This grant supports the development of a new drug to tackle hunger and obesity with PWS. Inversago, a newly started, specialized biotech company, proposes that its CB1 blockers would treat a wider spectrum of symptoms than anything presently in development for PWS. The drug targets the endocannabinoid pathway, which is known to be altered in PWS. Unlike previous drugs that targeted the same pathway, this modified version does not enter the brain – thus it is expected to have a beneficial effect on metabolism and weight without psychiatric side effects. FPWR funding will help support this company's development of their drug for PWS by supporting the ‘preclinical’ studies needed to move the drug into human clinical trials.
FPWR thanks the Storr Family Foundation whose generous support made this grant possible.
Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Watch the full webinar describing the 11 research projects funded in this grant cycle here.
Inversago is developing novel Cannabinoid-1 Receptor (CB1) blockers. CB1 blockers is a class of drugs with proven efficacy in humans for appetite suppression, weight loss, insulin and leptin resistance as well as liver diseases. Inversago intends to test its lead molecule, a 3rd generation CB1 blocker, in monkeys to demonstrate its safety. This is a pivotal step in bringing back CB1 blockers in clinical development because 1st generation CB1 blockers had the propensity to cause psychiatric adverse events in humans and monkeys, even more so in individuals with PWS based on clinical data. The observed adverse psychiatric effects are known to be caused by CB1 blockers entering the brain and acting on central CB1 receptors, causing anxiety and depression. Inversago has novel molecules specifically designed to only hit peripheral CB1 receptors (GI tract, liver, pancreas, fat cells, muscles, lungs, etc.), avoiding the brain and its associated adverse events, while still providing the beneficial metabolic parameter balancing effect. Given individuals with PWS were recently shown to have chronically activated CB1 receptors, a peripherally-restricted CB1 blockade has the potential to reverse this over activation, known to drive appetite, lower energy expenditure and slow gastrointestinal transit rate (chronic constipation). If unsuccessful in preventing psychiatric adverse events in monkeys, and in establishing a safe therapeutic window for human trials, Inversago would test its follow-on molecule, a 4th generation CB1 blocker. However, if successful, this first step will establish a therapeutic window for the first-in-human clinical trials (Phase 1), providing hope for the first time since 2008 that a CB1 blocker could help PWS patients. It is expected that upon completion of a positive monkey study, first-in-human trials (Phase 1) could be launched within 18-24 months. For the PWS community, if shown to be safe, this product is expected to provide appetite reduction (hyperphagia), but also provide the clinically-demonstrated beneficial metabolic effects of CB1 blockers such as weight loss, reversing insulin (type-2 diabetes) and leptin resistance, reducing fat and fibrosis in the liver, increase energy expenditure, and increase in gastrointestinal transit rate, useful to treat chronic constipation. Overall, Inversago's CB1 blockers would cover a wider spectrum of symptoms than anything presently in development for PWS.
Francois Ravenelle, PhD.
Francois Ravenelle, PhD.