Ascletis Announces 3CLpro Inhibitor ASC11 Demonstrated Potential to be Effective Treatment for COVID-19

– In antiviral cellular assays, antiviral potency (EC₉₀) of ASC11 is 31-fold of that of Nirmatrelvir, 120-fold of that of S-217622, 16-fold of that of PBI-0451 and 7-fold of that of EDP-235.

– ASC11 is an in-house discovered oral small molecule drug candidate, targeting 3CLpro, with global intellectual property rights.

– It is expected that IND of ASC11 will be filed in the second half of 2022 and Phase I clinical trial in healthy subjects will be completed by the end of 2022.

HANGZHOU, China and SHAOXING, China, April 19, 2022 /PRNewswire/ — Ascletis Pharma Inc. (HKEX: 1672) today announces that its oral small molecule drug candidate ASC11, a 3-chymotrypsin like protease (3CLpro) inhibitor, demonstrated potential to be effective treatment for COVID-19.

In antiviral cellular assays with infectious SARS-CoV-2, antiviral potency (EC₉₀) of ASC11 is 31-fold (155/5) of that of Nirmatrelvir; 120-fold (600/5) of that of S-217622; 16-fold (78/5) of that of PBI-0451 and 7-fold (33/5) of that of EDP-235 (Table 1). Importantly, ASC11 activity was retained against different SARS-CoV-2 variants.

Table 1. Antiviral Potency (EC₉₀) of ASC11 versus Global Leading 3CLpro Inhibitors

Notes:
[1]. EC_90: a measure of drug potency showing a concentration that is effective in producing 90% of the maximal virus reduction. Lower the numbers, greater the antiviral potency. Compared to EC₅₀ (a concentration that is effective in producing 50% of the maximal virus reduction), EC₉₀ can predict more precisely the effective concentration of an antiviral drug in humans.
[2]. Data from the antiviral cellular assay with infectious SARS-CoV-2 conducted at IIT Research Institute, headquartered at Illinois Institute of Technology in Chicago, Illinois, U.S.
[3]. Data from Owen et al., Pfizer Worldwide Research, medRxiv, July 2021, https://doi.org/10.1101/2021.07.28.21261232. 
[4]. EC₉₀ estimated from Unoh et al., Shionogi Pharmaceutical Research Center, bioRxiv, January 2022. https://doi.org/10.1101/2022.01.26.477782.
[5]. Data from the presentation by Pardes Biosciences, Inc. at International Conference on Antiviral Research 2022 (ICAR 2022).
[6]. Data from the antiviral assay with primary human airway epithelial cells, press release October 19, 2021 by Enanta Pharmaceuticals, Inc.

ASC11 is an in-house discovered oral small molecule drug candidate using various proprietary technologies including molecular docking. ASC11 has global intellectual property rights.

Molecular docking showed that compared to Nirmatrelvir, ASC11 formed stronger hydrogen bond interaction with Glutamic acid 166 of 3CLpro, created new hydrogen bonds with other key amino acids of 3CLpro and fitted more tightly in hydrophobic Pocket 4 (P4) of 3CLpro, resulting in much higher antiviral potency (EC₉₀) of ASC11.

Molecular docking showed ASC11 bound to 3CLpro differently from S-217622, resulting in much higher antiviral potency (EC₉₀) of ASC11.

In Vero E6 cells, safety window (cytotoxicity versus antiviral potency) of ASC11 is more than 10,000-fold.

Together with other preclinical data including Caco-2 permeability, in vitro metabolism, microsomal stability and animal pharmacokinetic studies, ASC11 demonstrated potential for best-in-class antiviral treatment of COVID-19.

Ascletis expects that the Investigational New Drug (IND) of ASC11 will be filed in the second half of 2022 and Phase I clinical trial in healthy subjects will be completed by the end of 2022.

The Company’s second 3CLpro preclinical candidate (PCC), which is also discovered in-house with global intellectual property rights, demonstrated the same antiviral potency and safety window in Vero E6 cells as compared to ASC11.

 “We are excited about our oral small molecule preclinical drug candidates for their potential to be best-in-class antiviral treatment of COVID-19,” said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, “These preclinical drug candidates demonstrate our discovery capability as a leading antiviral biotech.”

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 (HBV functional cure), ASC10 and ASC11(oral small molecules for COVID-19), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne).

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

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