Ascletis Announces First Patient Dosed in the Phase III Clinical Trial of FASN Inhibitor ASC40 Combined with Bevacizumab for Treatment of Recurrent Glioblastoma

HANGZHOU and SHAOXING, China, Jan. 23, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX code: 1672) today announces the dosing of the first patient in the Phase III registration clinical trial of ASC40 combined with bevacizumab for treatment of recurrent glioblastoma (rGBM). ASC40 is an oral, selective inhibitor of fatty acid synthase (FASN), a key enzyme which regulates de novo lipogenesis (DNL). ASC40 inhibits energy supply and disturbs membrane phospholipid composition of tumor cells by blocking de novo lipogenesis.

The Phase III registration study (ClinicalTrials.gov Identifier: NCT05118776) is a randomized, double-blind, placebo-controlled, multi-center clinical trial in China to evaluate progression-free survival (PFS), overall survival (OS) and safety of patients with rGBM. Approximately 180 patients will be 1:1 randomized to Cohort 1 (oral ASC40 tablet once daily + Bevacizumab) and Cohort 2 (matching placebo tablet once daily + Bevacizumab). Approximately 80% of such 180 patients with rGBM in the Phase III clinical trial are expected to be randomized and enrolled by the end of December 2022.

The Phase II study, completed in the U.S., in patients with rGBM has shown that the objective response rate (ORR) for ASC40 plus Bevacizumab treatment was 65% including a complete response (CR) of 20% and a partial response (PR) of 45%.

Based on published data, in China, glioblastoma (GBM) represents 57% of gliomas and has an incidence rate of approximately 2.85 to 4.56 per 100,000 population per year, suggesting approximately 40,000 to 64,000 new cases of GBM per year. More than 90% GBM patients will relapse after surgery, radiation and chemotherapies. In the U.S., GBM represents 56.6% of gliomas and has an incidence rate of approximately 3.21 per 100,000 population per year. 

"I am pleased that the first patient has been successfully dosed in the Phase III clinical trial of ASC40 combined with bevacizumab for treatment of recurrent glioblastoma. As the first clinical trial targeting tumor lipid metabolism in China, we are looking forward to the results of the trial," said Dr. Wenbin Li, Vice Chairman and Secretary General of Glioma Committee of Chinese Cancer Association, Director of the Comprehensive Tumor Treatment Center, Beijing Tiantan Hospital, Capital Medical University.

"Dosing the first patient in ASC40 Phase III registration study is a significant milestone for our oncology pipeline. We are looking forward to the data from this Phase III study," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

In Ascletis' oncology pipeline, in addition to FASN inhibitors, there are two oral PD-L1 small molecule inhibitors developed in-house, namely ASC61 and ASC63. Ascletis has filed a U.S. Investigational New Drug (IND) application of ASC61 for the treatment of advanced solid tumors.

About Ascletis
Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), a global platform covering the entire value chain from discovery and development to manufacturing and commercialization. Ascletis is committed to developing and commercializing innovative drugs in the areas of viral diseases, NASH/PBC, and cancer (oral cancer metabolic checkpoint and immune checkpoint inhibitors) to address unmet medical needs both in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis targets those therapeutic areas with unmet medical needs from a global perspective, and efficiently advances the developments of pipelines with an aim of leading in global competition. To date, Ascletis has three marketed products and 20 robust R&D pipelines of drug candidates with global competitiveness, and is actively exploring new therapeutic areas.

1. Viral Diseases: (1) Hepatitis B Virus (functional cure): focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 and Pegasys® as cornerstone drugs. (2) COVID-19 pipeline: currently includes (i) ritonavir oral tablet (100 mg), an authorized product, (ii) ASC10, an oral RNA dependent RNA polymerase (RdRp) inhibitor and (iii) ASC11, an oral 3-chymotrypsin like protease (3CLpro) inhibitor. (3) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. (4) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen).
2. Non-alcoholic Steatohepatitis/Primary Biliary Cholangitis: 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, three fixed-dose combinations for NASH and one PBC program targeting FXR.
3. Cancer (oral cancer metabolic checkpoint and immune 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 immune checkpoint inhibitors.
4. Exploratory Indications: Acne: Following NASH and recurrent GBM, the third indication for ASC40 has been approved to enter Phase 2 clinical trial. For more information, please visit www.ascletis.com.