Facio validates over 300 compounds with the potential to tackle the cause of FSHD
April 3, 2017
Facio Therapies announced today that it has validated more than 300 compounds (so-called “hits”) that repress the production of the muscle-toxic DUX4 protein in cultured muscle cells derived from FSHD patient biopsies. Undue production of DUX4 in skeletal muscle is the cause of FSHD.
When produced in muscle tissue, DUX4 is highly toxic due to a cascade of events that eventually result in the devastating effects of FSHD. In people without FSHD, the production of DUX4 is repressed by regulatory mechanisms in the muscle cell. Facio’s single goal is to develop a therapy that restores this repression as much as possible.
In December 2016, Facio announced that, together with its drug discovery partner, Evotec, it had tested about 34,000 compounds using the first-ever screening platform that enables reliable quantification of natural DUX4 protein in cultured FSHD-affected muscle cells. The more than 300 hits now identified are labeled “validated” because they came through an extensive battery of tests. For example, their repressive effect on DUX4 in Facio’s screening system is reproducible and grows with increasing concentration, going as high as 100% repression. In addition, these compounds are not toxic to the muscle cells in Facio’s system.
“This is by far the largest recorded hit pool in the FSHD field”, commented David Dasberg, Facio’s Managing Director. “Even more important, our hits have been thoroughly validated and come out of a broad pool of compounds that we tested in our proprietary screening system uniquely capturing the natural biology of FSHD. We therefore have quantity as well as quality, but there is more. Perhaps the most exciting finding is that our hits span a variety of compound families with different biological modes of action. That raises the possibility of developing a portfolio of DUX4-repressing compounds, giving us multiple shots on goal.”
Facio and Evotec have begun work to further characterize the hits, especially with respect to how they work on DUX4. On that basis, selected hits will undergo chemical modification to optimize their safety and efficacy. “Hits are like raw material,” David Dasberg noted. “They are not directly therapeutics, and need to be refined in order to become truly viable drug candidates. That will take time, but we are definitely on our way.”
About Facio Therapies
Arising from the FSHD community, Facio is translating breakthrough results of 25 years of basic research into a therapy that stops the progressive muscle wasting caused by FSHD. That is Facio’s product mission. Facio also aims to make its therapy widely available by using a transparent model for fair and reimbursable pricing. That way, Facio aims to generate sustainable profits to fund additional quality-of-life projects for people with FSHD and to provide liquidity to its shareholders. That is Facio’s socio-economic mission.