Aelis Farma gets EMA nod for phase 2B trial of AEF0217 in down syndrome

AEF0217 is a first-in-class CB1 receptor signaling-specific inhibitor

Aelis Farma, a clinical-stage biopharmaceutical company developing treatments for brain and peripheral disorders involving the CB1 receptor, has received all necessary regulatory approvals to begin a multinational Phase 2B clinical trial of AEF0217 in individuals with down syndrome.

The authorizations were granted by the European Medicines Agency (EMA) through the Clinical Trials Information System (CTIS), as well as by national competent authorities and ethics committees in France, Italy, and Spain.

AEF0217 is a first-in-class CB1 receptor signaling-specific inhibitor (CB1-SSi), designed to selectively modulate only certain CB1 receptor pathways. This novel mechanism enables therapeutic effects while avoiding the adverse events that led to the discontinuation of earlier CB1 antagonists, which non-selectively blocked all CB1 activity. AEF0217 is being developed as a potential first pharmacological treatment for adaptive behavior and cognitive impairments associated with neurodevelopmental disorders, including Down syndrome.

AEF0217 has already demonstrated encouraging results in a Phase 1/2 randomized, double-blind, placebo-controlled trial in 29 young adults with Down syndrome. Reported in November 2024, the study showed a very favorable safety and pharmacokinetic profile and, after just four weeks of treatment, produced statistically significant improvements in adaptive behaviors measured by the Vineland Adaptive Behavior Scales (VABS), along with meaningful changes in brain activity.

The newly authorized Phase 2B trial is designed to confirm and expand these findings in a larger population and over a longer treatment period. This randomized, double-blind, placebo-controlled study will enroll 188 participants aged 16 to 32 years across ten specialized centers in France, Italy, and Spain. Participants will receive one of three daily doses of AEF0217 (0.1 mg, 0.2 mg, or 0.6 mg) or placebo for 24 weeks, followed by an eight-week follow-up period.

Professor Rafael de la Torre Fornell, principal investigator and global coordinator of the study, commented: “Following the positive results from the Phase 1/2 trial, our teams in Barcelona, along with colleagues in France and Italy, are pleased to launch this pivotal Phase 2B study. There are currently no approved pharmacological treatments for the adaptive behavioral and cognitive difficulties associated with Down syndrome. Demonstrating benefits with AEF0217 in a trial of this scale could prove transformative for individuals and families living with these challenges.”

Pier Vincenzo Piazza, CEO of Aelis Farma, added: “The launch of this innovative Phase 2B trial marks a major milestone for our program and for the development of CB1-SSi therapeutics. We are pleased that regulatory authorities have endorsed the novel analyses and assessments specifically adapted to the needs of individuals with Down syndrome. Building on the strong results from the Phase 1/2 study, this trial aims to confirm the therapeutic potential of AEF0217 and pave the way for Phase 3 development. I want to thank our teams, investigators, and the many families who contributed to designing a trial tailored to the needs of people with Down syndrome.”