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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - KHON2bTREAT (Late Clinical Development of KH176: an innovative orphan drug to reach mitochondrial disease patients & market)

Teaser

Summary

Mitochondrial diseases (MD) are chronic debilitating progressive multi-system disorders which might have their age of onset at any age. There is a high unmet medical need for treatment development for these devastating disorders as currently supportive care is the only option to be offered. MD are caused by specific nuclear DNA or the mitochondrial DNA gene defects. Consequently, the final biochemical pathway involved in energy production, the oxidative phosphorylation system, fails causing a multitude of harmful cellular consequences like disturbed redox metabolism, lipid peroxidation induced cell death and inflammation. A prototypic example of MD caused by a mitochondrial DNA mutation are the so-called MELAS spectrum disorders caused by a mutation in the transfer RNA of Leucine (m.3243A>G). The burden of this orphan MD for individual patients, their families and society are huge. First, high-energy requiring organs like the brain, the eyes, skeletal muscle start to dysfunction leading to e.g. cognitive decline, refractory epilepsy, vision loss, and exercise intolerance. As the disease progresses organ involvement increases finally leading to full dependence of individual patients with respect to daily life activities. There is a high unmet medical need to stop disease progression and finally cure these devastating disorders as currently supportive care is the only option to be offered. At Khondrion, a clinical stage biopharmaceutical company, we have developed new chemical entities of which the potential of one of these (KH176 or Sonlicromanol) will be evaluated in a multi-center, phase 2b dose-finding study in adults with mitochondrial disease. The goal is to demonstrate a relevant clinical dose of KH176 in the mitochondrial disease patient population to include additional clinical readout parameters, all in preparation of the pivotal (Phase 3) trial. The project will allow Khondrion to secure a co-development deal with a (large) pharma company or investor financing for the pivotal clinical trial, market approval and market launch.

Work performed

Since the start of the project (October 1st 2018) all necessary requirements enabling the actual start of the clinical trial (first patient in Q1-2020) have been performed. These include among others design of the trial, European site selection, site visits and contract negotiations, GMP formulation studies, writing of the Investigator Brochure (IB) and updating the Investigational Medical Product Dossier (IMPD), preparation of the Informed Consent Letters and obtaining study approval by the regulatory and ethical bodies in the participating countries: The Netherlands, Germany and the UK. Next to that all licenses for the scales, questionnaires and computer assisted tools have been obtained and vendor selections (e.g. pharmacovigilance and data-management) have been completed.

Final results

There are no treatments for patients with multi-systemic MD on the market. Khondrion is one of the leading mitochondrial disease companies in the world and the companyâ€™s strategy to focus their developments on one (the most frequently occurring) MD in adults (m.3243A>G spectrum disorders) will, with support of the H2020 SME grant, change the life of individual patients but, as expected, also substantially reduce healthcare costs. If successful the project will bring Europe in a leading position with respect to MD treatments leading to increase employment within Khondrion and many companies indirectly involved.