Ascletis Announces Dosing of the First Patient in the Phase IIb Expansion Cohort of ASC22 (Envafolimab) for Chronic Hepatitis B Functional Cure

• After the pre-Phase III clinical trial meeting with Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) in June 2022, the pathway to the registration, including patient population, dose, treatment duration, etc. of ASC22 (Envafolimab) for functional cure of chronic hepatitis B (CHB) has been agreed
• The Phase IIb Expansion Cohort will enroll 50 CHB patients with baseline HBsAg≤100 IU/mL who will be treated with 1.0 mg/kg ASC22 or placebo (with the ratio of 4:1) in combination with Nucleot(s)ide analogues (NAs) for 24-week treatment plus 24-week follow-up
• The objective of this Expansion Cohort study is to confirm whether the rate of functional cure is similar to the data presented at oral session of the International Liver Congress™ 2022 (ILC 2022) held by the European Association for the Study of the Liver (EASL) in June 2022, which showed that 42.9% (3/7) of patients with baseline HBsAg ≤100 IU/mL obtained functional cure. The enrollment of 50 CHB patients is expected to be completed in early 2023

HANGZHOU and SHAOXING, China, Sept. 27, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, “Ascletis”) today announces dosing of the first patient in the Phase IIb Expansion Cohort (the “Expansion Cohort”) of subcutaneously administered PD-L1 antibody ASC22 (Envafolimab) for functional cure of chronic hepatitis B (CHB).

After the pre-Phase III clinical trial meeting with Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) in June 2022, the pathway to the registration, including patient population, dose, treatment duration, etc. of ASC22 (Envafolimab) for functional cure of CHB has been agreed.

The Expansion Cohort will enroll 50 CHB patients with baseline hepatitis B surface antigen (HBsAg) ≤100 IU/mL who will be treated with 1.0 mg/kg ASC22 or placebo (with the ration of 4:1) in combination with Nucleot(s)ide analogues (NAs) for 24-week treatment plus 24-week follow-up. The objective is to confirm whether the functional cure rate of ASC22 is similar to the data presented at oral session of the International Liver Congress™ 2022 (ILC 2022) held by the European Association for the Study of the Liver (EASL) in June 2022, which showed that 42.9% (3/7) of patients with baseline HBsAg≤100 IU/mL obtained functional cure. The enrollment of 50 CHB patients of the Expansion Cohort is expected to be completed in early 2023.

Prior to the initiation of the Expansion Cohort, Ascletis has completed a randomized, single-blind, placebo-controlled and multi-center Phase IIb clinical trial in China which evaluated the safety and efficacy of treating 149 patients with CHB for 24-week treatment plus 24-week follow-up of 1 mg/kg or 2.5 mg/kg ASC22 or matching placebo given once every two weeks (Q2W) in combination with NAs (ClinicalTrials.gov: NCT04465890).

CHB remains to be a significantly unmet medical need globally, with approximately 86 million people in China and 1.59 million people in the U.S. infected with hepatitis B virus (HBV) ^[1]. NAs inhibit only reverse transcription of HBV RNA into HBV DNA and do not inhibit the transcription of HBV cccDNA into HBV RNA, thus have no inhibitory effect on HBsAg.

ASC22 (Envafolimab) is the most advanced clinical-stage immunotherapy in the world for CHB functional cure, i.e. HBsAg loss, through blocking PD-1/PD-L1 pathway. Ascletis presented the latest Phase IIb clinical trial results of ASC22 in patients with CHB at oral session of EASL ILC 2022 in June 2022, which showed that 42.9% (3/7) patients with baseline HBsAg≤100 IU/mL obtained sustained HBsAg loss and no rebound has occurred up to now since the last dosing of ASC22 (Envafolimab), indicating a potential functional cure of CHB. For tumor indications, Envafolimab has been approved for treatment of adults with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors by China NMPA in November 2021.

“We are very encouraged by the exciting progress which ASC22 (Envafolimab) has made for CHB functional cure during the past few months. ASC22 (Envafolimab) has preliminarily demonstrated the potential of functional cure of CHB from our results presented at EASL ILC 2022. There is a huge CHB patient population base in China with baseline HBsAg≤100 IU/mL^[2]. While pursuing ASC22 (Envafolimab) as monotherapy for CHB patients with baseline HBsAg≤100 IU/mL, we are also engaging with global partners in discussion on combo therapies targeting patient population with baseline HBsAg>100 IU/mL, so as to benefit a broader spectrum of CHB patient population.” said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

[1]Lim J K, Nguyen M H, Kim W R, et al. Prevalence of Chronic Hepatitis B Virus Infection in the United States [J]. The American journal of gastroenterology 2020, 115(9): 1429-38.

[2] Jiang Haiyang, Gu Shengwang, Liu Huan, et al. Consideration on improving functional cure significantly based on the results of long-term follow-up of 1783 patients with chronic hepatitis B(in Chinese) [J] Liver, 2020, 25 (2): 4

About ASC22 (KN035)

Ascletis Pharma Inc (1672.HK) retains the global and exclusive rights to develop and commercialize ASC22 on viral indications. Progress has been made from clinical trials of ASC22 including:

1) Chronic hepatitis B (CHB) functional cure: first patient dosed in Phase IIb Expansion Cohort. Interim results from the China Phase IIb clinical trial showed 1mg/kg of ASC22 plus NAs for 24-week treatment were well-tolerated in CHB patients. 42.9% of patients with baseline HBsAg≤100 IU/mL obtained sustained HBsAg loss, which indicates the potential of functional cure. The abstract has been selected to oral presentation at EASL ILC 2022.

2) HIV functional cure: Phase II clinical trial of ASC22 as monotherapy has completed first subject dosing in China. The Phase I/II clinical trial in the U.S. has obtained IND clearance from U.S. FDA. Clinical trial of ASC22 in combination with Chidamide, initiated by Shanghai Public Health Clinical Center (investigator initiated trial), has completed patient enrollment.

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 treatment), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne).

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

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SOURCE Ascletis Pharma Inc.

Company Codes: HongKong:1672