Transcend Therapeutics announced on July 10, 2025, that the US Food and Drug Administration has granted TSND-201 (methylone) Breakthrough Therapy designation for the treatment of post-traumatic stress disorder (PTSD). This designation could potentially expedite the development and review of the investigational treatment for a condition affecting approximately 13 million Americans.
Addressing Critical Unmet Medical Need
The designation underscores the urgent need for new PTSD treatments, as only two FDA-approved medications—sertraline and paroxetine—are currently available, with modest efficacy at best. No new PTSD treatments have been approved in over two decades.
"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. "Only two FDA-approved medications are available today—and no new PTSD treatments have been approved in over two decades."
Promising Phase 2 Trial Results
The Breakthrough Therapy designation was based on positive results from IMPACT-1, a randomized, placebo-controlled Phase 2 clinical trial evaluating TSND-201 in 65 patients with severe PTSD. Patients received either four oral doses of TSND-201 or placebo, with each dose separated by one week, and were followed for 64 days.
The study demonstrated rapid, robust, and durable improvements in PTSD symptoms. Patients treated with TSND-201 showed a statistically significant -8.00 placebo-adjusted CAPS-5 improvement at day 10 (P = .012), with improvements continuing through day 64 at -9.64 placebo-adjusted CAPS-5 improvement (P = .011).
TSND-201 also achieved significant improvements on several secondary endpoints, including response rates with ≥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).
Safety Profile and Mechanism of Action
TSND-201, described as a rapid-acting neuroplastogen, is a proprietary formulation of methylone. The drug's primary site of action is at the monoamine transporters, with no activity at 5HT-2a receptors, meaning it is not hallucinogenic.
Patients well tolerated TSND-201, with no hallucinations or discontinuations due to adverse events. Common adverse events included headache, decreased appetite, nausea, dizziness, blood pressure increase, dry mouth, insomnia, muscle tightness, and feeling abnormal. One serious adverse event—a seizure—occurred in the TSND-201 arm but was considered unrelated to the study.
Potential Paradigm Shift in Psychiatry
Murray B. Stein, MD, MPH, distinguished professor of psychiatry and public health at the University of California San Diego and a consultant to Transcend, emphasized the potential clinical impact: "A rapid-acting, durable treatment for PTSD would be a paradigm shift in psychiatry—and offer a potential lifeline for patients. 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."
Next Steps and Development Timeline
The Breakthrough Therapy designation enables Transcend Therapeutics to work more closely with the FDA as the company prepares to launch its Phase 3 program. This designation provides organizational commitment from senior FDA managers, more intensive guidance on efficient drug development, and greater access to frequent communication throughout the development and review process.
Transcend Therapeutics, founded in 2021, is a clinical-stage neuroscience-focused company that has raised approximately $50 million to date. The company's leadership team has contributed to 14 FDA approvals and $7 billion in M&A and public company value.
