Genentech To Develop Exelixis Cancer Drug

Genentech, Inc. has exercised its option to further develop and commercialize Exelixis Inc.’s compound XL518, a selective and potent inhibitor of MEK that is currently in a Phase I trial. Under the terms of the agreement, Exelixis will continue that trial until the maximum tolerated dose (MTD) is determined. Genentech will then be responsible for completing the Phase I trial and subsequent clinical development.
   
“MEK inhibition is an exciting approach to cancer therapy. The MAP kinase pathway, of which MEK is a member, is one of the most frequently disregulated pathways in human tumors. Activating mutations of the pathway have been identified in many tumor types, including melanomas, thyroid carcinomas, non-small cell lung cancer and colon cancer. Pathway inhibitors are likely to find broad utility as both single agents and in combination with other targeted agents and chemotherapeutics,” said George A. Scangos, Ph.D., president and chief executive officer of Exelixis. “We believe the opt-in by Genentech is recognition of the potential of XL518 and MEK inhibition in the treatment of various tumor types.”
   
Under the terms of the agreement — signed in January 2007 — Exelixis received upfront and milestone payments totaling $40 million. Genentech will now pay $3 million for selection of the compound and another $7 million when a Phase II trial is initiated by Genentech. Exelixis has the option to co-promote in the U.S. and is entitled to receive an initial equal share in profits in the U.S., which will decrease as sales grow. Exelixis will receive royalties on any sales of the product outside the U.S.
   
Preclinical studies of XL518 indicate that the compound is a potent and selective non-ATP-competitive inhibitor of MEK1. XL518 shows dose-dependent tumor growth inhibition and regression in multiple preclinical human tumor xenograft models. The Phase I trial is currently enrolling patients with advanced solid malignancies in order to define the MTD as well as pharmacokinetic and pharmacodynamic effects of XL518.