Enanta Pharmaceuticals, Inc.

Good afternoon and welcome to Enanta Pharmaceuticals Fiscal Third Quarter 2021 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 financial results was issued this afternoon and is available on our website. On the call today is Dr. Jay Lulli, President and Chief Executive Officer, Paul Mellott, 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. And ANSA does not undertake any obligation to update any forward-looking statements made during this call. With that, I'd now like to turn the call over to Dr. Jay Lui. Jay?

Jay Lui Thank you, Jennifer, and good afternoon, everyone. Our fiscal third quarter was marked by the achievement of several important milestones and continued progress across our clinical portfolio. Starting with COVID-19, we are pleased to announce that we have identified a clinical development candidate, EDB235, an oral protease inhibitor specifically designed to treat SARS-CoV-2 infection and potentially other coronavirus infections. We are eager to progress this program into the clinic and are on track to initiate a phase one study of EDB235 early next year. In hepatitis B, we are excited by the progress we've made with EDP514 and EDP721, which we are developing as part of an all-oral combination regimen to achieve a functional cure. We expect to begin dosing in our Phase I study of EDP721, a novel oral HPV RNA destabilizer, this month. Additionally, this quarter, we announced positive Phase Ib 28-day data for our core inhibitor, EDP514, in two important patient populations, chronic HPV patients who have a high viral load, whom we refer to as viremic patients, and chronic HPV patients who are on a treatment with a nucleoside reverse transcriptase inhibitor, whom we refer to as nuke-suppressed patients. The significant progress we've made across our HPV program brings us closer to our goal of developing an all-oral functional cure for patients. Moving to the rest of our pipeline, we have three ongoing Phase II clinical studies investigating 938 for respiratory syncytial virus, or RSV, and two ongoing clinical studies for candidates to treat non-alcoholic steatohepatitis, or NASH. In addition to our clinical programs, we continue to progress our respiratory virus discovery initiatives to identify an L inhibitor for RSV, and an inhibitor for human metapneumovirus, or HMPV. With that, I'd like to dive deeper into each of the programs that make up our robust pipeline, beginning with SARS-CoV-2. We are pleased to have selected EDP-235, a direct acting antiviral oral protease inhibitor, as our clinical development candidate for SARS-CoV-2 and plan to initiate a clinical study early next year. As SARS-CoV-2 continues to mutate and new variants arise, we believe there remains a need for a potent oral treatment that is specifically designed to inhibit replication of this virus and are excited to progress this program. While vaccines and antibody therapeutics in development today target the viral spike protein, EDP235 has been specifically designed to target a conserved region in the active site of an enzyme essential for SARS-CoV-2 replication, so we do not expect mutations in the spike protein to significantly affect the activity of our candidate. Further, EDP235 potently and selectively inhibits SARS-CoV-2 replication in multiple cellular models including primary human airway epithelial cells, where it demonstrated an EC90 of 33 nanomolar. Importantly, activity is retained against currently circulating SARS-CoV-2 variants, and a high barrier to resistance has been observed. Additionally, EDP235 demonstrates preclinical properties supportive of once-daily oral dosing. If we are successful, our vision is for an early diagnosis of COVID-19 followed by outpatient treatment with a highly potent and targeted oral therapy. Shifting gears to HPV, we recently announced preliminary data from the first two dose cohorts of our Phase 1b study of EDP514 in viremic chronic HPV patients, which further demonstrated the compound's safety and tolerability, as well as its ability to reduce HPV DNA levels significantly over the 28-day dosing period. To briefly recap the data, 16 patients were randomized to receive daily doses of either 200 milligrams or 400 milligrams of BDP514 or placebo for 28 days. Mean reductions in HPV DNA of 2.9, 3.3, and 0.2 logs were observed in the 200 milligram, 400 milligram, and placebo groups respectively. with a maximum reduction of 4.2 logs in the 400 milligram group versus 0.5 log in the placebo group. More patients receiving EDP514 had HPV DNA below the lower level of quantitation compared to none who received placebo. Additionally, mean reductions in HPV RNA of 2.9, 2.4, and 0.3 logs were observed in the 200 milligram, 400 milligram, and placebo groups, respectively, with a maximum reduction of 4.8 logs with EDP514 versus 1.9 logs with placebo. HPV RNA was undetectable at day 28, and eight patients in the 514 group was compared to none in placebo. Further, EDP514 was shown to be safe and well-tolerated in this patient population. This study provides important clinical evidence of EDP514's safety profile, as well as kinetics of viral inhibition when used as a single agent over 28 days, and is a significant advance in our efforts to deliver an all-oral functional cure for hepatitis B. Building on that success, we also recently reported positive 28-day data from the first two cohorts, 200 and 400 milligrams, of our Phase 1b study of EDP514 in nuke-suppressed chronic HPV patients. Importantly, these 28-day data demonstrate that EDP514, when combined with a nuke, is safe and well-tolerated. Additionally, EDP-514 demonstrated reductions in HPV RNA, along with a pharmacokinetic profile supported of once-daily dosing. Together, these data support development of EDP-514 in combination with a nuke as a two-drug foundation on which to add other agents, such as EDP-721. Such an all-oral combination therapy is a differentiated approach that could potentially lead to a functional cure for patients with chronic HPV. To that end, we expect to begin dosing in the Phase I study of EDP721, our oral HPV RNA destabilizer, this month. Our enthusiasm for the development of EDP721 is based in part on the preclinical data we presented at EESL in June. In vitro, EDP721 potently reduced HPV surface antigen with pangenotypic HPV activity through its selective inhibition of PAPD5 and PAPD7. Moreover, EDP721 showed additive to synergistic antiviral activity in vitro when combined with nukes or HPV core inhibitors such as EDP514. Oral administration of EDP721 and the AAV HPV mouse model also demonstrated favorable efficacy characteristics, inducing up to a three-log drop in the HPV surface antigen. These preclinical data are particularly exciting because effective reduction of HPV surface antigen has presented a substantial challenge to achieving long-term HPV viral clearance. Moving to RSV, EDP938, the only N inhibitor in advanced clinical development today, is currently being evaluated in three ongoing Phase II studies. As a reminder, RSV is a severe respiratory infection associated with significant morbidity and mortality, not only in infants, but in the elderly and in immune-compromised adults as well. There is no safe and effective treatment for this viral infection. So we previously mentioned RSV, like flu, did not emerge during the most recent northern and southern hemisphere seasons due to COVID-19 mitigation measures. However, where social distancing measures have subsided, RSV has begun to reemerge and has already been observed with recent spikes of pediatric RSV cases in Australia and parts of the United States. In fact, in June, the Centers for Disease Control and Prevention issued a health advisory to notify clinicians and caregivers about increased inter-seasonal RSV activity across parts of the Southern United States. With this in mind, we've continued to establish additional trial sites in North America, Europe, Asia Pacific, and the Southern Hemisphere. These efforts will be key to our recruitment in our RSV clinical program, which includes RSVP, our Phase IIb study evaluating EDP938 in adults with a community-acquired infection, RSVTx, a Phase IIb study evaluating 938 in adult hematopoietic cell transplant recipients, and RSVPs, a Phase II study in pediatric RSV patients. Given that the recent reemergence of RSV is not following any normal seasonal pattern, it's very difficult to predict how significant or sustained the new incidence of RSV will be moving forward. Nonetheless, we are more hopeful that we will be able to complete enrollment in the RSVP study during the northern hemisphere winter season, as long as there are no renewed social distancing trends. Assuming this enrollment occurs, we would expect the data in the first half of 2022. As for RSVTX and RSVPs, which were initiated more recently than RSVP, we will continue to monitor the situation and update as appropriate. Beyond EDP938, our other two respiratory virus discovery initiatives targeting RSV and human metapneumovirus are also showing promise during lead optimization. RSVL inhibitors are another drug class that block viral replication and could potentially be used alone or in combination with other agents such as 938 to possibly broaden the treatment window or addressable patient population. As for HMPV, we believe this initiative is a natural adjacency for us as the virus is very similar to RSV. HMPV has been shown to have worldwide circulation with nearly universal infection by age five. Adults at highest risk include elderly, adults with underlying pulmonary disease, and those who are immune compromised. By year end, we hope to nominate another clinical candidate from either our HMPV or RSV-L inhibitor initiatives. Finally, I'll end with a summary of our work in NASH, a liver disease with a significant unmet need, where we are conducting clinical studies of two FXR agonists, EDP-305 and EDP-297. Recruitment and dosing in Argon-2, our Phase IIb study of EDP-305 in patients with biopsy-proven NASH with fibrosis, is progressing. Later this quarter, we'll have a planned internal interim analysis based on 12 weeks of treatment and a subset of patients from this study. Also later this quarter, we expect to report data from a Phase I first in human study of our follow-on FXR agonist candidate, EDP297. We anticipate that the combined data from this Phase I study and the EDP305 internal interim analysis will enable us to determine next steps, such as potential partnering and combination approaches for our NASH program. Before moving to our financials, I'd like to highlight our upcoming milestones, which we believe position us for a strong remainder of the year. For COVID-19, we've nominated EDP-235 as our lead oral protease inhibitor and expect to initiate a clinical study in early 2022. In HPV, we plan to dose the first patient in the Phase I clinical study of EDP721 this month. In NASH, we look forward to preliminary data from the Phase I study of EDP297 later this quarter and determination of next steps for our NASH program following an internal interim analysis of Argonne2. Finally, we continue to be excited about the early prospects coming out of our two other respiratory virology discovery initiatives and are eager to name a new clinical development candidate for RSV or human metapneumovirus by year end. We'd also like to take a moment to thank Dr. Natalie Otta, Senior Vice President and Chief Medical Officer for her dedication to the company over the last six years. during which she built and led the clinical development and regulatory team and helped advance our pipeline candidates. As announced, her retirement is planned for February, and we wish her the best. We're thankful that she is staying with us in a consulting capacity thereafter. With that, I'll stop here and turn the call over to Paul to discuss her financials for the quarter. Paul?