Mira Pharmaceuticals Advances Preclinical Trials Towards an IND Submission This Year for Ketamir-2, a Differentiated Oral Ketamine Analog

Investigative studies are underway testing Ketamir-2 as the potential first at home ketamine analog treatment for PTSD, depression, and neuropathic pain, including cancer pain 

MIAMI, May 20, 2024 /PRNewswire/ -- MIRA Pharmaceuticals, Inc. (NASDAQ: MIRA) ("MIRA" or the "Company"), a pre-clinical-stage pharmaceutical company focused on the treatment of neurologic and neuropsychiatric disorders, 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 (PTSD) 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 (FDA) by the end of this year, which if cleared by FDA would allow for human clinical testing of Ketamir-2.

Development Update: 

Initiation of Preclinical Trials with Pharmaseed for PTSD

MIRA has initiated a preclinical trial in collaboration with Pharmaseed Ltd ("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.

Head-to-Head Preclinical Study to be Conducted by Biotrial, Inc. for Locomotor Activity Evaluation of Ketamir-2 Compared to Ketamine

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.

Initiation of 7-Day Animal Studies with Frontage 

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.

Advancements in Ketamir-2 Manufacturing

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.

Potential of Ketamir for PTSD Treatment

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.

Exploring Collaborations for Cancer Pain Studies

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.

Management Comments

Erez Aminov, Chairman and CEO of Mira Pharmaceuticals, commented, "The initiation of these preclinical trials represents a significant milestone in our mission to develop next-generation treatments for severe mental health disorders as well as neuropathic pain.  Our collaboration with Pharmaseed and Biotrial underscores our commitment to advancing Ketamir-2 towards clinical development in humans and addressing the urgent needs of those suffering from PTSD and other debilitating conditions. The financial impact of medication-treated major depressive disorder in the U.S. stands at an overwhelming $92.7 billion annually, with $43.8 billion (47.2%) of this amount due to treatment-resistant depression¹. Additionally, the U.S. market for post-traumatic stress disorder treatments is on a significant rise, projected to reach $26 billion by 2031².  We are hopeful that Ketamir-2 can help address these critical public health issues."

Dr. Itzchak Angel, Chief Scientific Advisor of Mira Pharmaceuticals, added, "The data generated from these studies will be invaluable in demonstrating Ketamir-2's potential benefits. What sets Ketamir-2 apart from ketamine is its high oral bioavailability and lack of mu opioid interaction. As a result, Ketamir-2 potentially offers a safer and more effective option for oral administration, providing rapid relief for depression in a home setting. We are excited about the progress we have made in simplifying the drug's manufacturing process and are hopeful that Ketamir-2 can offer new hope for patients with PTSD and other mental health and pain conditions."

About MIRA Pharmaceuticals, Inc.

MIRA Pharmaceuticals, Inc. (Nasdaq: MIRA) is a pre-clinical-stage pharmaceutical development company with two neuroscience programs targeting a broad range of neurologic and neuropsychiatric disorders.  MIRA holds the exclusive U.S., Canadian and Mexican rights for Ketamir-2, a novel, patent pending oral ketamine analog under investigation to potentially deliver ultra-rapid antidepressant effects, providing hope for individuals battling treatment-resistant depression, major depressive disorder with suicidal ideation and post-traumatic stress disorder. The U.S. Drug Enforcement Administration's scientific review of Ketamir-2 concluded that it would not be considered a controlled substance or listed chemical under the Controlled Substances Act and its governing regulations. 

In addition, MIRA's novel oral pharmaceutical marijuana, MIRA-55, is currently under investigation for treating adult patients suffering from anxiety and cognitive decline, often associated with early-stage dementia.  MIRA-55, if approved by the FDA, could mark a significant advancement in addressing various neuropsychiatric, inflammatory, and neurologic diseases and disorders.

Additional information about the Company is available at: www.mirapharmaceuticals.com.

Ketamir-2 and MIRA-55 are in early stage pre-clinical development. There is no assurance that the products will proceed through development or will receive FDA approval for marketing.

Cautionary Note Regarding Forward-Looking Statements

This press release and the statements of the Company's management related thereto contains "forward-looking statements," which are statements other than historical facts made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements may be identified by words such as "Aims," "anticipates," "believes," "could," "estimates," "expects," "forecasts," "goal," "intends," "may," "plans," "possible," "potential," "seeks," "will," and variations of these words or similar expressions that are intended to identify forward-looking statements.  Any statements in this press release that are not historical facts may be deemed forward-looking. These forward-looking statements include, without limitation, statements regarding Ketamir-2's potential in treating certain mental health conditions or neuropathic pain and statements regarding the timing for the Company's preclinical studies and the filing of an IND for Ketamir-2.  Any forward-looking statements in this press release are based on the Company's current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties (many of which are beyond the Company's control) that could cause actual results (including the anticipated benefits of the Company's pre-clinical testing and pre-clinical data discussed herein) to differ materially and adversely from those set forth in or implied by such forward-looking statements. These and other risks concerning the Company's programs and operations are described in additional detail in Annual Report on Form 10-K for the year ended December 31, 2023 and other SEC filings, which are on file with the SEC at www.sec.gov and the Company's website at https://www.mirapharmaceuticals.com/investors/sec-filings. The Company explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

SOURCE MIRA Pharmaceuticals, Inc.