KRAS G12C inhibitors (Leidos Biomedical Research)

– First-in-human clinical trial evaluating QTX3034 as monotherapy and combination in patients with KRASG12D-mutated advanced solid tumors to begin in 1Q24 – – QTX3046, KRASG12D-selective inhibitor, continues advancement through IND-enabling activities; IND filing on track for 1H24 – – QTX3544, G12V-preferring multi-KRAS inhibitor, selected as development candidate and Quanta’s third KRAS-directed program – RADNOR, Pa. and SOUTH SAN FRANCISCO, Calif., Jan. 04, 2024 (GLOBE NEWSWIRE) -- Quanta Therapeutics, a privately-held biopharmaceutical company pioneering targeted therapies to treat RAS-driven cancers, today announced progress across its pipeline of KRAS-directed drug candidates, including U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) application clearance for QTX3034, a multi-KRAS inhibitor with G12D-preferring activity (G12D+ multi-KRAS), enabling the initiation of a Phase 1 clinical trial in the first quarter of 2024. Additionally, QTX3046, a KRASG12D-selective inhibitor continues its advancement through IND-enabling activities positioning the company to file an IND in the first half of 2024. Further, the company has recently selected QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS), as a development candidate, representing Quanta’s third KRAS inhibitor program. “We look forward to initiating the Phase 1 study for QTX3034 in the first quarter of 2024 and evaluating this highly potent drug candidate in patients with advanced KRASG12D-mutant solid tumors as monotherapy and in combination with cetuximab, a widely used EGFR inhibitor that has shown synergy in preclinical studies with QTX3034,” said Leonardo Faoro, MD, MBA, Chief Medical Officer of Quanta Therapeutics. “Patients with KRASG12D-mutant cancers face a poor prognosis and no targeted therapy options. QTX3034 is the first of our two G12D-focused clinical approaches with QTX3046 following in the first half of 2024. We are confident that advancing two chemically distinct oral small molecules with differentiated mechanisms of action will enable us to achieve our goal of delivering a best-in-class treatment for G12D-mutant patients.” “Although RAS is one of the most clinically validated targets in oncology, the field’s understanding continues to evolve concerning the mechanisms needed to optimally target and drug KRAS-driven cancer mutations beyond G12C, including G12D and G12V,” said Perry Nisen, MD, PhD, Chief Executive Officer of Quanta. “Quanta is uniquely positioned to lead further innovation in the field with our proprietary discovery platform and our RAS biology and medicinal chemistry expertise, enabling us to identify unique chemical scaffolds with functional activity that can then be optimized for best-in-class attributes.” Dr. Nisen added, “I am proud of the team’s dedication and focus that has delivered significant progress of our pipeline, particularly advancing our first program to the clinic. Over the next 18 months, we look forward to progressing multiple novel KRAS inhibitor programs and providing data readouts from the first-in-human clinical trials for our lead programs.” About QTX3034 and the Phase 1 Clinical TrialQTX3034 is a non-covalent, potent, orally bioavailable, and allosteric multi-KRAS inhibitor with G12D-preferring activity. The QTX3034 Phase 1 clinical trial will initially enroll patients with KRASG12D mutations in dose escalation cohorts as monotherapy and in combination with cetuximab. Dose expansion cohorts consist of patients with KRASG12D-mutant pancreatic, colorectal, lung, and endometrial cancers. Endpoints include safety and tolerability, determination of the maximum tolerated dose/ recommended Phase 2 dose, pharmacokinetic properties, antitumor activity, and molecular markers. The study will be conducted at clinical sites in the US. About RAS and the MAPK PathwayThe 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 TherapeuticsQuanta 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), anticipated to enter clinical trials in 1Q24; 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/ Follow us on LinkedIn: Quanta Therapeutics