Gilgamesh, a New York City-based biotechnology company developing psychedelic drugs to treat mental illness, is “in full swing” to close on a Series B round of funding in the next few months, according to Laszlo Kiss, Gilgamesh’s Chief Business Officer and Head of Research.
This round follows up on the company’s $27 million Series A fundraise from May, 2021, and will add to the $34 million raised to date.
“In this next round of financing, we hope to be able to continue to build the company and bring additional programs into the portfolio,” Kiss told Psychedelic Invest.
Both raises were led by Prime Movers Lab, with the May 2021 Series A including investors such as the Noetic Psychedelic Fund LP, Gron Ventures, Route 66 Ventures, JLS Fund and Palo Santo Investors. Y Combinator, a prominent American technology startup accelerator, also owns a stake in Gilgamesh.
The combined funding will advance the firm’s mission of developing psychedelic-related pharmaceuticals that are differentiated, novel and transformative for the treatment of mental disorders such as depression, anxiety and substance abuse, said Dr. Jonathan Sporn, Gilgamesh’s founder and CEO.
About 60% of the private company is held by Sporn and a handful of co-founders.
Gilgamesh will continue to focus on distinguishing itself from its psychedelic peers through the caliber of its team, the breadth and depth of its drug pipeline and investment in cutting-edge clinical technology, added COO Yoni Falkson.
After working as a researcher at Boston’s Mass General Hospital and then the National Institute of Mental Health, Sporn became interested in the potential of psychedelic drugs after remembering his own positive experiences with psilocybin in college.
Sporn founded Perception Neuroscience, which was later sold to ATAI Life Sciences (ATAI) and is now in phase two drug development of the R-Stereo isomer of ketamine. Sporn left Perception to found Gilgamesh in 2019.
Falkson’s background is in what he calls “the more business side of the industry.” He worked for Pfizer and then Generon on new product planning and early commercial development. He is also the co-founder of SpringWorks Therapeutics. Falkson advised Gilgamesh in its early days and joined as COO in the middle of 2021.
Kiss, a neuroscientist by training, spent 18 years in pharmaceutical R&D at Merck and then BMS. For the following few years, Kiss was increasingly involved in business development, research and evaluation in corporate venture-type roles at Pfizer and Biogen before joining Gilgamesh in late 2021.
Late 2021 saw several other experienced people also join Gilgamesh, including:
- Chief Medical Officer Gerard Marek, a renowned expert on serotonin system biology. Gerard is a former assistant professor at Yale University and was the Chief Scientific Officer of Psychiatric Disorders Discovery Biology at Eli Lilly and Company.
- Head of Clinical Development Daniel Umbricht was the Head of Early Clinical Research in Neuroscience at Roche and a former academic at Zurich University, bringing years of expertise in electrophysiology of psychedelic medicines and industry experience in experimental and translational medicine in neuroscience.
- Translational Medicine Scientist Ed Christian is a clinical and preclinical neurophysiologist, who served as Executive Director of Translational Medicine at Cadent Therapeutics and for two decades as a Senior Principal Neuroscientist at AstraZeneca.
The company also added three strategic members to its board of directors in late 2021:
- Amy Kruse is a General Partner at Prime Movers Lab (Gilgamesh Series A & B lead investor), neuroscientist/biologist entrepreneur and a former program manager at the Defense Advanced Research Projects Agency.
- Robert Berman was the lead author of the seminal study of ketamine in depressed patients (Berman et al 2000) and led clinical antidepressant development of aripiprazole (Abilify). He is a co-founder of Biohaven Pharmaceuticals.
- Phil Skolnick is a former director of the Division of Therapeutics and Medical Consequences at the National Institute on Drug Abuse, NIH. He was a Lilly Fellow in Neuroscience and served as the CSO and President of DOV Pharmaceutical, Inc. He is currently CSO of Opiant Pharmaceuticals.
“We’ve hired what we think may be the best small team in neuroscience and probably the best team of anyone that’s doing work in the psychedelic space. It’s a mixture of people that are chemists and that know how to design new psychedelic drugs and know the law and history of all the molecules that have been made in the psychedelic space. Along with people that have tremendous expertise in drug discovery and development, from the preclinical through the clinical space, from both the major pharmaceutical companies and the biotech world.”
The Drug Pipeline
“We’re not just pursuing one compound, we are pursuing a number of really exciting mechanisms within the psychedelic space,” Falkson said. “All of those programs are being pursued in a way that only is going after novel, new composition matter IP. So we’re looking to make clear improvements upon the known molecules, in ways that both create clear IP and have significant clinical and commercial improvements that we think have much greater upside to the patient and commercially.”
Gilgamesh has four main drug candidates now in its development pipeline:
GM-1020 is a ketamine analogue program which involves cyclohexylamine compounds that are being developed for the treatment of depression and substance abuse disorders, anxiety disorders, etc., Sporn explained.
“My last company Perception is developing R-ketamine, which is a great drug,” he said. “But what we’re trying to do is develop the next generation of novel agents.
We looked at this and thought, what would be the next iteration of novel compounds that would be differentiated? And what we concluded was that we’d like a molecule that was not a totally novel molecule, but that had some properties that were similar to R-ketamine in terms of its therapeutic index, its safety and efficacy, but be a novel molecule that was orally active, because ketamine has a lot of variability and high first pass metabolism and is not ideal for oral use…
The goal of this program was to create a molecule that had a little bit longer half-life, and that was orally active, but would be, at clinical doses, relatively non-dissociative”
GM-1020 is at the investigational new drug (IND) stage and moving into clinical testing later this year.
GM-2505 is a classic psychedelic 5-HT2A agonist. “The pharmacology of DMT is probably very attractive as a potential therapeutic in neuropsychiatry,” Sporn said.
“DMT itself has a very, very short half-life. It only lasts usually ten or 15 minutes, depending on how much you take of it. And so we wanted a molecule that had a longer activity than that, but not so long that, from a pharmaco-economic and logistic point of view it’s hard to really scale.
We didn’t want something that’s six or eight hours like psilocybin or LSD, but rather something around the one hour duration. We thought that that would be a good compromise in terms of being long enough for the brain to be well marinated in the drug but not too long.
What we found as well with this compound is that the drug has serotonin releasing properties, which makes it have some of the properties of the empathogen MDMA. So we think that this compound will be very much like DMT, but with a little bit of some of the socially binding antidepressant-like effects of MDMA. We’ll be able to use this drug in high doses as a reset treatment for psychiatric conditions, and maybe in a low dose maintenance type paradigm.”
GM-2505 is also at the IND stage and moving into clinical testing later this year.
GM-200X is a discovery effort to develop a 5-HT2A agonist compound that is relatively non-psychedelic, but will have therapeutic effects, much like small doses of LSD or psilocybin for treating anxiety or mood symptoms, Sporn explained.
“The idea here is it’s difficult with some of these compounds from a safety point of view because you don’t want people having a big bottle of LSD, because even if a small dose is very benign, people can take a very large dose and have a bad trip or something.
So we explored the world and found compounds that were described by experts who had tried them as being relatively non-psychedelic 2A agonists. And then we started to study those and evolve them in the discovery chemistry space. The idea here would be a molecule that people could use at home for the acute treatment, or the maintenance treatment of mood and anxiety disorders and similar conditions.”
GM-200X is a few months away from IND studies.
GM-300 is licensed from Columbia University and consists of a diverse set of analogues of the atypical psychedelic drug ibogaine, which is used clinically in some places in the world for conditions such as opiate use disorder. Columbia created a very large library of analogues of ibogaine, Sporn said.
“What we’re trying to do with this program is to improve the therapeutic index, to have high efficacy and also to reduce some of the side effects that are an issue with ibogaine in particular.
Ibogaine has the unfortunate property of causing cardiac arrhythmias that are increasing the QTC interval that can cause serious heart problems. And so what we’re looking at are 300 compounds that lack this cardiac risk. We’ve studied this in human cardiac cells from deceased individuals who donated their hearts.
Ibogaine is being developed by our competitor, ATAI, but like with all our programs here, we’re developing molecules that have strong intellectual property and innovation, so that they have a high commercial value.”
Sporn expects GM-300 to reach the human trials stage this year.
In addition, Gilgamesh also has a number of early stage programs, in which rather than using single molecule approaches such as the four main candidates, the others involve drugs used in combination approaches, he said.
“I think a lot of these will be able to advance quite quickly and move into the clinic,” Kiss said. “So our portfolio, over the course of the next year, is going to advance into the clinic for a number of programs and will also expand as well from a pre-clinical perspective.”
If clinical trials are encouraging for a particular drug, Gilgamesh will probably partner with a middle-sized or large pharmaceutical company, but in some circumstances Gilgamesh would consider moving a drug to final approval independently, Sporn noted.
The founder and CEO added: “We’ll develop everything to some sort of early demonstration of safety and efficacy in people and then explore those kinds of business development relationships.”
The company is also developing an AI-powered digital platform, ENKIDU, to accelerate the design and discovery of new drugs with improved safety, tolerability, duration and efficacy. According to Kiss:
“Because of the types of mechanisms that we are pursuing, there is an absence of higher resolution assays that can differentiate between things like compounds that have been reported to have dissociative versus non-dissociative effects in the clinic or hallucinogenic versus non-hallucinogenic effects.
That’s what we’re focusing on [with ENKIDU]. We’ve committed a lot of resources to building up the preclinical arm of this platform over the last six to nine months, with a vision towards translating those learnings over to biomarkers that we intend to ultimately use in the clinic.”
The ENKIDU platform will be able to determine what neurocircuits are engaged during exposure to a drug, the drug’s effects, as well as the long-term neuroplasticity changes that account for the durable effects of the drug, Kiss explained.
“These are the kinds of things that will help guide and enhance our lead optimization and candidate selection capabilities … We’re building a database too, with molecules that inform our understanding not only of these mechanisms, but also how it relates to other psychoactive compounds.”
This preclinical stage work is now “being validated at Bob Datta’s lab at Harvard and at Andre Fenton’s lab at NYU,” Kiss added.
Finally – why the name Gilgamesh?
“I didn’t want this to sound like a standard pharmaceutical company, and the epic of Gilgamesh is an interesting story in the sense that it’s both a very ancient story, but it’s also new in the sense that it wasn’t discovered until the 19th Century,” Sporn explained.
The Epic of Gilgamesh, written in Mesopotamia over 3,000 years ago by an unknown author, tells the story of a “king who starts out not being a very good leader, and through his journey is transformed and along the way he finds a medicinal plant that will cure the fear of death. So it’s a sort of hero story of transformation. Psychedelic drugs are potentially transformative for people more generally.”
Sporn concluded: “I think psychedelic drugs themselves have that characteristic of being both something recent and maybe transformative, but also something very old that may go back to the birth of modern man.”