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, like leriglitazone, 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 novel, 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. Leriglitazone demonstrated robust preclinical proof-of-concept in relevant animal models of disease and successfully completed phase 1 clinical trials. Leriglitazone completed a phase 2/3 clinical study in adult patients with X-ALD (ADVANCE) in the EU and US showing a significant reduction of cerebral lesion progression and a reduction of incidence of progressive cALD and myelopathy symptoms. Additionally, a separate study in paediatric patients with cALD (NEXUS) is currently ongoing in EU and after 24 weeks of treatment, all evaluable patients in NEXUS were clinically stable and radiologically demonstrated disease arrest or lesion growth stabilization. Finally, a phase 3 study in adult male patients with progressive cALD (CALYX) is currently recruiting in the US. The marketing authorization application (MAA) for adult male X-ALD patients is currently under review by the EMA. 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. Leriglitazone is also being evaluated in other rare CNS disorders.