Ascletis Pharma Inc. announced that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for ASC10, an oral drug candidate targeting RNA-dependent RNA polymerase (RdRp) for COVID-19, to conduct the Phase Ib clinical trial in mild-to-moderate COVID-19 patients. Ascletis will immediately initiate the clinical trial in patients to collect ASC10's clinical safety, pharmacokinetics and preliminary efficacy data. ASC10 is an orally bioavailable double prodrug which has a new and differentiated chemical structure from the single prodrug molnupiravir. After oral administration, both ASC10 and molnupiravir are rapidly and completely converted in vivo into the same active metabolite ASC10-A, also known as ß-D-N4-hydroxycytidine (NHC). ASC10 was discovered and developed in-house. Ascletis has filed multiple patent applications for ASC10 and its use globally. ASC10 oral tablet formulation for the clinical study was developed with in-house proprietary technology of Ascletis. By applying a double prodrug strategy, ASC10's permeability in Caco-2 cells (human colorectal adenocarcinoma cells) and active metabolite exposure in monkeys reached 3.2-fold and 2.1-fold of molnupiravir's, respectively. In the SARS-CoV-2 infected mouse models, ASC10 at 240 mg/kg twice daily led to a 4.0 log reduction in viral titer in lungs, equivalent to molnupiravir at 500 mg/kg twice daily[1]. Preclinical studies demonstrated that ASC10-A has potent cellular antiviral activity against Omicron variant (EC50 = 0.3 µM), Delta variant (EC50 = 0.5 µM) and wildtype virus (EC50 = 0.7 µM). It also suggested that there were no drug-drug interactions between ASC10 and other common medicines. FDA recommended that Ascletis directly conduct the first clinical study of ASC10 in mild-to-moderate COVID-19 patients rather than in healthy subjects. This study is a randomized, placebo controlled Phase Ib clinical trial to determine the safety, tolerability, pharmacokinetics and preliminary efficacy in multiple ascending doses of ASC10 tablets (200 mg, 400 mg or 800 mg twice daily) in mild-to-moderate COVID-19 patients for 5.5-day treatment with 28-day monitoring. Previously, molnupiravir was granted Emergency Use Authorization by FDA for 800 mg twice daily.
Currently, Ascletis is actively communicating with regulatory authorities to explore the possibility of further accelerating the clinical development of ASC10.