Minoryx Therapeutics announced today that the first patient has been dosed in its phase 2a TREE study evaluating leriglitazone for the treatment of Rett syndrome, a rare genetic neurological disorder primarily affecting females.
The TREE study will assess the safety and efficacy of leriglitazone, a novel brain-penetrant and selective PPAR gamma agonist, in 24 female patients aged 5-12 years. Participants will receive either leriglitazone or placebo for 36 weeks at the Neurometabolic Disorders Unit of Hospital Sant Joan de Déu in Barcelona, Spain, under the direction of Dr. Ángeles García Cazorla.
"Following the positive results in the study NEXUS in boys with cerebral adrenoleukodystrophy (cALD), we will pursue additional orphan CNS indications with high unmet medical need," said Marc Martinell, CEO of Minoryx. "Rett syndrome is one such indication, and we look forward to collaborating with the team of excellent physicians from Hospital Sant Joan de Déu in Barcelona."
Promising Preclinical Evidence
Preclinical studies have shown encouraging results for leriglitazone in Rett syndrome models. The compound demonstrated recovery of bioenergetic alterations in human Rett fibroblasts and exerted anti-neuroinflammatory effects in mouse models, resulting in improved general condition and exploratory activity.
Dr. Ángeles García Cazorla, Head of Research in Neurology and Head of the Neurometabolic Disorders Unit at Hospital Sant Joan de Déu, expressed optimism about the trial: "The preclinical data for leriglitazone in Rett models is very encouraging as leriglitazone demonstrates effect on neuroinflammation and mitochondrial function which are hallmarks of Rett syndrome."
She added, "Patients with Rett syndrome have complex clinical pictures where a new treatment that could provide improvements in cognition, behaviour and communication skills would help not just the patient to have an improved quality of life but also the family too."
Study Design and Endpoints
The TREE study is designed as a 36-week, randomized 1:1, placebo-controlled trial. While safety is the primary endpoint, the study will also assess several secondary and exploratory endpoints, including:
- Rett Syndrome Behavior Questionnaire (RSBQ)
- Vineland Adaptative Behaviour Scale (VABS)
- Rett Syndrome Motor Evaluation Scale (RESMES)
- Various biomarkers
The trial aims to demonstrate improved cognition with stabilization or gain of communication skills, improved behavior, and delayed neuromuscular worsening resulting in better motor skills.
"We are excited to have initiated the TREE study. Leriglitazone has a mode of action relevant to the pathways associated with Rett syndrome," said Arun Mistry, CMO of Minoryx. "Thus far we have clinical safety and efficacy data in male paediatric patients, adult men and adult women from studies in X-ALD and Friedreich's ataxia, and the TREE study expands to paediatric female patients with Rett syndrome."
About Rett Syndrome
Rett syndrome is a rare genetic neurological and developmental disorder affecting approximately 1 in 10,000-20,000 females. It is almost exclusively caused by a de-novo genetic mutation in the MECP2 gene on the X-chromosome.
Children with Rett syndrome typically develop normally in early infancy but subsequently experience a progressive loss of motor skills and language. Over time, patients face increasing problems with movement, coordination, and communication. Most also experience seizures and intellectual disabilities.
The natural history of the condition suggests that many patients live into middle age, highlighting the importance of developing effective treatments to improve quality of life.
About Leriglitazone
Leriglitazone is Minoryx's orally bioavailable and selective PPAR gamma agonist with potential first-in-class status for CNS diseases. The compound has demonstrated brain penetration and a favorable safety profile in clinical trials.
Beyond Rett syndrome, leriglitazone has shown clinical benefit in adult and pediatric male X-ALD patients by reducing disease progression. The company plans to file a European Marketing Authorization Application for cerebral adrenoleukodystrophy (cALD) by mid-2025.
The compound has received orphan drug status for X-ALD and Friedreich's ataxia from both the FDA and EMA, as well as Fast Track and Rare Pediatric Disease designation from the FDA for X-ALD treatment.
Results from the TREE study are expected during the first half of 2026, after all patients have completed 36 weeks of treatment and 4 weeks of follow-up.
Expanding Treatment Portfolio
This trial represents Minoryx's strategic expansion into additional orphan CNS indications with high unmet medical needs. Founded in 2011 and headquartered in Spain with Belgian facilities, Minoryx has raised more than €120 million to support its development programs.
The company is backed by a syndicate of experienced investors, including Columbus Venture Partners, CDTI Innvierte, Criteria BioVentures, Fund+, Ysios Capital, Roche Venture Fund, and several others.
