Interview with Jan Smeitink, CEO of Khondrion
Eight years ago, Jan Smeitink looked at himself in the mirror and decided he is going to change the world. Today, Jan is the Chief Executive Officer of Khondrion and is starting Phase 2b clinical trials for his revolutionary drug, KH176 – which might well become the first treatment on the market for people suffering from the devastating mitochondrial diseases.
We visited Jan, and his colleague Julien Beyrath, Chief Operating Officer, at the headquarters of Khondrion, a high-tech lab in a labyrinth of hallways at the Radboud Medical University in Nijmegen, the Netherlands.
Catalyze and Khondrion started working together more than 7 years ago and this was a celebratory visit, since Khondrion has recently been awarded a €2.3 Million SME Instrument Phase 2 grant. We took this opportunity to talk more about the inspiring mission of Khondrion and their journey.
Catalyze: Jan, you’ve devoted your entire career to the care of mitochondrial disease patients. I’m curious to know how this mission started, what motivated you?
Jan: The true story behind my drive is that I lost a girlfriend at the age of 18 to mitochondrial disease. From that moment onwards I decided I wanted to work in this area, although my plan at the time was not necessarily to come up with treatment, but more to study this type of disorders.
So that is exactly what I did. First, I got the chance to do my PhD on a mitochondrial topic, followed by a training in pediatrics. Then I specialized in inborn errors of metabolism, and then I became the head of department, focusing on mitochondrial disease, mostly conducting fundamental research.
Then, eight years ago, I looked into the mirror and asked myself, “What are you going to do for the rest of your life?”, “Are you going to stay in the clinic and take care of the patients? Are you going to develop new assays, find new genes with mutations, or are you going to really change the world and do something about these devastating diseases, and develop drugs?”
Catalyze: Wow, that really sounds like a defining moment in your career trajectory. Can you explain, for our readers who might not know, how does mitochondrial disease affect those who suffer from it?
Jan: The easiest way to explain it is to make an analogy with a phone battery. Your phone stops working if you don’t charge it and, as your phone ages, the battery gets older and its capacity decreases.
In some phones, the batteries come half charged when you buy them, or empty, or broken. That is what happens as well in mitochondrial disease. Because these “batteries” are everywhere in the body (with the exception of the red blood cell), every organ can be affected: in the brain it can lead to mental retardation or epilepsy, in the eye to blindness; you can experience hearing difficulties, heart rhythm disturbances, cardiomyopathies, liver disease and so on.
We know now of more than 350 genes in which mutation leads to mitochondrial diseases, and there is a broad spectrum of manifestation and progression. It can start to manifest itself in babies, children or even adults, and although it is always progressive, it can be faster or slower in development. There is no cure.
At the moment all we can provide is supportive care, advice on nutrition, vitamins and physical exercise. There is only one drug aimed to alleviate eye-related symptoms in one disease that is now on the market under conditional approval.
Catalyze: Given the lack of treatment options and how severely it affects the individual, what are you developing to tackle the unmet need?
Jan: As part of the academic research we studied the consequences of these diseases. We asked a group of mathematicians to analyse the results and come up with the most important contributors to mitochondrial diseases, so that we could target them.
More or less by serendipity, we had a water-soluble vitamin E “on the shelf” which we used to try to target redox disturbances, one of the factors that the mathematicians came up with. When we actually saw a recovery of the cells, that was the “hit” moment. We understood what to do, and what to target.
From then on we used our expertise and experience in the biochemical mechanisms underlying disease, and came to our proprietary KH176, for which we just finished a Phase 2a clinical study. This compound has shown good tolerability and safety in the patients evaluated and sufficient evidence to continue.
Catalyze: This “hit” moment was only 6 years ago and you already have a phase 2a clinical study completed, and an SME Instrument grant to advance to 2b. That is an extremely fast headway, have there been any hurdles along the path?
Jan: Officially, this company became operational in 2012, so indeed this is extremely fast and that is part of what makes us unique, besides our deep understanding of these diseases and involvement with patients.
Of course, there were many hurdles. Every new phase we enter is a hurdle because we started this from scratch and we are not experts in this process, so every new phase is really new to us. The first hurdle was to establish a company from an academic starting position: finding a place to rent, getting the preliminary capital to buy the initial equipment and hire the first personnel.
We managed that by getting some informal investments, support from dedicated foundations, and some non-dilutive funding, also with the help of Catalyze. The €3 Million ZonMW grant was important at that time, as well as the Eurostars, but there were many more, small ones and large ones.
Catalyze: And now you are receiving an SME Instrument phase 2 grant. How did it feel to learn you were receiving this?
Jan: I was so pleased, I got a call about 19:00 on a Friday and I was extremely happy. Having access to funding has of course a big impact in the speed of our development. This is also thanks to Catalyze -we have a long working relationship, of more than 7 years.
Catalyze: We felt very strongly about this SME Instrument, so that day, when other projects received the good news we started getting eager for the outcome. We finally got the call that Friday evening, sent our congratulations to Jan, and immediately called each other as well. We were so excited to hear this news! Really rewarding for Khondrion, and rightfully so for them to get this SME Instrument awarded.
Jan, to wrap up, how has the collaboration between us and Khondrion been, helping you in your mission?
Jan: Catalyze helped a lot, our collaboration really paid off. A long term relationship together has been crucial, and you have always been reliable, pleasant, responsive and on time – you really have taken the burden off my shoulders.
When there were hardships, we stuck together and worked on things with joint responsibility. In the end, everything you go through pays off and you can enjoy the successes together!
Awarded grant: SME Instrument Phase 2 (2.3 M€)
For more information visit http://www.khondrion.com/