Depression can be treated with many medications, but for many patients, available therapies are simply not good enough. Treatment-resistant depression remains an unmet medical need and psychedelic compounds represent a growing area of research in search of better behavioral drugs. For a type of psychedelic, dosing is a challenge. Scientists at Lusaris Therapeutics believe their approach can win, and the biotech startup has raised $60 million to put its lead drug candidate into human testing.
The molecule Louzaris is working with has a clunky scientific name that is usually shortened to the slightly more manageable 5-MeO-DMT. This ancient drug, found in the secretions of some plants and in the glands of the Sonoran desert frog, produces a psychedelic effect. The drug can be synthesized in a laboratory, but the demand for the substance as it occurs in nature is there created a market that reportedly endangered the frog.
Regardless of the source of 5-MeO-DMT, how it is dosed matters. When taken orally, enzymes in the gut and liver quickly metabolize it, rendering the molecule useless as a drug. Those who take 5-MeO-DMT for spiritual or therapeutic purposes usually smoke it.
The old-fashioned pill is still the way most people prefer to take their medicine. 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 is then quickly dissolved and absorbed by the body, said interim CEO Andrew Levin. The effects of the fast-acting drug begin within minutes and disappear after about half an hour.
Although the psychedelic effect wears off once the drug wears off, the benefit lasts much longer, Levine said. The drug works through neuroplasticity, which is the brain’s ability to change. Lusaris aims to make its therapy a one-off. Levine said evidence from other tests of 5-MeO-DMT showed the compound was effective for at least a week. He added that patients have told the company that the effect can last much longer, perhaps up to a year.
“We don’t have hard data on that, we have to study it,” Levine said. “A very high percentage of patients with a single application can improve dramatically. How long this effect lasts, we do not know for any person.
Lusaris was created and incubated by RA Capital Management, where Levin is a partner and managing director. The venture capital firm has invested in many companies, but also launched them. Created by a team with expertise in neuroscience, Levin said Lusaris sought compounds that had high potential for efficacy, strong safety and could benefit patients in a large area of unmet medical need. They settled on 5-MeO-DMT to treat treatment-resistant depression, which is defined as depression inadequately treated by two prior lines of therapy.
RA Capital took a closer look at 5-MeO-DMT through an earlier investment. Last year, the firm co-led GH Research’s $125 million in Series B funding. The Dublin-based company’s flagship program, GH001, is an aerosol version of 5-MeO-DMT that is 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 administration and the other for injection. The company aims to offer these therapies as drug-device combination products.
Meanwhile, Beckley Psytech is preparing to move into 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. Beckley announced last week that he agreed acquire Eleusis Therapeutics, a company developing a Phase 1-ready infused formulation of the psychedelic compound psilocybin. The deal, an all-stock deal, follows unraveling from The SPAC merger that Eleusis announced earlier this year.
The rapid breakdown of 5-MeO-DMT in the gut is more specific to this compound than to psychedelics in general, said Neil Buckley, chief operating officer of Lusaris. Psilocybin can be taken orally. Ketamine can also be taken orally. Johnson & Johnson’s Spravato, whose active ingredient is ketamine, was developed for intranasal administration, which Buckley says offers a faster effect on the brain. By choosing to work with 5-MeO-DMT, Lusaris decided on a different way of application.
“We’ve seen flaws from other technologies and products in development,” Buckley said. “Ultimately, we wanted something that took the burden off [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 medication Nurtec ODT. This drug was relatively late in the newest class of migraine therapies called CGRP inhibitors, but its maker, Biohaven, described the fast-dissolving formula as a patient-preferred differentiator against competing 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 Catalent technology could go beyond treatment-resistant depression. Lusaris is also developing therapies for migraine and cluster headaches. One discovery-stage program, LSR-2000, is similar to the depression drug LSR-1019, Levine said. A third program, LSR-3000, is a discovery-stage next-generation neuroplastogen for other neuropsychiatric and neurological disorders. With this program, Lusaris recruits receptor activity that causes hallucinogenic effects to allow the drug to be dosed chronically.
Funding of Luzaris announced this week is a Series A round. Other participants in the funding include Venrock, Deep Track Capital, Boxer Capital and one other undisclosed investor. Levin said the capital should support Lusaris until 2025. He expects to bring the lead LSR-1019 program “to the clinic soon.” In addition to testing the molecule in treatment-resistant depression, Lusaris plans additional tests of this drug in other indications that the company is still choosing.
In the near future, the startup chooses office space. Although Lusaris is registered in Boston, it will set up shop in North Carolina’s Research Triangle Park area, where Buckley is based. Half of the employees will be based at that location, while the other half will work virtually, Buckley said.