By Fineline Cube Shanghai Leadingtac Pharmaceutical Co., Ltd. announced it has received U.S. Food and Drug Administration (FDA) clearance to initiate a clinical trial of LT-010391, an oral KRAS-G12D-targeted protein degrader based on PROTAC® (Proteolysis-Targeting Chimera) technology. An Investigational New Drug (IND) application for the same molecule has also been filed with China’s National Medical Products Administration (NMPA), enabling parallel development in both markets.
Drug Profile & Innovation
| Attribute | Detail |
|---|---|
| Molecule | LT-010391 |
| Class | Oral targeted protein degrader (PROTAC) |
| Target | KRAS G12D—a prevalent oncogenic driver mutation |
| Mechanism | Induces ubiquitination and proteasomal degradation of mutant KRAS protein, eliminating it at the source rather than merely inhibiting activity |
| Indication | Advanced solid tumors harboring KRAS G12D mutations (e.g., pancreatic, colorectal, non-small cell lung cancer) |
| Differentiation | Potential to more comprehensively block aberrant KRAS signaling compared to traditional inhibitors |
KRAS G12D is present in approximately 40% of pancreatic ductal adenocarcinomas and 10–15% of colorectal cancers, yet remains largely undruggable with conventional small molecules. While covalent KRAS-G12C inhibitors (e.g., sotorasib, adagrasib) have transformed care for G12C-mutant NSCLC, no approved therapies exist for G12D—making LT-010391 a potential first-in-class candidate.
Strategic Significance
- Technology Leadership: One of the first oral PROTACs targeting KRAS G12D to enter clinical trials globally
- Dual-Market Strategy: Simultaneous IND filings in U.S. and China accelerate global development timelines
- Unmet Need Focus: Addresses a high-priority mutation with no current targeted options
- Platform Validation: Success could validate Leadingtac’s proprietary degrader platform for other “undruggable” oncology targets
The upcoming Phase I trial will assess safety, pharmacokinetics, and preliminary efficacy in patients with KRAS G12D-mutant solid tumors refractory to standard therapies.
Competitive Landscape
Leadingtac joins a select group of biotechs—including C4 Therapeutics, Arvinas, and Monte Rosa Therapeutics—exploring KRAS-directed degraders. However, LT-010391 appears to be the first oral KRAS-G12D degrader cleared for clinical study in the U.S., offering a significant lead in this niche segment.
Forward‑Looking Statements
This brief contains forward-looking information regarding clinical development and regulatory status. Actual outcomes may differ due to trial results, safety findings, and competitive advances.-Fineline Info & Tech