Reunion Neuroscience has presented the design for its upcoming REKINDLE Phase 2 clinical trial, which will evaluate RE104 for the treatment of adjustment disorder (AjD) in patients with cancer and other serious medical illnesses. The study design was unveiled at the Anxiety & Depression Association of America (ADAA) 2025 Conference in Las Vegas, marking a significant expansion of the company's clinical development program.
Adjustment disorder represents a substantial unmet medical need, affecting approximately 500,000 people in the United States annually following medical or health-related stressors. The condition is characterized by a disproportionate reaction to stressful life events, manifesting as depression, anxiety, and other behavioral disturbances that significantly impact daily functioning.
"AjD is debilitating both in its own right, and in the impact it can have on overall health outcomes in patients suffering from medical illnesses," explained Mark Pollack, M.D., Chief Medical Officer of Reunion Neuroscience. "The importance of treating mental health in parallel with serious diseases is becoming increasingly well-recognized."
Currently, there are no FDA-approved therapies specifically for adjustment disorder, and existing treatment approaches show inconsistent effectiveness. For cancer patients and those with other serious illnesses, the condition can lead to poorer medical outcomes, reduced treatment compliance, diminished quality of life, and increased healthcare utilization.
Novel Psychedelic Approach to Mental Health
RE104, Reunion's lead product candidate, represents a novel approach to treating adjustment disorder. As a proprietary prodrug of 4-OH-DiPT, it is designed to deliver a psychedelic experience of shorter duration compared to other psychedelics like psilocybin.
"With RE104, we believe we can leverage the power of 4-OH-DiPT to offer a rapid onset, short duration psychedelic experience that delivers immediate, substantial and sustained improvement to patients with AjD," said Greg Mayes, President and Chief Executive Officer of Reunion Neuroscience.
In Phase 1 clinical trials, RE104 produced a psychedelic state similar in intensity and quality to psilocybin but lasting only about half the time (3-4 hours), while demonstrating a favorable safety profile. This shorter duration could offer practical advantages for clinical administration and patient experience.
Notably, RE104 is currently the only psychedelic therapeutic in advanced clinical development for an adjustment disorder indication in the United States.
REKINDLE Trial Design and Endpoints
The REKINDLE Phase 2 clinical trial is designed as a randomized, double-blind, parallel-group, dose-controlled study evaluating the safety and efficacy of RE104 specifically for adjustment disorder in adult patients with cancer and other medical illnesses.
The primary endpoint of the trial will measure the change in total Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline at Day 14. This clinician-rated scale is a well-established measure of depression severity. A key secondary endpoint will assess the change in Hamilton Anxiety Scale (HAM-A) from baseline at Day 14, providing insight into the treatment's impact on anxiety symptoms.
The study will also comprehensively evaluate the safety and tolerability profile of RE104 in this specific patient population. Trial initiation is expected in mid-2025.
Expanding Clinical Development Program
The REKINDLE trial represents an expansion of Reunion Neuroscience's clinical development program for RE104. The company is already evaluating the compound in the RECONNECT Phase 2 clinical trial (NCT06342310) for postpartum depression (PPD).
"Similar to postpartum depression, where we are currently evaluating RE104 in the RECONNECT Phase 2 clinical trial, AjD is a devastating psychiatric condition that meaningfully impacts quality of life and is often marked by depression and/or anxiety," Mayes noted.
The RECONNECT trial is a multicenter, randomized, double-blind, active dose-controlled study evaluating the safety and efficacy of a single subcutaneous dose of RE104 in adult female patients with moderate-to-severe PPD. Initial data from this trial are expected in mid-2025, coinciding with the planned initiation of the REKINDLE trial.
Potential Impact on Cancer Care
For cancer patients specifically, the development of effective treatments for adjustment disorder could have far-reaching implications. The psychological burden of a cancer diagnosis and subsequent treatment can significantly impact overall outcomes, with mental health increasingly recognized as a crucial component of comprehensive cancer care.
By addressing the psychological aspects of serious illness, RE104 could potentially improve not only mental health symptoms but also overall treatment adherence and outcomes for patients with cancer and other medical conditions.
Reunion Neuroscience, which completed a Series A financing co-led by MPM BioImpact and Novo Holdings in 2024, is positioning itself at the forefront of psychedelic medicine development for underserved mental health conditions. The company is actively investigating RE104 for postpartum depression and adjustment disorder, with plans to explore additional neuropsychiatric indications where significant unmet needs remain.
