Facio validates over 300 compounds with the potential to tackle the cause of FSHDLeiden, the Netherlands - April 3, 2017
Facio Therapies announced today that it has validated more than 300 compounds (so-called “hits”) that repress the production of the muscle-toxic DUX4 protein in cultured muscle cells derived from FSHD patient biopsies. Undue production of DUX4 in skeletal muscle is the cause of FSHD.
When produced in muscle tissue, DUX4 is highly toxic due to a cascade of events that eventually result in the devastating effects of FSHD. In people without FSHD, the production of DUX4 is repressed by regulatory mechanisms in the muscle cell. Facio’s single goal is to develop a therapy that restores this repression as much as possible.
In December 2016, Facio announced that, together with its drug discovery partner, Evotec, it had tested about 34,000 compounds using the first-ever screening platform that enables reliable quantification of natural DUX4 protein in cultured FSHD-affected muscle cells. The more than 300 hits now identified are labeled “validated” because they came through an extensive battery of tests. For example, their repressive effect on DUX4 in Facio’s screening system is reproducible and grows with increasing concentration, going as high as 100% repression. In addition, these compounds are not toxic to the muscle cells in Facio’s system.
“This is by far the largest recorded hit pool in the FSHD field”, commented David Dasberg, Facio’s Managing Director. “Even more important, our hits have been thoroughly validated and come out of a broad pool of compounds that we tested in our proprietary screening system uniquely capturing the natural biology of FSHD. We therefore have quantity as well as quality, but there is more. Perhaps the most exciting finding is that our hits span a variety of compound families with different biological modes of action. That raises the possibility of developing a portfolio of DUX4-repressing compounds, giving us multiple shots on goal.”
Facio and Evotec have begun work to further characterize the hits, especially with respect to how they work on DUX4. On that basis, selected hits will undergo chemical modification to optimize their safety and efficacy. “Hits are like raw material,” David Dasberg noted. “They are not directly therapeutics, and need to be refined in order to become truly viable drug candidates. That will take time, but we are definitely on our way.”
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).