Ascletis Announces U.S. IND Approval of Oral PD-L1 Small Molecule Inhibitor ASC61 for Treatment of Advanced Solid Tumors

• The objectives of the U.S. Phase I trial are to find a recommended Phase II dose and obtain preliminary efficacy in patients with advanced solid tumors
• The first U.S. patient is expected to be dosed in the first half of 2022
• ASC61 shows significant antitumor efficacy as a single agent in various animal models

HANGZHOU, China and SHAOXING, China, Feb. 6, 2022 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672) announces today the approval of the Investigational New Drug (IND) application by U.S. Food and Drug Administration (FDA) for in-house developed oral PD-L1 small molecule inhibitor, ASC61, for the treatment of advanced solid tumors. This is Ascletis' second U.S. IND approval in 2022 after ASC22 (Envafolimab) U.S. IND approval for functional cure of chronic hepatitis B (CHB).

The ASC61 Phase I trial in the U.S. is a dose escalation study in patients with advanced solid tumors. The objectives of such study are to find a recommended Phase II dose (RP2D) and obtain preliminary efficacy in patients with advanced solid tumors. The first U.S. patient is expected to be dosed in the first half of 2022.

ASC61 is an oral potent and highly selective PD-L1 small molecule inhibitor and blocks PD-1/PD-L1 interaction through inducing PD-L1 dimerization and internalization. As a single agent, ASC61 demonstrated significant antitumor efficacy in multiple animal models such as the humanized mouse model. Preclinical studies showed that ASC61 has good safety and pharmacokinetic profiles in animal models.

ASC61 oral tablets, which will be used in the clinical trial, were developed with the in-house proprietary technology.

Compared to injectable PD-1/PD-L1 antibodies, ASC61, as an oral PD-L1 inhibitor, has the following benefits: (1) ease of dosing and no need for hospital visits for injections; (2) all-oral combinations with other oral anti-tumor drugs; and (3) rapid titration of doses for better management of immune-related adverse events (irAEs).

"We are excited about U.S. IND approval of ASC61," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, "This IND approval demonstrates Ascletis' global R&D capability in oncology. As we are advancing the phase III clinical trial of ASC40, a fatty acid synthase (FASN) inhibitor, in combination with Bevacizumab for the treatment of recurrent glioblastoma (rGBM), this U.S. IND approval is another significant milestone for Ascletis' oncology pipeline. Furthermore, we are exploring opportunities for all-oral combinations between oral PD-L1 small molecule inhibitor ASC61 and ASC40 as well as other oral anti-tumor drugs from our business partners."

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.