a new source of energy

Khondrion is advancing its wholly-owned clinical and preclinical pipeline of potential medicines.

our approach

Our priority is to take the path which best ensures the rapid development of our innovative pipeline to deliver transformative medicines for patients living with mitochondrial disease.

Khondrion is advancing its proprietary science through a wholly-owned clinical and preclinical small molecule pipeline of potential medicines. Cellular consequences like abnormal mitochondrial architecture, reactive oxygen species production and alterations in the cellular redox-state are common findings in mitochondrial diseases.

Khondrion’s drug development strategy is based on counteracting these cellular consequences to stop disease progression and to restore normal cellular function.

technology platform

Khondrion’s in-house discovery engine is using unique live-cell imaging technologies, patient-derived cell lines 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 mitochondrial diseases.

pipeline

Khondrion’s lead asset, KH176, is a potential first-in-class oral small molecule in phase IIb clinical development to treat a range of mitochondrial diseases including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) spectrum disorders.

The phase IIa KHENERGY study, published in September 2018, showed consistent pharmacokinetic, safety and tolerability data for KH176, and significant improvement in a number of clinical endpoints which supported further development of the potential medicine. Planning for KHENERGYZE, a dose-exploration phase IIb study, is now underway with the first patient in that study expected to be dosed in Q2 2019.

KH176 has been granted Orphan Drug Designation for MELAS spectrum disorders and Leigh disease in Europe and for all inherited mitochondrial respiratory chain disorders in the USA.

Preclinical research is underway exploring the potential of Khondrion’s pipeline to target diseases resulting from a cellular reduction–oxidation (redox) imbalance. Redox imbalance occurs when the redox signaling processes in cells – the fundamental processes by which cells detect damage and then start their repair mechanisms – are not controlled. Diseases currently under investigation include genetic forms of Parkinson’s disease, congenital muscular dystrophy and inborn errors of metabolism.

scientific articles


“Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD+”

Eligio F. Iannetti, Jan A. M. Smeitink, Peter H. G. M. Willems, Julien Beyrath & Werner J. H. Koopman

Cell Death & Disease, 2018, volume 9, 1135.


“The KHENERGY study: Safety and efficacy of KH176 in mitochondrial m.3243A>G spectrum disorders.”

Mirian CH Janssen, Saskia Koene, Paul de Laat, Pleun Hemelaar, Peter Pickkers, Edwin Spaans, Rypko Beukema, Julien Beyrath, Jan Groothuis, Chris Verhaak, Jan Smeitink

Clinical Pharmacology & Therapeutics, 2018, July 30th


“KH176 Safeguards Mitochondrial Diseased Cells from Redox Stress-Induced Cell Death by Interacting with the Thioredoxin System/Peroxiredoxin Enzyme Machinery”

Julien Beyrath, Mina Pellegrini, Herma Renkema, Lisanne Houben, Svetlana Pecheritsyna, Peter van Zandvoort, Petra van den Broek, Akkiz Bekel, Pierre Eftekhari & Jan A. M. Smeitink

Scientific Reports 2018, April 26; 8:6577


“KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers”

Saskia Koene, Edwin Spaans, Luc van Bortel, Griet van Lancker, Brant Delafontaine, Fabio Badilini, Julien Beyrath and Jan Smeitink.

Orphanet Journal of Rare diseases 2017 Oct 2; 12:163


“Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease.”

de Haas R, Das D, Garanto A, Renkema HG, Greupink R, van den Broek P, Pertijs J, Collin RWJ, Willems P,
Beyrath J, Heerschap A, Russel FG, Smeitink JA.

Scientific Reports 2017 Sep 15;7(1):11733.


“Multiplexed high-content analysis of mitochondrial morphofunction using live-cell microscopy”

Eligio Iannetti, Jan Smeitink, Julien Beyrath, Peter Willems, Werner Koopman.

Nature Protocols (2016) 11, 1693-1710


“Mitochondrial disorders in children: toward development of small‐molecule treatment strategies”

Werner Koopman, Julien Beyrath, Cheuk‐Wing Fung, Saskia Koene, Richard Rodenburg, Peter Willems, Jan Smeitink.

EMBO Molecular Medicine (2016) emmm.201506131.


“Toward high-content screening of mitochondrial morphology and membrane potential in living cells”

Eligio Iannetti, Peter Willems, Mina Pellegrini, Julien Beyrath, Jan Smeitink, Lionel Blanchet, Werner Koopman.

The International Journal of Biochemistry and Cell Biology, 63 (2015) 66-70.


“Mitochondrial diseases: Drosophila melanogaster as a model to evaluate potential therapeutics”

Sarah Foriel, Peter Willems, Jan Smeitink, Annette Schenck, Julien Beyrath.

The International Journal of Biochemistry and Cell Biology, 63 (2015) 60-65.


“Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning”

Lionel Blanchet, Jan A.M. Smeitink, Sjenet E. van Emst-de Vries, Caroline Vogels, Mina Pellegrini, An I. Jonckheere, Richard J.T. Rodenburg, Lutgarde M.C. Buydens, Julien Beyrath, Peter H.G.M. Willems and Werner J.H. Koopman.

Scientific Reports, 26;5:8035 (2015).


“New treatments for mitochondrial disease—no time to drop our standards”

Gerald Pfeffer, Rita Horvath, Thomas Klopstock, Vamsi K. Mootha, Anu Suomalainen, Saskia Koene, Michio Hirano,Massimo Zeviani, Laurence A. Bindoff,Patrick Yu-Wai-Man, Michael Hanna, Valerio Carelli, Robert McFarland, Kari Majamaa, Douglas M. Turnbull,
Jan Smeitink and Patrick F.Chinnery

Nature Review Neurology 9, 474–481 (2013).


“Monogenic mitochondrial disorders”

Koopman WJ, Willems PH, Smeitink JA.

New England Journal of Medicine. 366(12):1132-41 (2012).


“Towards the harmonization of outcome measures in children with mitochondrial disorders.”

Koene S, de Laat P, van Tienoven DH, Vriens D, Brandt AM, Sweep FC, Rodenburg RJ, Donders AR, Janssen MC, Smeitink JA.

Developmental Medicine & Child Neurology. 55(8): 698-706 (2013).


“Serum FGF21 levels in adult m.3243A>G carriers: clinical implications.”

Koene S, de Laat P, van Tienoven DH, Vriens D, Brandt AM, Sweep FC, Rodenburg RJ, Donders AR, Janssen MC, Smeitink JA.

Neurology. 83(2):125-33 (2014).