PTSD treatment is on the cusp of a paradigm shift. This biotech hopes to Transcend the competition

All of a sudden, there’s a flurry of activity in developing treatments for PTSD—meaning companies […]

All of a sudden, there’s a flurry of activity in developing treatments for PTSD—meaning companies have to bring compelling data. Transcend Therapeutics is hoping to rise above the competition with an early cut of phase 2 data showing its MDMA analog reduced the severity of the condition in patients.

Transcend’s MDMA analog treatment showed rapid and persistent reduction in a small cohort of patients with severe PTSD, according to data presented late Tuesday afternoon. The drug, methylone, is a chemical analog of MDMA, the more widely-known psychedelic treatment that is soon to reach the FDA’s desk to treat PTSD. Methylone is not a hallucinogen but is psychoactive, similar to Johnson & Johnson’s esketamine drug, Spravato.

In part A of an ongoing phase 2 trial, 14 patients between 23 and 65 years old received four doses of methylone—also known as TSND-201—over four weeks. All recruited patients had a CAPS-5 score of at least 35, an 80-point measurement of PTSD symptoms where higher scores reflect more severe cases.

Two days after the first dose, patients averaged a more than 8-point reduction in CAPS-5 scores. Two days after the second dose, that average score reduction almost tripled, to a 23.3-point reduction. Six weeks after the last dose, the average point reduction was 36.2 points and roughly 60% of patients were in remission, assessed as a CAPS-5 score equal to or lower than 11.

Transcend CEO Blake Mandell was cautious about making grandiose claims based on the small sample size, but was encouraged nonetheless.

“We think it’s a great start to show that we have that signal we’re looking to find in the open-label study,” he said in an interview with Fierce Biotech. “But it’s only a start.”

Transcend is now kicking off a randomized control trial in patients with PTSD. Considered part B of the ongoing phase 2 study, Transcend is looking to enroll between 40 and 64 patients, with data expected in the first half of 2025.

The early data stack up well against fellow PTSD drugmakers, including the Multidisciplinary Association for Psychedelic Studies (MAPS), which for decades has been developing MDMA to treat PTSD. The compound—commonly known as ecstasy—spurred a 23.7-point drop in CAPS-5 scores in a phase 3 study, while placebo plus therapy showed a 14.8-point reduction. Transcend’s candidate also exceeded the roughly 20-point CAPS-5 drop for Bionomic’s phase 2 PTSD med.

Transcend’s data add to mounting evidence that the treatment paradigm for patients with PTSD is set for a seismic shift, away from the two selective serotonin reuptake inhibitors (SSRIs) that are currently approved. Mandell is hoping for TSND-201 to follow in the footsteps of a drug like Spravato, an adjunctive, intranasal esketamine treatment for major depressive disorder, which he describes as part of a growing field of interventional psychiatry.

Efficacy aside, treatment would be episodic, meaning it would be provided if patients had a PTSD relapse or if they were acutely ill. That spares patients the chronic side effects, like weight gain, often associated with SSRIs. And while methylone is in the same chemical family as MDMA, Mandell believes not being a psychedelic will be a selling point to most patients.

“We’ve spoken to a lot of physicians and patients and all things considered, they prefer not to hallucinate but still have therapeutic effects,” Mandell said. The lack of a hallucinogenic effect also means that TSND-201 could be administered in outpatient facilities rather than university medical centers, he added.

Assuming that Transcend’s phase 2 timeline holds true, an end-of-phase 2 meeting with the FDA should occur in 2025 to prepare for the launch of an international pivotal program. The company secured $40 million in series A funds in February and added a three-year, $1 million grant from the U.S. Department of Defense in September. That’s enough to last through the phase 2 part B readout in 2025, but Mandell says he’s always open to more funding opportunities.

“I’m always looking to see how we can improve our financial situation as a company,” he said, without explicitly committing to fundraising off the new data.

If and when Transcend raises next, that money would go toward follow-up uses of TSND-201, namely major depressive disorder. A secondary endpoint in the open-label portion was the change in symptom severity assessed using the Montgomery-Asberg Depression Rating Scale, which assesses the severity of depression. Six weeks after the last dose, treated patients averaged a 21.4-point drop in score, a significant reduction that if maintained in follow-up studies would go toe-to-toe with Axsome’s recently-approved Auvelity. Still, Mandell affirmed that fully funding the PTSD development plan would be the priority of any new financing.

Original Article: (https://www.fiercebiotech.com/biotech/budding-psychiatry-biotech-looks-transcend-ptsd-competition-sample-phase-2-data)