D3 Bio, a clinical stage biotechnology company focused on developing transformative oncology therapies, has received clearance from the US Food and Drug Administration (FDA) for two Investigational New Drug (IND) applications, marking an advancement in KRAS-targeted cancer pipeline.

The FDA has cleared D3 Bio to initiate a Phase I first-in-human clinical trial of D3S-003, an orally bioavailable, allele-specific KRAS G12D inhibitor. The compound is designed to target both the GDP-bound (OFF) and GTP-bound (ON) conformations of KRAS G12D. Preclinical studies have demonstrated potent anti-tumour activity, favourable drug-like properties and a promising safety profile. The Phase I study will enrol patients with advanced solid tumours harbouring KRAS G12D mutations.

In addition, the FDA has cleared a Phase II combination trial evaluating D3S-001 (elisrasib), D3 Bio’s next-generation KRAS G12C inhibitor, in combination with D3S-002, a selective oral ERK1/2 inhibitor. The study will focus on patients with KRAS G12C–mutant Non-Small Cell Lung Cancer (NSCLC) who have progressed following prior KRAS G12C-targeted therapies. The trial is expected to commence in the first half of 2026 and will assess safety, pharmacokinetics and early signals of clinical efficacy, with the aim of addressing treatment resistance and improving durability of response.

Commenting on the development, George Chen, Founder, Chairman and Chief Executive Officer, D3 Bio, said, “The FDA clearances represent important progress for the company’s KRAS franchise." He noted that D3S-003 addresses one of the most prevalent and challenging KRAS mutations, while the combination strategy involving elisrasib and D3S-002 is designed to offer new treatment options for patients who have exhausted existing KRAS G12C therapies.