Artificial intelligence and machine learning technology are now seemingly sprinkled across all corners of drug discovery, but one biotech is wielding large language models to advance a class of medicines that’s just now blossoming.
Mindstate Design Labs has submitted its first IND, asking the FDA to greenlight a clinical trial for its lead asset targeting 5-MeO-MiPT, also known as moxy, a psychedelic selected from more than 70,000 “trip reports” to classify states of consciousness. Those reports—often detailed, self-reported accounts from psychedelic users—were plucked from all regions of the internet, including the social media platform Reddit, drug forums, clinical data sets and the dark web.
According to CEO Dillan DiNardo, those 70,000 reports represent basically “every trip report in existence.”
“It's raw structured data, but there's so much richness there,” DiNardo said in an interview with Fierce Biotech. “There's so much qualitative diversity in the ways that these things change consciousness. And each of those drugs has a different biochemical profile.”
Using large language models and natural language processing, Mindstate has built a platform that segments experiences by drug or psychedelic receptors. In some cases, the platform can visualize an experience, like color transformation. This has some intriguing implications, given that one of the larger critiques of psychedelic drug development to date is that there’s no clear explanation of the link between a drug’s chemistry and associated biological effects.
That’s arguably the hardest part of a burgeoning clinical area, particularly in neuroscience, where it can take years for a druggable hypothesis to be proven—as Alzheimer's disease drug developers have found when targeting amyloid beta. DiNardo explained that practically speaking, Mindstate is a “biological insights platform” that uses said insights to pick drug targets,
“What our platform allows us to do is to experiment with states of consciousness that are not possible with the first-generation psychedelics,” he said. “If you have new states of consciousness, you can potentially go into disease indications that no one else in psychedelics is even thinking about at the moment.”
Moxy, listed as MSD-001 in the pipeline, was selected as Mindstate’s first candidate because, in DiNardo’s words, it’s like “psychedelic tofu,” meaning it meshes with whatever else is co-administered alongside it. The plan is to administer moxy with an approved generic that, when combined, achieve a precise consciousness state. In fact, combining a psychedelic “primer” with a generic “probe” is the foundation of Mindstate’s entire platform.
The phase 1 trial will be conducted at one site, across five cohorts of 10 healthy volunteers. Those patients will receive moxy by itself, with Mindstate expecting to nail down a precise indication and weave in the generic sidekick in a phase 2a study.
The biotech's ambitions, which can sometimes sound other-worldly, have been made more credible by its backers. The company was a Y Combinator startup and raised a $11.5 million seed round backed by Initialized Capital, Negev Capital and Day One Ventures, among others. The company’s angel investors include Max Hodak, one of the co-founders of Neuralink, and Instacart founder Apoorva Mehta. Mindstate’s head of clinical development, David Hough, M.D., was the vice president of esketamine compound development at Johnson & Johnson's Janssen unit, work that became the basis for approved depression med Spravato.
DiNardo said he and the team are considering future financing plans but wouldn’t elaborate. The company has enough money to pay for clinical trial expenses.
The biotech’s potential foray into the clinic comes as psychedelics are finally catching mainstream attention, with Lykos Therapeutics and its MDMA-assisted therapy on track to be the first FDA-approved psychedelic therapy later this year. Gaurav Gupta, M.D., an investor on J.P. Morgan’s life science private capital team, recently told Fierce that his team is actively assessing psychedelic bets. And Biogen’s EVP and head of corporate development, Adam Keeney, Ph.D., said he was interested in companies that are separating good pharmacology from the disassociative effects of a hallucinogenic.
“We're tracking companies that are working on those second-generation opportunities,” Keeney told Fierce in an interview last month.
One of the common criticisms about the first-gen psychedelic options, like MDMA or psilocybin, is the long administration time, which limits how many patients can be administered to in a day and puts increased pressure on clinic staffing. For now, DiNardo isn't discarding the value in potential medicines that induce longer trips.
“It's just going to be a balanced approach,” he said. “But ultimately, the therapeutic impact of psychedelics comes from the subjective experience.”