A single subcutaneous dose of RE104 produced rapid and durable improvements in postpartum depression, supporting advancement into phase 3 development.
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.
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:
Baseline disease severity and duration were high in both arms of the study:
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%).
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
“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.
