Goley Pharmaceutical Co., Ltd. announced on its wechat official account on the morning of Oct 10 that its phase I multi-dose escalation clinical trial of ASC10, a novel coronavirus oral polymerase (RdRp) inhibitor, was completed in the National Center for Infectious Diseases and the First Affiliated Hospital of Zhejiang University School of Medicine with 24 healthy subjects in the first three cohorts.
This multi-dose escalation phase I trial will enroll 72 healthy subjects, including 60 subjects in six dose escalation cohorts and 12 subjects in the food effects trial. Enrollment is expected to be completed in the fourth quarter of 2022. Sixty healthy subjects will be randomized into six cohorts to receive multidose escalation of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg ASC10 tablets or placebo twice daily (BID) for 5.5 days. The trial was double-blind and placebo-controlled to evaluate the safety, tolerability, and pharmacokinetics (PK) of ASC10 tablets. The remaining 12 subjects will be randomized to receive two single doses of 800 mg ASC10 tablets (postprandial or fasting) to assess the PK effect of food on ASC10 in healthy subjects.
Goley is the first Chinese biotechnology company to receive approval from both the US Food and Drug Administration (FDA) and China's National Medical Products Administration (NDA) to conduct a new clinical trial (IND) of an oral RdRp inhibitor. On August 3, 2022, Golly announced that the FDA has approved an IND application for ASC10 to conduct a Phase Ib clinical trial in patients with mild-to-moderate COVID-19 (Golly announced that the oral RdRp inhibitor ASC10 received FDA approval to conduct a randomized, placebo-controlled phase Ib clinical trial in patients with mild-to-moderate COVID-19). On August 22, 2022, Golly announced that China's National Food and Drug Administration has approved an IND application for ASC10 to conduct phase I clinical trials in healthy subjects (Golly announced that China's National Food and Drug Administration has approved a new clinical trial application for ASC10, a novel oral RdRp inhibitor). Golly is in active communication with regulatory authorities to explore the possibility of further accelerating the clinical development of ASC10.
ASC10 is an oral dual prodrug with a new differentiated chemical profile compared to molnupiravir, a single prodrug. After oral administration, both ASC10 and monupivir are rapidly and completely converted to the same active metabolite ASC10-A, also known as β-D-N4-hydroxycytidine (NHC) in vivo. The ASC10 was developed entirely by Golly itself. Golly has filed a number of patent applications for ASC10 and its uses worldwide. The ASC10 oral tablet used in this clinical study is a product developed with Gollie's proprietary technology.
By using the dual prodrug strategy, ASC10 permeability in Caco-2 cells (human colorectal adenocarcinoma cells) and active metabolite exposure in monkeys were 3.2-and 2.1-fold higher than monupivir, respectively. In a mouse model of COVID-19 infection, ASC10 at 240 mg/kg twice daily reduced the viral titer in mouse lung tissue by a value of 4.0, consistent with the effect of monupivir at 500 mg/kg twice daily [1]. Studies have shown [2,3] that ASC10-A (also known as EIDD-1931) is highly resistant to Omicron variant virus (BA.1 EC50=0.3 µM; BA. 2 EC50 = (including 0.25 M; BA. EC50 = 0.23 (including 5 M; BA.2.75 EC50=0.90 µM), Delta variant virus (EC50=0.5 µM) and wild-type virus (EC50=0.7 µM) showed potent cellular antiviral activity. This study also showed no drug-drug interactions between ASC10 and other commonly used drugs.
