Facio selects first series of potential drug development candidates

Leiden, the Netherlands - January 19, 2018

Facio Therapies announced today that it has selected its first series of potential FSHD drug development candidates. This series comprises several families of small-molecule compounds that are associated with a narrowly defined target class. Neither the compound families nor the target class have ever 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 November 2017, Facio announced it had started building an innovative portfolio of potential drug development candidates based on a battery of tests using its screening platform. Today, Facio’s managing director, David Dasberg, explained Facio’s main selection criteria.

“Basically, a compound can only be developed into a therapeutic drug if it is safe, effective, and drugable,” he said. “In FSHD, safety is of prime importance as a therapy is likely to be chronic. As announced previously, we require compounds to leave muscle cell formation intact because that process underlies repair and regeneration of muscle tissue. In order to restrict the potential for undesired side effects, we also require that interaction between a compound and its target protein or enzyme, which via a certain pathway results in the desired downward effect on DUX4, be as selective as possible. For the same reason, we additionally require that the compound’s target itself be part of a limited number of pathways that, moreover, should not be key to any process basic to maintaining overall health. While we continue to work on the safety profile of our first series of small-molecule compounds, we can already disclose that they do not interfere with muscle cell formation and do show selective pharmacology.” 

David continued by pointing out that any compound purported to effectively reduce DUX4 levels should be shown to do exactly that. “Our screening platform remains the only system capable of reliably quantifying natural DUX4 protein in cultured FSHD-affected muscle cells. We have reproducibly shown that the compounds in our first series reduce DUX4 levels in a drug-like concentration-dependent fashion. Additionally, the chemical properties of these compounds should enable them to reach their target when administered systemically, for example through oral intake. In other words, indications are that these compounds are drugable. We now look forward to completing target validation for these compounds later this year. That is a crucial step in confirming their pharmacological effect on DUX4 levels.” 

While for competitive reasons the compound families in Facio’s first series or the associated target class were not identified at this time, Facio did disclose that drug repurposing – using a drug to treat a disease other than the disease(s) for which it is approved – is not involved. Having screened over 34,000 compounds, including marketed drugs, Facio found that only beta-2 adrenergic receptor (b-2AR) agonists, which have been approved for treatment of certain lung diseases, might qualify for repurposing in FSHD until, as announced last month, Facio discovered that these compounds show strong inhibition of muscle cell formation. According to the scientific literature, common side effects of b-2AR agonists include fast or irregular heartbeat, tremor, headache, nervousness, and anxiety. 

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).