Minoryx focuses on orphan diseases of the central nervous system (CNS), a large group of rare diseases often characterized by neurodegeneration and for which there are currently no treatments available. These diseases are usually chronic, progressively debilitating and often life-threatening, with high unmet medical need.

Some orphan CNS diseases are of genetic origin, but they can also be triggered by external unknown factors and may affect other organs in addition to the brain. Several complex, interplaying pathways are contributing to the neurodegenerative process: mitochondrial dysfunction, oxidative stress, and neuro-inflammation all play an important role in neurodegeneration, independent of the underlying cause of disease. Research into novel effective treatments, addresses this complexity, rather than focus on a single pathway approach.

PPAR gamma controls multiple genes that are central to mitochondrial biogenesis, oxidative stress, inflammation, and myelination. The potential beneficial effects of PPAR gamma agonists in CNS disorders have been demonstrated preclinically in several orphan and non-orphan indications such as Multiple Sclerosis, Parkinson’s Disease, Alzheimer’s Diseases, Huntington’s Disease, Amyotrophic Lateral Sclerosis, Stroke and Traumatic Brain Injury. However, to date clinical studies failed to show beneficial effects of PPAR gamma agonists in these indications, due to insufficient target engagement in the CNS.

Minoryx have discovered and developed a brain penetrant selective PPAR gamma agonist, leriglitazone, which is currently in clinical development for multiple orphan CNS disorders. The lead indication for leriglitazone is X-linked Adrenoleukodystrophy (X-ALD), a devastating neurodegenerative disease that exists in two forms: cerebral ALD (cALD), characterized by brain lesions that can become rapidly progressive leading to death, and adrenomyeloneuropathy (AMN) characterized by spinal cord degeneration.

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization under exceptional circumstances for NEZGLYAL (leriglitazone) as treatment of Cerebral Adrenoleukodystrophy (cALD) in males with c Adrenoleukodystrophy (ALD) aged 2 to 12 years with non-gadolinium (Gd) enhancing lesions (i.e. Gd negative) in brain Magnetic Resonance Imaging (MRI), with a Neurological Functional Score (NFS) of 0 or 1.

Leriglitazone has shown preclinical proof-of-concept in animal models of disease by modulating pathways leading to neuroinflammation, demyelination, mitochondrial dysfunction, oxidative stress, and axonal degeneration. In clinical trials, it has shown clinical benefit in both paediatric cALD patients in the NEXUS clinical trial and adult cALD patients in the ADVANCE trial. Results from NEXUS demonstrate that paediatric cALD patients are clinically and radiologically stable after over 96 weeks of treatment or at a visit prior to Haematopoietic Stem Cell Transplantation (HSCT). Data from ADVANCE showed that leriglitazone reduced cALD progression. More than 170 patients with cALD have received treatment to date.. Additionaly, a phase 3 study in adult male patients with progressive cALD (CALYX) is currently ongoing.. Leriglitazone offers a strong potential for indication expansion into other CNS diseases. In this regard, a proof of concept study in Friedreich's Ataxia (FRDA) showed clinical benefit in this population and by the end of 2026 we will obtain read-out from our phase 2 trial (TREE) in Rett syindrome.