PS CB1 Receptor Antagonist Program

 

Jenrin’s most advanced program is targeting peripherally selective (PS) CB1 receptor antagonists for the treatment of metabolic disorders. Because of the risk of psychiatric side effects, all development programs associated with brain-penetrant CB1 antagonists have been halted, and the only marketed product has been withdrawn. In addition to producing weight loss, these brain-penetrant CB1 antagonists (e.g., rimonabant) improve lipid levels and glycemic control, increase fat metabolism, and decrease fatty liver.

The Jenrin PS CB1 receptor antagonist program capitalizes on the discovery that blockade of CB1 receptors in peripheral tissues (e.g., liver, muscle, adipose tissue, pancreas, GI tract) is sufficient to produce metabolically favorable effects, delivering an alternative to brain-penetrant CB1 antagonists associated with psychiatric and neurologic liabilities. Jenrin has established a dominant P-S CB1 patent estate, more than 800 compounds in three distinct chemical scaffolds have been synthesized, and multiple lead candidates have been identified. By using clinically advanced CB1 antagonists as starting points for our drug discovery efforts, Jenrin capitalizes on years of medicinal chemistry that optimized the original parent drug. This increases the likelihood that Jenrin proprietary compounds will retain the essential druggable properties of the parent drug, reducing investment and development risk.

PS CB1 antagonists developed at Jenrin reduce body weight, decrease fatty liver, and lower serum levels of insulin and triglycerides in animals exposed to a high-fat diet. These ‘re-designed’ CB1 antagonists also have a very favorable psychiatric side effect profile compared to brain-penetrant CB1 antagonists. One lead compound, JD-5006, is currently being advanced toward an IND filing, and a number of back up candidates are also being characterized. Jenrin has selected liver diseases and type 2 diabetes as initial clinical indications for its pipeline of P-S CB1 receptor antagonists, and is looking for a collaboration to help advance these compounds.