Psychedelic: Exclusive talk with biotech company Compass Pathways

In this edition of “Psychedelic”, The Fly conducted an exclusive interview with Dr. Steve Levine, Chief Patient Officer at Compass Pathways (CMPS), a biotechnology company focused on accelerating patient access to evidence-based innovation in mental health. Here are some highlights:

PSYCHEDELIC MEDICINES: Compass Pathways is pioneering a new paradigm for treating mental health conditions focused on rapid and durable responses through the development of its investigational COMP360 synthetic psilocybin treatment. The formulation has received a Breakthrough Therapy designation from the U.S. Food and Drug Administration as well as an Innovative Licensing and Access Pathway designation in the UK for treatment-resistant depression.

“There is a tremendous unmet need in multiple mental health indications, starting with TRD, which of itself is an enormous area of unmet need with about 3M U.S. adults every year meeting those criteria,” Levine said. “Our strategy is to develop a promising class of medications in psychedelics, starting with COMP360, through the FDA-approved pathway, for reimbursement by payors within the existing healthcare system and delivery by licensed healthcare providers.”

TRD is the company’s most advanced program with ongoing Phase 3 studies, he said, and Post-Traumatic Stress Disorder follows right behind with Compass generating Phase 2 data last year.

“We are currently designing our next study, which will be a late-stage study,” the CPO said. “We see the pathway to accelerating patient access to this innovation through the FDA-approved paradigm, which stands in contrast to some of the other activity happening in the psychedelic space today.”

DIFFERENTIATION: When asked about competition in the psychedelic biotech space, Levine said that the company does not view others in the industry as competitors due to the tremendous unmet needs in mental health.

“First of all, we are the most advanced company, the only company that has positive topline Phase 3 data in a classical psychedelic at this point,” he said. “But it’s difficult to think about the space as a group of competitors. Naturally multiple organizations are developing differentiated products across a range of potential indications, but even in the areas where there is overlap, as there is with TRD, we need many new options because the unmet need is too great.”

The CPO added that there are two approved products for TRD today, but really only one is used, which is Johnson & Johnson’s (JNJ) Spravato. He said the treatment only made its way to around 50,000-60,000 of the 3M patients with TRD last year.

“If you want to dive into some potential points of differentiation, then there will be differences in terms of the duration of the psychedelic, the quality of it and potentially the durability of response for those who benefit,” Levine said. “There will likely be different aspects of patient preference among all these considerations and ultimately these treatments are likely to be delivered in settings of care that will deliver all of them if they are FDA approved. They are looking to add as many effective, safe and approved products to their platform as possible that they usually deliver in an agnostic way.”

He noted Compass has recently been hearing some assumptions that shorter-acting compounds may be better, but said it is a point that is probably worth pushing back on.

“If you look at the case of Spravato, which is shorter, it’s two hours of monitoring after the patient self-administers, ultimately a three-hour appointment, that then requires the site to fill that room all day,” the CPO said. “This means they need to turn that room over multiple times and that adds operational complexity and administrative costs. In many ways, it makes operations more difficult. It’s not necessarily a provider’s preference, particularly since we now have new reimbursement codes that providers can use for the administration day and they’re reimbursed on an hour-by-hour basis regardless of the length of the session.”

COMP360 PHASE 3 DATA: In June, Compass announced the achievement of the primary endpoint in its ongoing Phase 3 COMP005 trial, the first of two Phase 3 trials evaluating COMP360 for TRD. 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 less than 0.001 and a clinically meaningful difference of -3.6 in change at the primary endpoint.

“It is a limited dataset because the study is ongoing, it’s blinded out until week 26 and this was our week 6 endpoint,” Levine said. “We purposely requested from our contract research organization the minimal amount to be able to report out on the topline results. What we found is that in the study, when patients with TRD were administered either a single dose of 25mg of COMP360 or a true placebo, there was a difference in those two arms from baseline to that primary endpoint at week 6 of 3.6 points on the MADRS scale. We reported the associated confidence interval around that as well as the p-value which demonstrated that this was highly statistically significant.”

He stated the company also received a statement from its independent data safety monitoring board, which has been reviewing data not just from COMP005 but also COMP006 on an ongoing basis.

“Their statement applied to both studies, and it was a very reassuring one in that they saw no new safety signals and no imbalance between the two arms, particularly around suicidality,” the CPO said. “With there being some attention after Phase 2 to a perception that there may have been a difference in suicidality in the 25mg arm, because there was a small numerical difference in suicidal behavior that happened at least 30 days post administration, this really was a discharge of any concerns about safety with COMP360.”

PHASE 3 COMP006: Along with those results, Compass said its second ongoing pivotal Phase 3 COMP006 trial continues to enroll well, with 26-week data expected in 2H26.

“In 006, we bring back some elements of our Phase 2b study where we have three different doses of COMP360, 1 mg, 10 mg and 25 mg,” Levine said. “In the Phase 2, it seemed to be a design that not only confused participants, but also investigators, in being less clear about what they received. It was effective in terms of managing unblinding, but it also helped to establish a clear dose response effect to show if there is a drug effect that drives an outcome.”

The difference between the Phase 2 study and the 006 design is Phase 2 was a single initial administration, he said, and in 006, there will be two initial administrations on a fixed interval three weeks apart. In Phase 2, the primary endpoint was at week 3, while 006 will have a six-week primary endpoint, the CPO said.

“It’s important to point out that because there are two administrations, that primary endpoint will be read just three weeks after the second dose,” he said. “Both 005 and 006 have similarities in the sense of Part A, but they have a Part B, which runs from week 6 to week 26 in 005, week 9 to week 26 in 006. In both of those studies patients are eligible for up to one retreatment, driven by MADRS and that is if they have not yet remitted or they have previously been in relapse. Then both studies have an open label extension that runs from week 26 to week 52.”

COMP360 IN PTSD: Compass is in the process of designing its late-stage clinical program for COMP360 in PTSD following a Phase 2 open label safety and tolerability study in May 2024, which showed COMP360 was well tolerated and demonstrated both rapid and durable improvement in symptoms from baseline observed following a single administration.

“We’re really excited about that,” Levine said. “This is building on data that we announced last year from our smaller Phase 2a study, which did include an efficacy outcome measure in the CAPS-5 and the data was really encouraging. It was a well-tolerated treatment by the participants with a very encouraging efficacy signal. That is part of what is motivating us to move that forward as quickly as possible as it is another indication where we see tremendous unmet need.”

STRATEGIC COLLABORATIONS: In April, Compass entered a strategic collaboration with HealthPort, a multi-site comprehensive community health organization that employs an integrated model centered around social determinants of health. The collaboration will help inform the potential delivery of COMP360 treatment in underserved communities, if FDA approved. This agreement expanded the set of collaborations that Compass has, representing a broad spectrum of settings where people living with TRD receive their care in the U.S.

“HealthPort was the sixth of such strategic collaborations that we have announced and represents community behavioral health services,” the CPO said. “The other representation amongst those strategic collaborations includes a hospital system, an integrated delivery network, a decentralized model and a couple of large-scaled interventional psychiatry practices. What they represent in totality is the diversity of the types of sites of care where mental health care is delivered in this country.”

Compass is hoping to create a deep bilateral exchange of information through the collaborations, he said.

“It will help providers understand how we are delivering COMP360 today within our clinical trials,” Levine said. “And we can learn about patients they’re caring for, their diagnoses, the treatments they are delivering, the workforce that is involved, how that workforce is trained, the patient journey and the economics associated with delivering care. The ultimate aims are to understand any potential challenges to implementation if we wind up having an approved product and to ensure that there are not any unnecessary bottlenecks or gaps in the translation of this model from clinical trials into real-world care delivery.”

SCHEDULING: Several psychedelics are listed as Schedule I drugs under the Controlled Substances Act, and the CPO said it creates a barrier in the near-term as it adds complexity to conducting clinical trials, but the scheduling will change once a treatment gets FDA approval.

“If our product gets FDA approved, it can no longer be a Schedule I,” he said. “It would technically not meet the Schedule I definition because that includes no approved medical use. What would happen is that FDA approval would trigger a DEA review, and they would have 90 days to reschedule the product. After that it then moves to the states, because the states have their own rescheduling process.”

Roughly half of states have trigger laws, where they automatically follow federal DEA guidance on rescheduling, while the other half require administrative or legislative action to make that change, Levine said.

“We’ve been active in these states from a government affairs and public policy perspective,” he said. “We’re already doing work to educate on this process and to support legislation that helps with the timely rescheduling of FDA approved products.”

TRUMP ADMINISTRATION: In the 2024 election, Donald Trump was elected president and in subsequent months, several of his administration’s appointees have made positive remarks regarding psychedelics.

“Certainly, we pay attention to the statements coming out and we are also active at the federal level on the hill,” the CPO said. “There have been statements by many within the administration including the Department of Health & Human Services, Veteran Affairs and the FDA from high-level leadership that all sound very supportive of the potential approval of psychedelic treatments. It is very encouraging to hear those notes of support. We still continue to guide investors that we hear all that as neutral at worst and it does potentially represent some tailwinds and maybe some opportunities to accelerate.”

CHALLENGES: When asked about the largest hurdles facing the psychedelic biotech space, Levine said he believes they are the same challenges that any biotech company faces.

“This is long, difficult and expensive work and particularly in psychiatry, the halls are littered with late-stage failures,” he said. “It’s been incredibly validating and reassuring that we are seeing late-stage tremendous successes from multiple companies across multiple compounds and indications in the recent past. But nonetheless, this is still difficult work and the outcomes are uncertain.”

The CPO said Compass is very proud that the company is now two for two in its TRD studies but will not be taking anything for granted.

“The transition from Phase 2 to Phase 3 in larger populations is always a challenging one and funding is always a challenge in biotech and psychiatry in particular,” he said. “I don’t know that these are unique to psychedelics in any way, and in fact psychedelics amongst the leading companies seem to be succeeding where many others have failed.”

OPPORTUNITIES: As the psychedelic biotech industry develops and matures, Levine said he believes the opportunities are almost limitless given the limited tools across psychiatric indications.

“With a class of compounds that at least so far looks like it might have efficacy pretty broadly, there really is a tremendous amount of opportunity,” he said. “What is so exciting about that to Compass and to me is we have an opportunity to make an enormous impact in the lives of patients, people who are suffering in many cases, they are feeling hopeless and many have given up on treatment. Particularly with our topline positive data at hand, it brings us just one step closer to that. We’re starting to feel pretty close to potentially having an approved product and being able to bring a new option to patients.”

The CPO added as hype increases around the psychedelic space, Compass will continue to take its role as a leader very seriously and approach its work rigorously.

“We don’t make assumptions about the potential of our product,” he said. “We keep our heads down and design very robust studies, generate credible data and feel very proud that approaching it in that way we have has been able to yield such positive results.”

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), Clearmind (CMND), Cybin (CYBN), Entheon Biomedical (ENTBF), Enveric Biosciences (ENVB), Filament Health (FLHLF), GH Research (GHRS), Incannex (IXHL), Mind Medicine (MNMD), MIRA Pharmaceuticals (MIRA), Mydecine Innovations (MYCOF), NRx Pharmaceuticals (NRXP), 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), Seelos Therapeutics (SEEL) and Silo Pharma (SILO).