Fulcrum Therapeutics Licenses Failed GSK Drug for Possible Muscular Dystrophy Indication
Cambridge, Mass.-based Fulcrum Therapeutics just acquired a worldwide license with GlaxoSmithKline (GSK) to develop and commercialize losmapimod. The drug was abandoned by GSK about three years ago after it failed in a late-stage myocardial infarction (heart attack) study. Fulcrum Therapeutics was one of BioSpace’s NextGen “Class of 2017” startup life sciences companies to watch.
Fulcrum intends to develop the drug in a type of muscular dystrophy called facioscapulohumeral muscular dystrophy (FSHD). The company has tested it in preclinical studies and plans to launch a Phase IIb clinical trial in humans in the middle of this year.
Losmapimod is a selective p38a/b MAPK inhibitor. Fulcrum’s proprietary product engine identified inhibitors of p38a/b MAPK as powerful inhibitors of DUX4 expression. The DUX4 gene is the root cause of FSHD, and losmapimod has the potential to decrease DUX4 expression.
GSK had already studied losmapimod in more than 3,500 healthy volunteers and patients in 24 clinical trials in numerous indications, but not in types of muscular dystrophy.
“Losmapimod is a foundational clinical asset for Fulcrum that has the potential to become the first approved therapy that targets the root cause of FSHD,” stated Robert J. Gould, Fulcrum’s president and chief executive officer. “Fulcrum believes losmapimod has the potential to slow or halt the progressive muscle weakness that characterizes the condition, which would significantly improve patients’ quality of life.”
He went on to say, “The agreement shows confidence in our unique approach to rebalancing gene expression in severe genetically defined disorders. We will work urgently to advance the compound through the clinic.”
Under the terms of the deal, GSK received Fulcrum preferred stock shares representing a high single-digit ownership percentage. GSK will also be eligible for future milestone payments and royalties.
Fulcrum picked up worldwide development and commercialization rights for the drug, as well as existing drug substance and drug product materials to use in its clinical trials. Fulcrum also gained a right of reference to INDs filed with the U.S. Food and Drug Administration related to losmapimod as well as an exclusive license to all related patents and data.
FSHD is one of the most common muscular dystrophies. It is progressive, degenerative and extremely disabling. It affects about 1 in 8,333 to 1 in 20,000 people globally. There are no approved treatments.
The symptoms usually appear in adulthood and begin with muscle weakness in the face, causing an inability to smile. The weakness progresses to the upper body and then the lower limbs. Many patients cannot lift their arms above shoulder level or rise from a sitting position. They have difficulties performing daily tasks and usually experience severe fatigue and pain.
The DUX4 gene is typically switched off in the earliest stages of embryonic development. But in FSHD patients, a mutation causes the gene to stay on and keep producing a protein that is toxic to muscle tissue.
Fulcrum launched in 2016 and focuses on gene control mechanisms for drug production. In September 2018, the company raised $80 million in a Series B financing round. The financing was led by Foresite Capital, with participation by Fidelity Management and Research Company, 6 Dimensions Capital, Casdin Capital, Sanofi Ventures, Section 32, NS Investments, entities affiliated with Leerink Partners and undisclosed institutional investors.
In GSK’s numerous studies, the drug appeared well-tolerated.