Clovis Oncology and Avila Therapeutics entered an agreement for the development and commercialization of Avila’s EGFR mutant-selective inhibitor (EMSI) program, currently in preclinical development for the treatment of non-small-cell lung cancer (NSCLC).
In addition to research support, Avila will receive an up-front fee and be eligible to receive development, regulatory, and sales-based milestone payments, with a total potential value of $209 million. Avila will also receive tiered royalties on product sales and will share in selected sublicense income.
The EMSI program targets the T790M mutant form of the EGFR associated with clinical resistance to Tarceva® and Iressa®, Avila explains. It also reportedly targets the initial activating EGFR mutations including L858R and exon 19 deletions while sparing the wild-type EGFR. Because the program targets both the sensitive activating mutations as well as the primary resistance mechanism, it has the potential to treat both first- and second-line NSCLC patients with EGFR mutations, the companies note.
“The T790M mutation seems to be the predominant mechanism underlying the development of resistance of EGFR-mutant lung cancers to specific EGFR kinase inhibitors, and it may well explain why the dramatic responses seen in these cases are of relatively short duration,” says Daniel Haber, M.D., Ph.D., director of the Massachusetts General Hospital Cancer Center, who led the team that initially discovered EGFR mutations in lung cancer.
“The development of a drug that is both mutant-specific and capable of irreversibly binding the enzyme is one of the most exciting new developments in this field. Such an inhibitor could overcome this resistance mutation at dosage levels that would spare the wild-type EGFR in normal tissues.”
Avila and Clovis Oncology will collaborate on preclinical development. Clovis Oncology will be fully responsible for all aspects of development and commercialization, including development of companion diagnostics to prospectively identify patients with clinically arising resistance mutations of the EGFR.
Clovis Oncology has one other molecule in clinical development. CO-101 is in Phase II trials for the treatment of pancreatic cancer. The company is also collaborating with Ventana Medical Systems to develop a companion diagnostic to identify patients with low tumor expression of hENT1, who are expected to benefit from CO-101.