MIAMI, FL / ACCESS Newswire / March 4, 2025 / MIRA Pharmaceuticals, Inc. (NASDAQ: MIRA), a preclinical-stage pharmaceutical company focused on developing therapies for neurological and neuropsychiatric disorders, today announced the approval and upcoming initiation of its Phase 1 clinical trial for Ketamir-2, the Company's novel oral ketamine analog in development for neuropathic pain, with subject recruitment scheduled to begin in Q1 2025.

The study has received authorization from the Israeli Ministry of Health and the Institutional Review Board (IRB) and will be conducted at the Clinical Pharmacology Unit, Hadassah Medical Center in Jerusalem, Israel. This Phase 1, randomized, double-blind, placebo-controlled, single-center study is designed to evaluate the safety, tolerability, and pharmacokinetics of orally administered Ketamir-2 in healthy adult volunteers.

The trial consists of two parts:

• Single Ascending Dose (SAD) Part: 32 participants

• Multiple Ascending Dose (MAD) Part: 24 participants

In addition to assessing the frequency and severity of adverse events (AEs) and serious adverse events (SAEs), the study will closely evaluate ketamine-related behavioral side effects and assess Ketamir-2's distinct pharmacological profile.

The decision to conduct the study in Israel was made to accelerate timelines and optimize costs, allowing Mira to efficiently allocate resources and extend its operational runway. The Company expects Phase 1 to conclude by Q4 2025, paving the way for a Phase 2a study in neuropathic pain patients to be initiated by the end of the year.

Addressing a Large and Unmet Market for Neuropathic Pain

Neuropathic pain is a rapidly growing market, projected to reach $5.2 billion in North America by 2030, driven by an aging population, increasing diabetes prevalence, and chemotherapy-induced nerve damage. Existing treatments, including gabapentin, pregabalin, and opioids, offer only limited relief and carry significant side effects such as sedation, dizziness, addiction, and withdrawal risks. The urgent need for safer, more effective non-opioid therapies presents a significant opportunity for innovation, and Ketamir-2 is uniquely positioned to meet this demand.

Advancing a Safe and Effective Alternative for Neuropathic Pain

MIRA's preclinical studies demonstrate Ketamir-2's superior efficacy, safety, and optimized pharmacokinetics, supporting its advancement into Phase 1 clinical trials.

Key Findings from Animal Models:

• Full Neuropathic Pain Reversal:

  • In a nerve ligation model, Ketamir-2 fully normalized pain thresholds, while oral ketamine had no effect.

• Superior to FDA-Approved Gabapentin and Pregabalin:

  • In a chemotherapy-induced neuropathy model (PTX), Ketamir-2 restored normal pain sensitivity, outperforming gabapentin by 60%.

  • Up to 112% more effective than pregabalin in reducing neuropathic pain at higher doses.

• No Hyperlocomotor Activity, Reducing Risk of Behavioral Side Effects:

  • Unlike traditional ketamine, Ketamir-2 did not induce hyperlocomotor activity, a side effect often associated with ketamine's psychotomimetic effects.

• Optimized for Oral Absorption & Brain Delivery:

  • Not a P-glycoprotein (P-gp) substrate, allowing better absorption and brain penetration.

  • Selective, low affinity NMDA receptor binding reduces dissociative side effects.

• Enhanced Bioavailability & Prolonged Effect with Nor-Ketamir-2:

  • Nor-Ketamir-2 is the primary active metabolite of Ketamir-2, formed in the body after oral administration.

  • Unlike traditional ketamine, which is rapidly metabolized and cleared, Nor-Ketamir-2 remains in circulation longer, leading to sustained therapeutic effects.

  • The Pamoate salt formulation of Ketamir-2 enhances drug absorption and bioavailability, achieving extended oral bioavailability and higher brain exposure, of nor-ketamir-2 supporting longer-lasting pain relief.

• Strong Safety Profile:

  • No cardiovascular or respiratory concerns at high doses.

  • High selectivity and cleaner pharmacological profile than traditional ketamine, reducing risks of side effects.

These findings reinforce Ketamir-2's potential as a breakthrough oral treatment for neuropathic pain, offering greater efficacy, improved safety, and convenient administration over existing therapies.

"The neuropathic pain market continues to grow, yet current treatments leave millions of patients without adequate relief," said Erez Aminov, Chairman and CEO of MIRA Pharmaceuticals. "Ketamir-2 has demonstrated remarkable potential in reversing neuropathic pain while maintaining a strong safety profile. With this Phase 1 trial now set to begin, we are moving closer to bringing a much-needed oral treatment to patients suffering from chronic neuropathic pain."

Expanding Research into PTSD and Topical Pain Relief

Beyond neuropathic pain, MIRA Pharmaceuticals is conducting ongoing preclinical studies evaluating Ketamir-2 in PTSD and a potential topical formulation for localized pain relief. These additional indications could significantly broaden the clinical and commercial potential of Ketamir-2.

Dr. Angel, Chief Scientific Advisor at Mira Pharmaceuticals, added: "Ketamir-2 continues to show great promise as we are now ready for the clinical trials. Its strong safety profile and targeted mechanism of action differentiate it from traditional ketamine and other pain treatments, giving us confidence in its potential for multiple indications."

Advancing Mira-55 for Memory Enhancement

In parallel, the Company is assessing Mira-55 for its potential in memory enhancement. This program aligns with MIRA's commitment to neurological innovation, exploring treatments that could address cognitive decline and neurodegenerative conditions.

Regulatory and Development Timeline

With Phase 1 expected to conclude by year-end, Mira is on track to initiate Phase 2a studies in neuropathic pain patients in Q4 2025, further advancing the potential of Ketamir-2 as a novel treatment for neuropathic pain and other neuro indications.

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 treat neuropathic pain (NP), treatment-resistant depression (TRD), major depressive disorder with suicidal ideation (MDD-SI), and post-traumatic stress disorder (PTSD).

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

The U.S. Drug Enforcement Administration's scientific review concluded that both Ketamir-2 and MIRA-55 would not be considered controlled substances or listed chemicals under the Controlled Substances Act and its governing regulations.

Additional information about MIRA Pharmaceuticals is available at www.mirapharmaceuticals.com.

Cautionary Note Regarding Forward-Looking Statements

This press release and the statements of MIRA Pharmaceuticals' (or the "Company") management related thereto contain "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 the Annual Report on Form 10-K for the year ended December 31, 2024, 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.