Targeting the key underlying mechanisms in mitochondrial disease.
Khondrion’s in-house discovery engine is using unique live-cell imaging technologies and 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 mitochondrial diseases.
Khondrion’s wholly-owned investigational lead asset, sonlicromanol (formerly known as KH176), is a potential first-in-class medicine and one of the most advanced disease-modifying drug candidates for primary mitochondrial disease in clinical development.Sonlicromanol targets the key underlying mechanisms of mitochondrial disease based on its scientifically validated and unique triple mode of action. Sonlicromanol is a reductive and oxidative distress modulator with anti-inflammatory properties.
KHENERGY – Early clinical proof of concept was achieved for sonlicromanol in the Company’s Phase IIa KHENERGY study. The study generated consistent pharmacokinetic, safety and tolerability data and sonlicromanol demonstrated significant cognition and mood -related patient improvements. Publication of the KHENERGY study results.
KHENERGYZE – In January 2020 Khondrion commenced its international multi-centre Phase IIb KHENERGYZE study of sonlicromanol in adult patients with Classic MELAS Syndrome spectrum disorders. The study’s objective was to reconfirm and expand on the positive findings from the KHENERGY study. The double-blind, randomised, placebo-controlled 3-way cross-over study investigated the effect of sonlicromanol in 27 adult patients with a m.3243A>G PMD mutation which is responsible for Classic MELAS Syndrome spectrum disorders as well as pre-confirmed cognitive impairment using a cognition-related inclusion test. In addition to the endpoints that were assessed in the Phase IIa study, the KHENERGYZE study added several cognition related endpoints developed by Cogstate which are broadly validated in a number of CNS indications as well as several outcome parameters in other domains that were not studied before. Last patient enrolled in Phase IIb KHENERGYZE trial.
KHENEREXT – Patients who had successfully completed the KHENERGYZE study were offered to participate in a 12 month open label extension study, announced in October 2021. The main objective of this trial was to enable continued sonlicromanol treatment for those patients while collecting additional insightful longer-term data. Khondrion announces first patients dosed in KHENEREXT Phase IIb extension study examining long-term safety and efficacy of oral sonlicromanol in mitochondrial disease patients.
The results of the Khenergyze and Khenerext trials – the Phase 2b program – have been published in Brain
KHENERGYC – In April 2021 Khondrion commenced its paediatric Phase II study to explore the pharmacokinetics, safety and efficacy of sonlicromanol in children. The double blind, placebo-controlled study is investigating the effect of sonlicromanol in 24 children (from birth to 17 years) with genetically confirmed primary mitochondrial disease of which the gene defect is known to hamper the functioning of one or more oxidative phosphorylation system enzymes and who are suffering from movement disorders. The study’s primary objective is to evaluate the effect of sonlicromanol on motor function using a range of validated, quantitative assessments including the Gross Motor Function Measure-88 and the Nine Hole Peg Test. Khondrion announces first patients dosed in 6-month paediatric Phase II study of sonlicromanol for mitochondrial diseases.
Sonlicromanol has been granted Orphan Drug Designations for the treatment of MELAS, Leigh disease and patients with MIDD in Europe and for all inherited mitochondrial respiratory chain disorders in the USA. It has also been granted a Rare Pediatric Disease designation by the US FDA for the treatment of MELAS.
Khondrion is exploring the potential of its pipeline to target other diseases.
Press release – Khondrion announces publication in Scientific Reports outlining an additional anti-inflammatory mode of action for its lead phase IIb-stage drug candidate sonlicromanol
Press release – Khondrion announces publication in PLOS ONE of new research showing normalisation of prostate cancer stem cell mPGES-1 overexpression and inhibition of cancer spheroid growth by sonlicromanol’s active metabolite
