Psychedelic: Compass Pathways achieves primary endpoint in COMP360 trial

In this week’s “Psychedelic,” The Fly’s recurring series focused on psychedelic stock news, The Fly looks back on a primary endpoint achievement, a clinical site addition and additional development candidate data.

COMPASS PATHWAYS ACHIEVES PRIMARY ENDPOINT IN COMP360 TRIAL: Compass Pathways (CMPS) announced Monday the achievement of the primary endpoint in the ongoing Phase 3 COMP005 trial, the first of two Phase 3 trials evaluating COMP360, a synthetic, proprietary formulation of psilocybin, for treatment-resistant depression. The primary endpoint is the difference in change from baseline in the Montgomery-Åsberg Depression Rating Scale scores between the active treatment group and the placebo group at week 6. A single dose of COMP360 25 mg versus placebo demonstrated a highly statistically significant reduction in symptom severity with a p-value of <0.001 and a clinically meaningful difference of -3.6 in change at the primary endpoint. The company plans to discuss these preliminary COMP005 data with the U.S. Food and Drug Administration, which has not yet reviewed the data. The ongoing Phase 3 COMP005 trial is the first study of an investigational, synthetic psilocybin, and the first classic psychedelic to report Phase 3 efficacy data. This randomized, double-blind, placebo-controlled study, which dosed 258 participants with TRD across 32 sites in the United States, aims to assess the efficacy and safety of a single dose of COMP360 25 mg versus placebo for reducing symptom severity in TRD. KBased on the latest review of the data for the 005 and 006 studies, safety findings are consistent with previous studies of COMP360 and there are no new or unexpected safety findings. From this review of the data, there is no evidence of a clinically meaningful imbalance between treatment arms in suicidality in either study. "The positive top-line results at week 6 from the COMP005 trial underscore the innovative potential of psilocybin treatment in mental health care for which Compass Pathways continues to pave the way," said Kabir Nath, CEO. "We are proud of this significant progress, which reflects our scientific rigor, operational excellence and steadfast commitment to serving patients living with TRD. We eagerly anticipate further insights once we have the full dataset, and also look forward to findings from COMP006, which will explore the efficacy of two fixed doses. We remain focused on our goal of transforming the landscape of mental health treatment." Following the report, Evercore ISI downgraded Compass Pathways (MNMD) initiation, durability is a key component for commercial success and this will remain a question with relatively unclear durability in the Phase 2b and a weaker effect at 6 weeks here, the analyst said.

Meanwhile, H.C. Wainwright said that meeting the primary endpoint in the Phase 3 COMP005 trial in treatment-resistant depression marks “a historic first for a psychedelic therapy.” In addition to this readout representing the first-ever positive Phase 3 efficacy data for a classic psychedelic, it positions COMP360 as “a potential first-in-class treatment in a large, underserved depression market,” said the analyst, who reiterated a Buy rating and $45 price target on the shares.

Stifel acknowledged that the 3.6 point MADRS delta between drug-vs-placebo for COMP360 was “a little lighter than expected,” but argued that the magnitude of the stock reaction is “significantly overdone”. The COMP360 data represents “a clearly positive result from a regulatory perspective,” and the effect-size is “actually pretty good for a treatment-resistant population,” according to the analyst, who added that it is “simply not clear” that effect size is a major driver of commercial success in neuropsychiatry. The firm has a Buy rating and $11 price target on Compass shares.

Additionally, Canaccord said the weakness in Compass Pathways following the release of top-line results from its eagerly-awaited COMP005 Phase 3 trial is a buying opportunity. Canaccord believes updates from the FDA could eventually move the stock and there is no change to their model pending additional data. Canaccord reiterated its Buy rating and $15 price target on Compass Pathways shares.

BTIG lowered the firm’s price target on Compass Pathways to $7 from $12 but kept a Buy rating on the shares. The firm noted that COMP360 represents the “very careful development of a mediocre drug” relative to other options in the psychedelic and neuro-plastic pipeline, the analyst said.

CLEARMIND ADDS ISRAELI CLINICAL SITE TO AUD TRIAL: Clearmind Medicine (CMND) announced Monday the addition of Tel Aviv Sourasky Medical Center in Tel Aviv, Israel, as an additional clinical site for its ongoing Phase I/IIa clinical trial evaluating CMND-100, a proprietary MEAI-based oral drug candidate, for the treatment of Alcohol Use Disorder. This expansion follows the recent enrollment of the first patient in the trial. The study at Tel Aviv Sourasky Medical Center will be led by Dr. David Zeltser, Director of the Emergency Medicine Department. Tel Aviv Sourasky Medical Center joins other institutions participating in the trial, including Yale School of Medicine’s Department of Psychiatry and Johns Hopkins University School of Medicine. The inclusion of Tel Aviv Sourasky Medical Center further strengthens Clearmind’s clinical network, enhancing the trial’s capacity to evaluate the safety, tolerability, and pharmacokinetic profile of CMND-100, while also exploring its potential to reduce alcohol cravings and consumption in patients with AUD.

“We are pleased to welcome Tel Aviv Sourasky Medical Center to our Phase I/IIa clinical trial, alongside esteemed partners like Yale and Johns Hopkins,” said Adi Zuloff-Shani, CEO. “The enrollment of our first patient earlier this month was a pivotal moment, and expanding our clinical trial to additional leading clinical sites like TASMC underscores our commitment to addressing the global burden of AUD, which affects millions and accounts for 2.6M deaths annually.”

ENVERIC REPORTS ADDITIONAL DATA ON EB-003: On Tuesday, Enveric Biosciences (ENVB) unveiled additional data indicating that its lead development candidate, EB-003, acts as an agonist of the serotonin receptor 5-HT1B, in addition to its other previously disclosed receptor engagement activities. The 5-HT1B receptor is a recognized therapeutic target for treating several central nervous system conditions, including major depressive disorder, Parkinson’s disease, migraines, and cluster headaches. The study results demonstrated agonism of 5-HT1B by EB-003 and added to the existing receptor engagement data supporting that EB-003 acts as a partial agonist of the 5-HT2A receptor, which is key to the compound’s potential ability to elicit neuroplastogenic effects without inducing adverse hallucinogenic outcomes. EB-003 is currently in preclinical development, with IND-enabling activities planned to continue through 2025.

“The 5-HT1B receptor, found predominantly in the frontal cortex, basal ganglia and hippocampus, is a validated therapeutic target of some well-known CNS drugs,” said Joseph Tucker, CEO. “Enveric previously announced positive pharmacology, in vitro safety and oral bioavailability data of EB-003, including achieving therapeutically relevant brain exposure in rodent models. The newly revealed ability to target 5-HT1B illustrates EB-003’s differentiated and multifaceted mechanism of action and broadens its utility and the range of potential target indications to pursue in future development.”

SILO PHARMA ENTERS LOI FOR JV WITH HOTH: Silo Pharma (SILO) announced Wednesday that it has entered into a non-binding letter of intent to form a strategic 50:50 joint venture with Hoth Therapeutics (HOTH) to develop and commercialize a potential treatment for obesity and metabolic disease based on technology Hoth has exclusively licensed from the U.S. Department of Veterans Affairs that was co-developed by the VA and Emory University. The novel therapeutic platform centers on glial cell line-derived neurotrophic factor, a VA-invented biologic with demonstrated anti-obesity effects and metabolic regulation in preclinical models. The platform is protected under U.S. Patent No. 10,052,362 and targets multiple high-burden conditions, including non-alcoholic fatty liver disease, type 2 diabetes, and central obesity.

“With obesity at epidemic levels and no curative therapies available, we believe the VA’s biologic GDNF is potentially a game-changer,” said Eric Weisblum, CEO. “We believe that our potential JV collaboration with Hoth aligns with our mission to accelerate groundbreaking science into human trials.”

HOPE THERAPEUTICS TO ACQUIRE INTEREST IN COHEN: HOPE Therapeutics, a wholly-owned subsidiary of NRx Pharmaceuticals (NRXP), announced Thursday the signing of a binding Letter of Intent to purchase a 49% interest in Cohen and Associates, founded by Dr. Rebecca Cohen. Cohen is expected to serve as a foundational clinic for HOPE in the Sarasota-Bradenton region of western Florida. The clinic offers a full range of treatments for suicidal depression, PTSD and other CNS disorders, including ketamine, Spravato, Transcranial Magnetic Stimulation as well as medication management.

“We are delighted to welcome Rebecca and her team to the HOPE family. Her extensive experience with neuroplastic therapies, combined with compassionate patient care exemplify our culture of bringing HOPE to life,” said Jonathan Javitt and Matthew Duffy, Co-CEOs of HOPE.

Additionally on Monday, NRx Pharmaceuticals announced filing for the newly-announced FDA Commissioner’s National Priority Voucher program on behalf of NRX-100, its patent-pending, preservative-free formulation of ketamine for intravenous use. Concurrent with the CNPV process, the company is preparing a citizen petition to seek withdrawal of preservative-containing forms of ketamine, based on the toxicity associated with the benzethonium chloride preservative used in the historic formulation. The company has also filed a patent on its preservative-free manufacturing process.

“NRx is highly encouraged by the newly-announced Commissioner’s National Priority Voucher Program, and believes that NRX-100 meets each of the criteria for acceptance,” said Jonathan Javitt, CEO. “As previously determined by FDA, our products are innovative treatments that address the current health crisis of suicidal depression and PTSD, and address an unmet medical need. We will be seeking New Drug Approval for NRX-100 in the treatment of suicidal depression and PTSD. The FDA’s announcement has now validated our company’s focus on manufacturing and CMC by identifying CMC as a pre-requisite to the CNPV program. The timelines announced for the CNPV program are consistent with NRx’s previous guidance of FDA decisions by year-end 2025. Our application under the CNPV program is accretive to the Abbreviated New Drug Application filed last week for preservative-free ketamine, for which we are seeking priority review.”

OTHER PSYCHEDELIC STOCKS: Publicly-traded companies in the space include Algernon Pharmaceuticals (AGNPF), Allied Corp. (ALID), atai Life Sciences (ATAI), BetterLife (BETRF), Bright Minds (DRUG), Cybin (CYBN), Entheon Biomedical (ENTBF), Filament Health (FLHLF), GH Research (GHRS), Incannex (IXHL), MIRA Pharmaceuticals (MIRA), Mydecine Innovations (MYCOF), Numinus Wellness (NUMIF), Optimi Health (OPTHF), Pasithea Therapeutics (KTTA), PharmAla (MDXXF), PharmaTher (PHRRF), Psyence Biomedical (PBM), Psyence Group (PSYGF), Quantum BioPharma (QNTM), Relmada Therapeutics (RLMD), Revive Therapeutics (RVVTF), SciSparc (SPRC) and Seelos Therapeutics (SEEL).