In all of us, genes are regulated through a balance of active and repressive states. There are hundreds of serious human disorders for which a controlled change in the expression of a particular gene might significantly ameliorate disease. By unlocking the mechanisms of gene regulation, Fulcrum’s product engine represents an opportunity to develop disease-modifying therapies for many diseases across therapeutic areas: neurodevelopmental, neuromuscular, neurodegenerative and many others.

Fulcrum’s unique and differentiated approach addresses the genetic cause of disease. In our initial efforts, we will be focusing on monogenic diseases that arise due to a faulty regulation of a single gene.

Fulcrum Therapeutics Pipeline

Central Nervous System Disorders

  • Fragile X Syndrome

    Fragile X syndrome (FXS) is the most common monogenic cause of severe cognitive disability in boys. FXS is found in about 1 in 4,000 boys (girls also may be affected, but in a less severe manner). About 1,000 boys are born with FXS in the US and Europe each year, and there are more than 50,000 boys and men living with FXS in these regions. The most severely affected patients have little or limited use of language and often have significant behavioral problems, often related to profound social anxiety.

    FXS arises because of a genetic mutation – the expansion of a triplet repeat in the FMR1 gene. This triplet repeat mutation leads to the silencing of an otherwise healthy gene. Because of this silencing, cells do not make the FMRP protein, which is important for proper neuronal function.

    Fulcrum is developing a small molecule that counters the expansion to permit expression of the otherwise healthy FMR1 gene.

    Currently there is no cure available for FXS, and current therapies do not target the fundamental cause of the disease nor slow progression.

    Our approach to developing new medicines for Fraxile X Syndrome

    Click to enlarge


    Our Patient Community Partners

Neuromuscular Disorders

  • Facioscapulohumeral muscular dystrophy

    Facioscapulohumeral muscular dystrophy (FSHD) is a disorder that often renders persons unable to walk by early adulthood. FSHD is a genetic neuromuscular disease marked by its progressive skeletal muscle weakness due to the death of muscle cells and tissue. This slowly progressive muscle disorder affects about 1 in 20,000 persons. The clinical course varies among people, but about 80% eventually lose the ability to walk. In the U.S. and Europe, more than 30,000 persons are living with FSHD.

    FSHD arises due to a mutation in a repetitive stretch of DNA. The causative mutation is a contraction in this repetitive DNA that permits the expression of a gene, DUX4, that is silent in unaffected individuals. DUX4 is toxic to muscle cells and its expression leads to muscle cell death.

    To address this pathogenic gene activation, Fulcrum is developing a small molecule that stabilizes the disease process through the restoration of the repressive DUX4 gene regulation.

    While there are steps that patients can take to minimize complications from FSHD, there are currently no known treatments that will reverse the muscle weakness and wasting in FSHD.

    Our approach to developing new medicines for Facioscapulohumeral Muscular Dystrophy

    Click to enlarge


    Our Patient Community Partner

Our Commitment

At Fulcrum –  above all else – our goal is to make a positive impact in the lives of patients and families impacted by severe disease.

For each of its two lead programs, Fulcrum is gratified to be working closely with patient groups who are partners in our search to better understand the disorders and to develop breakthrough medicines. For every program the company starts, we regard partnership with patient groups as essential to our work.