Fulcrum Therapeutics announced an exclusive worldwide license agreement with GlaxoSmithKline for development and commercialization of the investigational drug losmapimod. Fulcrum intends to advance losmapimod into a Phase 2b trial in the rare and genetic disease facioscapulohumeral muscular dystrophy (FSHD).
Under the terms of the agreement, as payment for the license, GSK received shares of Fulcrum preferred stock representing a high single-digit ownership percentage of the company on a fully diluted basis, and will be eligible to receive future milestone payments and royalties. Fulcrum obtained all worldwide development and commercialization rights for losmapimod, as well as existing drug substance and drug product materials for use in its clinical trials. Fulcrum also received a right of reference to INDs filed with the FDA relating to losmapimod and an exclusive license to all related patents and data, which build on Fulcrum-generated intellectual property.
GSK evaluated losmapimod in more than 3,500 healthy volunteers and patients in 24 clinical trials across multiple indications, including several Phase 2 trials and a Phase 3 trial in acute coronary syndrome. In 2015 GSK discontinued the development losmapimod following the results from the phase 3 trial in patients with acute coronary syndrome. The study found losmapimod was no better than placebo at preventing major adverse cardiovascular events. The drug was well tolerated.
Fulcrum’s proprietary product engine identified inhibitors of p38α/β mitogen activated protein kinase (MAPK) as powerful inhibitors of DUX4 expression. DUX4 is the gene that is the root cause of FSHD. Losmapimod is a selective p38α/β MAPK inhibitor. Fulcrum’s novel insight into the DUX4 regulatory pathway led the team to review existing p38α/β MAPK inhibitors, and Fulcrum identified losmapimod as a compound with the potential to address the root cause of FSHD by decreasing DUX4 expression.
About facioscapulohumeral muscular dystrophy (FSHD)
FSHD, one of the most common muscular dystrophies, is a progressive, degenerative and profoundly disabling disorder estimated to affect about 1 in 8,333 to 1 in 20,000 people globally. There are no approved treatments. Symptoms typically arise in adulthood, often beginning with muscle weakness in the face. The weakness progresses to the upper body and advances to the lower limbs. FSHD is caused by a single mutated gene, DUX4.
Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK). Fulcrum identified the compound as a potent regulator of the expression of the DUX4 gene, which causes FSHD.