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 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.

Fulcrum Therapeutics Pipeline

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.

Neuromuscular Disorders

  • Facioscapulohumeral muscular dystrophy
    • •   IND-Enabling studies ongoing
    • •   Anticipated 2019 IND filing
    • •   Ongoing clinical biomarker studies

    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.

    Fulcrum has discovered a novel biochemical mechanism to restore repressive DUX4 gene regulation. We are currently conducting IND-enabling studies for a small molecule inhibitor of this mechanism, and anticipate filing an IND in early 2019.

    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.

    FSHD Patient Resources

    Fulcrum is proud to partner with the FSHD advocacy community to advance new therapies for patients and their families. The short videos below offer additional information about the disease as well as ongoing research efforts to support the development of new treatments:

    FSHD 101

    Into The Light: The FSH Society's journey to solve FSH muscular dystrophy

    Growing up with FSHD: A short documentary

    Our approach to developing new medicines for Facioscapulohumeral Muscular Dystrophy

    Click to enlarge


  • Duchenne muscular dystrophy

    Duchenne Muscular Dystrophy (DMD) is an incurable, life-limiting disease characterized by muscle weakness and loss, including the cardiac muscle. DMD is found in about 1 in 5,000 males. Nearly 1,000 boys in the U.S. and EU are diagnosed with DMD each year. Although care for DMD patients has improved in recent years, there remains no cure for DMD. The average life expectancy is only in the mid-20s, often limited by the cardiac aspects of the disease.

    DMD is caused by mutations in the gene dystrophin (DMD). The dystrophin protein provides a critical connection between the cytoskeleton and extracellular matrix of a muscle fiber. Dystrophin is required for proper muscle function, but its function can be satisfied by expression of a related protein, utrophin (UTRN).

    Fulcrum is developing a small molecule medicine that enhances the expression of UTRN.

    There is currently no cure for DMD or treatment of the cardiac aspects. Fulcrum seeks to provide the first medicine that modifies both the skeletal and cardiac muscle aspects of the disease.

Our patient community partners

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 DNA of 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 silencing 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.

  • α-synuclein / Parkinson's Disease

    Neurodegeneration is one of the greatest human health challenges of our time. Fulcrum is applying its precision medicine product engine to neurodegeneration, with a first application on alpha-synuclein (α-syn). α-syn is an abundant protein in the human brain that has the potential to from insoluble aggregates (Lewy bodies) that characterize multiple pathologic conditions, including: multiple systems atrophy (MSA), Lewy Body Dementia, and Parkinson’s Disease.

    Fulcrum is developing a blood brain barrier penetrant small molecule that represses α-syn expression. Through repression of α-syn, this medicine will halt α-syn mediated neurodegeneration. Fulcrum will develop a precision medicine for genetically-defined α-synucleinopathy patient populations.

    There is currently no cure for α-syn mediated neurodegeneration.

Our patient community partners

Hematologic Disorders

  • Sickle cell disease

    Sickle Cell Disease (SCD) is an incurable, life-limiting disease. SCD leads to Sickle-cell crisis (attacks of pain), anemia, profound swelling, infections, ischemic events, and reduced life expectancy. SCD affects greater than 4 million people in the world and nearly 200,000 people in the U.S. and EU. Despite advances in the management, SCD remains a major burden for patients and healthcare systems.

    SCD is caused by mutations in the β-globin gene (HBB). β-globin partners with α-globin to create human, adult hemoglobin. In the presence of HBB mutations the hemoglobin has an altered affinity for oxygen. This leads to the characteristic sickled red blood cells responsible for SCD pathology. A form of globin named γ-globin is made early in life and can substitute for β-globin.

    Fulcrum is developing a small molecule medicine that activates γ-globin. γ-globin combines with α-globin to form a healthy form of hemoglobin, fetal hemoglobin. Fetal hemoglobin has been shown to rescue SCD in the context of individuals who have a hereditary persistence of fetal hemoglobin.

    There is currently no cure for SCD.

Sponsored Research Studies

Fulcrum is committed to working with academic scientists, key thought leaders, and patients to identify disease-relevant biomarkers, and to define clinically meaningful outcomes. We intend to rapidly and efficiently transition our discoveries into clinical development strategies. Learn more about these studies here:

Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD (ReSolve FSHD)

FXS – Hair Follicle Pilot Study