Alliance targets 11beta-HSD-1 for the treatment of metabolic syndrome disorders.
Vitae Pharmaceuticals received a $14 million milestone payment from Boehringer Ingelheim with the initiation of a Phase I trial. Under the firms’ alliance, a small molecule inhibitor of 11beta-hydroxysteroid dehydrogenase (HSD)-1 has advanced into clinical testing as a treatment of diabetes and metabolic syndrome-related diseases.
“Inhibition of 11beta-HSD-1 represents an important new mechanism of action for treating diabetic patients,” according to Richard Gregg, Ph.D., Vitae’s CSO. “This program addresses several features of the metabolic syndrome, a combination of disorders including abdominal obesity, high blood pressure, and insulin resistance or glucose intolerance, all of which contribute to an increased risk of coronary heart disease, stroke, and type 2 diabetes.”
11beta-HSD-1 is an enzyme that converts the biologically inactive steroid cortisone into the active hormone cortisol. Cortisol is known to cause resistance to the action of insulin in multiple target tissues including liver, muscle, and adipose tissue.
Overexpression of 11beta-HSD-1 in mouse adipose tissue leads to a metabolic syndrome-like phenotype including increased central obesity, hypertension, impaired glucose tolerance, and hypertriglyceridemia. In contrast, 11beta-HSD-1 knockout mice resist visceral obesity and diabetes through improved function of insulin in liver and adipose tissues.
Early clinical evidence has shown that inhibiting 11beta-HSD-1 can reduce glucose and lipids in diabetic patients. Data indicates that elevated levels of adipose and liver 11beta-HSD-1 are detrimental to metabolic control.
Vitae and Boehringer Ingelheim initiated their collaboration, which is focused on 11beta-HSD-1, in October 2007. Under the terms of that agreement, Vitae received $36.5 million in an up-front fee, an equity investment, and committed research funding over two years. The companies combined their respective research programs and decided to work together to identify and advance novel 11beta-HSD-1 inhibitors.
Vitae reports that it has achieved three performance milestones, totaling $26 million of a potential $300 million in success-based fees. Vitae is also eligible to receive royalty payments from Boehringer Ingelheim on sales of products commercialized under the collaboration.
The companies have a separate arrangement focused on beta-secretase (BACE) inhibitors for the treatment of Alzheimer disease; BACE is involved in the formation of amyloid-beta plaques. Under the terms of the Alzheimer agreement, Vitae received $42 million in up-front and near-term payments. In addition, it is eligible to $200 million in precommercial milestones. Vitae will receive commercial performance fees and royalties on all product sales.
The companies will work jointly to identify and advance candidates for clinical development. Thereafter, Boehringer Ingelheim will lead development and commercialization of all products.