“I am excited to continue the collaboration with
Migraine is a common neurological disorder characterized by recurrent headaches of moderate to severe intensity, which can last from a few hours to several days. Current treatments focus on relieving symptoms and preventing additional attacks. The available medicines comprise over-the-counter painkillers and prescription medicines such as triptans and calcitonin gene-related peptide (CGRP) antagonists. According to Evaluate Pharma the annual world-wide sales of prescription medicines are expected to increase from
The Cephagenix program is aimed at identifying subtype-selective ATP-sensitive potassium channel (KATP) inhibitors for the treatment of migraine. It has been demonstrated in the clinic that drugs which induce dilation of intracranial blood vessels may induce migraine attacks in migraineurs [1] and a KATP channel activator, levcromakalim, is by far the most effective agent studied to date as inducer of migraine attacks [2]. Based on this, KATP channels has been suggested to be a unifying mechanism for the induction of migraine pain, e.g by NO, CGRP and PACAP [3]. This is also supported by the finding that blocking KATP channels in rodent models of migraine is an effective pain-reducing treatment [4].
Cephagenix has managed to produce highly selective inhibitors of the specific KATP channel subtype expressed in the intracranial arteries and first-generation compounds from this series has now shown efficacy in a relevant rodent migraine model. The drug candidates from the Cephagenix program are initially intended for acute migraine treatment with potential for preventive treatment in chronic migraine patients. Cephagenix’s novel subtype-selective inhibitors of KATP channels were successfully developed using Saniona’s Ionbase® technology platform. Most recently selected compounds from the series have demonstrated both in vitro and in vivo preclinical results validating the concept and initial tool compounds from the series.
[1] Ashina et al., Nat. Rev. Neurol., 2017;13:713-724
[2] Al-Karagholi et al., Brain, 2019;142:2644-2654
[3] Clement et al. Cells, 2022;11:2406.
[4] Christensen et al., Cephalalgia, 2020;40:650-664
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