By Fineline Cube D3 Bio announced FDA clearance for two clinical programs: a Phase I first‑in‑human study for D3S‑003, an oral allele‑specific KRAS G12D inhibitor, and a Phase II trial for the combination of D3S‑001 (KRAS G12C inhibitor) plus D3S‑002 (ERK1/2 inhibitor) in KRAS G12C‑mutated NSCLC, positioning the company at the forefront of next‑generation KRAS‑targeted oncology.
Regulatory Milestone
| Item | Detail |
|---|---|
| Company | D3 Bio (private) |
| **Programs | D3S‑003 (KRAS G12D inhibitor) & D3S‑001 + D3S‑002 combo (KRAS G12C + ERK1/2) |
| **FDA Approvals | Phase I for D3S‑003; Phase II for D3S‑001 + D3S‑002 |
| **Indications | Advanced solid tumors (G12D) & KRAS G12C NSCLC (combo) |
| **Study Start | H1 2026 (both programs) |
| **Innovation | First G12D inhibitor targeting both OFF/ON conformations; CNS‑penetrant G12C inhibitor with ERK1/2 resistance‑breaker |
Drug Profiles & Mechanism of Action
D3S‑003 (KRAS G12D Inhibitor)
- Mechanism: Oral, allele‑specific, binds GDP‑bound (OFF) and GTP‑bound (ON) KRAS G12D conformations
- Preclinical: Potent antitumor activity, favorable drug‑like properties, promising safety window
- Clinical Plan: Phase I dose‑escalation in advanced solid tumors harboring G12D mutations
D3S‑001 (Elisrasib, KRAS G12C Inhibitor)
- Mechanism: Next‑gen G12C inhibitor with rapid, robust, selective target engagement and CNS penetration
- Preclinical: Achieves complete KRAS G12C occupancy at clinically relevant exposures
- Clinical Plan: Phase II combo trial with D3S‑002 (ERK1/2 inhibitor) in KRAS G12C NSCLC
D3S‑002 (ERK1/2 Inhibitor)
- Mechanism: Selective ERK1/2 inhibitor designed to overcome acquired resistance to KRAS G12C inhibitors
- Synergy: Blocks downstream signaling, prevents tumor escape
Market Opportunity & Competitive Landscape
| Program | Target | Addressable Population (2030E) | Market Value (2030E) | Key Competitors |
|---|---|---|---|---|
| D3S‑003 | KRAS G12D (pan‑solid tumor) | 180,000 (China), 900,000 (global) | ¥12 B / $7.5 B | Mirati’s MRTX1133 (Phase I), Revolution Medicines (pre‑clinical) |
| D3S‑001 + D3S‑002 | KRAS G12C NSCLC (post‑1L) | 42,000 (China), 95,000 (global) | ¥8 B / $5.2 B | Mirati adagrasib, Amgen sotorasib, Roche divarasib (all monotherapy) |
- Differentiation: D3S‑003’s dual‑conformation targeting vs. competitors’ OFF‑only inhibitors; combo’s ERK1/2 resistance‑breaker vs. single‑agent G12C inhibitors
- CNS Penetration: D3S‑001’s ability to cross blood‑brain barrier offers advantage in brain metastases, a key unmet need
Strategic Positioning
- Manufacturing: D3 Bio’s Shanghai facility (robotic synthesis) will supply both programs; scale‑up to 10,000 doses by 2027
- Clinical Development: Rapid Phase I readout for D3S‑003 expected Q4 2026; combo Phase II topline Q2 2027
- Global Licensing: D3 Bio plans ex‑China partnerships post‑Phase I for D3S‑003 and post‑Phase II for combo; potential deal value $800M‑1.2B
- Platform Validation: Success validates next‑gen KRAS platform, supporting earlier‑stage assets (D3S‑004, D3S‑005)
Forward‑Looking Statements
This brief contains forward‑looking statements regarding clinical development timelines, regulatory pathways, and commercial projections for D3S‑003 and the D3S‑001 + D3S‑002 combo. Actual results may differ due to competitive responses, clinical trial outcomes, and manufacturing scale‑up challenges.-Fineline Info & Tech