CONNECTA Therapeutics starts Phase IIa trial of CTH120 in fragile X
CONNECTA Therapeutics has initiated a Phase IIa clinical trial of CTH120, its lead small-molecule candidate targeting the tropomyosin receptor kinase B (TrkB) pathway, in adult males with fragile X syndrome (FXS). The Barcelona-based company said the study builds on encouraging Phase I safety data and marks what it describes as a key value-inflection milestone for the business.
FXS is the most common inherited cause of intellectual disability, affecting an estimated three in every 10,000 individuals. The condition is caused by silencing of the FMR1 gene on the X chromosome, which disrupts production of a protein required for normal synaptic function. Despite decades of research, no disease-modifying therapy has received regulatory approval; available treatments address behavioural symptoms only.
Trial design and endpoints
The Phase IIa study is a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial registered under EU CT number 2025-522972-97-00. Thirty adult males aged 18 to 45 will be randomised 1:1 to receive CTH120 twice daily or placebo. The primary endpoint is safety and tolerability; secondary endpoints include pharmacokinetic characterisation and exploratory measures of clinical efficacy. The study will be conducted at Hospital del Mar Research Institute (HMRIB) in Barcelona and Parc Taulí Research and Innovation Institute Foundation (I3PT) in Sabadell, both of which have established expertise in neurodevelopmental disorders.
Principal investigator Rafael de la Torre Fornell, PharmD, PhD, at HMRIB said FXS "remains a condition with significant unmet medical need, with no approved disease-modifying treatments," adding that the Phase IIa trial "provides an important opportunity to evaluate a promising new mechanism of action." In parallel, a biomarker sub-study led by Mara Dierssen at the Centre for Genomic Regulation will aim to identify disease-specific biological indicators capable of tracking treatment response.
The trial has been authorised by the Spanish Agency of Medicines and Medical Devices (AEMPS) and is co-funded by the Spanish Ministry of Science, Innovation and Universities and the European Union's NextGenerationEU programme.
Market context and competitive landscape
The FXS therapeutic landscape has been the site of repeated late-stage failures. Roche and Novartis both terminated Phase 3 programmes targeting the mGluR5 pathway in the 2010s, and more recent entrants — including small-molecule and gene-therapy approaches — are at various preclinical and early clinical stages. CTH120's TrkB mechanism represents a distinct biological rationale, aiming to restore neuronal architecture rather than suppress a single pathway, though proof of clinical efficacy in humans remains to be established.
The broader rare neurodevelopmental disease sector has attracted sustained investor attention in recent years, driven partly by the FDA's Rare Pediatric Disease priority review voucher programme and the EU's orphan medicinal product framework, both of which offer commercial incentives that offset the challenge of small patient populations. CONNECTA says it is also preparing to advance CTH120 into paediatric populations under the FRAXCURE project, which is co-funded by the European Union. The company's preclinical platform additionally targets Rett syndrome, Down's syndrome, DiGeorge syndrome, and autism spectrum disorder, though none of these programmes have entered clinical development.
With a modest 30-patient study designed primarily around safety, the near-term catalyst for CONNECTA will be whether the trial generates sufficient efficacy signal in the secondary endpoints to justify a larger, powered study. Investors and potential partners will be closely watching the timing of topline data readout, which the company has not yet announced.