Cogent Biosciences Announces Pipeline Expansion into KRAS and Poster Presentations at the 2024 EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics
Cogent Biosciences announced the expansion of its pipeline with a new KRAS inhibitor program and presented preclinical data at the 2024 EORTC-NCI-AACR Symposium. The company showcased two programs: CGT6737, a pan KRAS(ON) inhibitor with selectivity over HRAS and NRAS, demonstrating 90% PD inhibition in mouse models, and CGT6297, a PI3Kα inhibitor targeting H1047R mutations affecting over 55,000 cancer patients annually. CGT6297 showed 25-fold selectivity over PI3Kα WT with superior efficacy compared to approved therapies. IND-enabling studies for CGT6297 are planned for 2025.
Cogent Biosciences ha annunciato l'espansione del suo pipeline con un nuovo programma di inibitori KRAS e ha presentato dati preclinici al Simposio EORTC-NCI-AACR 2024. L'azienda ha mostrato due programmi: CGT6737, un inibitore pan KRAS(ON) con selettività per HRAS e NRAS, che dimostra un'inibizione del 90% della PD in modelli murini, e CGT6297, un inibitore di PI3Kα che colpisce le mutazioni H1047R che interessano oltre 55.000 pazienti affetti da cancro ogni anno. CGT6297 ha mostrato una selettività 25 volte superiore rispetto a PI3Kα WT con una maggiore efficacia rispetto alle terapie approvate. Studi di abilitazione IND per CGT6297 sono previsti per il 2025.
Cogent Biosciences anunció la expansión de su pipeline con un nuevo programa de inhibidores de KRAS y presentó datos preclínicos en el Simposio EORTC-NCI-AACR 2024. La compañía mostró dos programas: CGT6737, un inhibidor pan KRAS(ON) con selectividad sobre HRAS y NRAS, que demuestra una inhibición del 90% de la PD en modelos de ratón, y CGT6297, un inhibidor de PI3Kα que se dirige a las mutaciones H1047R que afectan a más de 55,000 pacientes con cáncer anualmente. CGT6297 mostró una selectividad 25 veces superior a PI3Kα WT con una eficacia superior en comparación con las terapias aprobadas. Se planean estudios de habilitación IND para CGT6297 para 2025.
코젠트 바이오사이언스는 새로운 KRAS 억제제 프로그램으로 파이프라인을 확장했다고 발표하고, 2024 EORTC-NCI-AACR 심포지엄에서 전임상 데이터를 발표했습니다. 회사는 두 가지 프로그램을 소개했습니다: CGT6737, HRAS 및 NRAS에 대한 선택성을 가진 팬 KRAS(ON) 억제제로, 생쥐 모델에서 PD 억제 효과가 90%에 달하며, CGT6297, 매년 55,000명 이상의 암환자에게 영향을 미치는 H1047R 변이를 목표로 하는 PI3Kα 억제제입니다. CGT6297는 PI3Kα WT보다 25배 높은 선택성을 보여주었으며, 승인된 치료법에 비해 우수한 효능을 나타냈습니다. CGT6297에 대한 IND 승인 연구는 2025년으로 예정되어 있습니다.
Cogent Biosciences a annoncé l'expansion de son pipeline avec un nouveau programme d'inhibiteurs de KRAS et a présenté des données précliniques lors du Symposium EORTC-NCI-AACR 2024. L'entreprise a mis en avant deux programmes : CGT6737, un inhibiteur pan KRAS(ON) avec sélectivité pour HRAS et NRAS, démontrant une inhibition de la PD de 90 % dans des modèles murins, et CGT6297, un inhibiteur de PI3Kα ciblant les mutations H1047R affectant plus de 55 000 patients atteints de cancer chaque année. CGT6297 a montré une sélectivité 25 fois supérieure à celle de PI3Kα WT avec une efficacité supérieure par rapport aux thérapies approuvées. Des études pour la mise en œuvre de CGT6297 sont prévues pour 2025.
Cogent Biosciences gab die Erweiterung seiner Pipeline mit einem neuen KRAS-Inhibitor-Programm bekannt und präsentierte präklinische Daten auf dem Symposium EORTC-NCI-AACR 2024. Das Unternehmen stellte zwei Programme vor: CGT6737, ein pan-KRAS(ON)-Inhibitor mit Selektivität gegenüber HRAS und NRAS, der in Mausmodellen eine PD-Hemmung von 90 % zeigt, und CGT6297, ein PI3Kα-Inhibitor, der sich auf H1047R-Mutationen konzentriert, die jährlich mehr als 55.000 Krebspatienten betreffen. CGT6297 zeigte eine 25-fache Selektivität gegenüber PI3Kα WT mit überlegener Wirksamkeit im Vergleich zu genehmigten Therapien. IND-Studien zur Durchführung von CGT6297 sind für 2025 geplant.
- Addition of new KRAS inhibitor program expanding pipeline
- CGT6737 achieved 90% PD inhibition in mouse xenograft models
- CGT6297 demonstrated 25-fold selectivity over PI3Kα WT
- CGT6297 showed superior efficacy compared to approved therapies
- IND-enabling studies for CGT6297 not starting until 2025
- Both programs still in preclinical stage
Insights
The pipeline expansion into KRAS inhibitors represents a significant strategic move. The CGT6737 pan KRAS(ON) inhibitor shows promising picomolar activity and selectivity over H/NRAS, targeting one of cancer's most prevalent mutations. The data demonstrating
The H1047R mutant-selective PI3Kα inhibitor CGT6297 addresses a substantial market with >
This pipeline expansion significantly strengthens Cogent's competitive position in precision oncology. The KRAS inhibitor market is particularly valuable, with existing KRAS-targeting drugs generating substantial revenue. The company's approach of developing potentially best-in-class molecules with differentiated properties could capture meaningful market share.
The advancement of both programs demonstrates strong R&D execution and pipeline diversification beyond the company's lead mastocytosis program. The focus on genetic mutations with clear clinical validation reduces development risk. With IND-enabling studies for CGT6297 planned for 2025, investors can expect multiple value-creating catalysts in the coming years.
Preclinical data highlight company’s fourth discovery stage program, a novel potent and selective KRAS(ON) inhibitor
Updated preclinical data from CGT6297, Cogent’s H1047R mutant-selective PI3Kα inhibitor demonstrates robust inhibition of downstream signaling and efficacy
WALTHAM, Mass. and BOULDER, Colo., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced the addition of a potent and selective KRAS inhibitor to its pipeline. Preclinical data from this program as well as its newly announced H1047R mutant-selective PI3Kα clinical candidate will be presented in two poster presentations at the 2024 EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics taking place in Barcelona, Spain October 23-25, 2024.
“Our Research team continues to make amazing progress, and we are excited to announce our third clinical candidate and fourth preclinical program today,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “Building upon earlier data presentations and recent advancements in the field, our first poster describes the properties of CGT6297, which we believe has the potential to emerge as a best-in-class H1047R mutant-selective PI3Kα inhibitor. Separately, for the first time, we outline our progress toward developing a potential best-in-class KRAS(ON) inhibitor, which in addition to its mechanistic attributes, has pharmacological properties differentiated from existing compounds in the class. Each of these programs align with our long-term strategy of creating and developing best-in-class molecules with the potential to have a broad impact on patients with genetically defined diseases.”
Poster Details
The posters can be accessed in the ‘Posters and Publications’ page of Cogent’s website.
Title: Identification of a Pan KRAS(On) Inhibitor with Selectivity Over KRAS over H/NRAS and pM Activity Across Prevalent KRAS Mutations
Session Date and Time: Wednesday, October 23, 2024 – 12.00 - 19.00 CEST
Location: Exhibition Hall, Centre de convencions internacional Barcelona (CCIB), Barcelona, Spain
Poster Number: PB108
Abstract Number: 120
Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally-developed pan KRAS(ON) inhibitor with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations without the potential liabilities of molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with
Title: Preclinical Characterization of a Novel PI3Kα H1047R Mutant Selective Inhibitor
Session Date and Time: Wednesday, October 23, 2024 – 12.00 - 19.00 CEST
Location: Exhibition Hall, Centre de convencions internacional Barcelona (CCIB) Barcelona, Spain
Poster Number: PB133
Abstract Number: 145
Cogent is also developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the H1047R mutation, which affects >55,000 cancer patients each year. The phosphoinositide 3-kinase (PI3K) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα.
The poster presented today highlights Cogent’s clinical candidate CGT6297, a potent allosteric inhibitor of PI3K, with 25-fold selectivity over PI3Kα WT. CGT6297 has high oral bioavailability and low clearance across species, providing robust inhibition of downstream signaling and efficacy in animal models. Importantly, when compared to a clinically relevant dose of a currently approved therapy in a mouse tumor model, CGT6297 demonstrated superior efficacy with no increase in insulin. IND-enabling studies are expected to be initiated in 2025.
Upcoming Investor Conference
Cogent will participate in the following upcoming investor conference:
Guggenheim Healthcare Innovation Conference - November 12, 2024 at 10:30 a.m. ET.
A live webcast of the fireside discussion will be available in the Investors & Media section of Cogent’s website at investors.cogentbio.com/events. A replay of the event will be archived on Cogent’s website for up to 30 days.
About Cogent Biosciences, Inc.
Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2, ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential for CGT6297 to be a best-in-class H1047R mutant-selective PI3Kα inhibitor, the expectation that the company will initiate IND-enabling studies for CGT6297 in 2025, and the potential for the company’s KRAS program to produce a best-in-class KRAS(ON) inhibitor with pharmacological properties differentiated from existing compounds in the class and without the potential liabilities of molecules in the class. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof.
Contact:
Christi Waarich
Senior Director, Investor Relations
christi.waarich@cogentbio.com
617-830-1653
FAQ
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