MIRA Pharmaceuticals, Inc. announced that it has advanced new preclinical studies using Ketamir-2, its differentiated oral ketamine analog, towards clinical development for the treatment of severe post-traumatic stress disorder and other leading mental health disorders and neuropathic pain indications. MIRA continues to advance studies of Ketamir-2 in animal studies while improving manufacturing optimization as the company prepares for human testing in 2025. MIRA anticipates that positive results from these preclinical studies will enable the submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration by the end of this year, which if cleared by FDA would allow for human clinical testing of Ketamir-2. MIRA has initiated a preclinical trial in collaboration with Pharmaseed to evaluate the efficacy of Ketamir-2 as compared with Ketamine in a rat model of severe PTSD.

This study, designed to assess the alleviation of symptoms of chronic stress and behavioral consequences of dysfunctional processing of fear and fear memory, leverages established models demonstrating the effectiveness of ketamine in treating PTSD symptoms. While ketamine has demonstrated rapid and sustained reduction in PTSD symptoms in several clinical studies, it has to be given through intravenous, intramuscular or intranasal administration. The current study is designed to provide robust data on the potential for the orally administered Ketamir-2 through behavioral tests, biomarker analysis, and immunohistochemistry to support future clinical applications. Ongoing studies at Pharmaseed are already exploring the potential of Ketamir-2 in treating depression and several forms of pain, including neuropathic pain.

In parallel, MIRA has initiated a study with Biotrial, Inc. (Biotrial) to evaluate the acute effects of Ketamir-2 on spontaneous locomotor activity in mice. This study will assess Ketamir-2's impact compared to ketamine and a control vehicle, providing crucial data on the pharmacodynamics of Ketamir-2. Ketamine is known to produce a biphasic effect on locomotion (meaning high and low doses of ketamine have very different effects). The initial hypolocomotion (reduced movement) phase observed in rodents after ketamine administration is consistent with the sedative and dissociative effects reported with ketamine in humans, which can lead to impaired coordination and motor function.

The subsequent hyperlocomotion (increased movement) phase in rodents mirrors the agitation, confusion and psychotic effects seen in humans, particularly at higher doses of ketamine. Since Ketamir-2 has a different chemical profile that ketamine, MIRA anticipates that these head-to-head studies can be predictive of Ketamir-2's side-effect profile in humans. MIRA is also advancing towards regulatory IND-enabling study and has also initiated 7-day rat and dog toxicology studies with Frontage Laboratories.

These studies are critical steps towards ensuring the safety and efficacy of Ketamir-2 in preparation for human clinical trials. In recent weeks, MIRA has also made significant advancements in the manufacturing process of Ketamir-2, markedly simplifying and optimizing the synthetic process while reducing production costs and overall cost of goods. These improvements are critical as MIRA scales up production under Good Manufacturing Practices (GMP) to enable the required regulatory toxicology studies and to prepare for an IND for Ketamir-2 submission later this year.

According to the National Institutes of Health, PTSD affects approximately 8 million adults annually in the United States, with current treatments often providing limited relief and significant side effects. Ketamir-2, as an oral ketamine analog, offers a promising alternative due to its potential for ultra-rapid antidepressant effects and improved safety profile. Unlike traditional SSRIs and benzodiazepines, Ketamir-2 targets NMDA receptors in the brain, which play a crucial role in synaptic plasticity and cognitive function, potentially offering more effective and faster relief from PTSD symptoms. In addition to its current initiatives, MIRA is also in discussions with several research centers to potentially collaborate on studying Ketamir-2's efficacy in treating cancer pain.

These collaborations could expedite the IND submission for Ketamir-2 and the commencement of human clinical trials, while increasing the potential therapeutic applications of Ketamir-2.