Officials at Quanta Therapeutics reported that QTX3544, a multi-KRAS inhibitor, demonstrated a favorable preclinical profile, including high selectivity and potent activity against multiple KRAS mutations with preference for the G12V mutation. Additionally, QTX3544 significantly inhibited KRASG12V tumor growth in preclinical animal models and exhibited promising oral bioavailability and pharmacokinetic properties.
The results were announced at a poster presentation during the American Association of Cancer Research (AACR) Annual Meeting in San Diego.
“We continue to advance our pipeline of candidates against KRAS-driven cancer mutations focusing on the most prevalent drivers, G12D and G12V,” said Perry Nisen, MD, PhD, CEO of Quanta. “Along with our two lead G12D-focused programs in or near the clinical stage, we are excited about this third program, which will focus initially on the approximately 20% of KRAS-driven cancers with the G12V mutation.
“We look forward to completing IND-enabling studies for QTX3544 this year to support future clinical studies in patients with G12V-mutated solid tumors, a population without targeted treatment options.”
Data from the QTX3544 presentation are summarized as follows:
- QTX3544 selectively prevents KRAS activation and locks the protein in an inactive conformation, incompetent for effector signaling
- High target engagement results in disruption of protein-protein interaction between various KRAS mutants and RAF1
- Dose-dependent inhibition of MAPK signaling in multiple cancer cell lines derived from colorectal, pancreatic, ovarian, and gastric cancer patients carrying various KRAS mutations, with preference for targeting KRASG12V
- Significant, dose-dependent anti-tumor activity in various KRAS-driven solid tumor mouse models, including pancreatic, lung, ovarian, and gastric tumors
- Favorable oral bioavailability and pharmacokinetic properties in preclinical animal studies
