RE104 · program
Luvesilocin (RE104) for Generalized anxiety disorder
Indications for RE104: Postpartum depression · Phase 2 Generalized anxiety disorder · Phase 2
Luvesilocin (RE104), a subcutaneous prodrug of the short-acting psychedelic 4-OH-DiPT, for generalized anxiety disorder — the third and newest RE104 indication, behind postpartum depression (lead) and adjustment disorder. RECLAIM (NCT07489651, RE104-203-GAD) is a multicenter, randomized, double-blind, PLACEBO-controlled Phase 2 in 64 adults with GAD, testing a single subcutaneous 30 mg dose against placebo with a primary endpoint of change from baseline in Hamilton Anxiety Rating Scale (HAM-A) total score at Week 4. It is the only RE104 trial to use a true placebo rather than a 1.5 mg active control, which should give a cleaner read on effect size than the dose-controlled PPD design did. The program was created and funded on 2025-09-16, when the Series A final tranche was upsized on the strength of the RECONNECT PPD efficacy result, and Reunion earmarked the proceeds for GAD expansion. Guidance was for a Q1 2026 start; the registry records an actual start of 2026-04-20 (recruiting). Estimated primary completion is February 2027 and the company expects data in Q2 2027. No results, publications or regulatory designations exist for this indication. The dose is carried over from PPD with no GAD-specific dose-ranging.
Development timeline
- UpcomingTopline results from the RECLAIM Phase 2 trial of a single 30 mg subcutaneous dose of RE104 versus placebo in generalized anxiety disorder (primary endpoint: change from baseline in HAM-A total score at Week 4), expected 2Q 2027.↗
- UpcomingClinicalTrials.gov estimated primary completion of RECLAIM (NCT07489651): February 2027, with estimated study completion April 2027.
- RECLAIM (NCT07489651, RE104-203-GAD) actual study start per ClinicalTrials.gov; status recruiting, record last updated 2026-06-26. Slipped roughly one quarter against the guided Q1 2026 initiation reiterated in the 2025-09-16 financing release and the 2026-01-12 milestones release. Reunion has never publicly characterised this as a delay.
- Program created and funded, before any trial existed: on final close of its Series A — upsized to $133 million because RECONNECT met prespecified efficacy parameters in PPD — Reunion announced plans to advance RE104 into clinical development for generalized anxiety disorder via a multicenter, randomized, double-blind, dose-controlled Phase 2 (RECLAIM) with a HAM-A Week 4 primary endpoint, guided to start in Q1 2026. Phase recorded as 'unknown' rather than 'phase_2' because on this date no GAD study had been designed into the registry and no patient had been dosed in this indication.↗
Readouts
- 2Q 2027AnticipatedTopline dataNCT07489651
Topline results from the RECLAIM Phase 2 trial of a single 30 mg subcutaneous dose of RE104 versus placebo in generalized anxiety disorder (primary endpoint: change from baseline in HAM-A total score at Week 4), expected 2Q 2027. ↗
- February 2027AnticipatedRegistry resultsNCT07489651
ClinicalTrials.gov estimated primary completion of RECLAIM (NCT07489651): February 2027, with estimated study completion April 2027.
Clinical trials in Generalized anxiety disorder
NCT07489651RE104-203-GADPhase 2Recruitingn=64
A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of RE104 for Injection in the Treatment of Generalized Anxiety Disorder — RECLAIM
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| RE104 for Injection (subcutaneous, single 30 mg dose)cleavable glutarate ester prodrug Single subcutaneous injection. Phase 2 RECLAIM (GAD): 30 mg vs placebo — the only RE104 trial to date using a true placebo comparator rather than a 1.5 mg active control. Phase 2 RECONNECT (PPD) and Phase 2 REKINDLE (adjustment disorder): 30 mg vs 1.5 mg active control. Phase 1 single ascending dose: 5, 10, 20, 30, 35 and 40 mg SC across six cohorts (36 active, 12 placebo). No GAD-specific dose-ranging was run; the 30 mg dose was carried over from the successful PPD study. No repeat-dose regimen has been studied. | Subcutaneous | Single dose | t½ 3.4 h · Tmax 1 h · F 88.6% |
Mechanism of action
RE104 is an inactive-by-design ester prodrug: it is cleaved to 4-OH-DiPT in under 30 minutes in mouse, rat and human plasma at 37 degrees C, and is undetectable in plasma within 5 minutes of subcutaneous administration in vivo. The prodrug itself binds 5-HT2A only weakly (Ki 4,300 nM) and is functionally inactive (inositol-phosphate EC50 >30,000 nM); the pharmacology belongs entirely to the liberated 4-OH-DiPT, which binds 5-HT2A with Ki 120 nM and behaves as a near-full agonist at 5-HT2A in G-protein dissociation assays, with agonist activity also at 5-HT2B and 5-HT2C. 4-OH-DiPT is a positional/alkyl analogue of psilocin and is reported to be more selective across the 5-HT receptor family than psilocin. It produces the head-twitch response in mice, and HTR intensity tracks plasma 4-OH-DiPT concentration (r-squared 0.7019), consistent with classical 5-HT2A psychedelic pharmacology. The anxiolytic rationale specific to this indication is preclinical: in mice, 4-OH-DiPT enhanced fear extinction by activating basolateral-amygdala interneurons via 5-HT2A to increase GABAergic inhibition of principal neurons — a plausible mechanism for suppressing learned fear, and the closest published mechanistic support for a generalized-anxiety indication. The defining property remains kinetic rather than receptor-level: subcutaneous delivery of a rapidly cleaved ester gives a Tmax of ~1 h and a terminal half-life of 2.72-4.12 h for 4-OH-DiPT, roughly halving the acute psychedelic window relative to psilocybin.
| Target | Action | Affinity |
|---|---|---|
| 5-HT2AprimaryHTR2A | Agonist | Ki 120 nMⓘ |
| 5-HT2BHTR2B | Agonist | —ⓘ |
← Full RE104 compound page (identity, identifiers, all indications)
Sources
- NCT07489651 (RE104-203-GAD, RECLAIM) — A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of RE104 for Injection in the Treatment of Generalized Anxiety Disorder — ClinicalTrials.gov (U.S. National Library of Medicine)
- RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine. ACS Chem Neurosci. 2024 Jun 19 — ACS Chemical Neuroscience (American Chemical Society) via PubMed Central
- Reunion Neuroscience — Programs: RECLAIM Phase 2 in GAD (multicenter, randomized, double-blind; data expected Q2 2027), plus PPD, adjustment disorder and the discovery-stage RE245 — Reunion Neuroscience Inc.
- Reunion Neuroscience Announces Final Closing of its Series A Financing and Plans to Advance RE104 into Clinical Development for Generalized Anxiety Disorder (GAD) (2025-09-16) — Series A upsized to $133 million — Reunion Neuroscience Inc. (via GlobeNewswire)
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study. J Clin Psychopharmacol. 2025 Sep-Oct — Journal of Clinical Psychopharmacology (Wolters Kluwer) via PubMed Central