Reunion Neuroscience’s RECONNECT Phase 2 trial in postpartum depression met its primary endpoint with a clinically meaningful reduction in MADRS through Day 28 following a single subcutaneous dose of RE104, alongside a favorable safety and tolerability profile. Those data are informing a Phase 3 start in 2026 and anchor the company’s expansion into adjacent mood and anxiety indications.
The company has now dosed the first patient in REKINDLE, a randomized, double-blind, parallel-group, dose-controlled Phase 2 study of RE104 in adjustment disorder among adults with cancer and other medical illnesses (NCT07002034). The trial’s primary endpoint is change from baseline in MADRS, with HAM-A as a key secondary, and topline results are expected in 2027. RE104, a patented subcutaneous prodrug of 4-OH-DiPT designed for a shorter acute psychedelic experience than psilocybin or LSD, is also slated to enter a Phase 2 study in generalized anxiety disorder in the first quarter of 2026.
The move into adjustment disorder is a calculated attempt to leverage a rapid-acting, single-dose paradigm in an indication with no FDA-approved therapies and substantial off-label variability. It also tests whether the shorter-session profile of RE104 can address a core bottleneck that has hamstrung psychedelic development: therapy room time, staffing intensity, and site throughput. By targeting patients embedded within oncology and other specialty care pathways, Reunion is positioning RE104 where screening and referral could be operationally streamlined and where symptom relief may have a downstream impact on adherence and medical outcomes.
Execution risk in REKINDLE is nontrivial. Adjustment disorder is heterogeneous in precipitating stressors, symptom mix, and natural course, driving high placebo response and endpoint sensitivity. The choice of MADRS in a population that often presents with mixed depression and anxiety will place added emphasis on the secondary HAM-A and on prespecified subgroup analyses across underlying illnesses. The inclusion of patients with active medical comorbidities will test RE104’s safety, drug–drug interaction profile, and monitoring logistics in settings not traditionally configured for psychedelic administration. Blinding and expectancy effects remain class-wide challenges; dose-controlled design mitigates but does not eliminate them.
For sites, the opportunity is balanced by operational demands. Oncology and specialty clinics will need protocols for acute psychoactive monitoring, therapist or trained-facilitator availability, and post-session observation, all within environments accustomed to infusion-like workflows rather than psychotherapy blocks. If RE104’s shorter duration translates to three-to-four-hour visits, scheduling may fit more naturally into infusion suite templates and reduce staffing friction compared with six-to-eight-hour psilocybin sessions. CROs and vendors should anticipate higher coordination requirements across oncology and behavioral health teams, robust rater training for MADRS and HAM-A to control variability, and careful SAE adjudication in medically complex patients.
The near-term watch list is clear. In PPD, the Phase 3 protocol will need to clarify psychotherapy requirements, durability beyond 28 days, and any maintenance strategy. In AjD, recruitment velocity, screen failure rates, and site mix across oncology, palliative care, and academic psychiatry will be early signals of feasibility. Regulators are scrutinizing psychedelic programs for reproducible administration frameworks, bias control, and safety governance; any movement toward standardized guidance on session oversight or risk mitigation could materially influence study design and eventual labeling. If RE104 can replicate rapid, durable benefit with manageable site burden, Reunion could carve out a scalable niche within a field where operational complexity has constrained adoption. The unresolved questions are whether the signal will hold in a heterogeneous, medically ill population and whether the shorter-session thesis materially lowers the cost of care enough to support broad commercialization.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
