Clovis Oncology, Inc, a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents, and Avila Therapeutics, Inc, a biotechnology company designing targeted covalent drugs, announced an agreement for the development and commercialization of Avila's epidermal growth factor receptor (EGFR) mutant-selective inhibitor (EMSI) programme, currently in pre-clinical development for the treatment of non-small cell lung cancer (NSCLC).

The EMSI programme targets the T790M mutant form of the EGFR associated with clinical resistance to Tarceva (erlotinib) and Iressa (gefitinib)i, 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 thus treat refractory NSCLC while minimizing dose-limiting side effects. Because the programme 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.

"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," said 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," he added.

Under the terms of the agreement, Avila and Clovis Oncology will collaborate on the pre-clinical 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 US$ 209 million. Avila will also receive tiered royalties on product sales and will share in selected sub-license income.

"Avila's EMSI programme has demonstrated very encouraging data against both the T790M resistance mutation and the initiating activating mutations and we are very pleased to initiate this partnership with them," said Patrick J Mahaffy, president and CEO of Clovis Oncology. "We plan to file an IND as rapidly as possible and initiate an accelerated clinical development program, including the use of a companion diagnostic to identify patients with NSCLC who possess the T790M mutation. We believe that this program has the potential to meaningfully improve outcomes in patients with EGFR-mediated non-small cell lung cancer."

"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," said Katrine Bosley, president and CEO of Avila Therapeutics. "Resistance mutations in cancer-causing proteins are uniquely amenable to the targeted covalent inhibition enabled by Avila's platform and working together with Clovis will accelerate advancement of this program."

Clovis Oncology is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the US, Europe and additional international markets.

Avila focuses on design and development of targeted covalent drugs to achieve best-in-class outcomes that cannot be achieved through traditional chemistries.