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spk11: Good afternoon, ladies and gentlemen. Welcome to the ITEA Pharmaceuticals Third Quarter 2022 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 up the call for your questions. In order to ask a question, please dial star 11 on your telephone keypad. I will now turn the call over to Janae Barnes, Senior Vice President of Investor Relations and Corporate Communications at Attea Pharmaceuticals. Ms. Barnes, please proceed.
spk07: Thank you, Operator. Good afternoon, everyone, and welcome to Attea Pharmaceuticals' third quarter 2022 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 irateafarma.com. With me today from Atea, our Chief Executive Officer and Founder, Dr. John Pierre Sommadosi, Chief Development Officer, Dr. Janet Hammond, Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, and our Chief Commercial Officer, John Zabrica. They will all be available for the Q&A portion of today's call. Before we begin the call, as outlined on slide two, I would like to remind you that today's discussion will contain forward-looking statements that involves 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.
spk05: Thank you, Janai. Good afternoon, everyone, and thank you for joining us. We have a number of updates to review with you today that demonstrate the considerable progress we have made so far this year across our three clinical programs. Turning to slide four, as we assess today COVID-19 landscape with the rapid increase in dominance of multiple new variants in different regions of the world, Combined with social dynamics back to near pre-pandemic norms, epidemiologists predict that COVID-19 will persist with multiple waves as we currently see today. The warning durability associated with vaccines and natural infection and the low uptake in the number of people receiving their Omicron booster vaccine with only less than 10% in the U.S. currently, we continue to close large numbers of infected individuals and reinforce the need for new direct acting oral antivirals. Looking forward, as we start enrollment of Sunrise 3, our global Phase 3 registration or trial, these ongoing waves with variants not susceptible to currently available preventive tools should enable timely enrollment of patients for this trial. Pandemic COVID-19 waves can be life-threatening to those at high risk over 65 years old, particularly to those with risk factors causing increased hospitalization and deaths. New all-volunteer valves with improved profile are urgently needed due to the limitations of the current antiviral options. In addition to relapse and safety concerns, the major issue of drug-drug interaction between Paxlovin and commonly prescribed life-saving drugs lead to a major unmet need among patients that are at risk for severe disease. With venifosbuvir, we have the potential to address many of these limitations, and it is our top priority to deliver this direct candidate as fast as possible. Turning to slide five, as SARS-CoV-2 variants continue to splinter, we are confident that Benifazil will remain fully active against ongoing and future new variants based on the consistency potent in vitro antivalent activity that has been demonstrated against variants of concern. Indeed, our most recent dataset demonstrates in vitro antivalent activity against omicron subvariants BA.4 and BA.5, similar to the potency observed with alpha, beta, gamma, epsilon, delta, and omicron subvariants BA.1 and BA.2. I will now turn the call over to John to review the overall anti-viral market opportunity for COVID-19. John?
spk02: Good afternoon, everyone. Turning to slide six, while initial COVID-19 revenues were driven by advanced government purchases, we believe the COVID-19 anti-viral market will remain a very large market opportunity for years to come. Paxlovid and Ligabrio are each multibillion-dollar products despite the limitations which cause prescribing hesitancy. Turning to slide seven, over the next year, the U.S. Department of Health and Human Services has suggested and we anticipate the U.S. market will transition from advanced government purchases to more traditional channels, which we expect will continue to be a multibillion-dollar opportunity. Projected annual COVID oral antiviral demand using IQVIA retail prescriptions suggests an estimated annual market between $10 and $20 billion. Beyond that, we believe there is an opportunity to expand this market by simplifying prescribing for patients where Paxlovid drug-drug interaction is a concern. There are several important classes of commonly prescribed drugs that limit the ability to safely prescribe Paxlovid. including seizure medications, antipsychotics, anticoagulants, and more. Additionally, the government is expected to move beyond advanced purchases to recurring stockpile purchases once oral antivirals against COVID-19 are fully approved. I'll now hand the call over to Janet. Janet?
spk08: Good afternoon. Turning to slide A. Our COVID-19 strategy is focused on the current highest unmet medical need. We're targeting the most vulnerable patient populations who are at the greatest risk for disease progression to severe COVID-19 or mortality, and for whom there are the fewest treatment options available currently. The Mifosbuvir's results to date demonstrate its very favorable profile, including clinical benefits, its safety and tolerability, and the low risk for drug-drug interactions. This profile should allow benifospivir to become a cornerstone of mono and combination oral therapy for the treatment of COVID-19. Our combination antiviral cohort in the Sunrise 3 trial will inform our future development strategies, and we are at the forefront of developing combination therapy for specific populations, such as the immunocompromised. Demnifosavir has already demonstrated additive benefits in vitro in combination with authorized direct acting antivirals, including protease inhibitors, and we continue to advance our internal protease inhibitor program for combination therapy with demnifosavir. Moving to slide 9, the statistics show unequivocally that hospital rates and deaths from COVID-19 remain highest in the population which we plan to study. And these are the primary endpoints for the Sunrise Tree trial. In the US, alarmingly, COVID-19 is now the third leading cause of death after heart disease and cancer, with hundreds still dying daily. According to the CDC, approximately 75% of COVID-19 deaths are in patients 65 years of age or older. The CDC has also stated that 50% of hospitalized patients over 65 have had at least three shots of vaccine, with rates of hospitalization a further three times higher in unvaccinated adults. It's important to note that in immunocompromised patients, rates of hospitalization in excess of 20% have continued to be reported with Omicron. Moving to slide 10. Let's now review our COVID-19 study design for Sunrise Tree. our phase three registrational trial that will assess demnifosavir as both mono and combination antiviral therapy. This global phase three trial is a randomized, double-blind, placebo-controlled study which will evaluate demnifosavir or placebo administered along with the local standard of care. We expect to enroll at least 1,500 high-risk patients with mild or moderate COVID-19. Patients will be randomized one-to-one to receive either benfosfibir 550 milligrams or placebo twice daily for five days. Two study cohorts defined by the type of standard of care the patients receive will be studied. The first cohort is a monotherapy cohort, which will be comprised of patients receiving supportive care, and this represents the primary analysis population. The second cohort is a combination antiviral cohort, that will be comprised of patients who are receiving a compatible antiviral against COVID-19 as part of their locally available standard of care. The primary endpoint of the study is all-cause hospitalization or death through day 29 in at least 1,300 patients from the monotherapy cohort. You will recall we have already evaluated hospitalization in the Morning Sky trial, and demnifosbuvir showed a 71% reduction in hospitalization versus placebo. Importantly, in addition, the subgroup analysis showed an 82% reduction in patients over the age of 40. Moving to slide 11, Sunrise 3 will focus on high-risk patients that are at the greatest risk for disease progression to severe COVID-19 or mortality. This includes patients 80 years or older, patients 65 or older with one or more major risk factors for severe COVID-19, or immunocompromised patients over 18, all regardless of vaccination status. The study is expected to have a large global footprint with up to 300 sites in 25 countries, which will include the United States, Europe, Japan, and also the rest of the world. We will imminently begin enrollment of the Sunrise 3 trial in the United States, and we have submitted or are in the process of submitting clinical trial applications in other countries. Turning to slide 12, let's now review our dengue program. Dengue is the most prevalent mosquito-borne viral disease globally and affects almost 400 million individuals on a yearly basis. Dengue is endemic in over 100 countries, and more than half of the world's population is at risk. Despite all of this, there are no currently approved treatment options for dengue. The FENDT2 is a randomized phase two proof of concept study in patients with dengue fever that is enrolling in dengue endemic areas. It is designed to assess antiviral efficacy, safety, and the pharmacokinetics of multiple doses of AT752 with a primary endpoint of change in dengue virus viral load from baseline. AT752 or placebo are administered orally for five days and up to 60 patients in three cohorts may be studied. Our second dengue study is a human challenge model that is being conducted in the United States. In this study, healthy volunteers are dosed with AT752 or placebo and then administered a live dose of dengue virus. Subjects are closely monitored within a very controlled setting, allowing assessment of viral load and the viral kinetics between the treatment groups. We expect to complete enrollment of the challenge study and enrollment of the first cohort of 20 patients in the defend-to study around the year end, with results to follow. Additionally, I would like to mention that we presented results from the AT752 Phase 1 study in 65 healthy volunteers last week at the American Society of Tropical Medicine and Hygiene 2022 Annual Meeting. These data demonstrated that AT752 was generally safe and well-tolerated without drug-related serious adverse events or discontinuations. Drug plasma levels above the in vitro EC90 were rapidly achieved. Based on these data, we anticipate that AT752 has the potential to rapidly inhibit dengue virus replication across all serotypes 1 through 5. Turning now to our hepatitis C program, as shown on slide 13, Our HCV combination program looks very promising and has potential to improve on the current standard of care. Our HCV combination profile includes the potential for a convenient and short-duration protease inhibitor-free treatment and the possibility for the first ribavirin-free therapy for decompensated disease. We believe Ruvozir, in combination with BEM-Methospervir, provides the opportunity to create a best-in-class, pan-genotypic HCV therapy. Clinical trial applications will be submitted around the end of the year, with the initiation of the Phase II clinical trial to follow. With that overview, I'll now hand the call over to Andrea to review our financial information.
spk06: Thank you, Janet. As Joneigh mentioned in her introductory remarks, Earlier today, we issued a press release containing our financial results for the third quarter of 2022. The statement of operations and balance sheet are on slide 17 and 18. R&D expenses decreased by $38.1 million from $43.0 million for the three months ended September 30, 2021 to $4.9 million for the three months ended September 30, 2022. The decrease in R&D expenses was primarily due to the elimination of the cost-share arrangement with Roche, our former COVID-19 program collaborator, and includes a credit in the amount of $14.5 million related to the closeout by Roche of certain clinical trial activities that were previously the subject of the cost-sharing arrangements. General and administrative expenses remained relatively consistent at approximately $11.9 million for the three months ended September 30, 2021, and $11.4 million for the three months ended September 30, 2022. Also in Q3, we recorded interest and other earnings on our cash reserves in the approximate amount of $4.4 million, and we expect to receive a tax refund of approximately $3.7 million associated with the 2021 tax returns. In closing, with $665 million in cash, cash equivalents, and marketable securities at quarter end, we are pleased to reiterate our cash guidance with a runway through 2025. I'll now turn the call back over to Jean-Pierre for closing remarks.
spk05: Thank you, Andrea. This year we have made substantial progress advancing our three clinical candidates, which will take us to a pivotal year in 2023. Our team is operating with a sense of urgency because there is an immediate need for new oral treatment options for COVID-19. We will immediately begin enrollment of our global Sunrise III trial with the goal to deliver safe and effective oral direct acting antiviral to patients as quickly as possible. In addition, We soon expect enrollment completion of the challenge study and the first cohort of different two for dengue with results to follow and the initiation of our phase two combination program in HCV. I would like to take the opportunity to thank the entire TEA team for their tireless dedication to our mission of transforming the treatment of several viral diseases and without whom none of this progress would be possible. With that operator, We will now open the call up to your questions.
spk11: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press the star 1-1 on your telephone keypad and wait for your name to be announced. Please stand by while we compile our Q&A roster.
spk10: Our first question comes from the line of Ms.
spk11: Hannah Adeoye with J.P. Morgan. Hannah?
spk12: Hi, yeah, this is Hannah on for Eric. Thanks for taking the questions, just a few from us. So first, can you speak to just the rationale behind doing this mini-challenge study, and what questions do you think it's going to address separate from that of the inpatient ventricle study? And how informative do you think that human challenge data might be in addressing the clinical activity of AP5-752? And then also, can you characterize the data sets that we might be seeing from both phase two studies? Should we anticipate data from exploratory endpoints as well? And when might we expect updates from subsequent cohorts? Thank you.
spk05: Janet, do you want to take the questions?
spk08: Thank you. Yes. So in regard to the rationale for the challenge study, we think it's very complementary to the treatment study and should provide us with a really good idea of how AT752 performs in dengue. As mentioned, the patients or the volunteers in the challenge study are administered a live dose of dengue, but on the background of either treatment with 752 or placebo. And so I think here we really have a good example of the natural biokinetics, really, of infection in the placebo patients, the potential for protection against infection altogether, but also, I think, a good glimpse of whether the 7-type 2 is efficacious against the infection. And so I think, together, we get a good sense of what happens in a dengue infection and also what is likely to happen if the drug is administered prophylactically. So I think, altogether, the two studies together should give us a very good understanding of how 7.2 performs against this flavivirus and allow us to make the decisions around whether we need further cohorts and what type of dosing we're looking at for those in terms of treatment durations and so forth. So I think they're going to be very informative. It's unfortunately a disease which is not all that well understood. And so I think having some real world evidence in this way seems to be very important for us. And with regard to when we'll have data sets available, as we mentioned, we plan to complete both the challenge study as well as the initial cohort of patients in the phase two trials by year end. And then we will analyze and incorporate those data, and that will allow us to make decisions around what questions, if any, we need to answer as we plan the enrollment of subsequent cohorts if they're needed.
spk12: Okay, so we won't be getting data this year from any of those programs.
spk05: Well, we never committed to the data as indicated. It's going to be early next year, as we have indicated many times. So in the same time, what I would like to reiterate what Janet was saying is that we are going to be the pioneer here for the treatment of dengue. So far, as you know, there is not a single direct acting antiviral that has been successful. Everyone has failed. So we are the pioneer both in terms of treatment duration, how long do we need. We are right now for five days. We have two weeks for the prophylactic. We are learning from the experts in the field that there may be some rebound from the disease itself. So it's, as Janet has indicated, we are waiting to have both studies to make sense of both studies are highly complementary as proof of concept and understand how we are going to move forward into larger studies.
spk12: Okay, great. Thanks for taking the question.
spk11: Thank you. Our next question comes from the line of Matthew Harrison. of Morgan Stanley. Matthew, please stand by.
spk09: Thank you. So what level of viral load reduction of dengue is clinically meaningful, or are the kinetics more important? Thank you.
spk05: Jarrett?
spk08: So it's an interesting question, Matthew. I don't know the answer to it necessarily. I think we're going to learn a lot, as I said, from having both the the patients on the placebo group as well as on the active in the prophylactic study and also in the treatment study, I think to be able to compare and contrast. We know that the viral load declines very rapidly naturally after a couple of days, but what we're interested to see is whether we can get it to come down more quickly. But some of what you're asking, I think we don't really know the answer because there are no effective therapies I don't think it's possible really to make that assessment yet.
spk09: Okay. Thank you.
spk11: Okay. Our next question comes from the line of Umar Rafat with Evercore. Umar, please stand by. Umar, your line is open.
spk01: Thank you. A couple of questions, if I may. First, we saw Gilead post a phase three trial of their oral remdesivir pill. And there's a couple of things that stand out versus your trial design. First, Gilead's using almost 2X the powering. And second, they're limiting the trial to patients with at least four months or more since the last vaccine dose. Maybe if you could speak to those dynamics and those two dimensions as you thought about your trial design, number one. And secondly, back on dengue, perhaps just to pick up on the prior question, If the viral load truly is declining so rapidly after a couple of days, is that consistent in patients that do end up getting hospitalized too? Because I've got to imagine some sort of hospitalization endpoint is what leads to ultimate utilization and perhaps even approval. And if you could also speak to the human challenge study that you were attempting to run. There was only 12 patients. I didn't hear you say much on that. Where do we stand on that? Thank you.
spk00: Janet?
spk08: Thank you. So with regard to the Gilead H3 trial, I haven't seen the study design, so I can't comment on how their population compares to ours. So with regard to the powering, I'm really unable to comment. With regard to the more than four months requirements into the last vaccination, again, I don't know where they're doing their study, but I can say that for our study, we have a truly global footprint, as I mentioned, in more than 25 countries. And I think you'll be very aware of the fact that not everybody's getting the same vaccines and not everybody's getting them on the same schedule. So we think that in order to allow the study to enroll, the most pragmatic way is really to allow patients to come in regardless of vaccination status if they get COVID-19, because that's really what we care about. And we'll see what the hospitalization rates are like. Unfortunately, I think in the patient population that we're planning to study in this study, the immune response to the vaccine can be quite limited anyway. So we think that many of these patients are unfortunately still going to be fairly susceptible to COVID-19. And you'll recall I mentioned on the call around the data for 50% of patients over the age of 65 being hospitalized having had at least three shots of vaccine in the U.S. And so I think we're still likely, unfortunately, to see a fairly good representation of patients being hospitalized, even if they have been vaccinated. And again, it's a pragmatic approach in order to be able to help us to take the study forward. And we'll have to see how that translates. With regard to viral load and the rapidity of the decline, We know that the viral load does decline rapidly, and I think to some extent we don't yet know how that translates into the need for hospitalization. What we do know is that if patients are repeatedly infected with dengue, what really causes the hospitalization is the infection leading to cytokine storm, and how cytokine storm relates to rapidity of decline in viral load, I think it's uncertain. I think the main thing is that it's important to eradicate the virus as quickly as possible to help reduce the chances for that type of immune response. But again, I think this is really the front end of the learning curve for everybody with therapeutics for dengue.
spk05: Just to add, well, I'm sorry, just to add, and then I'll let you add for the challenge, just to add to Jan, it's about the viral load. the only correlation I've been made that would appear to suggest that viral load are important for severity of the disease is that the two strain, the strain, the dengue one and dengue two are the one with the highest viral load and they are the one that basically causing the majority of severe disease. So that's where there is some kind of correlation, but nothing very more direct than that. I'll let Janet address the challenge part also. Janet?
spk08: With regard to the challenge study, we're still in the process of enrolling the 12 patients into that cohort. So if There isn't much more that I can provide in the way of an update, but we anticipate that wrapping up fairly shortly now.
spk11: Thank you. Our next call will come from the line of Tim Lugo with William Blair. Tim, please stand by while I open your line up.
spk03: Taking the question.
spk11: Yes, can you hear me? Yes, your line is open.
spk03: Okay, great. For the combination patients that you're going to be getting out of Sunrise 3, is it safe to assume that those are going to be mostly elderly and immune compromised, or is that more of just a geographic, I guess, division between who would receive combination therapy and who wouldn't?
spk05: Janet?
spk08: I think it really is going to depend on the prescriber to some extent. Some of it will be geographic in terms of access to which antivirals are available and standard of care in an area. I think for many patients, particularly in the United States, it's likely that patients will be limited to monotherapy if there are significant drug interactions preventing them from getting Paxlovid, but they are still also able to be prescribed molnupiravir, although there doesn't seem to be much that is prescribed. So I think it's likely, and we anticipate that there will be more combination use really across the board in certain areas of the world. But I think, again, the unmet need seems to be even in those areas that the profile of the drugs which are currently available is rather causes some reluctance in prescribing often. Okay.
spk03: And do you have a sense of rebound? I know that's obviously very topical in the popular press a lot, but do we really have any good data on rebound rates for oral therapy, antiviral?
spk10: John?
spk08: Yes. I think you're probably reading the same literature that I am. And quite honestly, I think it's perplexing still. The rates seem to be variable. One hears also of patients not receiving therapy who also experience relapse. I think it's difficult to be certain. And the anecdotal experience that one has of people experiencing relapse or rebound And what is written in the literature also seem to be somewhat divergent. So, no, I don't have a good idea yet.
spk03: I understand. Thank you.
spk11: Our next question will come from the line of Nick Gassick with SVB Securities. Nick, please stand by while I open up your line.
spk04: Nick Gassick on Verona release. Thanks for taking our questions. First off, for the new phase three COVID-19 program, I'm just curious, are you planning to feature both primary and secondary endpoint data in the interim analysis? And if so, when do you expect to share these results?
spk05: Janet?
spk08: So we're anticipating that we'll have results from the interim analysis in the second half of next year. And I don't think we've discussed whether we're going to showcase data from both primary and secondary endpoints, so I can't answer that today.
spk04: Got it. Thanks, Janet. And then one follow-up on the COVID-19 program. Are you planning to stratify results based on individual patient status?
spk05: Janet?
spk08: I'm sorry, based on what individual patient? Zero status. No, we're not going to stratify based on anything. And I think the zero status will take a little while to get. So no, we will not be doing that.
spk04: Right, that's very helpful. And then a couple of questions on dengue, if you don't mind. Are there any adverse events or safety signals you're watching for in particular? at some of the higher doses of 752, maybe GI related for the two ongoing clinical trials.
spk08: So the dose that we've selected for our clinical trials with 752 is safe and well tolerated. And no, we don't believe that there would be a GI signal at the dose that we've selected.
spk04: That's very helpful. And lastly, how might the, I guess, broader availability of Decatur's new dengue vaccine, I guess, impact the landscape for new therapeutics in the space? And maybe what implications could this have for the development of 752 in the future?
spk05: John, do you want to address? So, John?
spk08: So, I can start, and then perhaps, John, you might like to take over. I think that the vaccine is unfortunately following on the heels of a vaccine which led to some severe adverse reactions. And so I think there is the concern, at least initially, about vaccine upticks. I think that may be a problem, unfortunately, for people. And I think the population that it's largely intended for is starting off with children, really. which makes a lot of sense, but I think leaves a large unmet need for many people who live in dengue endemic areas. And certainly, I think, secondly, the question is around the durability of the vaccine and people who don't live in dengue endemic areas potentially visiting dengue endemic areas and needing something shorter term for treatment or prevention. So I think the awareness to the vaccine may actually drive people being more aware of the need for therapy? John, I'll hand it over to you.
spk02: Yes. So, you know, I think a lot was said. So, obviously, in the endemic areas, you know, we welcome the fact that they could have a vaccine because there's been nothing there, but there is durability. Specifically, looking at the data vaccine after three years, it is starting to come down. Given the past experience in those areas with the Sanofi vaccine, and the disappointment by many of those countries, it's going to be interesting to see what the uptake is there. But for wealthier countries where it might be more of a traveler's market, particularly if you look at the traveler's market in the United States, a lot of travelers are reluctant to get a vaccine, particularly a series before they travel. We saw it with hepatitis A. We saw it with others. And oral prophylactic for, you know, for prophylaxis of travel really would be the preferred there. And then, of course, you know, even with the military and so forth where maybe you're not going to be on a vaccination schedule. Yeah. Can you hear me? Yeah. Can you hear me? Yes. Go ahead. Yeah, yeah. So, I was just saying that, and particularly for the travels-related market, an oral prophylactic would be preferred than getting a vaccination for dengue fever.
spk04: Got it. Very helpful. Thanks, all.
spk11: If you would like to pose a question, please feel free to dial star 11 on your telephone keypad. If there are no further questions, I would like to turn the call back over to Mr. JP Somadossi for his closing comments. JP?
spk05: Thank you again for joining us today. Thank you.
spk11: Thank you for your participation in today's conference call. This concludes the call. You may now disconnect.
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