Minoryx Therapeutics – Bringing new hope for people suffering from Orphan CNS diseases by discovering pioneering drugs

Minoryx is a clinical stage biotech company focusing on the development of novel therapies for orphan CNS diseases with high unmet medical needs. The company’s lead program, leriglitazone (MIN-102), a novel, selective PPARγ agonist, is currently being evaluated in X-ALD and Friedreich’s Ataxia. The company is backed by a syndicate of experienced investors and has support from a network of other organizations. Minoryx was founded in 2011, has operations in Spain and Belgium and has raised a total of €50M through Series A & B financing rounds.

Minoryx Therapeutics' core values that’s bringing about a difference

Commitment: One of the biggest assets of the company is its team, a group of professionals fully committed to the making new therapies available for patients suffering from severe, orphan diseases.

Social responsibility: the company is dedicated to bringing new hope for people suffering from rare diseases, especially children and their families.

Innovation & Dynamism: Minoryx innovates by exploiting state-of-the art technologies. It forms synergistic drug development partnerships and provide an environment which fosters creativity and open-mindedness.

Added Value: The company is making strides to provide life-changing treatments for diseases with high unmet medical needs.

Minoryx's Dynamic Portfolio

The company's lead program is a novel, selective and differentiated brain penetrant PPAR gamma agonist (leriglitazone), which is currently in clinical development for X-ALD and other CNS diseases. Leriglitazone demonstrated strong preclinical proof-of-concept in relevant animal models of disease and successfully completed phase 1 clinical trials. Leriglitazone was evaluated in a phase 2/3 study in adrenomyeloneuropathy (AMN) in EU and US with an open-label extension still ongoing. Leriglitazone significantly reduced the progression of cerebral lesions and myelopathy symptoms. The marketing authorization application (MAA) for adult male X-ALD patients is under review by the EMA and the launch preparations in the EU are underway. Also, discussions are currently ongoing with the FDA to define the next steps for its US approval path. In parallel, a separate study is ongoing on pediatric cALD patients in EU.

Minoryx Therapeutics Focus Area: Treating Orphan CNS and Other Neurological Conditions

Disease: Orphan CNS diseases

Minoryx focuses on orphan diseases of the central nervous system (CNS), which is 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.

The Cure: 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 is developing leriglitazone, a differentiated and selective brain penetrant PPAR gamma agonist able to reach the required CNS exposure in humans. Minoryx is developing leriglitazone for the treatment of X-linked Adrenoleukodystrophy (X-ALD) and Friedreich's Ataxia (FRDA), two rare orphan diseases of the CNS with high unmet medical need. The marketing authorization application (MAA) for leriglitazone as a treatment for adult male X-ALD patients is under review by the EMA. Leriglitazone is also being evaluated in other rare CNS disorders.

Disease: Adrenoleukodystrophy and Friedreich Ataxia

X-linked Adrenoleukodystrophy (X-ALD) is a rare inherited peroxisomal neurodegenerative disorder, chronically debilitating and potentially life-threatening, and has an incidence of 1 in 17,000 births. The disease is caused by inactivation of the peroxisomal ABCD1 gene located on the X-chromosome. The defective function of the transporter leads to an accumulation of very long-chain fatty acids (VLCFA) in several tissues and a pathogenic cascade of events that contribute to membrane destabilization of the myelin sheath, mitochondrial dysfunction, oxidative stress, neuroinflammation and compromised blood brain barrier (BBB) integrity. X-ALD is characterized by central inflammatory demyelination in the brain, axonal degeneration in the spinal cord and adrenal insufficiency. There is currently no satisfactory therapeutic treatment available for AMN, and the only treatment option for cALD is allogeneic Human Stem Cell Transplant (HSCT) which requires prior myeloablation with all inherent risks.

Friedreich's Ataxia (FRDA) is a rare genetic disease characterized by loss of coordination and muscle strength resulting from the degeneration of nerve tissue in the spinal cord and damage of the peripheral nerves that control muscle movement. Symptoms range from the inability to coordinate movements to gait instability with imbalance, muscle weakness and tremors. Patients lose their ability to stand, sit and walk within 10 – 15 years of onset. FRDA reduces life expectancy and becomes fatal, mainly due to cardiac failure. Friedreich's Ataxia is caused by a genetic defect which affects male and female children and is inherited as a recessive trait. Deficient expression of the mitochondrial protein, frataxin, is the primary cause of FRDA, which leads to adverse alterations in whole cell and mitochondrial iron metabolism causing iron accumulation, mitochondrial dysfunction and oxidative damage.

The Cure: Leriglitazone (MIN-102) is a novel, orally bioavailable and selective PPAR gamma agonist with a potential best-in-class profile indicated for CNS diseases. It is one of the several metabolites of pioglitazone and has a demonstrated sufficient brain penetration and favorable safety profile in humans, allowing PPAR gamma engagement in the CNS above the level that can be safely achieved with pioglitazone and other glitazones. It showed robust preclinical proof-of-concept in animal models of multiple diseases by modulating pathways leading to mitochondrial dysfunction, oxidative stress, neuroinflammation, demyelination and axonal degeneration.

As mentioned above, Minoryx’s lead program is a selective, differentiated PPAR gamma agonist (leriglitazone) being developed for the treatment of X-linked Adrenoleukodystrophy (X-ALD); it has the potential to treat both the severe cerebral form of ALD (cALD) and the chronic form, adrenomyeloneuropathy (AMN), as well as other orphan CNS diseases, such as Friedreich's Ataxia (FRDA).

Leriglitazone was evaluated in a double-blind, placebo-controlled phase 2/3 clinical study (ADVANCE) in adult AMN patients in EU and US, overall showing a significant effect on reducing progression of cerebral lesions and progression of myelopathy symptoms. An open-label extension is ongoing to generate long term safety and efficacy data. The marketing authorization application (MAA) for adult male X-ALD patients is under review by the EMA, and Minoryx is currently in discussions with the FDA to define the next steps for its US approval path. It is under discussions with regulatory authorities on the approval path for AMN population. A separate study in pediatric cALD patients is currently ongoing in EU (NEXUS) to further assess the impact of leriglitazone on the progression of cerebral lesions. Leriglitazone is also being investigated for other orphan CNS diseases, and a proof of concept study in patients with FRDA (FRAMES) was completed showing clinical benefit in this population. The design of the confirmatory phase 3 study in this population is now under discussion with regulatory authorities.

About | Marc Martinell, PhD

Marc martinell co-founded Minoryx in 2011 and since then has been taken the Chief Executive Officer role. He obtained a PhD in Chemistry from the University of Barcelona and has over 15 years of experience in drug discovery and development. Prior founding Minoryx, he worked at Crystax Pharmaceuticals and Oryzon Genomics where he managed several research projects and led the team in charge of target selection, structural biology, computational chemistry, and hit ID through a fragment-based approach. At Oryzon, Marc actively contributed to the identification of the first-in-class inhibitors for the epigenetic target LSD1 currently in clinical studies. Marc is co-author of several patents and publications and besides his activities in the technological field always had an entrepreneurial calling.

"We are focused on the discovery and development of novel therapies for severe, orphan genetic diseases of the central nervous system (CNS) with high unmet medical need."