DCC-2618 - GIST (pan cKIT inhibitor)

Deciphera's DCC-2618 is currently available for worldwide licensure. US patent allowance covering DCC-2618 and related analogs received December 2012.

DCC-2618 is a pan mutant cKIT inhibitor that is currently in preclinical development, and available for global licensure. cKIT kinase mutations drive approximately 90% of gastrointestinal stromal tumor (GIST) disease and human mast cell leukemia/ mastocytosis. Imatinib and sunitinib treat the primary mutant forms of cKIT in presenting GIST patients. However, approximately 70% of imatinib patients relapse after two years of therapy, and second-line sunitinib provides on average only four to six months of benefit before patients again relapse. Relapse is predominately due to the emergence of secondary cKIT mutations resistant to drug treatment. Approximately 10% of GIST patents have a primary D842V mutation in PDGFRα, which is also potently inhibited by DCC-2618.

There is a high unmet medical need to provide cKIT inhibitors that maintain high potency against such widespread secondary mutations, particularly exon 14 and 17 mutations. DCC-2618 potently inhibits all of these relevant primary and secondary cKIT mutations, as well as complex double mutant forms of cKIT. Moreover, mast cell leukemia and mastocytosis patients present with a primary exon 17 mutation, for which there is currently no available treatment.

• Deciphera has significant preclinical collaborations for its cKIT program with the laboratories of Jonathan Fletcher, M.D.(Dana-Farber/Brigham & Women's Cancer Institute) and Michael Heinrich, M.D. (Oregon Health Sciences University).
• DCC-2618 blocks cKIT mutated in a region called (exon 17) - GIST patients with these mutations are refractory to all marketed therapeutics.
• DCC-2618 blocks the mutant D816V form of cKIT causative of mast cell leukemia and mastocytosis. The D816V mutant cKIT is refractory to all currently marketed therapies.