Enveric Biosciences Releases New Mechanistic Data on EB-003
Enveric Biosciences announced new mechanistic data demonstrating that its lead candidate, EB-003, activates both Gq- and ss-arrestin-mediated signaling downstream of the 5-HT2A receptor. Multiple independent, peer-reviewed studies have previously shown that selective activation of 5-HT2A receptor, by either Gq-biased or ss-arrestin-biased agonists, can independently produce antidepressant- and anxiolytic-like effects in preclinical models, suggesting that therapeutic benefit can arise from activation of either pathway. The new data was generated using proprietary bioluminescence resonance energy transfer assays. Enveric developed and validated in-house BRET assays to characterize EB-003's intracellular signaling profile because commercial assays capable of reliably measuring pathway-specific 5-HT2A signaling were not available. The data demonstrate biologically relevant engagement of both Gq and ss-arrestin pathways. Enveric's new data also indicate that EB-003 exhibits a modest preference toward ss-arrestin over Gq signaling relative to serotonin, the native ligand of the receptor. Ongoing research is exploring the mechanistic significance of this apparent bias. Importantly, both pathways appear to be engaged at levels consistent with biological relevance. A recently published study in Nature employing BRET assays and complementary techniques provides additional mechanistic clarity regarding signaling downstream of 5-HT2A. The study reports that Gi signaling downstream of 5-HT2A was required for hallucinogenic effects in the experimental models evaluated, while Gq signaling mediated antidepressant- and anxiolytic-like benefits in preclinical systems. These findings indicate that therapeutic benefit and hallucinations may arise from distinct intracellular pathways. The company continues to advance EB-003 through IND-enabling studies.
