Reunion Neuroscience Inc. announced the publication of the results of preclinical studies in ACS Chemical Neuroscience that validate the decisions to pursue RE104, a proprietary, patented prodrug of 4-OH-DiPT as a potential therapeutic in depressive disorders. The paper, titled ?RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine,? was co-authored by Robert Alexander, Ph.D., Reunion?s Chief Medical Officer, and Michael D. Ehlers, M.D., Ph.D., Chief Scientific Officer and Venture Partner at Apple Tree Partners, with Nathan Bryson, Ph.D., Reunion?s Chief Scientific Officer, as senior author.
RE104 is a 4-OH-DiPT prodrug comprising a glutarate pro-moiety that cleaves rapidly in situ, providing excellent bioavailability of the active drug shortly after administration. The newly published study describes the synthesis, as well as the chemical, preclinical, and translational characterization of RE104, including conversion to 4-OH-DiPT and subsequent metabolism in vivo. In a forced swim model of behavior to assess antidepressive activity, RE104 demonstrated efficacy similar to a psilocybin analog at Day 7, 14 and 28.
This study used RE109, a psilocin prodrug of similar structure to RE104, which is also described in the paper. The Company?s lead asset, RE104, is a proprietary, potential best-in-class, patented prodrug of 4-OH-DiPT. RE104 targets the serotonin 2A receptor (5HT2AR), which is the recognized target for the antidepressant effects of psychedelic compounds.
As psychedelic drugs require monitoring by trained healthcare providers, per recent FDA Guidance (June 2023), Reunion designed RE104 to deliver a short duration psychedelic experience and it requires only about half a day in-clinic, a significantly shorter time commitment than required for longer duration psychedelics, like psilocybin and MDMA. In a Phase 1 study, RE104 produced a psychedelic, psychoactive state similar in intensity and quality to psilocybin, but lasting only about half the time (3-4 hours) while demonstrating a similar, favorable safety profile. A Phase 2, Multicenter, Randomized, Double-Blind, Parallel-Group, Active Dose-Controlled study evaluating RE104 in moderate and severe PPD patients (The RECONNECT Trial) is expected to start enrolling patients this quarter (NCT06342310).
Results from the RECONNECT Trial are expected in Second Quarter 2025. Reunion is actively investigating the use of RE104 in additional neuropsychiatric indications, including adjustment disorder in cancer patients, where there remains a significant unmet need that is not addressed by the current standard of care.
About Reunion Neuroscience Inc.
Reunion Neuroscience is committed to pushing the boundaries of neuroscience to develop innovative therapeutic solutions for postpartum depression (PPD) and other underserved mental health disorders. In August of 2023, Reunion Neuroscience was acquired by MPM BioImpact, a world-leading biotechnology investment firm with three decades of experience creating and investing in innovative biotechnology companies seeking to deliver transformative therapies to patients. As part of the MPM BioImpact portfolio, the Company is evaluating its lead asset, RE104, a proprietary, potential best-in-class, serotonergic psychedelic compound and the only 4-OH-DiPT prodrug in clinical development, as a potential treatment for postpartum depression, (NCT06342310), that could provide rapid symptom relief and durable efficacy. Reunion is actively investigating the use of RE104 in additional neuropsychiatric indications where there remains a significant unmet need that is not addressed by the current standard of care.