Kallyope's Oral TRPM8 Antagonist Advances Toward Registrational Studies for Acute Migraine Treatment

Kallyope reported topline results this week from a phase 2b trial of elismetrep for the acute treatment of migraine, marking the first clinical readout for a TRPM8 antagonist in this setting. The double-blind, placebo-controlled study enrolled 431 US adults and used standard acute-migraine outcomes, including pain freedom, pain relief, and freedom from the most bothersome symptom. The invesitgational oral TRPM8 antagonist “delivered a favorable clinical profile through its novel mechanism,” according to a company statement.

The ion channel protein's performance “across all endpoints was competitive with marketed therapies.” Investigators observed no safety signals, and most tolerability-related adverse events were mild. No specific data points were included in the announcement.

The unmet need for effective acute migraine care is persistent, the company observed. “Migraines impact 1 in 6 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," Jay Galeota, Kallyope CEO and president said in the statement. Kallyope said added that migraines are estimated to have an economic impact of $36 billion annually in the US alone.

“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.”

Elismetrep blocks transient receptor potential meastatin 8, an ion channel protein expressed in trigeminal sensory neurons and linked genetically to migraine, according to Kallyope. These neurons differ from those targeted by current drug classes such as CGRP antagonists, raising the possibility that TRPM8 antagonism could complement existing approaches. Peer-reviewed studies show that roughly 25–40% of patients do not achieve satisfactory relief with currently available acute treatments, a gap that drives medication switching and ongoing frustration for both patients and clinicians.^2-4 Preclinical work with elismetrep showed "robust efficacy," Kallyope said, prompting the company to explore TRPM8 as a new pathway for therapeutic intervention.

“Our Phase 2b data strongly support elismetrep’s ability to deliver on key measures in the assessment of migraine drugs and potentially become an important part of the standard of care,” Brett Lauring, MD, PhD, Kallyope chief medical officer, said in the statement. “We look forward to sharing additional details on the novel TRPM8 mechanism, elismetrep, and expanded clinical analyses at an upcoming medical meeting.”

Registrational Studies Slated for Mid-2026

Kallyope plans to begin registrational studies in mid-2026 and will present full results at a major medical meeting. The company positions these data as a positive milestone following several pipeline setbacks in 2025, including termination of a trial of its other investigational migraine therapy, K-645, and disappointing readouts from its metabolic program earlier in the year.

World-renowned neurologist and physician scientist, Peter Goadbsy, MD, PhD, professor of neurology at Kings College Londone and emeritus professor at the University of California, Los Angeles, highlighted the ongoing clinical need. “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,” he said. “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.”

References

1. Kallyope announces positive results from phase 2b study of elismetrep for the acute treatment of migraine. News release. Kallyope. Decmember 8, 2025. Accessed December 9, 2025. https://kallyope.com/kallyope-announces-positive-results-from-phase-2b-study-of-elismetrep-for-the-acute-treatment-of-migraine/

2. 2. Cameron C, Kelly S, Reed ML, Patterson J, Nevitt SJ, Robertson J. Triptans in the acute treatment of migraine: a systematic review and network meta‑analysis. Headache. 2015;55(1):221–235. doi: 10.1111/head.12601

3. Zhang L, Novick D, Zhong S, et al. Real‑world analysis of clinical characteristics, treatment patterns, and patient-reported outcomes of insufficient responders and responders to prescribed acute migraine treatment in China. Pain Ther. 2023;12(3):751–769. doi:10.1007/s40122-023-00494-1

4. Ikeda H, Walker CE, Jackson J, Barlow S, Cotton S, et al. A real‑world analysis of patient characteristics, treatment patterns, and level of impairment in patients with migraine who are insufficient responders vs responders to acute treatment. J Headache Pain. 2020;21:69. doi:10.1186/s10194-020-01166-8