By Fineline Cube Jiangsu Hengrui Pharmaceuticals Co., Ltd (SHA: 600276, HKG: 1276) announced that China’s National Medical Products Administration (NMPA) has approved clinical trials for the combination of subcutaneous SHR-9839 and liposomal HRS-4642 in advanced colorectal cancer (CRC), advancing a first‑in‑class bispecific pathway blocker plus novel KRAS G12D inhibitor regimen for patients who have failed standard therapy.
Regulatory Milestone
| Item | Detail |
|---|---|
| Company | Jiangsu Hengrui Pharmaceuticals Co., Ltd (SHA: 600276, HKG: 1276) |
| Combination | SHR-9839 (subcutaneous antibody) + HRS-4642 (liposomal KRAS G12D inhibitor) |
| Application | Clinical Trial Application (CTA) |
| Agency | NMPA (China) |
| Indication | Advanced/metastatic CRC (inoperable, post‑standard therapy failure) |
| Approval Date | 16 Jan 2026 |
| Innovation | First KRAS G12D inhibitor in China; subcutaneous bispecific pathway blocker |
Drug Profile & Mechanism of Action
SHR-9839 (Subcutaneous Dual‑Pathway Antibody):
- Mechanism: Simultaneously blocks two key signaling pathways involved in tumor development (specific targets undisclosed)
- Administration: Subcutaneous injection improves patient convenience vs. IV formulations
- Market Status: Only one drug targeting the same pathway approved globally, indicating novel target space
HRS-4642 (Liposomal KRAS G12D Inhibitor):
- Mechanism: Liposomal formulation enables targeted delivery; specifically binds KRAS G12D and inhibits MEK/ERK phosphorylation, blocking downstream oncogenic signaling
- Differentiation: First KRAS G12D inhibitor in clinical development in China; no global approvals for this class
- Innovation: Addresses undruggable KRAS G12D mutation present in ~4% of CRC patients
Market Opportunity & Competitive Landscape
| Parameter | China CRC Market | KRAS G12D CRC Segment |
|---|---|---|
| Advanced CRC Patients (2026E) | 180,000 | 7,200 |
| Failed Standard Therapy | 54,000 | 2,160 |
| Current Standard | Chemo ± anti‑VEGF/anti‑EGFR ± PD‑1 | No approved KRAS G12D inhibitors |
| HRS-4642 Market Share | 0% | 35% (post‑approval) |
| Annual Cost (USD) | – | $85,000 |
| Peak Revenue (2032E) | – | $85 million (KRAS G12D segment) |
| Combo Therapy Value | Extends SHR-9839 into refractory CRC | Validates KRAS platform |
Key Competitors:
- Mirati Therapeutics – MRTX1133 (KRAS G12D inhibitor, Phase I)
- Revolution Medicines – RAS(ON) G12D inhibitor (pre‑clinical)
- Amgen – Sotorasib (KRAS G12C, not G12D)
- Hengrui – First KRAS G12D inhibitor in China; subcutaneous delivery offers convenience
Strategic Positioning
- Manufacturing: Hengrui’s Lianyungang biologics facility (capacity 30,000 L) will produce SHR-9839; Nanjing ADC/lipid plant will manufacture HRS-4642
- Clinical Development: Phase I/II dose‑escalation planned Q2 2026; primary endpoint: objective response rate (ORR); secondary: PFS, OS, safety
- Platform Synergy: Success validates Hengrui’s bispecific antibody platform and KRAS inhibitor pipeline, supporting future combos (e.g., KRAS G12D + EGFR ADC)
- Global Ambitions: Hengrui plans US IND filing for HRS-4642 in 2027, leveraging China data
Forward‑Looking Statements
This brief contains forward‑looking statements regarding clinical development timelines, regulatory pathways, and commercial projections for SHR-9839 and HRS-4642. Actual results may differ due to clinical trial outcomes, competitive dynamics, and manufacturing challenges.-Fineline Info & Tech