IMPACT-EXT: EVALUATING THE DURABILITY AND REDOSING OF TSND-201 (METHYLONE) FOR THE TREATMENT OF PTSD

Background

TSND-201 (methylone) is under clinical investigation as a treatment for post-traumatic stress disorder (PTSD), a debilitating psychiatric condition affecting an estimated 12 million adults in the US each year. Current therapies have limited efficacy, highlighting the need for novel treatment approaches. Non-hallucinogenic compounds that provide rapid and sustained therapeutic effects could offer practical advantages over classical psychedelics. TSND201 is a selective, fast-acting neuroplastogen that promotes neuroplasticity by releasing serotonin, norepinephrine, and dopamine. Consistent with its lack of direct activity at serotonin (5-HT)2A receptors, TSND-201 is non-hallucinogenic in both humans and preclinical models. Preclinical studies show that TSND-201 produces rapid, robust, and durable improvements in models of PTSD, depression, and anxiety. In a prior Phase 2 randomized, placebo-controlled trial (IMPACT-1), TSND-201 demonstrated rapid and sustained reductions in PTSD symptoms as measured by the CAPS-5. These promising results led to FDA Breakthrough Therapy Designation. In the present study, we assess the durability of TSND-201’s effects and evaluate the impact of redosing in participants who completed IMPACT-1.

Methods

The IMPACT-EXT study was a multicenter open-label extension clinical trial evaluating the durability and redosing of TSND-201. Participants were completers from the IMPACT-1 phase 2 clinical trial evaluating safety and efficacy of TSND-201 for PTSD who chose to enroll in the open-label extension trial. Participants of the IMPACT-1 trial were adults with PTSD and a CAPS-5 total score ≥ 35 who had tried at least one prior treatment (pharmacotherapy and/or psychotherapy) for PTSD. A total of 44 of 59 completers from IMPACT-1 enrolled (21 from the prior-TSND-201 arm and 23 from the prior placebo arm). Overall, CAPS-5 scores at the end of IMPACT-1 among those who enrolled in this extension study were notably higher than the average of all who completed IMPACT-1 (i.e., participants with more severe illness enrolled into the extension study). Participants attended monthly visits and were followed for up to 12 months. Treatment with a course of open-label TSND-201 (4 weekly doses) could occur upon two consecutive visits with a CAPS-5 score ≥ 28.

Results

Participants who received TSND-201 in the IMPACT-1 study and had a meaningful response (≥ 10-point improvement on CAPS-5) demonstrated sustained efficacy through Week 14 (-22.5 point change from IMPACT-1 baseline) and Week 18 (-17.4 point change from baseline). After an additional course of open-label treatment (e.g., one course in IMPACT-1 and one course in this study), participants experienced significant improvement in CAPS-5 scores lasting up to 16 weeks after the second treatment. There were no new safety findings after repeat treatment with TSND-201.

Conclusion

These results show that TSND-201 maintains therapeutic effects for about four months, informing redosing strategies and future Phase 3 study design. This study supports the development of TSND-201 as a treatment for PTSD.