Enanta Pharmaceuticals, Inc.

Good afternoon and welcome to Anantha Pharmaceuticals for Fiscal Third Quarter 2022 Financial Results Conference Call. At this time, all participants are in listen-only mode. There will be a question and answer session at the end of the prepared remarks. Please be advised that this call is being recorded. I would like now to turn the call over to Jennifer Vieira, Investor Relations. Please go ahead.

Thank you, operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal third quarter 2022 financial results was issued this afternoon and is available on our website. On the call today are Dr. Jay Lulli, President and Chief Executive Officer, Paul Mellet, our Chief Financial Officer, and other members of Enanta's senior management team. Before we begin with our formal remarks, we want to remind you that we will be making forward-looking statements, which may include our plans and expectations with respect to our research and development pipeline and financial projections, all of which involve certain assumptions and risks beyond our control that could cause our actual developments and results to differ materially from those statements. A description of these risks is in our most recent Form 10-Q and other periodic reports filed with the SEC. Ananta does not undertake any obligation to update any forward-looking statements made during this call. I'd now like to turn the call over to Dr. Jay Lulli, President and CEO. Jay?

Thank you, Jennifer, and good afternoon, everyone. Our vision at Ananta is to leverage our expertise in virology and liver disease to discover, develop, and deliver groundbreaking medicines as we've already done with Glicaprevir and AbbVie's Maverick for hepatitis C virus. This quarter, we made important strides toward achieving another breakthrough medicine. Today, I will start by detailing our recent positive data from the phase one trial of EDP-235 and Healthy Volunteers. As a reminder, EDP-235 is our oral antiviral inhibitor of the coronavirus 3CL protease, also known as the main protease, or mPro, which is in clinical development for the treatment of COVID-19. EDP-235 has fast-track designation and is designed to be a once-daily oral treatment without the requirement for ritonavir boosting. Our first in-human, randomized, double-blind, placebo-controlled Phase I study enrolled healthy volunteers to evaluate the safety, tolerability, and pharmacokinetics of oral EDP235 in single and multiple ascending doses for seven days along with the effect of food. A total of 72 subjects received at least one dose of EDP235 or placebo. There were 40 subjects in the single ascending dose phase and 32 in the multiple ascending dose phase. All SAD and MAD cohorts enrolled eight participants who were randomized to receive EDP235 or placebo in a three-to-one ratio. To optimize dose selections, the study evaluated a broad range of single and multiple doses in a fasted and fed state. The SAD phase included cohorts with doses of 50 milligrams, 100, 200, 400, and 800 milligrams fasted, and a 200 milligram fed crossover cohort. The MAD phase included cohorts with doses of 200 milligrams and 400 milligrams fasted, and 400 milligrams and 800 milligrams fed. Overall, ADP-235 was generally safe and well-tolerated in healthy subjects up to 400 milligrams for up to seven days. Adverse events were infrequent with headache and gastrointestinal-related symptoms such as nausea and abdominal discomfort being the most commonly reported AEs during the MAD phase. The majority of AEs were mild with the exception of three that led to study discontinuations. There was one moderate headache in the 400 milligram FASTED cohort, one severe headache in the 800 milligram FED cohort, and one grade 3 ALT grade 2 AST elevation in the 800 milligram FED cohort. The single subject with elevated ALT AST had no other lab abnormalities. and no clinically significant lab abnormalities were observed in any other patients. Furthermore, all AEs were subsequently resolved. EDB 235 exposure was enhanced with food administration of a standard meal and increased approximately proportionally with ascending single and multiple doses, with a half-life consistently ranging from 13 to 22 hours, resulting in a PK profile suitable for once daily dosing. Data demonstrated that EDP-235 had strong exposure multiples over the EC90, where EC90 is a measure of potency, namely the concentration of drug that results in 90% inhibition in vitro. Specifically, EDP-235, 200 milligrams taken once daily with food, resulted in mean trough plasma levels at steady state that were threefold and sixfold over the plasma protein-adjusted EC90 for the alpha variant and delta variant, respectively, while 400 milligrams resulted in levels that were six-fold and 12-fold over the plasma protein-adjusted EC90 for these respective variants. These target exposure multiples were achieved without the need for ritonavir boosting and its associated drug-drug interactions. Additionally, EDP235 is projected to have four times higher drug levels in lung tissue compared to plasma, which would be expected to drive the 400 milligram multiples to 24-fold and 48-fold over the EC90 for the alpha variant and the delta variant, respectively. This is significant because an antiviral drug's potency and exposure level often translates to clinical efficacy. EDP-235's preclinical and clinical profiles suggest the potential for a best-in-class antiviral treatment for SARS-CoV-2 infection. We plan to finalize a phase two protocol in alignment with the FDA and initiate the study during the fourth quarter of this year. Looking at the COVID-19 landscape, there continue to be infections globally due to new variants, and the BA.5 variant reportedly can circumvent much of the immunity arising from prior COVID infection or vaccination. This highlights the urgent need for convenient, easily prescribed antiviral COVID treatments for patients, potentially even beyond high-risk patients. EDP-235 has the potential to fill this need as it is designed to be used once daily without ritonavir boosting and easily prescribed quickly without the need to assess drug-drug interactions associated with ritonavir. We believe a one pill once a day antiviral treatment regimen with EDP-235 can enable a true test-to-treat model to facilitate rapid treatment of COVID infections. Beyond COVID-19 and continuing with our industry-leading respiratory virology treatment portfolio, we are also advancing our respiratory syncytial virus or RSV program. RSV is another virus that represents an important unmet need. as it can result in severe respiratory infection and is associated with significant morbidity and mortality in children, the elderly, and the immune compromised. Further, there are no targeted treatments or vaccines available. Our robust RSV program includes EDP938, the most advanced N-protein inhibitor in clinical development today, as well as EDP323, a potent L-protein inhibitor. We are confident in the potential of EDP938, which has fast-track designation from the FDA. We are evaluating EDP938 high-risk populations in ongoing and planned clinical studies, including pediatric patients, adult hematopoietic cell transplant recipients, and high-risk adults, all of which have significant unmet need. Last quarter, we announced data from RSVP, a Phase IIb trial in otherwise healthy adults, with community-acquired RSV infection. In this low-risk population, which had mild, self-resolving upper respiratory tract infection, EDP938 did not meet the primary endpoint of reduction in total symptom score compared to placebo or the secondary antiviral endpoints. However, we were pleased to observe a statistically significant difference in the number of subjects achieving undetectable RSV RNA at the end of treatment with EDP938 making this the only study that has reported a statistically significant antiviral effect in an otherwise healthy adult population with community acquired RSV. Even though patients were treated within 48 hours of symptom onset, a key observation in this study was that the viral load and symptoms had already peaked and were declining at the time of the first dose, indicating RSV infection resolves quickly in this otherwise healthy population. Importantly, EDP938 demonstrated a favorable safety profile in a data set that now includes approximately 500 subjects exposed to the drug. We continue to believe that RSV and any viral treatment, including EDP938, has the greatest potential to show optimal efficacy in high-risk populations, as these patients have reduced RSV immunity, which manifests in a higher and longer duration of viral load and greater disease severity. allowing a bigger window to realize the full potential of EDP938. Moving forward, our broad clinical development plan is focused on evaluating EDP938 and populations with the greatest unmet need, namely those who are at high risk for severe disease. Our ongoing studies include RSV-PEDS, a Phase II study in pediatric RSV patients, and RSV-TX, a Phase IIb study in adult hematopoietic cell transplant recipients with RSV. Both are expected to recruit beyond 2022, subject to the reemergence of RSV in broader populations at pre-COVID levels. Also in the fourth quarter of this year, we're planning to initiate another Phase IIb study in high-risk adults, including the elderly and those who have asthma, COPD, or congestive heart failure. We believe EDP938 has the potential to deliver a potent oral antiviral treatment for all populations at high risk from RSV infection. A robust RSV antiviral portfolio also includes EDP323, a novel oral therapeutic targeting the RSVL protein RNA polymerase. We believe EDP323 has the potential to be a standalone treatment or it may be used in combination with other agents such as EDP938 to potentially broaden the treatment window or range of addressable RSV patient populations. EDP323 is supported by preclinical data that demonstrates strong oral absorption and good plasma exposure across different species. Importantly, EDP323 has sub-nanomolar in vitro potency against both major subtypes of RSV, RSV-A and RSV-B. and is not expected to have cross-resistance to other classes of inhibitors. We plan to initiate a phase one study of EDP323 in the fourth quarter of this year. We also continue to pursue our respiratory discovery program in human metanemovirus, or HMPV, a virus that is similar to RSV in that it impacts a number of vulnerable populations, including the elderly, adults with underlying pulmonary disease, and those who are immune compromised. We're continuing lead optimization of potent nanomolar HMPV inhibitors and plan to select a clinical candidate in the first half of 2023. Turning to hepatitis B, we remain committed to developing a combination regimen as a functional cure for chronic HPV patients, as we believe the ultimate cure for this infection will involve combination therapy. Our commitment is based on the continued high unmet need for this disease. which is a global public health threat and the world's most common serious liver infection, making it the primary cause of liver cancer, the second leading cause of cancer deaths in the world. Last quarter at EASL, final data from two of our Phase 1B studies of EDP514 were presented. EDP514 is our HPV core inhibitor with fast-track designation, which is shown to be safe and potent in two different chronic HPV patient populations. those who have high viral load, whom we refer to as viremic patients, and those who are on treatment with a nucleoside reverse transcriptase inhibitor, whom we refer to as nuke-suppressed patients. Based on these data, we remain convinced that EDP514 has the potential to be a best-in-class core inhibitor for HPV. We believe that a core inhibitor such as EDP514 will ultimately be an important component of a successful combination regimen We continue to evaluate internal and external opportunities for additional candidates to develop in combination with EDP 514 and a NUC to create a triple drug regimen. Before moving to the financials, I want to address briefly our ongoing patent litigation in which we are seeking damages for Pfizer's infringement of our issued 953 patent in the manufacture, use, and sale of its COVID-19 antiviral, Paxlovid. We recognize the importance of Paxlovid's availability for patients, and we do not intend to seek an injunction or take other action in this litigation to impede the production, sale, or distribution of Paxlovid. In filing this lawsuit, we are taking steps to ensure that we will be fairly compensated for our intellectual property. Importantly, our 953 patent is completely separate from the patent estate covering our discovery of EDP-235 and our ongoing antiviral discovery work for coronaviruses. Indeed, we have a growing 3CL protease inhibitor patent to state, including several issued U.S. patents, one of which covers EDP-235. These patents describe compounds built on an independent and distinct chemical scaffold from the one described in the 953 patent and in Pfizer's patents for Paxlovid. At this point, I'd also like to take the opportunity to welcome our new chief medical officer, Dr. Scott Rottinghaus, who joins Enanta today. Scott is an infectious disease trained physician who has more than 20 years of experience in a broad range of therapeutic areas. He joins us from Alexion, now a part of AstraZeneca, where he was vice president, head of clinical development, hematology, and nephrology. He has also held positions at Pfizer where he worked on trials of a DNA vaccine for influenza and and on studies of anti-infectives, and continued to practice as an attending physician and assistant clinical professor in infectious diseases at Yale School of Medicine. His experience also includes multiple NDA and MAA submissions and FDA advisory committee participation. We're very excited to have Scott join us as we advance our antiviral development programs. Finally, I'd like to wrap up by highlighting our near-term milestones. We are thrilled with our Phase I results of EDP-235 and look forward to advancing the COVID-19 program into a Phase II study in the fourth quarter of this year. We're also on track to begin a new Phase II RSV study in high-risk adults in the fourth quarter of this year. And last, we're excited to initiate a Phase I study for EDP-323, our RSV-L inhibitor, in the fourth quarter of this year. as well as nominate a clinical candidate for human metapneumovirus in the first half of 2023. With that, I'll turn the call over to Paul to discuss the financials. Paul?