Q4 2023 Atea Pharmaceuticals Inc Earnings Call

Participants

Jonae Barnes; Senior Vice President, Investor Relations, Corporate Communications; Atea Pharmaceuticals Inc

Jean-Pierre Sommadossi; Chairman of the Board, President, Chief Executive Officer, Founder; Atea Pharmaceuticals Inc

Arantxa Horga; Chief Medical Officer; Atea Pharmaceuticals Inc

Janet Hammond; Chief Development Officer; Atea Pharmaceuticals Inc

John Vavricka; Chief Commercial Officer; Atea Pharmaceuticals Inc

Andrea Corcoran; CFO, EVP of Legal & Secretary; Atea Pharmaceuticals Inc

Eric Joseph; Analyst; JPMorgan Chase & Co

Maxwell Skor; Analyst; Morgan Stanley

Jessica Hui; Analyst; Evercore ISI Institutional Equities

Rosa Chen; Analyst; Leerink Partners LLC

Presentation

Operator

Good afternoon, everyone, and welcome to the Taro 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 ITI. pharmaceuticals. It's Barnes. Please proceed.

Jonae Barnes

Good afternoon, everyone, and welcome to the Taylor 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 dot karyopharm.com.
With me today from a payer are our Chief Executive Officer and Founder, Dr. Jean-Pierre Summa Doce sector rental HoReCa, 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 Beaver, Rita. 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 risk 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, gentlemen. And 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 achieve across our antiviral programs to 2023.
Highlights from our COVID-19 program include the ability to leverage global surges to meaningfully advance our Phase three SUNRISE three 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 shred, reflecting the continuing unmet medical need. We were granted fast track designation by the FDA for the evaluation of very positive year for COVID-19. We are continuing to demonstrate the benefits. We remain fully active against all variants tested in vitro, including the noise surveillance related to the O Micra profile for Beni fast Viviant is supported by robust clinical data, including favorable efficacy and safety with no drug-drug interactions. We believe that many falls Vivian has the potential to address the key limitations of current COVID-19 for therapies for HCV the 2023 highlights include achieving regulatory approvals of Assure eight-week treatment for the global Phase two trial of the combination of very fast Bolivia and resume for the treatment of HCV, the rapid enrollment of the leading score, which has led to exciting SVR results that we will review today. We demonstrated in vitro synergy of the combination of Beni Class V on the reservoir and the compelling potency profile against major HCV resistance mutations. We are now evaluating several fixed dose combinations, tablets in preparation for the Phase three program and subsequent commercialization and we've presented and published preclinical and clinical data in support of this program. We believe many positive in combination with resist via 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. Attaining a vision is focused on the discovery and development of antiviral drugs for the treatment and cure for 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 the new dominant variants like GEN-1 strive. And despite the latest vaccine booster and treatments. South CoV two virus is accumulating mutations with amino acid substitutions faster than any other endemic. Irene runs 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 three trial, and I'm very pleased to announce today that we have achieved another significant clinical milestone and surpass 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 Ray, we anticipate several upcoming events, including the first interim analysis in March, the second interim analysis in the second quarter of 2024 and top line results during the second half of 2024.
Benny first, maybe as a 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 for insurable as part of a multi-prong 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 two HCV program. As stated earlier, we share new results with confirm a 98% SVR4 post treatment in the leading cohort of our Phase two combination eight weeks that Randy 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 for the ACE 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 anticipation of 2026. And Ray will provide a detailed update on the financial position during today's call. I will now I'll turn the call over to Lorenzo for an update on our HCV program.

Arantxa Horga

Thank you, Cynthia.
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 US despite availability of oral treatments. Recent trends indicate they are more new infections and reinfection than peers on a yearly basis. And this statistics highlight the need to improve the HCV treatment landscape of the company, Benny plus from your angle, severe 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 need still exist in recent quantitative market research conducted by a payer with over 150 used physicians, call it high prescribers of it close on all matters. Only 6% of this physicians reported that they have no unmet needs.
Regarding HCV treatment key unmet needs. Emerging in this research was 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 mean convenient and shorter treatment durations of particular importance to prescribers.
Slide 8 outlines our Phase two open label study of 550 milligrams of the first full year in combination with 180 milligrams of Roche's via once daily for eight weeks, we plan to well up to So 180 DA. nice patients across all genotypes in the initial cohort, sustained biological response or SVR at week four was used as the decision criteria to reinitiate enrollment to complete the Phase two study. The primary endpoint of this study is SVR at week 12, and this will be reported for all patient at study completion.
Slide 9 highlights the patient demographics and baseline characteristics in the lead-in cohort of the Phase two open-label study of any fiscal year in rosacea, patients would be nice with a median age of 47 years old. This cohort was comprised of non-cirrhotic patients only. However, please note that 10 patients had fibrosis stage three or more advanced liver disease stage, which is borderline with cirrhosis. In the second part of the Phase two study conference, periodic patients will also be enrolled.
Moving to Slide 10. We are excited to share with you today that the final results from the Phase two combination study in the lead-in cohort confirm and SVR, four of 98% 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 and then 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 supports an eight week regimen and compare favorably. It is the only approved eight week treatment for HCV.
On slide 12, the combination of any force of year-end versus via was generally safe and well tolerated in this cohort of 60 patients. There were no drug-related serious adverse events. No discontinuations and adverse events were mostly mild.
Turning to Slide 13 to summarize our progress in HCV. Based on the positive lead-in cohort data, we reinitiated enrollment in January for the remainder of the Phase two 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 one studies in the U.S. for the selection of them fixed-dose combination tablet, which will be evaluated in the Phase three program and used for subsequent commercialization. We anticipate that the Phase three 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 Dennis to discuss our St. rice three Phase three trial.

Janet Hammond

Thanks, Art, and good afternoon, everyone. Covid-19 continues to be an established pathogen of concern and according to the World Health Organization, and we believe that COVID-19 will remain an ongoing serious pandemic issue. Alcoa for COVID-19 is to deliver safe and effective treatment for millions of patients for whom the current standard of care is not a surgical option. We believe that the compelling preclinical and clinical profile of any Hospira 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 three and patient enrollment has current with the latest winter wave. In particular, we've experienced strong enrollment in the US for sites being responsible for approximately 75% of the patients enrolled to date. The majority of patients globally continues to be enrolled in the monotherapy cohort despite the availability of other oral antivirals, which I'd like to share with you today.
The Sunrise three surpassed enrollment to 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 futility. Therefore, this winter, as predicted by the USCDC. respiratory diseases are showing similar high trends to last year. Patients. Most vulnerable to severe COVID infection remain the elderly immunocompromised and those with underlying risk factors for severe infection by 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 three global Phase three trial, discuss our inclusion criteria focused on high risk of patients with mild or moderate COVID-19 regardless of vaccination status. Interim onset is five or less days before randomization. The Phase three study is randomized, double-blind and placebo-controlled study drug either any faster than 550 milligrams BID or placebo. Is it 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 of the study is all cause hospitalization or death through day 29 in the supportive care monotherapy population, which will be approximately 2,200 patients. Secondary endpoints are COVID-19 related hospitalizations and death, medically attended visits and symptom RE/MAX now scare we were granted fast track designation for Benny foster there, reflecting the recognized unmet medical need that remains for COVID-19 patients. Overall, we're seeing strong operational execution for Sunrise three from our clinical team for sure best enrollment trends.
I'm now going to hand the call over to John to discuss the marketing marketing opportunity for Benny Foster.
John?

John Vavricka

Thank you, Jan. 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 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 multi-billion dollar opportunity for years to come. Projected annual COVID-19 oral antiviral US demand using IQ, the retail prescriptions suggest 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 Paxil, COVID and safety issues with the Gabriel, I'll now turn the call over to Andrea to discuss the details of financials.

Andrea Corcoran

Thank you, Dan. As Rene mentioned earlier this afternoon, we issued a press release containing our financial results for the fourth quarter and full year 2023 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 periods in 2022 be the primary driver for the higher since with the external expend related to our COVID-19 Phase three SUNRISE three clinical trials in our Phase two clinical trial of the combination of any fast bear interest there for the treatment of hepatitis C, general and administrative expenses remained relatively flat for the fourth quarter and full year versus the corresponding periods in 2022. Interest income increased for the fourth quarter and full year 2023 versus the corresponding periods 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 and closing. Following up a year of solid operational execution across our two clinical programs, our clinical momentum, server software, a transformational milestone, which 2024 for both our COVID-19 and HCV program for COVID-19, we anticipate meaningful clinical milestones beginning in the first quarter of 2024 was the first interim analysis from our global Phase three 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 two study and reporting results during the second half of 2024. We are continuing to target initiation of a Phase three around the end of the year, and we are extremely encouraged by the SVR4 and safety result in the lead-in 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 product. We are very excited about the opportunities ahead and are confident in our ability to double up and commercialize innovative products and create meaningful shareholder value. In particular, I'm very proud of the team how they work throughout the year. I care is a company with less than 80 employees, which is conducting two global studies in disease with 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.

Question and Answer Session

Operator

Certainly as a reminder, to ask a question, please press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star one once again and One moment for our first question. And our first question will come from Eric Joseph of JPMorgan. Your line is open.

Eric Joseph

No, thank you and thanks for taking the questions. A couple from us on just on the sizable accrual in patients for Sunrise three, do you have visibility in terms of them? I guess how those are apportioned across the different study arms, monotherapy versus combo gets? What visibility do you have in terms of a 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 week regimen. Thanks.

Jean-Pierre Sommadossi

Thank you. And we've been very, very fruitful for you and the important thing to differentiate your, but let's start with the recovery 19 questions of.
Great question. Janet, you want to give a little bit, but some granularity on two areas.

Janet Hammond

So thank you for the question. And in regard to how the patients are apportioned to the combination versus monotherapy. I mean, obviously, first of all, just to say that and this is at the discretion of the investigators and prescribers, it sees the patient and they're encouraged to prescribe combination therapy if they believe that is appropriate for the patient and actually educators and quite extensively AHA investigational agents in that regard and important, I think is quite surprising is that the vast majority of patients are actually being assigned to the monotherapy arm. And I think the reasons for this probably are and really the potential extent of potential for drug interactions associated with return of that and in particular with combination treatment, which I think deter 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 pass and frequency, I think at least in the past, we've observed that falling back and some downward trend in the number of cases until we get towards the hotter summer months when people move indoors again. And so we're somewhat dependent on that you're going to have to see, Thank you.

Jean-Pierre Sommadossi

So related to the HCV questions are, I think with the Solvay from a third party, I really exemplify the importance of a lack of protease inhibitor in the combination treatment, especially when we are talking about about 40% of HIV infected patients with HCV or you're going to have substantial drug-drug interaction if we are 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 importance from a commercial standpoint and then I will ask around. So from a patient standpoint, John, you want to address that from a commercial standpoint.

John Vavricka

Sure. So Eric, from a commercial standpoint, obviously being pretty three is really important to us for the logo drug in R & DDI. interaction, potential Kong and also it. There's also other advantages such as having a new food effect and also to be able to treat with a shorter treatment duration, particularly important because as Roger mentioned earlier, in the presentation on what conditions are finding is that the shorter time to treat it better. And to highlight this about, you know, maybe we have a obviously a protease inhibitor and when you look at the new Rx market shares, even despite being eight weeks versus 12, and there is a third, there's almost a little bit more than a 10 point share difference in favor of a closer. And so that should you maybe also tell us some things as well.

Jean-Pierre Sommadossi

I'll wrap. So from a Patriot endpoint, after your gas production was down a lot in prescriber growth.

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 my ability in the sense that it's an eight week regimen and we felt the drug-drug interactions. I actually quite calm on that Maverick and protease inhibitors, a class and these are common drugs we're talking about like contraceptives and the retroviral therapies that beans proton pump inhibitors, which you know, almost everybody over four based on something like that. And so this is this is very important for the patient as the market which research has indicated. But also when we talk to the KOLs on the field than when they were actually trying to reveal our protocol and participate in our clinical trials. All of them were very excited that we could actually develop these best-in-class regimen bringing and the best of both attributes both regimens.

Eric Joseph

Thank you, Lorenzo.

Operator

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

Maxwell Skor

Great.
Thank you for taking my questions. And 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

Andre, you want to address that question? Maybe just start I would like to to to indicate that our for the loans we have actually a supply on your far. We are fortunate to have to get an approval in the US but we will not see a substantial investment in manufacturing at risk prior to approval. So we will provide additional information as we get closer to lunch.
So with that parenthesis, Andrea, yes.

Andrea Corcoran

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 on discipline in our investments for both the COVID-19 program as well as C. and 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 three program for COVID will begin to wind down before the Phase three begins for Hep-C and But nonetheless, we will be preparing for commercialization. As you've said, there will be additional activities that we will be funding at that point.
So the expenses for '24 and '25 are expected to increase, but and 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, John.

Jessica Hui

Hi, this is Jessica on for John Miller. Thanks for taking our questions. I have two questions, if I may. One on COVID one on hep C front, so for COVID. So you said Sunrise top3 line data expected in second half of the year. So how should we think about the various scenarios that can occur, how like how well does the market appreciate that pre-existing immunity from infection and or vaccine vaccination can affect placebo rates possibly making the effect size smaller, it may be a direct comp to exploit the 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 a follow-up question. Thank you.

Jean-Pierre Sommadossi

Jeff, if you'd like to address the question, please?

Janet Hammond

Thank you, Jessica. And yes, I think and I think everybody realizes that and with vaccination and prior exposure to COVID-19. And this diversity will frequency unless that fortunately right was how we were going through in particular, I think the Delta wave and hospitalizations are an all-time high for us that is designed to show a delta in efficacy comparable. So I think and what Pfizer most recently reported in their outpatient study where there was about a 50% or in the 50s, a difference between the active and the placebo groups into that. 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 of the worst outcomes. And so if one can prevent boost and reduce the severity of disease. I think that's going to be really important.

Jean-Pierre Sommadossi

I'd just like to add anything on. Oh, go ahead, Jim. Sorry.

Janet Hammond

Yes, it's just going to ask you if you wanted to follow on with Jessica's other question, Randy scenario clearly fails to achieve the primary endpoint.

Jean-Pierre Sommadossi

Yes, correct.

Janet Hammond

Okay.
So I think I mean, certainly I mean, it's one of the things that is that is under consideration is, you know if we're unable to do that and other sort of avenues to pursue in terms of looking for trends and we have a fast track designation with FDA to assess how how to proceed. And we also have, as I think, has been mentioned, two interim analyses and gravity S and B will help us to make the decision not to proceed, should we and see that data and no 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 and that at the moment and things are moving forward well. And and we look forward to presenting results unless you need to update as we move forward.

Jean-Pierre Sommadossi

Thank you, John. And just what I wanted to add to the first question is I think he was very telling that the NIH actually recently reported that only 15% of high risk actually had taken impacts love it and actually saw 85% of aiWARE school should get an old therapeutic done, we'll very likely many of the reason of the limitation of banks love it. So you can see that there is a huge opportunity for a best-in-class pilot and including even with the challenging that the challenges that we face as Janet and Jessica, you recognize in term of number of low event. But we believe that the way this study has been built, it will maximize the results for the efficacy and safety of this drug.
So I understand you may have another question on HCV as well.

Jessica Hui

Yes.
Thank you.
So I'm on the hep C program, given the context that compliance with existing therapies is lacking with existing regimen. So there's an unmet need here and the patients you're presumably going after are the ones that we know already are better compliance or else they procured.
All right.
How do you guys plan to ensure for the Phase three that the protocol and clinical sites can optimize good drug adherence, especially since. But we've already seen that one patient in Phase two part here at Road was thus unable to achieve SVR four.

Jean-Pierre Sommadossi

It's a great question Jessica, I'll answer and we spend quite some time on that. So answer you like to address two questions.

Arantxa Horga

Yes, it is a great question. I think a nice bar and 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 is a bit of a mix of the patients who are not taking drugs and they are just generalizations, but also does have a large population of patients that are ex IV drug users or producers and those really benefit from short treatment durations. As so I think by all financial remuneration, you're already addressing some of the compliance issues because, you know, patients in general are very excited to take dress at the beginning of it. Then, you know, sometimes they forget towards the end of the treatment. I think we have all experienced that. So the eight-week duration already held. And we, of course, have, you know, the level of measurements of checking with the patients calling them being in the mean and very important in Phase three 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 virus is behaving into a kind of population, which includes these patients that are noncompliant in general.

Jean-Pierre Sommadossi

And obviously, we will we will finalize any protocol with the regulatory authorities. So but but based on our initial interaction, it's clear that a a comparator is required for our Phase three program seeking them.

Jessica Hui

Thank you, very much.

Operator

And one moment for our next question.
And our next question will be coming from Roanno Ruiz with Leerink Partners. Your line is open.

Rosa Chen

And here this is Joseph Chan on for honorees at Leerink Partners. Just a couple from us. First on COVID, so thinking of all the various high-risk patients you're enrolling and site three, which the population do you think that the software 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

Do you like to address the question first?

Janet Hammond

And I think with regard to the high-risk patient population mean it's quite interesting. But I think in the last few months, there have been a couple of publications really sharing best and from the most high responses to 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 and how many times they get vaccinated it doesn't really seem to reduce their risk of getting severely ill when they and do become infected with COVID. So I think and these are the patient populations, which are probably the ones where there's likely to be the greatest benefit. And I think another reason why ultimately and I think Pammi foster there 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 antagonist. And so I think these are the patient populations flare and frequently that actually in eligible to receive a drug such as Paxil and I 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, the combination group and what really drove them to educate ourselves, it's ready. And most important, I think because we have as Jean-Pierre mentioned in her remarks and a protease inhibitor, which is being developed and which we hope to share more information later in the year. And so I think and being able to see how combination therapy and in particular, appreciate instances having combinations and Hospira is able to provide synergy and potentially reduced versus the teams and allow patients to improve better and also we're going to be looking at such things as on drug interactions and follow kinetics on safety and tolerability. I think all of that information is important in understanding how best we use these drugs and maximize them just as we do as we move further down the line.
Thank you.

Rosa Chen

Thanks so much. And then on HCB., how should we think about the PK and efficacy of semi-soft there, Andrew, is that fair in the patient population that actually have compensated cirrhosis compared to those without cirrhosis in your lead-in cohort? And then are you considering including patients with decompensated cirrhosis and Alta HIV co-infection and your Phase three U.S.?
So it's a similar. It 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 I'll answer. Maybe you want to I'll start to address the question and then I have maybe a comment as well, so I'll answer.
Yes.

Arantxa Horga

Well, I think the PK, we don't anticipate major changes in PK. or even PKPV. and viral kinetics and as you saw in the in the data and a lot of change, the kinetics were very fast even in the S. threes, which are really borderline compensated cirrhotics. So we think that and we've seen also in previous trials that the PK should be the same.
And that is for the compensated cirrhotics for the compensation metrics. It's a great population.
I think that we are going to have targeted is probably a probably a little bit later for the HIV. Certainly we are considering inclusion in Phase three trial. It is like you said and great unmet need population.

Jean-Pierre Sommadossi

Yes, no, actually, just one comments are for the decompensated patient. Obviously, that will be a we believe, a major advance because we foresee at least we see the potential to eliminate the rebannering, which right now you have only one approved treatment, which is a combination of a crews and rebalance in those patients.
Now let's not forget that this is it patient population that is very difficult, very likely in trial. You have interest from the U.S. So obviously, we foresee that this population will be very likely not part of the Phase three program unless the regulatory authorities will request that, but more as a first NDA commitment. But definitely we definitely want to go there, maybe not with a eight week, probably a 12 week would be already highly differentiated with the elimination of free Bhavin. And obviously, these patients do we acquire are they the best chance of success and that the length of treatment are less of an importance than what we have with a patient population that I will answer just share with you before.

Rosa Chen

Got it. Thanks, so much for taking our question.

Jean-Pierre Sommadossi

You're welcome.

Operator

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

Jean-Pierre Sommadossi

And thank you all for joining our fourth quarter and full year of 2023 Earnings Conference Call, and thank you as well for. We'll continue to support.

Operator

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