Alphamab Oncology announced that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of gastric cancer and gastroesophageal junction cancer (GC/GEJ).

GC/GEJ is the fifth most common cancer and the fifth leading cause of cancer death worldwide. According to the 2022 Global Cancer Statistics report released by the International Agency for Research on Cancer (IARC), a subsidiary of the World Health Organization, there are approximately 960,000 new cases diagnosed and 660,000 deaths worldwide annually. In the U.S., the SEER database model predicts that there will be 26,890 new cases and 10,880 new deaths of GC/GEJ in 2024, with a five-year overall survival rate of less than 40%. Fluoropyrimidine and platinum-based regimens are commonly used as first-line treatments. Available second-line or later-line treatment options include paclitaxel plus ramucirumab, paclitaxel, docetaxel or irinotecan monotherapy, and best supportive care, with objective response rates of approximately 15-25%. The median overall survival is approximately 8-9 months for second-line treatment and 4-6 months for later lines.

JSKN003 is an anti-HER2 biparatopic ADC developed inhouse with Alphamab's proprietary glycan-specific conjugation platform. The antibody molecule KN026 is site-specifically modified via enzyme catalytic reaction and click chemistry to achieve a drug-to-antibody ratio (DAR) of approximately 4. It can bind HER2 on the surface of tumor cells, and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exert anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window. Research results from the Phase I clinical study JSKN003-101 (NCT05494918) conducted in Australia and the Phase I/II clinical study JSKN003-102 (NCT05744427) in China have demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with high HER2-expressing gastrointestinal tumors. Detailed data were presented at the 2024 European Society for Medical Oncology (ESMO) Congress for the first time and subsequently updated at the 2025 Annual Meeting of American Society of Clinical Oncology (ASCO) in June 2025.

The "Orphan Drug Designation", originated from the Orphan Drug Act (ODA), is a U.S. FDA initiative aimed at encouraging the development of innovative drugs for the treatment of diseases affecting fewer than 200,000 people in the U.S. The designation of JSKN003 will be beneficial to obtain relevant policy supports for subsequent research and development, registration, and commercialization in the U.S., including funding for research and development costs, tax credits for clinical trial expenditures, waiver of prescription drug user fee, accelerated review and approval processes, and, upon approval, the potential for seven years of market exclusivity in the U.S.