RE104 30 mg demonstrates efficacy and safety in new phase 2 data for postpartum depression

Full results from a phase 2 clinical trial suggest that a single dose of RE104 may deliver rapid and sustained symptom improvement in women with moderate-to-severe postpartum depression (PPD), according to data presented by Reunion Neuroscience at the American College of Neuropsychopharmacology (ACNP) Annual Meeting.¹

According to a press release from Reunion, the company is aligned with the FDA for a registrational path for RE104—a proprietary, potential best-in-class, patented prodrug of 4-OH-DiPT, administered via a single subcutaneous injection—to initiate a phase 3 trial in 2026.

Results of phase 2 RECONNECT trial of RE104 for postpartum depression

The RECONNECT Phase 2 trial (NCT06342310)² evaluated RE104 in adult females with moderate-to-severe PPD. The primary end point of a statistically significant and clinically meaningful reduction of the Montgomery-Åsberg Depression Rating Scale (MADRS) on day 7 was met. Clinically meaningful reductions in MADRS scores were observed as early as the first day following administration of RE104 30 mg and were maintained through the 28-day follow-up period, as approximately 70% of participants who received RE104 were in remission by day 7 and through day 28, according to a study poster presented at ACNP.^1,2

Specifically, at day 7, “MADRS response was observed in 77.1% of participants receiving 30 mg RE104 compared with 61.5% of participants receiving 1.5 mg RE104,” with 71.4% of participants who received RE104 having achieved MADRS remission vs 41% of participants on 1.5 mg RE104.

Key study characteristics included:

• 84 adult female patients with moderate-to-severe PPD
• PPD defined as a Hamilton Depression Rating Scale (HAMD-17) score of 24 or higher
• Randomization to RE104 30 mg or a subperceptual 1.5 mg dose
• Generally similar baseline demographics between treatment groups

Baseline disease severity and duration were high in both arms of the study:

• In the 30 mg group, the average MADRS score was 33.4, and the average duration of disease was 7.64 months
• In the 1.5 mg group, the average MADRS score was 33.2, and the average duration of disease was 7.02 months

A higher proportion of patients receiving the 30 mg dose were on concurrent treatment at baseline, including selective serotonin reuptake inhibitors, psychotherapy, or both (31.7% versus 14.0%).

Broad improvements across secondary end points

In addition to the primary end point, RE104 demonstrated substantial and clinically meaningful improvements across multiple secondary end points. These included MADRS response rates defined as at least a 50% reduction in score, remission rates defined as a MADRS score of 10 or lower, and improvements on the Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression–Improvement scale (CGI-S), and the Barkin Index of Maternal Function (BIMF):²

• HAM-A: On day 7, 65.7% of participants receiving 30 mg RE104 and 52.6% of participants receiving 1.5 mg RE104 achieved a HAM-A response, which was maintained through day 28
• BIMF: On day 7, mean change from baseline in BIMF score (30 mg RE104: 65.4 [16.0]; 1.5 mf RE104: 68.6[16.2]) was 30.7 in the 30 mg RE104 arm vs 18.6 in the 1.5 mg arm (P < 0.01). At day 28, mean change was recorded as 31.8 in the 30 mg arm vs 23.9 in the 1.mg arm (P < 0.05).

“These data demonstrate the totality of RE104’s rapid and durable impact – across a range of physician- and patient-reported outcomes and measures of depression, anxiety and well-being,” said Mark Pollack, MD, chief medical officer of Reunion Neuroscience, in a statement. Together, these data highlight the ability of a single dose of RE104 to deliver a rapid, sustained benefit, potentially changing the course of a disease that can otherwise have significant negative impacts on mothers and their babies. We look forward to advancing into a pivotal Phase 3 trial this year, as we work to deliver a much-needed option to women facing the serious complications of PPD.”¹

References:

1. Reunion Neuroscience presents full data from RECONNECT phase 2 clinical trial of RE104 for the treatment of postpartum depression at ACNP Annual Meeting. Reunion Neuroscience. Press release. Published January 20, 2026. Accessed January 20, 2026. https://reunionneuro.com/2026/01/20/reunion-neuroscience-presents-full-data-from-reconnect-phase-2-clinical-trial-of-re104-for-the-treatment-of-postpartum-depression-ppd-at-acnp-annual-meeting/

2. Clayton AH, Hoffman MC, Hendricks PS, et al. RE104: A novel serotonergic psychedelic 4-OH-DiPT prodrug for the treatment of postpartum depression. Poster. Presented at: American College of Neuropsychopharmacology Annual Meeting. January 12-15, 2026. Paradise Island, Bahamas.