Great. Hi, everyone. Thanks so much for joining us here today. My name is Hannah Adeoye, and I'm an Associate Biotech Analyst here at J.P. Morgan. Our next presenting company is Atea Pharmaceuticals, and presenting on the behalf of the company is CEO, JP Sommadossi, and some other members of the management team. Just want to say we're gonna be doing Q&A in the room after the presentation. There should be some mic runners around the room. For those who wanna ask questions, simply raise your hand and we'll get you a microphone. If you are listening online or you wanna ask a question online, you can also ask via the conference digital conference book. With that, I'm gonna hand it off. Thank you, JP.
Thank you so much. Before I begin, I would like to thank J.P. Morgan for the opportunity to present today and give you the latest developments at Atea Pharmaceuticals. Before I go further in the presentation, this slide shows a standard forward-looking statement and further information can be found in our most recent regulatory filings. Since the founding of Atea, our vision has not changed and has been centered on the discovery, development, and commercialization of antiviral drugs for severe viral infections where there is a significant unmet medical need or where we can make a huge difference. Following a year of solid execution across all three clinical program, we enter the new year in a position of strength. As you can see, with a pivotal year, which is really milestone reach for 2023.
For our COVID-19 program, we expect to complete the enrollment at the end of the year. Before that, actually, we will have an interim analysis in the second half after the enrollment of about 60% of the monotherapy arm. I'm going to go over the details of our study design for this SUNRISE-3. We expect to file an IND/CTA around the end of the year with our second-generation protease inhibitor discovered in-house, for which we foresee to develop for combination therapy with bemnifosbuvir in 2024 and beyond. For our dengue program, we anticipate proof of concept, clinical result this quarter actually, which is evaluating the impact of AT-752 on dengue virus infections. These results will tell us how we are going to advance the clinical program.
Finally, for our HCV program, we are very excited, after a hold due to the pandemic to reinitiate this very promising combination therapy of two very potent drug, bemnifosbuvir and ribavirin, in phase II. We're past phase II. We have started regulatory submissions, and we anticipate first patient will be dosed next quarter with the initial result of the leading cohort, and I'm going to go over a little bit later on the study design also about this robust phase II with initial results around the end of the year as well. Atea has a very experienced management team, scientific team with a proven track record of success in the field of antiviral drug discovery, clinical development, and commercialization. Along this deep pipeline, as you can see in this slide, our goal is to become a leading antiviral company.
Importantly, and especially in these days, we are very well capitalized to fund our robust mid-to-late stage clinical programs through key inflection points and beyond, and with a cash runway, we believe through at least 2025. Let's go now about the detail of the update on the COVID-19 program, including our global SUNRISE-3 trial. Our COVID-19 strategy is really focused on the current highest unmet medical needs. We are targeting the most vulnerable patient population who are the greatest risk for disease progression to severe COVID or mortality and where there is only very few options. Currently, as you may know, vaccine and therapies have some key limitations, including waning immunity. We see failure in certain patient population to mount immune response to vaccine. The monoclonal antibodies are no longer effective, especially with the new surveillance, the XBB.1.5 point.
We know the limitations of oral authorized antiviral as well. As a monotherapy, we believe that bemnifosbuvir profile fulfill an unmet need for safe-well tolerated and easily prescribed oral antiviral for COVID-19. This profile should enable us to have bemnifosbuvir as a cornerstone therapy for both monotherapy and combination therapy. You will see this is why we have a very unique study design for the phase III SUNRISE 3 that I'm going to go over in a few minutes. Indeed, there's already. We are going to study this combination therapy approach. We are the first one to do so in SUNRISE 3. Data from that trial will inform us how we are going to develop for some specific patient population which unable to mount an immune response.
Obviously, we are thinking about immunosuppressed patients where you can have viral replication actually for weeks and even months, and that's where our variants and sub-variants actually are being produced as well around the world. Our combination strategy include the development of a second generation protease inhibitors at Atea. We have already shown additive benefits with bemnifosbuvir and other protease inhibitors. Really the rationale for developing the PI is really to have a major impact in immunosuppressed patient or where there is basically a very weak immune response.
As I'm sure you read in the news or see on TV, it's clear that what we have today is a pandemic of the elderly with very high rate of hospitalization and death in that patient population. This is the patient population that actually is targeted in our phase III SUNRISE 3. Let's not forget that COVID-19 still today is the third leading cause of death in the United States after heart disease and cancer, with the majority obviously in 65 years old and older. This is the first time, just put in perspective, this is the first time in 100 years that the life expectancy has decreased in this country. We have 300 to 400 deaths every day due to COVID-19.
So far in the United States, almost 280,000 individuals have died in 2022 because of COVID-19. It's essentially is like if you have a jumbo jet crashing every day in the United States. Doesn't make headline anymore today? It would do if it was a jumbo jet crashing every day. This is what we have to think about and what we are confronted there. Are we going to basically, let COVID-19 continue? Because it's going to continue, it doesn't go anywhere, for the next 10 years and beyond, until there's going to be a vaccine that will prevent transmission. The technology is not even available today. In SUNRISE 3, we are going to enroll, elderly regardless of vaccination status, so 80 years old, regardless of morbidity or comorbidities.
65 years old with at least one major risk factor such as diabetes or obesity. Anyone above 18 years old are immunocompromised. Just to put in perspective, you have as many as 20% of immunocompromised patient hospitalized today because of COVID-19, and at risk of death with very limited options for treatment. Where, as I'm showing, I'm going to show in a few minutes, PAXLOVID is mostly contraindicated in those individuals. Let's review now our SUNRISE-3, which is a phase III registrational trial in mild to moderate COVID-19, but is an enriched, high-risk patient population. This is a randomized double-blind, placebo-controlled, assessing bemnifosbuvir or placebo administered along with the local standard of care.
That mean that you have a add-on with bemnifosbuvir or placebo to the local standard of care. We expect to enroll about 1,500 patients. High risk, as I have indicated, regardless of vaccination status, symptom onset less than five days before randomizations. We anticipate, as you can see here, a very large footprint, global footprint, with 25 countries, about 300 clinical sites. We are already enrolling in the United States, and submitting application where we get very good actually feedback with some already being approved by regulatory authorities around the world. We will initiate very soon Enrolment in Europe, Japan, Latin America, Africa, North Africa, Australia, you can see a very large footprint.
Those patients will be randomized one to one, either to 550 mg BID of bemnifosbuvir or placebo. Twice daily for five days. That's where it's very unique for a phase III for COVID. We believe that we are really the first one, that the FDA has basically endorsed this study due to the significant unmet medical need in this very high-risk COVID-19 outpatients. We have two studies, two cohort, I'm sorry, derived from the type of standard of care that is going to be used locally. A supportive care patient population, which is a monotherapy. And that monotherapy will be the primary analysis of the phase III .
The second cohort, which will be a combination antiviral population, which will be comprised that patients that are going to receive compatible antivirals as the local standard care, such as PAXLOVID or molnupiravir, as part of their basically local treatment. We have two cohorts. The primary endpoint will be all-cause of hospitalization or death so day 29. We anticipate at least 1,300 patients will be in the supportive care population. This, we are targeting a 4%- 6% hospitalization rate to have a sufficient statistical power to differentiate, obviously, the treatment against placebo.
As I have mentioned at the beginning of my presentation, we will have an interim analysis second half, when 60% of the supportive care population will have been enrolled, with an independent DSMB. Ongoing development work for bemnifosbuvir and including also the development of second generation tablet. We are very proud of this accomplishment in 2022. Because as you can see here, the second generation achieved much higher plasma drug concentration, also a higher trough, which obviously are essential for the efficacy of the drug, without any food effect, regardless of fat content. We try both with low and high fat content. This in contrast to the first generation of formulation, which was used, you know, for phase III Morning Sky study.
I like to remind you that in that study, we had an endpoint with hospitalization, and that endpoint showed actually a 71% decrease of hospitalization, even with the first generation. Actually, when we analyze patients above 40 years old, that rate increased even up to 82%. Obviously with this improved formulation, we feel even more confident in the potential of bemnifosbuvir for the treatment of COVID-19. I'm sure you see every day in the news, we have new variants globally that continue to spread.
hat bemnifosbuvir will remain fully active against future variants and subvariants, as we have shown here with all the strains that have been reported as a concern, including all the Omicron subvariants. Where you see that basically the EC90, so this is the concentration in vitro, which inhibit 90% of viral replication, it remain essentially the same. This consistent potent antiviral activity really bodes well with what we believe is going to be a drug that basically is going to be efficacious regardless of the future variants that we are going to have. Let's now review the commercial opportunity. The projected annual COVID-19 oral antiviral, you can see a demand, will be between $8 billion and $16 billion.
This is basically based on IQVIA retail prescription, mostly in the United States. Beyond that, we believe that there is definitely an opportunity to expand that market by prescribing for patients when PAXLOVID drug-drug interaction with mostly with DDI are a concern. You can see the millions of individuals here in the United StatesWere basically the drug-drug interaction issue is a major concern. They were mostly the PAXLOVID or use is contraindicated. We are talking, as I mentioned before, the immunosuppressive drugs, but also elderly, who is not on anticoagulant, who is not statin, you can stop for five days for sure. You can see that the calcium blockers for hypertension and other definitely an issue with PAXLOVID.
Putting in perspective, over the next 10 years, we believe that this is going to remain the largest antiviral, oral antiviral market that we are going to have. A huge opportunity with very few product that, as I have mentioned, are definitely key limitations. We anticipate that definitely in 2023, there's going to be a transition in the U.S. to a payer market. You're going to have a transition to Medicare, Medicaid, and then private insurers. What are they going to look? They are going to look for the economic burden of COVID-19, that mean the hospitalization cost. The hospitalization cost, what CMS has reported as an average cost for hospitalization is around $22,000.
You can see that, with a $13 billion total expenses from Medicare, with 70% of those hospitalization are actually Medicare patients, we are going to need real drug, real oral antiviral that are going to be safe, convenient, and obviously efficacious. This will clearly oral antiviral provide a clinically and cost-effective solution. It is a position that has been shared by drug research organization like ISO and ASB. Now let's move on our dengue program. The AT-752 that we have in the clinic, both as a treatment and a prophylaxis. Actually, we receive a Fast Track designation by the U.S. FDA for treatment of dengue.
As you may know, it is the most prevalent mosquito-borne viral disease that affect about 400 million individuals every year. It is endemic in 100 countries, about half of the world population. We're talking about 4 billion individuals are at risk for dengue. There is no approved treatment options, and we are real pioneers here in terms of both treatment and prophylaxis. AT-752 is a purine nucleotide prodrug from our platform. It has shown potent in vitro activity against all serotype. There is five serotypes of dengue. Actually, we have also shown its potency and efficacy in a small animal model, which is basically well-recognized.
as an update to DEFEND-2, we have completed enrollment of the first cohort with 21 patient. This, just to remind you, it's a randomized double-blind placebo control conducted in dengue endemic countries. We are assessing the antiviral activity with viral load, safety, and PK, and this after oral administration of AT-752 at 750 mg TID or placebo, obviously, for five days. We have also completed the human challenge infection model at a single site in the United States, in a academic setting. The study basically evaluate the effect of AT-752 or placebo.
The way it is conducted, the healthy volunteer receive the first day AT-752 on 750 mg at TID, and then receive the next day, an attenuated live virus of dengue type 1. The administration of AT-752 is continued at 750 mg TID for the next 14 days. As part of the development, we wanted to know, are we going to achieve with the 750 mg TID sufficient levels of the active metabolite?
I remind you that this drug need to be activated inside the cell to an active metabolite, which is a triphosphate, and the triphosphate is going to basically shut down the RNA viral replication by being like a monkey wrench and causing what we call chain termination. Do we achieve in patients, what we hope a really good level of this active metabolite, interfering with the replication. Obviously, you want to see that it's going to achieve at the target site where you have viral replication, and that's occurring in peripheral blood mononuclear cells. Actually we do. As you can see, 750 mg TID, which are the dosing regimens that were used in both studies, achieve rapidly the highest levels.
Of interest, even with the BID, we could achieve actually comparable levels at steady state. That introduced some flexibility to us, especially for the prophylactic program, where we can move from a TID to a BID. We look forward to report the proof of concept results in this quarter. Obviously, we are encouraged with the potential of AT-752 with this data. Moving now to the commercial opportunity. As I have mentioned, there is no approved treatment for dengue. There is a significant unmet medical need. As you see, the annual global economic burden is $8 billion-$9 billion.
We foresee that there is essentially two major market, a treatment in the endemic countries, and most importantly for the U.S., a very robust U.S. travel market. Just to put in perspective, you know that there is no malaria in the United States, but actually 600,000 prescription of Malarone were prescribed in the U.S. as prevention, as a prophylactic before the pandemic. Those numbers actually are getting back quite nicely recently. A very significant opportunity for dengue. Now let's review our third program in the clinic, hepatitis C, which we believe has the potential to become a best-in-class combination.
We look very promising, with belief that it has the potential to improve the current standard of care. As you can see, with a convenient and short duration protease inhibitor-free treatment. We have also the potential for the first ribavirin-free therapy for decompensated liver disease. This is a very advanced stage of liver disease. We have submitted already the regulatory form for the phase II study, we anticipate patient enrollment, as I have indicated, next quarter. Let's review now the study design for this robust phase II. Total of 280 infected individual with HCV, including compensated cirrhosis. These are enrolling naive patients, I want to call direct-acting antiviral naive, all genotypes are assigned.
We have a leading cohort of 60 patients, and we anticipate to report the result of that cohort before the end of the year. This is an administration of 550 mg QD of bemnifosbuvir in combination with 180 mg QD of ribavirin, and this for eight weeks of treatments. The primary endpoint is standard, as I'm sure you know very well and accepted by all regulatory authorities around the world, with safety and obviously importantly, sustained virologic response at week 12. We also are going to evaluate other endpoints such as virologic failure resistance and also SVR at week 24. The market is very large, growing with net sales globally around $4 billion, 50% in the United States.
You see that despite the availability of two combination treatment, the incidence in the U.S. with new infection actually exceeds the cure with antivirals. This is really with the opioid crisis, with the IV drug abusers. That's why you need short duration, you need convenient, no food effect, no interaction with methadone substitute, for example. That's one of the issue with protease inhibitors, including in the combination. We believe that with our combination of riesgasvir and bemnifosbuvir, we have really the potential to capitalize on this significant and growing market. In closing, we have a really exciting pivotal year ahead of us with a number of infection points.
You can see clinical, well-defined endpoints across each of our three clinical program with obviously the late stage of phase III. It's always exciting to be in phase III with COVID-19 and really with a drug that we believe really fulfill the need and cover the really the major unmet medical needs. We are well-capitalized to achieve these milestones throughout the year and beyond. I would like to take this opportunity to thank our talented and dedicated team that they're really working tirelessly in order to really lay the foundation for a successful 2023. Again, thank you very much to J.P. Morgan for hosting us today, and continued interest and support our mission to transform really the treatment of severe viral diseases. Thank you.
Okay, great. Okay, just checking. Yeah, thank you so much, JP, for the presentation. As mics get positioned, I can start with the first few questions. Starting off with just your bemnifosbuvir program and COVID-19. Just wondering if you could talk a little bit about your expectations for enrollment cadence with the SUNRISE trial. Just are there any regions with slower or faster pace of COVID transmission that you would expect faster enrollment?
Yeah.
How quickly do you think you could monitor COVID transmission and adapt trial sites to more quickly enroll the trial?
I have with us today, our colleague, Janet Hammond, who is our Chief Development Officer, and she will address that question and maybe some other questions as well. Go ahead, Janet.
Thank you, Hannah. We're very pleased with the progress that we're making with our trial. We have an extensive footprint, I think as JP mentioned, with sites in 25 countries, 300 sites all in all that we anticipate having up and running. We're in the process of getting countries on board. It takes a little time, you know, at the beginning of a trial, to go through all of the regulatory processes that are necessary for countries to approve protocols and get sites activated. We're still ramping up in some areas. I think as you know, we see wave upon wave of COVID. Once the sites are up and running, they should be there and ready to receive as patients come through.
I think we've all been caught a little by surprise by what's happened in China. I don't think we'll be ready to enroll patients in China anytime soon, particularly with hospitalization being our primary endpoint. Obviously we want the endpoint to be a robust one and for there to be fairly normal conditions when patients are hospitalized rather than what is a rather extreme situation, unfortunately. As things evolve there too, we hope that it may be possible even to have sites there and really to capture patients around the world as they fall sick.
Okay, great. Early in the pandemic, we were seeing some pretty large variances in placebo performance in COVID trials due to differences in standard of care and differences in treatment experience with the virus across regions. You mentioned the power, the study's power, assuming a 4%-6% placebo rate, right?
Yes.
Yeah. Wondering if from your research, that's a normal assumption across regions, or do you think there might be some variance across.
Janet?
the study?
I think there are a lot of variabilities with COVID. I think, I mean, I think there's been great variability in terms of the pathogenicity of the variants, obviously the immunity of the population, the extent to which patients are vaccinated, and then obviously the underlying immune susceptibility of different subgroups of patients. I think all of those things continue to factor into what we're going to see. In areas such as the U.S., where the patient population is actually relatively highly vaccinated, hospitalization rates are being reported as being around 1% or less. I think as unfortunately the immunogenicity of the vaccine wanes, so we're likely to see those numbers rise, but potentially.
Also I think as new variants come along and elude the immune response which has been generated by vaccines and by prior infections. I think overall a rate of 4% to 6% in the placebo group might be considered quite high. When you look at the group of patients that we're anticipating enrolling in our trial, we think it's actually an achievable number, and not unrealistic. That's really because the patient population that we're going after is so highly vulnerable, and unlikely to mount a good immune response. It's difficult to get accurate numbers from the literature. As you mentioned, there is this ongoing variability, so you never really get to a point where you feel that this is a consistent number.
Certainly in, highly immunocompromised transplant patients, last year in 2022 in Holland with Omicron, they were able to show that approximately 20% of patients, who in a center, who had been vaccinated and boosted were actually hospitalized with Omicron infection. I think the number in the patient population that we're going after is higher than in the average patient population, which is why we think that our study isn't unrealistically designed.
Okay, great. Thank you. You have an interim analysis built into the study. Just wanted to understand what some of the key decisions that are going to be made on the other side of that interim analysis are. Would you seek to maybe file with that data, or would you seek to fully enroll the study?
Janet?
Thank you. The idea with the interim analysis is to look particularly at the monotherapy group of patients in the study, so those who are receiving either bemnifosbuvir alone or placebo alone, 'cause that is the primary endpoint of the population. We're aiming to have an independent group of people analyze our data for us when we achieve 60% enrollment in that group of patients. The idea there would be that there would really essentially be three outcomes.
Either they could say to us that the hospitalization rate is lower than we're anticipating and the study is actually futile, or that we are in good shape and should continue to complete the study, or that we might need to upsize the number of patients in order to achieve the endpoint, which is, yes, within our sights, but our sample size is not quite suitable for that. I think it's possible if Emergency Use Authorization exist, and in the best case scenario, that we might be able to file an EUA off the interim analysis if we're seeing really encouraging results. We'll have to keep an open mind about that.
I think also even if we were to achieve that type of a result at the interim analysis, we would still want to continue the trial to the numbers that we've projected, really because, we'll need those numbers for an NDA and an adequate and well-controlled trial.
Okay, great. Thank you so much. I think we're gonna leave it here at that. Just wanna thank everyone so much for joining us here today.
Thanks, Hannah.
Thank you so much again.