Mira Pharmaceuticals announces insights from additional Ketamir-2 data

MIRA Pharmaceuticals announced new insights garnered from additional, recently received preclinical study data regarding the mechanism of action and toxicology data for its novel oral ketamine analog, Ketamir-2. Ketamir-2 is MIRA‘s drug candidate being investigated as a potential treatment for neurological and neuropsychiatric disorders. The new preclinical study results announced today are the latest in a string of positive research developments which are progressing MIRA’s goal of submitting an Investigational New Drug Application to the U.S. Food and Drug Administration for Ketamir-2 later this year. The latest preclinical data reveals that Ketamir-2 is a selective inhibitor of the NMDA receptor of glutamate, the primary excitatory neurotransmitter in the human brain, specifically interacting at the PCP-binding site of the NMDA complex. Ketamir-2 has a 30-50-fold lower affinity to the PCP site compared with ketamine. The lower affinity is important because at high affinity, compounds may affect neurobehavioral functions, potentially leading to side effects such as dissociation and hallucinations. Unlike traditional ketamine, which also affects several other sites on the NMDA receptor and interacts with opioid receptors, dopamine and serotonin transporters, and various acetylcholine receptors, Ketamir-2 exhibits unique selectivity and does not interact with these additional receptor sites. This selectivity is notable as it may contribute to a distinct pharmacological profile for Ketamir-2, potentially reducing the risk of side effects associated with these other interactions. The potential benefits of Ketamir-2’s selective binding also include: 1. Reduced Side Effects: By targeting only the NMDA receptor at the PCP-binding site, Ketamir-2 appears to avoid the broader spectrum of ketamine interactions with other receptors and transporters. This specificity may help minimize unwanted side effects, such as dissociation, hallucinations, and addictive potential, often observed with ketamine use. 2. Improved Safety Profile: The selective inhibition allows for a cleaner pharmacological profile, potentially leading to better tolerability and fewer adverse reactions in patients. These advantages could enhance patient compliance and overall treatment outcomes. 3. Enhanced Therapeutic Effectiveness: With a selective mechanism of action, Ketamir-2 could potentially deliver more consistent and predictable therapeutic effects, which may be particularly beneficial in treating conditions like depression, treatment-resistant depression, and post-traumatic stress disorder. Complementing its novel mechanism, recently conducted toxicology studies in rats and dogs have shown no toxicity at very high doses of Ketamir-2. These findings underscore Ketamir-2’s excellent safety margin, further supported by its pronounced antidepressant and anxiolytic activities observed at oral doses five to tenfold lower than those tested in the toxicology studies. The substantial therapeutic window of Ketamir-2 offers promising potential for safe and effective use in human therapies. The additional data announced today builds on previous findings highlighting Ketamir-2’s superior brain penetration and bioavailability. Unlike traditional ketamine, Ketamir-2 is not a substrate for P-glycoprotein, a membrane protein that pumps drugs out of cells, including those in the brain. This characteristic may allow Ketamir-2 to penetrate the blood-brain barrier more effectively, enhancing its therapeutic potential.