Depression can be treated by many drugs, but for many patients the available therapies just aren’t good enough. Treatment-resistant depression remains an unmet medical need and psychedelic compounds make up a growing area of research in the hunt for better behavioral medications. For one type of psychedelic, dosing poses challenges. Scientists at Lusaris Therapeutics believe their approach can win out and the biotech startup has raised $60 million to bring its lead drug candidate into human testing.
The molecule that Lusaris is working with has an unwieldy scientific name that’s typically shortened to the slightly more manageable 5-MeO-DMT. This old drug, which is found in the secretions of some plants and the glands of the Sonoran Desert toad, sparks a psychedelic effect. The drug can be synthesized in a lab but demand for the substance as it is found in nature has created a market that is reportedly endangering the toad.
Regardless of the source of 5-MeO-DMT, how it is dosed matters. When taken orally, enzymes in the gut and liver rapidly metabolize it, rendering the molecule useless as a drug. Those taking 5-MeO-DMT for spiritual or therapeutic uses typically smoke it.
The old-fashioned pill is still the way most people prefer taking their medications. Lusaris is developing an oral version of 5-MeO-DMT with a twist. Its pill, code-named LSR-1019, is designed to be placed under the tongue where it then rapidly dissolves and is absorbed by the body, said interim CEO Andrew Levin. The fast-acting drug’s effects start within minutes and are gone after about half an hour.
Though the psychedelic effect disappears after the drug wears off, its benefit lasts much longer, Levin said. The drug works by neuroplasticity, which is the brain’s ability to change. Lusaris aims to make its therapy a one-time treatment. Levin said evidence from others’ tests of 5-MeO-DMT indicate that the compound is effective for at least a week. He added that patients have told the company the effect can last much longer, perhaps up to one year.
“We don’t have hard data on that, we need to study it,” Levin said. “A very high percentage of patients with a single administration can get dramatically better. How long that effect lasts, we don’t know for any individual.”
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Lusaris was formed and incubated by RA Capital Management, where Levin is partner and managing director. The venture capital firm has invested in numerous companies but it also starts them. Formed by a team with neuroscience expertise, Levin said Lusaris went looking for compounds that have a high potential of efficacy, strong safety, and could benefit patients in a large area of unmet medical need. They settled on 5-MeO-DMT for addressing treatment-resistant depression, which is defined as depression inadequately treated by two earlier lines of therapy.
RA Capital got a closer look at 5-MeO-DMT through an earlier investment. Last year, the firm co-led GH Research’s $125 million Series B financing. The Dublin-based company’s lead program, GH001, is an aerosolized version of 5-MeO-DMT that’s inhaled. The now publicly traded company has reached Phase 1/2 testing. GH Research is also developing two additional versions of the drug, one for intranasal delivery and the other for injection. The company aims to offer these therapies as drug-device combination products.
Meanwhile, Beckley Psytech is preparing to advance to Phase 2 testing in depression and alcohol use disorder with its intranasally administered formulation of 5-MeO-DMT, codenamed BPL-003. The Oxford, England-based company has also expanded its pipeline. Last week, Beckley announced it agreed to acquire Eleusis Therapeutics, a company developing a Phase 1-ready infused formulation of the psychedelic compound psilocybin. The deal, an all-stock transaction, follows the unraveling of the SPAC merger that Eleusis announced at the beginning of this year.
Rapid degradation of 5-MeO-DMT in the gut is specific to that compound rather than characteristic of psychedelics broadly, said Neil Buckley, Lusaris’s chief operating officer. Psilocybin can be taken orally. Ketamine can also be dosed orally. Johnson & Johnson’s Spravato, whose active ingredient is ketamine, was developed for intranasal administration, which Buckley said offers a more rapid effect on the brain. In choosing to work with 5-MeO-DMT, Lusaris decided on a different route of administration.
“We saw drawbacks from other technologies and products in development,” Buckley said. “We ultimately wanted something that removed the burden [to patients].”
The technology Lusaris uses to make its drug an orally disintegrating tablet comes from Catalent. Called Zydis, this technology is part of more than 35 commercialized products, including migraine drug Nurtec ODT. That drug was a relative latecomer in the newest class of migraine therapies called CGRP inhibitors, but its maker, Biohaven, has described the quick-dissolving formulation as a patient-preferred differentiator against rival products that are infused or injected.
Lusaris has licensed the rights to Zydis for all applications of 5-MeO-DMT. That means the biotech’s research with its molecule and the Catalent technology could go beyond treatment-resistant depression. Lusaris is also developing therapies for migraine and cluster headache. One discovery-stage program, LSR-2000, is similar to depression drug LSR-1019, Levin said. A third program, LSR-3000, is a next-generation neuroplastogen in the discovery stage for other neuropsychiatric and neurological disorders. With this program, Lusaris is dialing out receptor activity that causes hallucinogenic effects in order to allow the drug to be dosed chronically.
Lusaris’s funding announced this week is a Series A round. Other participants in the financing are Venrock, Deep Track Capital, Boxer Capital, and one additional undisclosed investor. Levin said the capital should support Lusaris into 2025. He expects to bring lead program LSR-1019 “to the clinic soon.” In addition to testing the molecule in treatment-resistant depression, Lusaris plans additional tests of that drug in other indications that the company is still selecting.
In the near term, the startup is selecting office space. Though Lusaris was incorporated in Boston, it will set up shop in the Research Triangle Park region of North Carolina, where Buckley is based. Half of the employees will be based at that site while the other half will work virtually, Buckley said.
Photo by Flickr user Jernej Furman via a Creative Commons license
