Fulcrum plans to launch a Phase 2b clinical trial in FSHD in mid-2019
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Fulcrum
Therapeutics, a biotechnology company focused on discovering and
developing therapies to rebalance gene expression, today announced an
exclusive worldwide license agreement with GlaxoSmithKline (GSK) for
development and commercialization of the investigational drug
losmapimod. Fulcrum intends to advance losmapimod into a Phase 2b trial
in the rare and devastating genetic disease facioscapulohumeral muscular
dystrophy (FSHD), for which there are currently no approved treatments.
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.
“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. 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,”
said Robert J. Gould, Ph.D., Fulcrum’s president and chief executive
officer. “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.”
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, a
progressive muscle wasting disorder. Losmapimod is a selective p38α/β
MAPK inhibitor that GSK has tested extensively in clinical trials, but
never in muscular dystrophies. 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.
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.
The data provide evidence that losmapimod is a well-tolerated agent.
Fulcrum has conducted preclinical testing of losmapimod in
patient-derived cell models and observed precise and potent
downregulation of DUX4 expression and restoration of a healthy muscle
phenotype without an effect on myogenesis. Fulcrum has developed an
extensive clinical trial network of physicians working on FSHD. An
ongoing natural history study of the disease is informing the clinical
development plan. Fulcrum expects to initiate a Phase 2b clinical trial
of losmapimod in patients with FSHD at multiple clinical sites in the
U.S. and Europe in mid-2019.
About 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, leading to an inability to smile. The
weakness progresses to the upper body and advances to the lower limbs,
leaving many patients unable to lift their arms above shoulder level or
to rise from a sitting position. People with FSHD often have difficulty
performing daily tasks on their own and may experience severe fatigue
and pain. FSHD is caused by a single gene, DUX4, which is normally
switched off at the earliest stages of embryonic development. Patients
with FSHD have a mutation that causes the gene to remain “on” and to
continue producing a protein toxic to muscle tissue.
About Losmapimod
Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK)
inhibitor initially developed by GlaxoSmithKline and in-licensed by
Fulcrum Therapeutics. Fulcrum identified the compound as a potent
regulator of the expression of the DUX4 gene, which causes FSHD.
Losmapimod has been evaluated in more than 3,500 healthy volunteers and
patients in 24 clinical trials across multiple indications, including in
several Phase 2 trials and a Phase 3 trial. It has been shown to be
generally well-tolerated.
About Fulcrum Therapeutics
Fulcrum Therapeutics is discovering and developing small molecule
therapies to treat genetically defined diseases at their root cause by
modulating the expression of the genes known to drive or ameliorate
disease. Fulcrum’s proprietary approach to studying disease biology in
patient-derived and other relevant human cell lines, coupled with a
computational biology engine, generates valuable insights into a wide
array of genetically defined diseases. Please visit www.fulcrumtx.com.
Contacts
Stephanie Simon
Ten Bridge Communications
stephanie@tenbridgecommunications.com
617-581-9333