Why it matters: Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder and the most common known cause of inherited intellectual disability. Despite decades of drug development, no mechanistically targeted therapy has yet been approved.
- The condition is usually caused by an expansion in the FMR1 gene that switches the gene off, resulting in little or no FMRP protein. The resulting disruption of neuronal function can cause intellectual disability, learning difficulties, behavioral symptoms and features of autism.
Zoom in: New investor Clave Capital led the €3.1 million financing through its Innvierte Science Tech Clave Innohealth fund. Existing investors Inveready, CDTI Innvierte and Prous Institute for Biomedical Research also participated.
- Connecta has also attracted public funding around CTH120. A Spanish public-private project received €2.7 million to support the adult Phase 2a program in 2024, while the company secured a €2.5 million European Innovation Council grant for its FRAXCURE project to prepare CTH120 for pediatric development.
How it works: CTH120 is a small molecule targeting the tropomyosin receptor kinase B (TrkB), a receptor involved in neuroplasticity, the brain’s ability to form and adapt neural connections. Connecta says treatment improved cognitive and behavioral deficits and normalized abnormalities in neuronal connections in Fragile X mouse models.
- Connecta’s Phase 2a study is recruiting 30 men aged 18 to 45 and testing 75 mg of oral CTH120 twice daily against placebo. The randomized study began in May and is expected to complete in May 2027, with topline results planned for mid-2027.
- A previous Phase 1 trial in 76 healthy volunteers found CTH120 was safe and well tolerated, according to the company. The ongoing study is its first test in patients, meaning there is not yet clinical evidence that the drug improves Fragile X symptoms.
The big picture: Fragile X remains a difficult drug-development target. Shionogi’s PDE4D inhibitor zatolmilast recently missed the primary endpoints of pivotal studies, while Harmony Biosciences suspended development of its cannabidiol gel ZYN002 after another Phase 3 failure in 2025.
- Several mechanistically targeted programs nevertheless remain in development. Mirum Pharmaceuticals is testing another PDE4D inhibitor, MRM-3379, in a Phase 2 study with results expected in 2027, while Spinogenix is advancing the BK-channel modulator codabakalner into an adaptive Phase 2b/3 trial. Servier is also preparing clinical development of KER-0193, another BK-channel modulator acquired from Kaerus Bioscience in 2025.
What they’re saying: CEO Jordi Fàbrega said the mid-2027 Phase 2a readout will be “an important step in demonstrating the potential of CTH120 to address the underlying biology of the disease.”
What’s next: The 30-patient trial will provide the first indication of whether Connecta’s neuroplasticity approach can translate its preclinical findings into patients. In parallel, the company is preparing a future pediatric Fragile X study through FRAXCURE.
Sign up for our newsletter!
