Ascletis Announces Completion of 149 Patient Enrollment and Positive Interim Results of Phase IIb Chronic Hepatitis B Study in China for its Subcutaneously Administered PD-L1 Antibody ASC22 (Envafolim

Ascletis Pharma Inc. today announces the completion of 149 patient enrollment and the positive interim results of Phase IIb study on chronic hepatitis B (CHB) patients in China treated with ASC22 (Envafolimab) -- a first-in-class, subcutaneously administered PD-L1 antibody, in combination with nucleos(t)ide analogs (NAs).

The ASC22 Phase IIb study is a randomized, single-blind, placebo-controlled, multi-center clinical trial in China which evaluates the safety and efficacy of treating patients with CHB for 24-week treatment of 1 mg/kg or 2.5 mg/kg ASC22 or matching placebo given once every two weeks (Q2W) in combination with NAs. Patients enrolled in the study were hepatitis B surface antigen (HBsAg) < 10,000 IU/mL, HBV DNA < 20 IU/mL and negative hepatitis B e-antigen (HBeAg). A total of 149 patients with CHB were enrolled. Among them, 75 patients were 2:1 randomized to 1 mg/kg ASC22 Q2W dosed subcutaneously plus NAs and placebo Q2W dosed subcutaneously plus NAs. 74 patients were 2:1 randomized to 2.5 mg/kg ASC22 Q2W dosed subcutaneously plus NAs and placebo Q2W dose subcutaneously plus NAs (ClinicalTrials.gov Identifier: NCT04465890).

As of July 20, 2021, for the 1 mg/kg ASC22 Q2W plus NAs group, 37% of patients completed 24-week treatment per protocol; 35% of patients completed 14 to 22-week treatment and 28% of patients completed 1 to 12-week treatment; for the 2.5 mg/kg ASC22 Q2W plus NAs group, 7% of patients completed 14 to 24-week treatment and 93% of patients completed 1 to 12-week treatment. Based on the safety data available as of July 20, 2021, the interim analysis indicated the 1 mg/kg ASC22 Q2W plus NAs group had a rate of any adverse events of 75% which was comparable to that (73%) of the placebo Q2W plus NAs group. The rate of grade 3 and 4 adverse events (7%) for the 1 mg/kg ASC22 Q2W plus NAs group was also comparable to that (7%) of the placebo Q2W plus NAs group.

Based on the efficacy data available as of July 20, 2021, the interim analysis indicated that HBsAg reduction was observed for 1 mg/kg ASC22 Q2W plus NAs with more HBsAg reduction observed in patients with HBsAg ≤ 500 IU/mL at baseline while no HBsAg reduction was observed for placebo plus NAs.

Based on the pharmacokinetic data of the Phase IIb study in patients with 1 mg/kg or 2.5 mg/kg ASC22 Q2W plus NAs, the minimum concentrations (Cmin) of ASC22 at steady state are predicted to be > 3 μg/mL one month after both 1 and 2.5 mg/kg dosing, indicating > 90% receptor occupancy in CHB patients over one month after dosing. These data suggest that ASC22 has the potential to be given once a month, which will enhance the compliance and convenience of patients with CHB.

"I am delighted by the safety data so far for 1 mg/kg ASC22 Q2W plus NAs, which was comparable to that of placebo Q2W plus NAs," said Guiqiang Wang, MD, Principal Investigator of the Phase IIb Study, Vice-President of Chinese Society of Physicians for Infectious Diseases and Director of Centre for Liver Diseases at Peking University First Hospital, "Once-a-month dosing of PD-L1 antibody ASC22 will dramatically improve compliance and convenience of patients with CHB."

"The positive interim data of ASC22 plus NAs in the phase IIb study suggest that the combination of PD-L1 antibody ASC22 with other therapies will have great potential to offer functional cure for patients with CHB." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

"With its advantage in safety, convenience, and compliance, KN035 (ASC22) is potentially bringing solutions for chronical virus diseases, including HBV and HIV." said Dr. Ting Xu, Chairman of Alphamab.

On January 12, 2019, Ascletis entered a strategic partnership agreement for PD-L1 antibody ASC22 (KN035) with Suzhou Alphamab Co., Ltd. (Alphamab). Under the terms of the agreement, Ascletis has an exclusive license from Alphamab to develop and commercialize ASC22 (KN035) for all viral diseases including Hepatitis B and HIV in Greater China. For ASC22 (KN035) in viral indications worldwide outside Greater China, Ascletis will be eligible to share certain economics such as upfront, milestone payments and royalties, depending on the development and regulatory status of ASC22 (KN035) inside Greater China.

About ASC22

ASC22, also known as KN035 or Envafolimab, licensed exclusively by Ascletis for all viral indications from Alphamab, is a PD-L1 single domain antibody Fc fusion and has the advantages of subcutaneous injection and good stability at room temperature. These would be of great value to improve patients' compliance and quality of life and to help realize the goal of long-term management of chronic diseases such as chronic hepatitis B. Ascletis and Suzhou Alphamab Co., Ltd. announced on January 14, 2019 the strategic collaboration and licensing agreement for anti-PD-L1 to treat Hepatitis B and other viral diseases. Envafolimab has been enrolled in more than 1,000 patients and has shown good safety and efficacy in multiple tumor indications. Alphamab and its partner have submitted a biologic license application (BLA) for MSI-H solid tumors.

About Alphamab

Suzhou Alphamab Co., Ltd., focused on research and development of mAbs, fusion proteins and other biological macromolecule drugs. With multiple proprietary platforms in antibody screening, protein engineering, CMC development and pilot production set up in its 6000m2 laboratory in bioBAY Suzhou, Alphamab has created a robust pipeline of over 50 promgrams, of which 20+ are innovative. Alphamab aims to develop affordable and efficient biological drugs to address high unmet medical needs globally.

About Ascletis

Ascletis is an innovative R&D driven biotech and listed on Hong Kong, S.A.R., China 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, viral hepatitis and HIV/AIDS for unmet medical needs 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 seventeen R&D pipeline drug candidates or combination therapies (eleven of them developed in-house). 1. NASH: Gannex, a wholly-owned company of Ascletis, is fully 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, THR-beta and FXR, and three pre-clinical stage combination therapies. 2. Cancer lipid metabolism and oral checkpoint inhibitors: focus on 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 inhibitors as the next generation checkpoint inhibitors. 3. Viral hepatitis: (i) Hepatitis B: focus on breakthrough therapies for HBV clinical cure with subcutaneously injected PD-L1 antibody - ASC22 and Pegasys® as cornerstone drugs. (ii) Hepatitis C: successfully launched all oral regimen of ASCLEVIR® and GANOVO® combination (RDV/DNV regimen); and ASC18 fixed dose combination (FDC) is an upgraded version of RDV/DNV regimen with bridging study finished. 4. HIV/AIDS: ASC09F is a FDC treatment of HIV targeting protease. The clinical trial application of ASC09F has been approved.