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, J.P. Sommadossi, Founder, Chairman, and CEO.
Hello, everyone. Janet Hammond, I'm Chief Development Officer.
I'm John Vavricka, Head of Commercial Operations.
I am Arantxa Horga, I'm the Chief Medical Officer.
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. We are, obviously, very excited to have a non-inferiority statistical significance with the current standard of care with EPCLUSA. We believe that we have a best-in-class regimen with a short duration. What's important, obviously, in that phase III, which was performed in North America, predominantly in the U.S., and let's not forget that we were comparing an eight week treatment against a 12-week treatment for EPCLUSA in non-cirrhotic patients, which represent about 90% of the patients in the U.S. We performed very well from an efficacy and safety standpoint.
We look forward to have our ex-U.S. trial, C-FORWARD, 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. This second trial will allow us to support the first trial, but also to expand the robustness of the number of patients with genotype 1c, mostly in Western Europe, genotypes three, four, five, and six, which are the rare genotype. A label is essential today, as no one is doing genotyping before treatment. We have also a second program where we are very excited with hepatitis C. We are 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 C. 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. Again, thank you for allowing us to share those updates. The team, Janet, John, and Arantxa can go in 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?
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 eight week regimen as compared to the standard of care, which was a 12-week regimen. This is with the attributes of what people are expecting today in the hepatitis C landscape. That's a short treatment duration, low probability of drug interactions, no full effect, and we saw a good tolerability profile. 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. It's a trial that, as JP said, is running ex-U.S. in multiple countries, over 17 countries, and it has a broad global population and also viral genetic diversity with different genotypes, as J.P. mentioned.
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 two 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. This makes it very likely to reproduce what we saw in C-BEYOND. Also, the strength of C-FORWARD is that we are going to be seeing the primary endpoint in two populations, like we see in C-BEYOND, in the population, which is the MITT population, so that's everybody that received one 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 EMA. We think that in that way, because we met both in C-BEYOND, we have a lot of confidence that we're going to be seeing the same results in C-FORWARD.
Okay. Strong efficacy, clean safety profile. Maybe if we can just drill down a bit more on C-FORWARD. It includes a broader geographic and genotype mix than C-BEYOND, which you've noted. How could these population differences affect the results?
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. We already have experience in vitro that we are pangenotypic, we can treat all genotypes the same. Further, we also saw pangenotypic 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 three, which is the hardest to treat genotype. There we had efficacy rates of 100%, if you took the population that was compliant with the drug.
C-FORWARD is enriched for genotype three, and that should translate into very strong efficacy as well. That's it 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 U.S. We had to do, obviously, a clinical trial in the U.S. because that's a big medical need, but the population in C-BEYOND in the U.S. had a lot of issues and challenges. For example, more than half of them had a history of IV drug use, they had a history of, or they had actually concomitant medication use. 89% of them had concomitant medication use. They had psychiatry disorders.
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. That was a very challenging population for us to do a very rigorous test in the U.S. But C-FORWARD has a population that is easier in that sense, with less of those challenges. That should decrease the noise, the statistical noise in the trial, and the data has less variability because you don't have all that noise. That should really be able to help us highlighting our unique profile.
Okay, that's great. 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 non-inferiority?
That's a great question. I think that we powered these trials for non-inferiority. I want to remind you, non-inferiority, so the efficacy is matched with EPCLUSA, but we do it in eight weeks. In order to power for non-inferiority, we needed almost 1,000 patients per trial, which is pretty big for a phase III program. The cure rates are around 94%, 95%. To demonstrate statistical superiority above 95% cure, you will need thousands of patients, and that is really not realistic in a phase III program. Our goal is really not so much to demonstrate incremental 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 a short regimen, which is very important for patients because they really have a hard time even making it to eight weeks, much worse to 12. 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. Looking forward, 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 two approved therapies, what really resonates with physicians? Janet?
From a regulatory perspective, as J.P. mentioned, we are aiming to file the NDA mid-next year, and we are already actively preparing for that regulatory submission with drafting documents, drafting the label, and discussing things with physicians. I think what we have 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 are looking for above all else. 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 pangenotypic. We do not have a protease inhibitor, which helps, and the regimen obviously needs to be safe and well-tolerated.
Yeah.
All of that we are able to demonstrate. We are 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.
Just to add that we are preparing, as you know, Max, we will need just to complete the package for the EMA. It is closely similar, but actually they request some additional environmental and other packages that we are preparing, and we anticipate to file with the EMA end of 2027, about six months after we will have filed with the FDA.
Okay. Could we talk about potential label scenarios? How should we be framing expectations?
Jan.
I think our expectations are that the label should reflect that the regimen is an eight week regimen for non-cirrhotic patients, 12 weeks for patients with cirrhosis. There are minimal DDIs. The safety and tolerability are generally excellent, and we are looking for a pangenotypic 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 regimen?
John.
Right now, we haven't released anything on pricing, but we plan to be competitive within the pricing regimen, closely matching to what the two competitors currently are.
Okay. But I think a question for myself is just understanding the broader market. 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. We have 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 have so elegantly described, they showed great preference. Matter of fact, over 80% said they would be interested in writing it, and in fact, 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 is very potent, less likely to cause drug-drug interactions, and to be the shortest possible course of therapy. From that perspective, that is how we are 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. 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 is when they are 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.
It kind of explains why you may have 160,000 new patients each year diagnosed, but only half of them are being treated. 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 is 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. We are really confident that as the U.S. moves towards the test-and-treat model, our drug will really have the best profile for that.
Could you talk about the incidence population or the prevalence population, both in the United States and then Europe?
Well, for the U.S., what I can tell you is just some general numbers. It is estimated that you have roughly 4 million people that are infected in the United States. That number continues to grow. It is estimated, as I said, around 160,000 new chronic infections each year, with only half of them being treated. 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 are not treated. 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.
How should we think about the cirrhotic versus non-cirrhotic patients?
Well, I will let my colleagues talk about that, but from a commercial perspective, by far, the majority in the United States, they are a typical average type patient, and they are non-cirrhotic patients.
I think that what I would like to add also is, and that is why the C-FORWARD will be very important. As you probably know, Max, compensated cirrhosis genotype three are the most difficult patient to treat. We are excited with our regimen. We are also evaluating patients with resistant mutation. 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 will have a pretty good idea how we compete in term of those cirrhotic GT3 against EPCLUSA. MAVYRET physician do not like to put compensated patients on MAVYRET for many reasons, in term of the presence of protease inhibitor. We believe that that also will be one of the major advantage of our regimen.
When could we get an update around that?
When we will have the C-FORWARD data, very likely we can disclose that C-FORWARD almost 50% of the C-FORWARD patient are genotype three, with a lot of C-FORWARD genotype three.
Okay. That's helpful. And maybe if you can just walk us through, specifically in the U.S., 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.
Jan.
Potential sales force.
You want to do?
Yeah.
Oh.
Yeah.
John.
We're fortunate coming to market, being third to market 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 wealth of data in which you can mine. 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. That'll be done closer to launch, but we've already laid the groundwork for what we need to do.
Okay. Can you just discuss the competitive landscape in regards to the two regimens that are approved? How are sales going there, and how do you expect to, I would say, take market share?
Well, the product, it's over $1 billion in the U.S., and you have some fluctuations up and down within the quarters. It's interesting, you have an eight week regimen, you have a 12-week regimen. They roughly have 50/50 market share. The two 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 pharma, hypertension, and other types of retail products. They usually generally equalize around 30% 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 that 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. 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?
Yeah. As I said, traditionally it has been that a patient is diagnosed, it may be months before they actually get treatment. They are doing a lot to minimize that. They are not requiring genotyping anymore. Different scans are not required. But still, it is multiple visits to get those patients back. When you talk to most KOLs, that is what they say explains the fact you are only treating 50% of those that are diagnosed. With the test-and-treat, it is relatively straightforward where these centers are able to diagnose them and to treat them on the spot. They feel that you will get many more of those patients treated that have been diagnosed. It is 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 do not think it is eminent this year or next year, but I think within the first five years, you are likely to see some sort of federal initiative to address this ongoing problem. What they are at least appearing to, both right now, both sides are looking at a test-and-treat model.
Okay. In regards to potential strategic partners, what are your plans for ex-U.S.?
We will partner ex-U.S.
Whether it will be a sole partner or will be multiple partners, we have already interested parties. The only major market where we are not going to file with regulatory authority is Japan. We have some interest there, in term of partnership, with this company. We have two 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 on 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, U.K., Canada. We look forward to have a significant, I would say, return on ex-U.S. territories as well.
Okay. That's helpful. Then over the next 6- 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?
Oh, 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 term of drug exposure and safety. We are going to go into multiple ascending dose now, and end of the year will be completed and going to proof of concept. Obviously, the brunt will be our hepatitis C program. We felt that we want to have the two phase III completed to allow us to hopefully publish in a top journal, the two phase III at the same time. 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. I am 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 is a candidate that we have discovered internally. I think with the number of organ transplant increasing constantly in the U.S. and Europe, about 3% of those immunosuppressed individuals are at risk of hepatitis C, that if infected, they can develop cirrhosis within three to five years. We have only ribavirin. Ribavirin is an old antiviral drug that has a major toxicity, as you know. It is used basically all the time when you do not have anything else. 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 lifelong threatening actually infectious disease. We are very excited.
Janet, you can share where we stand in terms of phase I, what we have done so far and what we foresee to go to a proof of concept as well.
We are currently in phase I in healthy volunteers, looking at single and multiple ascending doses. This study, I think, is the threshold for us taking the program forward. What we are seeing so far is very pleasing safety and tolerability. Also, what we are 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 have seen from the preclinical model. To date, that is what we are seeing, and we look forward to taking the program forward, but obviously with a disciplined approach in terms of prioritizing high-value activities as we prioritize the HCV launch coming up, too.
Great. Maybe if we can just touch on the current financial position, how you are thinking about cash runway, et cetera.
Look, end of June, we had almost $220 million on our balance sheet. We have sufficient runway until end of 2027, early 2028. We are going to be opportunistic, as I said. We definitely will have a partnership ex U.S. where we will have a significant upfront as well. We will be opportunistic. We want to make sure that we will have a solid balance sheet for the launch in mid-2028. Based our forecast, we will be very rapidly profitable here. I think we shared before, low cost of goods with the deal we have, the licensing deal with Merck. We basically have a pretty high margin on our regimen. 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 is always, to me, exciting to have new drugs on board. We have seen the best view feedback we can get from both patients that were involved in our clinical trials and investigators, DSMB, is that we involve over 1,000 patients per trial in eight months. That tells you that there is a major appetite for a new regimen. The other two, okay, they cure a patient, which is great, but it is astounding that 10 years ago, we had 2.5 million infected individuals in the United States. We have 4 million today. Something is not working here. That is 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 5-10 years.
So, that's what's exciting to us. The second program is exciting to us as well. Look, we can never predict, but we think that we have tremendously de-risked our programs, so we look forward to launch those two products as soon as possible to all the patients and investigators.
Okay, then one macro question, if you.
Yep.
If you 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, anti-viral from China. We are working extensively with some Chinese colleagues in cloning, 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 Chinese research organizations and labs. But from the innovation standpoint, we have not seen much in our field, to be honest with you.
Okay. 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.