Facio expands portfolio with 100+ novel, chemically diverse DUX4 repressors

Leiden, the Netherlands - March 21, 2019

Facio Therapies announced today that it has significantly expanded its portfolio of DUX4 repressors. After rigorous selection, Facio identified over 100 novel, chemically diverse small molecules that repress production of the human DUX4 protein in cultured FSHD-affected muscle cells. Facio is the only company known to have a pipeline of proprietary, chemically diverse small molecules that target the cause of FSHD.

The central event in the pathology of FSHD is the undue production of the DUX4 protein in skeletal muscle. DUX4 sets in motion a cascade of cellular events that eventually result in the devastating effects of FSHD. People with FSHD have a genetic defect that impairs the regulatory mechanisms by which DUX4 is prevented from being produced in muscle. Facio’s single goal is to develop therapies that restore the natural repression of DUX4 as much as possible.

Facio has consistently followed a product portfolio strategy. In 2018, Facio announced the selection of its first two compound series, which resulted from an initial screen of 34,000 compounds. Today, Facio revealed the completion of a complementary screen of 60,000 compounds. While the first screen also included 5,000 known compounds (i.e., compounds previously described in the literature in relation to conditions other than FSHD), the recent screen only included novel compounds.

Facio’s R&D Director, Joris De Maeyer, said: “It is very rewarding to see our early investment in a discovery engine delivering such a rich return. In addition to our first two compound series, all of the 100+ novel compounds now selected have proven to satisfy essential criteria as they concentration-dependently repress DUX4 production while leaving muscle cell formation intact. Given the wide chemical diversity embodied by these compounds, we now have the unique ability to build a comprehensive pipeline of proprietary small molecules that target the cause of FSHD. As a next step, the compounds are undergoing further rigorous tests in order to qualify as leads for further development.”

Commenting on the novelty of the compounds, Joris added: “There has been a growing interest in the potential of so-called drug repurposing in FSHD. This means that an approved drug or a drug candidate in clinical development for a condition other than FSHD is evaluated for its use in FSHD. Drug repurposing is attractive because certain available human clinical data may be incorporated in the clinical dossier, which shortens clinical development for FSHD. However, having applied our extensive set of screening and validation platforms to thousands of known drugs and drug candidates, we have not retained any drug repurposing candidates that qualify for further development in FSHD. This is because at their clinical exposure levels they have no meaningful effect on DUX4; because they impair the formation of muscle cells; or because they have an otherwise undesirable safety profile. We therefore focus on building a pipeline of proprietary products specifically discovered for targeting the cause of FSHD.”

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).