FDA Grants TSND-201 Breakthrough Therapy Designation for PTSD

Transcend Therapeutics announced on July 10, 2025, that the US Food and Drug Administration (FDA) has granted TSND-201 (methylone) a Breakthrough Therapy designation for the treatment of PTSD.1

TSND-201, a rapid-acting neuropathogen, is a proprietary formulation of methylone. Its primary site of action is at the monoamine transporters, with no activity at 5HT-2a (thus not hallucinogenic).

“A rapid-acting, durable treatment for PTSD would be a paradigm shift in psychiatry—and offer a potential lifeline for patients," said Murray B. Stein, MD, MPH, distinguished professor of psychiatry and public health at the University of California San Diego and a consultant to Transcend. "The current treatment standard, SSRIs, can take up to 12 weeks to show maximal effect and often cause side effects during that time. Even then, many patients on SSRIs don't get adequate benefit. This designation offers new hope that faster, more effective treatment may be within reach."

Approximately 13 million Americans live with PTSD. Unfortunately for these individuals, treatments are limited. Only sertraline and paroxetine are FDA-approved to treat PTSD, and these drugs only have modest efficacy for this indication.

The Breakthrough Therapy designation was based on promising pivotal data from IMPACT-1, a phase 2, randomized, placebo-controlled clinical trial evaluating TSND-201 in 65 patients with severe PTSD. Patients received either 4 oral doses of TSND-201 or placebo, with each dose separated by 1 week, and followed for 64 days.2

In the study, patients on TSND-201 received rapid, robust, and durable significant improvements in PTSD symptoms, demonstrated by the – 8.00 placebo-adjusted CAPS-5 improvement at day 10 (P = .012). Improvements continued through day 64, with a – 9.64 placebo-adjusted CAPS-5 improvement (P = .011).

TSND-201 also brought significant improvements on several secondary endpoints, including response with a ≥ 50% improvement from baseline on CAPS-5 (57.1% vs 19.2%; P = .002), remission (≤ 11 points on the CAPS-5; 32.1% vs 11.5; P = .036), and loss of PTSD diagnosis (60.7% vs 30.8%; P = .014).

Patients well tolerated TSND-201, with no hallucinations or discontinuations due to adverse events. Common adverse events include headache, decreased appetite, nausea, dizziness, blood pressure increase, dry mouth, insomnia, muscle tightness, and feeling abnormal. The one serious adverse event in the TSND-201 arm—a seizure—was considered unrelated to the study.

"This designation underscores the urgent need for new, more effective treatments for the 13 million Americans living with PTSD," said Blake Mandell, co-founder and CEO of Transcend Therapeutics.1 "Only two FDA-approved medications are available today—and no new PTSD treatments have been approved in over two decades. This Breakthrough Therapy designation enables us to work more closely with the FDA as we prepare to launch our phase 3 program."

References

1. Transcend Therapeutics Receives Breakthrough Therapy Designation for TSND-201 (methylone) for the Treatment of PTSD. PR Newswire. July 10, 2025. https://www.prnewswire.com/news-releases/transcend-therapeutics-receives-breakthrough-therapy-designation-for-tsnd-201-methylone-for-the-treatment-of-ptsd-302501928.html. Accessed July 10, 2025

2. Transcend Therapeutics Announces Primary Endpoint Met in IMPACT-1 Phase 2 Study of TSND-201 in PTSD. Transcend. March 31, 2025. https://transcendtherapeutics.com/impact-1-primary-endpoint-met/. Accessed July 10, 2025.