information: Interim results
Announcement: undisclosed lead candidate
Company: Facio Therapies (The Netherlands)
Disease: facioscapulohumeral dystrophy (FSHD)
area: Rare diseases - Genetic diseases - Neuromuscular diseases
- • On October 31, 2018, Facio Therapies announced that oral treatment with one of its lead candidates results in significant reduction of the human muscle-toxic DUX4 protein in mice engrafted with human FSHD-affected muscle cells. Facio is the first in the FSHD field to achieve proof of principle in an animal model.
- 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.
- Together with its drug discovery partner, Evotec, Facio successfully developed a stable mouse model based on engrafting human FSHD-affected myoblasts onto a mouse thigh muscle. These human FSHD myoblasts then fuse and develop into mature muscle cells (myotubes), which produce DUX4. Facio’s mouse model represents an important improvement over similar models, which either rely on engrafting human myotubes with low throughput, or on engrafting so-called “immortalized” FSHD cells that deviate from natural FSHD biology because they have been altered to remain alive indefinitely. Facio, however, approximates natural FSHD biology as much as possible by using unadulterated (or “primary”) FSHD-affected muscle cells in its mouse model. Primary FSHD muscle cells are also the basis of Facio’s unique high-throughput DUX4 screening platform.
- Facio has begun expanding its in vivo proof of principle by including other lead candidates, by performing dose-response experiments, and by studying the effect of lead candidates on human muscle cell formation. Together with lead optimization, this will enable selecting two lead compounds for government-mandated pre-clinical safety studies. The lead compound with the best overall performance in terms of efficacy and safety will be taken into a first-in-human clinical trial. As announced previously, Facio currently plans to start a first-in-human trial in the second half of 2021. In consultation with leading clinical experts, Facio is developing an integrated regulatory and clinical development strategy specific to FSHD.