MIRA Pharmaceuticals Initiates Multiple Ascending Dose (MAD) Phase 1 Study of Oral Ketamir-2 and Selects Chemotherapy-Induced Neuropathic Pain as Lead Phase 2a Indication
MIRA (NASDAQ:MIRA) announced initiation of the multiple ascending dose (MAD) portion of its Phase 1 trial for oral Ketamir-2 in healthy volunteers and selected chemotherapy-induced peripheral neuropathy (CIPN) as the lead Phase 2a indication on October 24, 2025.
The randomized, double-blind, placebo-controlled study follows completed single ascending dose (SAD) dosing with no serious or dose-limiting adverse events reported to date. MAD cohorts will test repeat daily doses from 150 mg to 600 mg for five days. Pharmacokinetic analyses will be performed after unblinding. Preclinical and peer-reviewed data reported near-complete normalization of pain in a paclitaxel model and superiority versus ketamine, gabapentin, and pregabalin in animal neuropathic pain models.
MIRA (NASDAQ:MIRA) ha annunciato l'inizio della porzione di dose multipla crescente (MAD) della sua sperimentazione di fase 1 per Ketamir-2 orale in soggetti sani e selezionata neuropatia periferica indotta dalla chemioterapia (CIPN) come indicazione principale della fase 2a il 24 ottobre 2025.
Lo studio randomizzato, in doppio cieco, controllato con placebo segue la somministrazione di dose singola crescente (SAD) completata con nessun evento avverso grave o dose-limitante riportato fino ad ora. Le coorti MAD testeranno dosi ripetute giornaliere da 150 mg a 600 mg per cinque giorni. Le analisi farmacocinetiche saranno eseguite dopo lo sblocco del codice. Dati preclinici e peer-reviewed riportano quasi una normalizzazione completa del dolore in un modello di paclitaxel e una superiorità rispetto a ketamine, gabapentin e pregabalin in modelli animali di dolore neuropatico.
MIRA (NASDAQ:MIRA) anunció el inicio de la porción de dosis múltiples en aumento (MAD) de su ensayo de Fase 1 para Ketamir-2 oral en voluntarios sanos y la neuropatía periférica inducida por quimioterapia (CIPN) seleccionada como indicación principal de la Fase 2a el 24 de octubre de 2025.
El estudio aleatorizado, doble ciego, controlado con placebo sigue a la pauta de dosis única en aumento (SAD) completada sin informes de eventos adversos graves o dosis-limitantes hasta la fecha. Las cohortes MAD probarán dosis diarias repetidas desde 150 mg hasta 600 mg durante cinco días. Se realizarán análisis farmacocinéticos tras el cegamiento. Datos preclínicos y revisados por pares reportan una normalización casi completa del dolor en un modelo con paclitaxel y superioridad frente a ketamine, gabapentin y pregabalin en modelos animales de dolor neuropático.
MIRA (NASDAQ:MIRA)는 건강한 지원자와 선택된 치료 약물로 유발된 화학요법 관련 말초 신경병증(CIPN)를 대상으로 하는 경구용 Ketamir-2의 1상 시험의 다중 증가 용량(MAD) 부분 개시를 2025년 10월 24일에 발표했습니다.
무작위, 이중 맹검, 위약 대조 연구는 현재까지 심각한 이상반응이나 용량 제한적 이상반응이 보고되지 않은 단일 증가 용량(SAD) 투약을 마친 뒤를 따릅니다. MAD 코호트는 5일간 150 mg에서 600 mg까지의 반복적인 일일 투여를 테스트합니다. 언블링 후 약동학 분석이 수행될 예정입니다. 전임상 및 동료 심사 데이터는 파클리탁셀 모델에서 거의 완전한 통증 정상화 및 동물 신경병성 통증 모델에서 케타민, 가바펜틴, 프리가발린에 비한 우월성을 보고합니다.
MIRA (NASDAQ:MIRA) a annoncé l’initiation de la partie posologique multiple croissante (MAD) de son essai de phase 1 pour Ketamir-2 oral chez des volontaires sains et l’neuropathie périphérique induite par la chimiothérapie (CIPN) sélectionnée comme indication principale de la phase 2a le 24 octobre 2025.
L’étude randomisée, en double aveugle et contrôlée par placebo suit le schéma de dosage en dose unique croissante (SAD) terminé sans événements indésirables graves ou limitants de dose rapportés à ce jour. Les cohortes MAD testeront des doses quotidiennes répétées de 150 mg à 600 mg pendant cinq jours. Des analyses pharmacocinétiques seront effectuées après le déblindage. Des données précliniques et évaluées par les pairs montrent une quasi-normalisation complète de la douleur dans un modèle à base de paclitaxel et une supériorité par rapport au ketamine, gabapentin et pregabalin dans des modèles animaux de douleur neuropathique.
MIRA (NASDAQ:MIRA) gab die Einleitung des MAD-Teils (mehrstufige steigende Dosen) ihrer Phase-1-Studie mit oralen Ketamir-2 bei gesunden Freiwilligen und ausgewählter CIPN (chemotherapieinduzierte periphere Neuropathie) als führende Indikation der Phase 2a am 24. Oktober 2025 bekannt.
Die randomisierte, doppelblinde, placebokontrollierte Studie folgt auf eine abgeschlossene single ascending dose (SAD) Dosierung, bei der bislang keine schweren oder dosislimitierenden Nebenwirkungen berichtet wurden. MAD-Kohorten werden wiederholte tägliche Dosen von 150 mg bis 600 mg über fünf Tage testen. Nach dem Aufdecken der Blindung werden pharmakokinetische Analysen durchgeführt. Präklinische und von Fachkollegen begutachtete Daten berichten von nahezu vollständiger Normalisierung des Schmerzes in einem Paclitaxel-Modell und einer Überlegenheit gegenüber Ketamin, Gabapentin und Pregabalin in tierischen neuropathischen Schmermodellen.
MIRA (NASDAQ:MIRA) أعلنت عن بدء جزء الجرعات المتعددة المتزايدة (MAD) من تجربة المرحلة 1 للدواء Ketamir-2 فموياً لدى متطوعين أصحاء وبالتحديد اعتلال الأعصاب المحيطي الناتج عن العلاج الكيميائي (CIPN) كإشارة رئيسية للمرحلة 2a في 24 أكتوبر 2025.
تتبع الدراسة العشوائية مزدوجة التعمية والتحكم بالدواء الوهمي نمط جرعات الزيادة المنفردة (SAD) التي اكتمت حتى الآن دون تقارير عن أحداث جانبية خطيرة أو مقيدة للجرعة. ستختبر مجموعات MAD جرعات يومية متكررة من 150 مجم إلى 600 مجم لمدة خمسة أيام. سيجري التحليل الدوائي الحركي بعد فك التعمية. البيانات قبل السريرية ومراجعات الأقران تفيد بتقريب التماثل الكامل للألم في نموذج باكليتاسل وتفوق مقابل الكيتامين والجابابنتين والبريغابالين في نماذج الألم العصبي الحيواني.
- MAD Phase 1 portion initiated in healthy volunteers
- SAD completed with no serious or dose-limiting adverse events
- MAD dosing range defined: 150 mg–600 mg daily for five days
- Preclinical PTX model showed near-complete normalization of pain
- No human efficacy data reported yet from Phase 1
- Pharmacokinetic characterization pending unblinding
- Phase 2a for CIPN is planned but not yet initiated
Insights
MIRA advanced Ketamir-2 into the MAD portion of Phase 1 and named CIPN as the lead Phase 2a target; early safety looks clean.
The company progressed from the single ascending dose (SAD) phase into the multiple ascending dose (MAD) portion of its randomized, double-blind, placebo-controlled Phase 1 study, dosing repeat daily oral cohorts at 150–600 mg for five days. Reported facts include completion of SAD dosing and that no serious or dose-limiting adverse events were observed to date; comprehensive pharmacokinetic analyses are planned after unblinding.
Preclinical and peer-reviewed data cited claim robust efficacy of Ketamir-2 in validated neuropathic pain models, including the paclitaxel (PTX) model and comparisons versus ketamine, gabapentin, and pregabalin; these data support selecting chemotherapy-induced peripheral neuropathy (CIPN) as the lead Phase 2a indication and potential consideration for FDA Fast Track.
Key dependencies and risks include confirmation of safety and tolerability in the MAD cohorts, PK characterization after unblinding, and the translation of animal-model efficacy into clinical benefit for CIPN. The preclinical superiority claims are encouraging but remain non‑clinical evidence until supported by human efficacy data.
Watch for MAD safety readouts and the unblinded PK summary in the near term and any announcement of a Phase 2a trial design or regulatory interactions; expect these items across the next 6–18 months as the company moves toward a Phase 2a initiation.
Advancing toward Phase 2a clinical evaluation in chemotherapy-related pain, a condition with no approved treatments and potential for FDA Fast Track consideration
MIAMI, FLORIDA / ACCESS Newswire / October 24, 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 the initiation of the multiple ascending dose (MAD) portion of its ongoing Phase 1 clinical trial evaluating its lead oral candidate, Ketamir-2, in healthy volunteers. The Company also announced that it has selected chemotherapy-induced peripheral neuropathy (CIPN) - a common and debilitating side effect of cancer treatment - as the lead indication for its planned Phase 2a clinical evaluation.
Phase 1 Progress
This milestone follows the completion of dosing in the single ascending dose (SAD) portion of the study. According to data reviewed to date, no serious or dose-limiting adverse events have been observed, and no clinically significant safety concerns have been reported. Comprehensive pharmacokinetic analyses will be performed following unblinding to further characterize Ketamir-2's absorption and half-life profile.
The ongoing randomized, double-blind, placebo-controlled Phase 1 study is evaluating single and multiple oral doses of Ketamir-2 to assess its safety, tolerability, and pharmacokinetics in healthy volunteers. The MAD portion includes three cohorts of repeat daily oral dosing (150 mg to 600 mg for five days), building on the safety and PK data from the SAD phase.
Peer-Reviewed and Preclinical Data Support Ketamir-2's Promise in Chemotherapy-Related Nerve Pain
Ketamir-2's advancement is supported by a growing body of preclinical and peer-reviewed research demonstrating efficacy in validated neuropathic pain models.
In a poster presented at the Pain Therapeutics Summit in Boston and a peer-reviewed article published in Frontiers in Pharmacology titled "Oral Administration of Ketamir-2, a Novel Ketamine Analog, Attenuates Neuropathic Pain in Rodent Models via Selective NMDA Antagonism," Ketamir-2 was shown to outperform ketamine, gabapentin, and pregabalin across gold-standard models of neuropathic pain.
In the well-established paclitaxel (PTX) chemotherapy-induced neuropathy model, Ketamir-2 produced near-complete normalization of pain sensitivity and demonstrated greater efficacy than gabapentin, the current FDA-approved standard for neuropathic pain. Additional studies showed superior performance versus ketamine and pregabalin in restoring sensory function in sciatic nerve ligation models, supporting its potential as a next generation, non-opioid therapy.
About Chemotherapy-Induced Peripheral Neuropathy (CIPN)
CIPN is a painful nerve damage condition caused by certain chemotherapy drugs that leads to persistent pain, tingling, numbness, and burning sensations, most commonly in the hands and feet. It affects up to 70 percent of cancer patients during treatment (source), and for many, symptoms continue long after therapy ends, often limiting their ability to complete potentially lifesaving chemotherapy.
Despite its impact, there are no FDA-approved treatments for CIPN. Physicians typically use off-label antidepressants, anticonvulsants, opioids, or ketamine infusions, each with limited and inconsistent benefit and significant side effects. This unmet need represents a global market estimated near
Why Ketamir-2 Could Fill a Major Gap
While ketamine has shown pain-relieving effects, its clinical use is limited by the need for intravenous administration, short duration of action, and undesirable psychoactive effects.
Ketamir-2 was designed to overcome these limitations as a novel, non-scheduled oral analog of ketamine with:
Good oral absorption and once-daily dosing convenience
No hallucinogenic or dissociative effects
Strong preclinical efficacy and favorable safety data supporting continued development
These features position Ketamir-2 as a potentially safe, oral, non-opioid candidate to address the large unmet need in chemotherapy related nerve pain and broader neuropathic pain indications.
Given the absence of FDA-approved treatments for chemotherapy-induced neuropathic pain and the high medical unmet need in oncology supportive care, the Company believes Ketamir-2 may qualify for consideration of regulatory incentives such as Fast Track designation.
Management Commentary
"We view Ketamir-2 not only as a promising clinical asset but as a potential value-creating platform for MIRA and our shareholders," said Erez Aminov, CEO of MIRA. "Our preclinical and clinical findings suggest that Ketamir-2 could represent a differentiated, non-opioid approach in a multi-billion-dollar pain market where effective therapies simply don't exist. Advancing this program through Phase 2a development positions MIRA to address a major medical and commercial opportunity while maintaining our disciplined, data-driven approach."
Dr. Itzchak Angel, Chief Scientific Advisor of MIRA, added: "The combination of clean pharmacology, good oral bioavailability, and robust preclinical efficacy sets Ketamir-2 apart from existing therapies. We look forward to completing the ongoing Phase 1 study and advancing its Phase 2a clinical evaluation in neuropathic pain."
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. Preclinical data support its potential in neuropathic pain, PTSD, and depression, without the dissociative effects associated with ketamine. The U.S. Drug Enforcement Administration has determined that Ketamir-2 is not classified as a controlled substance under the Controlled Substances Act.
About MIRA Pharmaceuticals, Inc.
MIRA Pharmaceuticals, Inc. (NASDAQ:MIRA) is a clinical-stage pharmaceutical company focused on developing and commercializing novel oral therapeutics for neurologic, neuropsychiatric, and metabolic disorders. Its pipeline includes innovative drug candidates targeting major unmet needs in 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 did MIRA announce about Ketamir-2 on October 24, 2025?
What safety results did MIRA report from the Ketamir-2 Phase 1 SAD phase?
What MAD dosing will MIRA test for Ketamir-2 in Phase 1 (MIRA)?
What preclinical evidence supports Ketamir-2 for chemotherapy-induced neuropathic pain (MIRA)?
When will MIRA report Ketamir-2 pharmacokinetic results?
Has MIRA started a Phase 2a trial of Ketamir-2 for CIPN (MIRA)?
