-- Drug-Drug interactions of ASC41/ASC41-A with strong CYP3A4 inhibitor or inducer were low, showing competitiveness to other THRβ agonists in the late stage clinical development

--It is unlikely that there will be clinically significant drug-drug interactions between ASC41/ASC41-A and the most frequently used antidepressants and statins, indicating broad application in patients with NASH

-- ASC41/ASC41-A pharmacokinetic profiles were comparable between healthy subjects and patients with NAFLD and between U.S. and Chinese populations

Shanghai, China, September 8, 2021-- Gannex, a wholly owned company of Ascletis Pharma Inc. (HKEX: 1672), today announces positive topline results from the U.S. Phase I trial of drug-drug interactions in healthy subjects and pharmacokinetics (PK) in patients with non-alcoholic fatty liver disease (NAFLD) for ASC41 oral tablets, a liver-targeted prodrug. ASC41 is mainly metabolized by CYP3A4 to form an active metabolite ASC41-A, a selective thyroid hormone receptor beta (THRβ) agonist.

This clinical study consisted of two cohorts. The first cohort evaluated the safety, tolerability and PK of ASC41 after oral administration of 5 mg tablets in the presence of itraconazole (a strong inhibitor of CYP3A4) or phenytoin (a strong inducer of CYP3A4) in heathy volunteers. The second cohort evaluated the safety, tolerability and PK of ASC41 after oral administration of 5 mg tablets in patients with NAFLD.

The drug-drug interaction data demonstrated that there were no clinically significant changes in the exposure of the active metabolite ASC41-A in the presence of itraconazole or phenytoin, as compared to that in the absence of the strong inhibitor or inducer. These data show competitiveness of ASC41 to other THRβ agonists in the late stage clinical development. Furthermore, these findings suggest that clinically significant drug-drug interactions would be unlikely between ASC41/ASC41-A and antidepressants (selective-serotonin/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs), most of them are mild/moderate CYP3A4 inhibitors), which are commonly used in the non-alcoholic steatohepatitis (NASH) patient population. In addition, in vitro transporter studies predicted no significant effect of ASC41/ASC41-A on statin exposure.

This study also revealed that the PK of ASC41/ASC41-A in healthy volunteers was not significantly different from that in patients with NAFLD.

Furthermore, the PK results from this study which was conducted in the U.S. were comparable to those of the Phase I ASC41 study conducted in China, indicating no significant PK differences between Chinese and U.S. populations.

Dr. Handan He, Chief Scientific Officer of Ascletis, stated, “Overall, the potential drug-drug interactions of ASC41/ASC41-A were low, showing competitiveness to other THRβ agonists in the late stage clinical development. We completed this U.S. phase I study in approximately 4 months, demonstrating again execution excellence of our clinical team.”

Dr. Melissa Palmer, Chief Medical Officer of Gannex, stated, “These results are very important, as patients with NASH who are taking SSRIs/SNRIs and statins will be able to participate in upcoming clinical studies of ASC41. Furthermore, these results will likely translate to ease of use in patients with NASH in a real world setting, as these patients are typically on numerous medications to manage their comorbidities, such as hyperlipidemia, type 2 diabetes and depression.”

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK). Ascletis is committed to developing and commercializing innovative drugs in the areas of NASH, cancer lipid metabolism and oral checkpoint inhibitors, and viral diseases to address unmet medical needs both in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis has developed into a fully integrated platform covering the entire value chain from discovery and development to manufacturing and commercialization. Ascletis has three marketed products and a robust R&D pipeline of drug candidates.

(1) NASH: 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, and three fixed-dose combinations. (2) Cancer lipid metabolism and oral 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 checkpoint inhibitors. (3) Viral diseases: (i) Hepatitis B: focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 and Pegasys® as cornerstone drugs. (ii) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen). (iii) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. For more information, please visit www.ascletis.com.

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