• The positive results from this preclinical study underscore Ketamir-2's potential as a superior alternative to traditional ketamine
• Unlike ketamine, which requires intravenous or intranasal administration, Ketamir-2's oral formulation promises ease of use and better patient compliance and is not a controlled substance under DEA rules

MIAMI, June 10, 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, today announced positive preclinical study results highlighting the potential efficacy and safety profile of Ketamir-2, MIRA's novel oral ketamine analog designed to treat depression and treatment-resistant depression (TRD).

The highly encouraging study results further MIRA's goal of submitting an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) later this year which, if granted, would allow for human clinical trials of Ketamir-2.

Key Findings from the Study

The study, conducted by Pharmaseed Ltd., evaluated the anti-depressive and anxiolytic effects of oral Ketamir-2, in comparison with oral ketamine, using established behavioral tests in male mice. The tests included the Open Field Test (OFT), Elevated Plus Maze (EPM), and Forced Swim Test (FST).  Under the experimental conditions of these studies, it was possible to use 10 fold-higher oral doses of Ketamir-2, compared with ketamine, which induced major sedative and other side effects already at low doses.

The following findings were observed:

1. Open Field Test (OFT)
   • Mice treated with Ketamir-2 showed dose-related, significantly greater locomotor activity, higher travel speed and a trend towards an increased time spent in the center of the arena, indicating reduced anxiety levels.
2. Elevated Plus Maze (EPM)
   • In this model of depression, significant increases in travel distance and speed were observed in mice treated with Ketamir-2. Furthermore, Ketamir-2 treated mice spent more time in the open arms of the maze, suggesting reduced anxiety.
3. Forced Swim Test (FST)
   • In this model of depression and anxiety, mice in the Ketamir-2 treated arm demonstrated reduced swimming distances and speed, indicating reduced behavioral despair and anti-depressant effect.
   • In addition, Ketamir-2 treatment resulted in significantly reduced immobility times, highlighting its potential antidepressant properties.

Traditional ketamine was used as a positive control in this study.  In many of the above parameters, traditional ketamine given orally at the highest dose feasible was inactive, again pointing to the comparative potential benefits of Ketamir-2, which is designed to be delivered orally.

Clinical Implications and Future Directions

The positive results from this preclinical study underscore Ketamir-2's potential as a superior alternative to traditional ketamine.  Ongoing studies with third-party research organizations Pharmaseed and Biotrial are evaluating Ketamir-2's efficacy in treating post-traumatic stress syndrome and neuropathic pain, as well as conducting further safety studies in comparison to ketamine.

"We are thrilled with the promising results from these preclinical trials, which demonstrate Ketamir-2's efficacy and improved safety profile over traditional ketamine," said Erez Aminov, Chairman & CEO of Mira Pharmaceuticals. "These findings represent a significant milestone as we prepare for an IND submission to the FDA later this year. We are hopeful that Ketamir-2 will offer a new, safe and orally effective treatment option for patients suffering from depression and TRD."

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. Its demonstrated activity by the oral route, its pharmacological profile and lack of unwanted side-effects make Ketamir-2 a potentially safer and more effective option for treating depression in a home setting."

About MIRA Pharmaceuticals

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 analog, MIRA-55, is currently under investigation for treating adult patients suffering from neuropathic pain as well as 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. The U.S. Drug Enforcement Administration's scientific review of MIRA-55 concluded that it would not be considered a controlled substance or listed chemical under the Controlled Substances Act and its governing regulations. Additional information about the Company is available at: www.mirapharmaceuticals.com

Ketamir-2 and MIRA-55 are in early-stage preclinical 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 the anticipated benefits of the study results described herein as well  as the timing for the Company's other 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 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.