Addressing an Aggressive Pediatric Disease with No Treatment Options

Spanish biotech Minoryx has carved out a critical position in orphan CNS diseases by developing leriglitazone for X-linked adrenoleukodystrophy (X-ALD), a genetic condition where patients in the most aggressive phenotype face a devastating trajectory. In cerebral ALD (cALD), patients develop brain lesions that can grow exponentially, leading to death within 3-4 years from onset of rapid growth.

Currently, the only treatment option in Europe is hematopoietic stem cell transplant (HSCT), but this high-risk procedure is only suitable for a minority of patients due to significant morbidity and mortality risks. In the US, patients have access to ex-vivo gene therapy in addition to HSCT, but again, this treatment option serves only a small subset of patients.

“Leriglitazone modifies the disease trajectory by slowing brain lesion growth and stabilizing patients, thus prolonging life expectancy and quality of life,” explains CEO Marc Martinell. If approved in the EU, leriglitazone would become the only pharmacological treatment available for these patients.

Leveraging Unique Brain-Penetrating Properties

What sets Minoryx apart in the competitive landscape is leriglitazone’s distinctive mechanism and delivery approach. The compound is the only brain-penetrating PPAR-gamma agonist currently under development, enabling it to cross the blood-brain barrier and directly modify disease progression in the central nervous system.

This oral bioavailability offers significant advantages over existing treatment modalities, potentially expanding treatment access to patients who are ineligible for stem cell transplant or gene therapy. The PPAR-gamma agonism mechanism also positions leriglitazone for expansion into other orphan CNS conditions, including Rett Syndrome.

Building Strategic Networks for Rare Disease Success

Founded in 2011 by Marc Martinell, Joan Aymamí, and Xavier Barril—three entrepreneurs who had previously collaborated at another biotech—Minoryx has raised more than EUR 150 million to advance their pivotal clinical program. The funding has proven critical in navigating the unique challenges of rare disease development.

“Being in the rare disease space, the key challenges relate to the lack of proper understanding of the disease in terms of natural history, endpoints, etc. and the scarcity of patients,” Martinell notes. The company addresses these obstacles through close collaboration with leading key opinion leaders worldwide and patient advocacy groups.

Over the company’s 14-year evolution, Martinell emphasizes that the ALD community—encompassing patients, families, researchers, and investigators—has become their critical network. This community-centered approach has been essential for patient recruitment and clinical trial design in a disease affecting a limited population.

Streamlined Manufacturing Strategy with Expert CDMO Partnerships

Rather than building extensive in-house manufacturing capabilities, Minoryx has adopted a lean but expert-driven approach to their CMC strategy. The company maintains a small team of in-house CMC and Quality experts who work closely with select contract development and manufacturing organizations (CDMOs) to produce leriglitazone.

This partnership model has enabled the company to maintain manufacturing control without the capital intensity of building internal production capabilities. Martinell reports that manufacturing remains “well under control and without specific challenges other than those typically occurring in drug development.”

The streamlined approach allows Minoryx to focus resources on clinical development while ensuring manufacturing scalability through proven CDMO relationships. This strategy has successfully supported their progression from early development through regulatory filing, demonstrating the effectiveness of their outsourced manufacturing model for small molecule production.

Regulatory Milestones and US Expansion

With their European MAA now validated by the EMA, Minoryx is targeting European approval within the next 12 months. Simultaneously, the company continues advancing their US Phase 3 study, CALYX, working to complete patient recruitment.

The dual-track regulatory strategy positions Minoryx to potentially serve both European and US markets, significantly expanding their addressable patient population. This approach also provides regulatory risk mitigation, with multiple pathways to market approval.

Strategic Advice for Scaling Biotechs

Drawing from Minoryx’s journey from foundation to regulatory filing, Martinell emphasizes the critical importance of early network development for biotech success. His experience highlights how drug development complexity requires diverse expertise that small companies can only achieve through strategic partnerships.

“Drug development is very complex and requires various expertise. For a small company, this is only achievable through a committed internal team supported by a large network of collaborators, advisors and trusted providers. Building this network takes time, so I would recommend biotech founders work on establishing this from early on,” Martinell concluded.