Enabling continued treatment in 52-week multi-centre study for patients who have completed ongoing KHENERGYZE Phase IIb study investigating sonlicromanol, one of the most advanced disease-modifying drug candidates in development for primary mitochondrial diseases.

NIJMEGEN, the Netherlands – 19 October 2021: Khondrion, a clinical-stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial diseases, today announces that the first patients have been successfully dosed in its KHENEREXT Phase IIb open-label extension study (NCT04604548) to investigate long-term safety and efficacy of sonlicromanol in adult patients with a genetically confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation who have completed the KHENERGYZE study.

Sonlicromanol, Khondrion’s wholly-owned, investigational lead asset, is currently being investigated in the ongoing KHENERGYZE Phase IIb study in adult patients and the KHENERGYC Phase II paediatric study. The compound is a first-in-class, oral small molecule targeting key underlying mechanisms of mitochondrial disease based on its unique triple mode of action: redox modulation to help restore the cell’s metabolism, radical trapping preventing ferroptotic cell death, and mPGES-1 inhibition resulting in anti-inflammatory effects.

The multi-centre, open-label KHENEREXT study is underway at internationally recognised mitochondrial disease centres in Europe. First patients have been dosed at both the Radboud University Medical Center, Nijmegen, the Netherlands, and the Friedrich-Baur-Institute, Dept. of Neurology, LMU Hospital, Munich, Germany.

The main objective of this 52-week study is to enable continued sonlicromanol treatment for patients who have completed the ongoing KHENERGYZE Phase IIb study while collecting additional insightful longer-term data. Since sonlicromanol is expected to be a chronic treatment for mitochondrial diseases, this new study aims to establish sonlicromanol’s  long-term safety profile. To this end, a twice daily oral dose of 100 mg of sonlicromanol  (deemed safe and well tolerated by the target group in an earlier study), will be administered over the course of one year. In addition, at three months intervals the KHENEREXT study will assess, next to safety, primary and secondary functional clinical outcome measures, including cognition, fatigue and motor-function related parameters.  

Prof. Dr. Jan Smeitink, Chief Executive Officer at Khondrion, said: “When mitochondria are defective, this can result in a wide variety of serious and debilitating diseases, that require long-term care and treatment. Current options are extremely limited and largely supportive  so there is an urgent need for new, disease modifying therapies.

“While our ongoing Phase IIb study in adult patients with MELAS spectrum disorders will provide us with crucial data to support sonlicromanol’s continued clinical development, it is important for us to also understand its longer-term efficacy and safety profile. Our KHENEREXT study, offering treatment extension to patients who have completed the initial Phase IIb study, is an important step in our sonlicromanol journey.”

Prof. Dr. Thomas Klopstock, the German Principal Investigator for the KHENEREXT study, said: “Physicians treating patients with mitochondrial disease currently have a limited therapeutic arsenal of specific disease-modifying therapies, but potential tailored treatments are emerging. Through this next trial of sonlicromanol we have an opportunity to study its effects over the longer term and gain a better understanding of its potential to improve the clinical outcomes of patients.”

– ENDS –


Khondrion BV

Prof. Dr. Jan Smeitink, CEO

E-mail: info@khondrion.com

Tel: +31-24-7635000



Consilium Strategic Communications
Mary-Jane Elliott, David Daley, Melissa Gardiner
E-mail: khondrion@consilium-comms.com
Tel: +44 20 3709 5700


About Khondrion

Khondrion is a privately held clinical-stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial diseases. Founded by Prof. Jan Smeitink, a world-leader in mitochondrial medicine, the company is advancing its proprietary science through a wholly-owned clinical and preclinical small molecule pipeline of potential medicines.  


The company’s in-house discovery engine is using unique live-cell imaging technologies and predictive cell-based disease models to build a portfolio of promising compounds. Active discovery programmes are underway developing new therapies, biomarkers, and new read-out technologies in the field of primary mitochondrial diseases.


To accelerate the discovery and development of its potential medicines for primary mitochondrial diseases, Khondrion collaborates with a global clinical and academic network and patient organisations internationally. For more information visit www.khondrion.com


About mitochondrial disease

Mitochondrial disease occurs when mitochondria, found within all cells of the human body and responsible for producing the energy necessary for cells to function, are defective. This can result in a wide range of serious and debilitating illnesses occurring shortly after birth or later in life. Signs and symptoms of these can include cognitive problems, learning disabilities, blindness, deafness, heart failure, diabetes, fatigue, intolerance to exercise, muscle weakness and gait problems, and stunted growth. Orphan diseases of the oxidative phosphorylation system like Leigh disease, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) spectrum disorders including MIDD (maternally inherited diabetes and deafness), LHON (Leber’s hereditary optic neuropathy) and other respiratory chain/ oxidative phosphorylation disorders, are all examples of mitochondrial disease.