Ascletis Announces Positive Phase IIa HBV Results on Subcutaneously Administered PD-L1 Antibody ASC22 (Envafolimab)

-One patient achieved Hepatitis B surface antigen (HBsAg) reduction of 1.2 log10 IU/mL in the 2.5 mg/kg single dose cohort (n=3)

-Trend of dose dependent HBsAg reduction observed

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Ascletis Pharma Inc.

May 04, 2021, 20:30 ET

HANGZHOU and SHAOXING, China, May 4, 2021 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672) today announces the positive Phase IIa clinical results of ASC22 (Envafolimab), which is a first-in-class, subcutaneously administered PD-L1 antibody for chronic hepatitis B (CHB) functional cure.

ASC22 Phase IIa clinical trial is a single dose escalation study of three subcutaneously administered doses (0.3, 1.0 and 2.5 mg/kg, three patients per dose) with 12-week follow-up to explore the safety and preliminary efficacy of ASC22 in CHB patients (ClinicalTrials.gov Identifier: NCT04465890). The primary efficacy endpoint is HBsAg reduction during 12-week follow-up after the single dose administration. Median baseline HBsAg of nine CHB patients enrolled was 3.0 log₁₀ IU/mL.

The phase IIa data indicated that there is a trend of dose dependent HBsAg reduction after single dose administration of 0.3, 1.0 or 2.5 mg/kg ASC22. Eight out of nine patients treated with ASC22 exhibited some decline in HBsAg at the end of 12-week follow-up. Among three patients receiving 2.5 mg/kg dose, one patient achieved a maximum HBsAg reduction of 1.2 log₁₀ IU/mL during the 12-week follow-up.

ASC22 is safe and well tolerated at all three dose levels with only grade 1 adverse effects. There were no grade 2 or above adverse effects observed during 12-week follow-up. Single dose administrations up to 2.5 mg/kg ASC22 did not affect alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (all below upper limit of norm) during 12-week follow-up.

On January 12, 2019, Ascletis entered an exclusive licensing 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.

"I am excited by > 1.0 log HBsAg reduction with only single dose ASC22," said Guiqiang Wang, MD, Principal Investigator of the Study, Vice-President of Chinese Society of Physicians for Infectious Diseases and Director of Centre for Liver Diseases at Peking University First Hospital, "As an immunotherapy, ASC22 has the potential to functionally cure CHB and offers convenient subcutaneous injections for patients. I am looking forward to the data from ASC22 Phase IIb HBV trial with much larger sample sizes."

"We are thrilled by positive Phase IIa data and believe this first-in-class immunotherapy has great potential to functionally cure CHB." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

The single dose results are really intriguing. With its advantage in safety, convenience, and compliance, KN035 (ASC22) is potentially bring solution for chronical virus diseases, including HBV and HIV." said Dr. Ting Xu, Chairman of Alphamab.

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

SOURCE Ascletis Pharma Inc.