Ascletis Pharma has announced the approval of the investigational new drug (IND) application by China National Medical Products Administration (NMPA).
The approval is for an in-house developed oral PD-L1 small molecule inhibitor prodrug, ASC61, for the treatment of advanced solid tumors. The ASC61 phase 1 dose escalation study is ongoing in the U.S. IND approval in China will accelerate the global development of ASC61.
ASC61’s 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.
Ascletis promising safety profile
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: higher patient compliance with easy and safe administration with no need of hospital visits for injections; ease of all oral combination therapies with other oral anti-tumor drugs; easier to manage immune-related adverse effects (irAEs) with dose adjustment; relatively lower cost; and higher permeability to distribute into targeted tissues.
Jinzi J. Wu, founder, chairman and CEO of Ascletis, said: “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.”