CTH120, A NOVEL TREATMENT FOR FRAGILE X SYNDROME AND OTHER NEURODEVELOPMENTAL DISORDERS

Background: CONNECTA Therapeutics’ CTH120 is a first-in-class small molecule targeting tropomyosin receptor kinase B (TrkB, NTRK2), a key mediator in neuroplasticity, the brain’s ability to reorganize, adapt, and form new neural connections. By modulating neuroplasticity, CTH120 has been designed to restore the disrupted neuronal architecture underlying neurodevelopmental disorders like Fragile X syndrome (FXS), the leading known cause of inherited intellectual disability.
Goals: Non-clinical studies aimed to demonstrate that the investigational medicinal product CTH120 holds the potential to improve, in a clinically relevant manner, disabling manifestations in neurodevelopmental disorders like FXS.
Methods: In vivo and ex vivo experiments in the Fmr1-KO mouse model of FXS, after acute and oral chronic administration, were performed to assess the efficacy of CTH120.
Results: CTH120 restored the cognitive and behavioural manifestations in the Fmr1-KO mice. Moreover, CTH120 also rescued the spine phenotype in FXS, normalizing spine density and morphology in treated mice.
Conclusions: These findings provide strong evidence supporting the efficacy of CTH120 in reversing core cognitive deficits and behavioural dysfunctions in FXS, confirming its therapeutic potential in FXS and other neurodevelopmental disorders.
On-going work: CTH120 is currently in Phase 2a clinical trial to assess its safety and efficacy in FXS adult males, following the Phase 1 clinical trial where the safety and tolerability of the product were demonstrated. Through the FRAXCURE project, co-funded by the European Union, CONNECTA is preparing additional non-clinical studies to include paediatric population and females in future clinical trials.
The pipeline is being extended to other molecules and indications.