Mira Pharmaceuticals announces preclinical results for Ketamir-2

MIRA Pharmaceuticals announced new preclinical study results for its novel oral ketamine analog, Ketamir-2. The additional data announced continues a string of preclinical results announced by MIRA in recent months for Ketamir-2 as MIRA works towards its goal of submitting an Investigational New Drug application to the U.S. Food and Drug Administration by the end of this year which, if granted, would allow for human testing of Ketamir-2. Ketamir-2 is under investigation for its potential in treating neurological and neuropsychiatric disorders, including depression, treatment-resistant depression, and post-traumatic stress disorder. Ketamir-2 has demonstrated in in vitro studies that it is not a substrate for interaction with P-glycoprotein, a membrane protein that typically pumps many drugs out of cells, including cells located in the brain. This characteristic might allow Ketamir-2 to have a better oral absorption and to penetrate the blood-brain barrier more effectively than traditional ketamine, which is a substrate of P-gp. Key Areas of Recent Data Investigation: Patient Compliance and Convenience: Traditional ketamine requires intravenous administration, necessitating hospital visits and medical supervision. As an oral formulation, Ketamir-2 could potentially offer greater convenience and improved patient compliance if further studies confirm these benefits. Brain Penetration: P-gp is highly expressed in the blood-brain barrier and limits the entry of many drugs into the central nervous system. Studies have shown that Ketamir-2’s non-substrate status for P-gp may allow better brain penetration. Drug Resistance: P-gp also plays a role in multidrug resistance, particularly in cancer cells. Ketamir-2, not being a substrate of P-gp, is therefore potentially less susceptible to this resistance. Bioavailability: P-gp further limits drug absorption in the intestines by pumping drugs back into the intestinal lumen. MIRA’s preclinical research indicates that Ketamir-2 exhibits better oral bioavailability, which could ensure higher efficacy at lower doses compared to traditional ketamine. Potential for Lower Dosing: MIRA’s preclinical also suggest that improved penetration into target tissues would allow for lower doses of Ketamir-2 to achieve therapeutic effects. Preclinical Results and Ongoing Research: MIRA previously announced that Ketamir-2’s oral bioavailability is predicted to be around 80%, significantly higher than traditional ketamine’s less than 30%. Additionally, preclinical studies have shown that while oral Ketamir-2 has been shown to be safe at high doses and is effective in several anti-depressant and anxiolytic models, and it does not appear to induce hyper-locomotor activity, a common side effect of traditional ketamine. Moreover, Ketamir-2 has shown no interaction with the mu-opioid receptor, unlike traditional ketamine. This could potentially mean a reduced risk of opioid-related side effects and dependency. Recent studies further highlight Ketamir-2’s anti-depressive and anxiolytic effects in a mouse model, with significant improvements in behavioral tests compared to traditional ketamine. Expanding Indications and Exploring Orphan Drug Status: Building on these promising preclinical results, MIRA has additional ongoing preclinical studies to demonstrate Ketamir-2’s potential efficacy in treating chemotherapy-induced depression and cancer-related neuropathic pain. Due to its novel chemical profile, MIRA is exploring options for orphan drug indications such as multiple sclerosis-induced depression and Huntington’s disease-induced depression. Models are being developed to validate these designations and ongoing studies have been designed to help support these efforts.