TSND-201 Receives Breakthrough Therapy Designation From FDA for PTSD

Sanom/Adobestock

BREAKING NEWS

The US Food and Drug Administration granted Transcend Therapeutics with the Breakthrough Therapy designation for their compound TSND-201 for (methylone) for the treatment of posttraumatic stress disorder (PTSD) following positive results from its IMPACT-1 study.¹

In March 2025, Transcend shared the results of IMPACT-1, a randomized placebo controlled clinical trial that evaluated efficacy of TSND-201 in the treatment of PTSD. The trial consisted of 65 participants who had severe PTSD as defined as Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) ≥ 35 and had attempted previous treatment. Participants received 4 oral doses of the agent or placebo and were monitored for 64 days after the initial dose. The study met the primary endpoint with placebo-adjusted CAPS-5 improvement of -9.64 points on Day 64 (-23.28 points vs. -13.64 points; p = 0.011). Moreover, improvements were seen as early as day 10, with a statistically significant placebo-adjusted CAPS-5 improvement of -8.00 points (-17.83 points vs. -9.83 points; p = 0.012). Importantly, the improvement was durable for the length of the study.²

IMPACT-1 also demonstrated a good safety and tolerability profile. Most of the reported adverse events were transient and occurred on the day that the participant received the dose, and most events resolved that same day. Headache, decreased appetite, nausea, dizziness, increased blood pressure, dry mouth, insomnia, muscle tightness, and feeling abnormal were the most commonly reported events. A patient with a history of seizures also reported a seizure 7 days after the last dose; the event was not considered related to the TSND-201. The company added that it had “a safety profile consistent with its non-hallucinogenic pharmacology.”²

Considered a rapidly acting neuroplastogen, TSND-201 is Transcend Therapeutics’ proprietary form of methylone. The monoamine transporters are considered its primary site of action, and the company reports no activity at 5HT-2a.²

"This designation underscores the urgent need for new, more effective treatments for the 13 million Americans living with PTSD," Blake Mandell, co-founder and CEO of Transcend Therapeutics, said in a statement to the press. "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."¹

Murray B. Stein, MD, MPH, distinguished professor of psychiatry and public health at the University of California San Diego and a Transcend consultant, was equally excited about the designation and its meaning 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,” he said in a press statement. "A rapid-acting, durable treatment for PTSD would be a paradigm shift in psychiatry—and offer a potential lifeline for patients."

“This designation offers new hope that faster, more effective treatment may be within reach," Stein added.¹

After nearly 2 decades without a new treatment for PTSD, there was renewed hope last year when Lykos’ MDMA-assisted therapy was reviewed by the FDA. Veterans and first responders advocates advocated for careful consideration at the time, noting “PTSD is one of the few psychiatric disorders that reliably predicts suicidal ideation, suicide attempts, and suicide mortality, significantly contributing to our nation's veteran suicide epidemic, which claims between 17 and 44 veteran lives daily.”³ Unfortunately, approval at the time was not granted.

References

1. Transcend Therapeutics Receives Breakthrough Therapy Designation for TSND-201 (methylone) for the Treatment of PTSD. Press release. Jul 10, 2025. Accessed 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

2. Transcend Therapeutics Announces Primary Endpoint Met in IMPACT-1 Phase 2 Study of TSND-201 in PTSD. Press release. March 31, 2025.

3. Duerr HA. Officials, Veterans Urge Careful Consideration for MDMA-Assisted Psychotherapy. Psychiatric Times. August 8, 2024. Accessed July 10, 2025. https://www.psychiatrictimes.com/view/officials-veterans-urge-careful-consideration-for-mdma-assisted-psychotherapy