AEF0217 · program

AEF0217 for Down Syndrome

Phase 2RecruitingAelis Farma S.A. (AELIS)

Lead indication. AEF0217 is in an international, multicenter Phase 2b dose-finding trial (NCT07334912; AEF0217-201) for behavioral and cognitive impairments in Down syndrome (Trisomy 21). The randomized, double-blind, placebo-controlled, parallel-group study plans to enroll ~188 participants aged 16-32 across 10 expert centers in France, Italy and Spain, comparing once-daily oral AEF0217 (0.1, 0.2 or 0.6 mg) to placebo for 24 weeks with an 8-week treatment-free follow-up. The primary endpoint is change from baseline at week 24 in the normalized scores of the nine subdomains of the Vineland Adaptive Behavior Scales, Third Edition (VABS-3). The first patient first visit was performed in December 2025 after regulatory approval, and recruitment was announced as successfully underway across all three countries in March 2026; preliminary results are expected in 2027. The program follows a positive Phase 1/2 study (NCT05748405) that met its safety primary and showed improvements in VABS adaptive-behavior domains and CB1-dependent EEG target engagement. On 2026-01-12, Aelis announced a positive opinion from the EMA Pediatric Committee (PDCO) on the Pediatric Investigation Plan (PIP) for AEF0217 in Down syndrome, agreeing a pediatric clinical program (birth to <18 years, stepwise descending approach) and accepting the current formulation and existing preclinical/PK package.

Data current as of

Development timeline

Phase 2Dec 2025 – Dec 2027
  1. UpcomingpendingPhase 2b dose-finding trial of AEF0217 in Down syndrome (NCT07334912): preliminary results anticipated in 2027.↗
  2. EMA Pediatric Committee (PDCO) delivered a positive opinion on the Pediatric Investigation Plan (PIP) for AEF0217 in Down syndrome, agreeing a stepwise pediatric program (birth to <18 years) and accepting the current formulation and preclinical/PK package.↗
  3. International Phase 2b dose-finding trial (NCT07334912; AEF0217-201) started; first patient first visit performed in December 2025 after initial regulatory approval, with recruitment underway across France, Italy and Spain (announced 2026-03-21).↗
Phase 1/2Dec 2022 – Nov 2024
  1. metPositive Phase 1/2 in young adults with Down syndrome: safety primary met; AEF0217 0.2 mg improved several VABS adaptive-behavior domains and modified a CB1-dependent EEG target-engagement marker vs placebo.↗
  2. Phase 1/2 trial (NCT05748405) completed (primary completion and completion date 2024-10-07). On 2024-11-18 Aelis announced positive results: the safety primary endpoint was met and AEF0217 0.2 mg improved several VABS adaptive-behavior domains and a CB1-dependent EEG target-engagement parameter vs placebo.↗
  3. First patient recruited into the Phase 1/2 trial (NCT05748405; AEF0217-102), a randomized, double-blind, placebo-controlled 4-week study in young adults with Down syndrome.

Readouts

  • 2027AnticipatedTopline datapendingNCT07334912

    Phase 2b dose-finding trial of AEF0217 in Down syndrome (NCT07334912): preliminary results anticipated in 2027. ↗

  • 2024-11-18ReportedTopline datametNCT05748405

    Positive Phase 1/2 in young adults with Down syndrome: safety primary met; AEF0217 0.2 mg improved several VABS adaptive-behavior domains and modified a CB1-dependent EEG target-engagement marker vs placebo. ↗

Clinical trials in Down Syndrome

NCT07334912AEF0217-201Phase 2Recruitingn=188

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase 2b Trial to Assess the Efficacy, Safety and Tolerability of AEF0217 for 24 Weeks in Adults and Older Adolescents With Down Syndrome

Started Dec 2025· Primary completion Dec 2027

NCT05748405AEF0217-102Phase 1/2Completedn=40

A Double-blind, Randomized, Placebo-controlled, 4-week, Phase 1/2 Trial in Young Adult Participants With Down Syndrome to Assess the Safety, Tolerability, Plasma Exposure, and Preliminary Indications of Pharmacodynamic Activity of AEF0217

Started Dec 2022· Primary completion Oct 2024

mixedexploratoryCognitive flexibility (NIH-Toolbox Cognitive Battery) and CB1-dependent EEG target engagement — cognitive flexibility trend P<0.09 (APOE4-negative); EEG working-memory activity decreased P<0.012; gamma ITC during 40 Hz ASSR modified P<0.05 (<0.05)

A consistent trend toward increased cognitive flexibility (P<0.09 in APOE4-negative participants) plus statistically significant changes in EEG parameters indicating reduced strain to perform a working-memory task and modification of a CB1-dependent EEG parameter (gamma intertrial coherence during the 40 Hz auditory steady-state response, P<0.05), supporting target engagement.

metsecondaryAdaptive behavior (Vineland Adaptive Behavior Scale, VABS) after 28 days, AEF0217 0.2 mg vs placebo — improved 5 of 9 VABS skills (e.g., expression P<0.002, personal daily living P<0.003, community living P<0.03, interpersonal relationships P<0.01) (<0.01)

AEF0217 0.2 mg significantly improved several VABS adaptive-behavior domains (communication/expression, daily living skills, social/interpersonal) vs placebo after 28 days. Company PR reports 29 participants randomized across two Spanish centers (Hospital del Mar, Barcelona; Hospital de la Princesa, Madrid); ClinicalTrials.gov lists enrollment of 40.

metprimarySafety and tolerability (incidence of adverse events / treatment-emergent AEs; ECG, vital signs, labs) — primary

AEF0217 was safe and well tolerated with no safety concerns identified, confirming it can be safely used in the fragile young-adult Down syndrome population (primary safety objective met).

Formulations

FormulationRouteRegimenPharmacokinetics
AEF0217 oral tablet
0.2 mg/day (2 x 0.1 mg tablets dispersed in 10 mL water) once daily for 28 days in the Phase 1/2 Down syndrome study
OralOnce daily—

Mechanism of action (compound-wide)

First-in-class CB1 receptor signaling-specific inhibitor (CB1-SSi), a pregnenolone-derived biased negative allosteric modulator of the CB1 cannabinoid receptor (CNR1). AEF0217 selectively inhibits a subset of disease-related CB1 signaling while preserving the receptor's physiological activity, providing the benefits of CB1 inhibition without the adverse psychiatric effects of orthosteric CB1 antagonists/inverse agonists (e.g., rimonabant). In Down syndrome, target engagement was supported by a statistically significant change in a CB1-dependent EEG parameter (gamma intertrial coherence during the 40 Hz auditory steady-state response) in the Phase 1/2 study, alongside improvements in adaptive behavior (VABS).

TargetActionAffinity
CB1primaryCNR1NAM—ⓘ

← Full AEF0217 compound page (identity, identifiers, all indications)

Sources

  1. AEF0217 in Participants With Down Syndrome — Phase 2b (NCT07334912; AEF0217-201) — ClinicalTrials.gov
  2. Aelis Farma announces the positive results of its clinical Phase 1/2 study with AEF0217 in young adults with Down syndrome — Aelis Farma / Euronext
  3. Aelis Farma announces the successful start of the recruitment of the Phase 2b clinical trial with AEF0217 for the treatment of behavioral and cognitive impairments of people with Down syndrome (Trisomy 21) — Aelis Farma / Euronext
  4. Aelis Farma receives a positive opinion from EMA Pediatric Committee on the Pediatric Investigation Plan for AEF0217 in Down syndrome — Aelis Farma / Business Wire (Morningstar mirror)
  5. CB1 receptor (cannabinoid receptor 1, gene CNR1) — IUPHAR/BPS Guide to PHARMACOLOGY, objectId 56 — IUPHAR/BPS Guide to PHARMACOLOGY
  6. Phase 1/2 Trial of AEF0217 in Participants With Down Syndrome (NCT05748405) - oral 0.2 mg/day once daily x 28 days — ClinicalTrials.gov