Good morning. Welcome to the 44th Annual JPMorgan Healthcare Conference. My name is Yue Huang. 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 ruzasvir, 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 seven years ago, and we are very excited to finally, after seven years, to be within six months for the data on the first trial, CB-ARC, which this is a North American trial. We announced last month that the enrollment was completed. Actually, we had more than 900 patients enrolled. With the result, this would 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 result 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 is 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 2028, 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 preparing 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 ourselves or KOL or specialists in hepatology, after the introduction of two 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 two active regimens, we have in excess of 4 million individuals. When 20 years ago, we thought that HCV would be eradicated, as you can see on this slide, by 2030, so five years from now, well, 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-$60 billion.
This is why, actually, has been predicted by experts, physicians in the field, that the number of liver cancers in the United States will increase by 50% over the next five years, from about 800,000 to 1.4 million, with more than 1.2 million deaths per year, five years from now. The majority is what is responsible is Hepatitis C. 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 combines Bemnifosbuvir, which is the most potent nucleotide inhibitor. It's about 10 to 50 times more potent than Sofosbuvir , which is part of the Velpatasvir-Sofosbuvir combination called Epclusa. Our regimen also includes a highly potent NS5A inhibitor, which we licensed global rights from Merck about three, four years ago. Our 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 to basically 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 combination of 10-15 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 a per-protocol population a 98% efficacy cure rate or sustained virologic 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 billion-dollar drug. And actually, we just had two KOL events in the past year. The last one as part of the liver meeting in Washington, D.C. in November. And what you can see, the message essentially is the same. 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 number two. And everyone now, it was quite interesting that at the liver meeting in November in Washington, D.C., 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 increased actually almost exponentially and definitely exceeding, fortunately, 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 eight 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 by 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 in the high 98%. Following the phase II clinical results, IQVIA, independently, they're the quantitative market researcher for us with 153 high prescribers. 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.
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. We think that probably in the range of 75-100 at the cost of about $25-$30 million fully loaded. So something that can be done even by with a biotech with experts like us in the field 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 eight months and enrolled 900 patients in this trial in the United States in less than eight 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 genotypes, mostly in the U.S., genotype one, two, and three.
We cover all genotypes because we want a label that is fully pan-genotypic with countries like South Africa, you have genotype five, Southeast Asia, Vietnam, Thailand, you have genotype six, and Middle Eastern countries where you have genotype four. So we anticipate completion, as I say, Q2 and result by the end of the year. So let's just quick review this program. So we have two pivotal trials, CB-ARC and C-FORWARD , combined with almost 1,800 patients. It's a head-to-head. This is the first head-to-head against an active competitor, which is the standard of care or combination of Sofosbuvir and Velpatasvir. Our regimen is eight weeks compared to 12 weeks of Epclusa, and in that, in non-cirrhotic patients. In cirrhotic patients, it's a 12-week comparison of the two regimens.
Importantly, so that we are not unblinded, physicians know what they prescribe, patients know what they receive, but the sponsor does not have access. You can see that the assessment of the SVR is at the same time, 24 weeks after treatment initiation. The primary endpoint is sustained virologic response occur after 24 weeks. We just presented with our colleague from Los Alamos, which is the group from Alan Perelson, who is the major expert in the world for viral kinetics. You can see that based on the result on the phase II, we had a very potent efficacy for the eight-week treatment regimen. The median time to cure with this model does support our eight-week short-term duration with an expectation around seven weeks. For the cirrhotic, the F4 need a little bit longer treatment in excess of eight weeks.
But you can see we have really a significant margin going to 12 weeks. And that's why 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 two different SVRs 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 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%-9% discontinuation. When you have those patients that discontinue before dosing and then those during treatment. But at least the FDA agreed that we should only include in 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 experts and statisticians called imputation models.
So if the discontinuation is, let's say, in the second part of the trial, 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% non-inferiority standard for this high rate of response with 90%. And that gives us the 880 patients size trial. And so, as I said, we enroll about 900 patients. And that's what we basically want to make sure.
The analysis will be with each trial and then the two trials combined. In the per protocol, there will be an analysis on the combined two trials for superiority as well. 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 two tablets once a day with a blister pack. It's packaged in a carton with four weekly blister cards. This is for a one-month supply. As you know, in the United States, the payer reimburses only for one month for 30 days. Patients will come back for a second carton. Very convenient. There will be the labels day one, day two, day three. We'll be ready with tens of thousands of treatments at launch for the end of 2027 or early 2028.
Our cost of goods related to net price is a 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. We'll say less than 24 months, even not including that. We will obviously evaluate and execute a partnership for the countries outside the United States. So let's now review the new program on Hepatitis E. Hepatitis E, you have four genotypes but two different types 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 in immunocompromised developed countries. This is U.S. and Europe. In U.S., you have more than 90% of slaughterhouses infected with Hepatitis E. And mostly, it's due to infections due to undercooked meat, especially pork.
So here, you see, as I mentioned, the population who are at risk are solid organ transplant, hematopoietic stem cell transplant, hematologic malignancies. So the first line basically is to reduce immunosuppression. It takes cyclosporine, tacrolimus. You decrease the dose. But obviously, the major risk is organ rejection. There is also an off-label with ribavirin. We all know the toxicity of ribavirin, and only about 60% cure are observed with ribavirin. And so why is it so important? Because 15%, for example, of those solid organ transplant recipients can develop rapidly a cirrhosis in less than three to five years. In contrast to Hepatitis B or Hepatitis C, where it will take 20-25 years to develop a cirrhosis and potentially hepatocellular carcinoma. So from a commercial opportunity standpoint, this is also a billion-dollar opportunity. Orphan drug designation, about 450,000 patients yearly between U.S. and Europe.
3% are at risk. So you take 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 drug 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 had two potential clinical candidates.
And this was selected based on an in vitro profile. As you see, very potent regardless of the genotype three that we are using. It's also active against the ribavirin clinical resistance-associated substitution or RAS. And recently, we got the data that we expected in two animal species, in monkey and rat. We have a very good activation to this active triphosphate. We measure this with a surrogate in plasma. And 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 BAM is extremely potent against Hepatitis C. And here, you have even a conversion to this active triphosphate metabolite in human hepatocyte, which is the site of viral replication, so of infection, even three times.
So far, the in vitro safety profile is very clean, as you can see. The IND-enabling study with the GLP tox underway. We anticipate an IND. CTA probably will file a CTA in Europe in Q2 during the phase I, and then after, followed by a proof of concept. You can see that in closing. I cannot really stress more than this is that you will understand this is a pivotal year for Atea. We are on track to deliver top-line phase III results from CB-ARC in Q3. We'll have results for the 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 on phase Ib to evaluate the dose and treatment duration, probably between 12-24 weeks.
And the primary endpoint, obviously, will be a sustained viral response or cure. And that's we anticipate in the second half of 2027 to initiate a pivotal trial or probably two pivotal trials 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 addressing 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 burden 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 JP 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. 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 three to five 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 two 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, these are patients who often fall through the cracks of the health care system.
And we believe that this test and treat model where when people have any encounter with the health care system, they can get a fingerstick 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 webcasts 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 M.D., 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 JP 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 eight 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 clear the virus. And these types of things weigh on the prescriber's 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.
We believe that with the 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 four million people currently living with HCV in the United States.
I think we have time for one last question. Moving on to your new program in Hepatitis E virus, what would be the primary endpoint in the proof of concept study?
And Jean, tell you anything. We obviously are going to look for a cure. As the way we have designed early clinical trial for Bemnifosbuvir, we'll do the same.
So phase Ib was probably about two or three doses 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 six or seven patients. And we had the same approach we did with Bemnifosbuvir at each dose. That will allow us to look for the best dose or two of the best dose. Then we will share the data with our colleague at Los Alamos. As you've seen, they will 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, 3 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 six and nine months to be able to, if needed, to go to 24 weeks. So just to remind for those that know Hepatitis C initial trials started, we all started with 24 weeks. And then after we came back to when we showed that there was effectiveness, we went from 24 weeks to 12 weeks and now to eight 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, JP and the Atea Pharmaceuticals team.