WE ARE DEVELOPING A NOVEL, PEPTIDE-BASED INHIBITOR OF FAK, AS WELL AS A COMPANION DIAGNOSTIC AND PROGNOSTIC TEST
FAKNOSTICS STAPLED PEPTIDE INHIBITOR
FAKnostics has developed a series of hydrocarbon-stapled peptides that block the FAK FAT domain.
Our peptides have demonstrated enhanced alpha helicity, permeability, binding affinity, proteolytic resistance, and pharmacokinetic properties.
OUR STRATEGY TARGETS THE FAK FAT DOMAIN
Traditional methods of targeting the kinase domain have not proven effective because the kinase reprogramming happens fast (15 minutes), resulting in cancer evasion from therapy. Numerous trials failed because of this.
We target the FAT (Focal Adhesion Targeting ) domain that regulates the Focal Adhesion Complex, Metastasis, and apoptosis. Disrupting FAT interactions (i.e. with Paxilin) de-localizes FAK from the critical signaling complex and renders the inhibition strategy much more effective.
FAK KINASE INHIBITORS
The approach of inhibiting the FAK kinase domain is not selective for cancer cells vs. normal cells, and micromolar cellular activity does not correlate with biochemical potency.
FAKNOSTICS BIVALENT PEPTIDE INHIBITOR
The liposomal formulation of our stapled peptide is highly potent in cancer cells at nanomolar quantities. It has a 10-fold selectivity for cancer cells over normal cells. Its biochemical potency correlates with cellular activity.
Our first therapeutic focus is metastatic melanoma that has progressed on other treatment regimens. Our precision-targeted approach to specific molecular markers will offer another treatment modality for this aggressive cancer
FAK is considered to be an especially promising cancer drug target for melanoma and other tumors, as it is involved in multiple aspects of cancer progression, including migration, invasion, metastasis, apoptosis, proliferation, angiogenesis, and immune-cell suppression. In healthy cells, it controls cellular adhesion, motility, proliferation, and survival.
Despite substantial progress in melanoma therapeutics with the advent of immunotherapy and B-RAF targeted inhibitors, significant unmet needs remain for recurrent and metastatic disease. Because FAK is a driver of progression of this disease, we will target precise molecular subtypes of melanoma in our initial clinical trials.
NRAS-mutant melanoma (30% of all melanoma cases and current unmet need) has shown a unique sensitivity to treatment with our FAK FAT inhibitors. FAKnostics efforts to develop a FAK inhibitor for use in NRAS-mutant melanoma are ongoing.
WE ARE CURRENTLY AT THE PRECLINICAL STAGE WITH PROGRAMS
IN NRAS-MUTANT MELANOMA AND COLORECTAL CANCER