Why We Invested in Gilgamesh
Transforming mental health through a deep understanding of psychedelic compounds
If you’ve been a reader of my previous blogs you know that I’m extremely passionate about mental health and the transformative potential of psychedelic medicines. (The Psychedelic Renaissance: Part 1 and Part 2). So it won’t surprise you that a main focus of mine since joining Prime Movers Lab has been to identify promising companies in this domain in which to invest. It’s truly been an embarrassment of riches — and I’ve had the privilege and pleasure of interacting with tens of companies who are focused on making the psychedelic renaissance a reality. Their work is an inspiration to me — and serves as additional motivation to help make this field a tangible reality through my role as an investor.
From that perspective, I’m excited to share that one of those companies, Gilgamesh, has recently raised their Series A, led by Prime Movers Lab with participation from Noetic Psychedelic Fund LP, Gron Ventures, Route 66 Ventures, JLS Fund, and Palo Santo Investors. Their partnership, and the partnership of these other deeply engaged investors, has been one of the best parts of working in this field.
As a quick reminder — we are on the cusp (if not over the tipping point) of an opportunity for once illicit psychedelic compounds to definitively impact mental health outcomes. Through the tireless work of foundations, like MAPS and the Beckley Foundation, among others — it has been demonstrated that compounds like ketamine, psilocybin, 5-MEO-DMT, MDMA, and ibogaine have the potential to not only treat mental health issues, but to be disease-modifying or curative. Every time I talk to someone about the potential of psychedelics — this is the part where I get goosebumps — explaining it not just as a treatment — but as a potential cure. Imagine the global impact.
Given the number of outstanding companies in this space, I thought it might be useful to share why Prime Movers Lab chose to invest in Gilgamesh.
At Prime Movers Lab, the team is as important to us as the underlying science or technology. We aim to work with founders who are mission-driven and motivated by contributions well beyond their own immediate sphere.
From the moment I met the Gilgamesh founders, I knew this was a team that not only believed in the potential of these compounds but was completely dedicated to bringing them to market for clinical use. Gilgamesh was founded in 2019 by Jonathan Sporn, MD; Dalibor Sames, PhD; Andrew Kruegel, PhD; Jeff Witkin, PhD; and Mike Cunningham, PhD. In particular, Co-founders, Jonathan Sporn and Andrew Kruegel make a fantastic pair — with Jonathan’s experience as both a clinician and pharmaceutical executive and Andrew’s brilliance in medicinal chemistry combining together to make a wonderful balance of creativity and pragmatism (and a wicked sense of humor).
This blend is similarly found in breadth of experience in the larger Gilgamesh team, which includes a mix of hard-won, practical knowledge from the pharmaceutical industry and cutting-edge science from both academia and commercial pursuits. Jonathan, Dalibor, and Andrew have all had prior startups (Perception, Kures) and exits in this space, which certainly adds “been there” energy to strategy and decision making. The recent Series A funded the expansion of the team to include top talent in the COO and CBO roles, among others. I had the pleasure of meeting the entire team in person in NYC last month and was blown away by the energy, intellect, and drive of the team to deliver clinical results as quickly as possible.
The one thing you might note about the psychedelic medicine domain is that it is still evolving. MAPS, Johns Hopkins, and other organizations have done a truly remarkable job of showing the potential of what I will call the “original” compounds — those directly extracted from the biological sources (e.g, psilocybe cubensis, iboga root bark), synthesized to be identical (psilocybin, psilocin), or novel synthetics (MDMA, LSD). It has been extremely important to establish the clinical efficacy of these compounds so the case might be forcefully made for their rescheduling. As a reminder, most of these compounds are Schedule 1, which means according to the government they have NO accepted medical treatment and a high potential for abuse. It is important that this work continues to destigmatize and legitimize these compounds and their potential.
However, nature isn’t perfect. Therefore, Gilgamesh is focusing on novel chemical entities that may serve some of the same outcomes for mental health, but in more clinically accessible formats. The beauty of this development approach is that they are able to leverage the substantial human anecdotal observations combined and link that with an understanding of the medicinal chemistry to develop new molecules with more favorable performance profiles.
Without getting too deep into the chemistry — Gilgamesh has several programs that are of particular interest. First, they are working on an oral ketamine analog. Ketamine is the ONE thing from the psychedelic-related medicine category that is actually approved for use in treatment-resistant depression. However, its delivery mechanisms are currently limited to infusion or intranasal delivery, and both require constant clinical supervision during use (and take several hours). The potential of an oral ketamine analog, especially if less dissociative than ketamine, opens up the clinical utility to potential home use, keeping the neuroplastic effects while reducing the side effects typically associated with ketamine. This is a very exciting development for the field and has enormous clinical potential.
Ibogaine is another psychedelic compound of natural origins and has complex pharmacology with multiple drug targets (ibogaine is not a synthetic but a natural substance) that can be improved upon. Ibogaine has been demonstrated to have a powerful disruptive effect in addiction, but the natural compound itself has several less desirable features, including cardiac toxicity in some individuals. The Gilgamesh team is working on a safer, possibly more efficacious ibogaine analog that has the potential to disrupt the treatment of substance abuse disorders with a better therapeutic index. The potential of these compounds to impact addiction is profound — and badly needed.
And finally, in the tweaking nature category — the Gilgamesh team is working on a compound that targets 5HT2A (serotonin receptor for the classic psychedelic drugs like psilocybin), but in a manner that is closer in performance to a micro-dose. By removing some of the hallucinogenic aspects, while keeping the activity at the receptor — they propose it may afford the opportunity for a “take home” or maintenance type of clinical profile that can be independent of or in conjunction with a larger reset experience. Again, leveraging the power of the natural compounds while increasing their clinical utility.
There are other programs in development and some very sophisticated screening technologies that have helped accelerate these findings, but I will stop there for now. I hope this paints a clearer picture of our excitement around Gilgamesh. Their “multiple shots on goal” approach is compelling in this developing space.
But most importantly, these “shots on goal” represent hope, and real progress in the race to provide healing for the hundreds of millions of individuals worldwide suffering from mental health conditions. This is truly the type of scientific breakthrough that motivates us every day. We are grateful to be partnered with Gilgamesh, and the larger community, in this critical endeavor.
Prime Movers Lab invests in breakthrough scientific startups founded by Prime Movers, the inventors who transform billions of lives. We invest in companies reinventing energy, transportation, infrastructure, manufacturing, human augmentation and agriculture.
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