–The exposure of active drug ASC10-A after twice daily dosing 800 mg double prodrug ASC10 in Chinese subjects was 94% of that after twice daily dosing 800 mg single prodrug molnupiravir in Japanese subjects
–Based on Ascletis’ Phase I results of ASC10 and molnupiravir’s clinical efficacy data in American, Japanese and Chinese patients, 800 mg twice daily of ASC10 is selected for the registrational trial
–All doses of ASC10 including 800 mg twice daily were safe and well tolerated in Chinese subjects. Safety profiles between ASC10 and placebo treatments were comparable
HANGZHOU, China and SHAOXING, China, Dec. 12, 2022 /PRNewswire/ — Ascletis Pharma Inc. (HKEX: 1672, “Ascletis”) today announces positive topline results from its Phase I multiple ascending dose (MAD) study (NCT05523141) in healthy subjects for oral RNA-dependent RNA polymerase (RdRp) inhibitor ASC10 for COVID-19 treatment. ASC10 is an innovative orally available double prodrug, which has a new and differentiated chemical structure from the single prodrug molnupiravir. After oral dosing, both ASC10 and molnupiravir are rapidly and completely converted in vivo into the same active drug ASC10-A, also known as β-D-N4-hydroxycytidine (NHC). Double prodrug approach significantly increased oral bioavailability of active drug ASC10-A.
The Phase I data demonstrated that all doses of ASC10 including 800 mg twice daily were safe and well tolerated in Chinese subjects. Safety profiles between ASC10 and placebo treatments were comparable. The exposure of active drug ASC10-A after twice daily dosing 800 mg double prodrug ASC10 in Chinese subjects was 94% of that after twice daily dosing 800 mg single prodrug molnupiravir in Japanese subjects. The plasma concentrations of the double prodrug ASC10 in Chinese subjects were below detection limit (0.2 ng/mL) after 800 mg dosing. Similarly, the plasma concentrations of the single prodrug molnupiravir in American subjects were negligible after 800 mg dosing .
After the body weight normalization, the exposures of active drug ASC10-A are also equivalent between 800 mg double prodrug ASC10 in Chinese subjects and 800 mg single prodrug molnupiravir in American subjects .
The food had no effect on ASC10-A’s exposure, indicating that ASC10 can be taken with or without food.
Molnupiravir has been approved or authorized for the emergent use in many countries including Japan and the U.S. Furthermore, recent publication indicated that molnupiravir demonstrated exciting clinical efficacy against omicron infections in Chinese patients .
Based on Ascletis’ Phase I results of ASC10 and molnupiravir’s clinical efficacy data in American , Japanese and Chinese patients, 800 mg twice daily is selected for the registrational trial.
The active drug ASC10-A has potent antiviral activity against various Omicron variants such as BA.5 and BA.2.75. 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.
“Based on Phase I results, ASC10 is very safe in Chinese subjects and its druggability is high. I believe ASC10 has potential to play an important role in fighting against COVID-19 pandemic.” Said Prof. Yunqing Qiu, Vice President of the First Affiliated Hospital, School of Medicine, Zhejiang University and principal investigator of ASC10 Phase I study.
“The Phase I clinical data have confirmed the druggability of ASC10 for COVID-19. With the global patent filings, we expect that ASC10 will make contributions to fighting against COVID-19 pandemic inside and outside China.” said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.
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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 22 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (HBV 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.