Atea Pharmaceuticals, Inc.

Good afternoon, ladies and gentlemen. Welcome to the Atea Pharmaceuticals fourth quarter and full year 2022 financial results and business update conference call. At this time, all participants are in a listen-only mode. Following the formal remarks, we'll open the call up to your questions. To ask a question during the session, you need to press star 1-1 on your telephone. You'll then hear an automated message advising you that your hand is raised. To withdraw your question at any time, press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to turn the call over to Joneigh Barnes, Senior Vice President of Investor Relations and Corporate Communications at Atea Pharmaceuticals. Ms. Barnes, please proceed.

Thank you, Operator. Good afternoon, everyone, and welcome to Atea Pharmaceuticals' fourth quarter and full year 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 ir.ateafarma.com. With me from Atea are Chief Executive Officer and Founder, Dr. Jean-Pierre Samadosi, Chief Development Officer, Dr. Janet Hammons, Chief Medical Officer, Dr. Arantxa Horga, Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, and our Chief Commercial Officer, John Bavrica. 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 involve risks and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on the 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. As you will see on slide three, this year we are forced to continue the meaningful progress made across our advanced clinical development programs following strong execution in 2022. Clinical advocacy results from the Morning Sky trial informed our Phase III, Sunrise III trial of Beniposivir for the treatment of COVID-19, which was initiated in the first quarter of 2022. We anticipate an interim analysis from the Sunrise III trial in the second half of this year, followed by completion of enrollment by year end. We also made meaningful progress advancing our preclinical second-generation protease inhibitor program, and we anticipate finding an IND for a clinical candidate around the end of the year. With our HCV program, we completed preclinical and manufacturing work needed for the initiation of a phase two combination trial of benifosgravir and erizosvir in the second quarter. With our dengue program, we conducted two proof of concept studies for AT752, and the results will be shared with you today. Let's now move to CAVI-19. Turning to slide five, benifosbuvir is an oral nucleotide prodrug that targets viral RNA polymerase, a highly conserved enzyme critical to viral replication and transcription. We believe that benifosbuvir profile addresses the key limitations of current therapies. It has low risk of drug-drug interactions, and may be co-administered with commonly prescribed drugs for high-risk COVID-19 patients, a key limitation of PaxLogin. Scientific presentation demonstrating beneficiary lack of drug-drug interaction were presented last week at the Conference on Retroviruses and Opportunistic Infections, also called CORE. The U.S. COVID-19 public health emergency is set to expire on May 11, and the market dynamics for COVID continue to shift. Based on the current variants, there are very limited treatment tools available, with essentially only Paxlovid for outpatients or Vagluri or Remdesivir for hospitalized patients. The last thing of the public health emergency is going to make it even harder for this patient population to assess diagnostic and treatment. This is likely to lead to further mobility and mortality, particularly in the most vulnerable. Moving to slide six, we believe COVID-19 will continue to remain endemic throughout the world and particularly impact the patient population that we are studying in Sunrise Street. We believe that oral therapeutics will remain a multi-billion dollar opportunity for years to come, and projected annual COVID-19 oral antiviral U.S. demand using Acuvia retail prescriptions suggests the current estimated annual market opportunity over $10 billion. Beyond that, we believe that there is an opportunity to expand this market to patients where drug-drug interactions associated with Paxlovid are a concern, limiting and complicating prescribing. These include commonly prescribed drugs such as seizure medications, antipsychotics, anticoagulants, and more. Let me remind you that Paxlovid currently has 90% of the prescription market share, and there is still a significant unmet medical need as less than 30% of COVID-19 patients are being prescribed an oral antiviral. Turning to slide seven, as we are moving to a traditional payer market, it is clear that we will have to demonstrate a value proposition of the impact of Benipozivir against COVID. This will be achieved by using a primary endpoint of decrease in hospitalization and deaths. We believe that this will be the key consideration for drug reimbursement for COVID therapies in the future. This is why we are targeting the most vulnerable patient populations in Sunrise 3 who are the greatest risk for disease progression to severe COVID-19 or mortality and for whom there are limited treatment options. Let's keep in mind that CMS estimates an average cost approaching $22,000 per hospitalization. And approximately 70% of COVID-19-related hospitalizations of hospitalized patients were covered under Medicare. Moving to slide eight, let's now review our innovative Sunrise III trial, our Phase III registrational trial, which is evaluating Benifazovir as monotherapy and that's combination enteral terbine. Enrollment continues in this global phase three randomized double-blind placebo-controlled study, which will evaluate benifazovir or placebo administered at the same time as locally available standard of care. Patients will be randomized one-to-one to receive either benifazovir at 550 milligram twice daily or placebo. We expect to enroll at least 1,500 high-risk patients with mild or moderate COVID-19. Two study cohorts defined by the type of standard of care the patients receive would be studied. The first cohort is a monotherapy cohort that would be comprised of patients receiving supportive care, which represents the primary analysis population. The second cohort is a combination antiviral cohort that would be comprised of patients who are receiving a compatible antiviral against COVID-19 as part of the standalone care. The primary endpoint of the study is all-cause hospitalization of deaths through day 29 in at least 1,300 patients from the monotherapy cohort. You will recall that we have already evaluated hospitalization in the Morning Sky trial and been in foster care showed a 71% reduction in hospitalization versus placebo. And importantly, in addition, a subgroup analysis showed an 82% reduction in patients over 40 years old. Sunrise 3 will focus on high risk patients that are the greatest risk for disease progression to severe COVID-19 or mortality. The study is expected to have a large global footprint with up to 300 clinical sites in 25 countries, including the United States, Europe, Japan, and the rest of the world. Moving now to our hepatitis C program, which we believe has the potential to become a best-in-class combination with the potential to improve upon the current standard of care by offering a shorter duration protease-inhibitor-free treatment for patients with HCV. Slide 10 outlines our Phase II open-labeled study of benifosvivir and risosvir in HCV patients. The study will enroll approximately 280 HCV-infected direct-acting antivalve naive patients across all genotype including a leading cohort of approximately 60 patients. Patients will be administered 550 mg benifosbuvir in combination with 180 mg risosvir once daily for eight weeks. The primary endpoints of the study are safety and sustained biological response, or SVR, at week 12 post-treatment. Other virologic endpoints include virologic failure, SVR at week 24 post-treatment, and resistance. Regulatory submissions for the initiation of the trial are ongoing, and dosing of patients in this clinical trial is expected to begin during the second quarter. Initial data from the leading cohort of approximately 60 patients is anticipated around the end of the year. Turning to slide 12, I will now provide an update on our program for AT752 intervention against dengue. We have been a pioneer in the development of our normal antiviral therapeutic for dengue. Our proof of concept study, DEFEN2, demonstrated that AT752 treatment led to a faster resolution of fever, which is the major clinical sign of dengue. However, the FEN-II also highlights the need for better diagnostics to identify patients earlier in the course of the disease and also the need for a large sample size to account for the high variability for treatment and for prophylaxis as well. To address these factors, robust Phase II studies would require long clinical timelines with major associated costs, which has led to the business decision to deprioritize the dengue program. Turning to slide 13, as you may recall, we have been conducting two studies to assess the efficacy of AT752 in the treatment and prevention of dengue fever. First, the different two phase two clinical trial was randomized placebo control and conducted in dengue endemic areas. It involved patients with dengue fever within 48 hours of the onset of fever and the diagnosis of dengue confirmed with a positive NS1 antigenemia test. The primary endpoint of this trial was changed in dengue viral load from baseline with exploratory analysis looking at the change in viremia, NS1 level, and fever. In the first cohort of the FEM2, we enrolled 21 patients in India, Thailand, and the Philippines. We have also been conducting a human infection challenge trial under a US IMD. The healthy subjects were treated on day one with AT752 placebo and then injected with a live attenuated strain of Dengue Type 1 on the following day. Subjects were dosed with AT752 or placebo for a total of 14 days. Subjects were then monitored for symptoms, viremia, NS1 level and safety. Let's move to slide 14. This schematic depicts our understanding of the time course of dengue illness. As you can see, there is a lag between infection and viremia, and viremia precedes the development of symptoms and sign. Our study was designed to enroll patients around day six of infection. Based on the data that we will now review, patients likely presented later in the course of the disease at enrollment. On slide 13, you can see that the viral load changes over time through day 7 as measured by PCR. Placebo patients are depicted in red and AT752 patients on the right in blue. Please notice that the study enrolled patients with all four serotypes of dengue, and it is well known that the viral kinetics of each serotype are quite different. At enrollment, patients presented late in the course of the disease with high variability and low viremia level at baseline, particularly in the placebo arm, which had three patients with viremia levels below the lower level of quantification. As a consequence, The primary endpoint of change in viral load decline, as you can appreciate from baseline, is unavoidable. Moving to slide 16. Platelets are a biomarker of dengue progression. You can see in this slide the trajectory of platelet counts from baseline to day seven for both the AT752 treatment arms and placebo. Consistent with the viremia data at baseline, platelets were already low or below the lower limit of normal in the majority of patients further demonstrating late presentation of disease at enrollment. Turning to slide 17, as I have mentioned, the fever is the major clinical sign of diabetes. This slide demonstrates the time to resolution of fever defined as a temperature of 37 degrees Celsius or less sustained for 24 hours and maintained through day five. In a pre-specified exploratory endpoint, in patients who presented with body temperature above 37 degrees Celsius, The median time to fever resolution was four days in the AT752 arm and greater than five days in the placebo arm. Slide 18 shows the change in body temperature for those patients who presented with a temperature of more than 37 degrees Celsius at baseline. In a post-hoc analysis, there was a difference in body temperature change from baseline of 0.9 degrees Celsius at day three in favor of the 87 as compared to the placebo. Also, at day three, 100% of patients who presented with baseline body temperature above 37 degrees Celsius at the reduction in body temperature below the baseline levels in the AT752 arm versus only 33% of patients in the placebo arm. Moving to slide 19, the safety profile of AT752 was favorable in the study, and there were no drug-related assays. An adverse event, were largely mild to moderate and occur at similar frequency with those in the placebo group. Two non-drug-related SAEs, which were hospitalization due to thrombocytopenia and disease progression to severe dengue, occurred. One out of seven in placebo and one out of 14 in the AT752R. Other non-serious adverse events were mostly mild and moderate, self-limiting, and occurred in comparable frequency in active and placebo. Turning to slide 20, the human interaction challenge study was also a randomized double-blind placebo control trying evaluating AT752 dose of 750 mg TID. where dosing was initiated prophylactically 24 hours ahead of subject receiving an injection of attenuated live dengue 1 virus. The available results in five healthy volunteers were uninterpretable due to the high variability observed in term of viremia, antigenemia, and the onset and severity of symptoms. there were much lower drug exposures than those observed in phase one with normal volunteers and in different two study with treatment patients, very likely due to a lack of dosing compliance. For this type of the study, it is clear that a much larger sample size of greater than 50 healthy volunteers would be needed to account for this high variability. I will now turn the call to Andrea Coccone, our CFO, to review our financial update.