Navitor Pharmaceuticals Initiates a Clinical Study of NV-5138

Navitor Pharmaceuticals announced the initiation of a Phase 1 clinical study with its lead pipeline candidate, NV-5138, for treatment-resistant depression (TRD). NV-5138 is a novel small molecule that directly activates mTORC1, a master cellular regulator that has recently been shown to be a central signaling pathway required for the efficacy of several rapid acting antidepressants. NV-5138 is initially being evaluated in TRD but may offer future potential for the treatment in the broader disease category of major depressive disorder (MDD)"We are enthusiastic about initiating clinical development with NV-5138 for major depressive disorder, as we believe this novel activator of mTORC1 has the potential to offer a unique approach to meeting many of the unmet needs of this serious and chronic disease. Millions of patients with depression do not adequately respond to standard pharmacological therapies which can take weeks or months before patients experience their effects, if at all," said George P. Vlasuk, PhD, President and Chief Executive Officer of Navitor. "We see the development of NV-5138 in MDD/TRD as a pioneering advance toward realizing the therapeutic potential of modulating the mTORC1 signaling pathway to treat a wide range of chronic human diseases."

The Phase 1, multicenter, two-part, double-blind, placebo-controlled study will evaluate the safety, tolerability and pharmacokinetics of NV-5138 in up to 88 subjects, including healthy volunteers and patients diagnosed with TRD. In Part A, the single-ascending-dose portion of the study, up to 48 healthy volunteers will be randomly assigned to double-blind treatment in six dosage-level cohorts. Within each cohort, six subjects will be randomized to receive NV-5138 and two subjects will be randomized to receive placebo. In Part B of the study, approximately 40 subjects diagnosed with TRD will be randomly assigned to double-blind treatment at a single dosage level that will be established based on data from Part A of the study. Other prespecified outcome measures to be evaluated in Part B include standard depression rating and symptomology scores such as the Montgomery-Åsberg Depression Rating Scale (MADRS).

"Initiation of this clinical study is supported by preclinical studies demonstrating the potential of NV-5138 as an oral treatment for depression through activation of mTORC1, a cellular pathway that appears to underlie the beneficial effects of several in a new class of rapidly acting antidepressants," said Maurizio Fava, MD, Director of the Division of Clinical Research of the Massachusetts General Hospital (MGH) Research Institute and member of the Navitor Clinical Advisory Board.

Previously, Navitor has presented preclinical results on the efficacy of NV-5138 in multiple models of depression-like behavior, which demonstrated that NV-5138 produced behavioral responses and concomitant increases in new synapses (synaptogenesis) consistent with a rapid-acting antidepressant through transient, direct activation of the mTORC1 signaling pathway in the brain. Navitor leveraged multiple preclinical observations that have shown mTORC1 activation is required for the efficacy of many rapid-acting antidepressant compounds including several modulators of the NMDA (N-methyl-D-aspartic acid)-mediated signaling pathway like ketamine, which is an active area of innovative drug development for depression.