Ascletis' Subcutaneous PD-L1 Antibody ASC22 Demonstrated Potential of Functional Cure of Chronic Hepatitis B as 42.9% of Patients with Baseline HBsAg≤100 IU/mL Obtained Sustained HBsAg Loss

--Ascletis presented Phase IIb clinical trial results of subcutaneous PD-L1 antibody ASC22 for functional cure of CHB at oral session of EASL ILC 2022 on June 25, 2022, Beijing Time

--The Phase IIb clinical trial results further demonstrated the potential of ASC22+NAs treatment as a functional cure for CHB

--On-treatment ALT flares might be used as a predictor or monitor of patients' responses to the CHB treatment

HANGZHOU, China and SHAOXING, China, June 26, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, "Ascletis") today announces the latest Phase IIb clinical trial results of subcutaneous PD-L1 antibody ASC22 (Envafolimab) in patients with chronic hepatitis B (CHB) at an oral parallel session of the International Liver Congress™ 2022 (ILC 2022) held by the European Association for the Study of the Liver (EASL).

The interim report is based on a randomized, single-blind, multi-center Phase IIb clinical trial to assess the efficacy and safety of ASC22 in treatment of CHB patients (ClinicalTrials.gov Identifier: NCT04465890). In 1.0 mg/kg ASC22 cohort, 75 CHB patients were randomized to be treated with 1.0 mg/kg ASC22 (n=60) or placebo (PBO, n=15) once every 2 weeks (Q2W) plus nucleos(t)ide analogs (NAs) for 24-week and then followed for another 24 weeks.

The following sets forth the key findings from the Phase IIb clinical study on ASC22:

• 42.9% patients with baseline HBsAg ≤100 IU/mL (n=7) obtained sustained HBsAg loss.
  
  
• ALT flares were observed on 21% patients in ASC22 group (n=48) while none in PBO group.
  
  
• Patients with ALT flares had more HBsAg reduction. Among the three patients with sustained HBsAg loss, two experienced ALT flares.
  
  
• One patient obtained sustained HBsAg loss starting at Week Four after two doses of ASC22 and experienced a transient seroconversion of anti-HBs at Week 28. This patient stopped NAs treatment three days after 24-week treatment of ASC22, and HBsAg still remained negative until end of the study.
  
  
• Most adverse events (AEs) (97.5%) were Grade 1-2, and no study drug-related serious adverse event (SAE) was reported.

"For the past years, Ascletis has been dedicated to developing therapy for the functional cure of CHB. ASC22 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. It's a great honor that our industry leading clinical trial result on immunotherapy has been recognized by the reviewers and scientific committee of EASL and accepted as oral presentation in ILC. We are very encouraged by the promising efficacy and safety profile that ASC22 has achieved as a potential functional cure for CHB. We expect to further advance the clinical studies to benefit more patients." Said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

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.

Abstract presented at ILC 2022 is as follows:

ALT flares were linked to HBsAg reduction, seroclearance and seroconversion: interim results from a phase IIb study in chronic hepatitis B patients with 24-week treatment of subcutaneous PD-L1 Ab ASC22 (Envafolimab) plus nucleos(t)ide analogs

Presentation Type: Oral Presentation

Abstract Number: OS091

Session: Abstract session: Hepatitis B emerging therapies

Presenter: Prof. Guiqiang Wang, Director of Infectious Diseases Department and Liver Disease Center of Peking University First Hospital

Presentation time: June 25, 2022, Saturday, 15:15-15:30 (Beijing Time)

*The abstract can be accessed at: https://easl.eu/event/international-liver-congress-2022/abstract-information/ 

[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.

About EASL

EASL is the world's leading medical association dedicated to liver diseases research. As the annual flagship event with over 10, 000 representatives participating every year, ILC is one of the most influential congress on hepatology research globally where the advances, best practices and latest scientific breakthroughs are shared with the global community. Among the 1,993 abstracts accepted by ILC this year, total nine Chinese abstracts have been admitted to oral presentation. Ascletis' ASC22 on CHB functional cure is the only China biotech-initiated, HBV-related study that has been selected for oral presentation at ILC 2022.

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.

SOURCE Ascletis Pharma Inc.