By Fineline Cube Signet Therapeutics, incubated by Xtalpi Inc. (HKG: 2228), announced completion of preclinical studies for SIGX2649, a pan‑TEAD inhibitor developed using its “AI + organoid” platform. The company plans IND filings with regulatory authorities in China and the United States for this potential first‑in‑class and best‑in‑class solid tumor therapy.
Drug Profile & Mechanism of Action
- Target: Pan‑TEAD inhibitor blocking all four TEAD transcription factor subtypes (TEAD1‑4)
- Dual Blockade Mechanism: Inhibits TEAD activity while promoting binding of transcriptional repressor VGLL4 to TEAD, achieving synergistic transcriptional repression
- Platform: Discovered via XtalPi’s AI + organoid platform, integrating computational drug design with human‑derived tumor models
- Differentiation: First TEAD inhibitor to demonstrate dual blockade and AI‑driven discovery
Preclinical Data Highlights
| Endpoint | SIGX2649 | Competitor TEAD Inhibitors | Advantage |
|---|---|---|---|
| TEAD Subtype Inhibition | All 4 subtypes | Partial/Selective | Broader coverage |
| Anti‑tumor Activity | Strong | Moderate | Superior potency |
| Kidney Toxicity | Significantly lower | High | Improved safety |
| Mechanism | TEAD blockade + VGLL4 promotion | TEAD blockade only | Dual blockade |
- Efficacy: Demonstrated robust tumor growth inhibition across multiple solid tumor organoid models (colorectal, pancreatic, lung)
- Safety: Minimal off‑target effects and significantly reduced kidney accumulation vs. other TEAD inhibitors
Market Opportunity & Competitive Landscape
| Parameter | China | Global |
|---|---|---|
| Solid Tumor Incidence (2026E) | 4.2 million | 18.5 million |
| TEAD‑Driven Tumors (Hippo pathway) | 1.5 million | 6.5 million |
| Addressable Market (2030E) | ¥28 billion | $18 billion |
| TEAD Inhibitor Penetration | 0 % | 0 % |
| SIGX2649 Peak Revenue (2032E) | ¥3.5 billion | $2.2 billion |
Key Competitors:
- Vivace Therapeutics – VTX‑1 (TEAD inhibitor, Phase I)
- Ikena Oncology – IK‑930 (TEAD1 inhibitor, Phase I)
- Signet/XtalPi – SIGX2649 – First pan‑TEAD inhibitor with dual blockade and AI‑driven discovery
Strategic Positioning & Next Steps
- IND Filings: Planned for Q2 2026 (China) and Q3 2026 (US)
- Clinical Development: Phase I study to evaluate safety, PK, and preliminary efficacy in TEAD‑positive solid tumors
- Manufacturing: XtalPi’s robotic synthesis platform will enable rapid scale‑up for clinical supply
- Pipeline Value: SIGX2649 is Signet’s second pipeline after SIGX1098 (undisclosed target); validates AI + organoid platform for first‑in‑class oncology assets
Forward‑Looking Statements
This brief contains forward‑looking statements regarding IND filing timelines, clinical development, and commercial projections for SIGX2649. Actual results may differ due to regulatory approval processes, clinical trial outcomes, and competitive dynamics.-Fineline Info & Tech