Targeting Novel Neural Circuits to Transform Migraine Treatment

Elismetrep (K-304): Bringing Innovation to a Global Market Defined by Low Patient Satisfaction

Our first-in-class migraine candidate elismetrep (K-304) targeting TRPM8 represents an entirely new approach for the treatment of migraine.

Debilitating migraines that impede the ability to participate in daily life affect tens of millions and create an addressable market for the acute treatment of migraine that is expected to exceed $16 billion by 2033. Despite its size, the migraine market is in urgent need of mechanistic innovation. Migraine drugs fall into several classes with each only effective in a small proportion of patients – often inconsistently. The most recent class focuses on antagonizing the effects of the neuropeptide calcitonin gene-related peptide (CGRP). Patients often switch between available classes of medication to seek relief. 

Human genetic studies have consistently shown a link between TRPM8 and migraine and that higher expression of TRPM8  increases the risk for migraine. These findings suggested that TRPM8 blockade with elismetrep could represent a novel approach to treating migraine. 

TRPM8 is a polymodal gated non-selective ion channel expressed in neurons distinct from those expressing CGRP, suggesting it could be used in a complementary way. TRPM8 biology is also entirely distinct from other members of the TRPM family of proteins, further differentiating Kallyope’s approach. Elismetrep is a novel, oral highly selective TRPM8 channel blocker. If approved, TRPM8 channel blockers would represent a major expansion of therapeutic options for migraine patients. 

Our nearly 450-patient Phase 2b study strongly supports elismetrep’s clinical benefit to migraine sufferers and validated our novel approach to migraine. Phase 3 studies are currently underway. 

About Migraine:

Migraine is a common and frequently debilitating condition of the trigeminovascular system that affects over 10% of individuals worldwide.¹ Migraine is the third most common disease in the world and the second leading cause of disability worldwide.² The condition is approximately three times more common in women compared to men, and in the United States approximately 17% of women and 6% of men self-reported experiencing migraine, representing approximately 40 million people in the country. Migraine is characterized by recurrent, pulsating headache attacks of moderate to severe pain intensity that can last from 4 to 72 hours, is often associated with nausea, noise sensitivity, and light sensitivity and is exacerbated by movement, visual, auditory and other sensory stimuli.³ These attacks lead to functional disabilities, including cognitive impairment and perceptual disturbances. After resolution of headache attacks, patients often describe continuing disability due to mental fog, residual fatigue, and mood changes. The underlying cause of migraine is believed to be a combination of genetic and environmental factors that affect the function of nerve cells.⁴

Despite the availability of several classes of medications for migraine, there remains a substantial unmet medical need for drugs acting by novel mechanisms of action due to the limitations in responder rates, efficacy, safety, contraindications and/or tolerability of available options.⁵