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

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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

3CLpro inhibitor






Vero E6 Cell EC90[1] (nM)






[1]. EC90: 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 Pharma 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 Pharma, “These preclinical drug candidates demonstrate our discovery capability as a leading antiviral biotech.”

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