Investigational TRPM8 Antagonist Elismetrep Achieves Positive Phase 2b Data in Acute Migraine

According to a new company update, Kallyope has announced positive results from its phase 2b study (NCT06848075) assessing elismetrep, an investigational oral transient receptor potential melastatin 8 (TRPM8) antagonist in development for the acute treatment of migraine. Overall, elismetrep demonstrated a favorable clinical profile in the study through its novel mechanism, further supporting further its evaluation as a potential therapeutic option for patients with acute migraine.¹

"The treatment of migraine is in urgent need of therapeutic innovation. Only a minority of patients respond to any specific approved drug and often inconsistently. Elismetrep targets TRPM8 and represents an entirely new approach for the treatment of migraine," Brett Lauring, MD, PhD, chief medical officer at Kallyope, told NeurologyLive^®. "Elismetrep has the potential to expand the range of therapeutic options for patients, so we are determined to realize this potential for the many millions of migraine sufferers without adequate relief."

The study, a double-blind, placebo-controlled, phase 2b, dose-ranging trial, randomized 431 participants in the United States to evaluate the efficacy and safety of elismetrep for acute migraine. Kallyope noted that outcome measures were consistent with standard acute migraine trial assessments and included pain freedom, pain relief, and freedom from the most bothersome migraine-associated symptom at 2 hours after dosing. The company also reported that elismetrep demonstrated performance across all these end points that were comparable with currently marketed therapies. In addition, no safety signals were observed, and the treatment was generally well tolerated, with most tolerability-related adverse events described as mild.

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“Migraines are among the leading causes of disability globally, and suboptimal treatment of migraine through existing drug classes results in reduced quality of life for millions of people worldwide,” Peter Goadsby, MD, PhD, DSc, professor of neurology at King’s College London, said in a statement.¹ “Given the variable and inadequate response to existing therapies, patients and physicians urgently need new approaches to managing this debilitating condition, making elismetrep a compelling addition to the innovation pipeline in migraine.”

In prior research, studies have shown that approximately 30% of patients achieve favorable outcomes with any given medication used for the acute treatment of migraine, contributing to frequent switching among therapies.² Kallyope noted that elismetrep targets TRPM8, an ion channel with a reported genetic association with migraine that has shown efficacy in preclinical models for migraine.³ TRPM8 is expressed in trigeminal sensory neurons implicated in migraine and differs from the pathways targeted by existing treatments, including calcitonin gene–related peptide antagonists, indicating potential applicability in combination approaches.

“Migraines impact one in six Americans, leading to debilitating pain, nausea, and sensitivity that can strike at a moment’s notice and prevent people from participating fully in their lives. Migraines are estimated to have an economic impact of $36 billion annually in the U.S. alone,” Jay Galeota, president and CEO at Kallyope, said in a statement.¹ “As the only TRPM8 antagonist being studied for the acute treatment of migraine, elismetrep has demonstrated the potential to bring relief and a sense of control back to the lives of millions of people who suffer from migraines. We look forward to initiating registrational studies in 2026 and working with great urgency to bring this important potential therapy to patients in need.”

REFERENCES
1. Kallyope Announces Positive Results from Phase 2b Study of Elismetrep for the Acute Treatment of Migraine. News release. Kallyope. December 8, 2025. Accessed December 11, 2025. https://kallyope.com/kallyope-announces-positive-results-from-phase-2b-study-of-elismetrep-for-the-acute-treatment-of-migraine/
2. Bentivegna E, Galastri S, Onan D, Martelletti P. Unmet Needs in the Acute Treatment of Migraine. Adv Ther. 2024;41(1):1-13. doi:10.1007/s12325-023-02650-7
3. Wei C, Kim B, McKemy DD. Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide-induced migraine-like pain behaviors in mice. Pain. 2022;163(12):2380-2389. doi:10.1097/j.pain.0000000000002635