Relmada Therapeutics, Inc. announced the publication of REL-1017 preclinical data in the peer-reviewed journal, Frontiers in Pharmacology. The article is titled, "REL-1017 (Esmethadone), A Novel NMDAR Blocker for the Treatment of MDD is Not Neurotoxic in Sprague-Dawley Rats," and is available online at: Frontiers | REL-1017 (Esmethadone), A Novel NMDAR Blocker for the Treatment of MDD is Not Neurotoxic in Sprague-Dawley Rats | Pharmacology (frontiersin.org). The aim of the study was to determine whether the novel, low affinity, low potency, NMDAR channel blocker, REL-1017, administered once daily via oral gavage for 1–4 days to male and female Sprague-Dawley rats, would induce transient (Olney's lesions) and irreversible (necrosis) pathomorphological changes to the posterior cingulate and retrosplenial brain cortical neurons as compared with animals treated with another NMDAR channel blocker, dizocilpine (MK-801), a positive control.

In REL-1017 treated rats, early Olney's lesions, which usually appear one day after MK-801 treatment, were not observed. Similarly, REL-1017 treated rats did not show necrotic neurons both at the cingulate and olfactory bulb cortex at later time points (Day 3 and 5). This effect is statistically different from what was observed in cortical neurons by using MK-801.

Additionally, in contrast with MK-801 treated rats, REL-1017 treated rats did not show evidence of impaired behavior. These preclinical data, in addition to clinical data to date, have been encouraging to the development of REL-1017 as a potentially safe and effective treatment option for MDD. REL-1017, a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission, is currently in late-stage development for the treatment of MDD.

The ongoing RELIANCE Clinical Research Program is designed to evaluate the potential for REL-1017 as a rapid-acting, oral, once-daily antidepressant treatment. In a Phase 2 trial, REL-1017 demonstrated robust, rapid, and sustained antidepressant effects with statistically significant improvements compared to placebo. The Phase 2 study also showed a favorable pharmacokinetic, safety, and tolerability profile of REL-1017 consistent with results observed in previously completed Phase 1 studies.