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Welcome to Tricycle Day. We’re the psychedelics newsletter that went home instead of going big. Joke’s on us though. Home is within, and it’s infinite in here. ♾️

Florian Brand had no interest in medicine until he watched his best friend get chewed up and spit out by the mental healthcare system. That friend was Lars Wilde, and together they'd build Atai Life Sciences into one of the most ambitious psychedelic biotech platforms ever attempted.

We asked Florian how Atai came together, why he believes 5-MeO-DMT will fit into modern healthcare, and the barriers to patient access that have nothing to do with FDA approval.

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What led you to starting a psychedelic biotech company?

My best friend and cofounder of Atai Life Sciences (now AtaiBeckley), Lars Wilde, and I started our very first company together back in 2012. A couple of years after founding that startup, Lars developed a severe depression, and I watched him go through first, second, and third-line treatments that led to a lot of side effects but did nothing to help him. He eventually came across the psychedelic research at Johns Hopkins and Imperial and decided to try a high-dose psilocybin experience in a therapeutic setting. He described it as transformative and curative, allowing him to get to the root causes of his suffering.

Around the same time, my wife went through a similar journey, and for her, a psychedelic experience was equally profound and healing. Finally, as a teenager, I had my own struggle with anxiety, depression, and suicidal ideation. Unlike Lars and my wife, I was fortunate that psychotherapy and establishing a robust daily meditation practice worked really well for me. But seeing people I love failed by conventional treatments is what got me into biotech and starting Atai. The “why” was deeply personal.

We quickly realized that despite the significant unmet need in mental health, no new innovative approaches had made it to patients in decades. For example, when Spravato (a version of ketamine) was approved in 2019, it was widely celebrated as the first antidepressant with a truly novel mechanism of action since the introduction of Prozac in 1987!

In psychiatry, only about 7% of drug candidates make it from Phase 1 to approval, compared to 24% in Hematology. One of the key reasons for psychiatry being one of the riskiest areas in drug development is the poor translational validity of animal models. A drug that makes a mouse "less anxious" in a maze rarely translates perfectly to a human suffering from anxiety. The human brain is much more complex than that of a mouse.

That’s why, at Atai, we decided to focus on drug candidates with prior evidence in humans. Psychedelics have been ritualistically used for centuries, if not millennia, for healing purposes and were studied in clinical trials in the 1950s and 60s before being banned for political reasons. To further increase our odds, we decided to work simultaneously on multiple drug candidates. This “multiple-shots-on-goal” approach allowed us to be radically truth-seeking and only progress compounds with excellent data.

AtaiBeckley's 5-MeO-DMT drug candidate BPL-003 earned the FDA's breakthrough therapy designation this year. Congrats. What went into Atai's decision to acquire and merge with Beckley Psytech?

From my perspective, 5-MeO-DMT is a very compelling compound. The total treatment experience is four to five times shorter than a long-acting compound like LSD. The experience with Atai’s formulation of 5-MeO-DMT lasts around two hours, which is in line with the established treatment window of Spravato and should significantly improve patient access. If you only need to keep somebody in a safe space for two hours versus six to eight, you can suddenly treat three or four patients in a given day. That obviously increases capacity.

When it comes to the merger, there was strong philosophical alignment with the Beckley team early on, which led to Atai’s initial strategic investment in Beckley in January 2024. Both companies were very patient centric and had strong conviction in short-duration psychedelics—Beckley with intranasal transmucosal 5-MeO-DMT and Atai with oral transmucosal DMT. Given the high degree of alignment and continuously strong data from Beckley’s clinical trials, it was a logical step that Atai and Beckley joined forces fully this year.

5-MeO-DMT is known for producing some of the most profound mystical experiences of any psychedelic. Does the intensity of that experience create concerns that might outweigh the benefit of the two-hour treatment window?

That's an excellent question, and I think it's a totally valid concern. 5-MeO-DMT can be extremely intense and sometimes overwhelming when inhaled, which is the standard route of administration that therapists in the underground and even some drug developers like GH Research use.

But here's what gives me comfort about BPL-003. Atai is using an intranasal approach that leads to a much gentler subjective experience. Atai’s formulation of 5-MeO-DMT does not lead to the hyper-extreme experience you might see on YouTube.

When developing and testing the intranasal formulation, investigators asked healthy volunteers at multiple time points to rate the intensity of their subjective experience on a scale from zero to ten. In this Phase 1 study of BPL-003, the 8mg dose, which is now moving forward into Phase 3, maxed out at about eight out of ten. The onset of effect was also delayed, and the overall experience was longer and more gentle. With an inhaled formulation, they’d certainly hit a ten on the intensity scale within minutes of administration, allowing very little time for introspection.

This gentler profile of Atai’s formulation of 5-MeO-DMT, paired with the benign and manageable adverse events data from the Phase 2b, gives me confidence this treatment is integratable into the mental healthcare system, similar to Spravato.

Since stepping back from Atai, you've been focused on the barriers to patient access beyond FDA approval. What have you learned so far?

One theme that keeps coming up is that those of us working in psychedelics still live somewhat in a bubble, even 10 years in. There's a large share of healthcare practitioners outside the large urban coastal areas who have not even heard of the therapeutic potential of psychedelics and, due to remaining stigma, might be reluctant to offer these therapies to their patients when they are approved.

We saw a similar pattern with Spravato. It took a while for J&J to gain adoption and reach the impressive $1.8bn sales figures that Spravato is making now on an annualized basis. Initially many health care providers didn't feel sufficiently prepared to deliver this new treatment. If I am new to this field as a psychiatrist, one barrier is the fear around what could go wrong. If there's an adverse event, how do I respond appropriately? And that was for a version of ketamine. If you project that hesitancy to psychedelics, which might be perceived as even more unpredictable, we could see similar reluctance. This underscores the importance of educating stakeholders, especially health care providers, long before approval.

On the clinical infrastructure side, we might be okay for the first year or two when Compass, Usona, and Resilient (formerly Lykos) make it to market. But by year two or three, we could quickly hit capacity constraints. The existing health care delivery infrastructure is already quite fragmented. Something like 10% of healthcare providers that are certified to deliver Spravato prescribe 90% of all doses. It's pretty skewed with a long tail of occasional prescribers. Fortunately, investors and entrepreneurs seem to have identified this gap and are finding opportunities to grow the clinical infrastructure, ahead of the first approval of a psychedelic therapy. See for example Radial’s recent Series A announcement. I predict that we will see a lot more funding flow into building out the clinical infrastructure for psychiatry in 2026.

Then for reimbursement, you have to prove these treatments are cost-effective, not just efficacious. That requires so-called health economic outcome models looking at prevented hospitalizations, reduced medication costs, improved productivity. It's very different from what you need for FDA approval. But given the speed, magnitude, and durability of improvements with only a single dose of compounds like Atai’s BPL-003 in clinical trials, I am very confident we will achieve broad reimbursement for psychedelics by health insurance providers.

You mentioned you found relief from anxiety yourself through meditation and therapy. Do you think meditation could ever be part of a prescribed protocol alongside psychedelic medication?

I would be shocked if it's not going to become part of it. There's a huge, legitimate role for mindfulness and meditative practices in this space. It doesn't have to be a one-hour transcendental meditation practice. It could be as simple as integrating basic mindfulness and grounding techniques.

There's great evidence for the efficacy of mindfulness practices on mental health outcomes. If I were to start a clinic, I would definitely look into that area with the goal to positively change the behavior of mental health patients and help them form healthy habits. I'd be shocked if therapists active in the underground are not already combining these approaches.

The question becomes: What should be included in the drug approval process versus what's part of broader clinical practice? If we reflect on what happened with the FDA’s review of MDMA, it was too much to expect drug developers to solve everything at once—to develop the drug and establish how it will be delivered within a psychotherapeutic context post-approval. The mandate of drug developers is really to get the drug approved by the FDA, so that practitioners have more tools available to treat mental health patients. There's a role for clinicians, professional associations like the American Psychiatric Association, and everyone else in health care delivery to figure out how exactly we want to see this type of care delivered in the real world.

The balance we must strike is: What sacrifices are we willing to make to allow for greater patient access, while maintaining a firm line around minimum requirements for quality care? These are important questions we need to answer collectively as an ecosystem.

Want more from Florian?

Subscribe to his Substack newsletter, Where Psychedelics Meet Entrepreneurship.

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DISCLAIMER: This newsletter is for educational and informational purposes only and is not intended as a substitute for professional medical advice. The use, possession, and distribution of psychedelic drugs are illegal in most countries and may result in criminal prosecution.