Enveric Biosciences Selects EB-003 as Lead Drug Candidate from EVM301 Series

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 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.

From the top three candidates, EB-003 was chosen as lead based on its superiority in numerous relevant measures.

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 K_i 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 K_i 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.

“Selection of EB-003 as the lead development candidate from our EVM301 Series is an important inflection point for Enveric and our mission to develop groundbreaking, psychedelic-inspired drug technologies that offer the potential to treat severe mental health disorders without the hallucinogenic effect typically associated with psychedelic-based molecules,” said Joseph Tucker, Ph.D., Director and CEO of Enveric. “Importantly, moving EB-003 into our development pipeline marks a transformative step for Enveric as we complete our period as a discovery phase company and fully transition to the next phase as a drug development company. With EB-003, we have identified a novel, neuroplastogenic molecule that exhibits several key properties that align with favorable tolerability and efficacy in relevant animal models. We now look forward to initiating IND enabling activities in early 2024 that will enable us to file an IND and start clinical trials of EB-003 as we seek to introduce a new treatment paradigm for depression and anxiety disorders.”