Jiangsu Hengrui Pharmaceuticals Co., Ltd. (SHA: 600276, HKG: 1276) announced that HRS-4642, its KRAS G12D-targeting liposomal inhibitor, has been granted Breakthrough Therapy Designation (BTD) by China’s Center for Drug Evaluation (CDE) for first-line treatment of advanced or metastatic pancreatic cancer with KRAS G12D mutation, in combination with gemcitabine and nab-paclitaxel. The designation recognizes HRS-4642 as the first-in-class KRAS G12D inhibitor globally to reach this regulatory milestone.
HRS-4642 addresses larger mutation subset than G12C
Combination Rationale
Chemotherapy backbone + targeted inhibition
Potential for synergistic efficacy without overlapping toxicity
Strategic Positioning & Market Context
KRAS G12D Market Opportunity: KRAS G12D represents the single most prevalent oncogenic driver in pancreatic ductal adenocarcinoma (PDAC), lung, and colorectal cancers—collectively representing a multi-billion dollar unmet need.
Hengrui Innovation Pivot: BTD for HRS-4642 validates Hengrui’s transition from generics to first-in-class oncology innovation, leveraging its liposomal formulation expertise and KRAS biology platform.
Competitive Landscape: While Mirati (Bristol Myers Squibb), Revolution Medicines, and Intellia pursue KRAS G12D programs, HRS-4642’s BTD positions Hengrui as global leader with potential first-to-market advantage in the world’s second-largest pharmaceutical market.
Breakthrough Therapy Benefits: CDE BTD provides accelerated development and review pathways, enhanced regulatory dialogue, and potential conditional approval based on Phase II data—compressing time-to-market by 12-18 months.
Development Roadmap
Phase
Activity
Anticipated Timeline
Current
BTD granted; Phase I/II trial ongoing
Q1 2026
Near-term
Phase II registrational data in first-line pancreatic cancer
2026-2027
Expansion
Monotherapy and combination studies in lung/colorectal KRAS G12D
2026-2028
Global Strategy
US/EU IND filing based on China efficacy data
2027
Forward‑Looking Statements This brief contains forward‑looking statements regarding HRS-4642 clinical development in KRAS G12D-mutant cancers, regulatory timelines for BTD-enabled approval, and Hengrui Pharmaceuticals’ global KRAS franchise expansion. Actual results may differ due to Phase II trial outcomes, competitive dynamics in the KRAS inhibitor space, and regulatory requirements for novel liposomal formulations.-Fineline Info & Tech
By Fineline Cube