Alphamab Oncology Receives IND Approval for First-in-Class Bispecific ADC JSKN022 Targeting PD-L1 and Integrin αvβ6
核心洞察
Alphamab Oncology (搜索)'s IND application for JSKN022, a novel bispecific antibody-drug conjugate targeting both PD-L1 (搜索) and integrin αvβ6 (搜索), has been officially accepted by China's NMPA.
JSKN022 represents the first ADC worldwide to target either integrin αvβ6 (搜索) or PD-L1 (搜索), with all related investigational candidates currently remaining in clinical development stages.
The innovative therapy utilizes a glycan-specific conjugation platform and topoisomerase I inhibitor (搜索) to potentially overcome resistance to PD-1/PD-L1 (搜索) inhibitors in multiple cancer types.
Alphamab Oncology (搜索) announced that China's National Medical Products Administration (NMPA) has officially accepted the Investigational New Drug (IND) application for JSKN022, marking a significant milestone for the first-in-class bispecific antibody-drug conjugate targeting PD-L1 (搜索) and integrin αvβ6 (搜索). The Hong Kong-listed company (stock code: 9966.HK) plans to initiate a first-in-human clinical study for treating advanced malignant solid tumors (搜索).
Novel Dual-Target Mechanism of Action
JSKN022 represents a breakthrough in ADC design, simultaneously targeting and binding to both PD-L1 (搜索) and integrin αvβ6 (搜索) on tumor cell surfaces. The molecule utilizes Alphamab's proprietary glycan-specific conjugation platform to achieve enhanced stability and homogeneity. After binding to either target, JSKN022 enters the lysosome through target-mediated endocytosis, where proteolytic enzymes such as cathepsin B (搜索) specifically hydrolyze the cleavable linker.
This process releases the cytotoxic topoisomerase I inhibitor (搜索) (T01), which induces apoptosis in PD-L1 (搜索) and/or integrin αvβ6 (搜索) positive tumor cells. The inhibitor can also penetrate cell membranes to enter antigen-negative tumor cells, creating bystander effects that effectively inhibit tumor cell growth across multiple cell populations.
Addressing Unmet Medical Need
Currently, no ADC targeting integrin αvβ6 (搜索) or PD-L1 (搜索) has received marketing approval worldwide, with all related investigational candidates remaining in clinical development stages. Preclinical data demonstrate that JSKN022 exhibits potent antitumor activity in both in vitro and in vivo models against tumor cells expressing integrin αvβ6 and/or PD-L1.
The therapy is designed to address a critical gap in cancer treatment by potentially providing a novel therapeutic approach for cancers that are refractory or resistant to PD-1/PD-L1 (搜索) inhibitors. Target indications include non-small cell lung cancer (搜索), head and neck squamous cell carcinoma (搜索), and colorectal cancer (搜索).
Phase I Clinical Trial Design
The upcoming Phase I clinical study will evaluate multiple parameters including safety, tolerability, pharmacokinetics (PK)/pharmacodynamics (PD), and antitumor activity of JSKN022. The trial will enroll patients with advanced malignant solid tumors (搜索) who have failed standard therapies, with primary objectives to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D).
Technology Platform Integration
JSKN022 is built upon Alphamab's independently developed Envafolimab, integrating immuno-oncology mechanisms with ADC approaches. The company leverages multiple proprietary technology platforms including single-domain antibodies, bispecific antibodies, glycan-specific conjugation, linker-payload systems, dual-payload antibody conjugation, and subcutaneous high concentration formulation for biologics.
Alphamab Oncology (搜索) has established strategic collaborations with partners including CSPC (搜索), ArriVent (搜索), and Glenmark, while maintaining one approved product, Envafolimab, recognized as the world's first subcutaneously injectable PD-(L)1 inhibitor.