–Strong anti-tumor activity, favorable oral bioavailability and drug-like properties demonstrated in preclinical models –
–Data support ongoing IND-enabling studies for planned clinical evaluation in KRASG12V-driven solid tumors –
RADNOR, Pa. & SOUTH SAN FRANCISCO, Calif., April 08, 2024 (GLOBE NEWSWIRE) -- Quanta Therapeutics, a privately-held biopharmaceutical company leading innovative development of direct, oral therapeutics for RAS-driven cancers, announced the presentation of QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS), in a late-breaking poster presentation session at the American Association of Cancer Research (AACR) Annual Meeting.
QTX3544 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.
“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, Chief Executive Officer of Quanta. “Along with our two lead G12D-focused programs in or near the clinical stage, we are very 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 presentation are summarized below. Data for QTX3544 demonstrated:
- High biochemical potency against multiple KRAS variants, particularly G12V
- 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
Poster Presentation details:
Title: Discovery and characterization of QTX3544, a potent, selective, and orally bioavailable allosteric G12V-preferring multi-KRAS inhibitor
Date and Time: Monday, April 8, 2024, 1:30 PM - 5:00 PM
Session Name: Late-Breaking Research: Experimental and Molecular Therapeutics 2
Abstract Number: LB163
Location: Poster Section 52
About RAS and the MAPK Pathway
The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that regulates cellular growth, proliferation, differentiation, and survival. When one of the proteins in the pathway is mutationally activated, it can drive tumor development and growth. RAS is the most frequently mutated oncogene in cancer, with KRAS mutations occurring in nearly one-quarter of all human cancers. RAS mutations impair the ability of RAS to convert from its active GTP-bound “ON” form into its inactive GDP-bound “OFF” state, leading to the sustained activation of the MAPK signaling pathway and ultimately driving tumorigenesis. KRAS mutations, especially G12D, G12V, and G12C, are highly prevalent in pancreatic, colorectal, and lung cancers. First-generation KRAS inhibitors have demonstrated clinical benefit, but their impact is limited to a subset of patients with a single type of KRAS mutation (G12C).
About Quanta Therapeutics
Quanta Therapeutics is a private biopharmaceutical company focused on the most prevalent and elusive target in oncology—RAS. Our vision is to develop novel small molecule cancer medicines by selectively targeting protein-protein interactions that are key to oncogenic RAS activity. Driving Quanta's success is our unique high-throughput platform that applies Second Harmonic Generation (SHG) optical technology to identify allosteric modulators of protein complexes. The Quanta team has extensive drug development expertise and substantial research experience in the RAS space. By applying innovative medicinal chemistry and its unique protein conformation detection technology, Quanta aims to advance differentiated, next-generation RAS programs that address the resistance paradigms of targeted therapy in oncology. Quanta’s KRAS inhibitor pipeline includes three programs: QTX3034, a multi-KRAS inhibitor with G12D-preferring activity (G12D+ multi-KRAS), currently in a Phase 1 clinical trial; QTX3046, a G12D-selective KRAS inhibitor, expected to enter the clinic in mid-2024; QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS) projected to complete IND enabling studies in 2024. Quanta is headquartered in South San Francisco, CA, and has a site in Radnor, PA.
Find more information at https://www.quantatx.com/
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Quanta Therapeutics
Heather Meeks
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