I don’t think a price of $1.25 billion seems expensive with a $400 million cash position, if you consider that Spravato, based on its latest quarterly results, is hitting $2 billion in annual sales, and a product with similar potential at Compass could get marketing authorization and FDA rescheduling—meaning commercial readiness—this fall with this Trump executive order…?
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We should look into this more regarding the competition. The Usona Institute is a non-profit organization that also researches psilocybin in MDD (“major depressive disorder”) at a Phase 3 level. They also have BTD.
The study started in 2024, apparently the last patient was dosed in 1/2026, with an estimated study completion of 1/2027 (patients are followed for one year). It’s a small study, with only 240 patients and 1 Phase 3 trial.
MDD and a small patient number, could the efficacy perhaps be “striking”?
RFK/MAHA dislikes Big Pharma and profiting from medicines. If political pressure affects the advancement of psychedelic treatments, could this non-profit organization come and ruin Compass’s business? Could Usona be one of these three CNPV recipients? (At the Phase 3 level in psychedelic therapies and BTD: Compass, Definium, Helus, Usona, and then MDMA+ psychotherapy, i.e., Lykos, which previously failed to get marketing authorization during the previous administration, now Resilient, could perhaps be a candidate for CNPV receipt, perhaps as early as this week.)
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I haven’t actually invested in magic mushrooms yet, so I have been following this (also) high-quality thread with interest and am trying to bring myself up to speed on the subject in the background.
I don’t really have anything to add to @JusaVaan’s excellent post other than the statement made by the FDA’s Martin Makary on April 18th: “Next week the FDA will issue three national priority vouchers for serotonin 2a agonists also known as psychedelics.” Direct YouTube link to the quote.
A question for the pros: is this statement enough to remove Resilient’s MDMA-assisted therapy from the list of potential CNPV recipients, since based on my limited understanding, MDMA is not a direct 5-HT2A agonist?
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Thanks for the great catch! Based on that, I think Resilient Therapeutics can be removed from the list of candidates at this initial stage.
Compass is an obvious choice as a voucher recipient.
In terms of a short trade, it might be interesting to speculate who the other two getting the voucher will be (apparently already) this week.
In my opinion, the most likely options are Definium, Usona, and Helus.
(Atai also has BTD, but Phase 3 is only just starting, so I don’t think it’s in this group yet, even though as an investor I’d hope so).
I’m betting on Definium and Usona (Usona because the MAHA crowd might sympathize with a non-profit).
(Helus Pharma could offer a quick profit if they were to get a voucher (the share price has performed poorly and even dropped further this week, even though others have jumped). It could be a favorable risk-reward to keep some chips in this for a few days, but I still believe more in Usona getting a voucher and I don’t have those chips right now anyway…)
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Is there something wrong with my layman’s line of reasoning when I see Usona’s potential CNPV voucher as a significant risk for Compass Pathways?
Usona is testing practically the same active molecule (just crystallized differently) for the treatment of major depression (non-TRD). Keeping the JFK/MAHA point in mind, if Usona receives the same CNPV voucher and marketing authorization on an accelerated timeline, won’t this cannibalize Compass Pathways’ potential patient pool?
Presumably, no one starts with a TRD diagnosis, and apparently, at least two failed drug trials are required before a TRD diagnosis is given. If even one of these in the future were to be Usona’s psilocybin, why try the same active ingredient from Compass Pathways again once the patient falls under a TRD diagnosis?
I cannot evaluate the dynamics of the currently available drug arsenal, but is the bull case for Compass Pathways (despite Usona) based on the idea that even if Usona’s treatment were approved, it would first have to carve out a space alongside traditional, already proven antidepressants, which might not be expected to happen overnight?
Edit: Could Compass Pathways be considered to have a bull case despite Usona also because, while Usona is a non-profit and can push the price of psilocybin lower than Compass Pathways, the cost of a treatment day with two therapists present is still so high that it wouldn’t easily become part of first-line treatment?
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I also think it looks like worrying competition for Compass if Usona gets CNPV and might possibly even be a Maha-favorite in some way as a non-profit organization.
AI even thinks that Usona could benefit from the data Compass has gathered at great expense:
” 1. The 505(b)(2) Regulatory Pathway
The FDA’s 505(b)(2) pathway allows a drug sponsor to rely on safety and efficacy data not developed by the applicant. If Compass’s COMP360 is approved first, it could become a "Reference Listed Drug." Usona could then potentially reference Compass’s extensive clinical findings to support its own application, provided they can demonstrate their psilocybin formulation is sufficiently similar in its active moiety. This would allow Usona to avoid the massive expense of replicating the large-scale trials Compass has already funded”
In principle, I don’t know if payers, e.g., insurance companies, would be in any way tied to a specific diagnosis/definition, MDD or TRD. I suppose one could say that they would reimburse therapy with Usona’s molecule for MDD, as long as, for example, 2 antidepressants have first been tried with proper dosages?
One thing then is which clinic systems each psilocybin company gets their products into; could Compass have a moat here, as partnerships have been created and the cash position is undoubtedly better than Usona’s. On the other hand, could the administration help in improving the availability of affordable care with taxpayer money?
If, for example, Johnson & Johnson (Spravato) were to buy out COMP360 and push it into use at the same clinics quickly, could Usona’s product still be left for smaller-scale use in different types of public sector clinics?
Compass has pushed through a reimbursement code for psychedelic-assisted therapy (i.e., so that the clinics’ effort is compensated on an hourly basis); could Compass have some kind of moat here? Compass apparently has other patented elements in the overall package besides just the molecule—at least they’ve tried; I haven’t looked into it more closely.
I once wondered with Clark why Compass’s valuation seemed to be lagging compared to others. Could Usona be the reason?
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I’ll have to continue investigating other aspects of the matter, but as I understand it, Usona cannot use this pathway for the following reason.
Compass Pathways is seeking approval for its drug via the 505(b)(1) pathway, meaning all data comes from their own studies. Since the FDA has not previously approved psilocybin in any form or crystal structure, it receives NCE (New Chemical Entity) exclusivity, which grants Compass Pathways 5 years of data exclusivity. During these 5 years, the FDA may not approve any 505(b)(2) applications related to this active substance that reference Compass Pathways’ data.
For this reason, Usona is also seeking approval via the 505(b)(1) pathway. Usona should also receive 3 years of protection from the FDA for its own data regarding psilocybin, as they are producing new clinical data required for marketing authorization.
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Wow, thanks!
Usona’s study is indeed small, a much more modest dataset than Compass’s.
Still, there is a risk that MAHA is on the non-profit’s side. That is, is one Phase 3 (n=240) sufficient for approval after all, if there is a political tailwind? And does it indirectly affect the decisions of the FDA and, for example, insurance companies that both studies have investigated psilocybin, even if the data officially has exclusivity?
What should also be investigated is Usona’s Phase 3 study protocol in more detail. For example, whether it includes more elements of therapy, which could affect the FDA assessment (so far, therapy has had to be minimized to demonstrate that it is specifically a pharmacological effect, as the FDA evaluates drugs and not therapy).
For conventional depression, it is more sensible to use other medications because psilocybin is generally quite impractical, as it requires long-term supervision of the patient in clinical facilities. That’s why I’m not particularly excited about that heavily contested MDD market and the drugs aimed at it, which other peer companies are pursuing, even though their market potential is larger on paper. As a business model, attempting to capture the entire smaller TRD market seems significantly more attractive to me for that reason.
I also think the first-mover advantages regarding branding are underestimated in discussions. COMP360 will likely be the ChatGPT/Ozempic of psychedelics. This is the drug that will be promoted in all the news and on Joe Rogan’s podcast. This is exactly the new breakthrough drug that all depressed individuals will be asking their doctors to try. The meme stock potential of WallStreetBets alone could be enough to tenfold the share price. If you treat the stock as just another generic pharmaceutical company among others, there is a serious risk of underestimating the explosive potential of both the stock and the sales.
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I agree about the share price’s explosive potential / meme stock potential.
However, in terms of diagnostic coding, TRD is not a separate entity from MDD; so for an MDD patient, once the number of conventional medications defined by the insurance company has been tried and the doctor/psychiatrist deems psilocybin appropriate, Usona’s product could presumably be an option just like COMP360, if it’s available at the clinic where the patient is referred.
By the way, I just bought more CMPS at 8.42 USD, I notice…
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According to the news, the FDA announced 3 CNPVs today, 2 of which are psilocybin and 1 is methylone. Not named, Compass hasn’t released a PR yet. The psilocybins are likely CMPS and Usona (non-profit), and I think Otsuka just snatched up the methylone. I bought more CMPS again… high risk, but maybe a PR today and it jumps?
Edit: The Psychedelic Alpha site (a good source of information) reports that it’s Compass, Usona, and Otsuka.
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Competitive situation is an open question with Usona
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So while it was previously expected that final data would arrive in Q3, the NDA in Q4, and the FDA decision in early 2027, we could now, in the best-case scenario, receive the FDA decision as early as this year. The timeline for the Schedule I reclassification may still delay the start of sales, but there is now a genuine possibility to get the sales machinery running by the end of this year.
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” Makary went on to say decisions on some of these therapies could come as soon as this summer or fall.”
https://www.cnbc.com/2026/04/24/fda-psychedelic-drug-research-trump.html
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I’ve been thinking a lot about this Usona Institute setup lately; the situation with the Compass investment seems tricky to me.
In the slightly longer term and as a whole, I think this CNPV matter is likely a negative for Compass. The problem isn’t Compass’s CNPV, of course, but rather the granting of CNPV at the same time to a non-profit psilocybin developer. In reality, the situation is surely complex due to patent protection, CMPS’s potential to sue Usona for patent infringement and at least delay their market entry, the specific “therapy” protocols used with each molecule, how Compass has built its collaboration network with different actors, etc.
But “keep it simple, stupid”… it’s definitely a bad thing for COMP360 if a low-cost version of psilocybin gets marketing authorization around the same time, and at worst, it likely erodes Compass’s pricing power, which is a prerequisite for Spravato-like returns (Spravato treatment costs, for example, $30,000/year/patient for the drug alone, so to achieve a similar annual revenue per patient, COMP360 would need to be priced at, say, $7,500 per dose!).
So Usona is only doing one Phase 3 trial in MDD, n=240. For a for-profit firm, no one would likely have thought psilocybin could get approval with such a small, single study, but considering the FDA’s new guidelines (one “proper” Phase 3 is essentially enough) and the political/CNPV/MAHA tailwinds for such a non-profit/low-cost drug producer, it seems very possible that Usona could get that marketing authorization.
This is the bearish point; would it be wisest to sell with a reasonable profit?
On the other hand, an EO regarding psychedelic therapies has just been issued, CMPS is now among the “prioritized” names as a company, and the whole thing might just be starting to enter broader public awareness. If the Usona risk doesn’t feature prominently in the discussion, could stock demand and thus the price take off explosively in the coming days and weeks? Is this a terrible time to sell?
One more thing is the M&A potential. Looking at the case from, for example, Johnson & Johnson’s perspective: Spravato is their fast-growing drug, and they’re already hitting $2 billion in annual sales. Was $3.5 billion/year predicted? COMP360 and Usona’s low-cost psilocybin threaten this. Wouldn’t it make sense to buy COMP360 now at a reasonable price/premium, say $2-4 billion? Rapidly push COMP360 into clinics offering Spravato, start expanding indications/push Phase 3 for PTSD forward at speed, and challenge Usona with numerous patent infringement lawsuits to at least slow down Usona’s momentum? The logic would be there for J&J, and the Usona threat could also accelerate Compass’s willingness to make a deal, even if perhaps not at the sky-high price we once dreamed of.
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In my opinion, the M&A potential increased significantly also because big pharma Otsuka entered the scene, and the psychedelic market is no longer just a playground for a few small-time players. You would think others would wake up too.
I’ll also highlight a point that, to my knowledge, hasn’t been touched upon yet. In the current situation, I believe both CMPS and Usona will receive marketing authorization. CMPS in late 2026 or early 2027 and Usona about 6-9 months after that. Since it is a single-dose drug, Usona’s sample size should be sufficient to demonstrate safety. However, after digging into the subject, I don’t believe the companies will be starting from the same baseline with their research results.
As is known, the current cost of two therapists’ full-day labor to treat one person is a significant part of the treatment cost. Usona has conducted Phase 3 exclusively with this 2:1 model, and due to the small sample size, they shouldn’t have any chance of streamlining the REMS protocol. CMPS also did Phase 2b (n = 233) (practically the same sample size as Usona’s Phase 3) with the 2:1 model, but switched to a 1:1 model for Phase 3, where one person supervises one patient. Getting this approved would already be a significant economic leap, but I don’t think it will be quite that straightforward.
Lykos previously tried (2024) to seek FDA approval for its MDMA-assisted therapy for the treatment of PTSD, but only succeeded in tarnishing the industry’s reputation. Serious misconduct was revealed behind the studies (manipulation, sexual abuse), distortion of patient symptoms, lack of objectivity, etc., and the FDA expert panel rejected the application 10-1 regarding safety. I suspect that due to Lykos’s negligence and the vulnerability of patients during psychedelic treatment, a pure 1:1 model is also blocked for CMPS because it enables patient abuse. Instead, I believe in the approval of some kind of hybrid model where, for example, 1:1 treatment is underway in several rooms with a certified nurse, all supervised by one psychiatrist or doctor via a control room monitor.
The exact implementation model doesn’t matter that much, but CMPS will certainly aim to get what they studied in Phase 3. I consider it important that CMPS succeeds in getting some kind of streamlined version of the treatment model through immediately. Marketing authorization tied to a 2:1 model would mean, if not losing the war, at least losing the battle.
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Last year, there was also bretisilocin, which Abbvie acquired from Gilgamesh in a 1.2 billion deal
Thanks for the good thoughts. It’s a bit unclear to me regarding Usona’s marketing authorization application how much the FDA has to base its decision specifically on data produced by them, and how much weight other information obtained so far (even that produced by Compass!) regarding psilocybin carries. And can Usona only utilize investigator-initiated trials conducted with their product, or could any psilocybin serve as justification for safety, for example.
I don’t know if things would go the way you’re thinking regarding the REMS label? On the other hand, it is a bit against common sense if one 25 mg psilocybin dose required 2 supervisors/psychotherapists and for another, 1 would suffice.
I have been under the impression that Compass also still had 2 supervisors in phase 3, but I’m not sure.
Last week there was an interview with representatives from Compass, atai, Definium, and Helus (can be found at least via the CMPS and ATAI sites). They said in this regard that from a commercialization perspective, it’s very important not to create an excessive bottleneck with REMS guidelines regarding the availability of professionals, and that in recent years the FDA has moved in a favorable direction in this regard, and the idea was precisely that monitoring could partially be AV-based without someone sitting next to the patient all the time. At least this could probably replace the second therapist, but I understood the comment to mean that (in the opinion of Definium’s CEO) perhaps audio-video monitoring could suffice, with someone coming on-site at the point if it seems it might be good to go.
Edit: By the way, Otsuka has apparently made an early-stage investment in Compass, and someone from Otsuka has been or perhaps still sits on the board.
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I need to supplement the message I wrote just before falling asleep a bit, as I don’t have any completely ironclad evidence of the 1:1 model used by Compass in phase 3 either, only indirect evidence picked up here and there that they are trying to find alternative ways to the 2:1 model. Commerciality is evident here in the way that Compass has constantly spoken about the presence during treatment being psychological support, not therapy; therefore, their research aims to streamline this support to a minimum in terms of personnel and a maximum in terms of digitalization, which I of course fully understand.
Below are a few AI-assisted findings, all of which I’ve had time to check except the last one, as I couldn’t find it immediately, but on which I have based my conclusion. I put these in a spoiler to avoid cluttering the forum.
Data points
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(Verified) Usona has in its phase 3 firmly locked into a two “facilitator” model: ” Investigational Product (IP) will be administered in the context of a “Set and Setting” (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators.”
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(Verified) Compass, on the other hand, has in phase 3 left more room for maneuver regarding the number: “In this study, the aim is to assess the efficacy of COMP360, administered with psychological support in adult participants with TRD, in improving symptoms of depression.”
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(Verified, pretty much a smoking gun) In the Q&A section of the 2022 Q3 quarterly call, the following question was asked: “I think one of the changes for the Phase III from the Phase II is the need for one person to provide psychological support rather than 2. So I’m wondering if, first, can you confirm that change? And then can you discuss the implications of the change including the regulatory input received regarding it? And how it would be expected to impact the Phase III program and eventual commercialization?”
Kabir’s response: "So yes, we can confirm that. For the administration session, there will only be one person, one therapeutist required to be present. I think from a… without going into great detail around our regulatory strategy, clearly, it is not our intent to ask the FDA to regulate psychological support. That’s not their role. Their role is to regulate drug therapy. And therefore, there is discretion to some degree around how psychological support is provided, though clearly, that again is something that needs to be aligned as appropriate. From the point of view of how we think about that going forward, I think it’s important to recognize that a trial setting is clearly different from a potential commercial setting. In a trial setting, we are having to prepare patients for the possibility of different doses. There’s a very different set of preparation and expectation that’s required for that. So we are already working through some of the ways in which that may change when we actually get to commercialization. And as we talked about on October 12 as well, we are looking at ways in which we can look at different ways of optimizing psychological support, working with what are likely to be some of the commercial sites of treatment, such as the chains of clinics, ketamine clinics and so on that we referred to at that time. So that will be work in parallel with the Phase III to look at how we actually do optimize the psychological support piece as well. -
(Verified) In the risk factors section of the 10-K, the term “facilitator” is used in the singular: “any potential unfavorable publicity, including negative publicity associated with recreational, spiritual or medical use or abuse of psilocybin or other psychedelic drugs or with adverse
outcomes or side effects from the use of psilocybin or other psychedelic drugs such as unfavorable publicity related to use of psilocybin at Oregon state-licensed psilocybin service centers under the supervision of a state-licensed facilitator;”
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(This is still unverified) Compass organized a presentation for investors in October 2022: “Phase 3 program in TRD investor webcast”, where the following was allegedly communicated:
The company communicated to analysts that Phase 2b (COMP004) served as a necessary medical “proof-of-concept” regarding safety, but its heavy model is not ready as is for widespread clinical use.
Management also emphasized that the new Phase 3 program is designed specifically with commercial scalability in mind, which in this case should mean a more flexible psychological support model and the integration of digital monitoring tools.
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Okay, thanks! I probably haven’t listened to ones that old myself, or at least I didn’t remember them anymore. In that case, it sounds like one person sitting in the room would have been enough for the FDA.
Usona’s protocol is difficult to evaluate because outward communication is so scarce—for example, whether it includes therapy-like elements to such an extent that demonstrating the pharmaceutical efficacy of the drug would be difficult…
Did Usona also have external remote raters for the MADRS assessment, like listed companies? (Of course, I can look it up myself when I have time…)
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” Masking
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
The following roles will be blinded to the treatment group assignment in the Double-blind Period during the trial: Participant, Investigator, Site Personnel, Facilitators, Efficacy Raters (including Site Raters, Participant Raters, and Central Raters), Contract Research Organization (CRO) Staff, and Sponsor.
All roles other than the Sponsor, CRO, and Ethics Committees will also be blinded to the randomization ratio and Patient Health Questionnaire-9 (PHQ-9) score for re-administration eligibility.
The Central MADRS Rater will also be blinded to all aspects of the protocol and trial visit for each participant.
Blinded trial site personnel will complete administration of the IP.
Full blinding of trial personnel, Sponsor, and participants will be maintained until database lock at the conclusion of the trial.”
→ so it seems there is a ”central rater”, i.e., a separate blinded assessor
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