Reunion Neuroscience's RE104 Meets Primary Endpoint in Phase 2 Postpartum Depression Trial, Advances to Phase 3
核心洞察
RE104, a novel psychedelic prodrug, demonstrated a statistically significant 23.0-point reduction in depression scores on Day 7 in the RECONNECT Phase 2 trial for postpartum depression (搜索) (p=0.0094).
The single subcutaneous dose showed rapid and durable efficacy starting as early as Day 1 and continuing through Day 28, with substantial improvements across mood and anxiety measures.
Following FDA alignment on the registrational path, Reunion Neuroscience (搜索) plans to initiate a pivotal Phase 3 trial in 2026, with a single successful trial potentially sufficient for registration.
Reunion Neuroscience (搜索) has achieved a significant milestone in postpartum depression (搜索) treatment, with its lead candidate RE104 meeting the primary endpoint in the Phase 2 RECONNECT clinical trial. The novel psychedelic prodrug demonstrated a statistically significant 23.0-point reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) total score on Day 7 compared to control (p=0.0094), marking a potentially transformative approach to treating this common pregnancy complication.
Rapid and Sustained Therapeutic Benefits
The RECONNECT trial enrolled 84 adult female patients with moderate-to-severe postpartum depression (搜索), defined as a Hamilton Depression Rating Scale (HAMD-17) score of ≥24. Patients were randomized to receive either a single 30mg subcutaneous dose of RE104 or a subperceptual 1.5mg control dose. The treatment groups showed similar baseline characteristics, with patients in the 30mg group presenting an average MADRS total score of 33.4 and 7.64 months duration of disease.
RE104's therapeutic effects emerged remarkably quickly, with clinically meaningful reductions in MADRS scores observed as early as Day 1 following administration. These improvements were maintained throughout the 28-day follow-up period, demonstrating the durability of the single-dose treatment approach. The drug also showed substantial improvements across key secondary endpoints, including MADRS response and remission rates, as well as other measures of postpartum depression (搜索) symptoms.
"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, M.D., Chief Medical Officer of Reunion. "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."
FDA Alignment Accelerates Development Timeline
Following the successful Phase 2 results, Reunion completed an End-of-Phase 2 meeting with the FDA in December 2025, receiving critical guidance on the registrational pathway. Based on FDA feedback, the company expects that results from a single Phase 3 trial, if successful, would complete the data package required to support potential registration of RE104 for postpartum depression (搜索).
The FDA also provided supportive feedback regarding the enrollment of breastfeeding women in the planned Phase 3 trial, with mothers able to return to breastfeeding on the same day of treatment following discharge. This represents a significant advantage for new mothers who wish to continue breastfeeding while receiving treatment for postpartum depression (搜索).
Reunion plans to initiate the pivotal Phase 3 trial in 2026, positioning RE104 as a potential first-in-class treatment for a condition that affects 12.5 percent of new mothers within the first year of giving birth.
Expanding Therapeutic Applications
Beyond postpartum depression (搜索), Reunion is advancing RE104 across multiple mental health indications. The company is currently enrolling patients in the Phase 2 REKINDLE trial (NCT07002034) evaluating RE104 in adjustment disorder (搜索) related to cancer and other medical illnesses, with topline data expected in the first quarter of 2027.
Additionally, Reunion plans to commence the Phase 2 RECLAIM clinical trial in generalized anxiety disorder (搜索) during the first quarter of 2026. This indication expansion strategy leverages the RECONNECT data to de-risk development across other mental health disorders characterized by depression and anxiety.
"We are entering 2026 with tremendous momentum across our business," said Greg Mayes, President and Chief Executive Officer of Reunion Neuroscience (搜索). "These results unlock a blockbuster opportunity in PPD, where we believe we are advancing a best-in-class therapy poised to disrupt a significant and still underserved market."
Novel Mechanism and Design
RE104 is a proprietary, patented prodrug of 4-OH-DiPT (搜索), administered via a single subcutaneous injection. Reunion designed the compound to deliver a shorter acute psychoactive experience compared to longer-duration psychedelics such as psilocybin or LSD, potentially improving patient acceptability and clinical practicality.
The company is also developing RE245, a non-psychedelic serotonergic neuroplastogen designed to deliver 5HT2A (搜索)-mediated neuroplasticity without producing hallucinations or cardiotoxicity. Reunion plans to file an investigational new drug application for RE245 in 2026 and commence Phase 1 trials in 2027.