For those interested in Compass and psychedelic therapies as a sector, I would also like to recommend the Psychedelic Alpha website as an excellent source of information for this sector.
By following this, you get a very good overall picture of the sector, stay up to date, and also get various relevant “rumors”—for instance, that recent executive order was reported here before it became more widely known/confirmed. The content is partly free and partly paid; I have been paying for the content for a few months now, and I have found the content to be worth the price for me.
“Industry insiders” also regularly refer to this site, and the administrator clearly has a lot of personal contacts with industry players, obtaining both named and anonymous insider comments on various developments and rumors.
Very interesting and thought-provoking commercial reflection on the possibilities and conditions for success for COMP360. Written by a psychiatrist working at a clinic that provides Spravato treatment. According to him, there are obstacles and challenges to success, even if there is nothing wrong with the clinical efficacy:
”Five variables will determine whether psilocybin-assisted treatment is commercially viable in the clinics that currently deliver interventional psychiatry, or whether it becomes another treatment that works but that patients cannot access at scale.
The first is the REMS staffing requirement. MA versus licensed therapist; this single regulatory decision will do more to determine psilocybin’s commercial trajectory than any efficacy readout. The second is actual payer reimbursement for the 0820T-series codes. Category III codes with no payment history are promises, not revenue. The third is drug pricing and buy-and-bill margin: whether Compass prices COMP360 for clinic-level profitability or payer palatability. The fourth is DEA scheduling and state-level implementation; friction that does not appear in national adoption models.
There is a fifth variable I have not addressed in detail because it is mechanistic rather than economic, but its economic consequences are real. Psilocybin’s Phase 3 program required withdrawal from serotonergic antidepressants before dosing. Whether this is pharmacologically necessary remains an open question.5 Meanwhile, esketamine has demonstrated monotherapy efficacy without any oral antidepressant requirement [23]. If psilocybin’s labeling requires SSRI discontinuation and esketamine’s does not, the delivery friction compounds everything else in this essay: additional clinic visits for taper management, a window of untreated or undertreated depression before the dosing session, and patient attrition during the gap.
I started this essay with a spreadsheet. Small clinics like where I work might be willing to absorb a revenue reduction for the right patients. But willingness to take a loss is a personal clinical decision, not a scalable business model. Seven thousand treatment sites will not adopt a treatment that costs them money. The question is whether the reimbursement architecture can be built fast enough and priced generously enough to prevent psilocybin from becoming another entry in the catalog of treatments that psychiatry could not deliver; not because the pharmacology failed, but because the economics did.
The clinical model may work at the level of the patient. The question is whether it works at the level of the room.”
This is related to Compass only in that psilocybin research (on healthy volunteers) has been published in the journal Nature Communications, and apparently, this research result is also making news in other press (e.g., The Guardian). Anatomical changes were observable 1 month after a 25 mg dose of psilocybin, but not after a 1 mg dose. The amount of change correlates with how much increase in brain activity entropy was observed during administration (a known effect of psilocybin); on the other hand, anatomical changes can be considered the opposite of those observed in, for example, dementia, and correlate with positive psychological changes at the 1-month mark. These preliminary results may help strengthen the understanding of a psychedelic dose as a treatment that promotes neuroplasticity.
It seems I am sharing more in-depth reading here. I thought this was a good analysis of how the seemingly large differences in efficacy between COMP360 and short-acting psychedelics (competitors coming up behind) are largely explained by study design. It also includes reflections on commercial realities. It is a long article, so don’t bother starting to read it in the middle of a rush, or at all if “deep dives” into the sector don’t interest you.
Thanks. Keep them coming if you find any interesting articles. This also comes at a perfect time, as I’ve only just managed to scratch the surface regarding the competitors.
I’d like to better understand if this is just about a first-mover advantage for bringing psilocybin to market and WSB potential, or if the company has other long-term competitive advantages compared to others. That 6–8 hour duration of effect is quite a challenging equation for clinics if other competitors can demonstrate that the patient doesn’t gain any significant benefit from the longer time spent on the trip.
Psilocybin has been used extensively worldwide for a long time and has been studied much more compared to 5-Meo-DMT, meaning there is more data available. 5-Meo-DMT is also a more rarely used psychedelic, so there is less anecdotal information as well (though it seems convincing!). In this regard, GHRS and ATAI are worth checking out (it will take years to reach the market, but deals/M&A could happen quickly).
This article also highlights the fact that ultimately, the patient also decides what they agree to try!
(I have personally resolved this by investing in all of them, though I temporarily moved my stakes entirely from GHRS → ATAI because I consider the potential for a rapid price increase in ATAI to be higher right now, although I already took a hit on that adjustment I have the largest position in Compass; I find the risk/reward ratio to be the most attractive at the moment in the short term).
For example, you can use this to outline the competitive landscape. In the center, the “bullseye” represents those with FDA approval, i.e., Spravato, and then around it, the proximity indicates the current phase:
Yep! And from that, the PTSD market jumps out as favorable for Compass: over ten million US patients annually, and COMP360 is the only actual psychedelic in that slice of the pie with Phase 3 already underway!
COMP360 versus Lykos’s MDMA+psychotherapy are completely different from an implementation standpoint; in its current form, COMP360 is likely much more scalable (especially if the REMS doesn’t require a psychotherapist to be present—I’ll be surprised if the FDA actually ends up requiring that!).
Methylone is an MDMA-related substance that Otsuka just acquired; I haven’t checked how much psychotherapy has been part of that protocol.
I don’t know if this is a reliable “survey,” but according to Polymarket, there is an over 99% probability that the FDA will approve a psychedelic for medical use this year.
(For anyone new to the thread, this practically refers to Compass Pathways, which has successfully completed two Phase 3 trials and received a Commissioner’s National Priority Voucher. This might enable FDA approval as early as late summer or early autumn; no other company has a chance for such a quick approval (Usona might not be far behind if they release their topline data and duration of treatment efficacy earlier than planned, and if a single Phase 3 trial with 240 patients is sufficient).)
This was a good one; the same guy from the interventional psychiatry clinic (in a piece published in March) analyzes the comp005 and -006 results from a clinician’s perspective and, among other things, considers what kind of patients the drug could be offered to if it is approved.
” For now, the most honest summary of the COMP360 dataset is a modest one:
The molecule cleared the bar, but now we find out whether the system can catch it”
Well damn, there sure is no shortage of these plot twists. But… the executive order has been signed and the CNPV has been granted to Compass. There is a lot in the bag. Of course, if FDA leadership support was considered a factor that increases the likelihood of marketing authorization, then as a result of this, we would have no idea about that support. But fundamentally, the FDA evaluates research results, and accelerated processing has been granted.
Policy and major strategic decisions come directly from the White House, so it can be assumed that this won’t have an impact—though there could certainly be delays
Actually, from Compass’s perspective, it might be better if there isn’t “full-on” support for psychedelics from the FDA. Optimally, the FDA would process both Compass’s and Usona’s applications in 1-2 months, and Compass (with over a thousand patients in phase 2b + 2 x phase 3) gets marketing authorization, while Usona’s phase 3 with 240 patients isn’t quite enough, and they are asked for more “n” (sample size)!
I have the largest position in Compass; I find the risk/reward ratio to be the most attractive at the moment in the short term).
