Enanta Pharmaceuticals, Inc.

Good afternoon, and welcome to Enanta Pharmaceuticals Fiscal Fourth Quarter and Year-End 2021 Financial Results Conference Call. At this time, all participants are in a 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 fourth quarter and year-end 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 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. Reflecting on our fiscal 2021 year, I am proud of the exceptional advancements we've made across our entire portfolio. By leveraging our years of drug discovery experience and knowledge, we have developed a robust pipeline of small molecule candidates that have the potential to bring new treatment options to patients. Our accomplishments this past year advancing this pipeline puts us in a strong position to help patients and create long-term sustainable value for our shareholders. I continue to be extremely proud and grateful to my colleagues for their collective efforts and dedication to progress our pipeline. We ended our fiscal year strong. with continued advancements across our clinical virology portfolio this quarter. Starting with hepatitis B, we are furthering our clinical program with the vision of developing a combination regimen to deliver a functional cure for chronic HPV patients. EDP514, our HPV core inhibitor, has been evaluated in two Phase I studies in different chronic HPV patient populations. those who have a 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. Recently, we announced final clinical data from both of these trials in conjunction with the liver meeting hosted by AASLD, where we received a presidential poster of distinction for our viremic studies. Overall, final data from both studies show that the 200 milligram, 400 milligram, and 800 milligram doses were safe and well-tolerated through 28 days and displayed pharmacokinetics supportive of once-daily dosing. In viremic patients, treatment with EDP514 resulted in mean HPV DNA reductions of 2.9, 3.3, and 3.5 logs, at 28 days for the 200, 400, and 800-milligram cohorts, respectively, compared to 0.2 log reduction in the placebo group. Mean HPV RNA reduction in each of the three viremic treatment cohorts was at least two logs compared to a 0.02 log reduction in the placebo group. Taken together, these results demonstrate that EDP514 has clear clinical evidence of a strong safety profile alone and in combination with a nuke and displays significant antiviral activity over 28 days with a pharmacokinetic profile consistently supportive of once daily oral dosing. As recently announced, we discontinued development of EDP721 and oral HPV RNA destabilizer based on our recent emerging safety observations and the single ascending dose part of the Phase I study. Patient safety is our top priority, and so we decided to discontinue further development of this compound. We are grateful to our principal investigator and his study team and the participants in the Phase I study for their commitment to HPV research, as well as our team at Enanta for all their efforts in supporting the discovery, development, and clinical evaluation of EDP721. We remain committed to developing a functional cure for chronic hepatitis B patients, and we also believe that EDP514 will be an important component of a successful combination regimen. We look forward to advance our HBV program with additional mechanisms from internal discovery efforts external opportunities for both. I would now like to turn to our respiratory virology programs where we continue to build a leading oral antiviral treatment portfolio. Our lead RSV program includes our end protein inhibitor, EDP938, currently in multiple Phase II studies, and our preclinical work developing a compound targeting the RSVL protein. As a reminder, RSV is a severe respiratory infection associated with significant morbidity and mortality that has no treatments or vaccines available. The virus can cause serious disease in children, the elderly, and the immune compromised. Our lead molecule, ADP938, targets the replication of both RSV-A and RSV-B. It has shown robust clinical data in a Phase IIa challenge study where it was safe and well-tolerated and had significant effects on viral load and reduced symptoms of infection. Currently, EDP938 is being evaluated in three clinical studies, including RSVP, a Phase IIb study in adults with community-acquired RSV infection, RSVTX, a Phase IIb study in adult hematopoietic cell transplant recipients, and RSVP, a Phase II study in pediatric RSV patients. While RSV, like influenza, was significantly suppressed while there were strong mitigation measures in place to control COVID-19, there has been recent increased RSV activity in various regions of the world, including parts of the United States and Europe. Given this activity, we expect that enrollment in the RSVP study will be complete during the Northern Hemisphere winter season if there is no further significant increase in COVID-19 or mitigation measures in these regions. Assuming this enrollment occurs, we will have data in the first half of 2022. As for RSV-TX and RSV-PEDS, which were initiated during the pandemic, enrollment is expected to require more than one global RSV season subject to the uncertainties of the continuing pandemic. Additionally, in RSV, our discovery initiatives are advancing as we work to develop an RSV-L inhibitor. L inhibitors are another drug class that block viral replication that could potentially be used alone or in combination with other agents, such as EDP-938, to broaden the treatment window or addressable patient populations. Our L inhibitor program has continued to progress extremely well this year. We are confident that we will select an optimal development candidate in this RSV mechanism by year end. A new L inhibitor candidate, along with BDP-235, would achieve our stated goal of identifying two new clinical candidates among our respiratory discovery programs in 2021. We also continue to pursue our third respiratory discovery program in human metapneumovirus, or HMPV, which was first identified 20 years ago and has worldwide circulation with nearly universal infection by age five. Like with RSV, there are other vulnerable populations, including the elderly, adults with underlying pulmonary disease, and those who are immune compromised. we are nearing completion of lead optimization of potent nanomolar HMPV inhibitors and hope to select another clinical candidate in the coming months. Our SARS-CoV-2 program continues to progress as we develop EDP-235, our oral 3CL protease inhibitor specifically designed for the treatment of COVID-19. This quarter, we were excited to present the first preclinical data for EDP-235 at the International Society for Influenza and Other Respiratory Virus Diseases and World Health Organization virtual conference. These data show that EDP-235 demonstrated highly potent antiviral activity against SARS-CoV-2 with pharmacokinetic properties supporting a once-daily oral dosing regimen. In a biochemical assay, EDP-235 inhibited the SARS-CoV-2 protease with an IC50 of 5.8 nanomolar and maintained its activity against proteases from SARS-CoV-2 variants. Additionally, BDP235 potently blocked the replication of SARS-CoV-2 in multiple cellular models, including primary human airway epithelial cells, where an EC90 of 33 nanomolar was observed, positioning EDP-235 among the most potent direct acting antivirals currently in development for SARS-CoV-2. EDP-235 was also shown to have potent activity across a range of variants, as well as other human coronaviruses. Importantly, data demonstrated that EDP-235 has good oral bioavailability without ritonavir boosting, and favorable distribution into lung cells as well as other key target tissues. EDP-235 is projected to have a long half-life of 16 hours with an efficacious dose of 100 to 500 milligrams once daily in humans. In summary, the preclinical profile of EDP-235 indicates its potential to be a best-in-class once-daily oral therapy for the treatment and prevention of COVID-19. While the pandemic may be far from over, we see COVID-19 eventually progressing from the current situation toward a more endemic disease where effective therapeutics will continue to play a significant role. We've completed the IND-enabling preclinical studies of EDP-235, and are eager to advance the candidate into the clinic in early 2022. Lastly, this quarter we announced the decision to prioritize combination approaches for both of our NASH FXR agonists, EDP305 and EDP297, through an out-licensing strategy. NASH is a complex disease that we believe will likely require a combination of multiple mechanisms to provide an optimal treatment regimen. Therefore, we do not plan to continue development of either program internally, but instead we'll seek external opportunities to pursue these programs in a combination approach. Before moving to our financials, I'd like to wrap up by reiterating our upcoming milestones. We expect to select the clinical development candidate for our RSVL inhibitor program by year end. Looking ahead to 2022, we expect multiple milestones, including the initiation of a phase one study of our oral 3CL protease inhibitor, EDP235, in the early part of the year. We also expect, given the reemergence of RSV in the U.S. and Europe, that enrollment in the RSVP study will be complete during the northern hemisphere winter season, if there is no further significant increase in COVID-19 in those regions. Accordingly, we plan to report data from our RSVP study also in the first half of 2022. With that, I'll stop here and turn the call over to Paul to discuss our financials. Paul?