Khondrion completes enrolment in KHENERGYZE Phase IIb trial evaluating sonlicromanol in adult patients with MELAS spectrum disorders

Khondrion completes enrolment in KHENERGYZE Phase IIb trial evaluating sonlicromanol in adult patients with MELAS spectrum disorders

NIJMEGEN, the Netherlands – 10 January 2022: Khondrion, a clinical stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial diseases, today announced that the last patient has been dosed with sonlicromanol in the KHENERGYZE Phase IIb clinical study. Sonlicromanol is Khondrion’s wholly-owned, lead asset being developed to treat a range of mitochondrial diseases in children and adults. Topline data from KHENERGYZE is expected in the third quarter of 2022.

The study’s primary objective is to evaluate the dose-effect of sonlicromanol on the attention domain score of cognitive functioning, as assessed by the computerised Cogstate visual identification test. Cognitive impairment is becoming increasingly recognised in mitochondrial disease patients and can have a significant and debilitating impact on many aspects of their lives. Sonlicromanol’s potential to counteract cognitive decline is supported by preclinical research and results from a completed Phase IIa study, which showed a significant improvement in attention and mood related outcomes in patients treated with sonlicromanol compared to placebo.

Prof. Dr. Jan Smeitink, Chief Executive Officer at Khondrion, said: Completing enrolment in our Phase IIb study is an important milestone and brings us another step closer to providing an urgent and much needed disease-modifying therapy to patients with severe and debilitating mitochondrial diseases. I would like to express my gratitude to all the patients and their families for their participation in this trial, and to the investigators and wider team, whose dedication has been vital in advancing this important clinical programme. We look forward to receiving results from the trial later in the year.”

Sonlicromanol 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. In Phase I and Phase IIa studies, sonlicromanol showed a good safety and tolerability profile well beyond target therapeutic dosing levels.

KHENERGYZE is a double-blind, randomised, placebo-controlled, multi-centre, three-way cross-over study examining cognitive function in adult patients with a specific genetically confirmed DNA mutation in the mitochondrial transfer RNALeu(UUR) (MT-TL1m.3243A>G). This mutation is responsible for MELAS spectrum disorders, including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), MIDD (maternally inherited diabetes and deafness) syndromes, and mixed phenotypes.

Sonlicromanol’s development programme also includes two other ongoing clinical studies: the KHENEREXT Phase IIb open label extension study, examining the long-term safety and efficacy of sonlicromanol in adult patients who have completed the KHENERGYZE study, and the KHENERGYC Phase II study in children.

Further details of the KHENERGYZE study are available on


Khondrion BV
Prof. Dr. Jan Smeitink, CEO
Tel: +31-24-7635000

Consilium Strategic Communications
Mary-Jane Elliott, David Daley, Melissa Gardiner
Tel: +44 20 3709 5700

About Khondrion
Khondrion is a clinical stage biopharmaceutical company developing therapies for patients with inherited mitochondrial diseases. Based on proprietary science and a deep biological understanding of mitochondrial dysfunction, the company is advancing its lead drug candidate sonlicromanol, a first-in-class, oral small molecule targeting key underlying mechanisms of mitochondrial disease based on the drug’s unique triple mode of action.

One of the most advanced disease-modifying drug candidates for mitochondrial disease in development, sonlicromanol is currently being tested in a Phase IIb trial and a 12-month open-label extension study in adult patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) spectrum disorders, as well as in a 6-month Phase II study in children with genetically confirmed primary mitochondrial diseases and who suffer from motor symptoms. The compound has been granted orphan drug designations for the treatment of MELAS, Leigh disease and patients with maternally inherited diabetes and deafness (MIDD) in Europe, and for all inherited mitochondrial respiratory chain disorders in the US. It has also been granted a Rare Pediatric Disease designation in the US for the treatment of MELAS. Sonlicromanol and other compounds from Khondrion’s proprietary library have the potential to be developed for a wide range of diseases and conditions with the aim of benefiting patients whose daily lives are severely impacted by mitochondrial impairment.

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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), and other respiratory chain / oxidative phosphorylation disorders, are all examples of mitochondrial disease. MELAS spectrum disorders are some of the most frequently observed primary mitochondrial diseases, in which all patients are characterised by an underlying point mutation (m.3243A>G) in the maternally inherited MTTL1 gene.