Ascletis Announces IND Approval of Oral PD-L1 Small Molecule Inhibitor ASC61 for Treatment of Advanced Solid Tumors by China NMPA

--While the ASC61 Phase I study is ongoing in the U.S.,the Investigational New Drug (IND) approval in China will accelerate the global development of ASC61,an in-house developed oral PD-L1 small molecule inhibitor

HANGZHOU and SHAOXING,China,Nov. 17,2022 -- Ascletis Pharma Inc. (HKEX: 1672,"Ascletis") announces today the approval of the Investigational New Drug (IND) application by China National Medical Products Administration (NMPA) for the in-house developed oral PD-L1 small molecule inhibitor,ASC61,for the treatment of advanced solid tumors. While the ASC61 Phase I dose escalation study is ongoing in the U.S.,IND approval in China will accelerate the global development of ASC61.

ASC61 is an oral small molecule inhibitor prodrug. Its active metabolite,ASC61-A,is a potent and highly selective inhibitor which 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 including humanized mouse model. Preclinical studies showed that ASC61 has good safety and pharmacokinetic profiles in animal models.

In a head-to-head comparison study using the human PD-L1 expressing cells and fresh peripheral blood mononuclear cells (PBMCs) co-culture assay,ASC61-A treatment induced secretion of IFNγ in a concentration dependent manner,with an EC50 of 2.86 nM. Maximal levels of IFNγ induced by ASC61-A were similar to that induced by Keytruda,a marketed PD-1 antibody.

Compared with PD-1/PD-L1 antibody injections,the oral PD-L1 inhibitor ASC61 has the following benefits: (1) higher patient compliance with easy and safe administration with no need of hospital visits for injections; (2) ease of all oral combination therapies with other oral anti-tumor drugs; (3) easier to manage immune-related adverse effects (irAEs) with dose adjustment; (4) relatively lower cost; and (5) higher permeability to distribute into targeted tissues.

"Immunogenicity and the poor permeability into tumor tissues are the major limitations of therapeutic antibodies,which can cause a low response rate of PD-1/PD-L1 antibodies. As a highly differentiated small molecule PD-L1 inhibitor,ASC61 showed promising safety profile in the dose escalation study in patients with advanced solid tumors in the U.S. so far. With two IND approvals in the U.S. and China,we expect to accelerate the global development of ASC61 and provide more options for patients with advanced solid tumors." said Dr. Jinzi J. Wu,Founder,Chairman and CEO of Ascletis.

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 22 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.