Khondrion start met de KHENERGY studie: een fase 2 klinische trial met KH176 in MELAS/MIDD syndromen.

Khondrion, het farmaceutisch bedrijf wat zich richt op de ontwikkeling van behandelingen voor mitochondriële ziekten, meldt vandaag de start van de fase 2 klinische trial bij volwassen met energiestofwisselingsziekten – de zogenaamde KHENERGY studie. Binnen deze studie zal de veiligheid en de effectiviteit van KH176 getest gaan worden in volwassen patiënten met MELAS en MIDD syndromen. Patiënten met deze mitochondriële ziekten hebben een mutatie in het mitochondriële DNA wat in de mitochondriën zelf zit.

KH176 is een oraal beschikbaar klein molecuul ontwikkeld voor de behandeling van mitochondriële ziekten.

Jan Smeitink, Khondrion’s CEO en hoogleraar mitochondriële geneeskunde aan het Radboud Universitair Medisch Centrum in Nijmegen zegt “Met de succesvol verlopen fase 1 studie en nu de start van de KHENERGY studie hebben we een volgende belangrijke stap gezet in onze missie om een medicijn te ontwikkelen voor patiënten met energiestofwisselingsziekten.”

Uitgebreider persbericht in het Engels:

Khondrion initiates the KHENERGY study, a phase 2 clinical trial of KH176 in MELAS/MIDD and mixed mitochondrial syndromes

NIJMEGEN, The Netherlands – Khondrion, the clinical-­‐stage pharmaceutical company focusing on small molecule therapeutics for mitochondrial diseases, announces today the initiation of the KHENERGY study, a Phase 2 clinical trial with KH176 in patients harboring the m.3243A>G mutation in the mitochondrial genome. This mitochondrial DNA mutation is associated with Mitochondrial

Encephalomyopathy, Lactic Acidosis and Stroke-­‐like episodes (MELAS syndrome), Mitochondrial Diabetes and Deafness (MIDD syndrome) and mixed phenotypes.

Khondrion’s KH176 is an orally bio-­‐available small molecule developed by Khondrion for the treatment of mitochondrial (-­‐related) diseases. The compound is a member of a new class of Khondrion drugs essential for the control of oxidative and redox pathologies. In December 2015 Khondrion reported that KH176 demonstrated a favorable pharmacokinetic profile and an acceptable safety profile in randomized, placebo-­‐controlled, double blind Phase 1 clinical trials, performed in healthy male volunteers.

Jan Smeitink, Khondrion’s CEO and Professor of Mitochondrial Medicine at the Radboud University Medical Center, Nijmegen, The Netherlands, said “With the successful outcome of the KH176 phase I clinical trials and now the initiation of the KHENERGY STUDY in adult patients we have set an important step to accomplish our mission – making a substantial contribution to the development of drugs for patients suffering from mitochondrial (-­‐related) diseases. Based on anticipated learning’s from the KHENERGY study we will be initiating discussions with the EMA to develop pivotal trials to better characterize the potential benefits of KH176 in patients with mitochondrial disease”. Khondrion expects to have enrolled all 20 patients in the fourth quarter of this year.

The KHENERGY STUDY will be a single-­‐center, double-­‐blinded, randomized, placebo-­‐controlled 2-­‐way cross over Phase 2 trial. Patients will receive KH176 orally in a twice a day dosing schedule. The primary efficacy endpoint will be objective, quantitative, clinical relevant gait assessments. The study will also explore changes in other measures of clinical relevance and biomarkers associated with mitochondrial functioning.

About mitochondrial diseases

Mitochondria, the cell’s powerhouses, produce the energy necessary for life. Mitochondrial failure, due to either mutations in the mitochondrial genome or the nuclear DNA, is associated with a broad range of diseases, including orphan diseases of the oxidative phosphorylation system like Leigh

disease, MELAS, MIDD and LHON syndromes as well as diseases like Parkinson’s Disease. Cellular consequences like abnormal mitochondrial architecture, reactive oxygen species production and alterations in the cellular redox-­‐state are common findings in these diseases. Khondrion’s drug development strategy is based on counteracting these cellular consequences to stop disease progression and to restore normal cellular function.

About Khondrion

Khondrion is an innovative clinical-­‐stage pharmaceutical company focusing on developing small molecule therapeutics for mitochondrial (-­‐related) diseases. The potential of several lead compounds to serve as new treatment modalities for mitochondrial disease is currently being explored. Khondrion’s KH176 has been granted Orphan Drug Designation (ODD) for Leigh disease and MELAS syndrome in Europe and for all inherited mitochondrial respiratory chain disorders in the

USA. Thanks to its strategic partnership with the Radboud Center for Mitochondrial Medicine of the Radboud University Medical Center, Nijmegen, The Netherlands, Khondrion has access to all mitochondrial tools, technologies and expertise. Besides, Khondrion has established collaborations with patient organizations, patient advocacy groups and university research groups around the world as well as with small, medium and large enterprises. Khondrion is a privately held pharmaceutical company, among others supported by the Dutch Foundations Energy4All, Join4Energy, Road4Energy,

Ride4Kids, Tim Foundation, Zeldzame Ziekten Fonds, and National and European Governments. 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 www.khondrion.com

Cautionary Note Regarding Forward-­‐Looking Statements

This press release contains forward-­‐looking statements. All statements, other than statements of historical facts, contained in this press release, including statements regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-­‐looking statements. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions are intended to identify forward-­‐looking statements, although not all forward-­‐looking statements contain these identifying words. Any forward-­‐looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. 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. While we may elect to update these forward-­‐looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change.


Khondrion BV
Prof. dr. Jan Smeitink CEO