Building on an exceptional track record of innovation, this team brings a wealth of cross-functional expertise to successful rational drug design. We focus on pioneering best-in-class therapeutics to improve upon existing drugs with clear liabilities, as well as to create new breakthroughs for diseases where others have been unable to find solutions.
Established and emerging science will guide our plans, with an emphasis on rare disease patient populations with well-characterized biology, allowing us to move rapidly and create meaningful impact for patients.
Our pipeline is focused on creating breakthroughs for diseases where others have been unable to find solutions, pioneering best-in-class therapeutics to improve upon existing drugs with clear liabilities. Established and emerging science will guide our plans, with an emphasis on rare disease patient populations with well-characterized biology, allowing us to move rapidly and create meaningful impact for patients.
KIT mutations serve as driver mutations in up to 80% of gastrointestinal stromal tumors (or GIST) and over 90% of systemic mastocytosis (SM), a hematologic disease of clonal mast cells. Bezuclastinib is a novel type I tyrosine kinase inhibitor developed as a potent and selective inhibitor of KIT A loop mutations, including D816V to address diseases driven by mutated KIT.
Kit mutations serve as driver mutations in up to 80% of gastrointestinal stromal tumors (GIST) and in over 90% of systemic mastocytosis (SM)
In GIST, patients often relapse after front-line imatinib treatment due to secondary mutations in ATP-binding domain (ABD) or Activation Loop (AL). Although, second-line sunitinib is active against ABD mutations it is not active against all AL mutations. Inhibitors targeting AL mutations, notably D816V (a common AL mutation in SM), have shown activity in the treatment of advanced SM, but off-target toxicities of available compounds may limit optimal clinical dosing.
Bezuclastinib is a novel type I TKI that was developed as a highly potent and selective inhibitor of KIT D816V and may avoid off-target toxicities to provide a better clinical profile.
Inhibition Ligand Independent Signaling in FGFR 2/3 Altered Tumors is a Clinically Proven Approach
FGFR2 and FGFR3 are Well-Established Oncogenic Drivers in Multiple Indications
• Fibroblast growth factor receptors (FGFRs) are a family of transmembrane receptors consisting of isoforms FGFR1-FGFR4
• Binding of a ligand to the inactive FGFR monomer leads to receptor dimerization, phosphorylation, and downstream signaling
• Receptor mutations, amplifications, and fusions can result in activation of FGFRs and are recognized as well-established oncogenic drivers in multiple indications
•Inhibition of FGFR3 mutations in urothelial cancer and FGFR2 fusions in cholangiocarcinoma has led to improved clinical outcomes in defined patient populations
The Cogent team is driven to discover and develop novel precision medicines. Beginning with bezuclastinib, we strive to improve the lives of patients fighting rare, genetically driven diseases.
