Reunion Neuroscience has announced the completion of patient enrollment and dosing in its RECONNECT Phase 2 clinical trial, which is evaluating RE104 for the treatment of moderate-to-severe postpartum depression (PPD). The company expects to report topline results from the study in the third quarter of 2025.
The trial, which enrolled 84 adult female patients, represents a significant milestone in the development of novel treatments for PPD, a condition characterized by persistent depression and anxiety in new mothers.
"The completion of patient dosing in RECONNECT is a noteworthy accomplishment and reflects the significant enthusiasm from new mothers and their doctors for options that can offer rapid relief for the persistent depression and anxiety that characterizes PPD," said Greg Mayes, President and Chief Executive Officer of Reunion. "Achieving this milestone on time and as planned per protocol also demonstrates the operational excellence of our team and clinical partners."
Trial Design and Endpoints
The RECONNECT Phase 2 clinical trial (NCT06342310) is being conducted across 38 clinical research sites in the United States. It employs a randomized, double-blind, parallel-group, active dose-controlled design to evaluate the safety and efficacy of a single subcutaneous dose of RE104.
The primary endpoint of the trial is the change from baseline at Day 7 in total Montgomery-Åsberg Depression Rating Scale (MADRS) score, a clinician-rated scale measuring depression severity. Key secondary endpoints include:
- Changes in MADRS at other timepoints
- Response rates (≥ 50% MADRS reduction)
- Remission rates (MADRS ≤ 10)
- Change in Hamilton Anxiety Rating Scale (HAM-A)
- Clinical Global Impression of severity and improvement
- Overall safety and tolerability
Mayes noted that the upcoming data readout "will provide key insights into RE104's potential as a fast-acting, short-duration psychedelic therapy for the treatment of PPD and other mental health disorders."
RE104: A Novel Approach to Psychedelic Therapy
RE104 is Reunion's lead product candidate, a proprietary prodrug of 4-OH-DiPT that has been designed to deliver a shorter psychedelic experience compared to traditional psychedelics like psilocybin or LSD.
In a Phase 1 clinical trial, RE104 produced an acute psychedelic state similar in intensity and quality to psilocybin, but lasting only about half the time (3-4 hours), while demonstrating a comparable safety profile. This shorter duration could potentially offer practical advantages for clinical use, making treatment sessions more manageable for both patients and healthcare providers.
The company will present a poster reviewing the Phase 1 results at the upcoming American Society of Clinical Psychopharmacology (ASCP) Annual Meeting on May 28, 2025, in Scottsdale, Arizona. The presentation will cover safety, pharmacokinetics, and pharmacodynamics data from the first-in-human trial.
Expanding Clinical Program
Beyond postpartum depression, Reunion is also preparing to evaluate RE104 for the treatment of adjustment disorder (AjD) in adult patients with cancer and other medical illnesses. The company has secured IRB approval and initiated site selection for REKINDLE, a Phase 2 clinical trial in this indication, with the first patient expected to be enrolled by mid-2025.
Adjustment disorder represents another area of significant unmet need, particularly among patients dealing with serious medical conditions who may experience psychological distress that doesn't respond adequately to conventional treatments.
Postpartum Depression: A Significant Unmet Need
Postpartum depression affects approximately 1 in 8 women who give birth in the United States, according to the Centers for Disease Control and Prevention. The condition can have serious consequences for both mothers and their infants, including impaired maternal-infant bonding, developmental delays in children, and in severe cases, thoughts of self-harm or harm to the infant.
Current treatment options for PPD include traditional antidepressants, which may take weeks to show effect, and brexanolone, an intravenous treatment that requires a 60-hour hospital stay. The development of a rapid-acting treatment with a shorter administration time could potentially address significant gaps in the current treatment landscape.
About Reunion Neuroscience
Reunion Neuroscience is a clinical-stage biopharmaceutical company focused on developing next-generation psychedelic-inspired therapeutic solutions for underserved mental health disorders. The company became private in 2023 and completed Series A financing in 2024, co-led by MPM BioImpact and Novo Holdings.
In addition to postpartum depression and adjustment disorder, Reunion is exploring the potential of RE104 in other neuropsychiatric indications where significant unmet needs remain despite current standard of care treatments.
