After prematurely ending two phase 3 depression trials last year, Relmada Therapeutics has formally given up on the asset they were testing. The Florida-based biotech terminated its license agreement for esmethadone on July 7, with all of their obligations under the deal set to expire on Oct. 5.
Relmada has tested esmethadone, which it called REL-1017, in several phase 3 trials for various major depressive disorder (MDD) indications. The prospect flopped in just about every one of them.
In October 2022, REL-1017 failed to top placebo as an MDD monotherapy in the phase 3 RELIANCE III trial. Another stumble followed just months later, this time as an adjunctive MDD treatment in late-stage RELIANCE I, which the company attributed to “a limited number of high-enrolling sites with unplausible placebo response.”
Esmethadone did better in a 2023 open-label trial, successfully improving depression symptoms, but the study had no placebo arm.
The third phase 3 strike for REL-1017 came in December 2024, when Relmada revealed that its RELIANCE II trial, which was testing esmethadone as an adjunctive treatment for MDD, was unlikely to hit its primary endpoint. As a result, Relmada scrapped the trial and another related study, RELIGHT, which used a similar design, and announced plans to pursue strategic alternatives like a merger or sale of the company.
Esmethadone is a component of methadone, the pain and substance use medication. Relmada originally licensed the candidate in January 2018 from Charles Inturrisi, Ph.D., and Paolo Manfredi, M.D., for an upfront fee of $180,000. Inturrisi, a pharmacologist at Cornell University, originally developed esmethadone and licensed it to Medeor, which Manfredi co-founded. Relmada merged with Medeor in 2013.
Manfredi’s Medeor is not to be confused with kidney transplant company Medeor Therapeutics.
As part of the licensing deal, Relmada was paying Inturrisi and Manfredi $45,000 every three months, a stipulation that was set to continue until esmethadone was sold as a commercial product or the patent on it expired.
Relmada is now focused on making strategic asset acquisitions, according to its website, as well as advancing remaining assets NDV-01 and sepranolone. NDV-01 is currently being tested in an open-label phase 2 trial in non-muscle invasive bladder cancer, while sepranolone is a phase 2 Tourette syndrome asset that Relmada purchased in February from Asarina Pharma.