CFON-026 is a non-covalent BTK inhibitor with a covalent-like binding profile for both BTK wild-type as well as all clinically relevant BTK mutant variants. It not only inhibits signaling of the BTKC481S mutant variant associated with CLL resistance to covalent BTK inhibitors (which for their binding on the cysteine at position 481), but also BTK mutant variants that arise following treatment with non-covalent BTK inhibitors like pirtobrutinib. CFON-026 is in preclinical development, showing high selectivity, good manufacturability and promising PK/PD properties.
A First in Human (FIH) trial with CFON-026 is expected to be initiated the second half of 2025.