Atea Pharmaceuticals, Inc. Q4 FY2023 Earnings Call

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.

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.

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 remains fully active against all variants tested in vitro, including the newest of variants related to 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 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 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. 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-week protease inhibitor-free treatment, which has been well tolerated and has limited potential for drug-drug interactions. Moving to Slide 4. Atea's 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 reminds 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 a 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 the 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, 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 detail. Our goal for this program is to substantially enhance the current standard of care by offering a short eight-week protease inhibitor-free treatment that is well-tolerated with low potential risk for drug-drug interactions 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.

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 the 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 fewer 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 side 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. This cohort was comprised of non-cirrhotic patients only. However, please note that 10 patients have a 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 topline 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 compares favorably to Mavyret, which is the only approved eight-week treatment for HCV. On Slide 12, the combination of bemnifosbuvir and ruzasvir was 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.

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, 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 the 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 of critical importance to protect against hospitalization and complications. 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 fewer 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.

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 antiviral 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.

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 for 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 equivalents, 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.

Thank you, Andrea. In closing, following a year of solid operational execution across our two clinical programs, our clinical momentum sets us up for a transformational milestone-rich 2024 for both our COVID-19 and HCV programs. 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. Topline 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 study 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's hard work throughout the year. Atea is a company with fewer than 80 employees, which is conducting two global studies in diseases with multibillion-dollar market opportunities with a high degree of efficiency as well as significant financial discipline. With that, I will turn the call back over to the operator.

And our first question will come from Eric Joseph of JPMorgan. Your line is open.

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 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.

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 of granularity to Eric?

Sure. Thank you, Eric, for the question. So, in regard to how the patients are apportioned to the combination versus monotherapy, first of all, just to say that this is at the discretion of the investigator and prescribers who see 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. I think reasons for this probably are really the 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 if we have any visibility as to when we might complete accrual in the monotherapy arm, 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.

Regarding the HCV questions, the survey from a third party highlights the significance of not including a protease inhibitor in the combination treatment, particularly since 40% of HIV-infected patients also have HCV, which could lead to considerable drug-drug interactions with a protease inhibitor. This distinction is crucial. John, could you elaborate on this from a commercial perspective? It’s important to note that this isn’t just a marketing point; it holds real value commercially. After your input, I’ll provide insights from a patient perspective. John, would you like to discuss this commercially?

Certainly. From a commercial perspective, being protease-free is crucial for the low load drug regarding potential drug-drug interactions. Additionally, there are other benefits such as having no food effect and the ability to reduce treatment duration. This is particularly significant because, as Arantxa noted earlier, clinicians are discovering that shorter treatment times are more effective. To put this into context, Mavyret contains a protease inhibitor. When we examine market shares, it's evident that despite Mavyret's eight-week regimen compared to Epclusa's twelve weeks, Epclusa has over a ten-point advantage in market share. This indicates important insights as well.

Arantxa?

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 contraceptives, 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.

And one moment for our next question. Our next question will be coming from Maxwell Skor of Morgan Stanley. Your line is open, Maxwell.

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.

Andrea, do you want to address the question? Maybe just I would 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 Andrea.

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 discipline in our investments for both the COVID-19 program as well as the HCV 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 HCV, but nonetheless, we will be preparing for commercialization, as you've said. So, there will be additional activities that we will be funding at that point. Therefore, the expenses for '24 and '25 are expected to increase, but in a very measured way.

And one moment for our next question. Our next question will be coming from Jon Miller of Evercore ISI. Your line is open, Jon.

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 HCV front. So, for COVID, you said SUNRISE-3 top line data is 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 comparison to Paxlovid trial data may be limited? And then, also, worst-case scenario, how should we think about the company's direction in the bear-case scenario that the primary endpoint is not met? And then, I have a follow-up question. Thank you.

Janet, do you like to address the question, please?

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 during particular COVID waves, especially the Delta wave when hospitalizations were at an all-time high. Our study is designed to show a delta in efficacy comparable to what Pfizer most recently reported in their outpatient study, where there was about a 50% 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. If one can prevent those and reduce the severity of the disease, I think that's going to be really important.

And just to add, go ahead, Janet. Sorry, go ahead.

Okay. It's something we're considering regarding what to do if we can't meet our primary endpoint. We have a Fast Track designation from the FDA to explore our options. Additionally, we have two interim analyses where the Data Safety Monitoring Board will assist us in deciding whether to continue if we observe a number of patients not meeting our success projections. Those are scenarios we are certainly mindful of. However, everything is progressing well for now, and we look forward to sharing results and keeping you updated as we continue.

Thank you, Janet. And just what I wanted to add to the first question is I think it was very telling that the NIH recently reported that only 15% of high-risk individuals are actually taking Paxlovid. In fact, 85% of high-risk individuals who should be receiving an oral therapeutic drug are not. So, you can see that there is a huge opportunity for a best-in-class product, even considering the challenges that we face. Janet and Jessica, you recognize the need to focus on the number of low events, but we believe that the way this study has been designed will maximize the results for the efficacy and safety of this drug. So, I understand you may have another question on HCV as well?

Yes. Thank you. So, on the HCV 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 poor at compliance, or else they'd be cured already. How do you 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 the Phase 2 report who was thus unable to achieve SVR4?

That's a great question, Jessica. Arantxa, you spent quite some time on that. So, Arantxa, would you like to address the question?

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 is in high unmet need right now. It's a bit of a mix of patients who are not taking drugs and 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.

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.

Thank you. One moment for our next question. Our next question will be coming from Roanna Ruiz with Leerink Partners. Your line is open.

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?

Janet, do you like to address the question, please?

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 those aged 75 and above, and those that are highly immunocompromised, in particular, 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. Another reason why 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. 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. I think these are the patient populations where frequently, they're ineligible to receive a drug such as Paxlovid and have been fortunate enough to have received monoclonal antibodies in the past. But as you know, the monoclonal antibodies haven't been able to keep pace with the evolution of the virus. Regarding the combination group, the most important aspect we need to explore is how the combination therapy and in particular, the protease inhibitor in combination with bemnifosbuvir can provide synergy and potentially reduce severity symptoms and allow patients to improve better. We're again looking at various factors such as drug interactions, viral load kinetics, 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.

Thank you very much. Regarding HCV, how should we assess the pharmacokinetics and efficacy of bemnifosbuvir and ruzasvir in patients with compensated cirrhosis compared to those without cirrhosis in your primary cohort? Additionally, are you planning to include patients with decompensated cirrhosis and HIV co-infection in your Phase 3 study? Is your goal to pursue a similar label as Epclusa? Lastly, who are the patients you see as low-hanging fruit that could be targeted if the treatment is approved?

So, Arantxa, maybe you want to start to address the question, and then we have maybe a comment as well. So, Arantxa?

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. For the decompensated cirrhotics, 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 the Phase 3 trial. It's like you said, a great unmet need population.

I would like to make a comment regarding the decompensated patients. We believe this would represent a significant advancement, as we see the potential to eliminate ribavirin. Currently, the only approved treatment involves a combination of Epclusa and ribavirin for these patients. It's important to note that this patient population is very challenging; it's highly likely that there will be some fatalities in a trial. Therefore, we think this group will likely not be included in the Phase 3 program unless it is requested by regulatory authorities, but rather, it would be part of a post-NDA commitment. We definitely aim to address this area, possibly not with an eight-week study, but a 12-week study would be highly differentiated by eliminating ribavirin. These patients require the best chance of success, and the duration of treatment is less crucial than what we have observed in the patient population that Arantxa previously discussed.

Got it. Thanks so much for taking our questions.

You're welcome.

Thank you. I would now like to turn the conference back to Jean-Pierre for closing remarks.

Thank you all for joining our fourth quarter and full year 2023 earnings conference call, and thank you as well for your continued support.

Ladies and gentlemen, this concludes today's conference. You may now disconnect.