Ascletis Announces Positive Data of Oral Double Prodrug ASC10 and Its Antiviral Nucleoside Analog ASC10-A Against Omicron Variant

• ASC10-A demonstrated strong in vitro antiviral activity against multiple SARS-CoV-2 virus variants including Omicron
• By applying a double prodrug strategy, ASC10's permeability in Caco-2 cells and ASC10's oral bioavailability in monkeys were 3.2-fold and 2.3-fold of Molnupiravir, respectively
• Based on drug exposure relationship between monkeys and humans, oral double prodrug ASC10 is predicted to have higher drug exposure in patients, that may lead to better efficacy against COVID-19 in clinical trials compared to Molnupiravir

HANGZHOU, China and SHAOXING, China, Feb. 7, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672) today announces the positive in vivo and in vitro data of oral double prodrug ASC10 and its antiviral nucleoside analog ASC10-A against multiple SARS-CoV-2 virus variants including Omicron.

ASC10-A is a potent inhibitor of RNA dependent RNA polymerase (RdRp) of SARS-CoV-2 virus. ASC10-A demonstrated an excellent in vitro antiviral activity against multiple SARS-CoV-2 virus variants including Omicron. Compared to wildtype or early variants of SARS-CoV-2 virus, ASC10-A remained the same inhibitory activity in vitro against Omicron variant despite that Omicron variant carried many mutations including a mutation in RdRp. Furthermore, the drug exposure of ASC10-A required for efficacy against Omicron is likely achievable in clinical trials of patients based on bioavailability studies in monkeys.

Discovered and developed in-house to treat COVID-19, ASC10 is the orally bioavailable double prodrug of the antiviral nucleoside analog ASC10-A. After taken orally, double prodrug ASC10 is adsorbed mainly at gut into blood circulation. ASC10 is then rapidly cleaved in blood into the antiviral nucleotide analog ASC10-A.

By applying a double prodrug strategy, ASC10's permeability in Caco-2 cells was 3.2-fold of Molnupiravir. As a result of increased permeability, ASC10's oral bioavailability in monkeys was 2.3-fold of Molnupiravir. Based on drug exposure relationship between monkeys and humans, double prodrug ASC10 is predicted to have higher drug exposure in patients, that may result in better efficacy against COVID-19 in clinical trials compared to Molnupiravir. 

Based on the positive data, the submission of investigational drug applications (INDs) for clinical trials in China, the U.S. and other countries may be sooner than that expected by the Company earlier.

To date, Ascletis has filed multiple patent applications for ASC10 and its use globally.

"I am very excited by in vivo and in vitro results of ASC10 and ASC10-A," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, "While quickly moving ASC10 forward to the clinical trials, our team is also accelerating IND submission of ASC11, an oral direct-acting antiviral drug candidate targeting 3-chymotrypsin like protease (3CLpro), for clinical trials in China, USA and other countries."

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), a global platform covering the entire value chain from discovery and development to manufacturing and commercialization. Ascletis is committed to developing and commercializing innovative drugs in the areas of viral diseases, NASH/PBC, and cancer (oral cancer metabolic checkpoint and immune checkpoint inhibitors) to address unmet medical needs both in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis targets those therapeutic areas with unmet medical needs from a global perspective, and efficiently advances the developments of pipelines with an aim of leading in global competition. To date, Ascletis has three marketed products and 20 robust R&D pipelines of drug candidates with global competitiveness, and is actively exploring new therapeutic areas.

1. Viral Diseases: (1) Hepatitis B Virus (functional cure): focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 and Pegasys® as cornerstone drugs. (2) COVID-19 pipeline: currently includes (i) ritonavir oral tablet (100 mg), an authorized product, (ii) ASC10, an oral RNA dependent RNA polymerase (RdRp) inhibitor and (iii) ASC11, an oral 3-chymotrypsin like protease (3CLpro) inhibitor. (3) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. (4) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen).
2. Non-alcoholic Steatohepatitis/Primary Biliary Cholangitis: Gannex, a wholly-owned company of Ascletis, is dedicated to the R&D and commercialization of new drugs in the field of NASH. Gannex has three clinical stage drug candidates against three different targets - FASN, THRβ and FXR, three fixed-dose combinations for NASH and one PBC program targeting FXR.
3. Cancer (oral cancer metabolic checkpoint and immune checkpoint inhibitors): a pipeline of oral inhibitors targeting FASN, which plays a key role in cancer lipid metabolism, and a pipeline of oral PD-L1 small molecule next generation immune checkpoint inhibitors.
4. Exploratory Indications: Acne: Following NASH and recurrent GBM, the third indication for ASC40 has been approved to enter Phase 2 clinical trial. For more information, please visit www.ascletis.com.