China NMPA Approves Phase III Clinical Trial of ASC40 Combined with Bevacizumab for Treatment of Patients with Recurrent Glioblastoma

--Phase III trial will evaluate progression-free survival and overall survival of patients with recurrent glioblastoma

--Glioblastoma has an incidence rate of approximately 2.85 to 4.56 per 100,000 population per year in China, suggesting approximately 40,000 to 64,000 new cases of glioblastoma per year. More than 90% glioblastoma patients will relapse after surgery, radiation and chemotherapies

--This is the first Phase III trial of ASC40 as a first-in-class drug candidate targeting tumor lipid metabolism

--Phase II data of patients with recurrent glioblastoma have shown that the overall response rate for ASC40 plus Bevacizumab treatment was 65% including a complete response of 20% and a partial response of 45%

--Phase I data of ASC40 alone and with a taxane have demonstrated promising responses in patients with advanced breast cancer and non-small cell lung cancer containing KRAS mutations

News provided by

Ascletis Pharma Inc.

Jul 21, 2021, 20:30 ET

HANGZHOU, China and SHAOXING, China, July 21, 2021 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX code: 1672) today announces that China National Medical Products Administration (NMPA) has approved the Phase III clinical trial application of ASC40 combined with Bevacizumab for treatment of patients with recurrent glioblastoma (rGBM).

The Phase III registrational study 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 QD + Bevacizumab) and Cohort 2 (matching placebo tablet QD + Bevacizumab).

On May 25, 2021, the Company announced that the clinical trial application for rGBM was accepted for review by China NMPA (Details referring to press release: https://www.ascletis.com/news_detail/175/id/494.html).

Based on published data, in China, glioblastoma (GBM) represents 46.1% 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 United States, GBM represents 56.6% of gliomas and has an incidence rate of approximately 3.21 per 100,000 population per year.

Bevacizumab is the only drug which has been approved for rGMB indication in China as of September, 2020. The data of BELOB Trial indicated that median PFS was three months for patients with rGBM after Bevacizumab treatment.

Lipid metabolism has been reported to play a critical role in various cancers. Fatty acid synthase (FASN) is one of the most important proteins which regulate lipid metabolism. Many solid and hematopoietic tumors overexpress FASN, including rGBM, non-small cell lung, breast, ovarian, prostate, colon, pancreatic cancers, and non-Hodgkin lymphoma.

ASC40 (known as TVB-2640 outside China) is a potent, selective and safe oral small molecule inhibitor of FASN. The data from the Phase II trial have shown that the overall response rate (ORR) for ASC40 (TVB-2640) plus Bevacizumab was 65% including a complete response (CR) of 20% and a partial response (PR) of 45%. Furthermore, the Phase II data indicate that the progression-free survival at six months (PFS6) observed for ASC40 (TVB-2640) plus Bevacizumab was 47%, representing a statistically significant improvement in PFS6 over the historical Bevacizumab monotherapy PFS6 of 16% (BELOB Trial) (P=0.01). ASC40 (TVB-2640) in combination with Bevacizumab was safe and well tolerated in such patient population (ClinicalTrials.gov Identifier: NCT03032484).

"I am thrilled to be the principal investigator leading the ASC40 Phase III trial for rGBM," 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, "Based on strong Phase II data, I hope and expect that targeting tumor lipid metabolism with ASC40 will offer a promising therapeutic approach to treat rGBM which is one of the most devastating cancers."

"ASC40 Phase III clinical trial approval by NMPA is a significant milestone for our oncology pipeline since the Company announced, in March this year, an investment escalation in R&D of cancer lipid metabolism and oral checkpoint inhibitors." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. "With the strong momentum from the ASC40 Phase III approval, our talented R&D team is accelerating the clinical development programs of ASC40 for other oncology indications as well as oral PD-L1 small molecule inhibitor programs."

A Phase I clinical trial was completed on 136 patients with advanced tumor from the United States and United Kingdom. The patients were treated with ASC40 (TVB-2640) alone and with a taxane. The data from this Phase I trial have demonstrated FASN target engagement, good safety, pharmacokinetics as well as promising responses of ASC40 (TVB-2640) in patients with advanced solid tumors, particularly in lung cancer with KRAS mutations, ovarian cancer, and breast cancer (ClinicalTrials.gov Identifier: NCT02223247).

There are additional clinical trials of ASC40 (TVB-2640) ongoing in the United States in patients with KRAS mutation non-small cell lung cancer (ClinicalTrials.gov Identifier: NCT03808558) and breast cancer (ClinicalTrials.gov Identifier: NCT03179904).

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 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.