Adagrasib

– IND for QTX3544 is third for Quanta within one year – – Initiated combination portion of Phase 1 clinical trial of QTX3046, an oral KRASG12D-selective dual ON/OFF state allosteric inhibitor, with the EGFR inhibitor cetuximab – – Phase 1 clinical trial of QTX3034, oral G12D-preferring multi-KRAS progressing; data readout anticipated in 2025 – Jan. 08, 2025 -- Quanta Therapeutics, a privately-held clinical-stage biopharmaceutical company leading the development of innovative, oral therapeutics for RAS-driven cancers, 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 QTX3544, an oral G12V-preferring, dual ON/OFF state, multi-KRAS inhibitor, enabling initiation of a Phase 1 clinical trial. The Company has also initiated the combination portion of the ongoing Phase 1 clinical trial evaluating QTX3046, an oral KRASG12D-selective dual ON/OFF state allosteric inhibitor, with cetuximab. Combining allosteric KRAS inhibition with EGFR blockade generally represents a synergistic approach to enhance the depth and durability of tumor response in high unmet need indications, such as colorectal cancer (CRC) and pancreatic adenocarcinoma (PDAC). Clinical validation of this combination has been demonstrated with the approval of adagrasib in KRASG12C-mutated CRC. Additionally, the Phase 1 clinical trial evaluating QTX3034, an oral G12D-preferring multi-KRAS inhibitor, as a monotherapy and in combination with cetuximab, continues to enroll patients, and data is anticipated from this program in 2025. “With the initiation of the Phase 1 clinical trial for QTX3544 in patients with KRASG12V-driven solid tumors, we will have three KRAS inhibitor programs in the clinic focused on the most prevalent KRAS-driven cancers,” said Leonardo Faoro, MD, MBA, Chief Medical Officer of Quanta Therapeutics. “QTX3034 has demonstrated a robust oral pharmacokinetic profile, tolerability and encouraging activity at doses predicted from preclinical studies. We look forward to sharing significant progress in conference presentations as our pipeline of novel KRAS inhibitors reach Phase 1 data readouts this year.” “This is an exciting time at Quanta as we embark on our third clinical trial within a year, a testament to the diligent execution by the team,” said Perry Nisen, MD, PhD, Chief Executive Officer of Quanta. “Powered by our proprietary research and translational platform, we believe our pipeline of oral KRAS inhibitors, designed to provide potent and selective direct inhibition of KRAS mutations, in both the ON and OFF state, can significantly broaden the range of treatable KRAS-driven cancers beyond G12C.” QTX3034 and QTX3046 are two chemically distinct, non-covalent, potent, orally bioavailable, allosteric, clinical candidates targeting KRASG12D-mutated cancers. QTX3034 is a multi-KRAS inhibitor with G12D-preferring activity. QTX3046 is a KRASG12D-selective, dual ON/OFF state inhibitor. Both Phase 1 clinical trials are enrolling patients with solid tumors with KRASG12D mutations in dose escalation cohorts as monotherapy and in combination with cetuximab. Dose expansion cohorts will consist of patients with KRASG12D-mutant pancreatic, colorectal, and lung cancers. QTX3544 is a multi-KRAS inhibitor with G12V-preferring activity. The Phase 1 clinical trial will initially enroll patients with KRASG12V mutations in dose escalation cohorts as monotherapy and in combination with cetuximab. The Phase 1 clinical endpoints for each of the foregoing trials include safety and tolerability, determination of the maximum tolerated dose/recommended Phase 2 dose, pharmacokinetic properties, antitumor activity, and molecular markers. The clinical trials are being conducted at clinical sites in the U.S. More information about the QTX3034 clinical trial (NCT06227377), the QTX3046 clinical trial (NCT06428500), and the QTX3544 clinical trial (NCT06715124) can be found on https://clinicaltrials.gov/. 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). 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 as monotherapy and in combination with cetuximab; QTX3046, a G12D-selective KRAS inhibitor, currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS) that has received U.S. FDA clearance to initiate a Phase 1 clinical trial as a monotherapy and in combination in patients with KRASG12V-driven solid tumors. 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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SAN DIEGO--( BUSINESS WIRE )--Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, today announced the appointment of Peter Olson, Ph.D. to the role of chief scientific officer. Dr. Olson, who was most recently vice president, research at Mirati Therapeutics, a Bristol Myers Squibb (BMS) company, will join Iambic’s executive leadership team. A specialist in cancer biology and genetics, Dr. Olson will lead a team focused on driving small molecule programs from target identification through to clinical proof-of-concept. At Mirati, he led in vitro and in vivo pharmacology and translational research across its portfolio, which included pre-clinical efforts for KRAZATI™ (adagrasib), a KRAS G12C inhibitor approved by the US Food and Drug Administration (FDA) in 2022. “We couldn’t be more excited to welcome Pete Olson to the Iambic team,” said Tom Miller, PhD, Iambic’s chief executive officer. “He brings extraordinary drug discovery and development leadership experience as we advance and expand our pipeline of clinical candidates for oncology and other disease areas.” Iambic is developing an internal pipeline of candidates, discovered using its platform that integrates AI models for protein structure prediction and wholistic drug design with high-throughput chemistry and biology experimentation. The Company’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs. “Iambic’s AI-driven discovery platform enables the rapid identification of promising drug molecules and provides predictive insights into clinical properties of potential medicines,” said Dr. Olson. “I am excited to join the Iambic team to further advance their promising pipeline as we work to deliver innovative breakthroughs for patients.” Dr. Olson has over twenty-five years of basic, pre-clinical and translational cancer biology experience in academia and industry and is the author of close to 50 peer-reviewed papers. Prior to Mirati he was a senior principal scientist in Pfizer’s Oncology Research Unit, where he was the translational project leader for OGSIVEO™, the first FDA approved treatment for progressive desmoid tumors. Before Pfizer, he was a postdoc in the Hanahan Laboratory at the University of California, San Francisco. He received his Ph.D. in Biology from the University of California, San Diego and a B.S. in Biochemistry from the University of California, Davis. About Iambic’s AI-Driven Discovery Platform The Iambic AI-driven platform was created to address the most challenging design problems in drug discovery, leveraging technology innovations such as Enchant, a multi-modal transformer model that predicts clinical outcomes from the earliest stages of discovery, and NeuralPLexer, the best-in-class predictor of protein and protein-ligand structures. The integration of physics principles into the platform’s AI architectures improves data efficiency and allows molecular models to venture widely across the space of possible chemical structures. The platform enables identification of novel chemical modalities for engaging difficult-to-address biological targets, discovery of defined product profiles that optimize therapeutic window, and multi-parameter optimization for highly differentiated development candidates. Through close integration of AI-generated molecular designs with automated experimental execution, Iambic completes design-make-test cycles on a weekly cadence. About Iambic Therapeutics Founded in 2019 and headquartered in San Diego, California, Iambic Therapeutics is disrupting the therapeutics landscape with its unique AI-driven drug-discovery platform. Iambic has assembled a world-class team that unites pioneering AI experts and experienced drug hunters with strong track records of success in delivering clinically validated therapeutics. The Iambic platform has been demonstrated to deliver high-quality, differentiated therapeutics to clinical stage with unprecedented speed and across multiple target classes and mechanisms of action. The Iambic team is advancing an internal pipeline of clinical assets to address urgent unmet patient needs. Learn more about the Iambic team, platform, and pipeline at iambic.ai .