Youzhiyou Biopharma's PD-L1/TGF-β Bispecific Antibody Y101D Receives FDA Clearance for Clinical Trials in Advanced or Metastatic Cancers
On January 23, 2021, Wuhan Youzhiyou Biopharmaceutical Co., Ltd. (hereinafter referred to as “Youzhiyou Biopharma”) independently developed its ““Recombinant Anti-PD-L1 and TGF-β Bispecific Antibody Injection” (Code: Y101D), received approval from the U.S. Food and Drug Administration (FDA) to conduct clinical trials in the United States, initiating clinical studies targeting locally advanced or metastatic tumors. This marks the fourth bispecific antibody new drug approved by the U.S. FDA for clinical development by Youzhiyou Biopharmaceutical, following M802, M701, and Y150.
Immunotherapy is one of the most promising treatment approaches for cancer. PD-1/PD-L1 monoclonal antibodies have garnered significant attention due to their broad anticancer spectrum, durable efficacy, and manageable side effects; however, their response rate is limited to approximately 20% of cancer patients. To enable more patients to respond to these immunotherapies, numerous clinical trials are evaluating combination therapies that pair anti-PD-1/PD-L1 agents with other targets, as well as developing bispecific antibodies. TGF-β signaling in the tumor microenvironment promotes tumor progression and is a well-established immunosuppressive factor. Preclinical studies have demonstrated potential complementary interactions between the PD-L1 and TGF-β pathways. By simultaneously blocking these two immunosuppressive signaling pathways, it is possible to relieve immune suppression, thereby reactivating and restoring the body’s antitumor immune response and ultimately controlling tumor growth.
Leveraging YZY Biopharma’s proprietary CHECK-BODY platform for tetravalent symmetric bispecific antibodies, the novel drug candidate Y101D, which simultaneously targets PD-L1 and TGF-β, isThe first true bispecific antibody targeting both PD-L1 and TGF-β.Unlike Merck’s investigational dual-function fusion protein M7824 (Bintrafusp alfa), which targets the same molecule, Y101D bispecific antibody features a specific F(ab)2-(Fv)2-Fc structure. In Y101D, the TGF-β-binding moiety is the Fv domain of an anti-TGF-β antibody, whereas in M7824, the TGF-β-targeting component is the extracellular domain of the receptor TGFBRII. Preclinical pharmaceutical studies have shown that:The Y101D antibody candidate drug exhibits high expression levels, good stability, and a simple glycan profile.and demonstrated efficacy in multiple murine tumor modelsSignificant tumor suppression effect.
Schematic Diagram of Y101D Structure
Dr. Zhou Pengfei, CEO of Wuhan Youzhiyou Biopharmaceutical Co., Ltd., stated: “Wuhan Youzhiyou Biopharmaceutical is one of the earliest biotechnology companies in China to establish a strategic presence in bispecific antibody drugs, having accumulated substantial expertise in CD3-engaging bispecific antibodies. The recently developed novel tetravalent symmetric bispecific antibody technology can be broadly applied to the construction and design of bispecific antibody therapeutics. We anticipate that the PD-L1/TGF-β bispecific antibody will effectively enhance response rates in tumor immunotherapy and expand the indications for PD-1/PD-L1 immune checkpoint inhibitor therapy.”