Good afternoon. Welcome. I'm Eric Joseph, Senior Biotech Analyst with J.P. Morgan. Our next presenting company is Atea Pharmaceuticals, and presenting for the company is Jean-Pierre Sommadossi. There's a Q&A after the presentation. If you have a question, we'll bring—if we have mics, we'll bring them around to you. And for those tuning in via the webcast, feel free to submit questions through the portal. So with that, J.P., thanks for joining us.
Thank you, Eric. Before I begin, I would like to thank J.P. Morgan for the opportunity to present today. We have here on the podium Arantxa, our CMO, and John Vavricka, our Chief Commercial Officer, and they will address some of the questions that you may have after the presentation. We have exciting new updates on our regimen for the treatment of Hepatitis C with bemnifosbuvir and ruzasvir, and new data as well from our third-party market research supporting the, we believe, large market opportunity. Just a usual forward-looking statement, and I encourage you to look over the latest update with our regulatory filings. Atea is going to have a very exciting year as we plan to initiate our global phase III program, evaluating the regimens of bemnifosbuvir and ruzasvir during the first quarter of this year.
We enter the phase III program for HCV following positive data that we just reported in part about a month ago. We will share with you some new data as well, showing that this phase II Global study actually demonstrated a 98% cure rate in the primary efficacy analysis with a short eight-week treatment. This very high rate, as you know, demonstrates really the robust potency of this regimen, and you will see across genotype, and meeting our criteria, we have selected a 95% efficacy to move the program toward the Global phase III, which, as I said, we will initiate this quarter. Actually, we are going to meet with the FDA at the end of the month for an End of phase II meeting, and we anticipate that we will initiate shortly thereafter.
We believe that our regimen, if approved, has the opportunity to really disrupt the global HCV market, which represents about $3 billion in annual sales. Importantly, we have a quite solid cash balance with almost $455 million at the end of last month. And so this strong financial position put us in a good position to execute and complete our phase III program, as we anticipate that our cash runway will go at least well into 2028. So why do we believe that we have a great value proposition here? You will see with the data that we have a potential best-in-class regimen with robust phase II results. As I said, 98% efficacy. We have a fixed-dose combination tablet that will be ready for the phase III and will be similar for commercial launch with large market opportunities and a patent life that is going until 2042.
Most importantly, we strongly believe that this regimen now, after this very positive phase II data, is de-risked. It's quite well known in the field of antiviral therapies that when you have robust phase II results, we have historically seen around 75%-80% probability of success in those phase III studies. We are very pleased with where we are with a fully de-risked program, and we look forward to initiating very rapidly this global phase III program. As you know, we have had direct-acting antiviral now for the past decade, and despite the presence of these DAA treatments, we still have really a significant global healthcare issue with HCV. For someone that has worked in HCV for most of my career, it's really humbling to see that you still have 50 million infected individuals worldwide, one million new infections annually, 250,000 deaths.
And really, in the U.S., we have reached a plateau in the treatment of HCV-infected patients, and this for about, as you can see, the last five years or so. We are very far to cover the new infections with about 160,000 newly reported annual infections. This is CDC numbers. We still have a pool of almost 4 million infected individuals. And so it's clear that these numbers underscore the need for new, differentiated, and optimized therapy. And let's not forget that, you know, we talk about oncology, liver cancer treatment. Let's not forget that 70% of liver cancer in the United States, in Japan, and the EU, actually are caused by this Hepatitis C infection that are going to progress over 15-20 years into fibrosis and cirrhosis. So this really large burden of untreated HCV disease translates, as you can see, in a large untapped commercial opportunity.
There are two product markets. There's no one in clinical development. So the treatment of about 90,000 patients in the United States every year leads to about $1.5 billion in net sales for a $3 billion global dollar market. So we believe that with a best-in-class profile of our regimen, with the anticipated removal of some of the barriers that we have seen so far with the payers, and hopefully that the government, and there is some consensus across the aisle, that we need to eradicate in the United States HCV infections. It's clear that with the availability, hopefully, of this new treatment, we are going to expand the number of patients cured from this severe viral disease. Ultimately, because a large proportion of these patients will, unfortunately, develop liver cancer, it will lead to healthcare cost saving.
As you can see here, through our third-party market research, an overwhelming majority of U.S., prescribers want improvements to current HCV treatments. About 20% of the patients are not compliant with DAA. This is what the healthcare prescribers are reporting. Either they don't complete the treatment or they are missing the doses. And you will see that actually in a few minutes, this substantial number was confirmed as well in our phase II study. It's clear that an ideal HCV treatment should provide high efficacy, short treatment duration, and something very important that we don't talk much is drug forgiveness. Because even with this non-adherence, you will see with our regimen, we are going to—we are showing in the high 90% of cure rate.
So in addition, prescribers prefer a direct-acting antiviral regimen with a low risk of drug-drug interaction, as these HCV patients today, in contrast to 10 years ago, are taking several concomitant medications. So in this slide now, what you can see is we believe that the regimen of bemnifosbuvir and ruzasvir—so bemnifosbuvir is the most potent HCV nucleotide and ruzasvir, which is a highly potent HCV NS5A inhibitor, which we license from Merck. You can see a very rational way here that this regimen has the potential for best-in-class profile. We are talking about short duration, eight weeks. This is about 90% of patients in the United States. The compensated cirrhosis numbers continue to decline according to the KOLs. And so it's essential that this regimen should have not only short duration, but also very limited drug-drug interaction, no food effect, obviously pangenotypic efficacy as well.
So in this slide, actually, that's really demonstrating the importance of this drug-drug interaction profile as compared to Mavyret and Epclusa. This, with 80% of HCV patients taking concomitant medication, and we are talking about commonly prescribed drugs. So oral contraceptives, statins, proton pump inhibitors. You can see that our regimen is the only one that is really clean for drug-drug interaction. We are still two ongoing phase I studies in more volunteers with statins and antiarrhythmics, but we feel pretty confident that these studies will also show that we have no drug-drug interaction with these medications. So let's move now to the phase II results, a little bit in more detail that we have reported in the top-line just a month ago, and as well as the design of what we anticipate will be our phase III program. So the phase II was a global study.
It was an open label with a single arm, 550 milligram and 180 milligram—I'm sorry, 550 milligram of bemnifosbuvir and 180 milligram of ruzasvir, this once daily for eight weeks. We enrolled about 275 patients, treatment naive patients, chronically infected with HCV, including patients with compensated cirrhosis. And this study with two efficacy populations. So the primary efficacy endpoint was in a per-protocol treatment in a per-protocol population, which had 213 patients, and also a secondary efficacy analysis evaluating the SVR12 in the same population, but including also the non-adherent patients. So that's had 256 patients that they likely will be the one we anticipate will be this efficacy evaluable population will be the one that will be the primary analysis in the phase III when we will compare on a head-to-head with an approved marketed drug.
You see that when we look at the total enrollment, 275, so we have about a 7% follow-up loss. This is quite high as compared to the data in phase III 10 years ago. That's basically to demonstrate that this is a difficult patient population younger today. The one that we are lost to follow up, obviously, is the one that we do not have SVR12 data, and so could not be analyzed. Also just a quick remark. It's interesting that regardless of the market research we do, and now with a robust phase II study, still we are around 20% of non-adherence as measured by pill counts and PK as well.
The next slide, you see the efficacy, the primary efficacy endpoint that where we show 98% in all the adherent patients after eight-week treatment, and 95% was achieved in patients regardless of treatment adherence. This patient population also included the cirrhotic patients where we had 88% SVR12. What is important to note here is that in these cirrhotic patients, on treatment, viral kinetics were definitely slower, but we could see 100% viral clearance at the end of the treatment after eight weeks. We feel very strongly that we are going to see very high rate as well within cirrhotic by extending the treatment duration to a 12-week study rather than eight-week.
Actually, when we analyze the data across genotype in non-cirrhotic, either treatment-adherent or non-adherent patients, you can see that out of 179 patients in the adherent patients, we only lost to one patient that did not succeed. So extremely high cure rate in non-cirrhotic patients. I'd like to remind you that this is 90% of the patient population in the United States and also in the five EU countries. In Japan, it's a little bit patients with disease that are more on the late stage. But for the team, what we are really impressed here is when we analyze patients that were also non-adherent, and especially with genotype III, which historically is the genotype that is more difficult to treat. I never seen with other DAA 100% success in genotype III, but most importantly is having a 98% regardless of adherence.
So again, we lost only one patient, even if we had still about 20% of non-adherence when we compare these genotype 3 patients. From a safety standpoint, the regimen was generally safe, well tolerated, no drug-related severe adverse event, no premature treatment discontinuation, no trend in adverse event or safety laboratory parameters as well. So we're really eager to interact with the regulators, especially with the FDA at the end of the month, so we can promptly advance to phase 3 development. It's quite well known that the HCV regulatory pathway is well defined. Clear guidelines have been published from the FDA and other regulators. We anticipate two open label phase 3 trials, one conducted in the U.S., and Canada, so in North America, and one outside North America.
We anticipate about 800 patients per trial with head-to-head, very likely against sofosbuvir and velpatasvir on eight weeks of our regimen, against 12 weeks in non-cirrhotic head-to-head, and 12 weeks for both regimens in cirrhotic patients. This will be a non-inferiority trial within two percentage points, and if one of the trials will have three percentage points, that we can also demonstrate superiority. We have a 90% power, so we feel that we have a very powerful study design, and we look forward, obviously, to see the feedback from the FDA, so let's now review data. There are new data from third-party market research supporting really the unique commercial market opportunity, so on this slide, we can see the highly positive reaction to our regimen from the U.S., prescribers. About 90% of these U.S. ,prescribers were very positive to the profile of bemnifosbuvir and ruzasvir, and this across specialties.
As you can see, basically, those are the four major specialties we prescribe DAA. Also, please note that this U.S. HCV prescriber base is highly concentrated. Only about 6,000 prescribers write 80% of direct-acting antivirals for the treatment of hepatitis C. So we're seeing that this will really make it optimal for efficient commercialization. Now, from a payer standpoint, the profile also was extremely well received. You can see that our market research actually covered payers that are covering 130 million lives in the United States, and their feedback was this profile was either superior or comparable to Epclusa and Mavyret, and definitely they foresee to include in the formulary, obviously, if approved. So we believe that our regimen should achieve a substantial market share.
Based on what we have seen with third entrants in highly entrenched class, but with a differentiated and best-in-class profile, you can see that actually they have been very successful in achieving market share between 35% and 40%. And this is basically what we anticipate with our regimen. So in closing, we believe that this regimen of bemnifosbuvir and ruzasvir has the potential to be a best-in-class profile for the treatment of hepatitis C if approved, and provide an opportunity to become the most prescribed treatment in the large multi-billion-dollar market. We offer potency, convenience, short-term duration, limited drug-drug interaction, no food effect, and I'd like to remind also drug forgiveness, because this is the type of drug today that you combine really exceptional drug potency and allowing a very significant drug forgiveness.
So we believe that this profile will provide a significant opportunity to address those large burden of untreated HCV disease. And if approved, we believe that this regimen will disrupt the global HCV market today at $3 billion annual net sales. Thank you, and look forward to addressing any questions you may have, Eric.
Thanks for the presentation. Yeah, maybe you have some time for questions. I just want to pick up on just sort of the remaining or the level of unmet need that remains, right, in the treatment of HCV. Aside from the treatment course or pill burden, what really, at the end of the day, comes down to sort of the challenge of achieving high compliance? What hurdles are there for patients?
It's really the drug potency that makes the difference. Our differentiation is really we are 10, 20, 30-fold more potent than the nucleotide that is part of the Epclusa regimen. We see that the adherence will decrease over time in the treatment duration. So the first months, very good adherence. That's why with a very potent regimen, really, you maximize the drug forgiveness and achieve those 98%-99%, even if you don't have basically missing doses, not completing treatment duration, and that's what we see from the prescriber. And by the way, talking to the prescriber in this third-party market research, the feedback is that the most they see is in the early 90% and not in the really high 90s as we see in our study.
Just, you also kind of cited the rate of new infections. I think about a million per year. It's been quite a rise recently. What factors do you think contribute to this reinfection or not reinfection, but new infection rate? To what extent are some part of those repeat infections in review? And I guess within all of that, I guess, is there any concentration or geographical localization to those cases?
Sure. Arantxa, you want to address the question?
Yes. It's both patients that were not treated before that continue spreading the virus. And then there is a certain proportion of patients that get reinfected because you don't build immunity, so you can get reinfected multiple times. And that is a little bit harder to evaluate, but it could be around 10%-20%.
Okay. Are there any genotypic activity gaps among the current standard of care regimens that would be addressed with bemnifosbuvir and ruzasvir?
You see it's the genotype 3. And even actually, we have some genotype 3B in this study, and they were 100% cured. So that's, again, it's the potency of this regimen. And the failure that we have had in the cirrhotic, actually, mostly in genotype 1, we didn't see much failure in genotype 3 cirrhotic, but we anticipate that we will get also in the 97-98%, regardless of the difference in those patients. And so GT3, we believe, the genotype that this regimen will be really very effective as compared to. It's not that the other ones are not. They are still around 94-95%, but we think that we can do better than that.
Can you talk about the adherence rate in your phase II study and sort of the pattern of where there may have been sort of gaps in compliance? I guess, was there non-adherence? How to put this eloquently, I'm not sure. I guess, did you have sort of oscillating use of drug, right? Or did patients sort of just fall off of usage and not come back to study?
You know the details of this.
Yes. Well, it's a little bit of both, but there is a clear trend that, and this is for all the antivirals and antibiotics, you start very strong, and then after a month or six weeks, you start forgetting, because a lot of these patients think that they're better, and they just have a hard time adhering to medication. So there is that trend of forgetting more and more towards the last couple of weeks. And then there is also a component of patients that take it for a couple of weeks, then they forget a few doses, and then they restart, particularly if they go back to the clinic and see the doctor. So it's what we see with all the antivirals and with any antiviral or any antibiotic.
The more potent the antiviral or antibiotic, and the sooner you can drive down the viral load, the better, because then it doesn't matter if you don't finish the last couple of weeks. That's why potency is very important.
I mean, in some sense, this adherence is almost like a function of the treatment course, right, that you lay out in the protocol, I would think, right? Just given the potency that you're observing in the high SVR rates, as you look to a pivotal study, what about, I mean, what kind of weight do you give to considering a shorter treatment interval, something shorter than eight weeks to sort of drive adherence rate?
Well, again, as you know, the patients will get basically a one-month supply. So at the end of the day, that you have six weeks or eight weeks doesn't matter. Maybe you want to report your interaction with the KOL also, suggesting that they don't see any difference between six weeks and eight weeks in terms of the value of the regimen.
In terms of pressure. Yeah. I mean, it's basically the same. And if you go to eight weeks, you'll capture almost everybody, as you've seen, like 100%. So why would you want to risk for a couple of weeks to lose a couple? It's just not that kind of six versus eight didn't seem to have enough value for us to really even push further.
We will have a presentation at CROI, a collaboration that we did with Alan Perelson, who is the guru on viral kinetics, and he has done with the other treatment, and showing that actually within 17 days, we cleared 99%, 99.99%, if I recall, of all the HCV-infected cells, and we know that to clear the last percent, you need four weeks, and this is also a very well-known parameter, so six weeks, you'll be borderline. Yeah, you will treat probably, I would say, 90% of the patients.
Oh, yeah, for sure.
But that's not what we want. What we want is to treat and cure 99% of the patients. And as you have seen, and I think that that's what the key KOL in the U.S. are very excited in this regimen since they will participate. This is after five years, this is the first time that Arantxa told me that she should enroll very fast in the U.S.
They are very excited.
In this trial.
Yeah.
That's why they are very excited, and because they see that this could be really transformational.
Can you talk a little bit about sort of, yeah, talk about cost associated with running a phase II trial?
I'm sorry?
The cost.
Cost.
Cost of the phase III.
For the phase III?
Yes.
Our CFO is going to be upset on me, but I said around $200 million. So we definitely have the cash balance to cover that and to execute. Again, we have a global COO that has helped us tremendously with our COVID program, enrolling ahead of schedule. We have already about 150 clinical sites in the U.S. About 150 have been identified outside. We have how many countries, Arantxa? About 30 countries or so?
Yeah, between 20 to 25 or so, yeah.
So we think that we are going to really accelerate that. And as I said, we have seen from both the prescriber and the physician that participate in the phase II, they are very excited, eager to participate in this phase III, especially in the United States.
How.
And by the way, we said so like this, we can discuss. We have had already in the U.S., a central IRB approval, right, Arantxa?
Yes, with a draft protocol, because we're, of course, waiting for the FDA to bless our approach, yeah.
Okay. Okay, great. And just thinking about, I guess there's additional data from the phase II study in the first half of this year. Is that still planned, the full 24-week post-treatment phase? I guess what incremental, I guess from that readout, how does that sort of incrementally inform?
No, that readout doesn't really have any regulatory value, because this is just something that historically used to be done, so we are still collecting it. But the value of the presentation is to give all the detail that we're going to be showing with the resistance and the safety and everything else that will go into the presentation.
Okay. All right. Great. Great. Looking forward to that. I think we'll leave it here for time. So thanks very much, JP.
Thank you, Eric.
We appreciate everybody for attending.