Enveric Biosciences (NASDAQ: ENVB) (“Enveric” or the “Company”), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders, today announced the GLP Safety and Toxicology Program of EB-373 is proceeding as planned thus far with favorable results.

In-life portion of the repeat dose toxicology studies have been completed, and the results are being analyzed. In addition, cardiac, respiratory, CNS safety pharmacology studies, an in vitro hERG current study, and genotoxicity studies have been completed and are undergoing analyses. Enveric expects to finalize all preclinical activities involving EB-373 in the first quarter of 2024 in preparation for a first-in-human clinical trial.

“Our research team has continued to diligently advance the preclinical program for our lead novel psilocin prodrug, EB-373, as we anticipate initiating first in human trials in 2024,” said Joseph Tucker, Ph.D., Director and CEO of Enveric. “Analyses of data collected to date have consistently confirmed the safety and oral bioavailability of EB-373, with a dose-dependent increase in EB-373 blood concentration detected followed by its rapid conversion to the active metabolite psilocin. Further, pharmacological properties observed in preclinical animal models have validated our AI-backed molecular design aimed at optimal control over the timing and length of the hallucinatory experience in humans, while also achieving the desired therapeutic effect for difficult-to-treat mental health indications.”

A summary of the EB-373 preclinical program is as follows:

• GLP toxicology studies of EB-373 in orally dosed rats and dogs are currently in advanced stages, with all in-life activities completed. Preliminary indications suggest a broad margin of safety and tolerability is maintained with repeat dose testing. Complete analysis and final reporting are expected by the end of Q1 2024.
• EB-373 safety pharmacology studies in rats and dogs, employing the core battery of respiratory, CNS and cardiovascular (CV) assessments, are completed. Preliminary results have demonstrated an acceptable range of safety for each of these vital organ systems in orally dosed animals. Complete analysis and final reporting are expected by the end of December 2023.
• In vitro assessment of cardiotoxicity potential, involving assays targeting key CV targets including hERG, Cav 1.2 and Nav 1.5 have been completed. Results suggest an acceptable range of cardiovascular safety well above the proposed clinical dose range.
• Non-GLP in vivo dose range finding (DRF) studies conducted in rats and dogs, completed in August 2023, demonstrated effective oral bioavailability of EB-373, with dose-dependent increase in psilocin blood concentration detected in both species.
  • Key outcomes from these PK assessments strongly suggest a broad range of tolerance, with a potential for reduced gastrointestinal (GI) upset and vomiting, as well as a rapid onset of action and systemic clearance, improving on PK characteristics of psilocybin.
• In vitro absorption, distribution, metabolism and excretion toxicology (ADME-tox) studies and a metabolic identification evaluation have been completed and confirmed minimal potential for adverse drug reactions (ADR), with no toxic metabolites identified, and no indication of any significant drug-drug interactions.
  • Results from this study also demonstrated rapid conversion of EB-373 to the active metabolite psilocin, consistent with previously reported pharmacokinetic (PK) studies.