Transcend Therapeutics, Inc.

Four weeks after receiving a 100 µg dose of the drug candidate, patients saw a significant reduction in anxiety symptoms compared to a placebo, shown by a 7.6 point drop in the Hamilton Anxiety rating scale (HAM-A). According to the scale, a score lower than 17 signals mild anxiety and 25-30 indicates moderate to severe anxiety. GAD is a common condition ​ that causes feelings of persistent anxiety, fear and excessive worry, and can negatively impact daily life. “The pharmaceutical industry has largely ignored GAD over recent decades as it has proved extremely difficult to target,” said Daniel Karlin, Chief Medical Officer of MindMed in a public statement. “Few new treatment options have shown robust activity in GAD since the last new drug approval in 2004, making the strong, rapid, and durable clinical activity of a single dose of MM-120 observed in the trial particularly notable.” MindMed’s trial enrolled 198 participants who received either MM-120 at 25, 50, 100 or 200 µg or a placebo. The participants had severe GAD at baseline, with an average HAM-A score of approximately 30. A total of 78% of patients receiving either 100 µg or 200 µg of the drug candidate saw a clinical response, a drop of 50% or more in their HAM-A score, compared to 31% in the placebo group. Meanwhile, half of the patients given 100 µg of MM-120 saw a clinical remission, represented by a HAM-A score of less than 7. The company saw the drug was overall well-tolerated and that the mostly mild-to-moderate adverse events, such as illusion, hallucinations, euphoric mood, happened on the day of dosing. googletag.cmd.push(function () { googletag.display('text-ad1'); }); MindMed now plans to discuss its results with the US Food and Drug Administration (FDA) in early 2024 and to launch a larger phase 3 trial in the second half of the same year. “We are excited by the strong positive results for MM-120 in GAD, particularly given that this is the first study to assess the standalone drug effects of MM-120 in the absence of any psychotherapeutic intervention,” said Robert Barrow, Chief Executive Officer and Director of MindMed. “These promising findings represent a major step forward in our goal to bring a paradigm-shifting treatment to the millions of patients who are profoundly impacted by GAD.” MM-120 is a small molecule drug with the name of lysergide d-tartrate, and is designed to partially activate the human serotonin-2A receptor. While there is a wide range of therapies to treat psychiatric disorders, many can take weeks to show a benefit and can come with side effects such as insomnia, nausea and headaches, according to MindMed’s website. Psychedelic drugs, meanwhile, are attracting increasing attention for their potential to rewire the brain in order to treat psychiatric disorders including depression and post-traumatic stress disorder. They can show benefits beginning as fast as the day of the treatment and can maintain the improvement for a long time with fewer major side effects. MindMed is also developing MM-120 for the treatment of attention hyperactivity deficit disorder. The company is also working on a form of MDMA for the treatment of autism spectrum disorder and another treatment candidate for opioid use disorder. There are many other players championing psychedelics for the improvement of mental health. In October, Transcend Therapeutics partnered ​ with Clerkenwell Health to trial the use of methylone in patients with severe PTSD. Meanwhile, Psycheceutical is developing ​ its own psychedelic to treat the same condition, this time based on a form of ketamine.

The news comes as psychedelics continue to gain scientific recognition as promising new treatments ​ for various mental health disorders. “ ​The status quo for mental health treatment just isn’t working, and the NHS is struggling to cope ​ with the pressure. By rolling out these clinical trials in the UK we hope to contribute to a growing body of research which supports the development of the next wave of innovative treatments for neuropsychiatric diseases,” Clerkenwell Health chief scientific officer Dr Henry Fisher said. The trial will be the first in the UK to assess whether the drug, which has been compared to MDMA, could offer a safe treatment for the condition. The phase 2 study is now underway, with the first patients having just been dosed at Clerkenwell Health’s facility near Harley Street in London. Participants with PTSD ​aged between 18 and 70 will receive methylone capsules once a week for 4 weeks, while another group will receive a placebo. After the trial is completed, patients will be monitored for a further 6 weeks. According to researchers, the drug could require less clinician time for administration, therefore making it well-suited for integration into the NHS. Methylone belongs to a class of psychoactive drugs called entactogen, which includes MDMA, that can elicit feelings of empathy ​, emotional openness and make people feel closer to others. However, the drug is short-acting and does not induce hallucinations. An estimated 1 in 10 people in the UK will experience PTSD at some point in their lives. Symptoms include recurrent distressing images, flashbacks and nightmares of a traumatic event, avoidance and numbness, and hypervigilance. Current treatments include talking therapy and antidepressant medications. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Transcend expects initial top-line data from the open-label portion of the study by the end of 2023. Following completion of this initial study, the company will launch part b, a randomized, double-blind, placebo-controlled, evaluation of methylone with up to 64 patients with PTSD. Blake Mandell, CEO and co-founder at Transcend Therapeutics, commented: “ ​We know from a published clinical case series and other research that methylone could hold tremendous promise for the treatment of PTSD. "We are grateful to Clerkenwell Health for partnering on this trial, which will provide invaluable data on the efficacy and safety of methylone for PTSD. We look forward to reviewing the results of this study, and ultimately bringing new and more effective treatments to the market for the millions of people globally who suffer from PTSD.”

Phalguni Deswal @Phalguni_GD Methylone (TSND-201) is a rapid-acting neuroplastogen (a biological substrate not a therapeutic). Image Credit: MargJohnsonVA / Shutterstock. The US Department of Defense has awarded a collaborative grant to Transcend Therapeutics and Yale University (US). The grant is to fund the preclinical research of Transcend’s lead candidate, methylone for treating post-traumatic stress disorder (PTSD). The funding builds on Yale University’s $1m Department of Defense (DoD) grant to study the mechanism of action of methylone and midomafetamine (MDMA) in PTSD . Recommended Reports Reports LOA and PTSR Model - Histamine Dihydrochloride in Chronic Traumatic Encephalopathy (CTE) GlobalData Reports LOA and PTSR Model - Bavisant Dihydrochloride in Hypersomnia GlobalData View all Companies Intelligence Bionomics Ltd Yale University Dod Transcend Therapeutics Inc View all Methylone (TSND-201) is a rapid-acting neuroplastogen (a biological substrate not a therapeutic). Transcend is conducting a placebo-controlled Phase I/II trial (NCT05741710) in the UK to evaluate the safety and efficacy of methylone in treating patients with severe PTSD. Part A of the study was an open-label study and was expected to enrol up to 15 participants with PTSD. Top-line data from this part is expected by the end of this year. Part B of the trial will be a randomised, double-blind, placebo-controlled study enrolling up to 64 patients. Transcend’s co-founder and medical adviser for the US Department of Veterans Affairs National Center for PTSD stated: “There is a tremendous demand, especially among veterans, for new and effective treatments for PTSD.” Multiple PTSD treatments currently in development include Halucenex’s synthetic psilocybin, which showed a 40% reduction in PTSD symptoms in the Phase II trial. Bionomics is expected to announce the Phase IIb trial (NCT04951076 ) results for BNC210 in Q3 2023 . BNC210 is a negative allosteric modulator of the α7 nicotinic acetylcholine receptor and has received a fast track designation from the Food and Drug Administration (FDA) for treating PTSD. The US DoD has also sponsored a PTSD Phase II trial (NCT05422612) for the combination therapy of Idorsia Pharmaceuticals’ Quviviq (daridorexant), fluoxetine and vilazodone hydrochloride.