Ascletis Announces FDA Clearance of Oral RdRp Inhibitor ASC10 to Conduct a Randomized, Placebo Controlled Phase Ib Study in Mild-to-Moderate COVID-19 Patients

-- ASC10 is an oral double prodrug that is rapidly and completely converted in vivo into the active metabolite ASC10-A, which is the same active metabolite of molnupiravir

-- Ascletis has filed multiple patent applications for ASC10 and its use globally. Compared with molnupiravir, ASC10 has a new and differentiated chemical structure

-- FDA recommended that Ascletis directly conduct the first clinical study of ASC10 in mild-to-moderate COVID-19 patients rather than in healthy subjects

HANGZHOU and SHAOXING, China, Aug. 3, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") today announces 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 ?-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.

"The COVID-19 pandemic continues to cause huge social and economic implications globally with over 572 million cases been confirmed including more than 6 million deaths^[2]. As a leading biotech with in-depth insights into viral diseases, Ascletis is committed to leveraging its proprietary pipeline including ASC10 (RdRp inhibitor) and ASC11 (3CLpro inhibitor) to fight against the pandemic. This IND approval of ASC10 from FDA marks a great recognition to our in-house R&D capabilities and enables us to expedite the clinical progress of ASC10. With other efforts made on capacity expansion and process optimization, we have further improved the accessibility and affordability of ASC10." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

[1] Wahl, et al., Nature. 2021 March; 591(7850): 451?457.
[2] WHO, WHO Coronavirus (COVID-19) Dashboard, https://covid19.who.int/

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has three marketed products, i.e. ritonavir tablets, GANOVO^® and ASCLEVIR^®, and 20 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (CHB functional cure), ASC10 and ASC11(oral small molecules for COVID-19 treatment), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne).

For more information, please visit www.ascletis.com.

SOURCE Ascletis Pharma Inc.