SON4PEM trial advances development of sonlicromanol, aiming to address chronic fatigue in Post-COVID patients with post-exertional malaise
NIJMEGEN, The Netherlands – May 19, 2026 – Khondrion today announced that the first patient has been dosed in the Phase II SON4PEM study (NCT07298005), a key clinical milestone in the development of sonlicromanol beyond primary mitochondrial disease. Sonlicromanol is a proprietary small molecule therapy targeting fatigue associated with post-exertional malaise (PEM) in post-COVID syndrome.
The SON4PEM study is an investigator-initiated, randomized, double-blind, placebo-controlled Phase II trial conducted at Amsterdam University Medical Center and supported by ZonMw, The Netherlands Organisation for Health Research and Development (11080022420008).
“This milestone represents an important step forward in advancing sonlicromanol into a new, high unmet need indication,” said Jasper Levink, CEO of Khondrion. “Post-COVID syndrome affects millions globally and for many patients the condition is life-altering. Individuals with post-exertional malaise can experience a severe worsening of symptoms after even minimal physical or mental activity—leaving them unable to work, care for their families, or participate in everyday life. We believe sonlicromanol’s mechanism of action, targeting mitochondrial dysfunction, positions it as a potentially differentiated therapeutic option for this urgent unmet need.”
Despite the scale of the problem, there are currently no approved therapies specifically addressing PEM-related fatigue due to post-COVID syndrome. Patients often face a prolonged and uncertain recovery, with limited treatment options and significant impact on quality of life. This underscores both the urgent medical need and the opportunity for therapies that can deliver meaningful, patient-relevant outcomes.
“The SON4PEM study is designed to generate proof-of-concept data that will inform further clinical development”, Levink added. “Equally important, it is focused on outcomes that matter most to patients—reducing fatigue, improving resilience to exertion, and enabling a return to daily activities.”
The study will enroll approximately 80 adult patients (≥18 years) with post-COVID syndrome experiencing PEM. Participants will be randomized 1:1 to receive either sonlicromanol or placebo over a 13-week efficacy evaluation period. Patients in the active treatment arm will receive 90 mg sonlicromanol dispersible tablets twice daily.
The primary endpoint is reduction in fatigue as measured by the Fatigue Assessment Scale (FAS), a validated patient-reported outcome. Secondary endpoints will assess functional improvement and broader quality-of-life measures.
“Post-exertional malaise is one of the most disabling symptoms experienced by many individuals with post-COVID syndrome, yet there are currently no approved therapies specifically targeting this condition,” said Prof. Michele van Vugt, Principal Investigator of the SON4PEM study at Amsterdam University Medical Center, on behalf of her team. “This study is designed to evaluate whether sonlicromanol can meaningfully reduce fatigue and improve patients’ ability to tolerate daily physical and cognitive activities. Given the increasing evidence implicating mitochondrial dysfunction and altered cellular stress responses in post-COVID syndrome, sonlicromanol represents a scientifically interesting investigational approach that warrants clinical evaluation.”
Jan Smeitink, Founder and Chief Medical Officer of Khondrion, commented: “This study represents an important inflection point for Khondrion. At the same time, it reflects our core mission—to develop therapies that make a tangible difference for patients who currently have very limited options. For individuals living with post-COVID and PEM, even modest improvements in fatigue can translate into meaningful gains in independence and daily functioning. Positive results could support further development in post-COVID and strengthen the broader clinical positioning of sonlicromanol across mitochondrial-related disorders.”
NOTES TO EDITORS
About Khondrion
Khondrion is a clinical stage biopharmaceutical company. The company’s lead asset, sonlicromanol, is a potentially first-in-class, brain-penetrant redox-modulator with anti-inflammatory properties, that targets key metabolic and inflammatory pathways, including pathways associated with prostaglandin E2 (PGE2) signaling. Sonlicromanol and other compounds from Khondrion’s proprietary library have the potential to be developed for a wide range of diseases and conditions with the aim of benefiting patients whose daily lives are severely impacted by mitochondrial impairment like primary mitochondrial diseases, the company’s main focus, and post-COVID. For more information visit www.khondrion.com.
Sonlicromanol has been tested in clinical trials in patients with primary mitochondrial disease (PMD), as well as in the first wave of a 6-month Phase II study in children with genetically confirmed PMD and who suffer from motor symptoms. The company recently announced first patient dosing in the pivotal Phase III KHENERFIN study which will run in the Europe Union, UK and US.
Sonlicromanol has been granted orphan drug designations for the treatment of inherited mitochondrial oxidative phosphorylation defects in Europe, and for all inherited mitochondrial respiratory chain disorders in the US. It has also been granted a rare pediatric disease designation in the US for the treatment of MELAS.
Forward-looking statements
This press release may contain certain forward-looking statements regarding, among other things, the results, conduct, progress and timing of the company’s clinical trials and presentation of data from clinical trials for sonlicromanol. Although the company believes its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “goal,” “intend,” “may,” “anticipate,” “foreseen,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “potential,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the company’s control that could cause the company’s actual results, performance or achievements to be materially different from the expected results, performance or achievements expressed or implied by such forward-looking statements. Except as required by law, the company assumes no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.
For more information on Khondrion , please visit the company's websiteat: www.khondrion.com.
Jasper Levink
E-mail: levink@khondrion.com
Tel: +31 24 763 50 00
Website: www.khondrion.com
