Kallyope is a late-stage biotechnology company focused on developing innovative migraine and metabolic disease therapies for health challenges faced by hundreds of millions of people globally. Today, the Company presented results from several clinical and preclinical studies that support the initiation of Phase 3 studies of elismetrep, a novel TRPM8 channel blocker. Elismetrep is a potentially new approach for migraine and the only agent known to be in late-stage development for the acute treatment of migraine. The data will be presented at the American Headache Society 68th Annual Scientific Meeting currently being held in Orlando, FL. Phase 3 studies of elismetrep for the acute treatment of migraine are anticipated to initiate mid-2026.
“The opportunity to provide a new treatment for millions of people who suffer the debilitating effects of migraine is unique and important,” said Jay Galeota, CEO and President, Kallyope. “As the only late-stage therapeutic in development for the acute treatment of migraine, Kallyope has the responsibility of advancing elismetrep quickly and carefully to potentially bring a new opportunity for pain and symptom relief to the millions of people struggling with migraine symptoms, many of whom are forced to put their lives on hold at a moment’s notice.”
Liquid-Filled Softgel Capsule Formulation Results in More Rapid Absorption which is Predicted to Improve Efficacy and Result in Earlier Onset of Pain Relief
A Phase 1 biocomparison study compared the pharmacokinetics (PK) and safety/tolerability of a novel liquid-filled softgel capsule (LSGC) formulation of elismetrep to those of the dry-filled capsule (DFC) formulation used in the Phase 2b study. Elismetrep absorption was rapid and accelerated with the LSGC formulation (median time to maximum concentration [Tmax] = 1-h) compared to the DFC formulation (median Tmax = 2.5-h). While absorption was more rapid with the LSGC formulation, the overall extent of absorption was similar and there was no meaningful difference in tolerability between the two formulations.
Exposure-response modeling and clinical trial simulations were used to estimate the impact of the new formulation on pain freedom and freedom from the most bothersome migraine-associated symptom. Model-based simulations with the PK data from the biocomparison study predicted ~50% and ~40% improvements in placebo-corrected response rates for 2-h pain freedom and 2-h freedom from the most bothersome symptom, respectively, as well as earlier onset of efficacy with the LSGC vs the DFC.
“TRPM8 is a unique therapeutic target highly associated with migraine and currently not targeted by approved migraine treatments,” said Peter J. Goadsby, MD, PhD, FRS, King Abdullah University of Science and Technology, Saudi Arabia. “With a unique mechanism of action and rapid absorption demonstrated by the liquid-filled softgel capsule formulation, elismetrep may provide much needed symptom relief to migraine patients who often have a narrow window to manage symptoms before debilitating symptoms take hold and force many to seek acute care.”
Pre-Clinical Profile of Elismetrep Supports Additive Efficacy in Combination with Other Mechanisms
Single cell sequencing studies of human and rat trigeminal ganglia neurons show that TRPM8 is expressed in a distinct type of neuron from those expressing targets of other migraine therapeutics such as CALCA (CGRP), HRT1B/D, or HRT1F (serotonin receptor subtypes targeted by triptans and ditans). Elismetrep efficacy as monotherapy and in combination with gepants and triptans was evaluated in the well-established nitric oxide donor-induced facial allodynia rat model of migraine. The study demonstrated that the combination of sub-efficacious doses of elismetrep + olcegepant or elismetrep + sumatriptan showed additive efficacy whereas the combination of sub-efficacious doses of sumatriptan + olcegepant did not show additive efficacy. These findings suggest elismetrep has the potential to work in combination therapy with gepants or triptans.
The company also presented results from the Phase 2b dose-ranging and proof of concept study of elismetrep (NCT06848075) previously shared at the 2026 American Academy of Neurology in an encore poster presentation.
Elismetrep Profile
“The five abstracts we are presenting at the 2026 American Headache Society meeting, including an encore of clinical data first presented at the 2026 American Academy of Neurology, collectively reinforce the differentiated potential of elismetrep as an investigational therapy for the acute treatment of migraine. Elismetrep’s profile as a highly selective TRPM8 blocker with favorable pharmacokinetics and promising efficacy support its potential as a novel migraine therapy,” said Brett Lauring, MD, PhD, Chief Medical Officer, Kallyope.
Results from several Phase 1 studies (single- and multiple-ascending dose studies, a formulation biocomparison study, and a statin drug-drug interaction study) and in vitro profiling suggest that elismetrep has a good profile for a novel migraine therapeutic. Elismetrep is a potent and selective inhibitor of TRPM8 with sub-nanomolar potency, is highly selective for TRPM8 vs other TRP channels, and had no meaningful off-target activities in standard screens against 81 receptors, enzymes, and ion channels. Elismetrep has been safe and well tolerated in 13 completed clinical studies with 1,055 people exposed to at least one dose and with single doses up to 900 mg and multiple doses up to 400 mg QD evaluated. In humans, absorption is rapid with the new LSGC formulation (median Tmax = 1-h). The pharmacokinetics are dose proportional up to 900 mg, and food has no meaningful impact on absorption, meaning elismetrep can be taken without regard to food. The half-life is long and ranged from 11-21-h following single doses. Multiple doses of elismetrep 150 mg had no clinically meaningful effect on the PK of rosuvastatin and simvastatin (CYP3A4 and OATP1B1 substrates) which together with in vitro profiling against other CYP isoforms and transporters all suggest a low risk of elismetrep perpetrating drug-drug interactions. Because elismetrep is metabolized by multiple pathways, there is a low risk for drug-drug interactions.
About Transient Receptor Potential Melastatin 8 (TRPM8)
Migraine is increasingly understood as a disorder of trigeminal sensory neuron hyperexcitability, in which trigeminal sensory pathways become sensitized, leading to sensory hypersensitivity and amplified pain signaling. TRPM8 is a polymodal gated ion channel expressed on a distinct subset of trigeminal neurons relevant to migraine pain signaling. In the context of migraine, TRPM8 activity is associated with trigeminal sensory neuron pathway activation, contributing to pain onset and heightened, sustained pain signaling. TRPM8 is a mechanistically distinct therapeutic target from current migraine treatments, including calcitonin gene-related peptide (CGRP) receptor antagonists and serotonin receptor-based agents, and is the only TRP channel with an established genetic association to migraine in genome-wide association studies.
About Elismetrep
Elismetrep (K-304) is an investigational, novel, oral, TRPM8 migraine-associated channel blocker (MACB) that is highly selective for TRPM8 migraine-associated channels vs. other TRP channels. Specifically designed to block TRPM8 activity, elismetrep has been shown to reduce migraine pain and associated symptoms. The Phase 2b dose-ranging and proof of concept trial for elismetrep for the acute treatment of migraine in adults demonstrated clinically meaningful efficacy that was competitive with current leading marketed therapies. No safety signals were observed. Elismetrep was well tolerated, and the large majority of reported adverse events were mild. Phase 3 trials for elismetrep for the acute treatment of migraine are planned to initiate in mid-2026. Elismetrep is an investigational product and has not been approved by the FDA or any other regulatory agency.
About Kallyope
Kallyope is a late-stage biotechnology company focused on developing innovative migraine and metabolic therapies for health challenges faced by hundreds of millions of people globally. Kallyope’s lead programs target previously unknown drivers of disease in neural signaling pathways. The Company’s most advanced candidate, elismetrep (K-304), is poised to begin Phase 3 trials for the acute treatment of migraine in mid-2026. The metabolism pipeline includes agents that target a novel target identified and validated by the Company’s Klarity™ platform, as well as oral small molecule approaches to the highly validated amylin pathway for the treatment of obesity. Kallyope was founded by world-leading neuroscientists and continues to explore the role of neural circuits in driving disease.
For more information, visit www.kallyope.com.
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