• In vitro pharmacology studies confirmed EB-003’s ability to target desired serotonergic receptors, supporting the potential of the neuroplastogenic therapeutic candidate to address difficult-to-treat mental health disorders without inducing hallucinations

• Analysis of off-target interactions indicate ability of EB-003 to minimize potential adverse cardiovascular and CNS events that are common to serotonin-like drug compounds

CAMBRIDGE, Mass. / Oct 15, 2024 / Business Wire / 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 positive results for preclinical safety and pharmacology studies, which evaluated off-target interactions of its lead drug candidate, EB-003, and confirmed selective activity with desired serotonergic neuroreceptors.

The in vitro pharmacological studies, which profiled EB-003 against a broad range of secondary targets (receptors, ion channels, enzymes and transporters), showed a low potential to induce undesirable cardiovascular, respiratory, and neurological reactions, or to have drug-to-drug interactions.

Results of this large in vitro screen suggest a favorable safety profile for EB-003 with no significant off-target interactions detected. Notably, EB-003 showed no meaningful activity against hERG or 5-HT2B, targets related to cardiovascular adverse drug reactions (ADRs). Drug interaction with hERG can elicit fatal cardiac arrhythmias, while off-target activation of the serotonin receptor 5-HT2B located in cardiac tissues is known to induce pulmonary hypertension and serious valvular heart disease. Several approved antidepressants and neuroactive drugs have seen reduced use and/or have been removed from the market based on interactions with these receptors, and the harmful downstream impacts on patient safety.

Additionally, EB-003 showed no activity against the M1 muscarinic acetylcholine receptor (mAChR), a target related to central nervous system (CNS) ADRs. mAChR is involved in regulating perception, attention, and cognitive function with the potential to provoke severe drug-induced-delirium.

Joseph Tucker, Ph.D., Director and CEO of Enveric, commented, “From our perspective, positive results from this key in vitro safety screen further derisk EB-003. These results, along with previously reported antidepressant, anxiolytic, and neuroplastogenic properties in animal models, enhance our confidence in this lead compound. We are excited to progress EB-003 through the final steps of the Company’s Investigational New Drug (IND) application, including in vivo toxicology and safety pharmacology activities, all scheduled to begin in Q4 of 2024.”

Enveric recently announced preclinical data confirming the oral bioavailability of EB-003 and its ability to produce brain exposure at therapeutically relevant levels. Enveric expects to file an IND application for EB-003 by the third quarter of 2025 and initiate clinical development by the end of 2025.

About Enveric Biosciences

Enveric Biosciences (NASDAQ: ENVB) is a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders. Leveraging its unique discovery and development platform, Psybrary™, Enveric has created a robust intellectual property portfolio of new chemical entities for specific mental health indications. Enveric’s lead program, EB-003, is a first-in-class approach to the treatment of difficult-to-address mental health disorders designed to promote neuroplasticity without inducing hallucinations in the patient. Enveric is also developing EB-002, a next generation synthetic prodrug of the active metabolite, psilocin, being studied as a treatment for psychiatric disorders. Enveric is headquartered in Naples, FL with offices in Cambridge, MA and Calgary, AB Canada. For more information, please visit www.enveric.com.

Forward-Looking Statements

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A discussion of these and other factors, including risks and uncertainties with respect to Enveric, is set forth in Enveric’s filings with the Securities and Exchange Commission, including Enveric’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Enveric disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.