elismetrep (MT-8554) / Tanabe Pharma, Kallyope - LARVOL DELTA

A Study to Assess the Efficacy and Safety of Elismetrep (K-304) in the Acute Treatment of Migraine (clinicaltrials.gov) - P3 | N=1500 | Not yet recruiting | Sponsor: Kallyope Inc.

New P3 trial • CNS Disorders • Migraine

A Long-Term Safety Study of Elismetrep (K-304) in the Acute Treatment of Migraine (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Kallyope Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Migraine

A Long-Term Safety Study of Elismetrep (K-304) in the Acute Treatment of Migraine (clinicaltrials.gov) - P3 | N=1000 | Not yet recruiting | Sponsor: Kallyope Inc.

New P3 trial • CNS Disorders • Migraine

A Study to Evaluate the Efficacy and Safety of Elismetrep (K-304) in the Acute Treatment of Migraine (clinicaltrials.gov) - P3 | N=1800 | Recruiting | Sponsor: Kallyope Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Migraine

Efficacy of Elismetrep, a Novel, Selective, and Oral Blocker of the Migraine-associated Channel TRPM8, as a Monotherapy and in Combination with Gepants or Triptans in Preclinical Models (AHS 2026) - "Elismetrep, a TRPM8 migraine-associated channel blocker is effective both as a monotherapy and when administered in combination with either olcegepant or sumatriptan in a preclinical periorbital allodynia model relevant to migraine. TRPM8 is an ion channel expressed on a distinct set of trigeminal ganglion neurons and represents a mechanistically distinct target from those targeted by current therapeutics for migraine including CGRP receptor antagonists and serotonergic (5-HT)-based agents."

Combination therapy • Monotherapy • Preclinical • CNS Disorders • Migraine • Pain • ADCYAP1 • TRPM8

A Study to Evaluate the Efficacy and Safety of Elismetrep (K-304) in the Acute Treatment of Migraine (clinicaltrials.gov) - P3 | N=1800 | Not yet recruiting | Sponsor: Kallyope Inc.

New P3 trial • CNS Disorders • Migraine • Pain

The safety and pharmacokinetics of a novel transient receptor potential melastatin 8 (TRPM8) antagonist, XG2002, in a phase 1 study (AHS 2026) - "Recently, a TRPM8 antagonist (elismetrep) showed positive results in an acute migraine trial. The novel peripheral acting TRPM8 antagonist, XG2002, showed linear systemic exposure following oral dosing, with consistent short Tmax. T1/2 prolonged with increased dose, which forms a basis for options of dose interval. Mild AEs were transient and well tolerated."

Clinical • P1 data • PK/PD data • CNS Disorders • Migraine • TRPM8

Liquid-Filled Softgel Capsule Formulation Results in More Rapid Absorption which is Predicted to Improve Efficacy and Result in Earlier Onset of Pain Relief (Businesswire) - "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...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."

P1 data • Migraine

Phase 3 studies of elismetrep for the acute treatment of migraine are anticipated to initiate mid-2026. (Businesswire)

New P3 trial • Migraine

TRPM8 channel blockade with elismetrep in a phase 2B study: A novel approach for treating migraine (AHS 2026) - "Elismetrep represents an entirely novel, mechanistically differentiated, and promising approach to the treatment of migraine."

P2b data • CNS Disorders • Migraine • Pain • TRPM8

Exposure–response modeling predicts enhanced anti-migraine efficacy of elismetrep with an optimized formulation enabling faster drug absorption (AHS 2026) - No abstract available

Clinical • CNS Disorders • Migraine • Pain

In vitro profile of elismetrep: A potent and highly selective blocker of the migraine-associated channel TRPM8 (AHS 2026) - "Elismetrep is a potent blocker of the migraine-associated channel, TRPM8. It is highly selective for TRPM8 vs. other TRP channels and has minimal off-target effects against all tested targets with low risk for drug-drug interactions."

Preclinical • CNS Disorders • Migraine • Pain • TRPC6 • TRPM8

The human pharmacokinetics of elismetrep, a TRPM8 migraine-associated channel blocker (MACB), are well-suited for a migraine therapeutic (AHS 2026) - "The PK properties of elismetrep are well-suited for a drug for the treatment of migraine with demonstrated rapid absorption, long half-life, absence of a clinically meaningful food, and a low risk for perpetrating drug-drug interactions via effects on CYP3A4 and OATP1B1. The PK attributes are ideally suited for migraine and support the development of elismetrep for the treatment of this debilitating disease."

PK/PD data • CNS Disorders • Migraine • Pain • CYP3A4 • TRPM8

Pre-Clinical Profile of Elismetrep Supports Additive Efficacy in Combination with Other Mechanisms (Businesswire) - "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."

Preclinical • Migraine

TRPM 8 Antagonism with Elismetrep: A Novel Approach for Treating Migraine (AAN 2026) - "The most common AEs in the 20 mg group were oral paresthesia (9.8%), feeling hot (9.8%), paresthesia (7.8%), hot flush (7.8.%), and flushing (5.9%). Conclusions Elismetrep represents an entirely novel direction for treatment of migraine."

CNS Disorders • Migraine • Pain • TRPM8

Kallyope’s Phase 2b Study of Elismetrep, A Novel Approach for Treating Migraine, Presented at the American Academy of Neurology Annual Meeting (Yahoo Finance) - "In the primary and supporting analyses for 2h pain freedom, response rates for elismetrep 20 mg vs. placebo were 17.6% vs. 9.1% (odds ratio [OR]=2.1, P=0.0650) (e-Diary only) and 19.6% vs. 9.1% (OR=2.4, nominal P=0.0344) (All Data) respectively. Response rates for 2h freedom from most bothersome symptom for elismetrep 20 mg vs. placebo were 38.3 % vs. 24.2% (OR=1.9, nominal P=0.0425). Response rates for 2h pain relief for elismetrep 20 mg vs. placebo were 58.8% vs. 42.4% (OR=1.9, nominal P=0.0293)...There were no serious adverse events (AEs). The incidence of AEs was dose dependent."

P2b data • Migraine

Kallyope to Present Phase 2b Study Results for Elismetrep for the Acute Treatment of Migraine at the 2026 American Academy of Neurology Annual Meeting (Businesswire) - "Clinically meaningful data establishes proof of concept for elismetrep as a promising therapeutic candidate for migraine and its progression into registrational studies anticipated to initiate mid-2026. Data validate novel TRPM8 migraine-associated channel blocker (MACB) and demonstrate a clinical profile competitive with leading approved therapeutics for migraine."

New trial • P2b data • Migraine • Pain

Study to Assess the Efficacy, Safety and Tolerability of MT- 8554 in Subjects With Painful Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: Tanabe Pharma Corporation | Phase classification: P2a ➔ P2

Phase classification • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Kallyope To Present at the 44th Annual J.P. Morgan Healthcare Conference (Businesswire) - "During the presentation, Mr. Galeota will provide an overview of the Company’s lead programs, including elismetrep (K-304), an oral Transient Receptor Potential Melastatin 8 (TRPM8) antagonist for the acute treatment of migraine, expected to begin pivotal studies in mid-2026, and K-554, which targets a non-incretin peptide receptor for weight loss and glucose control and will enter Phase 1 clinical studies in mid-2026."

New trial • Diabetes • Migraine • Obesity

CRISPR-Cas9 mediated editing of starch branching enzyme, SBE2 gene in potato for enhanced resistant starch for health benefits. (PubMed, Front Genome Ed) - "K301, K302, K303, K304, K305, K306, derived from distinct events, exhibited deletions and substitutions in the target exons...Furthermore, 1H-NMR study demonstrated a substantial decline in branch chain elongation in amylopectin, and thus a low degree of branching in a range of 1.15%-3.66% was reported in mutant lines, relative to the wild type (5.46%). The present study demonstrated the efficacy of CRISPR-Cas9-mediated mutagenesis of starch biosynthetic genes to develop high-amylose potato lines with elevated resistant starch content for improved health benefits."

Journal • Gene Therapies

Kallyope Announces Positive Results from Phase 2b Study of Elismetrep for the Acute Treatment of Migraine (PharmiWeb) - "Full data to be presented at a major medical meeting in 2026; Kallyope plans to initiate registrational studies in mid-2026...In the study, elismetrep delivered a favorable clinical profile through its novel mechanism, supporting its potential as a new therapeutic option for the large number of patients who are suffering from the debilitating effects of migraine...The performance of elismetrep across all endpoints was competitive with marketed therapies. No safety signals were observed, and the drug was well tolerated. Tolerability-related adverse events were mostly mild."

New trial • P2b data • Migraine

In silico mining of sn-1,3 regioselective Rhizomucor miehei lipase homolog with strict pH sensitivity from Cordyceps militaris. (PubMed, Food Chem) - "Molecular dynamic simulation revealed that the extended C-terminus (P270-K304) may endow rmCML2 with unexpected pH sensitivity by changing the H-bond network to expose the active site in pH-dependent manner. The sn-1,3 regioselectivity and pH sensitivity are expected to confer dual advantages of rmCML2 for processing lipid-related foods that require pH-dependent enzymatic conversion (e.g., cheese ripening)."

Journal

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine (clinicaltrials.gov) - P2 | N=431 | Completed | Sponsor: Kallyope Inc. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ Aug 2025

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: Kallyope Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Migraine • Pain

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: Kallyope Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Migraine • Pain