Khondrion receives Orphan Drug Designation for treatment of MELAS syndrome

NIJMEGEN – Khondrion, the Dutch pharmaceutical company focusing on small molecule therapeutics for mitochondrial diseases, announces today that the European Commission has granted Khondrion Orphan Drug Designation (ODD) for its frontrunner compound KH176 to treat MELAS syndrome.

An orphan designation allows a pharmaceutical company to benefit from incentives to develop a medicine for a rare disease, such as reduced fees in protocol assistance and protection from competition once the medicine is placed on the market. European applications for Orphan Designation are examined by the Committee for Medicinal Products (COMP), which adopts an opinion that is forwarded to the European Commission. The European Commission finally decides whether to grant an orphan designation for the medicine in question.

The European Commission has already granted Khondrion’s KH176 an ODD for treatment of the mitochondrial disease Leigh syndrome. The US Food and Drug Administration (FDA) granted Khondrion’s KH176 an ODD for all inherited mitochondrial respiratory chain disorders. KH176 is currently being evaluated in randomized, double blind, placebo-controlled dose-escalating studies in healthy volunteers in Phase 1 Clinical Trials.

“The positive COMP opinion on Orphan Drug Designation followed by the formal approval of the European Commission is another pivotal milestone in the development of KH176 to treat the rare and devastating mitochondrial diseases“ said Jan Smeitink, Khondrion’s CEO and Professor of Mitochondrial Medicine at the Radboud University Medical Centre, Nijmegen, The Netherlands. “The formal designation will enable resources for continued development, but more it provides an additional avenue with the EMA on the best path for bringing KH176 to market”.

About mitochondrial disease

Mitochondrial diseases are devastating, early fatal, multi-system disorders that affect 1:5000 live births. These rare diseases are caused by mutations in two different genomes: the nuclear DNA and the mitochondrial DNA. Mutations in the latter, like in MELAS syndrome, are maternally transmitted and consequently every child born in the family (100% recurrence risk) can be affected. As mitochondria, the cell’s powerhouses, are present in virtually every cell of the body all organs and tissues can be affected leading to symptoms like mental retardation, epilepsy, stroke-like episodes, deafness, blindness, heart- and liver failure, diabetes mellitus, muscle weakness and severe exercise intolerance.

About MELAS syndrome

MELAS syndrome belongs to the increasing family of mitochondrial diseases caused by a mutation in one of the transfer RNAs encoded by the mitochondrial genome. This particular mutation affects the so-called respiratory chain/oxidative phosphorylation system (OXPHOS) leading to isolated or combined OXPHOS enzyme deficiencies. OXPHOS is the final biochemical pathway involved in the cells energy currency, ATP. Disturbances of the respiratory chain/OXPHOS system lead to a plethora of cellular consequences disturbing normal cell metabolism. MELAS syndrome is a progressive disorder affecting organs and tissues with a high-energy demand, like the brain, the heart, the pancreas and the skeletal muscle for which there are no approved treatments.

About small molecules

For the synthesis, maintenance and functioning of mitochondria, cells need about 1000-1500 genes being 10% of the human genome. Currently, about 500 different gene defects are known to disturb normal oxidative phosphorylation, the final pathway in the production of the cell’s energy. Common consequences hereof include the increased production of reactive (toxic) oxygen species, an altered cellular redox-state, and disruption of the cellular mitochondrial network. Khondrion’s small molecules are able to (partially) correct most, if not all of these cellular alterations, and are currently in development for mitochondrial disease affecting the respiratory chain/OXPHOS-system. Khondrion’s small molecule pipeline includes compounds in different stages of development and with different modes of action.


KH176 is an orally bio-available small molecule developed by Khondrion for the treatment of MELAS syndrome and other mitochondrial respiratory chain/OXPHOS diseases. KH176 is a member of a class of drugs essential for the control of oxidative and redox pathologies. KH176 is currently being evaluated in Phase 1 Clinical Trials.

About Khondrion

Khondrion is an innovative Dutch pharmaceutical mitochondrial medicine company focusing on developing small molecule therapeutics for mitochondrial diseases. The potential of several lead compounds to serve as new treatment modalities for mitochondrial disease is currently being explored. Thanks to its strategic partnership with the Nijmegen Centre for Mitochondrial Disorders of the Radboud University Medical Centre, Nijmegen, The Netherlands, Khondrion has access to all mitochondrial tools, technologies and expertise. Besides, Khondrion has established collaborations with university research groups around the world as well as small, medium and large enterprises. Khondrion is a privately held pharmaceutical company, among others supported by the Dutch Foundations Energy4All, Join4Energy, Ride4Kids, Road4Energy, Tim Foundation, Zeldzame Ziekten Fonds, the Prinses Beatrix Fonds, and National (NWO, ALW, ZonMW) and European Governments (Marie-Curie ITN, Eurostars). Khondrion has established a strong intellectual property position protecting its emerging product portfolio through the filing of multiple broad patent applications. For more information, please visit

Cautionary Note Regarding Forward-Looking Statements

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995, including regarding product development and production. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Khondrion. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product development, including the uncertainties of clinical success and the timeline for the availability of KH176. None of the Khondrion Companies undertake to update any forward-looking statements as a result of new information or future events or developments.

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