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Sharp strategy, broad reach
BOULDER, Colo.—Avila Therapeutics will team with Clovis Oncology Inc. to develop and commercialize Avila's epidermal growth factor receptor (EGFR) mutant-selective inhibitor (EMSI), which is currently in preclinical development for the treatment of non-small cell lung cancer (NSCLC).
Under the terms of the agreement, Avila and Clovis Oncology will collaborate on the preclinical development of the EMSI product candidate. 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. In addition to research support, Avila will receive an upfront 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 (erlotinib) and Iressa (gefitinib), as well as targeting the initial activating EGFR mutations, including L858R and exon 19 deletions. It does so while also sparing the wild-type (normal) EGFR, and may therefore treat refractory NSCLC while minimizing dose-limiting side effects such as skin rash and diarrhea.
Because the program targets both the sensitive activating mutations as well as the primary resistance mechanism, T790M, it has the potential to treat both first- and second-line NSCLC patients with EGFR mutations, for whom there is great unmet medical need.
Katrine Bosley, Avila's president and CEO, explains that Avila is a biotechnology company that designs targeted covalent drugs.
"We're hypothesis-driven, and our clinical experience has taught us how to make a better medicine," she states. "Clovis Oncology is an ideal partner with whom to advance this exciting program given their deep experience developing oncology drugs and their commitment to develop a companion diagnostic to identify the right patients for the drug. Resistance mutations in cancer-causing proteins are uniquely amenable to the targeted covalent inhibition enabled by Avila's platform, and by working together with Clovis, we will accelerate advancement of this program."
Patrick Mahaffy, president and CEO of Clovis, a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents, estimates that 15 percent of NSCLC patients have EGFR-associated cancers, and that up to 50 percent of these would be candidates for the drug. As is its practice, Clovis will partner with a diagnostic-development firm to identify patient candidates. Mahaffy calls the program "very important" and expects to enter Phase I trials next year with a coterie that is enriched with patients who have the T790M mutant form of EGFR so efficacy will also be suggested. It's possible, he adds, that Phase II will be skipped as a result.
"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. 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," says Dr. Daniel Haber, director of the Massachusetts General Hospital Cancer Center, who led a team that initially discovered EGFR mutations in lung cancer. "Such an inhibitor could overcome this resistance mutation at dosage levels that would spare the wild type EGFR in normal tissues. This could prove to be of major clinical significance."