ALPHAMAB-B (09966) has announced that its JSKN003, developed in collaboration with Shanghai Jinmant Biotech Co., Ltd., a subsidiary of CSPC Pharmaceutical Group Limited (Stock Code: 1093), has received breakthrough therapy designation from the CDE for the treatment of patients with HER2+ advanced CRC who have failed prior treatments with oxaliplatin, fluorouracil, and irinotecan. Earlier, in March 2025, JSKN003 also received CDE breakthrough therapy designation for the treatment of PROC, without restriction on HER2 expression levels. CRC is one of the most common malignant tumors globally, and in China, its incidence ranks second only to lung cancer, with over 500,000 new cases reported annually and a continuously increasing trend. Currently, there are no approved anti-HER2 targeted therapies for CRC in China. For HER2+ advanced CRC patients who have failed treatments with oxaliplatin, fluorouracil, and irinotecan, the mPFS of approved therapies ranges from 2.0 to 3.7 months, with a mOS of approximately 7 to 10 months. This patient population still presents a significant unmet clinical need. The company previously presented a summary analysis of two clinical studies at the 2025 ASCO annual meeting focused on the monotherapy of JSKN003 for advanced HER2-high expressing (IHC3+) gastrointestinal tumor patients. The results demonstrated that JSKN003 monotherapy shows considerable efficacy with good safety for HER2-high expressing advanced CRC patients. 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 (including 23 CRC patients) were enrolled in both studies, with 38% having received ≥3 lines of anti-tumor therapy prior. The findings revealed that among the 21 HER2-high expressing CRC patients who had undergone at least one efficacy assessment, the ORR was 61.9%, DCR was 95.2%, mPFS was 13.77 months, and mDoR was 12.06 months. Notably, the ORR reached 65.0% among 20 BRAF V600E wild-type CRC patients. In terms of safety, among the 43 patients who received the recommended Phase II dosing (RP2D), only 6 patients (14.0%) experienced grade 3 or higher TRAEs, 3 patients (7.0%) had TRSAEs, and 7 patients (16.3%) required dose adjustments due to TRAEs. There were no TRAEs that resulted in treatment discontinuation or death. JSKN003 is a dual-targeted HER2 ADC that connects topoisomerase I inhibitors to the N-glycosylation sites of the KN026 antibody (a recombinant humanized anti-HER2 bispecific antibody) through glyco-point coupling technology. The click reaction coupling product during the coupling process exhibits better serum stability than the coupling products from the maleimide-Michael reaction. The dual-targeting of HER2 provides JSKN003 with enhanced endocytosis activity and bystander killing effects, giving it robust anti-tumor activity in HER2-expressing tumors. In September 2024, the company reached a licensing collaboration with Shanghai Jinmant Biotech Co., Ltd. for the development, sales, distribution, and commercialization of JSKN003 in mainland China for tumor-related indications. Currently, three Phase III clinical trials for JSKN003 are underway, targeting HER2+ BC, low HER2 expressing BC, and PROC.