On December 18, 2022 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315) reported that the US FDA has approved the Investigational New Drug (IND) application for a phase I study of YH008, an internally developed first-in-class PD-1 x CD40 bispecific antibody (bsAb) (Press release, Biocytogen, DEC 18, 2022, View Source [SID1234625367]). The IND application was completed by Biocytogen’s wholly owned subsidiary Eucure Biopharma.
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The trial is an open-label, dose-escalation study (No. YH008101) that will evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of YH008 monotherapy in patients with PD-(L)1-resistant advanced solid tumors or hematological malignancies.
YH008 exerts antagonistic and agonistic activities on PD-1 and CD40, respectively. In vitro and in vivo studies indicate that activation of the CD40 signaling pathway is dependent on PD-1 expression. Therefore, YH008 can conditionally activate CD40 pathway in the tumor microenvironment where tumor specific PD-1+ T cells are enriched, without systemic CD40 non-specific activation. Additionally, YH008 was engineered with an Fc-silent IgG1 isotype to avoid Fc-receptor-mediated non-specific immune activation. YH008 demonstrated superior anti-tumor activity than parental monoclonal antibodies (mAbs) or combination therapy in vivo. Moreover, the anti-tumor activity of YH008 was also superior to benchmark PD-1 mAbs and PD-L1 x CD40 bsAbs in syngeneic models. In vivo pharmacodynamic studies indicate that YH008 can activate tumor-infiltrating DCs and T cells. In addition, both in vivo studies and GLP toxicology studies indicate improved safety of YH008 compared with benchmark CD40 mAbs.
"The CD40 agonistic activity of YH008 is PD-1-dependent, which allows for more targeted immune cell activation and synergies," said Dr. Yi Yang, Chief Scientific Officer (CSO) of Biocytogen. "These characteristics prevent occurrence of liver toxicity, even at high doses, while enhancing anti-tumor activity, giving YH008 high clinical potential."
"YH008 is a first-in-class bispecific antibody discovered through large-scale in vivo efficacy screening, where it demonstrated excellent anti-tumor activity, even in cold tumors," said Dr. Rong Chen, CEO and CMO of Eucure Biopharma, VP of Biocytogen. "With this IND clearance for YH008, the company will have more products with diversified modalities entering the clinic to benefit patients."