Enveric Biosciences announced that it has named EB-003 as its lead drug candidate from the Company?s next-generation EVM301 Series. EB-003 was selected based on data analyses suggesting the molecule?s potential to be a first-in-class approach to addressing difficult-to-treat mental health disorders by promoting neuroplasticity without inducing hallucinations. Enveric plans to initiate preclinical development of EB-003 in early 2024 in preparation for an Investigational New Drug (IND) application for a first-in-human clinical trial.

EB-003 was identified following a rigorous selection process during which Enveric utilized its proprietary computational chemistry and artificial intelligence (AI) drug-discovery platform, PsyAI, to simulate interactions between indolethylamine derivatives and the 5-HT2A receptor to design novel molecules with reduced head-twitch response (HTR) in mice. HTR is a rodent behavioral model used to predict whether a molecule is likely to produce hallucinogenic effects in humans. In total, 51 proprietary indolethylamine analogs were screened, from which three candidates were selected based on the molecules?

ability to bind to the 5-HT2A receptor and induce neuroplasticity while eliciting no significant HTR across a wide dose range. EB-003: Demonstrated a low HTR profile in mice at all doses tested (up to 10 mg/kg)., Promoted neuroplasticity at a level similar to that induced by the hallucinogenic positive control N,N-dimethyltryptamine (DMT). Exhibited partial agonism of the 5-HT2A receptor, binding with a Ki of 0.2,mM, which is within the range of binding affinity of the known 5-HT2A agonists DMT and psilocin.

.Resulted in a return to pre-stressed behavior in both the marble-burying (MB) and sucrose preference (SP) tests, which are models for anxiety and depression, respectively, when administered to mice at a dose of 10 mg/kg by intraperitoneal injection., Bound the 5-HT1A receptor with a Ki of 3.3 mM. 5-HT1A receptor agonists and partial agonists have demonstrated clinical efficacy at relieving anxiety and depression. Was not an agonist of the 5-HT2B receptor.

5-HT2B receptor agonism can lead to cardiac valvulopathy and is therefore considered a toxicity signal sufficient to preclude clinical development. Showed moderate exposure in pharmacokinetic analysis with a half-life of approximately 30 minutes, which is anticipated to enhance optionality in the future determination of dosing regimens. Revealed high membrane permeability in assays, indicating the potential for excellent blood brain barrier permeability, an important consideration for drugs that target receptors in the brain.

Overall toxicity parameters were similar to or below those for DMT and psilocin.