CARLSBAD, Calif., Sept. 13 Isis Pharmaceuticals,Inc. (Nasdaq: ISIS) today announced a broad collaboration with Ortho-McNeil,Inc., a Johnson & Johnson company, to discover, develop and commercializeantisense drugs to treat metabolic diseases, including Type 2 diabetes. Aspart of the collaboration, Isis will grant to Ortho-McNeil worldwidedevelopment and commercialization rights to two of its diabetes developmentcandidates, ISIS 325568 and ISIS 377131, which selectively inhibit theproduction of glucagon receptor (GCGR) and glucocorticoid receptor (GCCR),respectively. Additionally, Ortho-McNeil will provide funding to Isis tosupport the joint discovery of novel drugs to treat metabolic diseases,including diabetes and obesity. After the initial collaboration phase,Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) willcontinue development of these drugs.
Ortho-McNeil will pay Isis a $45 million upfront licensing fee, and willprovide Isis with research and development funding over the period of thecollaboration. In addition to the licensing fee, Isis could receive over$230 million in milestone payments upon successful development and regulatoryapprovals of ISIS 325568 and ISIS 377131, as well as royalties on sales. Isiscould also receive milestones and royalties on the successful development andregulatory approvals of additional drugs discovered as part of thecollaboration. The agreement is subject to clearance under theHart-Scott-Rodino Antitrust Improvements Act. Prior to closing of thetransaction, Isis plans to purchase the equity in Symphony GenIsis, Inc. andreacquire the intellectual property related to the GCGR and GCCR programs aswell as regain full ownership of ISIS 301012, the Company's lipid-loweringdrug targeting Apolipoprotein B-100.
"We look forward to working with Ortho-McNeil, Inc. and J&JPRD to advanceour glucagon receptor and glucocorticoid receptor drugs through the clinic andto develop additional drugs against other promising targets," said LynneParshall, J.D., Executive Vice President and Chief Financial Officer, IsisPharmaceuticals. "This collaboration represents another major step for us incapturing value from our achievements in creating a new drug discoveryplatform technology and discovering commercially attractive antisense drugs."
"This collaboration has been enabled by the productivity of our metabolicdrug discovery program, which has evaluated more than 120 targets in animalmodels using antisense drugs," said Jeffrey Jonas, M.D., Executive VicePresident, Isis Pharmaceuticals. "Both ISIS 325568 and ISIS 377131 have broadand exciting therapeutic profiles that include lowering of blood lipids andbody fat, in addition to significant glucose-lowering effects. These drugshave demonstrated robust effects in extremely diabetic and hyperlipidemicanimals and have demonstrated a unique and preferential distribution totissues such as liver and fat, thereby potentially minimizing the systemicside effects that would be expected with traditional approaches against thesame gene targets. We are enthusiastic about our research collaboration,which should allow us to discover additional drugs against novel targets,thereby adding to our strong pipeline in this therapeutic area."
About glucagon receptor (GCGR), target of ISIS 325568
Glucagon is a hormone that opposes the action of insulin and stimulatesthe liver to produce glucose. In Type 2 diabetes, unopposed action of glucagoncan lead to increased blood glucose levels. Reducing the expression of liverGCGR using antisense inhibitors, and thereby reducing excessive liver glucoseproduction, is expected to lower blood glucose levels and help control Type 2diabetes. In preclinical studies, antisense inhibitors of GCGR led to improvedglucose control and reduced levels of blood triglycerides without producinghypoglycemia. In addition, treatment with