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Late Clinical Development of KH176: an innovative orphan drug to reach mitochondrial disease patients & market

Periodic Reporting for period 3 - KHON2bTREAT (Late Clinical Development of KH176: an innovative orphan drug to reach mitochondrial disease patients & market)

Okres sprawozdawczy: 2021-01-01 do 2022-06-30

Primary Mitochondrial Diseases (PMD) 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. PMD 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 PMD 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 PMD 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 and hearing loss, and exercise intolerance and fatigue. When 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) is currently being evaluated in a multi-center, phase 2b dose-finding study in adults with mitochondrial disease. Due to the Covid-19 pandemic a delay of the original predicted timelines has occurred and is discussed.

The goal of the study is to demonstrate a relevant clinical dose of KH176 in the mitochondrial disease patient population by studying an array of 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.
Following clinical batch formulation and release, CRO and site selection, as well as obtaining all required procedures in the Netherlands, Germany, and UK the phase 2b study has been initiated. Due to the pandemic a delay in the original predicted timelines has occurred. To try to finalize the phase 2b trial within the modified accepted timeframe one additional site (Denmark) was contracted. Monthly medical monitoring reports have been prepared. By the end of December 2021 full subject enrollment has been achieved. In parallel with this a detailed planning from Last Patient Last Visit (LPLV) towards finalization of the clinical trial results has been discussed, finalized and periodically monitored by all involved stakeholders. LPLV took place in May 2022 following which the process up to de-blinding and statistical analysis was initiated and the clinical trial results on the dose-finding phase 2b study are being prepared.
Except for idebenone for Leber’s Hereditary Optic Neuropathy, there are no approved prescription drug treatments for patients with primary mitochondrial disease (PMD) on the market. Khondrion is one of the leading mitochondrial disease companies in the world and the company’s strategy to focus their developments on one (the most frequently occurring) PMD 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 PMD treatments leading to increased employment within Khondrion and many companies indirectly involved.