Atea Pharmaceuticals (ticker: AVIR), in its Q4 2023 earnings call, detailed the advancements in its antiviral drug programs, including its COVID-19 and hepatitis C virus (HCV) treatments. The company's financial health remains robust, with a reported $578.1 million in cash and equivalents as of December 31, 2023.
Atea's COVID-19 drug candidate, bemnifosbuvir, has shown effectiveness against all tested variants, including Omicron, and is progressing through the SUNRISE-3 Phase 3 study. The company is also making strides in its HCV program, with successful Phase 2 trial results and plans for Phase 3 trials and commercialization.
Key Takeaways
- Atea Pharmaceuticals discussed progress in their COVID-19 and HCV programs during their Q4 2023 earnings call.
- Bemnifosbuvir, the COVID-19 drug candidate, is active against all tested variants, including Omicron.
- The company is expanding its COVID-19 clinical trial to 50 sites in 15 countries.
- Atea achieved a 98% SVR4 post-treatment in their HCV Phase 2 trial and is preparing for Phase 3.
- Financials are strong, with $578.1 million in cash and a runway through 2026.
Company Outlook
- Atea anticipates interim analyses of the SUNRISE-3 study in March and Q2 2024, with topline results expected in H2 2024.
- The company is targeting high-risk patient populations with its antiviral programs, including the elderly and immunocompromised.
- Atea plans disciplined investments with limited expense increases in 2023 and 2024.
Bearish Highlights
- The company addressed potential scenarios if the primary endpoint is not met in their studies.
- There are challenges and risks associated with including patients with decompensated cirrhosis in the Phase 3 program.
Bullish Highlights
- Atea is advancing a non-protease-based inhibitor treatment for HCV, aiming to offer a best-in-class regimen.
- The company's combination therapy has the potential to meet unmet needs by providing a shorter treatment duration and avoiding drug-drug interactions.
Misses
- No specific misses were discussed during the earnings call.
Q&A Highlights
- Analysts inquired about the potential benefits for high-risk patients and the company's strategy to include various patient populations in the Phase 3 trials.
- Atea is exploring the synergy between bemnifosbuvir and a protease inhibitor, considering factors like drug interactions and safety.
In summary, Atea Pharmaceuticals is making significant strides in its antiviral programs, with a strong financial position to support its endeavors. The company's focus on high-risk patient populations and the potential for its drug candidates to address current treatment gaps have been emphasized.
As Atea prepares for upcoming trial results and navigates the challenges of drug development, the healthcare community and investors will be watching closely for the impacts on patient care and market dynamics.
InvestingPro Insights
Atea Pharmaceuticals (ticker: AVIR) has been showing signs of resilience and potential in the market according to recent metrics from InvestingPro. The company's market capitalization stands at a modest $364.61 million, and while the P/E ratio is currently negative at -2.68, this is not uncommon for biotech companies in the development stage.
Notably, Atea's strong cash position is reflected in its price/book ratio of 0.66, suggesting that the company's assets are valued relatively conservatively by the market.
InvestingPro Tips for AVIR highlight that the company holds more cash than debt on its balance sheet, which is a positive sign for financial stability and future investments in its drug development programs.
Moreover, Atea's liquid assets exceed its short-term obligations, providing further evidence of financial health. These aspects are particularly relevant given the company's ongoing clinical trials and the capital required to support such endeavors.
On the performance front, Atea has experienced a strong return over the last three months, with a price total return of 38.14%. This could indicate investor confidence in the company's antiviral drug programs and its strategic direction.
Still, analysts do not anticipate the company will be profitable this year, which is typical for biotech firms in the growth phase focused on research and development.
For readers interested in deeper analysis and additional insights, InvestingPro offers more tips on Atea Pharmaceuticals. There are currently 8 additional InvestingPro Tips available that could provide further guidance on the company's performance and outlook. To access these tips and enjoy a comprehensive investment tool, use the coupon code PRONEWS24 to get an additional 10% off a yearly or biyearly Pro and Pro+ subscription.
Full transcript - Atea Pharmaceuticals Inc (AVIR) Q4 2023:
Operator: Good afternoon, everyone, and welcome to the Atea Pharmaceuticals Fourth Quarter 2023 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call up for your questions. I would now like to turn the call over to Jonae Barnes, Senior Vice President of Investor Relations and Corporate Communications at Atea Pharmaceuticals. Ms. Barnes, please proceed.
Jonae Barnes: Good afternoon, everyone, and welcome to Atea Pharmaceuticals fourth quarter and full year 2023 financial results and business update conference call. Earlier today, we issued a press release, which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the Investors section of our website at ir.ateapharma.com. With me today from Atea are our Chief Executive Officer and Founder; Dr. Jean-Pierre Sommadossi; Dr. Arantxa Horga, Chief Medical Officer; Chief Development Officer, Dr. Janet Hammond; Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran; and our Chief Commercial Officer, John Vavricka. They will all be available for the Q&A portion of today's call. Before we begin the call, and as outlined on Slide 2, I would like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on today's call. With that, I'll now turn the call over to Jean-Pierre.
Jean-Pierre Sommadossi: Thank you, Jonae. Good afternoon, everyone, and thank you for joining us. I will begin on Slide 3. Looking back at our substantial progress throughout 2023, I'm proud of the strong operational execution we achieved across our antiviral programs. The 2023 highlights from our COVID-19 program include the ability to leverage global surges to meaningfully advance our Phase 3 SUNRISE-3 study. This was made possible by the expansion of the global footprint and the broadening of the eligibility criteria for high-risk patients. So far in 2024, we continue to observe encouraging enrollment trends for SUNRISE-3. Reflecting the continuing unmet medical need, we were granted Fast Track designation by the FDA for the evaluation of bemnifosbuvir for COVID-19. We have continued to demonstrate that bemnifosbuvir remain fully active against all variants tested in vitro, including the newest of variants related to the Omicron. The profile for bemnifosbuvir is supported by robust clinical data, including favorable efficacy and safety, with no drug-drug interaction. We believe that bemnifosbuvir has the potential to address the key limitations of curing COVID-19 oral therapies. For HCV, the 2023 highlights include achieving regulatory approvals of a short eight-week treatment for the global Phase 2 trial of the combination of bemnifosbuvir and ruzasvir for the treatment of HCV. The rapid enrollment of the leading cohort, which has led to exciting SVR results that we will review today. We demonstrated in vitro synergy of the combination of bemnifosbuvir and ruzasvir and the compelling potency profile against major HCV resistance mutations. We are now evaluating several fixed-dose combination tablets in preparation for the Phase 3 program and subsequent commercialization. And we presented and published preclinical and clinical data in support of this program. We believe bemnifosbuvir in combination with ruzasvir can significantly improve upon the current standard of care by offering a differentiated short eight weeks protease inhibitor-free treatment, which has been well tolerated and has limited potential for drug-drug interactions. Moving to Slide 4. Atea vision is focused on the discovery and development of antiviral drugs for the treatment and cure of serious viral diseases where there is a significant unmet medical need and where we can make a huge difference. As you know, we believe that COVID is here to stay. And the recent winter surge remind us that new dominant variants like JN.1 are thriving despite the latest vaccine booster and treatments. The SARS-CoV-2 virus is accumulating mutations with amino acid substitutions faster than any other endemic RNA virus, highlighting the desperate need for broader and more diversified arsenal of safe, well-tolerated and easy-to-prescribe oral antiviral therapeutics. Our team continues to efficiently execute our global Phase 3 trial, and I'm very pleased to announce today that we have achieved another significant clinical milestone and surpassed enrollment of 1,400 patients, triggering our second interim analysis in the supportive care monotherapy cohort. This is an important milestone, allowing for the data review by the independent DSMB for safety and futility. For SUNRISE-3, we anticipate several upcoming events, including the first interim analysis in March, the second interim analysis in the second quarter of 2024 and topline results during the second half of 2024. Bemnifosbuvir has the potential to address many of the key limitations of current COVID-19 therapies, including safety, tolerability and drug-drug interactions. Our goal is to deliver best-in-class treatment to the millions of patients for whom the current standard of care is suboptimal or unsuitable. As part of a multipronged approach against COVID-19, we continue to also make progress with our discovery program focused on a highly differentiated second-generation protease inhibitor, and we expect to provide an update midyear. For our Phase 2 HCV program, as stated earlier, we shared new results. We confirmed a 98% SVR4 post-treatment in the leading cohort of our Phase 2 combination eight-week study. Arantxa will review these results in more details. Our goal for this program is to substantially enhance the current set of care by offering a short eight-week protease inhibitor-free treatment that is well tolerated with low potential risk for drug-drug interaction for all HCV patients. Importantly, we are in a strong financial position to execute our strategy with $578.1 million of cash and cash equivalents as of December 31, with a runway anticipated to 2026. Andrea will provide a detailed update on Atea's financial position during today's call. I will now turn the call over to Arantxa for an update on our HCV program.
Arantxa Horga: Thank you, Jean-Pierre. Turning to Slide 6. Despite current treatment options, HCV continues to be a health crisis in the U.S. As Jean-Pierre noted earlier, there are approximately 2.4 million people infected with HCV in the U.S. despite availability of oral treatment. Recent trends indicate there are more new infections and reinfections than cures on a yearly basis. And these statistics highlight the need to improve the HCV treatment landscape. The combination of bemnifosbuvir and ruzasvir has the potential to substantially improve upon the current standard of care by offering a short eight-week protease inhibitor-free treatment with less side effects and a low risk for drug-drug interactions. Based on our market research with KOLs and high prescribers, these attributes are very critical for a new treatment, as you will see on the next slide. Moving to Slide 7. While the introduction of direct-acting antivirals has transformed HCV treatment, significant unmet needs still exist. In recent quantitative market research conducted by Atea with over 150 U.S. physicians who are high prescribers of Epclusa or Mavyret, only 6% of these physicians reported that there are no unmet needs regarding HCV treatment. Key unmet needs emerging in this research were shorter length of treatment and higher efficacy, particularly in HIV co-infected patients as well as fewer contraindications, as detailed on the right hand of the slide. Please note that currently, approximately 17% of patients do not complete their treatment regimen, making convenient and shorter treatment durations of particular importance to prescribers. Slide 8 outlines our Phase 2 open-label study of 550 milligrams of bemnifosbuvir in combination with 180 milligrams of ruzasvir once daily for eight weeks. We plan to enroll up to 280 DAA-naive patients across all genotypes. In the initial cohort, sustained virological response, or SVR, at week four was used as the decision criteria to reinitiate enrollment to complete the Phase 2 study. The primary endpoint of the study is SVR at week 12 and this will be reported for all patients at study completion. Slide 9 highlights the patient demographics and baseline characteristics in the leading cohort of the Phase 2 open-label study of bemnifosbuvir and ruzasvir. The patients were DAA-naive with a median age of 47-years-old. This cohort was comprised of non-cirrhotic patients only. However, please note that 10 patients have cirrhosis stage of F3, a more advanced liver disease stage, which is borderline with cirrhosis. In the second part of the Phase 2 study compensated cirrhotic patients will also be enrolled. Moving to Slide 10, we are excited to share with you today that the final results from the Phase 2 combination study in the leading cohort confirm an SVR4 of 98% post treatment across all genotypes. In January, we reinitiated enrollment to complete this study in up to 280 patients with top line results anticipated in the second half of 2024. Slide 11 shows the on-treatment viral kinetics of individual patient data. By week four, all 60 patients in this cohort had viral load near or below the lower limit of quantification. Therefore, this very rapid kinetics across all genotypes support an eight-week regimen and compared favorably to Mavyret, which is the only approved eight-week treatment for HCV. On Slide 12, the combination of bemnifosbuvir and ruzasvir were generally safe and well tolerated in this cohort of 60 patients. There were no drug-related serious adverse events, no discontinuation and adverse events were mostly mild. Turning to Slide 13, to summarize our progress in HCV, based on the positive leading cohort data, we reinitiated enrollment in January for the remainder of the Phase 2 trial. To help advance enrollment and achieve representative genotype distribution, we are increasing this study's footprint to approximately 50 clinical sites in 15 countries. In addition, over the first half of 2024, we are conducting Phase 1 studies in the U.S. for the selection of the fixed dose combination tablet, which will be evaluated in the Phase 3 program and used for subsequent commercialization. We anticipate that the Phase 3 program will be initiated around the end of this year. Slide 14. Next, we will provide an update on our COVID-19 program. I'll turn the call over to Janet to discuss our SUNRISE-3 Phase 3 trial.
Janet Hammond: Thanks, Arantxa. Good afternoon, everyone. COVID-19 continues to be an established pathogen of concern according to the World Health Organization. And we believe that COVID-19 will remain an ongoing serious endemic issue. Our goal for COVID-19 is to deliver a safe and effective treatment to millions of patients for whom the current standard of care is not a suitable option. We believe that the compelling preclinical and clinical profile of bemnifosbuvir is differentiated with a low risk for drug-drug interactions, a favorable tolerability and a high barrier to resistance, and has the potential to become the treatment of choice for COVID-19 for millions of patients. Moving to Slide 16. Supported by our extensive global footprint, we are seeing robust enrollment into SUNRISE-3 and patient enrollment has correlated with the latest winter wave. In particular, we've experienced strong enrollment in the U.S. where sites have been responsible for approximately 75% of the patients enrolled to date. The majority of patients globally continue to be enrolled in the monotherapy cohort despite the availability of other oral antivirals. We're excited to share with you today that SUNRISE-3 surpassed enrollment of 1,400 patients in the monotherapy cohort, triggering the second interim analysis. The DSMB is expected to meet in March for the first interim analysis, and we expect the second interim analysis to occur during the second quarter. Just to remind you, the DSMB reviews are primarily geared towards safety and utility. So far this winter, as predicted by the U.S. CDC, respiratory diseases are showing similar high trends to last year. The patients most vulnerable to severe COVID infection remain the elderly, the immunocompromised and those with underlying risk factors for severe infection, where oral therapeutics are critical importance to protect against hospitalization and complication. Turning to Slide 17, I'll now go into detail on our SUNRISE-3 global Phase 3 trial. To start, our inclusion criteria focused on high-risk outpatients with mild or moderate COVID-19, regardless of vaccination status. Symptom onset is five or less days before randomization. The Phase 3 study is randomized, double-blind and placebo-controlled. The study drug either bemnifosbuvir 550 milligrams BID or placebo is administered concurrently with the locally available standard of care. There are two study populations depending on the type of standard of care received. The supportive care monotherapy cohort comprises the primary analysis population. While the combination cohort is part of the secondary analysis, and includes patients treated with local standard of care, including other compatible COVID-19 antiviral drugs. The primary endpoint for the study is all-cause hospitalization or death through day 29 in the supportive care monotherapy population, which will be approximately 2,200 patients. The secondary endpoints are COVID-19-related hospitalizations and death, medically attended visits and symptom rehabs. Last year, we were granted Fast Track designation for bemnifosbuvir, reflecting the recognized unmet medical need that remains for COVID-19 patients. Overall, we're seeing strong operational execution for SUNRISE-3 from our clinical team with robust enrollment trends. I'm now going to hand the call over to John to discuss the marketing opportunity for bemnifosbuvir. John?
John Vavricka: Thank you, Janet. Turning to Slide 19, we know that the U.S. prescription demand for oral antivirals to treat COVID correlates with the infection rates. The demand for oral antivirals in 2023 was very robust with a total of approximately 7.7 million scripts written. Last month, the scripts were approximately 920,000 which reflects the latest winter surge. On the next slide, Slide 20, late last year, the market for COVID-19 oral antivirals began transitioning to traditional payer markets such as Medicare, Medicaid and private commercial insurance. Oral antivirals therapeutics for COVID-19 are expected to remain a multibillion-dollar opportunity for years to come. Projected annual COVID-19 oral antiviral U.S. demand using IQVIA retail prescriptions suggests an estimated annual global market opportunity of over $4 billion to $5 billion, with only two products that each have key limitations. We believe there is still an unmet need with critical gaps, and there is the opportunity to expand this market to patients due to drug-drug interactions and tolerability with Paxlovid and safety issues with Lagevrio. I'll now turn the call over to Andrea to discuss Atea's financials.
Andrea Corcoran: Thank you, John. As Jonae mentioned, earlier this afternoon, we issued a press release containing our financial results for the fourth quarter and full year 2023. The statement of operations and balance sheet are on Slides 22 and 23. There was an increase in R&D expense for the fourth quarter and full year 2023 versus the corresponding period in 2022. The primary driver for the higher expense was the external spend related to our COVID-19 Phase 3 SUNRISE-3 clinical trials and our Phase 2 clinical trial of the combination of bemnifosbuvir and ruzasvir to the treatment of hepatitis C. General and administrative expenses remained relatively flat for the fourth quarter and full year versus the corresponding period in 2022. Interest income increased for the fourth quarter and full year 2023 versus the corresponding period in 2022. This was the result of investing in higher-yield marketable securities and higher interest rates. At the end of the fourth quarter of 2023, our cash, cash equivalent and marketable securities balance, as Jean-Pierre mentioned, was $578.1 million. Based on our current plans, we are reiterating our cash guidance with a runway through 2026. I'll now turn the call back over to Jean-Pierre for closing remarks.
Jean-Pierre Sommadossi: Thank you, Andrea. In closing, following a year of solid operational execution across our two clinical programs, our clinical momentum sets us up to a transformational milestone-rich 2024 for both our COVID-19 and HCV program. For COVID-19, we anticipate meaningful clinical milestones beginning in the first quarter of 2024 with the first interim analysis from our global Phase 3 trial, followed by a second interim analysis in the second quarter of 2024. Top line results are expected in the second half of 2024. For HCV, we anticipate completing enrollment of our Phase 2 study and reporting results during the second half of 2024. We have continued to target initiation of a Phase 3 around the end of the year, and we are extremely encouraged by the SVR4 and safety results in the leading cohort. We are targeting multibillion-dollar markets, each of which are currently comprised of only two primary products. We believe that our product candidates are very differentiated and have the opportunity, if approved, to fill the gap in the current unmet medical needs and become blockbuster products. We are very excited about the opportunities ahead and are confident in our ability to develop and commercialize innovative products and create meaningful shareholder value. In particular, I'm very proud of the team hard work throughout the year. Atea is a company with less than 80 employees, which is conducting two global studies in disease with multibillion-dollar market opportunities with a high degree of efficiency as well as with significant financial discipline. With that, I will turn the call back over to the operator.
Operator: [Operator Instructions] And our first question will come from Eric Joseph of JPMorgan. Your line is open.
Eric Joseph: Thank you, and thanks for taking the questions. A couple from us. Just on the sizable accrual in patients for SUNRISE-3, do you have visibility in terms of I guess, how those are apportioned across the different study arms, monotherapy versus combo? I guess what visibility do you have in terms of percent to enrollment completion of the monotherapy primary analysis population? And, on the HCV side, just picking up on a comment you made, JP, about potentially being a non-protease-based inhibitor option. What's the significance of that? Is there sort of a safety advantage that you'd highlight? Or is it more about just being an alternative mechanism compared to the other commercially available eight-week regimen? Thanks.
Jean-Pierre Sommadossi: Thank you, Eric. There is definitely an importance and a differentiation. But let's start with the COVID-19 questions. Great question. Janet, do you want to give a little bit some granularity to Eric?
Janet Hammond: Sure. Thank you, Eric, for the question. So, in regard to how the patients are apportioned to the combination versus monotherapy, I mean, obviously, first of all, just to say that this is at the discretion of the investigator and prescribers who sees the patient, and they are encouraged to prescribe combination therapy if they believe that is appropriate for the patient, and actually educated quite extensively at our investigation meetings in that regard. And what I think is quite surprising is that the vast majority of patients are actually being assigned to the monotherapy arm. And I think reasons for this probably are really the potential -- extensive potential for drug interactions associated with ritonavir in the Paxlovid combination treatment, which I think deters people from prescribing combination therapy to patients. And then, in regards to your question around when we -- if we have any visibility as to when we might complete accrual in the monotherapy arm, no, we don't. But I can say that enrollment is proceeding well. But of course, we're very dependent on the fluctuations in COVID cases as they occur. We've seen a very strong winter season, but frequently, I think, at least in the past, we've observed that that's followed by some downward trend in the number of cases until we get towards the hotter summer months and people move indoors again. So, we're somewhat dependent on that, and we're going to have to see. Thank you.
Jean-Pierre Sommadossi: So, related to the HCV questions, I think with the survey from a third-party really exemplify the importance of a lack of protease inhibitor in the combination treatment especially when we are talking about 40% of HIV infected patients with HCV, where you're going to have substantial drug-drug interaction if we have -- if you have a protease inhibitor. So, it is an important differentiation. John, you want to maybe also expand on that and really -- this is not just a gimmick here that we are talking, but really important from a commercial standpoint and then I will ask -- I'll answer from a patient standpoint. John, do you want to address that from a commercial standpoint?
John Vavricka: Sure. So, Eric, from a commercial standpoint, obviously, being protease free is really important to us for the low load drug in our DDI interaction potential. And also -- there's also other advantages such as having a no food effect and also to be able to treat with a shorter treatment duration, particularly important because, as Arantxa mentioned earlier in the presentation, what clinicians are finding is that the shorter time to treat is the better. And to highlight this about -- Mavyret has obviously a protease inhibitor. And when you look at the [indiscernible] market shares, even despite being eight weeks versus 12, there's almost a little bit more than a 10-point share difference in favor of Epclusa. And so that should maybe also tell us some things as well.
Jean-Pierre Sommadossi:
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Arantxa Horga: Yes. So, from a medical perspective, I think what we're trying to develop here is really a best-in-class regimen that combines the best of Epclusa and the best of Mavyret in the sense that it's an eight-week regimen and without the drug-drug interactions that are actually quite common that Mavyret and protease inhibitors have as a class. And these are common drugs. We're talking about things like contraceptive, antiretroviral therapy, statins, proton-pump inhibitors, which almost everybody over 40 is on something like that. So, this is very important for the patients as the market research has indicated, but also when we talk to the KOLs on the field and when they were actually trying to redo our protocol and participate in our clinical trial, all of them were very excited that we could actually develop this best-in-class regimen, bringing the best of both -- attributes of both regimens.
Jean-Pierre Sommadossi:
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Operator: And one moment for our next question. Our next question will be coming from Maxwell Skor of Morgan Stanley. Your line is open, Maxwell.
Maxwell Skor: Great. Thank you for taking my questions. Given your strong financial position, I was hoping you can elaborate a bit on your capital allocation strategy and how you're preparing for a potential launch in COVID while advancing your global HCV program? Basically, how should we think about spend over the next several quarters? Thank you.
Jean-Pierre Sommadossi: Andrea, do you want to address the question? Maybe just I'd like to indicate that for the launch, we have actually supply, if we are fortunate to get an approval in the US. But we will not put substantial investment in manufacturing at risk prior to approval. So, we will provide additional information as we get closer to launch. So, with that, [I'll turn it to] (ph) Andrea.
Andrea Corcoran: Yes. Thank you, Jean-Pierre, and thanks, Max, for the question. So, I think as you've seen or will see when you have the chance to review the financial statements, we continue to exercise really discipline in our investments for both the COVID-19 program as well as the hep C program. Expenses are increasing but in a very measured way quarter-over-quarter for 2023. We would expect the same type of limited increase in 2024. The Phase 3 program for COVID will begin to wind down before the Phase 3 begins for hep C, but nonetheless, we will be preparing for commercialization, as you've said. So, there will be additional activities and that we will be funding at that point. So, the expenses for '24 and '25 are expected to increase, but in a very measured way.
Maxwell Skor: Great. Thank you.
Operator: And one moment for our next question. And our next question will be coming from Jon Miller of Evercore ISI. Your line is open, Jon.
Unidentified Analyst: Hi. This is Jessica on for Jon Miller. Thanks for taking our questions. I have two questions, if I may, one on COVID, one on the hep C front. So, for COVID, so you said SUNRISE-3 top line data expected in the second half of the year. So, how should we think about the various scenarios that can occur? Like how well does the market appreciate that preexisting immunity from infection and/or vaccination can affect placebo rates, possibly making the effect size smaller and maybe a direct comp to Paxlovid trial data may be limited? And then, also worst-case scenario, how should we think about the company direction in the bear-case scenario that the primary endpoint is not met? And then, I have a follow-up question. Thank you.
Jean-Pierre Sommadossi: Janet, do you like to address the question, please?
Janet Hammond: Thank you, Jessica. So, yes, I think everybody realizes that with vaccination and prior exposure to COVID-19, the severity of disease is frequently less severe, fortunately, than it was when we we're going through, in particular, I think, the Delta wave and hospitalizations were at an all-time high. Our study is designed to show a delta in efficacy comparable to I think what Pfizer (NYSE:PFE) most recently reported in their outpatient study, where there was about a 50% -- or in the 50%s difference between the active and the placebo groups. And so that's what we're expecting to see. I think particularly when you're talking about high-risk patients and hospitalizations, that is still an important and meaningful difference. And of course, hospitalization and death are the worst outcomes. And so, if one can prevent those and reduce the severity of disease, I think that's going to be really important.
Jean-Pierre Sommadossi: And just to add -- go ahead, Janet. Sorry, go ahead.
Janet Hammond: No, I was just going to ask you if you wanted to follow on with Jessica's other question around the scenario where we fail to achieve the primary end point.
Jean-Pierre Sommadossi: Yes, go ahead.
Janet Hammond: Okay. So, I think -- I mean, certainly, I mean, it's one of those things that is under consideration is if we're unable to do that, are there further avenues to pursue in terms of looking for trends. And we have a Fast Track designation with the FDA to assess how to proceed. But we also have, as I think has been mentioned, two interim analyses where the DSMB will help us to make the decision not to proceed should we see that number of patients in what we are projecting would allow us to be successful. So, I think those are the scenarios that we're certainly aware of and thinking about. But at the moment, things are moving forward well, and we look forward to presenting results and alerting you to update as we move forward.
Jean-Pierre Sommadossi: Thank you, Janet. And just what I wanted to add to the first question is I think it was -- it's very telling that the NIH actually recently reported that only 15% of high risk actually are taking Paxlovid, and actually -- so 85% of high risk who should get an oral therapeutic drug. So, very likely many of the reasons of the limitation of Paxlovid. So, you can see that there is a huge opportunity for a best-in-class product, including even with the challenges that we face as Janet -- and Jessica, you recognize in terms of number of low event, but we believe that the way this study has been built will maximize the results for the efficacy and safety of this drug. So, I understand you may have another question on HCV as well?
Unidentified Analyst: Yes. Thank you. So, on the hep C program, given the context that compliance with existing therapies is lacking with existing regimens, so there's an unmet need here. And the patients you're presumably going after are the ones that we know already are bad at compliance or else they'd be cured already. How do you guys plan to ensure for the Phase 3 that the protocol and clinical sites can optimize good drug adherence, especially since we've already seen that one patient in Phase 2 report here and who is thus unable to achieve SVR4?
Jean-Pierre Sommadossi: That's a great question, Jessica. Arantxa, you spent quite some time on that. So Arantxa, you would like to address the question?
Arantxa Horga: Yes, it is a great question. I think in part, the compliance issues are just part of the nature of doing trials right now in hepatitis C. The population that we have that is in high unmet need right now. It's a bit of a mix of the patients who are not taking drugs and they are just general patients, but also there is a very large population of patients that are ex-IV-drug users or IV-drug users, and those really benefit from short treatment durations. So I think by offering a short treatment duration, you're already addressing some of the compliance issues because patients in general are very excited to take drugs at the beginning, but then sometimes they forget towards the end of the treatment. I think we have all experienced that. So, the eight-week duration already helps. We, of course, have the regular measurements of checking with the patients, calling them, bringing them in. And what's very important in Phase 3 is that we're going to have a comparator. So, the issues with compliance will affect both arms equally because the patients are randomized. And there, you're really going to see how the comparator is behaving in today's kind of population, which includes these patients that are non-compliant in general.
Jean-Pierre Sommadossi: Obviously, we will finalize any protocol with the regulatory authorities. But based on our initial interaction, it's clear that a comparator is required for our Phase 3 program.
Unidentified Analyst: Thank you very much.
Operator: And one moment for our next question. And our next question will be coming from Roanna Ruiz with Leerink Partners. Your line is open.
Rosa Chen: Thank you. This is Rosa Chen on for Roanna Ruiz, Leerink Partners. Just a couple from us. First on COVID. So thinking of all the various high-risk patients you're enrolling in Phase 3, which subpopulation do you think bemnifosbuvir can offer the most differentiated profile from currently available antivirals? And any thoughts on how you could leverage the data from the combination therapy arm?
Jean-Pierre Sommadossi: Janet, do you like to address the question, please?
Janet Hammond: Sure. So, I think, with regard to the high-risk patient population, I mean, it's quite interesting, but I think in the last few months, there have been a couple of publications really showing that for the most high-risk patients, the elderly, particularly, I think there's 75 and above and those that are highly immunocompromised, and I think in that regard, particularly solid organ transplant patients. However many times they get vaccinated, it doesn't really seem to reduce their risk of getting severely ill when they do become infected with COVID. So, I think these are the patient populations, which are probably the ones where there is likely to be the great benefit. And I think another reason why ultimately I think bemnifosbuvir would be an ideal drug for patients such as these is that these are patient populations that are on multiple concomitant medications. And as Jean-Pierre mentioned, and as we've alluded to, I think the potential for drug interactions, particularly with protease inhibitors is much higher than with nucleoside antagonists. And so, I think these are the patient populations where frequently, they're actually ineligible to receive a drug such as Paxlovid and have been in the past fortunate enough to have been able to receive monoclonal antibodies. But as you know, the monoclonal antibodies haven't been able to keep pace with the evolution of the virus. And then, with regard to the combination group and what we're going to do there to educate ourselves, it's really -- the most important, I think because we have, as Jean-Pierre mentioned in his remarks, a protease inhibitor, which is being developed in which we hope to show more information for later in the year. And so, I think being able to see how combination therapy and in particular, a protease inhibitor in combination with bemnifosbuvir is able to provide synergy and potentially reduce severity symptoms and allow patients to improve better. And also, we're again looking at such things as drug interactions, viral load kinetics and safety and tolerability. I think all of that information is important in understanding how best to use these drugs and maximize them as we move further down the line.
Rosa Chen: Thank so much. And then, on HCV, how should we think about the PK and efficacy of bemnifosbuvir and ruzasvir in the patient population that actually has compensated cirrhosis compared to those without cirrhosis in your leading cohort? And then, are you considering including patients with decompensated cirrhosis and also HIV co-infection in your Phase 3? So, it's a similar -- was to pursue a similar label as Epclusa? And then separately, who are these low-hanging fruit patients that you could target if it's approved?
Jean-Pierre Sommadossi: So, Arantxa, maybe you want to start to address the question, and then we have maybe a comment as well. So, Arantxa?
Arantxa Horga: Yes. Well, I think the PK, we don't anticipate major changes in PK or even PK/PD and viral kinetics as you saw in the data that we have shown. The kinetics were very fast even in the F3s, which are really borderline compensated cirrhotic. So, we think that -- and we've seen also in previous trials that the PK should be the same. That is for the compensated cirrhotics. For the decompensated cirrhotic, it is a great population. I think that we are going to target it. It's probably a little bit later. For the HIV, certainly, we are considering inclusion in Phase 3 trial. It's like you said, a great unmet need population.
Jean-Pierre Sommadossi: Yeah. No, actually, just one comment for the decompensated patients, obviously, that would be, we believe, a major advance because we foresee -- at least, we see the potential to eliminate ribavirin, which right now, you have only one approved treatment, which is a combination of Epclusa and ribavirin in those patients. Now, let's not forget that this is patient population that is very difficult, very likely in a trial, you are going to have some deaths. So, obviously, we foresee that this population will be very likely not part of the Phase 3 program unless the regulatory authorities will request that, but more as a post NDA commitment. But definitely, we definitely want to go there, maybe not with eight week, probably a 12 week would be already highly differentiated with the elimination of ribavirin. And obviously, these patients do require the best chance of success and that the length of treatment are less of an importance than what we have with the patient population that Arantxa just shared with you before.
Rosa Chen: Got it. Thanks so much for taking our questions.
Jean-Pierre Sommadossi: You're welcome.
Operator: Thank you. I would now like to turn the conference back to Jean-Pierre for closing remarks.
Jean-Pierre Sommadossi: Thank you all for joining our fourth quarter and full year 2023 earnings conference call, and thank you as well for your continued support.
Operator: Ladies and gentlemen, this concludes today's conference. You may now disconnect.
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