Khondrion develops drugs against energy metabolism diseases

The Nijmegen-based company Khondrion is researching medication for the treatment of energy metabolism diseases. With more than 300 known underlying gene defects and a range of conditions, the demand for a drug is great. Sonlicromanol, Khondrion's drug, is now in a phase 2b study. Founder of Khondrion Jan Smeitink and Herma Renkema, Director of Science, explain how Khondrion works.

Energy metabolism diseases, or mitochondrial diseases, are rare disorders. Mitochondria are found in almost every cell in the body and their main function is to generate energy. If there is something wrong, the cells in your body not only lack energy, but also form harmful compounds in the cell. "This affects the cells of your organs and especially those organs that need a lot of energy such as the brain, the eye and the muscles", explains Jan. "Energy metabolic diseases have a variety of consequences. From death just after birth to an initial onset and chronic course in adulthood."

Lack of medication

That the diagnostic process of mitochondrial diseases is complicated, Jan knows better than anyone. With 25 years of experience as Professor of Mitochondrial Medicine at Radboudumc, he founded Khondrion in 2012. "In my work as a professor, I was very much involved in the diagnostic process, patient care and applied and fundamental research. But I was missing medication to treat and perhaps cure my patients. That is why I founded Khondrion."

Herma joined in 2016, taking a broad experience in medical biology and mitochondrial biochemistry with her. At Khondrion, she is responsible for the strategy and research in the lab. Khondrion has a lot of specialised knowledge in house. "That knowledge was the starting point for us to see if we could develop medication from ourselves. After almost nine years we can say with our first drug in development, sonlicromanol, we have succeeded. We are now in the process evaluating the effects of sonlicromanol in clinical trials in the Netherlands, Germany, England and Denmark.

Adults and children

Khondrion focuses on energy metabolism diseases in both children and adults. "In children as the primary endpoint of the phase 2 trial, we are mainly looking at abnormal movement patterns of the muscles. Many of the children with mitochondrial diseases have abnormal movement patterns. In adults, the phase 2b trial looks at the brain. Jan explains that the research into the medication for adults is in a phase 2b trial.

"In the first phase you look at the safety, the pharmacokinetics and the tolerance of the drug that you study in healthy adults. We have completed that. In the second phase you first do an exploratory study with a small group of patients. On the basis of the positive signalson cognition, among other things, we set up an European phase 2b study. More patients participate in this international study, and two different doses of sonlicromanol are being tested."

Herma explains their choice of a second phase 2 study: "The phase 3 is called pivotal. You are no longer allowed to conclude that 'it seems like the medication works like this or like that'. That is no longer enough; you have to come up with a 'yes' or 'no' answer. The next step is to apply for authorisation to bring the medicine onto the market. So we wanted to be really sure that we are doing the right studies to be able to demonstrate that sonlicromanol works in patients."

The next step

Since September, Khondrion has no longer been working from Radboudumc, but from Novio Tech Campus in Nijmegen. "In the future, we want to become a major player in the field of mitochondrial diseases. To achieve this, we need to be able to grow and that is why we went looking for our own location. A bit like students moving in and out of their parents' houses." The choice of the campus was quickly made. "We are still centrally located in Nijmegen," explains Herma. "In addition, we already knew the campus, which makes the transition easier. We like the new location very much, with a combination of laboratories and office spaces."

Being modest

Jan and Herma hope to have good news in 8 to 9 months news when the first results of the phase 2b study will be known, but are emphatically cautious. "There is not yet a single drug available for patients with an energy metabolism disease. We think it is important to manage expectations towards patients well." Jan: "Whatever the outcome of our ongoing studies, we have made important steps in the development of a possible first drug treatment medication for these serious diseases. We do not shout out loud that we are one of the most advanced companies in this field. With the knowledge we have gained, we will build Khondrion into a global player.

This article will be published in the upcoming edition of Biotechnews magazine.