Vistagen Reports New Preclinical Data Supporting Itruvone (PH10) Nasal Spray’s Potential Antidepressant Activity via Peripheral Nasal Neurons without Entry into the Brain

Vistagen (NASDAQ: VTGN) a late clinical-stage biopharmaceutical company aiming to transform the treatment landscape for individuals living with anxiety, depression and other central nervous system (CNS) disorders, today announced new mechanism of action data from a preclinical tissue distribution study in laboratory rats. The study demonstrated that a single intranasal administration of radiolabeled itruvone ([¹⁴C]PH10) was essentially undetectable in the brain and most other tissues, including blood and plasma.

These new data further support the proposed mechanism of action of itruvone nasal spray as involving binding to receptors of peripheral chemosensory neurons in the nasal cavity, but not to neuronal receptors in the CNS, and thereby limiting transport of molecules to the circulatory system and minimizing potential systemic exposure.

“Itruvone’s unique mechanism of action is further demonstrated in this new carbon-labeled study,” said Shawn Singh, Chief Executive Officer of Vistagen. “These new data and previously announced preclinical electrophysiology data demonstrating that itruvone’s mechanism of action does not involve direct activation of GABA-A receptors in the brain, as well as other completed Phase 1 and Phase 2A clinical studies, provide a substantial body of evidence supporting itruvone’s exceptionally favorable safety profile. Currently approved medications to treat depression require systemic absorption. This can lead to unwanted side effects and create potential drug-drug interaction concerns for some individuals who require additional medications for other medical conditions. As a potential non-systemic treatment option, we believe itruvone has a vital opportunity to change the treatment paradigm for the growing numbers of individuals suffering from depression disorders across the globe.”

Vistagen recently reported that itruvone is now staged for potential Phase 2B clinical development in the U.S. as a stand-alone treatment for MDD, building on previously published results from a randomized, double-blind, placebo-controlled Phase 2A study of itruvone in MDD. In that study, itruvone was administered intranasally at a daily dose of 3.2 μg and 6.4 μg for 8 weeks. After one week of treatment, the mean reduction on the 17-item Hamilton Depression Scale (HAM-D-17) scores for the itruvone 6.4 μg group was 10.1 points, which was statistically greater (p = 0.03) than the mean reduction in the placebo group of 4.2 points from baseline. Also, at the end of the last week of treatment (Week 8) in that study, the itruvone 6.4 μg group showed a mean HAM-D-17 score reduction of 17.8, which was statistically greater than the mean reduction in the placebo group of 10.9 points from baseline (p = 0.02). Thus, in the itruvone 6.4 μg treatment group, the HAM-D-17 score improved significantly from the baseline within one week and this effect was sustained until the Week 8 study endpoint. Notably, both the itruvone 3.2 μg and 6.4 μg treatment groups showed strong effect sizes after one week of treatment (0.72 for the 3.2 μg dose and 1.01 for the 6.4 μg dose) and at the Week 8 study endpoint (0.74 for the 3.2 μg dose and 0.95 for the 6.4 μg dose). There were no reports of SAEs. Itruvone was well-tolerated and did not cause psychological side effects (such as dissociation or hallucinations) or other safety concerns that may be associated with other approved pharmacological therapies for MDD.