Enanta Pharmaceuticals, Inc. announced that will provide an update across its pipeline programs in virology and non-alcoholic steatohepatitis (NASH), including its newest candidate, EDP-721, a novel oral hepatitis B virus (HBV) RNA destabilizer and the expansion of its respiratory syncytial virus (RSV) platform with a new RSV-L inhibitor program, as well as provide an update on its plans for 2021 during Enanta’s presentation at the 39th Annual J.P. Morgan Healthcare Conference on January 12, 2021 at 8:20 a.m. ET. Pipeline Programs Update and Review: Hepatitis B Virus: EDP-721, Enanta’s newest clinical candidate, is a potent and selective HBV RNA destabilizer, which has demonstrated a robust reduction of viral transcripts in preclinical models, leading to reduced production of multiple HBV proteins, including HBV surface antigen (HBsAg) and e-antigen (HBeAg). By targeting HBV RNA, EDP-721 is expected to reduce HBsAg derived from both integrated and covalently-closed circular DNA (cccDNA). Since high levels of HBsAg are known to suppress innate and adaptive immune responses, which are believed to occur through multiple mechanisms, a sustained reduction of HBsAg is regarded as a key component of a functional cure for HBV. Enanta plans to develop EDP-721 for use alone or in combination with other mechanisms, such as EDP-514, with the ultimate goal of achieving a functional cure. Enanta expects to initiate a Phase 1 clinical study of EDP-721 in mid-2021. EDP-514, Enanta’s core inhibitor with Fast Track Designation from the FDA, is being developed in two Phase 1b studies for the treatment of HBV across different patient populations: subjects on treatment with a nucleos(t)ide reverse transcriptase inhibitor (NUC-suppressed patients), and chronic HBV subjects with high viral loads who are not currently on therapy (viremic patients). Preliminary data is expected for both trials in the second quarter of 2021. Respiratory Syncytial Virus: EDP-938, Enanta’s N-protein inhibitor with Fast Track Designation from the FDA, is being evaluated in a broad clinical development program, consisting of three trials. In December, Enanta initiated RSVTx, a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of EDP-938 in adult hematopoietic cell transplant recipients with acute RSV infection and symptoms of upper respiratory tract infection. The company plans to enroll, within 72 hours of symptom onset, approximately 200 adult subjects 18 to 75 years of age, who will receive EDP-938 or placebo for 21 days. The primary endpoint is the incidence of lower respiratory tract complications within 28 days of enrollment, while secondary endpoints include change from baseline in RSV RNA viral load, safety and pharmacokinetics. RSVP, a Phase 2b randomized, double-blind, placebo-controlled study in 70 adult outpatients with community-acquired RSV infection, is ongoing, but to date the 2021 RSV season in the Northern Hemisphere has not yet begun due to COVID-19 mitigation measures. Enanta has made extensive efforts to expand its clinical sites beyond North America, including sites across the EU and Asia-Pacific, to be ready when RSV infection arrives. The company will provide further guidance on trial completion once RSV becomes prevalent again. RSVPEDs, a Phase 2 randomized, double-blind, placebo-controlled study in hospitalized and non-hospitalized pediatric RSV patients age 28 days to 24 months, is expected to initiate in early 2021. Respiratory Syncytial Virus: The RSV L-protein is a viral RNA-dependent RNA polymerase that contains multiple enzyme activities required for RSV replication. Enanta announced the expansion of its RSV program with the introduction of an RSV L-inhibitor discovery initiative that includes potent nanomolar leads active against both RSV-A and RSV-B. An RSV-L-inhibitor is not expected to have cross-resistance to other classes of inhibitors, and therefore can potentially be used alone or in combination with agents targeting other RSV mechanisms, such as EDP-938. Human Metapneumovirus (hMPV): Enanta is developing nanomolar inhibitors of human metapneumovirus, a pathogen that causes upper and lower respiratory tract infections in young children and the elderly, as well as in immunocompromised patients or those with COPD or asthma. SARS-CoV-2: Enanta is working to discover direct-acting antiviral drug candidates for patients infected with the novel coronavirus, SARS-CoV-2, using a combination of drug target screening and drug design. The company is focused on polymerase and protease inhibitors and is currently optimizing potent lead molecules. Non-Alcoholic Steatohepatitis: EDP-305, Enanta's lead farnesoid X receptor (FXR) agonist with Fast Track Designation from the FDA, is currently being evaluated in ARGON-2, a Phase 2b randomized, double-blind, placebo-controlled 72-week study of approximately 340 patients with biopsy-confirmed NASH with fibrosis, using doses of 1.5 mg and 2.0 mg. A 12-week interim analysis on a subset of patients for the company’s internal assessment is planned for mid-year 2021. EDP-297, Enanta’s highly potent and targeted follow-on FXR agonist also being developed for the treatment of NASH with fibrosis, is currently being evaluated in an ongoing Phase 1 randomized, double-blind, placebo-controlled, first-in-human clinical trial. Enanta expects to report safety, tolerability and pharmacokinetics data in the second quarter of 2021. Enanta plans to use the results of the Phase 1 study of EDP-297 and the 12-week interim analysis in ARGON-2 to prioritize both FXR agonist compounds and seek opportunities for development of one or both of them in combination with other mechanisms for NASH with fibrosis.