Alphamab Oncology (stock code: 9966.HK) announced that the first patient has been successfully dosed at Sun Yat-sen University Cancer Center in the phase I clinical study (Study ID: JSKN022-101) of JSKN022, an independently developed innovative bispecific antibody-drug conjugate (ADC) targeting PD-L1 and integrin αvβ6, for the treatment of advanced malignant solid tumors. JSKN022 is the Company's fourth ADC candidate entering clinical development, as well as the world's first PD-L1/αvβ6 bispecific ADC to advance into clinical trials.

JSKN022 innovatively combines immuno-oncology (IO) mechanisms with ADC approaches, utilizing Alphamab Oncology's proprietary glycan-specific conjugation platform and linker-payload (Alphatecan) to significantly improve stability and homogeneity. The molecule is designed to bind to PD-L1 and/or integrin αvβ6 on the surface of tumor cells. After binding to either target, JSKN022 enters the lysosome through target-mediated endocytosis. The linker is hydrolyzed by proteolytic enzymes, releasing cytotoxic topoisomerase I inhibitor, which then induces apoptosis of PD-L1 and/or integrin αvβ6 positive tumor cells. In addition, the inhibitor can block TGFβ signaling to modulate immune function, and kill antigen-negative cells through the bystander effect, thereby achieving multiple anti-tumor activity. Preclinical data presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting, demonstrated that JSKN022 effectively inhibited the proliferation of cancer cells and demonstrated greater tumor suppression than single-target ADCs.

JSKN022-101 is an open-label, multi-center, phase I clinical trial of JSKN022, including dose-escalating and dose-optimization phases. This study aims to evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics (PD), and antitumor activity of JSKN022 in patients with advanced malignant solid tumors, and determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D).

At present, no ADC targeting integrin αvβ6 or PD-L1 has been approved for marketing worldwide, with all related investigational candidates remaining in clinical development stages. JSKN022 will potentially bring in novelty in the therapeutic approach for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors.