CAMBRIDGE, Mass. — Enveric Biosciences said it has generated new mechanistic data showing that its lead drug candidate, EB-003, engages multiple intracellular signaling pathways associated with antidepressant and anxiolytic effects, reinforcing the scientific rationale behind its non-hallucinogenic neuroplastogen program.
The company said proprietary bioluminescence resonance energy transfer, or BRET, receptor engagement assays demonstrated that EB-003 activates both Gq- and β-arrestin–mediated signaling downstream of the 5-HT₂A receptor. Prior peer-reviewed studies have shown that selective activation of either pathway can independently produce antidepressant- and anxiolytic-like effects in preclinical models, suggesting that therapeutic benefit does not require engagement of a single signaling route.
Enveric said it developed and validated its own BRET assays after determining that no commercial platforms were capable of reliably measuring pathway-specific 5-HT₂A signaling. The results showed biologically relevant engagement of both Gq and β-arrestin pathways by EB-003.
According to the company, the data also suggest that EB-003 shows a modest preference for β-arrestin signaling over Gq signaling when compared with serotonin, the receptor’s native ligand. Enveric said ongoing research is aimed at better understanding the mechanistic implications of this apparent bias, while noting that both pathways are activated at levels consistent with biological relevance.
The announcement also cited recently published independent academic research in Nature that used BRET assays and complementary methods to examine 5-HT₂A signaling. That study reported that Gi signaling downstream of the receptor was required for hallucinogenic effects in the experimental models evaluated, while Gq signaling mediated antidepressant- and anxiolytic-like benefits. The findings suggest that therapeutic effects and hallucinations may arise from distinct intracellular pathways.
“Growing mechanistic clarity around 5-HT₂A signaling strengthens confidence in the scientific foundation of our platform,” said Joseph Tucker, Ph.D., CEO of Enveric Biosciences. “Our proprietary BRET assay data show that EB-003 engages signaling pathways that prior peer-reviewed studies have linked to antidepressant- and anxiolytic-like effects in preclinical models.”
Dr. Tucker added that the independent academic findings are consistent with Enveric’s strategy of designing non-hallucinogenic neuroplastogens intended to deliver therapeutic benefit without the safety, monitoring, and scalability challenges associated with psychedelic compounds. He said the company plans additional BRET testing of EB-003, including evaluation of Gi signaling, to further characterize its signaling profile.
EB-003 is being developed as a non-hallucinogenic neuroplastogen intended to support simplified treatment paradigms, including potential at-home administration. Enveric said it continues to advance the compound through IND-enabling studies.
