Isis Pharmaceuticals, Inc. has completed a transaction with Symphony Capital Partners, L.P. and a group of co-investors to provide $75 million to fund the development of Isis' cholesterol-lowering drug, ISIS 301012, and two novel drugs from Isis' metabolic disease program.

According to the company release, the financing will support ISIS 301012 through the completion of registration-supporting clinical studies in patients with familial hypercholesterolemia and the completion of Phase 2b clinical trials in patients with high cholesterol. The financing will also support development of two novel diabetes drugs through initial proof of concept in human clinical trials. In addition to providing the financial support to move these drugs forward aggressively, the transaction allows Isis to continue to control and manage the development of ISIS 301012 and two other potentially valuable drugs through key development milestones.

Symphony Capital has formed Symphony GenIsis, Inc., capitalized with $75 million, to provide funding for the development of these three drugs in collaboration with Isis. Isis has granted a license to the intellectual property for the three programs to Symphony GenIsis, but retains the exclusive right to reacquire the intellectual property at any time by acquiring all of Symphony GenIsis' equity.

"This transaction with Symphony Capital accelerates and expands our development pipeline and enhances our future economic opportunities in these drugs, while minimizing dilution and financial risk. Symphony Capital will provide the funds necessary to progress ISIS 301012 and two drugs from our exciting diabetes programs through several value inflection points," said B. Lynne Parshall, Executive Vice President and CFO of Isis Pharmaceuticals.

"This transaction supports the development of our most important asset, ISIS 301012, and at the same time broadens our exciting diabetes pipeline. When this collaboration is complete, we expect to have data demonstrating that ISIS 301012 is a novel, safe, and effective drug to treat patients who have familial hypercholesterolemia and plan to register the drug initially for that indication," said Stanley T. Crooke, President and Chief Executive Officer at Isis Pharmaceuticals.

Glucagon receptor (GCGR) is the cellular receptor for glucagon, one of the counter-regulatory hormones that oppose the action of insulin and help maintain normal blood glucose levels. GCGR is mainly expressed in the liver, where it is responsible for initiating the signal that stimulates glucose production. In type 2 diabetes, unopposed action of glucagon can lead to excessive glucose production by the liver, resulting in increased blood glucose levels. Reducing the expression of GCGR using antisense inhibitors can thereby reduce excessive hepatic glucose production, which represents a novel approach to diabetes therapy. GCGR has been very difficult to target with small molecule drugs. Antisense oligonucleotides (ASOs) distribute preferentially to the liver and fat cells, making them ideal for this therapeutic approach.