Facio builds innovative portfolio of potential drug development candidates

Leiden, the Netherlands - November 9, 2017

Facio Therapies announced today that it is building a portfolio of potential FSHD drug development candidates comprising small-molecule compounds that repress the production of the muscle-toxic protein, DUX4, while leaving muscle cell formation intact. Never before have any of these compounds been linked to FSHD in the scientific literature.

Undue production of DUX4 in skeletal muscle is the cause of FSHD. DUX4 sets in motion a cascade of biochemical events that eventually result in the devastating effects of FSHD. In people without FSHD, the production of DUX4 in skeletal muscle is repressed by regulatory mechanisms. Facio’s single goal is to develop a therapy that restores this repression as much as possible.

In April 2015, Facio announced partnering with Evotec to set up a screening program aimed at identifying small molecules showing activity as a potential treatment to stop the progression of FSHD. In April 2017, Facio announced that it had identified over 300 DUX4-repressing small molecules using the first-ever screening platform that enables reliable quantification of natural DUX4 protein in cultured skeletal muscle cells derived from FSHD patients. Facio’s DUX4 platform also makes it possible to quantify the effects of these compounds on the formation of muscle cells.

Now, extensive tests using a suite of analytical methods are producing a still growing variety of small molecules that repress DUX4 in a drug-like fashion while muscle cell formation stays intact. Moreover, these compounds are associated with novel mechanisms of action in FSHD and are not specific to one type of genetic background. In FSHD research, different genetic backgrounds have been linked to different levels of disease severity.

“We have taken the next step: laying a solid foundation for developing innovative therapeutic drugs for FSHD,” commented David Dasberg, Facio’s managing director, who added: “With a broad range of promising validated compound series, we will be able to make multiple shots on goal. We now look forward to selecting our top development candidates in the course of 2018.”

David also stressed the importance of investigating potential negative side effects of compounds early on. “Healthy skeletal muscle is maintained by repair and regeneration mechanisms that involve the formation of new muscle cells. Due to the biochemical cascade caused by DUX4, FSHD patients lose skeletal muscle function, so the last thing you want to see is additional loss of muscle function as a side effect of treatment. However, that is just what might happen if FSHD patients would be exposed to compounds that appear to lower DUX4 levels but also interfere with the formation of muscle cells. Because we built our platform on primary human cells, we are able to only take forward those compounds that truly repress DUX4 and leave muscle cell formation intact,” he explained, while noting that so far this issue has received little or no attention in the scientific literature.

About FSHD

FSHD (facioscapulohumeral dystrophy) is a skeletal muscle wasting disease that devastates the lives of over 700,000 people worldwide and those close to them. The loss of muscle strength has a huge impact on daily life. Living with FSHD means living with pain, fatigue, and social isolation. Above all, the future becomes uncertain because the course of the disease is unpredictable. About 20% of people with FSHD end up in a wheelchair. Currently, no therapy for FSHD is available other than forms of temporary symptomatic relief.

About Facio Therapies BV

Facio Therapies, established in 2014, is a Netherlands-based company with a single focus: to overcome FSHD by developing a causal therapy that restores the natural repression of the muscle-toxic protein, DUX4. When unduly produced in skeletal muscle, DUX4 sets in motion a cascade of cellular events that eventually result in the muscle wasting seen in FSHD. Facio is the only one in the FSHD field with a fully automated, high-throughput screening platform based on quantifying the DUX4 protein in unadulterated (“primary”) FSHD-affected muscle cells. Facio delivered the first-ever therapeutically relevant proof of principle in FSHD by showing that one of its lead candidates, an orally active small molecule, represses DUX4 levels produced by human FSHD-affected muscle cells in a unique animal model (“in vivo”).

Rooted in, and dedicated to working for the FSHD community, Facio’s business approach is to have a positive impact on lives rather than to maximize financial gain. Since inception, Facio has raised over €16M in equity funding from FSHD-affected families, their friends, FSHD foundations, and Facio’s drug discovery partner, Evotec. Facio’s Board consists of business leaders from the FSHD community – Kees van der Graaf (Chairman; Netherlands), Neil Camarta (Canada), Dave Mackay (USA), Bill Moss (Australia), and Chip Wilson (Canada) – and Evotec’s CSO, Cord Dohrmann (Germany).