Alphamab Oncology Receives IND Approval for First-in-Class PD-L1/VEGFR2 Bispecific ADC JSKN027
核心洞察
Alphamab Oncology (搜索) announced that China's NMPA has accepted the IND application for JSKN027 (搜索), a first-in-class bispecific antibody-drug conjugate targeting both PD-L1 (搜索) and VEGFR2 (搜索) for advanced solid tumors.
JSKN027 (搜索) employs a unique three-fold synergistic mechanism combining targeted cell killing, anti-angiogenesis through VEGF (搜索)/VEGFR2 (搜索) blockade, and immune checkpoint disruption via PD-1 (搜索)/PD-L1 (搜索) pathway inhibition.
The upcoming Phase I clinical study will evaluate safety, tolerability, pharmacokinetics, and antitumor activity in patients with advanced malignant solid tumors (搜索) while determining optimal dosing.
Alphamab Oncology (搜索) announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has officially accepted the Investigational New Drug (IND) application for JSKN027 (搜索), an innovative bispecific antibody-drug conjugate targeting PD-L1 (搜索) and VEGFR2 (搜索). The Hong Kong-listed company (stock code: 9966.HK) plans to initiate clinical studies for this first-in-class therapy in patients with advanced malignant solid tumors (搜索).
Novel Triple-Action Mechanism
JSKN027 (搜索) represents a significant advancement in cancer (搜索) therapeutics through its unique three-fold synergistic mechanism. Beyond standard ADC effects of targeted cell killing and bystander activity, the drug simultaneously inhibits tumor angiogenesis by blocking VEGF (搜索)/VEGFR2 (搜索) signaling and reverses immune suppression by disrupting the PD-1 (搜索)/PD-L1 (搜索) checkpoint pathway. This integrated approach is designed to enhance overall anti-tumor efficacy and potentially overcome therapeutic resistance.
The bispecific ADC utilizes glycan-specific conjugation technology to precisely link its cleavable linker and topoisomerase I inhibitor payload to the antibody's Fc region. This design maintains a strong safety profile while delivering potent anti-tumor activity through targeted delivery of the cytotoxic payload.
Promising Preclinical Results
Preclinical data demonstrated that JSKN027 (搜索) exhibits potent anti-tumor activity in both in vitro and in vivo models. IND-enabling toxicology studies showed good tolerability at the highest tested dose, supporting the compound's advancement into human clinical trials. The combination of targeted chemotherapy, anti-angiogenesis, and immunotherapy represents a promising treatment strategy across multiple solid tumor types.
Phase I Clinical Study Design
The upcoming Phase I clinical study will comprehensively evaluate JSKN027 (搜索)'s safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity in patients with advanced malignant solid tumors (搜索). The study aims to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D), establishing the foundation for future development.
Company Pipeline and Strategic Position
Alphamab Oncology (搜索) has built a differentiated oncology pipeline leveraging proprietary platforms including single-domain antibodies, bispecific antibodies, glycan-specific conjugation, linker-payloads, dual-payload ADCs, and high-concentration subcutaneous formulations. The company has already achieved market approval for Envafolimab (KN035), the world's first subcutaneously injected PD-(L)1 inhibitor, and has four bispecific ADC candidates in clinical stages.
The NMPA has also accepted the new drug application for KN026 (Anbenitamab Injection (搜索)), a HER2 (搜索) bispecific antibody for second-line or later HER2-positive gastric cancer (搜索). Strategic partnerships with CSPC (搜索), ArriVent (搜索), and Glenmark support both product development and technology platform advancement as the company works toward its mission of making cancer (搜索) manageable and curable.