Pipeline and Publications

Each of our product candidates within our FSHD, SCD and beta-thalassemia programs is a small-molecule therapeutic that aims to treat the root cause of a genetically defined rare disease. We plan to utilize our product engine to complete four new drug target identification screens in 2019 in Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), Friedreich’s ataxia (FA) and alpha-synucleinopathies. We expect to advance the most compelling programs identified for development.

Our goal: To employ our proprietary product engine to systematically identify and validate cellular drug targets that can modulate gene expression to treat the known root cause of genetically defined diseases.

Fulcrum rare disease pipeline

    PHASE 1
    PHASE 2
    PHASE 3
  • FSHD (losmapimod)
    Actively recruiting
  • Sickle Cell Disease (FTX‑HbF)
    HBG 1/2
    Submit IND in mid-2020
  • β-Thalassemia (FTX-HbF)
    HBG 1/2
    Submit IND in mid-2020
  • Duchenne Muscular Dystrophy
    Target ID / Validation
  • Friedreich Ataxia
    Target ID / Validation
  • Myotonic Dystrophy 1
    Target ID / Validation
  • α‑Synucleinopathies
    Target ID / Validation
Additional 6 screens planned for 2020

Broad potential to change lives

Our approach to drug discovery and development is applicable across a large number of genetically defined diseases. We have developed a rigorous assessment and selection process to determine which of the approximately 7,000 rare, genetically defined diseases we intend to evaluate in drug target identification activities. We are applying our product engine to discover drug targets to modulate gene expression and develop product candidates for the potential treatment of the root cause of these diseases.

Muscle Disorders


CNS Disorders

central nervous system

Blood Disorders

red blood cells

We create value through our pipeline

By staying true to our passion and always prioritizing patients first, we plan to progress our programs and create significant value for all of our stakeholders.


Supporting Literature

February 1, 2019

MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD

Leo H Wang, Seth D Friedman, Dennis Shaw, Lauren Snider, Chao-Jen Wong, Chris B Budech Sandra L Poliachik, Nancy E Gove, Leann M Lewis, Amy E Campbell, Richard J F L Lemmers, Silvère M Maarel, Stephen J Tapscott, Rabi N Tawil. Human Molecular Genetics (2019).

August 1, 2018

Facioscapulohumeral dystrophy: activating an early embryonic transcriptional program in human skeletal muscle

Amy E. Campbell, Andrea E. Belleville, Rebecca Resnick, Sean C. Shadle, Stephen J. Tapscott. Human Molecular Genetics (2018).

November 14, 2017

Adding quantitative muscle MRI to the FSHD clinical trial toolbox

Karlien Mul, Sanne C.C. Vincenten, Nicol C. Voermans, Richard J.L.F. Lemmers, Patrick J. van der Vliet, Silvère M. van der Maarel, George W. Padberg, Corinne G.C. Horlings, and Baziel G.M. van Engelen. Neurology (2017).

Fulcrum Publications

June 20, 2019

Losmapimod Reduces DUX4 Expression Across Genotypes in FSHD Patient-Derived Myotubes

Alejandro Rojas, Erin Valentine, Joseph Maglio, Anthony Accorsi, Alan Robertson, Ning Shen, Angela Cacace, Lucienne Ronco, Owen Wallace. Fulcrum Therapeutics.

June 20, 2019

Phase 1 Clinical Trial of Losmapimod in FSHD

Michelle L. Mellion [1], Lucienne Ronco [1], Drew Thompson [1], Michelle Hage [1], William Tracewell [1], Sander Brooks [2], Emilie van Brummelen [2], Lisa Pagan [2], Umesh Badrising [3], Baziel Van Engelen [4], Geert Jan Groeneveld [2,3], Diego Cadavid [1]
[1] Fulcrum Therapeutics, Cambridge, MA, USA, [2] Centre for Human Drug Research (CHDR), Leiden, NL, [3] Leiden University Medical Centre, Leiden, NL, [4] Radboud University Medical Centre, Nijmegen, NL

June 20, 2019

Safety and tolerability of losmapimod, a selective p38α/β MAPK inhibitor, for treatment of FSHD at its root cause

Diego Cadavid, Michelle Mellion, Owen Wallace, Lucienne Ronco, Drew Thompson, Alejandro Rojas, Michelle Hage, Robert Gould. Fulcrum Therapeutics.