Facio expands portfolio with 100+ novel, chemically diverse DUX4 repressorsLeiden, 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.”