As 2021 draws to a close, Khondrion’s CEO Jan Smeitink reflects on the past year and the continued progress Khondrion has made in its development of new treatment options for patients suffering from mitochondrial disease and provides an insight into what’s to come in 2022.

2021 was a year of adjusting to a ‘new normal’. While the unprecedented challenges brought about by the COVID-19 pandemic have continued, it has been encouraging to see the life sciences sector continue to progress its research and the development of new therapies for patients under these new circumstances.

At Khondrion, we have continued to build on the progress we made in 2020, and I am incredibly proud of what the team has achieved in the past 12 months as we work towards our goal of developing innovative, transformative treatment options for patients with mitochondrial diseases.

The Phase IIb KHENERGYZE study of our wholly owned lead asset, sonlicromanol, in adults with MELAS spectrum disorders, continued to make good progress in 2021 and patient enrolment is ongoing. We look forward to reporting study results in 2022. In January, we were pleased to announce the acceptance by the European Medicines Agency (EMA) of our Paediatric Investigation Plan (PIP) for the development of sonlicromanol for children. Mitochondrial diseases present a serious unmet medical need in children, with in general a rapid progression of symptoms that can have a significant impact on their quality of life. Developing sonlicromanol in a paediatric population is a key part of our clinical research programme here at Khondrion and this important milestone paved the way for us in April to initiate our KHENERGYC paediatric Phase II trial in children with genetically confirmed primary mitochondrial disease and suffering from motor symptoms. At Khondrion, we don’t want to leave any mitochondrial disease patient behind, so this paediatric study, together with our ongoing studies in adult patients, will help us better understand the disease-modifying potential of sonlicromanol across all age groups.

In October, we also announced the start of our KHENEREXT Phase IIb open-label extension study to investigate the long-term safety and efficacy of sonlicromanol in adult patients who have completed the ongoing KHENERGYZE Phase IIb study. When mitochondria are defective, it can result in a wide variety of serious and debilitating diseases that require long-term care and treatment. This 52-week study will allow us to understand the longer-term efficacy and safety of sonlicromanol and its potential to be used as a longer-term treatment option for patients.

In addition to our clinical development progress, Khondrion has continued its pioneering research and 2021 saw the team publish exciting new findings outlining the broader potential of sonlicromanol in other diseases. In January, we announced our publication in the leading peer reviewed Nature Journal, Scientific Reports, describing an additional anti-inflammatory mode of action and potential applications for sonlicromanol’s in vivo active metabolite KH176m. The findings are of particular interest for the treatment of patients with mitochondrial diseases, but may also benefit patients with other diseases associated with inflammatory pain, inflammatory neurologic diseases, including Alzheimer’s disease, and Parkinson’s disease as well as inflammatory cancers.

We also saw the publication in PLOS ONE of new research detailing the effects of selective mPGES-1 targeting by sonlicromanol’s active metabolite, and its potential to decrease the aggressiveness of prostate cancer. Inhibition of mPGES-1 expression is an approach currently being investigated to identify new therapeutic avenues for prostate cancer, which is the most frequently diagnosed cancer in the Western world and the leading cause of cancer-related death in men over 65 years of age. Our research provides compelling evidence to support further studies investigating the potential of sonlicromanol as an anti-tumour drug in prostate and other human cancers.

In the summer, Khondrion moved to its new headquarters at the Novio Tech Campus, one of the Netherlands’ major science hubs. This was a major milestone and a next step in the evolution of our company. Our state-of-the-art facilities at the Novio Tech Campus provide the team with the necessary capacity to support our growth plans and will, I hope, bring about new opportunities to drive innovation within our labs and with others.

While we weren’t able to return to physical events and conferences this year, I am pleased that Khondrion has maintained its presence at a number of key mitochondrial research conferences, including the inaugural MITO2i Research Symposium, the UMDF Mitochondrial Medicine Symposium and Mitocon’s 11th Italian Meeting on Mitochondrial Diseases. These meetings remain extremely important to ensure that collaboration between researchers, physicians and, most critically, patients continues. It is only by working together, continuous knowledge-sharing and engaging with research colleagues and patients that we will be able to tackle these severe and debilitating mitochondrial diseases.

Following the establishment of our Scientific Advisory Board in 2020, I’m delighted to have been able to sit down with each member of the Board in our ‘A Coffee With the Scientific Advisory Board’ series. I am also proud to have been able to highlight the stories of some of the patients and families who are affected by mitochondrial disease in our ‘Patient Perspective’ series. These inspirational and often moving stories from both series can be accessed and read on our website.

2022 promises to be a significant year for Khondrion. We expect results from both our KHENERGYZE Phase IIb study of sonlicromanol in adults and our KHENEREXT Phase IIb open-label extension study. Both will provide important data to guide the final stage of sonlicromanol’s clinical development. I look forward to providing updates as they become available.

I would like to end my message by saying a huge thank you to our talented and devoted team for their continued hard work, steadfast dedication, and commitment to finding new and much needed treatments for patients with mitochondrial diseases. And to the patients themselves, for their contributions to our research and for the insights and guidance they provide us. Without them, none of our work would be possible. I would also like to thank the supporters of Khondrion who continue to believe in our mission. There are many exciting developments to come in 2022 and I look forward to sharing these updates with you and the wider mitochondrial disease community.

Wishing you all the very best for the holidays and the New Year.

Jan Smeitink

CEO & Founder