Atea Pharmaceuticals, Inc.

Good afternoon, everyone, and welcome to the ATF Pharmaceuticals 3rd Quarter 2025 Financial Results and Business Update Conference Call. At this time, all participants are in listen-only mode. Following the formal remarks, we'll open the call up for your questions. I would now like to turn the call over to Jonay Barnes, Senior Vice President of Investor Relations and Corporate Communication at ATF Pharmaceuticals. Ms. Barnes, please proceed.

Thank you, Operator. Good afternoon, everyone, and welcome to Atea Pharmaceutical's third quarter 2025 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 investor section of our website at ir.ateafarma.com. With me from Atea are our Chief Executive Officer and Founder, Dr. John-Pierre Sommadosi, Chief Development Officer, Dr. Janet Hammond, Chief Medical Officer, Dr. Arantja Horga, Chief Commercial Officer, John Vavrica, and Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, all of whom will be available for the Q&A portion of today's call. Before we begin the call, and as outlined on slide two, I would like to remind you that today's discussion will contain forward-looking statements that involve risk 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, Janae. Good afternoon, everyone, and thank you for joining us. I will begin our slides today. I'm pleased to share with you the significant progress and achievements we have made this quarter, which is a testament to strong execution across our team. Our global phase three program for the treatment of HCV is on track, and we expect to complete patient enrollment for our North American trial, CBR, next month. This timeline leads us to the first phase three top line result in mid-2026. For C-Forward, our trial outside of North America, we anticipate enrollment completion mid-2026 with top-line results anticipated by late-2026. And our answer will provide an update on our Phase III program. A few days ago, new modeling data was presented at the LIBER meeting 2025 in Washington, D.C., along with two additional data sets further demonstrating the antiviral potency with short treatment duration of our regimen for the treatment of hepatitis C. Janet will review the highlight of this data next. I'm pleased also to report that we announced today new exciting research findings. including evidence of a unique dual mechanism faction for benifazovir against HCV, further demonstrating its differentiation and potency, and I will review this data in a moment. In addition, I'm also very pleased to share with you that we are expanding our antiviral hepatitis pipeline for a major unmet medical need of immunocompromised patients living with hepatitis E infection. We have identified two new potent candidates derived from our nucleotide platform. IND enabling studies are ongoing to select the clinical candidate, which phase one initiation anticipated in mid-2026. We will discuss this program in more detail today's presentation. At the end of the third quarter, we maintain a strong balance sheet with approximately $329.3 million in cash, cash equivalent, and marketable securities, providing runway through 2027. This strong cash position enables us to fully fund our Phase III program launched the new regimen, and advanced our new HCV development program. With that, I will now turn the call over to Janet to review the highlights of the presentation at the LIVER meeting. Janet?

Thanks, Jean-Pierre. Let's move to slide five. I'm pleased to share with you that a few days ago, we presented multiple datasets at the LIVER meeting. These data reinforce the strong clinical and pharmacologic profile of our fixed-dose combination of regimen of Benifostavir and Ruvovir for the treatment of HCV. In an oral presentation, multi-scale modeling results predicted that our combination regimen inhibits both the intracellular replication of HCV as well as viral assembly and secretion of new HCV virions in the bloodstream. The model predicted a cure time of approximately seven to eight weeks. Because the regimen suppresses the virus at multiple critical stages, these data reinforce the potential of the combination regimen as a potent short duration therapy for chronic HCV. We also presented two posters. The first poster was identified as a poster of distinction. It highlighted a resistance analysis from the phase two study of our regimen, demonstrating that SVR12 rates were not impacted by NS5A-resistant variants at baseline. Viral kinetics and pharmacokinetics analyses indicated that most of the viral failures were due to treatment non-adherence and not to viral resistance. The second poster, reviewed the results from a phase one study in healthy participants, which demonstrated the high relative bioavailability of the Benifosavir and Bruzosvir commercial formulation for the fixed dose combination. These data also support dosing of the fixed dose combination with or without food and with famotidine, an H2 blocker, which can substantially diminish the effectiveness of oral antivirals. The fixed dose Commercial formulation is being used in our ongoing phase three program. Moving to slide six, we will host a virtual panel event featuring key opinion leaders or KRLs in hepatology, gastroenterology, infectious diseases, and hepatitis C tomorrow, Thursday, November the 13th at 10 o'clock Eastern time. The discussion will cover a wide range of HCV-related topics, including the needs of the current HCV patient population, the importance of early diagnosis and treatment, public policy initiatives including the test and treat model of care, and whether HCV eradication in North America is an achievable goal, what benefits a new optimized HCV therapy could provide for prescribers and patients. The link to register for this event can be found in our latest quarterly press release distributed earlier today. and on the investor section of our website under events and presentations. The virtual panel discussion will feature several HCV key opinion leaders, including Jordan Feld from the University of Toronto, Toronto General Hospital in Canada, Eric Lawitz from the Texas Liver Institute, University of Texas Health San Antonio, Anthony Martinez from the University of Buffalo Erie County Medical Center, and Nancy Rowe from Rush University Medical Center in Chicago. A live question and answer session will follow the formal discussion. We hope you can join us. I'll now hand the call over to Arantxa to review our phase three program for hepatitis C. Arantxa?

Good afternoon, everyone. On slide eight, let's now turn to our global phase three program, which is the first head-to-head phase three program for chronic hepatitis C. comparing our regimen against the current global standard of care, so Phosphovir and Belpatavir marketed as exclusive. Our regimen includes Benifosphovir, the most potent nucleotide inhibitor, and Ruscovir, a highly potent NS5A inhibitor. Data support our regimen as a potential best-in-class treatment option for patients infected with HCV. With a differentiated profile, featuring a short duration, low risk of drug-drug interactions, and convenience with no food effect. I would like to highlight that we have new study results demonstrating no risk of drug-drug interactions with proton pump inhibitors, which are estimated to be taken by at least 35% of HCV patients. These results will be presented at an upcoming scientific meeting. We view this as a key differentiator since proton pump inhibitors can substantially decrease the effectiveness of currently approved DAA therapies for HCV. Our Phase III program is designed to confirm the efficacy, safety, and tolerability demonstrated in our robust Phase II study, where we achieved a 98 percent sustained biological response at 12 weeks post-treatment, or SBR12. These Phase II results gave us confidence to move to our current Phase III late-stage program. Historically, in HCV development, Phase II data have proven to be highly predictive of Phase III outcomes, given the well-understood biology of the virus, and the reliability of SDR-12 as an established clinical endpoint for cure. Moving to slide nine, the Global Phase III program is composed of two pivotal trials, See Beyond, which is enrolling across approximately 120 sites in the U.S. and Canada, and See Forward, which includes another 120 sites across 16 countries outside of North America. Combined, these studies are expected to enroll approximately 1,760 patients. Both trials are open-label and randomized one-to-one against the active comparator. And they are stratified by cirrhosis status and genotype, including HIV co-infected patients. In non-cirrhotic patients, treatment duration is eight weeks. compared to 12 weeks with the standard of care. For patients with compensated cirrhosis, patients receive 12 weeks of either regimen. The primary endpoint for both studies is FVR-12, which is recognized as the definitive measure of HCV cure. Slide 10. I am pleased to confirm that enrollment in the North America CB-YON trial is on track for completion next month. with top line results anticipated mid-2026. For C-Forward, which has a broader global geographic footprint, enrollment completion is expected mid-2026, followed by top line results by year end of 2026. I will now hand the call over to Jean-Pierre to review our new mechanism of action data. Jean-Pierre?

Thank you, Reza. Let's now move to slide 12. As many of you know, venifosbuvir is a nucleotide NS5B polymerase inhibitor with an established mechanism of action of inhibiting HCV RNA through chain termination, thus blocking viral production and verification inside the cell. Our collaborators at Los Alamos National Laboratories, headed by Dr. Alan Pearson, have conducted HCV-valve kinetic modeling using data from the Phase I Benefosbuvir monotherapy trial. The new modeling suggested that Benefosbuvir may have an additional mechanism of action inhibiting HCV viral assembly secretion of new HCV variants in the bloodstream, significantly reducing extracellular HCV RNA, a mechanism previously only associated with NS5A inhibitors such as Ruzasvir and Velpastavir. On slide 13, In vitro studies conducted under another collaborator at Loyola University confirmed this dual mechanism of action for benifosbuvir. On this slide, the study showed that the level of the intracellular HCV RNA were comparable with selected concentrations of benifosbuvir and sofosbuvir. So while both agents produce these similar declines of intracellular HCV RNA, as you can see, Benifaz will be led to a far greater and faster reduction in extracellular RNA, indicating possible inhibition of viral assembly and release into the bloodstream. On slide 14 now, the other in vitro study shows that intracellular RNA, HCV RNA, were comparable with selected concentration of benifosbuvir and an NS5A inhibitor such as valpastavir. So of importance here, extracellular HCV RNA level decreased similarly with benifosavir or belpastavir, an NS5A inhibitor, demonstrating that benifosavir also inhibits HCV assembly and secretion into the bloodstream in addition to inhibiting viral replication. So in the slide 16, you can see this cartoon which illustrate on the left side, the HCV life cycle. And then on the right side, the dual mechanism of action for Benifazovir showing how Benifazovir blocks the virus from making copies inside the cell. And it also blocks new virus from entering the bloodstream. Therefore, on slide 16 what the data means. The data demonstrate that benifosavir is a potent and differentiated nucleotide prodrug with a unique dual mechanism of action, which may explain now the higher potency of benifosavir as compared to sofosbuvir. Even in the presence of NS5A resistance, benifosavir will continue to block violent assembly secretion due to its dual method of action. Lastly, these results further highlight the differentiation and the potency of the benifosavir and risosavir regimen for the treatment of hepatitis C. With that, I will now turn the call over to John for an overview of the new hepatitis E virus program. John?

Thank you, Jean-Pierre. As shared earlier by JP, we are expanding our pipeline of oral direct acting antiviral candidates to include hepatitis E virus, or HEV, a virus with no approved therapies and high unmet medical needs. As seen on slide 18, The WHO estimates that there are 20 million global infections annually. HIV is an inflammation of the liver caused by the hepatitis E virus. It is a growing public health challenge in both the developed and developing world. In developing countries, genotypes 1 and 2 are most prevalent, and the virus is transmitted primarily through contaminated water. In developed countries, genotypes 3 and 4 are most prevalent, and the virus is transmitted primarily through contaminated foods such as undercooked meat. Moving to slide 19. However, in recent years, there's been a growing incidence of chronic HEV genotype 3 and 4 infections in immunocompromised individuals. A population that includes solid organ transplant recipients, hematopoietic stem cell transplant recipients, as well as patients with hematological malignancies and preexisting liver disease. In these patients, HEV may not resolve spontaneously resulting in chronic HEV infection, which left untreated can quickly lead to liver inflammation, rapid fibrosis progression, and in some cases, cirrhosis within three to five years of infection. Currently, there are no approved therapies anywhere in the world for HEV. For at-risk populations, clinicians can reduce immunosuppression, which risks organ rejection or relapse of underlying disease. Some clinicians also use ribavirin, an older antiviral therapy approved for other viral infections, off-label for HEV, which yields inconsistent efficacy results and is often poorly tolerated and poses risk of significant toxicities. This leaves clinicians and patients with a significant unmet need for a safe, orally available, direct acting antiviral that can achieve sustained viral clearance or cure. Let's move on to slide 20. The number of immunocompromised patients continues to rise each year in the US and Europe. There are approximately 450,000 cases of solid organ transplants, hematopoietic stem cell transplants, and hematological malignancies per year across these markets. While advances in modern medicine, especially in transplantation and oncology, have led to an increased survival, it may likely also explain why more HEV is being observed in these at-risk populations. Approximately 3% of these at-risk patients go on to develop chronic HEV. While the overall prevalence of HED is high in the general population, a relatively smaller proportion of immunocompromised patients are at risk for poor outcomes. As such, there is the potential to seek an orphan drug designation, which can have development and regulatory advantages. These life-saving procedures continue to expand the population of immunocompromised patients that could be susceptible to chronic HEV infections. Using other viral infections such as hepatitis D virus as a guide to pricing, this HEV market opportunity could translate into roughly between $500 to $750 million per year or more. I will now turn the call back to Jean-Pierre to review preclinical data for our two candidates for HEV. JB?

Thank you, John. So moving to slide 21, the in vitro data on this slide shows the potent nanomolar antiviral activity of AT587 and AT2490 against hepatitis virus genotypes 1 and 3. And underscore YHEV represent the compelling extension of our antiviral platform. Our two candidates demonstrate approximately 200-fold higher antiviral activity in vitro as compared to ribavirin, which, as John mentioned, is used off-label for the treatment of hepatitis E virus. While in vitro and in vivo activity of benifosavir was also shown against HEV, and that's how we start to understand that our platform could have some anti-HEV activity, the tenfold higher activity for 8587 and 802490 led us to advance these two promising candidates. On slide 22, it is interesting to point out that only a fluoroatom in the sugar ring differentiate the active triphosphate metabolite 809068 from the two analogs 80587 and 802490 as compared to 809010, which is the active triphosphate of benifosbuvir. For particular importance, these two candidates efficiently convert to the active triphosphate form in human hepatocytes and have a clean preclinical safety profile to date, positioning them as leading candidates for first-in-class hepatitis E antivirals. IMD enabling studies are ongoing to select the clinical candidate for Phase I evaluation. We are also pleased to announce that we will be presenting more information on our HEV program at an upcoming scientific meeting early next year. I will now turn the call over to Andrea to discuss our financials. Andrea?

Thank you, Jean-Pierre. As Joneigh mentioned in her introductory remarks, earlier today we issued a press release containing our financial results for the third quarter of 2025. The statement of operations and balance sheet can be found on slides 24 and 25. In the third quarter of 2025, R&D expenses increased compared to the same period in 2024. This increase was principally attributable to increased spend in 2025 in our HCV clinical development program. For G&A, expenses in the third quarter of 2025 decreased in comparison to third quarter 2024. The decrease was primarily driven by lower 2025 stock-based compensation. Interest income in Q3 2025 decreased compared to the third quarter of 2024 due to lower investment balances. For the remainder of 2025, we expect our R&D expenditures will be driven principally by the conduct and advancement of our global phase three HCV program. As Jean-Pierre mentioned at the beginning of the call, at the end of third quarter of 2025, our cash, cash equivalent and marketable securities balance was $329.3 million. Continuing our strong financial discipline, we project our cash guidance runway through 2027. With respect to other matters, I would like to note that we continue to evaluate options to maximize shareholder value. As announced, we completed our share repurchase program after having repurchased the full $25 million of shares authorized by the Board. Under the program, we repurchased a total of 7.6 million shares of common stock at an average purchase price of $3.26 per share. All repurchased shares were retired and returned to authorized but unissued status. Regarding our strategic process, as we've previously stated, we believe the HCV phase three clinical development results will drive the shareholder value and catalyze business development discussions. While our discussions to date with potential counterparties have been positive, positive phase three outcome, would further significantly de-risk the program, strengthening our ability to maximize the value of this asset and to secure attractive terms. For this reason, today we announce the conclusion of our formal engagement with Evercore. While we now focus principally on the execution and completion of the phase three trials, which we believe is the best path forward at this moment to drive shareholder value, we remain open to all opportunities to drive shareholder value, including a potential strategic transaction. I'll now hand the call back to Jean-Pierre for closing remarks.

Thank you, Andrea. Slide 26. In closing, the significant progress and achievements we have made within the last quarter reflect strong execution across our team. We are on track with patient enrollment in our global Phase III program for the treatment of HCV. And we look forward to the top-line Phase III results from the U.S. and Canada trials C. b. young in mid-2026, followed by top-line results expected for the outside North American trials C. forward at the end of 2026. We continue to present new data supporting the potential best-in-class profile of Benefazvir and Resazvir for the treatment of hepatitis C. If approved, we believe it can become the most prescribed treatment for hepatitis C and disrupting and expanding the current global HCV market of approximately 3 billion in annual net cells. The new data we view today demonstrate a new and unique dual macrosulfaction for benifosbuvir against hepatitis C, highlighting its unique and differentiated profile as compared to sofosbuvir. And this data now can explain in part the potency of our regimen for the treatment of hepatitis C. In addition to our HCV program, I'm really pleased to share the information today about the potential of our proprietary preclinical candidates derived from our nucleotide platform, along with the expansion of our antiviral pipeline. These compounds may help to address the unmet needs of the many immunocompromised patients living with hepatitis E virus infection, and we look forward to providing More updates soon on this program. Before opening the call to your question, I would like to thank our talented and dedicated employees. Our team's relentless pursuit of excellence drives our dedication to advancing all antiviral therapeutics for patients worldwide. affected by severe viral diseases. With that, I would turn the call back over to the operator.

Thank you. We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed, and you would like to withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster.

The first question comes from Maxwell's call with Morgan Stanley.

Please go ahead.

Hello, this is Selena on for Max. Thank you for taking our question. How does your recent data set at the liver meeting showing no interaction with famotidine in addition to your prior data showing no interaction with PPI increase your differentiation from Ipclusa?

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

Certainly. Thank you. Thank you, Dina, for the question. So I think we know that there is in the label for Ipclusa a contraindication to the concomitant use of H2 reducing therapy with Aplusa and the recommendation in their label is for there to be at least a four hour window of separation between dosing of the one and dosing of the other. Proton pump inhibitor use is widespread in the U.S. I think I said on the last call about 10 to 20 percent of the U.S. population apparently uses this type of therapy generally over the counter. but it's actually even higher in patients with hepatitis C, and it's estimated to be around 35% of HCV patients use acid-reducing therapy. So this is a clear problem for patients when they're taking therapy because it can reduce the levels of antivirals that are achieved, and this can compromise efficacy. So we see this as a really important differentiator.

Thank you.

Great. Thank you.

The next question comes from the line of Andy Shea with William Blair. Please go ahead.

Thanks for taking our questions. I have two. One is from the modeling poster that you presented at AASLD. There is a chart basically showing time to undetectable. And interestingly, there is a separation between genotype one and genotype three, with three showing a more rapid, you know, time to undetectable. I'm curious, you know, if there's any significance in that. And also, maybe the observed, you know, trend, does that have to do with a dual mechanism that you announced earlier? So that's question number one. Question number two.

Maybe I can address it first, and then after we go over the second one. So, thanks for looking at the slide of the presentation, the deliver meaning. Indeed, you're correct. The modeling suggests that there is a more rapid decline with Genotype 3. We know that benifosbuvir is, interestingly, more potent in vitro, actually, against genotype 3 than genotype 1a or 1b. When we did the in vitro study about 10 years ago now, that's another differentiation with sofosbuvir, for example. where it's supposed to be less potent on genotype 3. So it's possible related to the dual mechanism. And as Andy had suggested and wrote in one of his reports a few months ago, that at least in the phase 2, we had 100% cure. in our genotype 3 non-serotic patient, which definitely, at least as compared historically to other regimens, were very high rate, very high cure rates.

Yeah, that's correct. Okay. Great. Thanks for sharing that perspective. The second question has to do with the compound that you outlined in the slides for hepatitis E, you know, maybe more of an academic question, but it doesn't employ the proteid technology. So I'm curious if that's kind of a deliberate decision, or maybe in this context, proteid doesn't, you know, is not optimized for proteid. I'm curious if you can comment on that as well.

Thank you. Sure. I can tell you that we did not include the chemical structure, but it is exactly the same prodrug that we have used for BEM, which is a phosphoramidate. So it's identical, so we feel very comfortable with the PK and the safety. and the efficacy as well. So as you have seen, interestingly, it's only the fluoroatom at the four prime position that differentiate between 587 and BAM, for example. And what's interesting is that while we are 10 times more potent with 587 and 2490 as compared to BAM in hepatitis E, these are less potent as compared to BAM in hepatitis C by about the same magnitude of about tenfold. So here we have a very specific inhibition of hepatitis E with this active triphosphate, and we are evaluating now really the molecular rationale of the binding of the polymerase, why we are more potent, but definitely has to be a better binding with the presence of the 4-prime fluoatom.

Oh, great. Thanks for that, JP. Great. Well, good luck with the Phase 3 readout, and look forward to additional information from the hepatitis E program.

Thank you so much for your questions. Thank you.

This concludes our question and answer session. I would like to turn the conference back over to John Peer for any closing remarks.

Again, thank you all for joining us. to our third quarter earnings conference call, and thank you for your continuous support.

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Thank you.