Transcend Therapeutics has glided over the bar for success, linking its MDMA analog to improvements in post-traumatic stress disorder (PTSD) symptoms that began on Day 8 and persisted through Day 64 of its phase 2 trial.
Lykos Therapeutics, formerly called MAPS Public Benefit Corporation, popularized the idea of using MDMA, commonly known as ecstasy, to treat PTSD. However, the FDA rejected Lykos’ request for approval last year. And, while the biotech was still seeking a path forward as of January, the fate of the program and MDMA-assisted therapy for PTSD more broadly remains uncertain.
Transcend is taking a different approach. While TSND-201 is an analog of MDMA, the biotech says the molecule is not hallucinogenic. Rather, Transcend characterizes the drug candidate as a triple reuptake inhibitor and releaser that acts on serotonin, norepinephrine and dopamine.
The phase 2 trial randomized 65 people with severe PTSD to receive TSND-201 or placebo. All patients had previously tried a PTSD treatment. Participants took TSND-201, also called methylone, orally once a week for four weeks. Unlike Lykos’ MDMA trials, the drug was given without psychotherapy.
By Day 64, scores on the CAPS-5 PTSD scale had fallen by 23.28 points in the TSND-201 arm and 13.64 in the placebo group, achieving the primary endpoint. Transcend assessed CAPS-5 scores at seven points in the trial, starting on Day 8, and saw statistically significant improvements over placebo every time.
The speed and depth of response look competitive, with the usual caveats about cross-trial comparisons. Lykos filed for FDA approval after seeing a 23.7-point drop in CAPS-5 on MDMA—and a 14.8-point dip on placebo—after 18 weeks, or 126 days.
Otsuka and Lundbeck are currently seeking approval for brexpiprazole plus sertraline in PTSD after seeing reductions of up to 19.2 points after 10 weeks across three phase 3 trials.
Transcend also saw significant improvements on secondary endpoints that assessed the rate of response, remission and loss of PTSD diagnosis. The biotech said 60.7% of participants lost their PTSD diagnosis on TSND-201, compared to 30.8% of the patients on placebo.
The most commonly occurring adverse events on TSND-201 were headache, decreased appetite, nausea, dizziness, increased blood pressure, dry mouth, insomnia, muscle tightness and feeling abnormal. There was one serious adverse event, a seizure, in the TSND-201 arm. But the event happened seven days after the last dose in a patient with a history of seizure and was deemed unrelated to the study drug.
Transcend started another phase 2 trial one year ago. That study, which is still enrolling, includes an initial open-label portion and a second part that will randomize patients to receive a low, medium or high dose of TSND-201.
The biotech closed a $40 million series A round in 2023 and has raised around $50 million in total to date. Talking in late 2023, Transcend CEO Blake Mandell said the company had enough money to get to the phase 2 readout in 2025.