D3 Bio Receives Breakthrough Therapy and Orphan Drug Designations for KRAS G12C Inhibitor D3S-001

Strategic Insights -

D3 Bio, Inc, a clinical-stage oncology company, announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to D3S-001, a next-generation KRAS G12C-selective inhibitor, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor. Additionally, D3S-001 has been granted Orphan Drug Designation for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC). The designations are based on clinical data from an ongoing Phase 1/2 study (NCT05410145) evaluating D3S-001 in patients with advanced solid tumors harboring a KRAS G12C mutation. The study demonstrated highly compelling and durable efficacy with a favorable safety and tolerability profile.

Key Takeaways:

  • The FDA has granted Breakthrough Therapy Designation to D3 Bio's KRAS G12C inhibitor D3S-001 for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor.
  • D3S-001 has also been granted Orphan Drug Designation for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC.
  • The designations are based on clinical data from an ongoing Phase 1/2 study (NCT05410145) evaluating D3S-001 in patients with advanced solid tumors harboring a KRAS G12C mutation.
  • Results from the study demonstrated highly compelling and durable efficacy with a favorable safety and tolerability profile.
  • KRAS mutations are among the most common oncogenic drivers in human cancers, found in approximately 25 to 30% of all tumors.
  • The KRAS G12C mutation occurs in approximately 12% of NSCLC cases and 3 to 4% of CRC.
  • Patients with KRAS G12C-mutated cancers often have more aggressive disease and limited responses to standard therapies.
  • D3S-001 is a next-generation KRAS G12C inhibitor designed to achieve rapid and complete KRAS G12C target engagement.
  • D3 Bio owns global rights for all of its programs.

Statistics:

  • Approximately 25 to 30% of all tumors harbor KRAS mutations.
  • The KRAS G12C mutation occurs in approximately 12% of NSCLC cases and 3 to 4% of CRC.
  • Patients with KRAS G12C-mutated cancers often have more aggressive disease and limited responses to standard therapies, such as immunotherapy and/or chemotherapy.
  • D3S-001 has demonstrated high covalent potency, complete engagement of KRAS G12C at clinically relevant doses, and CNS penetration properties in preclinical investigations.

Sources:

  • PR Newswire: D3 Bio Announces FDA Grants Breakthrough Therapy and Orphan Drug Designations to D3S-001 for Treatment of KRAS G12C-Mutated Cancers
  • Cancer Discov. (2024)14 (9):1675--1698. D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities.
  • Nat Med. 2025 Aug;31(8):2768-2777. D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial.