosing package. The drug product has a low cost of goods relative to net price. And based on our current projections, we anticipate achieving profitability relatively shortly post launch.

From a commercial standpoint, the U.S. HCV prescriber base is highly concentrated with approximately 6,000 prescribers writing 80% of the DAA prescriptions, making it optimal for efficient commercialization using a focused specialty sales force. We anticipate a commercial sales force of around 75 people, which includes the sales team and medical science liaisons.

Let's move on to Slide 16. Using our Phase II results, IQVIA conducted an independent quantitative market research study with 153 U.S. high prescribers. These physicians indicated that they would likely prescribe the BEM-RZR regimen to approximately half of their patients. And the results were similar for all patients regardless of their cirrhosis status. Our market research also showed that U.S. payers respond favorably about the potential to include BEM-RZR and the formulary based on the regimens profile.

I'll now hand the call back to Jean-Pierre to review the HEV program.

Thank you, John. Let's now move to Slide 18. [indiscernible] HEV is an acute and chronic liver disease. In developing countries, genotype 1 and 2 are most prevalent and the virus is transmitted primarily through contaminated water and mostly cause epidemics of acute self-limiting [indiscernible]. In developed countries, genotype 3 is predominantly transmitted primarily to contaminated food such as undercooked. This can cause chronic hepatitis in immunocompromised patients and can progress to cirrhosis within 3 to 5 years, which is much far more aggressive than what we've seen with hepatitis C or hepatitis B. With no approved therapies for HEV, there is a significant unmet need for a treatment option.

Moving to Slide 19. In recent years, with the increasing number of patients who are immunocompromised, which include solid organ transplant recipients hematopoietic stem cell transplant recipients, patients with hematologic malignancies such as multiple myeloma. There have been a growing incidence of chronic HEV infection in U.S. and Europe. In the absence of any approved therapies for HEV, the standard of care includes reducing immunosuppression and/or reviving administration, which both presents challenges.

On Slide 20, each year in the U.S. and Europe, about 3% of approximately 450,000 patients who have this underlying medical conditions are at risk to develop chronic HEV. We estimate that the unmet need for this patient population represents a market opportunity between $750 million to $1 billion per year. And obviously, this will follow an orphan designation.

On Slide 21, let's now review data supporting the selection of AT-587, our lead product candidate, a potential first-in-class direct-acting antiviral treatment option for chronic HEV. As you see on this slide, in vitro and in vivo activity of bemnifosbuvir was shown against hepatitis E. However, a more important in vitro activity of AT-587, combined with the positive PK data, which we'll discuss next, led us to select AT-587 as the lead product candidate.

The in vitro data in this slide show the potent normal antivalactivity of AT-587 against HEV genotype 3 and to remain also active against clinical revive and resist and associated substitutions over us. As noted earlier, ribavirin is off label for the treatment -- is used off label for the treatment of HEV.

On Slide 22, we observed that the in vivo single-dose PK studies in rats and monkeys, AT-587 achieved high plasma concentration of the active triphosphate metabolite [indiscernible], which were comparable to those obtained with bemnifosbuvir.

On Slide 23, of particular importance, we also demonstrated that AT-587 efficiently converted to its active [indiscernible] in human nepathocytes, which is the site of [indiscernible] application in HEV infection. To date, AT-587 has a clean preclinical safety profile, positioning this product candidate as a first-in-class direct acting [indiscernible] chronic HEV.

I will now turn the call over to Andrea to discuss the financials.

Thanks, Jean-Pierre. As Jonae mentioned in her introductory remarks, earlier today, we issued a press release containing our financial results for the fourth quarter and full year 2025. The statement of operations and balance sheet are on Slides 25 and 26.

We are pleased to report that our cash and investments were $301.8 million at December 31, 2025. The funds expended in 2025 were principally directed to the advancement of our HCV Phase III program, evaluating the combination regimen of bemnifosbuvir and ruzasvir and to discovery efforts leading to the nomination in January 2026 of AT-587 as the lead product candidate for the treatment of HEV.

In 2025, we also returned $25 million to our stockholders through a share repurchase program. Each of these investments and use of funds reflects our steadfast commitment to drive value for our stockholders.

For R&D expenses quarter-over-quarter and year-over-year, there was an increase in 2025 compared to 2024. The net increase in 2025 was principally driven by an increase in external spend for our HCV Phase III clinical development, offset by a decrease in 2025 in external spend for our COVID-19 clinical development and lower internal expenses, primarily related to a decrease in stock-based compensation expense and lower payroll and payroll-related expenses.

For G&A expenses quarter-over-quarter and year-over-year, expenses decreased. The net decrease was primarily related to lower stock-based compensation expense partially offset by increased professional fees.

For 2026, we intend to maintain our rigorous financial discipline while remaining laser-focused on execution and value-creating advancement of our HCV and HEV product candidates. As we complete our Phase III clinical trials, prepare to submit our regulatory filings and engage in prelaunch activities, including the manufacturing of commercial launch supply, the substantial majority of our spending in 2026 will be focused on the advancement of our HCV program.

With the resources in hand as of the end of the year, we expect to realize value-creating milestones for both programs and project our cash runway to extend through 2027. I'll now hand the call back to Jean-Pierre for closing remarks.

Thank you, Andrea. On Slide 27, in closing, 2026 will be a pivotal year for Atea. We are on track to deliver top line Phase III results from C-BEYOND media. These results will be followed by the top line results from C-FORWARD by the end of this year.

We believe that the target profile of our regimens securing high efficacy, short treatment duration, low risk of drug-drug interaction, convenience with no food effect. We're uniquely positioned us to address the need of today's patients and seamlessly fit in the test and treat model of care, which has the potential to bring us closer to the ultimate goal of HCV medication.

Our HEV program represents a strategic expansion of our anti viral pipeline and address a major unmet need in a highly [indiscernible] patient population for which there is no approved treatment available. We anticipate initiating a first-in-human study midyear with a proof of concept by the end of the year, and possible to advance to a Phase III trial in the second half of 2027.

With that, I will turn the call back over to the operator.

[Operator Instructions] The first question will come from Maxwell Skor with Morgan Stanley.

This is [ Selena ] on for Max. Having achieved your enrollment target for the cirrhotic population for C-BEYOND, does that increase your confidence in hitting your target in C-FORWARD?

[ Arantxa? ]

We are going to achieve our target overall for the program, both in C-BEYOND and C-FORWARD, the cirrhotic enrollment has not been an issue.

The next question will come from Jonathan Miller with Evercore ISI.

As we look forward to a commercial launch in HCV, I guess I'll focus there. Can you talk a little bit about how the commercial landscape is currently organized in terms of contracting? Are there centralized groups that you're going to have to convince to switch over from legacy systems, how is pricing in the commercial universe currently going to evolve as we've seen the legacy regimens get put under significant pricing pressure. So can you talk a little bit about how the commercial landscape has evolved over the past 6 to 9 months and how well you're positioned to deal with those changes?

Great question, Jon. John?

Sure. So as you know, that the market for -- the distribution market for specialty -- for DAA is the specialty market. And there are 3 segments, pretty much commercial, Medicare and Medicaid. All of these current distribution pathways are known and are fully utilized. And we're currently looking at all of those relative to the 3 segments as well as relative to the payers.

So it's a known quantity where we will have to be. We actually have conducted preliminary research with the payers and obviously seeing the profile, it is of interest to them. And it was stated that they would be eager to include a formulary.

As far as where pricing goes, the pricing, it's relatively stable. Year-over-year, [indiscernible] pricing went up a little bit. But [indiscernible] pricing did -- net pricing did go down. But overall, for the past at least 2 or 3 years, the pricing has been -- the relative overall net pricing has been relatively stable. And their market shares are getting pretty close to a 50-50 with the favoring at [indiscernible]. Did that answer your question?

Yes, it does.

The next question will come from [ Andy Shay ] with William Blair.

So looking at the primary endpoint of C-BEYOND based on the modified intend-to-treat population. Am I thinking about this correctly that based on this analysis plan, you can actually really expand the effect size because you can basically magnify a regimen that casually can have flexibility into missing doses and given the more potency profile compared to the standard of care. So that's part number one.

And part number 2 is in [indiscernible] where you can actually show material clinical benefit over the standard of care, say, maybe with a statistical perspective, John, based on your market analysis, how would that change some of the physician response in terms of their excitement or potential market uptake.

Good questions, Andy. [ Arantxa ], you want to try the first one?

Andy, the -- so the MITT, as you know, is everybody that gets a dose. So there will be a range there from people that will get 1 dose or maybe 5 days of dosing to people who will be almost done with a full picture. So with all the doses. So I think it will be interesting to see how it pans out. What's the minimum, I guess. But right now, we're really aiming for an 8-week regimen. We can do some analysis in the future.

John?

Yes. We're actually very excited because when we look at the market research that has been done just with the Phase II data, bearing in mind that these physicians have 10 years' experience with 2 DAAs and showing them a profile and which, as we talked about, the short duration, low [indiscernible] drug-drug interactions and the convenience of with or without food. Just seeing that profile over the first time they saw it being used in in approximately 50% of their patients regardless of their cirrhosis status. So the profile right now stains very, very well.

So your question about if there was some kind of a more favorable response in terms of BEM-RZR. Obviously, that would play into their likelihood to prescribe them RZR. But we're also very conscious that we play in the specialty arena. And in that specialty arena. Obviously, the distribution of market share tends to balance itself out to make sure that the market is preserved over time.

Just to add, Andy, it's clear from the KOL and the prescriber that. Number 1 key important feature is the treatment duration. So treatment duration, definitely, we will be in the shortest with [indiscernible] you evaluate all the, I would say, complex aspect with patient with poly medication, we feel that the prescriber will really highly favor our regimen.

And then we'll see the -- we have to wait the clinical data in terms of all the type of side effect with fatigue and nausea and the headaches that have been reported. So let's not forget that this is the first head-to-head. There is a lot of wild-type studies. But as a control, randomized clinical study, this is the first one. And let's see what we are going to learn.

Great. And maybe a quick housekeeping item. Just from an R&D perspective, it seems like there is a onetime [ Merck ] license agreement, can you talk about that just so you have a better sense of kind of going forward with the...

Okay. Sure. Andrea?

So yes, Andy, we have in-licensed ruzasvir, which is the combination product with bemnifosbuvir in the HCV product candidate. We are paying milestones, and we will pay royalties to Merck on successful commercialization. The next milestone will be due when we submit the NDA and the NDA is approved. And we believe that's in 2027.

This concludes our question-and-answer session. I would like to turn the conference back over to Jean-Pierre Sommadossi for any closing remarks.

Thank you all for joining our fourth quarter 2025 and full year earnings conference call, and thank you for your continued support.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Good morning. Welcome to the 44th Annual JPMorgan Healthcare Conference. My name is [indiscernible]. I'm an associate in the JPMorgan Healthcare Investment Banking team. It is my great pleasure to introduce our next presenting company, Atea Pharmaceuticals.

With that, please welcome CEO and Founder, J.P. Sommadossi.

Thank you, and good morning. And before I begin, I would like to thank JPMorgan for the invitation and the opportunity to share with you today some updates on our regimen of bemnifosbuvir and rizasvir, which is in Phase III -- global Phase III for the treatment of hepatitis C and some new data on our new program for the treatment of hepatitis E.

Before I begin, just the regular disclaimer and forward-looking statement. And you can see everything in our latest SEC filing. So this year has been really a flawless execution of our global Phase III program for the treatment of hepatitis C and really leading us to a pivotal year for 2026. We discovered bemnifosbuvir about 7 years ago, and we are very excited to finally, after 7 years to be within 6 months for the data on the first trial, C-BEYOND, which this is a North American trial. We announced last month that the enrollment was completed. Actually, we have more than 900 patients enroll. With the result, this will be the first set of data from the global Phase III program we expect mid-2026, I would say, Q3 this year.

The second program -- I'm sorry, the second clinical trial, Phase III is also on track, C-FORWARD. This is the one outside North America, 17 countries, 120 clinical sites. We are enrolling at the expected pace, actually probably also ahead of schedule, expected next quarter, end of next quarter for the announcement for the full enrollment and the results for the end of the year so that we anticipate to file an IND -- I'm sorry, an NDA with the FDA on the first quarter of 2026.

Our new program that we announced in November, it's the expansion of our antiviral pipeline with a potential treatment in immunocompromised patients. This is a very high-risk patient population that live with hepatitis E infections. And I'm pleased to share today that we have selected a clinical candidate, the AT-587. I'm going to go over the presentation with some recent data. We are very excited about this program, especially that there is no treatment for hepatitis E, and this could be a major issue for patients recipients of solid organ transplantation, for example, bone marrow transplant and hematologic malignancies.

Importantly, just a couple of weeks ago, so at the end of December, we have, as you can see, a very solid balance sheet in excess of $300 million in cash and investment with a cash runway all the way through 2027, beginning of '28, which will allow us to complete the Phase III program, as you will see the milestones at the end to be in the pivotal trial as well with our hepatitis E program and be ready to launch as we are already prepare in parallel the commercial activities with the commercial drug supply.

So maybe in contrast that we could expect for people not involved in the field like ourself or KOL or specialists in hepatology. After the introduction of 2 highly potent and safe leading to cures, you would expect that the prevalence and the infection rate in the United States will decrease. Well, actually, that's a dream because actually, 10 years ago, we had about 2.5 million infected individuals in the United States. And today, despite the fact that we have 2 active regimen, we have in excess of 4 million individuals. 20 years ago, we thought that HCV will be eradicated, as you can see on this slide, by 2030, so 5 years from now, as you can see that most of the countries in the world, including the United States, are not going to have an eradication program finalized until 2050, which is 25 years from now, at a cost that has been estimated by experts in the range of $50 billion to $60 billion.

And this is why actually has been predicted by expert physician in the field that the number of liver cancer in the United States will increase by 50% over the next 5 years from about 800,000 to 1.4 million with more than 1.2 million deaths per year 5 years from now. And the majority is -- what is responsible is hepatitis C.

So let's go now on reviewing our profile, which we believe is a best-in-class profile for the treatment of hepatitis C. Our regimen combined bemnifosbuvir, which is the most potent nucleotide inhibitor. It's about 10 to 50x more potent than sofosbuvir, which is part of the velpatasvir/sofosbuvir combination called Epclusa. And this is -- our regimen also includes a highly potent NS5A inhibitor we licensed global rights from Merck about 3, 4 years ago. Regimen, we believe, is significantly differentiated from the approved treatment. It offers a highly potent pan-genotypic, short treatment duration, low drug-drug interaction.

And I'm going to share with you why we think that this is so important today and especially with a new way that has been announced by specialists and including the current administration as a way, hopefully, to expand the treatment in the United States and make a dent toward eradication of hepatitis C. And this is a test-and-treat model of care, which we believe our regimen is ideal with -- basically to use in this approach. So for example, we show that we have no drug-drug interaction with proton pump inhibitor. Well, it may not be a big deal, but 35% of hepatitis C patients do take proton pump inhibitor. And actually, that can really have a negative impact on the hepatitis C regimen such as Epclusa.

Also, keep in mind that these individuals do not take just one drug, but actually a co-medication of 10 to 15 medications a day. So you can see why a lack of drug-drug interaction is very important. Our Phase III program is designed to confirm the efficacy, safety and tolerability. We demonstrated in the per-protocol population, a 98% efficacy cure rate or sustained biological response 12 weeks after treatment termination.

So now let's move to review also the supporting commercial opportunity, why we think that this is a $1 billion drug. And actually, just we had 2 KOL events in the past year. The last one as part of the liver meeting in Washington in November. And what you can see the message essentially is the same here. And it's shorter and better. It's very important for the compliance in this patient population. It's clear that drug-drug interaction is the #2. And everyone now -- it was quite interesting that at the liver meeting in November in Washington, everyone talked about this new model of test and cure -- I'm sorry, of test and treat as a way to really expand the treatment in this patient population for hepatitis C.

As I have mentioned before, so the rate -- the annual rate of new hepatitis C infection in the United States increase actually almost exponentially and definitely exceed unfortunately, the annual treatment. So the pool is not going down. The pool is increasing. And the only way we believe is to have an easy, convenient regimen, short-term duration, such as 8 weeks, low risk of drug-drug interaction that is going to be optimal for both physicians and patients. And we think that our regimen is ideally suited for this new model of care. Also, what we have seen is bipartisan legislative efforts, also CDC at the recent event and supporting this model of care with test and treat.

There is now availability of very rapid diagnostic and this will allow those physicians that they don't have to worry about drug-drug interaction with our regimen to prescribe the same day. And as you see, with a very high efficacy with -- in the high 98%. Following the Phase II clinical results, IQVIA independently did a quantitative market research for us with 153 high prescriber. Very interesting that this physician indicated that they will likely prescribe in half of the patients actually our regimen, either in non-cirrhotic patients or the same in compensated cirrhotic. And we did also -- IQVIA did a market research with the payer that covered more than 130 million lives in the United States. And actually, we were very pleased to see that there was a high willingness to add this regimen into the formulary.

From a commercial standpoint, the U.S. HCV prescriber is highly concentrated. Only 6,000 prescribers actually prescribe 80% of the direct-acting antiviral, either Mavyret or Epclusa. And so we believe that we can do a very efficient commercialization using a focused specialist sales force. So we think that probably in the range of 75 to 100 at a cost of about $25 million to $30 million fully loaded. So something that can be done even by -- with a biotech with experts like us in the field in the past -- for the past 25 years.

So now let's review the global Phase III program for the treatment of hepatitis C. As you can see, we have a very large geographic footprint for this global Phase III program. As we announced, as I mentioned just a few minutes ago, we completed the enrollment in December, the third week of December. We achieved also our target for the cirrhotic population, which was around 15%. And we anticipate the result, as I said, mid-2026. What I would like also to highlight is that we have screened in excess of 1,300 patients in less than 8 months and enrolled 900 patients in this trial in the United States in less than 8 months. So that tells you the need of new regimens in the United States as well.

C-FORWARD, as I said, is on track. 120 sites in 17 countries. And the reason also that we had to go outside extensively is to cover the entire series of genotype, mostly in the U.S., genotype 1, 2 and 3. We cover all genotype because we want a label that is fully pan-genotypic with countries like South Africa, you have genotype 5; Southeast Asia, Vietnam, Thailand, you have genotype 6; and the Middle Eastern countries where you have genotype 4. So we anticipate completion I say Q2 and results by the end of the year.

So let's just quick review of this program. So we have 2 pivotal trials C-BEYOND and C-FORWARD combined with almost 1,800 patients. It's head-to-head. This is the first head-to-head against an active comparator, which is the standard of care or combination of sofosbuvir and velpatasvir. Our regimen is 8 weeks compared to 12 weeks of Epclusa and that in non-cirrhotic patients. In cirrhotic patients, it's a 12 weeks comparison of the 2 regimens. Importantly, so that we are not unblinded, physicians know what they prescribe. Patients know what they receive, but the sponsor do not have access. And you can see that the assessment of the SVR is at the same time, 24 weeks after treatment initiation.

So the primary endpoint is sustained viral response occur after 24 weeks. We just presented with -- through our colleague from Los Alamos, which is the group from Alan Perelson, who is the major expert in the world for viral kinetics. And you can see that based on the results on the Phase II, we had a very potent efficacy for the 8-week treatment regimen. The median time to cure with this model do support our 8-week short-term duration with an expectation around 7 weeks. For the cirrhotic, the F4 need a little bit longer treatment in excess of 8 weeks. But you can see we have really a significant margin going to 12 weeks. And that's why we -- our target is to be also in the 97%, 98% efficacy in compensated cirrhosis.

I'm going to spend a few minutes on this slide, which is really important because we are going to release the data with 2 different SVR as primary endpoint. And the reason is that, as usual, I would say, the EMA is not in agreement with the FDA or the FDA is not in agreement with the EMA. We thought that -- as I remind you, the Phase II was a per-protocol population analysis. So that was our preference. The EMA agreed. And so it's -- the primary endpoint of the population will be those that are randomized, are dosed, are compliant with more than 80% of pill count and with an SVR assessment at week 24. And so this is really the way that we can really compare the true efficacy of both regimens.

And when we apply this, as I said before, the Phase II data were 98%. Now we are not very much different, let's face it, as well with the analysis that was preferred by the FDA. This is a modified intent-to-treat analysis. And the reason is that we can expect 8% to 9% discontinuation when you have those patients that discontinue before dosing and then dose during treatment. But at least the FDA agreed that we should only include the analysis. This is why it's a modified intent to treat. We should only include those that have been dosed. So if they discontinue after randomization, they will not be included in the analysis.

And then after it's the expert in statistics called imputation model. So if the discontinuation is, let's say, in the second part of the trial, where very likely those patients are going to be PCR negative, they have a high probability of success. That means they will count as a success. If they discontinue earlier, well, they will count as a failure. So essentially, the same method for assessing the non-inferiority will be conducted in both Phase III studies. And what I would like to also emphasize is we wanted to make sure that we have a sufficient power in those studies. And that's why we use the expected modified [ITT], 95% with a 5% noninferiority standard for this high rate of response with 90%, and that gives us the 880 patients size trial.

And so as I said, we enrolled about 900 patients, and that's what we basically want to make sure. And the analysis will be with each trial and then the 2 trial combined. And in the per-protocol, there will be an analysis on the combined 2 trial for superiority as well. So just as I mentioned, we are moving also in the commercial readiness. You can see here that we will have a simple weekly dosing package that is 2 tablets once a day with a blister pack. It's packaged in the cartoon with 4 weekly blister card. And so this is for a 1-month supply. As you know, in the United States, the payer are reimbursed only for 1 month for 30 days. And so patients will come back for a second cartoon. So very convenient. There will be the labels day 1, day 2, day 3.

And we'll be ready with tens of thousands of treatment at launch for the end of '27 or early '28. Our cost of goods related to net price is very low single digit. And obviously, the Street will be happy to know that we anticipate that we'll have a short time to profitability post launch, I will say, less than 24 months, even not including that. We will obviously evaluate and execute a partnership for the country outside the United States.

So let's now review the new program on hepatitis E. Hepatitis C, you have 2 genotype -- 4 genotype, but 2 different type of transmission. We are not going to go for waterborne transmission in developing countries. Really what we are really focusing on is the foodborne transmission immunocompromised in developed countries, this is U.S. and Europe. In U.S., you have more than 90% of slaughter house infected with hepatitis C. And mostly, it's due to infections due to undercook meat, especially pork. So here, you see, as I mentioned, the population who are at risk, solid organ transplant, hematopoietic stem cell transplant, hematologic malignancies.

So the first line basically is to reduce immunosuppression. Take cyclosporine, tacrolimus, you decrease the dose, but obviously, the major risk is organ rejection. There is also open -- off-label with ribavirin. We all know the toxicity of ribavirin and only about 60% cure observed with ribavirin. And so why is it so important? Because 15%, for example, of those solid organ transplant recipient can develop rapidly cirrhosis in less than 3 to 5 years, like in contrast to hepatitis B or hepatitis C, where it will take 20 to 25 years to develop a cirrhosis and potentially hepatocellular carcinoma.

So from a commercial opportunity standpoint, this is also $1 billion opportunity. Orphan drug designation, about 450,000 patients yearly between U.S. and Europe, 3% at risk. So you think about the treatment of about 15,000 patients potentially annually. And you see that only with a 30% treatment actually at a premium of around $200,000, which is expected also for hepatitis delta from other companies. I think the current treatment for hepatitis delta in Europe is in excess of EUR 150,000. So you can see that we are in the same ballpark as our expectation. We knew that bemnifosbuvir was also active.

Bemnifosbuvir is a very potent nucleotide prodrug and with broad spectrum against several RNA viruses. But we were not confident to go in the clinic because we knew that we would need a more potent drug to really go into a monotherapy for the treatment of hepatitis C. And you can see here, AT-587 has been selected. We had announced that we have 2 potential clinical candidate, and this was selected based on an in vitro profile. As you see, very potent regardless of the genotype 3 that we are using. It's also active against ribavirin clinical resistance associated substitution or RAS. And recently, we got the data that we expected in 2 animal species, in monkey and rat, we have a very good activation to this active triphosphate.

We measure this with a surrogate in plasma, you can see achieving concentration and drug exposure even higher than those obtained with bemnifosbuvir. And actually, another important parameter why we selected 587. You can see that -- we know that BEM is extremely important against hepatitis C. And here, you have even a conversion to this active triphosphate metabolite in human hepatocyte, which is the site of viral replications of infection even 3x. So far, the in vitro safety profile is very clean, as you can see, and IND-enabling study with the GLP tox underway, and we anticipate IND CTA probably will file a CTA in Europe in Q2 during the Phase I and then after followed by a proof of concept.

So you can see that in closing, I cannot really stress more than this is a -- as you will understand, this is a pivotal year for Atea. We are on track to develop -- to deliver top line Phase III results from C-BEYOND in Q3, and we'll have results for C-FORWARD in Q4 and filing the NDA in Q1 2027. As I said, for hepatitis E, we will initiate by the end of the year, proof of concept Phase Ib to evaluate the dose and the treatment duration, probably between 12 weeks to 24 weeks. And the primary endpoint, obviously, would be a sustained viral response or cure. And that we anticipate in the second half of 2027 to initiate the pivotal trial or probably 2 pivotal trial with U.S. and Europe. And we will obviously discuss the size of the trials with the regulatory authorities.

So again, thank you for your interest and your support today. We have John Vavricka, who is our Chief Commercial Officer; and Janet Hammond, who is our Chief Development Officer with us, and we look forward to address any questions you may have. Thank you.

Thank you, J.P. I would like to open up the floor to any questions you may have. Simply raise your hand, and we'll hand you a mic.

I would like to kick off with a question. Can you review the current trends of patients infected with hepatitis C virus in the U.S. There is the perception that the HCV prevalence is declining.

Janet?

So I think there was a slide that Jean-Pierre showed about this. But actually, I think there is a misperception that it's a disease which has been dealt with by the approval of highly effective antivirals about 10 years ago. The history of hepatitis C is really that for a long time, the virus was undetected and so blood transfusions were not safe from the perspective that we couldn't test for the virus. And so there was a large bolus of patients, particularly baby boomers who were initially the eager recipients of the direct-acting antivirals when they were approved.

However, what has happened since treating those patients is that the disease has really spread as a result of the opioid crisis. And so we now have a large and increasing population of people who are younger, mostly not cirrhotic because of their age and the duration with which they've been infected with the virus. But nevertheless, as J.P. mentioned, we estimate that probably in the United States, about 90,000 patients a year are being treated, but 160,000 patients are actually being infected each year.

Patients -- if you get infected with hepatitis C, you don't develop immunity, so you can get reinfected. Many of these people are getting reinfected. But it's estimated that each patient in this patient population where there's injection drug use, is potentially infecting 3 to 5 other people with hepatitis C. So actually, unless we do something actively about it, the number is actually going to unfortunately continue to increase.

Got it. A follow-up to that. Why do you think more hepatitis C virus patients are not being treated, especially since there are 2 direct-acting antivirals available?

So I think, again, it's a phenomenon of the patient population that is getting infected. It's also, I think, a silent disease largely. And so you need to actively screen people for it. The guidelines now call for everybody in the United States over the age of 18 to be tested at least once for hepatitis C. But as I mentioned also, I mean these are patients who often fall through the cracks of the health care system. And we believe that this test-and-treat model when people have any encounter with the health care system, they can get a fingerprint test in the doctor's office and actually be identified as having hepatitis C and receive treatment at that time may be the game changer, which is going to allow for more active access and treatment of these patients.

Understood. Do you think the advantages of the profile of your regimen over existing agents is sufficient to overcome current limitations with the treatments currently available and grow the market?

So we strongly believe that. And I think the feedback, if you listen to the webcast that we have on our website, will indicate to you that I think there are a number of constraints around prescribing to a patient population that I think is perceived, and I'm an MD. So this would be my perception, too, is that they're inherently unreliable for the most part. And so there's a reluctance to prescribe something which, although highly effective, needs to be taken relatively well in order to be effective. And there's always this concern that there could be resistance occurring if patients don't adhere to their therapy.

And I think what we see with our regimen is one which is extremely potent. And so as J.P. mentioned in the presentation, we saw an SVR rate or cure rate in our Phase II study of 98%, but actually 17% of those patients didn't fully adhere to therapy. And so what we saw when we looked at patients overall was that most patients were fairly good about taking their treatment during the first month. But during the second month, there was a falling off the wagon. But with a really highly potent regimen, and I think also the modeling data that J.P. showed from Alan Perelson at Los Alamos speaks to the same thing.

With a really highly potent therapy, if you can drive down the viral load, many patients are actually not even going to need the 8 weeks. So adherence becomes less important. And that's important for the prescriber, but I think -- and obviously, also for the patient. But the second thing, which is really important, again, is that many of these patients surprisingly are taking quite a lot of other medications. Many of them are co-infected with HIV and are on HIV antiretrovirals. A large proportion of them are taking proton pump inhibitors. It's estimated that 35% of patients with hepatitis C are using proton pump inhibitors.

And this becomes important because -- particularly with Epclusa, if you take a proton pump inhibitor and you take your Epclusa simultaneously, the alkaline environment achieved by the proton pump inhibitor actually reduces absorption by about 30%. So you may not actually get an adequate dose of your Epclusa to care the virus. And these types of things weigh on the prescribers' mind as well as, I think, impacting the efficacy in the patient. And so there's a reluctance to prescribe a drug to a patient who may be taking a whole variety of medications if you don't know what else they're taking and these patients often don't give you an adequate history or are taking things over the counter and don't think to tell you about it. So a regimen which has minimal drug interactions and is highly potent is ideally suited for this patient population.

And what do you think the commercial market opportunity will be when you launch your regimen?

John?

Well, currently, the global HCV market is around $3 billion in net sales with the U.S. comprising roughly 50% of that. And we believe that with further adoption of the test-and-treat model, along with our best-in-class profile, which really goes hand-in-hand with the test and treat, being short duration, low potential for drug-drug interactions and the convenience of taking it with or without food, really has the opportunity to expand diagnosis and treatment of the current 4 million people currently living with HCV in the United States.

I think we have time for one last question. So moving on to your new program in hepatitis E virus, what would be the primary endpoint in the proof-of-concept study?

Sure. We obviously are going to look for a cure. So we -- as the way we have designed early clinical trial with -- for bemnifosbuvir, we'll do the same. So Phase Ib was probably about 2 or 3 dose based on our drug exposure on the Phase I. And we will initiate 12-week treatment duration first, probably with a couple of doses in our Phase Ib. The beauty of antivirals is that we'll know very rapidly if we have a potent drug or not. And we would not need probably more than 12 to 14 patients for the proof of concept with probably 6 or 7 patients.

And we had the same approach we did with bemnifobuvir at each dose. That will allow us to look for the best dose with 2 of the best dose. Then we will share the data with our colleague in Los Alamos. As you've seen that we'll be able to do the same modeling with this data. And the importance of the modeling is to predict the time to cure. And therefore, we will know going for the Phase II/III, if we will need to go to a 12-week or 24-week treatment duration. And that's why actually the GLP chronic tox in monkeys and rats ongoing, we already go all the way to 6 and 9 months to be able to, if needed, to go to 24 weeks.

So just to remind, for those that know our hepatitis C initial trial started, we all started with 24 weeks. And then after we came back to -- when we showed that it was -- there was effectiveness, we went from 24 weeks to 12 weeks and up to 8 weeks as well. So the cure, so that means no detection of the virus 12 weeks after treatment basically being stopped after a 12-week regimen or 24 weeks, evaluating the SVR 12 weeks after, and we should not be able to detect the hepatitis E virus and so to have a cure.

Got it. Well, I think we're at time. Thank you so much, J.P. and the Atea Pharmaceuticals team.

Thank you.

Good morning, and welcome to the Atea Pharmaceuticals Virtual KOL event. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Atea website following the conclusion of the event.

I'd now like to turn the call over to Dr. Jean-Pierre Sommadossi, Founder, Chairman and Chief Executive Officer of Atea Pharmaceuticals. Please go ahead, JP.

Thank you, Tara. Good morning, everyone. I'm J.P. Sommadossi, CEO and Founder of Atea Pharmaceuticals. And thank you for joining us today for this hepatitis C KOL event. This event include a panel with the foremost leaders in hepatology, gastroenterology, infectious disease, with expertise in treatment of hepatitis C in North America.

Before we begin, on Slide 3, there's our forward-looking statement, and further information can be found in our most recent regulatory filings.

So we are very pleased to have the following KOL experts with us today, Dr. Jordan Feld from University of Toronto, Toronto General Hospital in Canada; Dr. Eric Lawitz from the Texas Liver Institute, the University of Texas Health, San Antonio; Dr. Anthony Martinez from University of Buffalo, in Erie County Medical Center; and Nancy Reau from Rush University Medical Center in Chicago.

Also with us today from Atea, John Vavricka, our Chief Commercial Officer, who will review the HCV commercial market opportunity; Dr. Janet Hammond, our Chief Development Officer; Dr. Arantxa Horga, our Chief Medical Officer, will review the profile of our regimen and the ongoing Phase III program. Janet and Arantxa will also moderate the fireside chat with our distinguished panel. And at the end of the day, then there will be a Q&A session.

So now let's initiate the meeting with Janet and Arantxa. Janet?

Thank you, J.P. Good morning, everyone. On Slide 5, let's now turn to our global Phase III program, which is the first head-to-head Phase III program for chronic hepatitis C comparing our regimen with the current global standard of care, sofosbuvir and velpatasvir, which is marketed as Epclusa. Our regimen includes bemnifosbuvir, the most potent nucleotide inhibitor, and ruzasvir, a highly potent NS5A inhibitor. Data support from our regimen as a potential best-in-class treatment option for patients infected with hepatitis C, with a differentiated profile featuring a short duration of treatment, a low risk for drug-drug interactions and convenience with no food effect.

I'd like to highlight that we have a new study result demonstrating no risk of drug-drug interactions with proton pump inhibitors, which are estimated to be taken by at least 35% of patients with hepatitis C. These results will be presented at an upcoming scientific meeting. We view this as a key differentiator since proton pump inhibitors can substantially decrease the effectiveness of current approved DAA therapies for hepatitis C.

Our Phase III program is designed to confirm the efficacy, safety and tolerability demonstrated in our robust Phase II study, where we achieved a 98% biological -- sustained biologic response at 12 weeks post treatment or SVR12. These Phase II results gave us confidence to move to our current Phase III stage program.

Slide 6. I'm pleased to share with you that a few days ago, we presented multiple data sets at the liver meeting. These data sets further demonstrate the antiviral potency with our short treatment duration of our regimen for hepatitis C. In an oral presentation, multiscale modeling results predicted that our combination regimen inhibits both intracellular replication of hepatitis C as well as viral assembly and secretion of new hepatitis C virus into the bloodstream. The model predicted a cure time of approximately 7 to 8 weeks. Because the regimen suppresses the virus at multiple critical stages, the data reinforce the potential of the combination regimen as a potent, short duration therapy for chronic hepatitis C.

We also presented 2 posters. The first poster was identified as a poster of distinction and has highlighted a resistance analysis from the Phase II study of our regimen, demonstrating that SVR12 rates were not impacted by NS5A resistant variant baseline. Viral kinetics and pharmacokinetic analyses indicated that most of the viral failures reduce the treatment noninherent and not to viral resistance.

The second poster reviewed the results from a Phase I study in healthy participants, which demonstrated the high relative availability of bemnifosbuvir and ruzasvir commercial formulation for the fixed-dose combination. These data also support dosing of the fixed-dose combination with or without food and with famotidine, an H2 blocker, which can substantially diminish the effectiveness of our anti-virals. The fixed-dose combination commercial formulation is being used in the ongoing Phase III program.

Slide 7. As mentioned, bemnifosbuvir is a nucleotide NS5B polymerase inhibitor with an established mechanism of action of inhibiting hepatitis C RNA through chain termination. Thus blocking viral production and replication inside the cell. Our collaborators at Los Alamos National Laboratories have conducted hepatitis C viral kinetic modeling using data from the Phase I bemnifosbuvir monotherapy trial. The new modeling suggested that bemnifosbuvir might have an additional mechanism of action, inhibiting hepatitis C viral assembly or secretion and the secretion of new hepatitis C virus into the blood stream, significantly reducing extracellular hepatitis C RNA, a mechanism previously only associated with NS5A inhibitors, such as ruzasvir and velpatasvir.

New in vitro results confirmed that extracellular hepatitis C viral RNA levels were comparable with the exposure of bemnifosbuvir or velpatasvir, demonstrating that bemnifosbuvir also inhibits hepatitis C viral secretion and assembly in addition to inhibiting viral replication.

Slide 9. [ Slide 8 ] [indiscernible]. This graphic on the slide visually illustrates on the left side, the hepatitis C viral life cycle. And then to the right, the dual mechanism of action of bemnifosbuvir, showing how bemnifosbuvir blocks the virus from making copies inside the cell, and it also blocks new virus from entering the bloodstream.

In conclusion on Slide 9, these new data demonstrate that bemnifosbuvir is a potent and differentiated nucleotide product with a unique dual mechanism of action, which may explain the high potency of bemnifosbuvir as compared to sofosbuvir in vitro. Importantly, even in the presence of NS5A resistance, bemnifosbuvir would continue to block viral assembly and secretion due to its dual mechanism of action.

Lastly, these new results further highlight the differentiation and the potency of the bemnifosbuvir and ruzasvir regimen, the treatment of hepatitis C.

I'll now hand the call over to Dr. Arantxa Horga, who will review the Phase III program. Arantxa?

Good morning, everyone. Moving to Slide 11. The global Phase III program is composed of 2 pivotal trials: C-BEYOND, which is enrolling across approximately 120 sites in the U.S. and Canada; and C-FORWARD, which includes another 120 sites across 16 countries outside of North America. Combined, these studies are expected to enroll approximately 1,760 patients. Both trials are open label and randomized 1:1 against the active comparator, and they are stratified by cirrhosis status and genotype, including HIV co-infected patients. In non-cirrhotic patients, treatment duration is 8 weeks compared to 12 weeks with the standard of care. For patients with compensated cirrhosis, patients received 12 weeks of either regimen. The primary endpoint for both studies is SVR12, which is recognized as the definitive measure of HCV cure.

Slide 12. I am pleased to confirm that enrollment in the North America C-BEYOND trial is on track for completion next month, with top line results anticipated mid-2026. For C-FORWARD, which has a broader global geographic footprint, enrollment completion is expected mid-2026, followed by top line results by year-end 2026.

I would like now to hand the meeting over to John Vavricka, our Chief Commercial Officer, John?

Good morning, everyone. On Slide 14, following the Phase II clinical results, we conducted quantitative market research study of high U.S. DA prescribers. IQVIA selected site participants and conducted the market research. 153 top U.S. DAA prescribers reviewed the BEM/RZR profile, including the Phase II results on their own prior to assessing their likelihood of prescribing. The study revealed a high preference for BEM/RZR, with 76% extremely likely to prescribe our regimen.

When asked about the percentage of their patients they would likely prescribe BEM/RZR to, the study showed that BEM/RZR would be used in approximately half of their patients. The results were similar for both noncirrhotic and compensated cirrhotic patients.

Moving on to Slide 15. I'd like to highlight that these latest quantitative market research results conducted following the BEM/RZR Phase II results, are consistent with the previous quantitative market research conducted over the past 2 years. The 3 market research studies consistently show significant preference for BEM/RZR with high U.S. DAA prescribers.

Now let's move on to the KOL panel discussion that will be moderated by Janet Hammond and Arantxa Horga.

Thanks, John. So thank you, and again, welcome to our panelists. We are delighted to have you with us today. Just coming off the heels of the AASLD meeting. And I think also a number of other events this year, which have been highlighting the epidemiology of hepatitis C and the crisis that we face in terms of this epidemic and our failure to eradicate it.

I thought it would be useful to start -- pass off with you, Jordan, talk a little bit about the epidemiology and the current HCV patient population, perhaps starting off with how you see the patient population to have evolved since direct-acting antivirals really became mainstream about 10 years ago? What about their age, are they the same comorbidities, risk factors, et cetera? What are you seeing in terms of these patients? And why do you think this continues to be such a problem there?

Thanks, Janet. It's nice to be here this morning. So I think things have changed a lot over the last number of years. When we started treating, we were primarily treating baby boomers, middle-age folks, many of whom had already been diagnosed, many of whom already advanced liver disease. And fortunately, we were able to cure those with the available regimens over time. And most of those people, fortunately now have either have -- have been cured of their infection.

And it's really changed quite dramatically in the last number of years, but also somewhat disconcertingly, when you look at the latest numbers from CDC, we see that actually the number of people living with chronic hepatitis C in the U.S. has not diminished significantly over the period of time that we've had DAA. So it was quite remarkable when you think about how effective these therapies are, and we're continuing to see new infections almost keep pace with cures, which really is a major challenge for us, and this reflects the ongoing opioid epidemic that we've seen throughout North America.

And this has really shifted the population in pretty dramatic ways. We are seeing younger people infected, reflecting of the [ epidemiology ] of those who use and inject drugs. And this means a number of things. One is, it means that the population has many challenges that are not liver-related. So unlike seeing patients with advanced liver disease, we're now seeing people with complicated lines related to injection drug use and many of the social determinants of health, property and other challenges.

We're also seeing very few with cirrhosis. So the typical people we see now being diagnosed with hepatitis C are younger people without advanced liver disease, often with many significant social rather than medical comorbidities. And this means that we've had to shift our practice and figure out models of care that work well for these populations. And that -- the key there is really focusing on very simplified regimens that can be taken by these populations that may have a lot going on in their lives, but also recognizing that fortunately, advanced liver disease has become less of an issue, and that's why much of the treatment has moved particularly out of hepatology practice and more than to infectious disease, addiction specialists and even primary care.

I could go on, but I think -- I don't know whether others want to join in there and talk about this at all or whether we wish to move on. Arantxa, would you like to perhaps follow on the next question?

Yes, I think maybe we can move on to the next question, which is related to innovations in screening and diagnosis, really with a focus on the test and treat strategy. And I'm going to direct this question to Dr. Anthony Martinez. For example, we looked at the recent meeting with the [indiscernible] and they emphasized the importance of same-day diagnosis and treatment. And so Dr. Martinez from your perspective, what is still needed to achieve that goal of same-day test and treat as standard of care.

We've moved very close to that to achieve that right now. In some spots in the United States, my clinic being one of them, we've actually reached that point where we're utilizing newly FDA-approved point-of-care testing machines. We've had these machines now for about 1.5 years, where we can deliver a diagnosis in under an hour. The next step there is obviously to have rapid access to medications, ideally providing the full supply of those medications.

To deploy a test and treat model, you need a couple of key things. You need a medication regimen that's simple, that's fast, obviously, efficacious and safe, and it has minimal drug-drug interactions. You want to take as many things off the table as you can so that it can literally get down to poking a patient's finger, getting a result and then give him the course of medication.

So I think that anything that can minimize some of these drug-drug interactions, Jordan highlighted exactly what we're seeing in the U.S. It's a younger patient population. We know that under age 45, almost 98% of these patients do not have advanced fibrosis. So that even raises the question, do you even need some of these additional labs? You probably don't.

So with the point-of-care testing, I think that if we have a regimen that can deliver a high SVR rate that eliminates a lot of these drug-drug interactions because even though these patients are young, they're on multiple concomitant medications, but these tend to be in the psychiatric disciplines. So they're on mood stabilizers or antidepressants, anti-anxiolytics. So they still are on multiple medications. So any regimen that can eliminate those potential drug-drug interactions becomes important. So I think this is uniquely suited to get us even closer to a true test and treat model of care.

Thank you, Dr. Martinez. We have a question related to this somehow. Do you differentiate in that context of test and treat? Do you differentiate acute versus chronic patients?

We stopped doing that a couple of years ago in my own practice, but you have to understand that, that we were able to do that because the state that I'm in New York, we eliminated all the barriers and restrictions. So there was no need to differentiate. That said, that's not the case throughout the United States. The new guidelines have moved toward eliminating these characterizations, and they've kind of moved toward just defining a patient as being viremic. That said, a lot of states have not yet caught up to that. A lot of payers have not yet caught up to that. So that still remains a bit of a barrier.

We now have 1 of the 2 regimens that's on the market that's indicated the treatment of acute hep C. But as we -- as the guidelines catch up with the payers, I think that, that becomes less of an issue. So the short answer is no, I don't differentiate between acute and chronic anymore. We've moved completely toward viremic.

Thank you. Janet, would you like to go to the next?

My next question, I was going to address to Dr. Reau. Sort of looking at the policy and system level changes and the cost of not treating hepatitis C patients. In spite of the available DAAs, the infections, as Jordan mentioned, have continued to increase in the U.S. and worldwide. In your opinion, where is the failure of the system that is allowing this to happen?

Yes. I think that the United States is very heterogeneous, and we've lacked a national policy, which we're hoping to fix now that the government is open. Senator Cassidy's bill for working towards hepatitis C elimination has bipartisan support, and we're really hoping that, that motivate states to work towards elimination in these local networks.

It is going to be an opt in. So it's not going to be mandatory, so states can still misbehave. And then I think that's really going to be where grades, you can look to see how your state is doing on hepatitis C elimination efforts. They're all given grades. And if you're an F state, then you can -- you have pretty low hanging fruit in order to be better. And if you're a B+ state, it's going to be a little bit harder for you. But I think that, that national policy, that national investment is going to be really important because we just don't have the resources to make hepatis C treatment a priority when there's so many other priorities at state and local levels.

Were there any changes that would improve the efficiency of health care, do you think in your practice? I mean, in delivering care to people?

Yes. I mean, anything that's automated is certainly better. So there are a lot of programs that have been shown to be effective, where the EMR flags individuals that had either been tested positive for hepatitis C, but not treated. I think that we've been discussing. But if you look at young people who lack insurance, about 1 out of 6 of them do not get treatment. So -- it's -- you know that there are people that are identified out there that are still not cured of their hepatitis, and that's low-hanging fruit. And your EMR can find those people for you, especially if they're still connected in your system.

I also think that we get like alert fatigue, but you're identifying individuals, especially if you're focusing on a young higher risk cohort or that have not yet been tested for hepatitis C. And then focusing your efforts, no one wants to talk about micro elimination because we want to have macro elimination. But there are places where there are enriched with hepatitis C. Like look at your incarcerated individuals, recent incarceration. I mean, again, these are easy places that local states can start with because they're going to be enriched in hepatitis C. No one wants to screen 10,000 people to find 3 people with hepatitis C. You want to screen a small population that is enriched with individuals that need treatment. And that's going to be unique to the location that the people are at.

So what is the cost of not treating people with hepatitis C?

Yes. The cost is significant. We don't want to forget that hepatitis C is an immune modulatory virus. It has an increase in all-cause mortality, independent of liver-related mortality and morbidity. And delay until someone has cirrhosis or advanced disease, increases the risk of developing liver cancer or requiring liver transplantation even after a cure.

Delay in treatment also increases the risk of transmission. So you now have to treat a lot more individuals than you would've if you treat someone early in their infection when they are more likely to transmit to the people around them. And there are lots of mathematic models demonstrating that engaging someone who is newly diagnosed with hepatitis C is incredibly cost effective. A delay from diagnosis to treatment is incrementally more expensive, independent of just waiting for advanced liver disease. So it's really an easy sell to demonstrate how cost-effective early treatment is.

And then looking at it from the perspective of the payers, what might changes to coverage policies, including Medicaid and Medicare, and how might they impact success to getting therapies and advancing eradication efforts? Do you see a blockage there or not really?

I mean I think there are blockages everywhere. Even when you remove a blockage, sometimes there's another speed bump a little bit further down the road. Like take Illinois, for example, we got rid of fibrosis restrictions. We got rid of restrictions based on substance abuse, but then we ended up having a restriction that was on provider type, which is kind of hard. I mean it's difficult to demonstrate if you have completed a module that allows you to be a trained hepatitis C provider. And so they're just ended up being a speed bump a little bit further down the road.

I believe that Senator Cassidy's bill is looking at something like a subscription model, where Medicare, Medicaid, these groups can get discounted drug in a way that makes it affordable, that cost is shared over a period of time. And I think this is going to be really important. I will state opt in that, I don't know why they wouldn't. That's why it's got bipartisan support. But I think that we do much better if we understand what's in our budget. And so if you can take the cost of treating your population with hepatitis C and divide it over a period of time so that it's predictable how much you're going to pay in each cycle, that should really get rid of some of the hesitancy in rolling out these much more inclusive elimination projects.

Yes. I mean, just to give you some of the raw numbers, just by having hep C, it costs the system on average about $20,000 per person per year. If that patient goes on to develop cirrhosis, the cost goes up to about $40,000 per person per year. If they decompensate, develop liver cancer, it's around $70,000 per person per year. The difference between making in early diagnosis and getting someone started on treatment, there's about a 58% higher mean annual cost for somebody who gets treated in a delayed system. On average, it's about $21,000 versus $8,000 when you look at those incremental costs. So all of that downstream is completely avoidable if you get people diagnosed and treated early.

And is one of the statistics that's really important in this young cohort -- we know that if you're specifically talking about people who inject drugs, which is where the base of this epidemic is, one person who's actively injecting will potentially infect up to 20 other people within the first 3 years of their diagnosis. So do the math on that with the numbers that I just gave you, there's tons of cost savings here. I mean this only makes sense.

And when you deploy a test and treat model of care, you're eliminating missed visits, which are billable, redundant laboratory testing, which happens a lot. You're really streamlining this and you're making it much more cost-effective. So this makes a lot of sense. It makes so much sense that that's why there's this federal elimination plan because when we look at this, I mean, the cost savings are in the tens of billions of dollars. So this makes sense to a lot of people. I think it's hard for the states because these downstream cost savings tend to occur 10, 15, 20 years down the line, and you have to answer to a more here and now world. So you have to look at the cost savings and the cost benefits in, say, 3 years and 5 years in addition to the downstream.

And so for the patients who have insurance, is navigating the insurance reimbursement and payment system, is that a hurdle to getting timely treatment? I mean, what has that?

It can be it. And this is, again, very state specific. So again, here in New York. No, there's no hurdle. I'm able to stock the medications on the shelf, poke your finger, give you the full supply of medication, no barriers, but we're a robust Medicaid state. Now if you go to some places in the South or out West, that's not the case. There are insurance hurdles. Nancy was pointing out some of the restrictions, whether it was prescriber type sobriety, need for a prior authorization, these are all just unnecessary barriers that are in place that inhibit elimination. So those things would go away with this federal elimination plan. But it's really state specific when you're looking at what some of these barriers are. Some places, very easy; some places, not so easy.

Arantxa?

Yes. I think the next section really ties very nicely with this one. It's also about integration of other public health initiatives and elimination goals. And I'm going to direct a couple of questions to Dr. Lawitz. In terms of a regimen like this that we are developing right now, which is an optimized -- kind of a next-generation regimen, how would that help and enable broader uptake of care and accelerate the progress towards the hepatitis C elimination in the U.S.?

Yes. Thanks for the opportunity to be here. One of the -- some of the facts that I like to think about is when we think about the number of treaters in the U.S., there's about 7,000 different treaters and how many overall treaters in the U.S. is about 700,000. So it's actually fairly amazing that only less than 1% of the treaters in the U.S. actually are treating hepatitis C today.

And then when you mirror that with the 33% undiagnosed, it's no wonder we're not doing so well on our efforts of eradication. So ultimately, what would be the goal would be to enhance screening and finding those undiagnosed, but probably more importantly, enlarging the treater and treater base. We think we have a lot of treaters now, but I was actually interested when I went back and looked, it's actually still 1% of the treaters in the U.S. So if we're able to even enlarge that by a handful of percentage, the multiple -- multiplier effect on getting treatment across the U.S. is going to be exponential.

So that raises the question, how do we enlarge the treater base? Well, we have a regimen that is uncomplicated and easy to use and one that people -- the providers aren't afraid of per se or worried about and feel like they need to refer their patients for treatment. So the things that we've already -- that you've already laid out nicely earlier in the call, the simple, safe, highly effective, low pill count, agnostic to genotype, agnostic to fibrosis stage. Really, some of the attributes that has been demonstrated in bemnifosbuvir and ruzasvir in Phase II. If they are reproduced in Phase III, I think are going to bring us towards the next step of enlarging the treater database, and ultimately bringing us much closer than we are today to more fully treating patients.

It's absolutely amazing that we have as many patients infected despite all the treatments we've done in San Antonio. I always thought I treated the whole city twice or 3 times, but ultimately, we still have a consistent -- a couple of hundred we treat a year. And actually, that number has not decreased or increased. Our flow of hepatitis C referrals over the last 10 years has really been very, very consistent without really a significant rise or fall, and we have a very broad population that see us. We have some of the rural areas in South Texas and the more sophisticated patients. But ultimately, it's amazing how people are still, despite all the information around hepatitis C, how many people are still -- 50, 60, 70 yesterday in clinic, I saw a 72-year-old gentleman, who never knew he had hepatitis C. And we're going to treat them, and he's had it for probably a couple of decades. But so despite all the aggressiveness, we need to continue to further our education, both to patients and providers.

And I think as we think about the possibilities with adding a new regimen that has a short duration, limited drug interaction profile, and we'll have the lowest [indiscernible] in the field is important because as Tony and Jordan and Nancy alluded to, these patients are -- can have challenges, socioeconomic challenges, psychologic challenges and having a limited number of pills and an ability to get people cured, while they're interested in the topic and kind of it's in the front of their mind, I think is going to be very useful. And ultimately, with the Phase II data showing the noncirrhotics having 180 out of 181 patients cured, we -- as long as Phase III reproduces our Phase II studies, we can see that this is going to be a highly, highly effective therapy.

The other nice thing about the regimen is it's second-generation antivirals. So we have a different resistance profile, more potency than the first-generation antivirals that have been on the market now for more than a decade, with -- are more potent and actually have activity against some of the resistance associated substitutions of the first generation. So I think it all kind of rounds out to really show how the community should be receptive to this. And the hope is that we can increase screening and probably more importantly is increase the treater base.

Great point. Thank you. And Janet, would you like to move on?

So back to you a little bit, I mean, if I may, Dr. Martinez, just to comment a little bit on practice challenges. I think Eric already perhaps highlighted some of these, but how does the fact that many of your patients are on multiple medications and some that you know about and some that you don't, influence your prescribing decisions? What are the most common medications that you see your patients actually taking that could lead to drug interaction issues?

Yes. So I mean the most commonly considered medications, obviously, the statins, the PPIs, some of the antipsychotics. I think those are the big groups in the younger population, especially the antipsychotics medications used for medically assisted therapy for opiate use disorder. So things like buprenorphine or methanone. Those are probably the most common medications.

But some of these other variables, I mean, I think everybody has pointed it out, with these patients, speed is the key. And that's true even right now with the regimens that we have available. The shorter the duration of the regimen and the closer to SVR, the better. Shorter is better. It's just a simple fact. So if you have shorter, less pill burden, no food effect, minimal DDIs, you're perfectly aligned with a rapid start model, a true test and treat model of care.

So it almost takes a lot of the thinking off the table. I don't need to worry about these DDIs. I know that if they get through the 8 weeks, they're going to get cured. I don't need to worry if they're eating with the medications. All of these things become a factor when you're trying to do this in a very quick way. You may not have these patients for long. So the quicker you can initiate them and get them through that treatment journey, the better.

I was just going to stress, I fully agree with everything Tony said. And that he mentioned the food effect, but I would actually highlight that, that is actually not a trivial consideration when you're treating folks that are really in a rough spot. So people experiencing homelessness or people that are actively using and really living pretty chaotic lives. That when they're eating their next meal and reliably eating is not always something that you can count on. And having to sort of just take that out of the picture with an 8-week regimen is actually, I think, quite impactful for the populations that we're treating now.

Arantxa?

So we want to talk a little bit about drug forgiveness in the context of these populations that you are describing. And this question is for Dr. Reau. Why would it be important to have a regimen that is forgiving to missing doses?

Yes. I think there is lots and lots of data showing that adherence -- even when people want to be adherent is difficult. And you want to make sure that missing doses or short treatment disruptions, especially in an unstable population, is going to be able to have wiggle room within the therapy and still result in the cure. There are great examples where there's heat maps of individuals who have missed multiple doses and still end up with curative outcomes. And we need to make sure that you don't slide back from that.

Obviously, we encourage all of our patients to take all of their medications, but the -- life happens, and we want to make sure that if you can't be cured, that the resistance or the outcome for retreatment opportunity are marginal. And if you are missing things, we want to make sure that there's enough wiggle room in there that we are -- that this regimen would not be inferior to another therapy where there is more wiggle room.

Janet?

Go ahead.

Yes. In fairness to the patients, I just want to make this point because it comes up in every single discussion about hep C for the history of hepatitis C. Adherence is in everybody problem. It's people who use drugs problem. It's people who don't use drugs problem. I'm a 50-year-old physician, and I have [ Z-Packs ] left over from 5 years ago. Adherences in every single human problem. People who use drugs, people who live with hep C right now, they inherently know how to follow a regimen. They do well with meds. Do they miss dosages? Yes, they'll make an 8-week regimen, 9 or 10 weeks.

But to Nancy's point, yes, it is very important that we don't slide back, that we have that forgiveness there because, yes, they will miss dosages. But I just don't want the perception to be that they're wildly adherent. We often talk -- we're talking about them as though they have these chaotic lives. And you have to understand that with this patient -- I have a chaotic life, Nancy has a chaotic life. We all have a chaotic live in our own way. This patient population is -- it's all about perception. Their chaotic life is very normal to them. They do perfectly fine. They do even better when they have a short, easy-to-take regimen. But the -- as long as we have that forgiveness there, I think it only amplifies why this regimen has such potential.

I did not mean to limit my adherence discussion to individuals that had engaged in high-risk behaviors. The heat maps are present from all of the clinical trials. And we became more and more brave with who we treated as we got to understand exactly how safe and effective these therapies were. But even the most well chosen patients for these clinical trials still occasionally missed doses. I have 3 children because I'm not always adherent in my chaotic lifestyle. So you can take that wherever you want. But just like Tony, we -- even in the best of circumstances, doing everything perfectly is challenging.

Great points.

And I'll add in, when you talk about compliance, the duration really matters because -- I was thinking about 3 months of an antifungal for [ anchomycosis ], and how many people actually can't get through that 3-month period. You do really well for the first month or maybe 2 and then that last month trickles off. So people say, hey, versus 12 weeks, maybe not that big a deal, but actually probably is because the intent and the focus on a shorter duration is very, very important.

And I'm equally bad as it gets longer in a duration of trying to take a pill a day. I find the pills in my pocket occasionally that I was supposed to take it or not. So not only is short important, but packaging is important, too, to help patients adhere. And if we have a 8-week regimen that has a very specific packaging and we can ensure that the patients know if they took it, because the worst thing in the world is to say, did I take my bill a day or not? Or was that yesterday? Was that tomorrow? But I think it's a combination of short duration and helping the patients succeed with the way the product is packaged will really go a long way to ensuring compliance.

Thank you very much for that. And then just adding to that, really just one last question around the absence of a protease inhibitor in an 8-week regimen. How do you see that affecting simplification of care and ease of use? Dr. Lawitz?

Sorry, I had to find the unmute button. So protease inhibitors obviously helped us in some ways originally, right? They brought the duration down, but they also carry the baggage of drug-drug interactions because they're metabolized in the liver and they also concentrate in the liver as you get more similar to liver disease, thus some cautionary tails and increasing levels of cirrhosis and also some complications on the drug-drug interaction.

We all -- in the -- as hepatitis C treaters, we've all understood the estrogen and a number of drug-drug interactions. And the University of Liverpool app has been very popular, particularly people using protease inhibitors, because it allows them to quickly trying to figure out if their patients at risk based on their concurrent medication.

So albeit the protease inhibitor has decreased the duration from nucleoside [indiscernible] inhibitor in NS5A from 12 to 8 weeks, it hasn't decreased the complications of caring for patients. So it's only taking care of part of the problem, which is shorter duration is always better, but it hasn't got rid of the complexity. And ultimately, if we want more people to treat, we can't have this long list of yellow, red and green stop lights on the Liverpool app to figure out which medications are okay, which I can continue, which I need to change, which I need to hold.

So as we move to simpler both decreased drug interactions and decreased duration of treatment are super -- are very important. And ultimately, that's why we tend to use the nucleoside NS5A, sofosbuvir and velpatasvir, and anybody that's got a decent medical list, right? If they have a bunch of -- if they're the usual internal medicine patient with 15 medications, I'm always going to turn to the nucleoside NS5A inhibitor because I know my risk of drug-drug interactions is significantly less. If I have a young person on no medications, then speed is better. And if they don't have advanced liver disease, I can get away with the 8-week protease-based therapy, but it would be nice to have one solution that fits everybody, regardless if you're young and no medicines or middle age or older with more medicines as I get older. Older is starting to be older and older. But I think we need this opportunity to have a short duration with minimal drug-drug interactions is going to be very popular for treaters and patients. And hopefully, we'll put less people on the Liverpool app for a shorter duration of time.

Thank you. Arantxa?

Yes. I'm going to turn it to Dr. Feld. Maybe you can also give us a little bit the ex U.S. experience. In terms of patient identification and engagement, how could screening and care coordination approach has been improved to ensure that all patients have equitable access to diagnostics and treatment?

So I think we've touched on a number of the things that will allow us to try to really expedite the cascade of care in every part of it. But it really does start with testing and diagnosis. And outside of the U.S., health care systems are different. And obviously, I'm in Canada, where we've got -- it's good that everyone has health insurance and coverage for their health care, but it still varies by provinces. So it's still complicated probably everywhere you go. But I think what we've been focusing on and what I think many of the countries, particularly with national health care systems have been able to do is to develop national strategies for addressing hepatitis C to really improve screening, get people diagnosed and into care.

And as Tony and Nancy nicely discussed about the importance of removing barriers, and we've been very effective at that in Canada, taking away some of those barriers to make getting people on to same-day starts, for example, very easy. So now we have access to point-of-care CRNA testing, like Tony described, and we're able to start people on therapy immediately because of the lack of need for preauthorization. And some of those barriers, as Nancy mentioned, we used to have provider barriers. Those have been taken away fibrosis barriers, [indiscernible] barriers went away a long time ago. So this allows us to really get people into care. And what we've found is that if we can get them on to their first dose of medication, our success rate of getting people to complete treatment is incredibly high, even with imperfect adherence as you heard from all of us that affects everybody, our cure rates are really remarkably high in the real world just as they were in clinical trials.

And I think the experience we've had in Canada is pretty similar to what's seen in Europe, where the health care systems are much more similar to ours and a little bit less fragmented than the U.S. system, where we have a little bit more unified access to care -- universal access to care, which I think streamlines really all of the HCV care, particularly for more marginalized populations.

I think we've had a problem in the U.S. with a reliance for too long on a patient readiness model of care. And that's kind of how we've always operated. Is the patient ready? And I don't know how you determine readiness. I can tell you in my own clinic, it's that you're sitting in front of me. And if we're going to achieve elimination, we have to move to a provider readiness model of care. And I think as these regimens come into play like this where it's even easier, even safer, even less complicated, you start to shift that mindset to a provider readiness model, where we're not -- we just accept the fact that this is how the patients live.

To treat hep C in 2025 with the patient base that's most affected, you have to make a truth with a reality that's not necessarily your own. You have to step one foot into their world, recognize this is how they live. It's perfectly fine. And you have to come to the readiness point. They may never be abstinate from drugs enough. They may never be stably housed enough. They may never be psychiatrically compensated enough. While you're waiting, they're spreading. So the quicker that we can get to a regimen where it takes all these kind of other variables off the table, it just makes it that much easier.

As we scale our deployment of point of care, viral first testing, especially in high risk and high prevalent areas, that goes a long way to getting to those diagnoses. Then if we can deploy a regimen like this, make things even easier. Short-duration duration, like Eric was saying, is the key. Shorter is better. Speed and simplicity is the name of the game.

Thank you so much. I think that's a wonderful summary. If we can, I'm going to turn it back now, I think, to the -- to the operator, and we're going to have some questions. And I believe, there are a couple of people who are dying to get our question in quickly. So Jonae, can I perhaps hand it over to you to help facilitate that?

Yes, Janet. Yes. I'll take it from here. So we have a question from [ Andy Sile ] at William Blair.

Actually 2 questions, if you don't mind. So one has to do with the -- maybe adherence. So upon commercialization, do you expect patients to receive the full regimen, so meaning 2 bottles or 2 months' worth of supply just to ensure that the compliance is really, really optimal there? So that's question number one.

Question number 2 has to do with the costs or health care economics analysis. I think -- I appreciate the fireside chat kind of alluded to that before. But I'm sitting back here looking at kind of magical [indiscernible], which is positioned to prevent the advancement into the cirrhotic stage and that's a chronic treatment versus this is a fixed-dose combination, right, and it has a fixed duration of treatment. And I guess the health economic argument is very strong here, preventing -- with a cure that prevents a lot of different adverse outcomes for patients, including cirrhosis. So maybe, John, you can comment on some of the health economics, the analysis that you've done, particularly looking at that as well.

So I'll answer the first question with regard to what amount of drug product is provided at the time. That is really provider-driven and what their rules are. Or in this case that you have test and treat, what the rules are there to what is provided. It doesn't come down to the manufacturer. So from that standpoint, obviously, our company would support what's in the best interest of the payer. But at the end of the day, it's a patient, but at the end of the day, it's in the eyes of the payer and test-to-treat models about how they conduct their business.

That said, it would be a very good strategic move if the manufacturer were able to package the full 8 weeks on a single dispense, that would be a game changer. And that's something that the other companies on the market now have been trying to achieve. And there is a role for whoever commercializes this to take that into consideration. But you did raise an important point in that this is not chronic disease management. This is the cost of cure. So it is a big differentiator there. And you're absolutely right. I mean this makes a ton of economic sense.

We do see the merits and obviously providing everything in the cure. I guess we can further look into that and explore payer's preferences and what they want to pay for.

I think perhaps if there are any other questions from outside, Tara?

Yes. This is Jonae. Yes, there is a question from Maxwell Skor at Morgan Stanley. Maxwell would like to know what proportion of patients present with cirrhosis?

Jordan, you touched on that, I think, quite nicely at the beginning. Do you want to rearticulate what you said there?

Sure. It's really changed dramatically, and it does look -- it depends a little bit on where you look. But we did some work with some colleagues around the U.S. last year looking at fibrosis assessment. And what we looked at based on where it really depends on the practice type. So in a specialized hepatology practice, you still might see up to 15% to 20% of people with cirrhosis. These are older data. I actually think from our own practice, that's gone down dramatically, it's probably closer to around 5% to 7%. And if you go into a primary care setting, it's under 5%. And that's consistent really across any primary care setting that the proportion that have cirrhosis has really, really diminished.

And I think as Tony nicely highlighted, there are now a number of models that show that if you take a population certainly under 35 and maybe even extending that out to 45 without significant other risk factors for advanced liver disease, so not heavy alcohol use disorder or major risk factors for advanced [ NASH ], the risk of cirrhosis is extremely low, which gives us confidence that you could actually move to either a very simplified fibrosis testing with [ FibroScan ] or other sort of point-of-care technologies or [ FID 4 ], a very simple serologic tests or to forgo it all together when you're doing sort of field deployment of test and treat models when you're doing like a needle syringe program or something like that, where you're actually doing outreach work, identifying people and treating them in very clearly the best harm reduction approach to cirrhosis and all of the complications is to treat people.

If you actually get it wrong and you inadvertently misrecognize cirrhosis, first of all, the treatment efficacy is still very high, even if you gave someone an 8-week course. And secondly, the risk of long-term complications. The biggest risk -- the biggest way to reduce the risk of long-term complications, mostly important with cancer, is to get their hep C cured, not to get them into a surveillance program. So fortunately, it's much less of a problem than it used to be.

Yes, and you're not going to hurt them. I mean, that's one of the key things that you're -- by treating them, even if you've missed the cirrhosis, you're addressing and eliminating the underlying hepatic insult. So the only thing you're going to do is help them.

I think that's probably a nice way to conclude.

So thank you. In closing trust, I would like to thank our KOL participants for their time, interest and really very interesting view, and they have a daily view unfortunately, in making a really difficult decision and very rapidly in rapid time. So we hope that our regimen, if approved, will provide an additional -- an important option for the prescriber and the patients infected with hepatitis C. We believe that our regimen may represent the potential best-in-class profile, as some of you have discussed. And really, we look forward to optimally play an important role in the eradication of this [indiscernible] chronic viral disease. And so thank you all for joining Atea HCV KOL panel today. Thank you again.

Good afternoon, everyone, and welcome to the Atea Pharmaceuticals Third Quarter 2025 Financial Results and Business Update Conference Call. At this time, all participants are in listen only mode. Following the formal remarks, we'll open the call up for your questions.

I would now like to turn the call over to Jonae Barnes, Senior Vice President of Investor Relations and Corporate Communication at Atea Pharmaceuticals, Ms. Jonae, please proceed. .

Thank you, operator. Good afternoon, everyone, and welcome to Atea Pharmaceuticals Third Quarter 2025 Financial Results and Business Conference Call. Earlier today, we issued a press release, which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the Investors section of our website at ir.ateapharma.com. With me from Atea are Chief Executive Officer and Founder; Dr. Jean-Pierre Sommadossi, Chief Development Officer, Dr. Janet Hammon; Chief Medical Officer; Dr. Ranshoga; Chief Commercial Officer, John Vavrica; and Chief Financial Officer and Executive Vice President of Legal, Andrea Corkran, all of whom will be available for the Q&A portion of today's call. .

Before we begin the call, and as outlined on Slide 2, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on today's call.

With that, I'll now turn the call over to John Pierre.

Thank you, Jonae. Good afternoon, everyone, and thank you for joining us. I will begin on Slide 3. I'm pleased to share with you the significant progress and achievements we have made this quarter, which is a testament to strong execution across our team.

Our global Phase III program for the treatment of HCV is on track, and we expect to complete patient enrollment for our North American trial C-BEYOND next month. This time line leads us to the first Phase III top line results in mid-2026. For C-FORWARD, our trial outside of North America, we anticipate enrollment completion mid-2026, with top line results anticipated by the late 2026. And Andrea will provide an update on our Phase III program. A few days ago, new modeling data was presented at the liver meeting 2025 in Washington, D.C. along with 2 additional data set further demonstrating the antiviral potency with short treatment duration of our regimen for the treatment of.

Janet will review the highlights of these data next. I'm pleased also to report that we announced today new exciting research findings, including evidence of a unique dual mechanism of action for bemnifosbuvir against HCV further demonstrating its differentiation and potency, and I will review this data in a moment. In addition, I'm also very pleased to share with you that we are expanding our anti val hepatitis pipeline for a major unmet medical need of immunocompromised patients living with hepatitis E infection. We have identified 2 new potent candidates derived from our nucleotide platform. IND-enabling studies are ongoing to select a clinical candidate which Phase I initiation anticipated in mid-2026.

We will discuss this program in more detail with today's presentation. At the end of the third quarter, we maintained a strong balance sheet with approximately $329.3 million in cash, cash equivalents and marketable securities, providing runway to 2027. This strong cash position enabled us to fully fund our Phase III program, launched the new regimen and advanced our new HCV development program.

With that, I will now turn the call over to Janet to review the highlights of the presentation at the liver meeting. Janet?

Thanks, Jean-Pierre. Let's move to Slide 5. I'm pleased to share with you that a few days ago, we presented multiple data sets at The Liver Meeting. These data reinforce the strong clinical and pharmacologic profile of our fixed-dose combination of regimen of Bemnifosbuvir and rules for the treatment of HCV.

In an oral presentation, multiscale modeling results predicted that our combination regimen inhibits both the intracellular replication of HCV as well as viral assembly and secretion of new HCV variants in the bloodstream. The model predicted a cure time of approximately 7 to 8 weeks. Because the regimen suppresses the virus at multiple critical stages, these data reinforce the potential of the combination regimen as a person short-duration therapy for chronic HCV.

We also presented 2 posters. The first poster was identified as a poster of distinction. It highlighted a resistance analysis from the Phase II study of our regimen demonstrating that SVR12 rates were not impacted by NS5A resistant variant baseline at variants at baseline. Viral kinetics and pharmacokinetic analyses indicated that most of the viral failures were due to treatment nonadherence and not viral-resistant.

The second poster reviews the results from a Phase I study in healthy participants which demonstrated the high relative bioavailability of the Bemnifosbuvir and Ruzasvir commercial formulation for the fixed dose combination. These data also support dosing of the fixed-dose combination with or without food and with famotidine and H2 blocker, which can substantially diminish the effectiveness of oral antivirals. The fixed dose commercial formulation is being used in our ongoing Phase III program.

Moving to Slide 6. We will host a virtual panel event featuring key opinion leaders or KOL in hepatology gastroenterology, infectious diseases and hepatitis C tomorrow, Thursday, November 13 at 10:00 Eastern time. So the discussion will cover a wide range of HCV related topics including the needs of the current HCV patient population, the importance of early diagnosis and treatment, public policy initiatives, including the test and treat model of care, and further HCV eradication in North America is an achievable goal, what benefits a new optimized HCV therapy could provide for prescribers and patients.

The link to register for this event can be found in our latest quarterly press release distributed earlier today and on the Investors section of our website under Events & Presentations. The virtual panel discussion will feature several HCV key opinion leaders, including Jordan Sell from the University of General Hospital in Canada. Eric Lawitz from the Texas Liver Institute University of Texas SanAntonia. Anthony Martinez from the University of Buffalo, Erie County Medical Center and Nancy Reau from Rush University Medical Center in Chicago. A live question-and-answer session will follow the formal discussion. We hope you can join us.

I will now hand the call over to to review our Phase III program for hepatitis C. Arana?

Good afternoon, everyone. On Slide 8, let's now turn to our global Phase III program, which is the first head-to-head Phase III program for chronic hepatitis C comparing our regimen against the current global standard of care. -- so for marketed asset close. Our regimen includes beniphosphoviar, the most potent nucleotide inhibitor and roster, a highly potent NS5A inhibitor. Data support our regimen as a potential best-in-class treatment option for patients infected with HCV with a differentiated profile featuring a short duration, low risk of drug-drug interactions and convenience with no food effect.

I would like to highlight that we have new study results demonstrating no risk of drug-drug interactions with proton pump inhibitors, which are estimated to be taken by at least 35% of HCV patients. These results will be presented at an upcoming scientific meeting. We do this as a key differentiator inhibitors and substantially decreased the effectiveness of currently approved DAA therapies for HCV. Our Phase III program is designed to confirm the efficacy, safety and letability demonstrated in our robust Phase II study where we achieved a 98% sustained biological response at 12 weeks post treatment or SVR12. These Phase II results gave us confidence to move to our current Phase III late-stage program.

Historically, in each CV development, Phase II data has proven to be highly predictive of Phase III outcomes given the well-understood biology of the virus and the reliability of SDS1 as an established clinical endpoint for cure. Moving to Slide 9. The global Phase III program is composed of 2 pivotal trials. C-BEYOND, which is enrolling across approximately 120 sites in the U.S. and Canada and forward, which includes another 120 sites across 16 countries outside of North America. Combined, these studies are expected to enroll approximately 1,760 patients. Both trials are open label and randomized 1:1 against the active comparator, and they have stratified the cirrhosis status and genotype, including HIV co-infected patients.

In non-cirrhotic patients, treatment duration is 8 weeks compared to 12 weeks with the standard of care for patients with compensated closes, patients received 12 weeks of either regimen. The primary endpoint for both studies is 12 which is recognized as the definitive measure of HCV care. Slide 10. I am pleased to confirm that enrollment in the North America C-Beyond trial is on track for completion next month, with top line results anticipated mid-2026. Foreseer, which has a broader global geographic footprint, and rolling completion is expected mid-2026, followed by top line results by year-end of 2026.

I will now hand the call over to Jean-Pierre to review our new mechanism of action data. Jean-Pierre?

Thank you, Asa. Let's now move to Slide 12. As many of you know, Venifosbevir is a nucleotide NS5B polymerase inhibitor with an established mechanism of action of inhibiting HCV RNA chain termination, thus blocking valve production and verification inside the cell. Our collaborators are loss Alamos, national laboratories, headed by Dr. Allan Person, I've conducted HCV using data from the Phase I before monotherapy trial.

The new modeling suggested that Bemnifosbuvir may have an additional mechanism of action, inhibiting HCV VA assembly secretion of new HCV variants in the bloodstream significantly reducing extracellular HCV RNA, a mechanism previously only associated with NS5A inhibitors, such as business via and velpastovia. On Slide 13, in vitro studies conducted under another collaborator at Laura University confirm this dual mechanism of action for Bemnifosbuvir.

On this slide, the study show that the level of the intracellular HCV RNA were comparable with selected concentrations of Bemnifosbuvir and so. So why both agents produce these similar declines of intracellular HCV RNA. As you can see, Bemnifosbuvir led to a far greater and faster reduction in extracellular RNA indicating possible inhibition of via assembly and release into the best.

On Slide 14 now, the order individual study shows that interest some RNA HCV RNA, we're comparable. We selected concentration of Bemnifosbuvir and NS5A inhibitors, such as. So of importance here, extra several HCV RNA level decreased similarly with benipostivir or the passover an NS5A inhibitor, demonstrating that Bemnifosbuvir also inhibit HCV assembly and secretion into the bloodstream. In addition to inhibiting viral replication.

Turning to Slide 16, you can see this 2, which illustrates on the left side the HCV life cycle. And then on the right side, the dual mechanism of action for Bemnifosbuvir showing how many positively blocks of ours from making copies inside the cell, and it also block new virus from intern tele stream. Trefor on Slide 16, a what the data means. The data demonstrate that Bemnifosbuvir is a potent and differentiated nucleotide prodrug with a unique dual mechanism of action, which may explain now the higher potency of many passives compared to sofosbuvir.

Importantly, even in the presence of NS resistance, Bemnifosbuvir will continue to van assembly secretion due to dual metastation. Lastly, these results further highlight the differentiation and the potency of the Bemnifosbuvir and is regimen for the treatment of hepatitis C. With that, I will now turn the call over to John for an overview of the new hepatitis E valve program. John?

Thank you, Jean-Pierre. As shared earlier by J.P., we are expanding our pipeline of oral direct-acting antiviral candidates to include hepatitis virus or AAV, a virus with no approved therapies and high unmet medical need. .

As seen on Slide 18, the WHO estimates that there are 20 million global infections annually is an inflammation of the liver caused by the hepatitis virus. It is a growing public health challenge in both the developed and developing world. In developing countries, genotypes 1 and 2 are most prevalent and the virus is transmitted primarily to contaminated water. In developed countries, genotypes 3 and 4 are most proven and the virus is transmitted primarily through contaminated foods such as undercooked meat.

Moving to Slide 19. However, in recent years, there's been a growing incidence of chronic HDV genotype 3 and 4 infections in immunocompromised individuals. A population that includes solid organ transplant recipients, emotive politics stem cell transplant recipients as well as patients with hematological malignancies and preexisting liver disease. In these patients, HCV may not resolve resolve spontaneously resulting in chronic HCV in fashion, which left untreated can strictly lead to liver inflammation, rapid fibrosis progression and in some cases, cirrhosis within 3 to 5 years of infection.

Currently, there are no approved therapies anywhere in the world for HCV. risk populations, clinicians can reduce immunosuppression, which risk organ rejection or relapse of underlying disease. Some clinicians also use ribavirin an older antiviral therapy approved for other viral section indications, off-label for HCV, which yields inconsistent efficacy results and is often poorly tolerated and poses risk of significant toxicities. This leaves clinicians and patients with a significant unmet need for a safe, orally available direct acting antiviral that can achieve sustained viral clearance or cure.

Let's move on to Slide 20. The number of immunocompromised patients continues to rise each year in the U.S. and Europe. There are approximately 450,000 cases of solid organ transplants, hematopoietic stem cell transplants and hematological malignancies per year across these markets. While advances in modern medicine, especially in transplantation and ecology, have led to an increased survival. It may likely also explain why more HEV is being observed in these at-risk populations. Approximately 3% of these at-risk patients go on to develop chronic HEV. While the overall prevalence of HCV is high in the general population, a relatively smaller proportion of immunocompromised patients are at risk for poor outcomes. As such, there is the potential to seek an orphan drug designation, which can have development and regulatory advantages. These life-saving procedures continue to expand the population of immunocompromised patients that could be susceptible to chronic HCV infections.

Using other viral infections such as hepatitis as a guide to pricing, this HEV market opportunity could translate into roughly between $500 million to $750 million per year or more. I will now turn the call back to Jean-Pierre to review preclinical data for our 2 candidates for AEV. JB?

Thank you, John. So moving to Slide 21. The in vitro data on this slide shows the potent animal and Teva activity of 8587 and 82490 against hepatitis various genotypes 1 and 3 and underscore why HEV represents a compelling extension of our anti-vi platform.

Our 2 candidates demonstrate approximately 200-fold higher antiviral activity in vitro as compared to reviver which, as John mentioned, is used off-label for the treatment of hepatitis E virus. One in vitro and in vivo activity of Bemnifosbuvir was also shown against HEV, and that's how we start to understand that our platform could have some anti-HEV activity, the tenfold higher activity for led us to advance these 2 promising candidates.

On Slide 22, it is interesting to point out that only a Fluor atom in the sugar range differentiate the active triphosphate metabolite, 1906 from the from the 2 analogs AT-587 and AT-2490 as compared to 890, which is the active triplicate of. For particular importance, these 2 candidates efficiently convert to the active triphosphate for in humanities and as a preclinical safety profile to date, positioning them as leading candidates for first-in-class hepatitis E antiviruls. IND-enabling studies are ongoing to select the clinical candidate for Phase I evaluation. We are also pleased to announce that we would be presenting more information on our HEV program at an upcoming scientific meeting early next year.

I will now turn the call over to Andrea, to discuss our financials. Andrea?

Thank you, Jean-Pierre. As Janea mentioned in her introductory remarks, earlier today, we issued a press release containing our financial results for the third quarter of 2025. The statement of operations and balance sheet can be found on Slides 24 and 25.

In the third quarter of 2025, R&D expenses increased compared to the same period in 2024. This increase was principally attributable to increased spend in 2025 in our HCV clinical development program. For G&A, expenses in the third quarter of 2025 decreased in comparison to third quarter of 2024. The decrease was primarily driven by lower 2025 stock-based compensation. Interest income in Q3 2025 decreased compared to the third quarter of 2024 due to lower investment balances.

For the remainder of 2025, we expect our R&D expenditures will be driven principally by the conduct and advancement of our global Phase III HCV program. As Jean-Pierre mentioned, at the beginning of the call, at the end of third quarter of 2025, our cash, cash equivalent and marketable securities balance was $329.3 million. Continuing our strong financial discipline, we project our cash guidance runway through 2027. With respect to other matters, I would like to note that we continue to evaluate options to maximize shareholder value. As announced, we completed our share repurchase program after having repurchased the full $25 million of shares authorized by the Board.

Under the program, we repurchased a total of 7.6 million shares of common stock at an average percent is of $3.26 per share. All repurchased shares were retired and returned to authorized but unissued status. Regarding our strategic process. As we've previously stated, we believe the HCV Phase III clinical development results will drive shareholder value and catalyze business development discussions. While our discussions to date with potential counterparties have been positive, positive Phase III outcome would further significantly derisk the program. Strengthening our ability to maximize the value of this asset and to secure attractive terms.

For this reason, today, we announced the conclusion of our formal engagement with Evercore. While we now focus principally on the execution and completion of the Phase III trials, which we believe is the best path forward at this moment to drive shareholder value. We remain open to all opportunities to drive shareholder value, including a potential strategic transactions.

I'll now hand the call back to Jean-Pierre for closing remarks.

Thank you, Andrea. Slide 26. In closing, the significant progress and achievements we have made within the last quarter reflect strong execution across our team. We are on track with patient enrollment in our global Phase III program for the treatment of HCV. And we look forward to the top line Phase III results from the U.S. and Canada trial CBN in mid-2026 followed by top line results expected for the outside North American trial forward at the end of 2026.

We continue to present new data supporting the potential best-in-class profile of Bemnifosbuvir reserve for the treatment of hepatitis C. If approved, we believe we can become the most prescribed treatment but IDC and disrupting and expanding the 2 global HCV market of approximately $3 billion in annual net sales. The new data we view today demonstrate a new and unique dual mechanism of action for Bemnifosbuvir against hepatitis C, highlighting its unique and differentiated profile as compared to Sofosbuvir. And this data now can explain in part the potency of our regimen for the treatment of hepatitis C.

In addition to our HCV program, I'm really pleased to share the information today about the potential of our proprietary preclinical candidates derived from our nucleotide platform aligned with the expansion of our anti valve pipeline. These compounds may help to address the unmet needs of the many immunocompromised patients living with hepatitis virus infection. And we look forward to providing more updates soon on this program. Before opening the call to your questions, I would like to thank our talented and dedicated employees. Our team relentless pursuit of excellence drives our dedication to advancing all antiviral therapeutics for patients worldwide affected by severe viral diseases.

With that, I would turn the call back over to the operator.

[Operator Instructions] The first question comes from Maxwell call with Morgan Stanley.

This is Selena on for Max. How does your recent data set at The Liver Meeting showing no interaction with famotidine in addition to your prior data showing no interaction with PPI increase your differentiation from Epclusa.

Janet, do you want to address the question, please?

Thank you, Gena, for the question. So I think we know that there is a label for a a contraindication to the concomitant use of H2 reducing therapy with Epclusa. And the recommendation in the label is for that to be at least a 4-hour window of separation between dosing of the 1 and dosing of the other. Person pump inhibitor use is widespread in the U.S. I think I said on the last call, about 10% to 20% of the U.S. population currently uses this type of therapy generally over the counter. But it's actually even higher in patients with hepatitis C and is estimated to be around 35% of HCV patients use acid-reducing therapy.

So this is a clear problem for patients when they're taking therapy because it can reduce the levels of antivirals that are achieved and this can compromise efficacy. So we see this as a really important differentiator.

The next question comes from the line of Andy Hsieh with William Blair.

I have 2. One is from the modeling poster that you presented at AASLD, there is a chart basically showing time to undetectable and interestingly, there is a separation between genotype 1 and genotype 3, with 3 showing a more rapid time to undetectable. I'm curious if there is any significance in that and also maybe the observed trend, does that have to do with the dual mechanism that you announced earlier? So that's question number one. Yes. .

Maybe I can add so we second one. So thanks for looking at the slide of the presentation. at the liver meeting. Indeed, you're correct. The modeling suggests that there is a more rapid decline with genotype 3. I think that we know that .

Bemnifosbuvir is interestingly, more potent in vitro, actually, again, time den genotype 1 A1 when we did the in-vitro study about more than about 10 years ago now. That banning that's a note differentiation with Sofosbuvir, for example, where sofosbuvir is less put on genotype 2. So it's possible related to the dual mechanism. And as Andy has suggested and Rod in 1 of his reports a few months ago that at least in the Phase II, we are 100% cure in genotype 3 non-cirrhotic patients, which definitely less compared historically to other regimens were very high rate very high cure rates. .

Yes, that's correct. Okay. The second question has to do with the compound that you outlined in the slides for hepatitis E maybe more of an academic question, but it doesn't employ the prototype technology. So I'm curious if that's kind of a deliberate decision or maybe in this context, protest is that optimized for I'm curious if you could comment on that as well.

It is -- I can tell you that not in the chemical structure. But it is exactly the same prodrug that we have used for them, which is a first to remit. So it's identical. So we feel very comfortable with the PK and and the safety and the efficacy as well. So as you have seen, interestingly, it's only that through item at the feline position that differentiate between of 587 and BAM, for example. And what's interesting is that while we are 10x more potent with 587 and 24.9% as compared to BAM in E. These are less potent as compared to BAM in hepatitis by about the same magnitude of about tenfold. So here, we have a very specific inhibition of hepatitis E with this active and we are evaluating now really the molecular rationale of the binding of the preliminaries why we are more potent, but definitely has to be a better binding with the presence of the full plant through.

Great. Thanks for that, Well, good luck with the Phase III readout and look forward to additional information from the hepatitis E program.

Thank you so much for your questions. SP999 Thank you.

This concludes the question-and-answer session. I would like to turn the conference back over to John Pierre for any closing remarks.

Again, thank you all for joining us. to our third quarter earnings conference call, and thank you for your continued support .

Thank you. This concludes -- the conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Thank you.

Great. Hello, everyone. I'm Max Skor with Morgan Stanley. And before we get started, I'm just going to read a quick disclosure. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So with that, I'd like to introduce the Atea team. Very happy to have everyone here. And maybe just to level set, could you introduce the Atea story to people in the audience who maybe aren't as familiar.

Yes, so Atea is a biotech company based in Boston, and we have a nucleoside platform, which we have been using against serious viral diseases. We had a trial in COVID, and we are currently in Phase III with our nucleoside analog bemnifosbuvir for hepatitis C.

Great. So yes, 2 ongoing Phase III trials. But maybe can we discuss a bit deeper, what's the core scientific rationale behind your regimen? And how does it aim to improve on the current standard of care for hep C?

So I think it's a bit underappreciated, but the direct factoring antivirals that are commonly used for hepatitis C were approved about 10 years ago. And today, there are over 50 million people still with hepatitis C around the world. And within the U.S., about 2.4 million to 4 million people are estimated to have hepatitis C. And what's even more disturbing perhaps is that, that number continues to increase. And there are some reasons for this. I think the patients who were first treated when the direct-acting antivirals were approved were largely baby boomers, but the population has changed and has now skewed younger. Most of the patients are now in their 30s and 40s. And it's interesting, but they're much more medically complex than those patients were previously and approximately 80% of them are on concomitant medications. And this becomes important because for the prescriber having to treat these patients, they're looking for ways to treat them effectively with problems with adherence and also problems often with the history on potential drug interactions.

And so looking for a profile which is simple, effective and easy to take for this patient population. And the World Health Organization and health organizations around the world have initiatives to eradicate hepatitis C ideally by 2030. And in order to do this, they are looking for a test-and-treat model. And we believe that our regimen of bemnifosbuvir, our nucleoside analog and ruzasvir, which is a highly potent NS5A is ideally suited to the test-and-treat model. Our regimen is highly potent once a day, short treatment course, 8 weeks and minimizes drug interactions. We have a really superior drug interaction profile and no food effect. So we see ourselves as ideally positioned to be able to help eradicate hepatitis C moving forward.

And I'll sure go into some of the details. So I think what we have right now is the best regimen for most patients. That's what we're going to potentially offer, which is a short course, 8 weeks with good profile with no drug-drug interactions, so very low potential for drug-drug interactions and no food effect. So we're going to be coming with a regimen that brings the best of both worlds of what's out there.

Okay. And before maybe diving into the posters that were recently presented at EASL, could we just talk about some recent market research the team has done. What does the opportunity look like? And has there been any impact from COVID potentially?

So following the Phase II data, we conducted another quantitative U.S. market research study, roughly 153 high writers of direct-acting antivirals in the U.S. It was done by IQVIA and they selected and did perform the study. What it showed was that 73 -- 76% actually said they were extremely likely to prescribe the asset. And when they ask them, where would you prescribe it, they saw the BEM/RZR product being used in roughly half the patients regardless of their cirrhotic state. And as far as for the reasons why, I mean -- and Arantxa just repeated it in terms of the potency, short duration and basically no DDIs. For me, personally, the results were very good, but what was even more impressive was these results are consistent with our other market research, showing a profile that is really highly preferred.

So it looks like based on your KOL feedback that doctors are looking for an alternative to the standard of care at this point?

Yes, it's really interesting. When you first talk to doctors and you say, "Hey, you're happy with what you currently have the 2 products out there." Yes, there's 2 cures and they're actually very happy. When you show them the profile that matches what Janet and Arantxa have just said, all of a sudden, it becomes, well, maybe their most preferred profile because they don't have to worry about any drug-drug interaction and it is giving them 8-week cures.

Okay. I think that's a good segue into the EASL 2025 posters that were presented. So these included the Phase II efficacy and safety updates. Can you synthesize the top takeaways and how these data reinforce the 8-week regimen?

Yes. So we presented at EASL our final data from the Phase II trial. The Phase II trial was a single-arm trial where we looked at the regimen treated for 8 weeks. We did the patients for 8 weeks in non-cirrhotics and in cirrhotics. And it was a large trial for Phase II. It didn't have a comparator because historically, hepatitis C trials didn't do comparators, but we enrolled 276 patients, and then we did analysis in different populations within that group. The first analysis was done and the primary endpoint was done in the patients who actually took the drug, they went as prescribed per the protocol. And there, we basically have cure rates of 98%. And if you look in the non-cirrhotic specifically, which is the majority of the population, we cure 99%, 100% of the patients who take the drug. So it's really extraordinary results for efficacy. And then after that, we also did some sub-analysis, the group of patients, for example, that were not compliant with the medication.

They were taking less than 90% or even less of the drug as prescribed. And even in those patients, we had cure rates of 95% because we're actually a regimen that's very potent, 10x more potent than Epclusa regimen. And so we have a lot of drug forgiveness even if you forget your drug, we're still going to cure 95% of the patients with only 8 weeks. And so those are the very exciting results that we presented there, also across genotypes, and that's what made us to believe that we really needed to move to Phase III. And in the Phase III, we're moving forward now with a comparator. And so we're going 8 weeks versus 12 weeks. So we're expecting a superior profile because it's a shorter regimen with the good attributes that we were speaking before, the no drug-drug interactions or very low potential for drug-drug interactions and no full effect.

Great. Also kind of -- I'd like to kind of talk about the pharmacokinetic posters where you evaluated the drug in hepatic and renal impairment, including dialysis, suggesting no dose adjustments were needed. So how do you see these findings translate to your Phase III inclusion criteria and to a potential label?

So we're very pleased with the results, obviously, because I think we showed that we can anticipate that you can dose patients with both hepatic and renal impairment with similar efficacy and safety and no dose adjustment. So it broadens that patient population. Not only did we show the 2 Phase I studies for the hepatic and renal impairment, but we also had a study where we did a Phase I trial with BEM/ruzasvir and Biktarvy. And there we showed also that with a standard HIV regimen, you can safely and efficaciously treat HIV co-infected patients. So that also helps broaden the population for our Phase III trial and hopefully a broad label ultimately, too.

Yes. And can you talk a bit more about the patient makeup in a sense based on the market research that the team has done. How many of these patients have comorbidities, understanding that, of course, it's a challenging group to adhere to therapy at times?

So we estimate that probably 80% of patients are on concomitant medications for a variety of diseases. HIV co-infection perhaps in 10% to 20% of patients. And then a variety of other diseases, they're not a simple population. So having a broad label and an easy-to-tolerate profile is really crucial for being successful in this space, I believe.

That's great. So just to summarize in many ways what I'm understanding, a potential label could be differentiated based on drug-drug interactions, the treatment regimen. Is there anything you'd like to call out?

Well, Max, yes, there's one thing I wanted to say. We haven't actually reported this previously, but we just had the readout from our Phase I study of BEM/ruzasvir with a proton pump inhibitor. And we show no effect of proton pump inhibitor. And this really does differentiate us from both of the other regimens where there are significant cautions around using proton pump inhibitors if you should use them at all. And for instance, for Epclusa, you have to separate dosing by 4 hours in order to achieve adequate levels. And there, we show no effect at all. And interestingly, about 10% to 20% of the U.S. population is estimated to be taking a PPI. So this is actually not trivial information. So we're really excited about that.

Yes. That's great. That's very encouraging. So now pivoting to the Phase III trials. Could you just walk us through the C-BEYOND and C-FORWARD designs?

Yes. So C-BEYOND is a trial that we're conducting in North America, basically United States, the majority of the sites, 120 sites roughly and also some sites in Canada. C-BEYOND is the trial that we started enrolling back in April. Everything is going on track. There is a lot of interest from investigators, a lot of excitement also from the patients. And the other trial, C-FORWARD is basically the same, but it's run outside of North America. It's a global trial. And part of the reason is that we need to be in many different countries to lead to a completely pan-genotypic label with multiple genotypes that are found only in regions of the world like genotype 6 in Southeast Asia, genotype 4 in North Africa. So for example, we have to go to Egypt, et cetera. So that trial is going a little behind because a lot of these regions have much longer regulatory approval time lines.

So it's still on track for our regulatory approvals, but it's moving forward a little bit slower for that reason. And so these are the 2 Phase III trials with the identical design. We're basically looking at an 8-week regimen for non-cirrhotic patients, which are the majority of patients, about 90% of patients in the world are right now non-cirrhotic. And we will include as well roughly around 10%, 15% of cirrhotic. So we have a broad label, but the cirrhotic population is less and less frequent. This is patients that have been infected with hepatitis C for many, many years, for decades, which it takes time to inflame the liver and eventually lead into fibrosis and scarring, et cetera. It's a population in decline.

That group of patients we will treat for 12 weeks because it just takes longer to penetrate the liver and just to be sure that they don't rebound. But again, they are a very small percentage. The majority of the patients in the trial will be treated for 8 weeks versus 12 weeks with the comparator. So they are dosed for 8 weeks. The comparator is dosed for 12 weeks, then you stop and then you measure cure 3 months after. You have to see the virus rebound. So you measure cure after they have been off treatment for about 3 months. And so we're enrolling we're on track, and we're expecting results for the first trial sometime mid-2026, mid next year, really. And the other one is coming a little bit later for the reasons I mentioned. So roughly, we're expecting towards the end of next year.

So can you give any feedback on what you heard from regulators? How did the end of Phase II feedback shape the Phase III clinical trial designs?

We had a great Phase II meeting. It was really -- it went very smoothly. The major comments were centering about how do you analyze these populations, especially in the context of a controlled trial because there has never been a controlled trial for hepatitis C before, a registrational controlled trial. And so how do you do analysis and that kind of discussion, it was very insightful. And then we also -- we are getting also approvals ex U.S. through the EMEA, et cetera, and that is also going very well. And that -- there was one thing that was very interesting talking about differentiation.

We talked about food effect. We talked about drug-drug interaction, but there is a genotype, genotype 3 in particular, that can be very resistant. And the FDA asked us not to take those patients and not to treat them with the control, not to treat them with Epclusa, but to just give them our regimen because our regimen is 10x more potent. And so resistance in that subgroup may also be a differentiation factor. So overall, it was a great meeting, and we advanced very quickly. We started enrolling in April right after. It didn't require a lot of modifications.

And what percentage of these genotype 3 patients will be enrolled in the U.S. study?

So you can find genotype 3 patients in the U.S., particularly in immigrant populations, but the majority of them come from places like Pakistan. Pakistan has a very high population of genotype 3. And we are -- in Pakistan, we had excellent results in Phase II, where we enrolled a significant amount of genotype 3s that did very well. In particular, in non-cirrhotics, we had 100% cure if they took the drug. Obviously, when they start not taking the drug, it goes down a little bit from maybe 99% to 95%, but still very, very remarkable.

Okay. And diving a bit deeper into the comparator arm and the overall margin for success. Could you speak to what non-inferiority margin and superiority hurdles you're targeting?

So we agreed with the FDA on study design endpoints and the non-inferiority margin and the non-inferiority margin is compatible with going against an active comparator with a high efficacy rate. And I think that's what we'll say there. But I think really, when you look at what we're doing, the profile of our combination is so vastly superior to Epclusa that the statistical study may be designed for non-inferiority, but the profile that we're describing of a highly potent once-a-day regimen with minimal drug interactions is superior. So that's really where we want to focus going forward.

And just can you remind me in regards to the competition out there, there are 2 players that are currently on the market. What is their IP position and your own IP position in that regard?

So Max, you're correct. There are 2 dominant players. One is Epclusa and the other is Mavyret. They have IP patent protection until 2034. You also likely know that Gilead has an authorized generic. This is not a true generic product. It is a captive product from Gilead. So we're not competing immediately against generics. The first generics wouldn't be available until 2034 or beyond.

Okay. That's helpful. And then remind me of the -- for the combination from Atea, what the IP position there is?

Ours will go to 2042.

Yes. Okay. That's what I thought. And then can we just talk about the patient journey overall, specifically in the United States, where these patients are being identified? How the treatment regimen is currently being rolled out and where potentially you can make the greatest impact?

Janet?

Janet?

So I think the patients are everywhere, but I think the problem is diagnosing and identifying them. And the ACIP guidelines suggest that everybody over the age of 30, I think it is, should be screened for hepatitis C at least once. But it's a -- I think it's the tip of the iceberg, unfortunately, that's getting treated. And it's about a static number of patients who are being treated everywhere, about 100,000 patients. But actually, the incidence is increasing. So there are more patients infected every year that are actually being treated. So the pool of patients is actually quite a lot more than that and continues to grow. And John, you might want to talk a little bit about the demographics as to who -- how you see that in terms of 1/3 being -- I've heard you say this, 1/3 Medicare, 1/3 Medicaid and 1/3 in private.

Yes. No. So -- and that's how the market kind of breaks out right now, if you like to think about it that way, 1/3 of Medicare, 1/3 Medicaid and 1/3 commercial lives. So it really does touch all aspects of society. I will mention that it's now becoming a top priority for the U.S. government right now. There's initiatives in Congress, the White House and at the CDC to start addressing hepatitis C and to try to figure out the best ways to do test and treat to get to a lot of these patient populations is becoming a priority for them.

Yes. Can you -- I've seen the headlines around that, too, can you speak to a bit more what those efforts look like, time lines around that and how that could shape the prescribing dynamics?

Sure. So right now, in the Senate, there's -- I think it's roughly a $10 billion bill that will be divided up between treatment as well as trying to figure out ways to better address the patient population. That one, it's just right now, the bill is written. So it's targeting prison populations, other types of Medicaid populations. It's just still a bill right now. The White House is doing something different. That's actually right now, it's $100 million, and that's an initiative right now to figure out what is the best way to go after difficult-to-treat populations, such as people who have used drugs and other types of conditions.

And finally, you have the CDC trying to pull together a 2-day meeting, which is going to take place rather soon to figure out what is the best way that we can increase the adherence to these and treatment for hepatitis C in the United States, up to 4 million. As you know, we have right now. And as Janet said, that it's only increasing every year. And we didn't state it, but the obvious is that if you let a patient go with hepatitis C, it's the leading cause of hepatocellular carcinoma in the United States. So if you treat them now or you're going to spend a lot more money treating them later.

Okay. That's helpful. So going back to a bit feedback around the end of Phase II meeting, what are the key end of Phase II agreements with the FDA, such as endpoint analysis sets, safety databases? Do you foresee pooling the 2 data sets to go to regulators and potentially get approval and how will that inform the ultimate label?

So yes. So we -- as I said, we did agree with them around endpoints and study design and non-inferiority margins, and we're powered at 90% with this study. We're aiming to pull the 2 studies, and we think that will give us a broad label, I mean, obviously, depending on the data that comes out, but we anticipate a broad label encompassing all genotypes patients with and without cirrhosis, co-infected patients and then potentially with our broad array of Phase I studies, also a broad label in terms of the medications that can be co-administered safely with the regimen. And so we think it's going to be a broad label, which will be suitable for the majority of patients with hepatitis C outcome.

Okay. And do you think there'll be the necessity for running another study for special populations, such as we discussed the renal impairment, HIV, HCV?

So we're including co-infected patients in the trial. So they should be part of the label that we achieve. And I don't believe that we'll need to -- because I think the Phase I data are sufficiently good that we should have indications for patients with both renal and hepatic impairment. I think for the vast majority of patients, this will be a really good treatment.

Okay. And then one follow-up question regarding the FDA and ex U.S. regulators. Where do you think they land on label languaging around drug-drug interactions or contraindications, cautions versus the 8 and the 12-week regimen? Do you think there'll be anything you would elaborate on or predict would come out in the labeling around that?

So we're anticipating that for patients with cirrhosis, our regimen is going to be efficacious with 12 weeks. So we would ultimately expect that for the vast majority of patients, as Arantxa said, are non-cirrhotic that our treatment regimen will be 8 weeks for everybody apart from patients with compensated cirrhosis, where the treatment duration would be 12 weeks. But that's what the studies are being designed to show. So it will be -- replicate what we're studying in our Phase III trials.

Okay. And then moving on to the financials. You have, I would say, a significant cash position with around $279 million after the second quarter, guiding to a runway through 2027. Any commentary around capital allocation, BD activities? Anything?

Sure. Thanks, Max. So the cash balance at the end of June was $379 million.

Oh, what did I say? Yes.

$279 million.

Oh, sorry. I did comment that it was significant.

Thanks for that, and we've been very careful stewards of those funds. And currently, for capital allocation, our main focus is, as you can appreciate, we'll be on the Phase III program and the completion of that. So we expect that, that program in its entirety will use approximately $200 million. So more than sufficient capital on the balance sheet right now allow us to complete the study as the program gets to the NDA approval and prepare for the commercial launch. So well, we're quite fortunate in that regard. With regard to BD activity, we are opportunistic, of course. We're always looking for something that might fit in our suite of products, but we have a really high bar. We'll first assess for BD activities for an in-licensing activity, something that has a large commercial opportunity and then would need to be best or first-in-class.

Our expertise is in the antiviral space, and so we're focused in that area. We're not deviating to other things. We also have a strategic process ongoing that will allow us to potentially evaluate partnerships that would assist us with the commercialization of our assets. We expect those discussions to get a jump start once we've had the Phase III results, but they've been very positive up to this point. But in order to maximize the value of the asset and ensure that we get the proper partner because this is such a special asset. We want to make sure that we treat it with that care and not enter into a deal with haste. We're going to wait to get those Phase III results before we include any partnership activity.

Okay. And maybe if you can elaborate a bit on what the partnership potentially could look like ex U.S.? Any commentary there?

Well, ex U.S., for sure. We've always said that we would be looking for ex U.S. partner, and that would be a full partnership that partner would get full right because of non-U.S. assets. For the U.S., we're open to a number of different strategies and different structures, one that would make sure that we have maximizing the value of the asset would be our ideal.

Okay. And then just to conclude in this sense, over the next 12 to, let's say, 18 months, we have the Phase III readout coming U.S. first, ex U.S. -- U.S. -- Canada first and then ex U.S. What other meaningful inflection points would you call out over the next 12 to 18 months?

Well, we have a couple coming up in November. We'll be at AASLD, which is the largest U.S. meeting similar to EASL in the spring of 2026, we'll be there as well. And we'll have additional KOL events. The most near term will be in November as well. So we recently had a KOL event in May. It's still on the website, but it gave us an opportunity to engage with 6 key opinion leaders there, and we're going to continue that work as we await the results from the Phase III trial.

And I mean, from my perspective, the data has been significant. The opportunity is obviously there. We have 2 competitors in the space. What do you think investors are kind of missing on the story overall?

We wish we knew. But for those that are with us, this is a great opportunity, we believe. The Phase III is -- the readout is imminent. It's the realization of objectives we had since inception of the company, and we're very much looking forward to an exciting 2026.

Okay. So if you don't mind, I'd like to move on to 3 survey questions we're asking most of our companies. So with China's rise in biotech innovation, how are you thinking about your competitive position here? And will it influence your R&D or BD strategy?

Probably not for us. We -- our BD strategy doesn't -- is not being impacted by China and R&D, we hope to be complete with that soon.

Okay. And then how are you currently leveraging AI or thinking about AI's future disruptive potential?

Yes. We're all learning about AI, right? So it's a whole new opportunity for all of us. It's likely to come into an area where John is the expert as we see changes in the commercial structure and arrangements. But for us, AI is -- we're using it in our early discovery activities where we have some interesting opportunities that we're exploring.

Okay.

We'll continue to use the historic methods as well, right? So we're not completely dependent upon AI. It's an emerging technology, but we're still using the expertise of our internal team.

That's great. And then lastly, what has been most impactful from the regulatory side? Would you say FDA, MFN or tariffs? Granted some of them may not apply to you at the moment, but maybe in the future.

We don't know. The landscape is so -- such evolving. We are uniquely positioned, we think, among the HCV manufacturers that we have, U.S. manufacturing right now. That, we think, is an advantage for us as we approach this evolving landscape. On MFN, we'll see really how that landscape evolves. But to the extent that MFN includes prices in Europe, we shouldn't be negatively impacted by that. And to the extent we're doing U.S. domestic manufacturing, tariffs should be of less concern.

And FDA, we -- I think that we spoke to it previously, but just in regards to interactions with the FDA and as things...

I'll leave this to my colleagues here, but the basic take is that we have not been impacted by the staff reductions at FDA, at least up until this point. And our engagements have been very, very constructive.

Okay.

And responsive, I mean no delays, nothing.

Okay. And then the last question. Anything I missed, anything of investor interest you think that I overlooked?

No, I think it's pretty thorough.

Okay. So great. Well, thank you very much for attending. I really appreciate it.

Great. Thank you, Max.

Thanks, Max.

Thanks.