ALPHAMAB-B: JSKN003 has once again received breakthrough therapy designation from CDE

According to the Zhitong Finance APP, ALPHAMAB-B (09966) announced that its JSKN003, developed in collaboration with the subsidiary of CSPC Pharmaceutical Group Limited (stock code: 1093), has received breakthrough therapy designation from the CDE for the treatment of HER2+ advanced CRC patients who have previously failed treatment with oxaliplatin, fluorouracil, and irinotecan. Previously, JSKN003 had also received breakthrough therapy designation from the CDE in March 2025 for the treatment of PROC, regardless of HER2 expression levels. CRC is one of the most common malignant tumors globally. In China, the incidence of CRC ranks second after lung cancer, with over 500,000 new cases each year and a continuous upward trend. Currently, there are no approved anti-HER2 targeted drugs for CRC in China. For HER2+ advanced CRC patients who have failed treatment with oxaliplatin, fluorouracil, and irinotecan, the approved therapies have a median progression-free survival (mPFS) of only 2.0-3.7 months and a median overall survival (mOS) of about 7-10 months. There remains a significant unmet clinical need in this patient population. The company previously presented a summary analysis of two clinical studies on JSKN003 monotherapy for advanced HER2 high-expressing (IHC3+) gastrointestinal tumor patients at the 2025 American Society of Clinical Oncology (ASCO) annual meeting. The results showed that JSKN003 monotherapy has significant efficacy in treating HER2 high-expressing advanced CRC patients, with good safety profiles. This summary analysis included a Phase I clinical study conducted in Australia (JSKN003-101) and a Phase I/II clinical study conducted in China (JSKN003-102). As of February 28, 2025, a total of 50 HER2 high-expressing advanced gastrointestinal tumor patients (23 of whom had CRC) were included in the two studies, with 38% of patients having previously received ≥3 lines of anti-tumor treatment. The study results indicated that among the 21 HER2 high-expressing CRC patients who had at least one tumor efficacy assessment, the objective response rate (ORR) was 61.9%, the disease control rate (DCR) was 95.2%, the mPFS was 13.77 months, and the median duration of response (mDoR) was 12.06 months. Among the 20 BRAF V600E wild-type CRC patients, the ORR reached 65.0%. In terms of safety, among the 43 patients who received the recommended Phase II dose (RP2D), only 6 patients (14.0%) experienced grade 3 or higher treatment-related adverse events (TRAEs), 3 patients (7.0%) experienced treatment-related serious adverse events (TRSAEs), and 7 patients (16.3%) had dose reductions due to TRAEs. No TRAEs led to treatment discontinuation or death. JSKN003 is a targeted HER2 bispecific antibody-drug conjugate (ADC) that connects a topoisomerase I inhibitor to the N-glycosylation site of the KN026 antibody (a recombinant humanized bispecific anti-HER2 antibody) through glycosylation point coupling technology. The click reaction conjugate during the coupling process has better serum stability than the maleimide-Michael reaction conjugate. The targeted HER2 bispecificity gives JSKN003 stronger endocytic activity and bystander killing effects, providing it with strong anti-tumor activity in HER2-expressing tumors In September 2024, our company reached an authorized cooperation with Shanghai Jinmant Biotechnology Co., Ltd. to develop, sell, promise to sell, and commercialize JSKN003 in mainland China for the treatment of tumor-related indications. Currently, three Phase III clinical trials of JSKN003 for HER2+BC, HER2 low-expressing BC, and PROC are underway