atai's Strategy Update
ataireleased fourth-quarter and full-year financial results this week. The press release is here, and a conference call transcript is here.
Updates on financials and the drug development pipeline got the lion’s share of the coverage, but the update on the company’s strategy is the most constructive area to explore.
atai is an instructive case study for understanding the trends shaping the intersection of psychedelics-as-medicines and digital health technology—two innovations that portend a dramatic shift in the treatment of mental illness.
CEO Florian Brand highlights the three strategic pillars at the beginning of the conference call (emphasis added):
2021 was a truly transformative year for atai. We made important progress across our programs, expanded our diverse pipeline with multiple shots on goal, and secured approximately US$410 million in financing. This allowed us to enter 2022 with US$362 million in cash, putting us into a very, very strong position to work up towards our strategic goal, achieving clinically meaningful and sustained behavioral change in mental health patients.
To achieve this goal, we will focus on three strategic pillars. One rapid acting intervention; two, ongoing digital support; and three, biomarker driven precision mental health.
(I’ll get to the highlighted ‘behavior change’ below and for a lengthier treatment of these points, see the quote from the conference call in the footnotes.)
The company has thirteen drug development projects and four ‘enabling technologies,’ so this ‘full-spectrum’ strategy begs the question, “is atai trying to do too much?”
But, directionally, they are correct.
We covered the trends more thoroughly in Atai’s Enabling Technologies; Trends in Digital Health & Neurotech: Part 1 and Part 2, in which I noted these three trends in a slightly different way:
“The study of neuroplasticity has matured from the lab to the clinic. Validated techniques that modulate the structure and function of neural pathways are here and will only get better.
The adoption of digital technology in healthcare has reached an inflection point. The FDA and other regulatory bodies are adopting frameworks for validating software as medicine, virtual reality, & immersive experiences as medicine and drug + software combination products.
The advancement of personalized medicine and precision psychiatry”
Psychedelic therapy combined with neurotechnologies and digital health tools will be the most powerful tools for leveraging the brain’s capacity to change—and thus the most potent treatments for addressing mental health, brain health, and personal transformation.
Whether a single company can pull this off is another question.
The bear case is that they have too many projects that will spread resources too thin.
Alternatively, given the unique constraints of psychedelic drug development (patentability, the time and labor-intensive nature of the treatment, etc.), such projects must be ambitious and need to combine drugs and software.
And if you can combine one psychedelic drug with software, why not do it thirteen times?
In June 2020, in Highlights and Analysis of ATAI’s Fireside Chat, we noted a comment from Chief Scientific Officer Srinivas Rao about the role of digital therapeutics in the overall patent strategy:
“Then the final bit is something we’ve been alluding to… we do actually have a strategy for a combination product with a digital device, a digital therapeutic. That is going to to markedly enhance our ability to block because do in fact have a combination product, we’ve had discussions with multiple regulatory attorneys, you can’t carve out the drug in such a product.”
So, not only is atai’s strategy instructive for understanding the emerging trends in which psychedelic medicine is coming of age and how digital technology might enable scalability of a labor and time-intensive process—but also how technology might allow for patent protection.
As we noted a few weeks ago in Naturalistic Research & Behavioral Psychedelics, I get the sense that health behaviors (sleep, diet, exercise, stress management, etc.) will become the target of mental health intervention:
I think the real significance is that these reviews point to how mental health conditions will be defined, quantified, and treated in the near future.
I say this because while we are seeing a rising interest in psychedelics as therapeutics, there are also two coinciding trends:
The advent of digital therapeutics, including Remote Patient Monitoring, Patient Reported Outcomes via smartphone, and Digital Phenotyping.
A shift in mental health research away from the traditional DSM-based diagnoses and towards the Research Domain Criteria (RDoc) with the goal of understanding mental health and illness in terms of varying degrees of dysfunction in general psychological/biological systems, which includes an emphasis on health-related behaviors.
These developments allow the tracking of day-to-day behavior—such as sleep, activity, food choices, social engagement, etc.—and for these measures to be considered in diagnosis and disease progression.
So, again note the language Brand uses:
“clinically meaningful and sustained behavioral change in mental health patients.”
For simplicity, the primary drivers of health are downstream of environment and behavior.
‘Environment’ usually means things from the literal environment like air pollution and water quality.
But it is more instructive to include literally everything that happens to us by chance as the environment. Including the family we are born into, the social norms we adopt, the economic circumstances, the quality of food we have access to, educational options, the neighborhood we grow up in, and the encounters with conflict, abuse, and other forms of psychological trauma.
The most impactful aspects of the environment on health happen early in life, so really, ‘environment’ should just be called ‘luck.’
On the other hand, there are behavior and choices. A few categories stand out in mental health, including diet, exercise, sleep, substance use, and stress management, not to mention less obvious aspects like conscientiousness or one’s ability to get along with others.
However, there is an unfortunate and unfair aspect to the human experience: the better your luck, the better your choices.
This phenomenon is as old as time; it even goes by the Matthew Effect, for the line in the Book of Matthew.
“For whoever has will be given more, and they will have an abundance. Whoever does not have, even what they have will be taken from them.”—Matthew 25:29
This makes insurance coverage and access all the more pressing so future treatments can be available to those for whom luck has been against them.
Models, Models, Models…
In December, researchers from Johns Hopkins published a paper describing a model of psychedelic drug action, the Cortico-Claustro-Cortical, or CCC Model:
Two prominent models of psychedelic drug action (the cortico-striatal thalamo-cortical, or CSTC, model and relaxed beliefs under psychedelics, or REBUS, model) have emphasized the role of different subcortical structures as crucial in mediating psychedelic drug effects. We describe these models and discuss gaps in knowledge, inconsistencies in the literature and extensions of both models. We then introduce a third circuit-level model involving the claustrum, a thin strip of grey matter between the insula and the external capsule that densely expresses 5-HT2A receptors (the cortico-claustro-cortical, or CCC, model).
It’s the therapeutic alliance, silly
A new paper from Imperial is the first scientific inquiry into the role of the therapeutic alliance in PAT.
“Here, via a sequential path model, we have demonstrated how a strong therapeutic alliance predicts pre-session rapport, which predicts greater emotional breakthrough and “mystical type” experience towards improved clinical outcomes in a trial of psilocybin-assisted therapy for depression. This work shows how the acute experience, previously established as critical to outcomes (Watts et al., 2017; Roseman et al., 2018; Johnson et al., 2019), is influenced by pre-session therapeutic alliance and rapport, supporting the idea that participants need to feel safely contained within the therapeutic relationship in order to surrender to the psychedelic experience and the vulnerabilities it may open up.”
NY Times Coverage
The New York Times has an article about the potential of psychedelic facilitated addiction therapy. The story, with the somewhat hyperbolic headline “The Next Big Addiction Treatment,” concludes with level headed equipoise:
Dr. Hendricks, however, warns that people shouldn’t get their hopes up too high. “The existing treatments are very ineffective,” he said. “I’m hoping to go from pretty darn ineffective to not bad or decent.”
Thanks for reading, and have a great weekend—Zach
The use of the lowercase ‘a’ is not a grammatical error; atai never appears with a capital ‘A.’
“And we’re especially interested in compounds with strong neuroplastic properties that open a therapeutic window to initiate behavioral change in patients. To give you an example, in the context of depression, this first pillar is really about lifting a patient out of depression in a quick and meaningful way, but then we want this patient to stay out of depression.
And this leads me to our second pillar, ongoing digital support. This pillar is about keeping mental health patients in state of remission. And it is grounded in innovative digital care provided patients before, during and after treatment.
While these tools are especially relevant for the psychedelic-assisted therapies that we’re developing, we see great potential to apply digital support across our entire drug development pipeline.
We believe pairing digital therapeutics with a rapid acting pharmacological agent from pillar one will allow us to achieve sustained behavioral change in mental health patients. What works for one patient, though, might not work for another. As we all know, the mental health patient population is highly heterogeneous.
Which brings me to our third strategic pillar, biomarker driven precision mental health. When it comes to mental health, there is no one size fits all approach. So, this pillar is about identifying patient subtypes using biological and digital biomarkers to treat patients with a therapy that is right for them at the right moment in time. We believe this will reduce the need for trial and error and give each patient the best chance of receiving the treatment that works for her or him.
Each of these pillars has a true disruptive potential on its own. But it’s by combining them that we can really unleash their full potential, allowing a true leap forward for mental health patients by achieving clinically meaningful and sustained behavioral change.” (source)