Facio develops breakthrough tool for FSHD drug discoveryLeiden, the Netherlands - August 31, 2016
Facio Therapies has established the first-ever validated platform that enables screening large numbers of compounds for their ability to repress the production of the DUX4 protein in cultured muscle cells derived from FSHD patient biopsies. With this tool, Facio expects to identify series of compounds with the desired effect before the end of 2016.
Facio’s single focus is on developing a causal FSHD therapy. The key event in FSHD is the unwanted production of the DUX4 protein. When produced in muscle tissue, DUX4 is highly toxic due to a cascade of events eventually resulting in the devastating effects of FSHD. In people without FSHD, the production of DUX4 is repressed by regulatory mechanisms in the muscle cell. Therefore, Facio pursues a therapy that restores this repression as much as possible.
“To the best of our knowledge, this is a first”, said David Dasberg, Managing Director of Facio. “The reliable quantification of naturally occurring DUX4 in FSHD-affected skeletal muscle cells is extraordinarily difficult because it is an elusive protein with very low and variable expression levels. This challenge has, in fact, made large-scale screens on DUX4 impossible – until now. We are proud to have overcome this challenge in little more than a year.”
“By screening on DUX4 in a system that captures the natural complexity of FSHD, we maximize the potential to discover compounds that will be clinically meaningful,” added Kees van der Graaf, Chairman of Facio. “We therefore believe our platform represents a major leap for the FSHD community, from which we originate and to which we hold ourselves accountable.”
Facio expects to identify series of compounds with the desired effect (known as “hits”) over the next few months. These hits will undergo further extensive testing in order to generate so-called lead compounds suitable for development into a human therapeutic. Facio conducts its drug discovery program in close collaboration with Evotec International (Germany) and with the support of its academic partners.
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).