Bristol-Myers Squibb and Isis Pharmaceuticals are collaborating to discover, develop, and commercialize antisense drugs for the prevention and treatment of cardiovascular disease. In particular, they will focus on compounds targeting proprotein convertase subtilisin kexin 9 (PCSK9), which helps regulate the amount of cholesterol in the bloodstream.
"There is a clear need for new treatment options for many patients at high risk for cardiovascular disease due to high LDL-cholesterol levels," says Francis Cuss, M.D., senior vp, discovery and exploratory clinical research, Bristol-Myers Squibb. "PCSK9 is an attractive, genetically validated target in the field of cardiovascular disease, and Isis' antisense technology offers us a strong therapeutic platform for potentially bringing new cardiovascular medicines rapidly to market."
Bristol-Myers Squibb will pay a $15-million upfront licensing fee and will provide at least $9 million in research funding over a period of three years. Isis will also receive up to $168 million for the achievement of prespecified development and regulatory milestones for the first drug in the collaboration as well as additional milestones associated with development of follow-on compounds. Bristol-Myers Squibb will pay Isis royalties on sales of products resulting from the collaboration.
Isis licensed to Bristol-Myers Squibb exclusive access to its PCSK9 research program. This initiative recently produced new data on the mechanism by which PCSK9 contributes to high levels of LDL cholesterol, according to Bristol-Myers Squibb. With its second-generation antisense PCSK9 compounds, Isis has shown in mice that reducing PCSK9 leads to increased levels of LDL receptor and consequently to lower LDL-cholesterol in the bloodstream.
While Bristol-Myers Squibb will fund all activities under the collaboration, both companies will be responsible for preclinical development. Bristol-Myers Squibb will be responsible for clinical development, regulatory, and commercialization activities. In addition, it will work with Isis to leverage Isis' extensive oligonucleotide medicinal chemistry expertise for identification of follow-on PCSK9 antisense drugs with advanced antisense chemistries.