Facio selects lead candidates for FSHD drug development

Leiden, the Netherlands - September 11, 2018

Facio Therapies announced today that it has selected several small-molecule compounds as lead candidates for FSHD drug development. Representing a novel mechanism to repress DUX4, these compounds selectively target an enzyme that is active in FSHD-affected muscle cells.

The key event in FSHD is the undue production of the DUX4 protein in skeletal muscle. 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 therapies that restore this repression as much as possible.

In January 2018, Facio announced the selection of a first series of potential drug development candidates spanning various families of DUX4-reducing small molecules. Facio’s lead candidates were selected from two such families. Based on extensive in vitro experimentation, Facio disclosed today that its lead candidates

  • reduce DUX4 expression in a concentration-dependent, drug-like fashion;
  • selectively inhibit an enzyme that is active in FSHD-affected muscle cells;
  • have the chemical properties required for entering FSHD-affected muscle cells from the bloodstream (after, for example, oral intake); and
  • leave intact the mechanism underlying muscle repair and regeneration in FSHD.

In addition, Facio found early indications that its lead candidates may also directly affect inflammatory processes, next to selective inhibition of the target enzyme. “This offers an exciting perspective because inflammation is a major cause of the progressive muscle damage seen in FSHD,” noted David Dasberg, Facio’s Managing Director. “The mechanism of action of our lead candidates may therefore provide a unique window on the relationship between the molecular event of DUX4 expression and the clinical event of inflammation.”

Next, Facio will tweak the chemical structure of its lead candidates in order to optimize their safety/efficacy profile for FSHD. David explained: “Lead optimization is crucial because it increases the chances of ultimate success in clinical studies. It is sometimes thought that promising compounds emerging from a screening campaign are fit for clinical testing for FSHD, but in reality they must undergo chemical modification in order to allow responsible use as a drug for FSHD.”

Finally, Facio plans to take one or two optimized lead compounds into pre-clinical testing (government-mandated toxicity studies in laboratory animals), which is the last stage before clinical studies. Facio currently envisages its first-in-human trial to start in 2021. David: “As a company founded and financed by FSHD-affected families and their friends, we want to move ahead as quickly as possible, but not at the expense of quality. Because progress creates hope, it must be founded in rigorous research.”

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).