The Albany Gazette - MIRA Pharmaceuticals Announces Favorable Topline Results from Phase 1 SAD Study of Oral Ketamir-2, a Next-Generation Non-Scheduled Ketamine Analog

Study demonstrated Ketamir-2 was safe and well tolerated at all dose levels, with a favorable safety and tolerability profile, with no severe or clinically significant adverse effects observed. The drug showed rapid and predictable absorption, a favorable duration of action supporting once-daily dosing, and no CNS side effects typically seen with ketamine.

MIAMI, FLORIDA / ACCESS Newswire / September 22, 2025 / MIRA Pharmaceuticals, Inc. (NASDAQ:MIRA) ("MIRA" or the "Company"), a clinical-stage pharmaceutical company developing novel oral therapeutics for neurologic, neuropsychiatric, and metabolic disorders, today announced topline results from the single ascending dose (SAD) portion of its ongoing Phase 1 clinical trial evaluating the safety, tolerability, and pharmacokinetics (PK) of its lead oral candidate, Ketamir-2, in healthy volunteers.

The randomized, placebo-controlled study enrolled 32 healthy adult participants across four escalating oral dose cohorts (50 mg to 600 mg). The primary endpoints were safety, tolerability, and PK characterization.

Key Pharmacokinetic Findings

• Dose-proportional increases in exposure (Cmax and AUC) were observed across all dose levels tested.

• Median time to maximum plasma concentration (Tmax) reached within 1-2 hours, consistent across cohorts, confirming rapid and predictable absorption.

• Terminal half-life (t½) of Ketamir-2 ranged from 2-5 hours, while its primary active metabolite, nor-Ketamir, demonstrated a longer half-life of 6.5-8.5 hours. This favorable duration of action supports convenient once-daily dosing and may contribute to sustained therapeutic benefit.

• This contrasts with oral ketamine, which is characterized by erratic absorption and a much shorter half-life, limiting its clinical use in chronic treatment. The predictable PK profile of Ketamir-2 supports convenient once-daily dosing for patients with neuropathic pain and potentially other CNS conditions.

Safety and Tolerability

• Ketamir-2 was generally safe and well tolerated across all four cohorts

• No dose-limiting toxicities or serious adverse events were observed

• Treatment-emergent adverse events were transient and resolved without intervention

• In addition to routine safety assessments, CNS effects were carefully monitored using validated tools (C-SSRS, Bowdle VAS, KSET). Across all SAD cohorts, Ketamir-2no clinically significant adverse effects observed.

Next Steps

Based on the data, MIRA is initiating the multiple ascending dose (MAD) portion of the Phase 1 study in healthy volunteers, to be followed by a Phase 2a trial in patients with neuropathic pain.

Management Commentary

"These first-in-human data clearly demonstrate a favorable safety profile and predictable pharmacokinetics across a wide dosing range," said Erez Aminov, CEO of MIRA. "Importantly, the absence of the hallmark CNS side effects typically associated with ketamine, which we first observed preclinically, has now been confirmed clinically - reinforcing Ketamir-2's differentiated profile. Given the significant unmet need for safe, effective, and non-addictive treatments for neuropathic pain, we believe Ketamir-2 is well positioned as a highly attractive development candidate, and the Company is actively exploring strategic partnering opportunities to accelerate its advancement."

Dr. Itzchak Angel, CSA of MIRA, added: "The Phase 1 pharmacokinetic data demonstrate that Ketamir-2 is rapidly absorbed, predictably metabolized, and suitable for once-daily dosing - a major advantage compared to oral ketamine, which suffers from poor bioavailability and short half-life. Importantly, we were able to confirm in a human clinical study that Ketamir-2 continues to differentiate itself from ketamine by showing a robust safety and pharmacokinetics profile well adapted for its intended use. These findings underscore its potential as a next-generation therapeutic."

About Ketamir-2

Ketamir-2 is a proprietary, orally bioavailable new molecular entity that selectively targets the NMDA receptor (PCP site) with low affinity and shows no significant off-target activity across a broad receptor panel.

Preclinical studies have demonstrated:

• Neuropathic pain: Superior efficacy upon oral administration versus ketamine, pregabalin, and gabapentin in gold-standard models, without the dissociative side effects associated with ketamine.

• PTSD: In the validated Single Prolonged Stress (SPS) model, Ketamir-2 restored normalized behavior in stressed animals, reversing hallmark PTSD-like behaviors consistent with non-stressed controls. A larger follow-on PTSD study is ongoing.

• Depression: Activity in established preclinical models supports the potential of Ketamir-2 as a differentiated treatment for major depressive disorders, including treatment-resistant depression (TRD).

• Inflammatory pain (topical formulation): In animal models, a topical formulation of Ketamir-2 demonstrated pain relief equal to injected morphine, underscoring its versatility and non-opioid potential across pain indications.

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.

About MIRA Pharmaceuticals, Inc.

MIRA Pharmaceuticals, Inc. (NASDAQ:MIRA) is a clinical-stage pharmaceutical company focused on the development and commercialization of novel therapeutics for neurologic, neuropsychiatric, and metabolic disorders. The Company's pipeline includes oral drug candidates designed to address significant unmet medical needs in neuropathic pain, inflammatory pain, obesity, addiction, anxiety, and cognitive decline.

For more information, please visit www.mirapharmaceuticals.com.

Cautionary Note Regarding Forward-Looking Statements

This press release and the statements of MIRA's 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. Any forward-looking statements in this press release are based on MIRA'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 MIRA's control) that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including related to MIRA's potential merger with SKNY Pharmaceuticals, Inc. These and other risks concerning MIRA'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 the Form 14A filed by MIRA on June 18, 2025, and other SEC filings, which are on file with the SEC at www.sec.gov and on MIRA's website at https://www.mirapharmaceuticals.com/investors/sec-filings. MIRA explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

Contact:
Helga Moya
[email protected]
(786) 432-9792

SOURCE: MIRA Pharmaceuticals

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