Reunion Neuroscience’s psychedelic has reduced the symptoms of postpartum depression in a phase 2 study, setting up the biotech to launch a late-stage trial next year.
The drug in question is RE104, a prodrug of 4-OH-DiPT that is designed to replicate the effects of the magic mushroom extract psilocybin but in a shorter time span. Reunion, which was acquired by MPM BioImpact in 2023, has been evaluating RE104 in 84 adult female patients with moderate to severe postpartum depression (PPD).
A total of 77.1% of patients treated with a single 30-mg subcutaneous dose of RE104 saw at least a 50% improvement in a depression score at Day 7, compared to 61.6% of patients from an active control arm who received 1.5 mg of RE104, Reunion said in an Aug. 18 press release.
The 30-mg cohort also saw a 23-point average reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline, compared to 17.2 points for the control arm.
When it came to patients who saw their MADRS score lowered to 10 or below—defined as entering remission—71.4% of patients in the RE104 arm had reached this marker by Day 7, compared with 41% of the control cohort.
Patients' response and remission rates maintained through a Day 28 follow-up, the biotech noted.
Key secondary endpoints, such a self-reporting measure of overall maternal functioning, were also supportive of the primary endpoint win, Reunion added.
When it came to safety and tolerability, almost 44% of patients suffered from nausea and 34% experienced a headache. However, these events were “generally mild to moderate, occurred primarily on the day of treatment, resolved spontaneously, and are consistent with those observed with other agents in the class,” Reunion pointed out.
A total of 92.7% of patients were ready for discharge within four hours of their treatment, the company said. Meanwhile, preliminary data from a lactation study suggested that mothers could “rapidly” return to breastfeeding their children, Reunion added.
“We are encouraged by the results from our Reconnect phase 2 trial, which provide strong clinical validation for RE104 as a well-tolerated and effective treatment for PPD offering rapid relief with minimal interruption to daily activities,” Reunion Chief Medical Officer Mark Pollack, M.D., said in the release.
“These data support our proposed plan to advance RE104 into a pivotal phase 3 trial in 2026,” Pollack added.
The company also plans to launch a phase 2 study of RE104 in the coming weeks for the treatment of adjustment disorder (AjD)—strong emotional and behavioral symptoms that happen after a stressful event—in patients with cancer and other illnesses. Another phase 2 in an undisclosed “significant mental health indication” is penciled in for the first quarter of 2026, according to the company's Monday press release.
“We strongly believe that RE104 has the potential to redefine the standard of care for debilitating disorders such as PPD and AjD, and look forward to realizing its broader application to address a range of underserved mental health conditions,” Pollack said.
Reunion helped fund its RE104 strategy via a $103 million series A in May 2024. At the time, executives pointed to an average effect time of the drug of less than four hours in a phase 1 study, compared to six to eight hours for Compass Pathways’ psilocybin study. This reduced administration time was a key attribute as Reunion attracted big name investors like Novo Holdings to back the series A.
Executives also argued at the time that the psychedelic sector had benefited from the example set by Johnson & Johnson’s intranasal S-ketamine therapy Spravato, which is approved as an adjunctive treatment for patients with treatment-resistant depression. Healthcare professionals are asked to monitor patients for at least two hours after administration of Spravato.
A notable recent development in the psilocybin space was Compass’ phase 3 win in treatment-resistant depression for COMP360, its synthetic form of the magic mushroom extract, in June. However, the data appeared to underwhelm investors.