Enanta Pharmaceuticals, Inc.

Good afternoon and welcome to Enanta Pharmaceutical's fiscal third quarter 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 now like 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 2023 financial results was issued this afternoon and is available on our website. Making formal remarks on today's call are Dr. Jay Lulli, President and Chief Executive Officer, and Paul Mellett, our Chief Financial Officer, Dr. Scott Rottinghaus, our Chief Medical Officer, And Dr. Tara Kiefer, our Senior Vice President of New Product Strategy and Development, will be available during the Q&A portion of the call. 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 10Q 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. At Enanta, we are committed to our mission of being a leader in the development of groundbreaking therapeutics for viral infections. In this quarter, we made important strides to bring us closer to impactful inflection points and ultimately our goals. I'm proud of the work our team has accomplished this quarter and throughout the year so far across our pipeline and business, most notably in our respiratory syncytial virus or RSV program and our COVID-19 program. We're in a strong position to continue to advance our pipeline, and I am confident in our team's efforts to progress antiviral small molecule medicines to treat life-threatening viral infections. Today, I'll provide an overview of our progress during the third quarter, beginning with our RSV program, and then I'll comment on our COVID-19 program and the rest of our pipeline. RSV is a severe respiratory infection associated with significant morbidity and mortality that can cause serious disease in children, the elderly, and the immune compromised. RSVs received a significant amount of attention recently with the approvals of new vaccines and monoclonal antibodies to help prevent severe infection. However, given the experience with COVID and flu vaccines, including limited adoption and breakthrough infections, We believe a safe and effective oral RSV antiviral medication can bring significant value to patients infected with RSV. Starting with our most current update, we recently announced positive data from the phase one trial of EDP323 in healthy volunteers. As a reminder, EDP323 is our L protein inhibitor in development as a once daily oral treatment for RSV with fast track designation from the FDA. This phase one study enrolled healthy volunteers to evaluate the safety, tolerability, and pharmacokinetics of oral EDP323 in single ascending doses and multiple ascending doses for seven days along with the effect of food. The SAD phase enrolled a total of six cohorts ranging in dose from 50 to 800 milligrams, and the MAD phase enrolled four cohorts with doses ranging from 200 to 800 milligrams. EDP-323 was found to be generally safe and well-tolerated, up to the highest dose tested of 800 milligrams over seven days. Most adverse events were mild, and there were no serious or severe adverse events. There was one study discontinuation due to syncope, which was deemed unlikely to be related to EDP-323. EDP323 exposure increased with increasing single and multiple dosing up to 600 milligrams with a half-life ranging from 11 to 17 hours supporting once daily dosing. EDP323 doses ranging from 200 to 800 milligrams once daily resulted in strong EC90 multiples against both RSV A and B strains And when administered for seven days, were found to result in C24 concentrations at steady state of 11 to 44-fold over protein-adjusted EC90 of 0.3 nanomolar against both RSC-A and B-string. Additionally, no food effect was observed with a high-fat meal, suggesting that EDP323 can be administered without regard to food. We are pleased with this encouraging safety and pharmacokinetic data. In virology, when a potent antiviral such as EDP323 achieves high multiples of EC90 safely, it is a very positive signal and an important de-risking step for the program. These data enhance our belief in EDP323 as a potential therapeutic and give us the confidence to continue to progress the program. We believe EDP323 could serve as a standalone treatment or be used in combination with other agents such as EDP 938 to broaden the treatment window or addressable patient population for RSC. We plan to initiate a human RSC challenge study evaluating EDP 323 early in the fourth quarter, and we anticipate having results in the second quarter of 2024. Our broad RSV program also includes ZP938, the only N-protein inhibitor in clinical development, which we are currently evaluating in multiple Phase II studies as a potential treatment in high-risk patient populations. These studies include RSV-PEDS, a Phase II randomized double-blind placebo-controlled study in hospitalized and non-hospitalized pediatric RSV patients, RSV-HR, a Phase IIb randomized double-blind placebo-controlled study in adults with RSV infection who are at high risk of complications, including the elderly and individuals with congestive heart failure, chronic obstructive pulmonary disease, or asthma, and RSV-TX, a Phase IIb randomized double-blind placebo-controlled study in adult hematopoietic cell transplant recipients with RSV and symptoms of upper respiratory tract infection. Enrollment for RSVP, RSVHR, and RSVTX is ongoing, and we're utilizing sites in both the northern and southern hemispheres to optimize our coverage of potential RSV surges. If there is a return to a normal pre-pandemic type of RSV season in the northern hemisphere, We expect to complete enrollment in one or more of these studies in the upcoming northern hemisphere season and to have data in fiscal year 2024. Turning to COVID-19, we announced additional analyses from the phase two SARS-CoV-2 sprint study, which built upon our positive top line results that we announced in May of this year. EDP-235 is our clinical stage once daily orally dosed inhibitor of coronavirus 3CL protease that was evaluated in SPRINT, a randomized double-blind placebo-controlled phase 2 clinical trial in 231 adults with mild or moderate COVID-19 who did not have risk factors for progression to severe disease. Patients received 200 or 400 milligrams of EDP-235 or placebo orally once daily for five days. In the Phase II study, EDP-235 was found to be generally safe and well-tolerated. A statistically significant dose improvement in symptoms was observed in the 400-milligram cohort starting as early as one day following the first dose. In a predefined subset of patients enrolled within three days of symptom onset, a statistically significant dose-dependent improvement in symptoms was observed at all time points and a two-day shorter time to improvement was observed in a subset of six symptoms in the 400-milligram cohort compared to placebo. Additional analyses announced in June demonstrated a virologic effect of EDP-235 in the subset of patients who had not recently been infected, as measured by lack of antibodies to the SARS-CoV-2 nucleocapsid, whom we refer to as nucleocapsid negative patients. Specifically, in nucleocapsid-negative patients, a 0.8 log decline in viral load was observed at day five with 400 milligrams of EDP-235 compared to placebo, and a one log viral load decline at day five in the subset of nucleocapsid-negative patients who were treated within three days after symptom onset. Looking ahead, our current plan is to conduct all future COVID-19 work in the context of a collaboration. In particular, we continue to focus on progressing EDP-235 into phase three trials with a partner and gaining regulatory feedback to further enable a partnership. Moving on to our dual inhibitor research program targeting HMPV and RSV, we plan to select a clinical candidate in the fourth quarter of this year. In preclinical studies, our prototype dual inhibitor potently inhibited both HMPV and RSV replication in a dose-dependent manner, demonstrating a significant reduction in viral load of each virus and maintains nanomolar activity against multiple genotypes and strains of HMPV and RSV in a range of cell types. Our dual inhibitor is broader spectrum antiviral that would allow respiratory infections diagnosed as either HMPV or RSV, both of which are significant causes of respiratory tract infections globally, to be treated with a single agent, aiding populations such as children and the elderly who are at greatest risk. In hepatitis B, we continue to monitor the field for compounds to develop in combination with EDP514, our potent core inhibitor with FDA fast track designation, and a nucleoside reverse transcriptase inhibitor. We believe a core inhibitor such as EDP514 will ultimately be an important component of a successful combination regimen, and that can potentially help us address the high level of unmet need in HPV. Finally, looking beyond virology, We are piloting new programs that leverage our core strength and small molecule drug discovery and look forward to sharing more details on these growth areas with you in the coming months. I'd like to wrap up by highlighting our near-term milestones. Again, we are thrilled with the progress of EDP323 and the positive results from our phase one study. And we plan to advance EDP323 into a human challenge study early in the fourth quarter. We anticipate having results in the second quarter of 2024. We plan to announce the selection of a dual inhibitor clinical candidate targeting both HMPV and RSV in the fourth quarter of this year. And if there is a return to a normal pre-pandemic type of RSV season in the Northern Hemisphere, we expect to complete enrollment in one or more of our phase two studies of EDP938 in the upcoming Northern Hemisphere season and have data in fiscal year 2024. With that, I'll turn the call over to Paul to discuss their financials. Paul?