MIRA Pharmaceuticals Announces FDA Clearance of IND for Ketamir-2, Enabling U.S. Clinical Trials in Neuropathic Pain

Rhea-AI Summary

MIRA Pharmaceuticals (NASDAQ:MIRA) announced FDA clearance of its IND application for Ketamir-2, a novel oral NMDA receptor antagonist for neuropathic pain treatment. The drug has shown superior efficacy to existing treatments in preclinical studies, demonstrating up to 112% greater pain relief than pregabalin and 70% more than gabapentin.

The company is completing the Single Ascending Dose (SAD) portion of its Phase 1 trial and preparing for Multiple Ascending Dose (MAD) studies. MIRA plans to initiate a U.S. Phase 2a clinical trial in Q4 2025. Additionally, MIRA's acquisition of SKNY Pharmaceuticals is expected to close in Q3 2025, bringing SKNY-1, a promising obesity and smoking cessation drug candidate, to its pipeline.

Positive

• FDA clearance of IND application for Ketamir-2, enabling U.S. clinical trials
• Superior efficacy demonstrated in preclinical studies - up to 112% greater pain relief than pregabalin
• Clean safety profile with no evidence of brain lesions or adverse CNS effects
• Planned acquisition of SKNY Pharmaceuticals on track for Q3 2025 closure
• Strong preclinical data showing good oral bioavailability and blood-brain barrier penetration

Negative

• Phase 1 trials still ongoing, with Phase 2a not starting until Q4 2025
• Multiple competing development programs may strain resources
• Clinical efficacy in humans yet to be demonstrated

Oral, non-opioid drug candidate advancing through Phase 1 and nearing completion of the single ascending dose (SAD) portion as the Company prepares to launch U.S. Phase 2a by year-end

MIAMI, FLORIDA / ACCESS Newswire / July 29, 2025 / MIRA Pharmaceuticals, Inc. (NASDAQ:MIRA), a clinical-stage pharmaceutical company developing novel therapies for neurologic, neuropsychiatric, and metabolic disorders, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for Ketamir-2, a novel oral NMDA receptor antagonist for the treatment of neuropathic pain.

The IND submission included a comprehensive data package encompassing preclinical pharmacology, safety, and toxicology studies, including a pivotal neurotoxicity study in Sprague-Dawley rats which showed no evidence of brain lesions or adverse CNS effects-a key distinction from traditional ketamine, which has been associated with NMDA-linked neurotoxicity and the formation of Olney lesions in similar preclinical models. These findings were reinforced by multiple validated neuropathic pain models-including chemotherapy-induced, diabetic, and nerve ligation-induced neuropathy-where Ketamir-2 consistently demonstrated potent analgesic effects and superior efficacy to gabapentin and pregabalin, with reversal of pain sensitivity observed in select models. The IND also incorporated the Company's Phase 1 readiness data and manufacturing documentation.

MIRA is nearing completion of the Single Ascending Dose (SAD) portion of its international Phase 1 trial at Hadassah Medical Center in Jerusalem, with dose escalation progressing smoothly. The Company is now preparing to initiate the Multiple Ascending Dose (MAD) portion of the study, which will assess the safety, tolerability, and pharmacokinetics of repeated dosing over several days. These data will help inform optimal dosing strategies as MIRA moves toward a Phase 2a study, with the goal of initiating its first U.S.-based efficacy trial in Q4 2025.

"This IND approval validates the strength of our preclinical data and the differentiated pharmacology of Ketamir-2," said Erez Aminov, Chairman and CEO of MIRA. "We are executing and advancing with precision and speed, and we believe Ketamir-2 may represent one of the most promising non-opioid, non-controlled neuropathic pain treatments in development today."

Building on Strong Preclinical Evidence

Ketamir-2 has consistently demonstrated robust efficacy and safety across a range of preclinical studies:

• In a chemotherapy-induced neuropathy model, Ketamir-2 achieved near-complete normalization of pain sensitivity and outperformed gabapentin by 60%

• In a validated diabetic neuropathy model induced by a high-fat diet and low-dose streptozotocin (STZ) in rats, Ketamir-2 significantly reduced pain sensitivity, with some animals returning to pre-diabetic baseline sensitivity

• In head-to-head studies using the chronic constriction injury (CCI) model-a widely accepted sciatic nerve ligation model of neuropathic pain-in rats, Ketamir-2 delivered up to 112% greater pain relief than pregabalin and 70% more than gabapentin

• No hyperlocomotion, sedation, or behavioral disturbances were observed, even at high doses

• A comprehensive neurotoxicity study confirmed absence of Olney lesions, a key safety concern in NMDA modulators like ketamine

• Ketamir-2 was shown to cross the blood-brain barrier efficiently, supported by its non-P-gp substrate status and evidence of CNS penetration in preclinical models, supporting oral CNS activity. Preclinical data indicate Ketamir-2 achieves good oral bioavailability-significantly higher than traditional ketamine, which has very low bioavailability when taken orally. This advantage, along with its selective receptor targeting and long-acting metabolite Nor-Ketamir-2, supports its potential as an at-home treatment option.

• Demonstrated antidepressant and anxiolytic-like effects in validated behavioral models, with no dissociative or psychotomimetic side effects

Select findings were recently published in Frontiers in Pharmacology, confirming the molecule's clean pharmacological profile and positioning Ketamir-2 as a differentiated and scalable alternative to existing treatments. Additional preclinical publications are in progress.

Phase 2a Pathway and Strategic Expansion

With IND clearance secured, MIRA plans to initiate a U.S.-based Phase 2a clinical trial in neuropathic pain in Q4 2025. In parallel, the Company is:

• In discussions with a leading U.S. institution to explore a dedicated trial in chemotherapy-induced peripheral neuropathy (CIPN)

• Evaluating a Phase 2a study in diabetic peripheral neuropathy (DPN), a large, underserved indication with rising prevalence

• Advancing formulation development for topical Ketamir-2 for localized pain applications

Neuropathic Pain: A High-Impact Opportunity Across North America

Neuropathic pain is a widespread and growing concern across North America, with prevalence expected to rise due to aging populations and increasing rates of diabetes and cancer-related treatments. Current therapies often provide only modest relief and are frequently associated with side effects such as sedation, dizziness, weight gain, and dependency risk, limiting their long-term use.

In chemotherapy-induced peripheral neuropathy (CIPN), a significant proportion of patients undergoing treatment experience chronic pain symptoms. Meanwhile, access to IV ketamine remains limited to specialized clinics with long wait times, high cost, and logistical burdens. Ketamir-2's oral, non-dissociative, and non-opioid profile may help overcome these barriers-offering a more accessible and scalable solution for patients in need.

"Ketamir-2 has demonstrated consistent, potent efficacy across preclinical pain models with a clean safety profile and broad therapeutic potential. The IND approval is a testament to our scientific rigor and may pave the way for meaningful clinical translation," said Dr. Itzchak Angel, Chief Scientific Advisor at MIRA.

Other Corporate Updates

MIRA also reports that the planned acquisition of SKNY Pharmaceuticals remains on track, with shareholder approval expected in Q3 2025. SKNY-1, the lead asset from SKNY Pharmaceuticals, is a next-generation oral therapy in development for obesity and smoking cessation. In a recent zebrafish model of obesity and craving, SKNY-1 demonstrated up to 30% weight loss, reversal of high-calorie and nicotine-seeking behavior, normalization of appetite hormones, and preservation of muscle mass. Additionally, SKNY-1 reversed anxiety-like behavior in a validated CB1 agonist-induced model, suggesting a favorable neuropsychiatric safety profile. Designed to avoid the psychiatric side effects linked to earlier CB1-targeting drugs and nicotine cessation agents, SKNY-1 could offer a differentiated, well-tolerated alternative to GLP-1s and other interventions. Meanwhile, MIRA-55, the Company's oral cannabinoid analog, recently showed comparable efficacy to morphine in inflammatory pain models and is under evaluation for further development.

"MIRA is executing at the highest level across all fronts," added Mr. Aminov. "Ketamir-2's clinical momentum, the SKNY-1 merger, and advancing MIRA-55 collectively reflect our commitment to delivering innovative, safe, and scalable therapies for patients with limited options. We're extremely proud of the team's performance, and we are just getting started."

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 areas such as neuropathic pain, inflammatory pain, obesity, addiction, anxiety, and cognitive decline.

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
info@mirapharma.com
(786) 432-9792

SOURCE: MIRA Pharmaceuticals

View the original press release on ACCESS Newswire

FAQ

What is the significance of MIRA's FDA IND clearance for Ketamir-2?

The FDA clearance allows MIRA to begin U.S. clinical trials for Ketamir-2, their novel non-opioid treatment for neuropathic pain, with Phase 2a trials planned for Q4 2025.

How does Ketamir-2 compare to existing neuropathic pain treatments?

In preclinical studies, Ketamir-2 showed 112% greater pain relief than pregabalin and 70% better efficacy than gabapentin, with no evidence of brain lesions or adverse CNS effects.

When will MIRA Pharmaceuticals complete its acquisition of SKNY Pharmaceuticals?

The acquisition is expected to receive shareholder approval and close in Q3 2025, adding SKNY-1, a promising obesity and smoking cessation drug candidate, to MIRA's pipeline.

What are the key advantages of MIRA's Ketamir-2 over traditional ketamine?

Ketamir-2 shows higher oral bioavailability, no neurotoxicity or Olney lesions, and no dissociative effects, making it potentially suitable as an at-home treatment option.

What potential market opportunities is MIRA targeting with Ketamir-2?

MIRA is targeting neuropathic pain, chemotherapy-induced peripheral neuropathy (CIPN), and diabetic peripheral neuropathy (DPN), with plans for both oral and topical formulations.