China-based Biocytogen Pharmaceuticals (Beijing) Co., Ltd has announced receiving approval from the China National Medical Products Administration (NMPA) to conduct an open-label Phase I dosage escalation study. The study will assess the safety, tolerability, and preliminary anti-tumor activity of YH008, an internally developed first-in-class PD-1 x CD40 bispecific antibody (BsAb) for the treatment of advanced tumors.
Mechanism of Action and Development
YH008 is designed to exert antagonistic and agonistic activities on PD-1 and CD40, respectively. In vitro and in vivo studies have shown that the activation of the CD40 signaling pathway is dependent on PD-1 expression. This unique mechanism allows YH008 to conditionally activate the CD40 pathway in the tumor microenvironment, where tumor-specific PD-1+ T cells are enriched, without causing systemic CD40 non-specific activation. To further enhance its safety profile, YH008 was engineered with an Fc-silent IgG1 isotype, minimizing Fc-receptor-mediated non-specific immune activation.
Clinical and Preclinical Efficacy
The molecule has demonstrated superior anti-tumor activity compared to parental monoclonal antibodies (mAbs) or combination therapies in vivo. Moreover, YH008 has shown enhanced efficacy over benchmark PD-1 mAbs and PD-L1 x CD40 BsAbs in syngeneic models. Pharmacodynamic studies indicate that YH008 can effectively activate tumor-infiltrating DCs and T cells. Additionally, both in vivo studies and GLP toxicology studies have shown that YH008 has improved safety compared to benchmark CD40 mAbs.
Licensing and Market Expansion
YH008 received clinical trial approval in the US in December 2022. The drug was the subject of a USD 85.88 million licensing deal between Eucure Biopharma, a wholly-owned subsidiary of Biocytogen, and Shenzhen Chipscreen Biosciences Co., Ltd (SHA: 688321). Under the terms of the agreement, Shenzhen Chipscreen Biosciences Co., Ltd acquired exclusive development and commercialization rights to YH008 in Greater China, highlighting the drug’s potential in the region and globally.-Fineline Info & Tech
