Announcement • Jul 16
Aelis Farma Receives Positive Recommendation from Independent Data Monitoring Committee to Continue Phase 2b Study of AEF0217 in People with Down Syndrome Without Modification
Aelis Farma announced that the Independent Data Monitoring Committee (IDMC) has recommended the continuation, without modification, of the ongoing Phase 2b clinical trial evaluating AEF0217 in adults and older adolescents with Down syndrome. The IDMC is an independent committee composed of experts in clinical pharmacology, clinical research, pediatrics and Down syndrome. Its role is to periodically review the safety and tolerability data generated during the study and provide independent recommendations regarding its continuation. The committee conducted the first scheduled safety review of the Phase 2b study after more than 30 participants had completed at least four weeks of treatment, in accordance with the study’s IDMC Charter. The review was based on blind safety data from 42 randomized participants, including 32 participants who had completed at least four weeks of treatment as of the June 4, 2026 data cut-off. The review showed that no severe or serious adverse events were reported, that all reported adverse events were mild and that no new safety concern was identified. In addition, none of the adverse events reported were considered by the investigators to be related to the investigational treatment. Finally, no participant discontinued treatment or withdrew from the study following randomization because of an adverse event. Following its review, the IDMC recommended that the trial proceed according to the current version of the protocol, without modifications. The findings from this first Phase 2b safety review are consistent with and further support the favourable safety and tolerability profile previously observed with AEF0217. In the previous randomized, double-blind, placebo-controlled Phase 1/2 study, 29 young adults with Down syndrome received either AEF0217 at 0.2 mg once daily or placebo for four weeks, according to a 2:1 randomization ratio. Safety and tolerability were the primary objectives of the study. In that study, adverse events were comparable between the AEF0217 and placebo groups, were predominantly mild and considered unrelated to treatment. No severe or serious adverse event was reported, and no participant discontinued treatment because of an adverse event. The current Phase 2b safety observations extend these earlier findings to the larger population of multi-country study which includes older adolescents and three doses of AEF0217—0.1 mg, 0.2 mg and 0.6 mg once daily. Taken together, the clinical data generated to date provide further support to the favourable safety profile of AEF0217 in people with Down syndrome. AEF0217 belongs to the new pharmacological class of Signaling Specific inhibitors of the CB1 receptor, or CB1-SSi, discovered and developed by Aelis Farma. CB1-SSi are based on the discovery of a natural regulatory mechanism used by the body to counteract pathological hyperactivity of the CB1 receptor. By mimicking this natural mechanism, CB1-SSi are designed to selectively inhibit the components of CB1 receptor signaling associated with diseases, while preserving the receptor’s normal physiological activity. This biomimetic and signaling-specific approach differs fundamentally from previous generations of CB1 receptor antagonists, which broadly blocked CB1 receptor activity and were associated with adverse effects that limited their clinical use. The favorable clinical safety observations obtained to date with AEF0217 are consistent with the expected profile of this selective pharmacological approach. The randomized, double-blind, placebo-controlled Phase 2b study is evaluating the efficacy, safety and tolerability of AEF0217 administered once daily for 24 weeks in adults and older adolescents with Down syndrome. A total of 188 participants aged 16 to 32 years are expected to be enrolled across clinical centers in France, Spain and Italy. Participants are randomized to receive one of three doses of AEF0217—0.1 mg, 0.2 mg or 0.6 mg—or placebo. To date, 65 participants have been randomized and 5 are currently completing the randomization process, representing approximately 37% of the planned study population. Aelis Farma maintains its objective of completing recruitment of all 188 participants before the end of 2026. Subject to the completion of recruitment and study follow-up as planned, the Company expects to report the study results by the end of 2027. The next planned IDMC review will assess the broader safety profile of AEF0217 once at least 40 participants have completed 12 weeks of treatment. AEF0217 is Aelis Farma’s second clinical-stage drug candidate and belongs to the new pharmacological class of Signaling Specific inhibitors of the CB1 receptor of the endocannabinoid system, or CB1-SSi, discovered and developed by the Company. Hyperactivity of the CB1 receptor is involved in several brain and peripheral disorders, including cognitive impairments associated with neurodevelopmental conditions and aging. Unlike previous-generation CB1 antagonists, which block the overall activity of the receptor, AEF0217 is designed to selectively inhibit only the components of CB1 signaling associated with pathological activity. This molecular selectivity is intended to preserve the receptor’s normal physiological functions while delivering beneficial pharmacodynamic and therapeutic effects. AEF0217 is being developed as a potential pharmacological treatment for cognitive impairments, with an initial focus on deficits in adaptive behavior and cognition associated with Down syndrome. AEF0217 has successfully completed a Phase 1 program in healthy volunteers, comprising three studies, as well as a randomized Phase 1/2 study in 29 young adults with Down syndrome, in which AEF0217 was well tolerated and showed statistically significant positive effects on adaptive behavior, cognition and electrophysiological parameters. The ongoing Phase 2b study (AEF0217-201) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 2b clinical trial designed to assess the efficacy, safety and tolerability of AEF0217 during 24 weeks of treatment. The study plans to enroll 188 participants aged 16 to 32 years, including older adolescents and young adults, who are randomized in a 1:1:1:1 ratio to receive AEF0217 at doses of 0.1 mg, 0.2 mg or 0.6 mg once daily, or matching placebo. The primary objective is to evaluate the effect of AEF0217 on adaptive behavior. The study also includes assessments of cognition, sleep, quality of life, safety and tolerability. The trial is being conducted at several clinical centers in France, Spain and Italy as part of the European H2020 ICOD project—Improving COgnition in Down syndrome, Grant Agreement No. 899986—which received EUR 6 million in funding from the European Commission.
