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.

Eli Lilly and Co. and Transition Therapeutics, Inc. have entered into a licensing and collaboration agreement granting Lilly exclusive worldwide rights to develop and commercialize Transition's gastrin-based therapies, including the lead compound TT-223, which is currently in early Phase II development. Gastrin-based therapies are a new class of potential disease-modifying therapies for patients with diabetes, and have shown sustained improvement in glycemic control in early clinical studies. Glycemic control is a key goal in order to alleviate the symptoms of hyperglycemia and to prevent diabetic complications.
   
Under the terms of the agreement, Transition will receive a $7 million upfront payment, and may also receive as much as $130 million in potential development and sales milestones, as well as royalties on sales. Both companies will participate in the planned Phase II trial with TT-223 in type 2 diabetes. Lilly will then be responsible for further development and the commercialization of all gastrin-based compounds worldwide.
   
"This agreement represents an exciting new direction for Lilly's diabetes care research," said David Moller, M.D., Lilly, vice president of endocrine and cardiovascular research and clinical investigation. "We plan to leverage Transition's experience in gastrin based therapies with our own internal expertise, including Lilly's strong biotechnology discovery platform, to continue our mission to develop innovative, beneficial and cost-effective treatments for patients with diabetes."

AstraZeneca and Silence Therapeutics have entered into a collaboration focused on the development of new approaches for the delivery of siRNA molecules. Silence has expertise in the delivery of siRNA molecules, in particular with the functional systemic delivery of siRNA in vivo using its AtuPLEX technology. Under the terms of the agreement, the two companies will be allowed to commercialize delivery systems developed under the collaboration. Financial details of the agreement were not disclosed.
   
Silence will retain the right to sign further agreements regarding its current AtuPLEX delivery technology as well as any improvements that it generates either independently or as part of this collaboration. The two companies also have a three-year collaboration, signed in July 2007, to develop novel siRNA therapeutics against specific AZ targets.
   
Jeff Vick, chief executive officer of Silence Therapeutics, said, "We are delighted to enter this new collaboration with AstraZeneca for the development of novel approaches for the delivery of siRNA molecules. This agreement highlights the significant progress we have made with our AtuPLEX platform, following our early realization of the importance of delivery to the development of successful RNAi therapeutics. This deal also reflects the strong working relationship we have developed with AstraZeneca and the progress of our ongoing collaboration in the development of AtuRNAi molecules against a number of their targets."
     
Claude Bertrand, global vice president, discovery respiratory and inflammation, at AstraZeneca said, "We are very happy with the working relationship we have developed with the team at Silence Therapeutics and the progress made over the last six months via our agreement to develop siRNA therapeutics against a number of our targets. This announcement is designed to generate the novel delivery approaches that are needed if this exciting class of novel drugs is to realize fully its potential."

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