Nezglyal (leriglitazone) / Minoryx, Neuraxpharm - LARVOL DELTA

Therapeutic Strategies in Adult Cerebral Adrenoleukodystrophy: Balancing Hematopoietic Stem Cell Transplantation and Leriglitazone (SSIEM 2026) - "Discontinuation may precipitate rapid progression in patients with uncontrolled disease, suggesting a rebound effect. The possible emergence of asymptomatic, non-inflammatory CSO lesions following HSCT in patients previously treated with leriglitazone warrants further investigation."

Clinical • Alzheimer's Disease • Bone Marrow Transplantation • Cognitive Disorders • Genetic Disorders • Inflammation • Transplantation • Plasma NfL

CALYX: A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adult Male Subjects With Cerebral Adrenoleukodystrophy (clinicaltrials.gov) - P3 | N=40 | Active, not recruiting | Sponsor: Minoryx Therapeutics, S.L. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders

NEZGLYAL (leriglitazone) receives a positive CHMP opinion for the treatment of cerebral Adrenoleukodystrophy (cALD), a rare neurodegenerative disease (The Manila Times) - "European Commission approval is expected by the end of September 2026....The opinion is based on results from the Phase 2/3 NEXUS1 study and additional real-world evidence from compassionate use programmes."

CHMP • EMA approval • CNS Disorders • Genetic Disorders

Omaveloxolone for Friedreich ataxia: What does 'Cochrane' have to say about it? (EAN 2026) - " Pharmacological treatments probably make little or no difference to change in ataxia rating scale (ARS) but improved upper limb dexterity (ULD) There was variation in that omaveloxolone helped ARS and leriglitazone helped ULD. The seven RCTs' outcomes were downgraded due to imprecision to small number of participants or wide confidence intervals. This would suggest that studies with approximately 200 or more events are required to help capture the subtle changes that occur over time in this slowly progressive disease."

Ataxia • Cardiomyopathy • Cardiovascular • Diabetes • Friedreich ataxia • Metabolic Disorders • Movement Disorders

Pharmacological treatments for Friedreich ataxia. (PubMed, Cochrane Database Syst Rev) - "In this updated Cochrane systematic review, meta-analysis of results on the ataxia rating scale showed that pharmacological treatments probably make little or no difference compared with placebo after 12 months of treatment. Given this result, the probable improvement that we found in upper limb dexterity was unexpected. Treatment-emergent adverse events leading to cessation of medication or death may be no more common in treatment groups than placebo groups as there were few adverse events detected in the treated groups. However, the studies may not have detected all rare and serious adverse events."

Clinical • Journal • Review • Ataxia • Cardiomyopathy • Cardiovascular • CNS Disorders • Depression • Diabetes • Friedreich ataxia • Metabolic Disorders • Mood Disorders • Movement Disorders • Muscle Spasticity • Psychiatry • CD99

MT-1-02: A PHASE?1, OPENLABEL, SINGLECENTER STUDY TO EVALUATE DRUGDRUG INTERACTIONS WITH GEMFIBROZIL, ITRACONAZOLE, AND CARBAMAZEPINE AND THE FOOD-EFFECT ON ORAL LERIGLITAZONE IN MALE HEALTHY SUBJECTS (clinicaltrialsregister.eu) - P1 | N=73 | Active, not recruiting | Sponsor: Minoryx Therapeutics S.L. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders

PPARγ activation by leriglitazone counteracts neurodegeneration and neuroinflammation in a disease-relevant mouse model of COASY dysfunction. (PubMed, Pharmacol Res) - "Leriglitazone treatment significantly improved motor performance, restored iron homeostasis, and attenuated both neuroinflammation and neurodegeneration. This study advances our understanding of the mechanism driving CoA-related neurodegeneration, highlights neuroinflammation as a pivotal pathogenic process, and demonstrates the therapeutic potential of PPARγ activation, underscoring leriglitazone as a promising candidate for CoPAN and potentially for the broader NBIA spectrum."

Journal • Preclinical • CNS Disorders • Inflammation • Metabolic Disorders • FTL • PPARG

Leriglitazone in adult patients with cerebral forms of X-linked adrenoleukodystrophy (SSIEM 2023) - No abstract available

Clinical • Genetic Disorders

Interim Results From The NEXUS Open-Label Registration Study on the Efficacy of Leriglitazone in the Treatment Of Childhood Cerebral Adrenoleukodystrophy (SSIEM 2023) - P2 | "At week 24, the study continuation criteria were met and all patients demonstrated early evidence of disease stabilisation."

Clinical • Bone Marrow Transplantation • CNS Disorders • Gene Therapies • Genetic Disorders • Transplantation

Compliance with the National Institute of Healthcare and Clinical Excellence (NICE) guidelines for the hospital discharge of patients with a Community Acquired Pneumonia (CAP) (ERS 2025) - "Data (1) show good compliance to NICE criteria, (2) caution discharging younger groups, (3) highlight criteria based on temperature, but (4) no different outcomes between respiratory and non-respiratory wards. table 1 NICE Criteria compliant non- compliant Temp >37.5C 112 7 Resp >24/min 118 1 HR >100/min 102 17 Syst BP <90 mmHg 117 2 O2 sat <90% on air 101 18"

Clinical • Compliance • Infectious Disease • Pneumonia • Respiratory Diseases

Leriglitazone improves iron homeostasis and ferroptotic markers in frataxin-deficient dorsal root ganglia neurons. (PubMed, Biomed Pharmacother) - "In summary, our findings in this neuronal model suggest that targeting the PPARγ pathway with leriglitazone may be a promising therapeutic strategy for FA by improving mitochondrial function, bioenergetic cell alterations, and iron homeostasis. Likewise, a combination therapy with omaveloxolone may be an alternative for FA patients."

Journal • Ataxia • Cardiomyopathy • Cardiovascular • CNS Disorders • Friedreich ataxia • Hypertrophic Cardiomyopathy • Movement Disorders

Inflammation and Immunomodulation in Cerebral X-linked Adrenoleukodystrophy: Review of Pathology and Interventions. (PubMed, J Child Neurol) - "Partial responses to cerebral adrenoleukodystrophy were noted with intravenous immunoglobulin, sirolimus, leriglitazone, and mycophenolate. Our findings suggest consideration for a randomized platform trial of immunomodulatory agents for advanced cerebral adrenoleukodystrophy."

Journal • Genetic Disorders • Immunology • Inflammation • Solid Tumor

Safety and efficacy of leriglitazone in childhood cerebral adrenoleukodystrophy (NEXUS): an interim analysis of an open-label, phase 2/3 trial. (PubMed, EClinicalMedicine) - P2 | "Additional follow-up will fully assess the safety and efficacy of leriglitazone in cerebral adrenoleukodystrophy. Minoryx Therapeutics."

Journal • P2/3 data • Bone Marrow Transplantation • Genetic Disorders • Pediatrics • Transplantation

Leriglitazone Achieved a Primary Endpoint Based on Disease Arrest in Patients with Childhood Cerebral Adrenoleukodystrophy in the NEXUS Open-Label Phase 2/3 Study (AAN 2025) - P2 | "Conclusions Leriglitazone treatment resulted in cerebral disease arrest with clinical and radiological stabilization in a significant number of patients and was well tolerated. These data demonstrate the efficacy and safety profile of leriglitazone in treating childhood cALD, with potential to address significant unmet treatment need."

Clinical • Late-breaking abstract • P2/3 data • Bone Marrow Transplantation • CNS Disorders • Genetic Disorders

A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients. (clinicaltrials.gov) - P2/3 | N=105 | Completed | Sponsor: Minoryx Therapeutics, S.L. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Pain

X-linked adrenoleukodystrophy in two male siblings; Endocrinological aspects of the disease, and therapeutic approaches (ESPE 2024) - "He is receiving experimental treatment with leriglitazone, a selective PPAR-γ (peroxisomal proliferator activating receptor gamma) agonist. VLCFA are thought to be directly cytotoxic to adrenocortical cells or disrupt their response to ACTH, leading to cortical atrophy. Early diagnosis of X-ALD, and administration of proper replacement therapy with hydrocortisone and fludrocortisone is important, as electrolyte fluctuations are associated with demyelination acceleration. Increases in ACTH, even with normal cortisol, are early signs of establishment of primary adrenal insufficiency."

Bone Marrow Transplantation • CNS Disorders • Endocrine Disorders • Genetic Disorders • Nephrology • Renal Disease

LERIGLITAZONE HALTS DISEASE PROGRESSION IN ADULT PATIENTS WITH CEREBRAL ADRENOLEUKODYSTROPHY (SSIEM 2024) - "These results suggest that leriglitazone can arrest disease progression in adults with early stage CALD and may be an alternative treatment to HSCT. Lately, we have treated 5 additional CALD adult patients with similar MRI results at 6 months."

Clinical • Alzheimer's Disease • Bone Marrow Transplantation • Cognitive Disorders • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease • Pain • Plasma NfL • PPARG

Leriglitazone halts disease progression in men with cerebral adrenoleukodystrophy (EAN 2024) - "These results show that leriglitazone can be an alternative treatment to HSCT in CALD, with a distinct action on the CST."

Bone Marrow Transplantation • Genetic Disorders • NEFL

Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy. (PubMed, Brain) - "One patient rapidly died from Covid19. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT."

Journal • Alzheimer's Disease • Bone Marrow Transplantation • Cognitive Disorders • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease • Transplantation • NEFL • Plasma NfL

Clinical pharmacokinetics of leriglitazone and a translational approach using PBPK modeling to guide the selection of the starting dose in children. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "A physiologically based pharmacokinetic (PBPK) model was developed for leriglitazone based on phase 1 data (SAD part) and incorporated CYP3A4 (fmCYP3A4 = 24%) and CYP2C8-mediated (fmCYP2C8 = 45%) metabolism, as well as biliary clearance (feBIL = 19.5%) derived from in vitro data, and was verified by comparing the observed versus predicted concentration-time profiles from the MAD part. The PBPK model was prospectively applied to predict the starting pediatric doses and was preliminarily verified with data from five pediatric patients."

Journal • PK/PD data • CNS Disorders • Pediatrics • CYP3A4

A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients. (clinicaltrials.gov) - P2/3 | N=105 | Active, not recruiting | Sponsor: Minoryx Therapeutics, S.L. | Trial completion date: Jun 2023 ➔ Jun 2025

Trial completion date • Genetic Disorders • Pain

Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome. (PubMed, J Transl Med) - "Our studies confirm the mitochondrial dysfunction in Rett syndrome, setting the differences through brain areas and disease stages. Its modulation through leriglitazone is a potential treatment for this disorder, along with other diseases with mitochondrial involvement. This work constitutes the preclinical necessary evidence to lead to a clinical trial."

Journal • CNS Disorders • Developmental Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Pediatrics

CALYX: A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adult Male Subjects With Cerebral Adrenoleukodystrophy (clinicaltrials.gov) - P3 | N=40 | Recruiting | Sponsor: Minoryx Therapeutics, S.L. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

NEXUS: A Clinical Study in Male Pediatric Patients With Cerebral X-linked Adrenoleukodystrophy (Cald) to Assess the Effects of MIN-102 Treatment on Disease Progression Prior to Human Stem Cell Transplant (HSCT) (clinicaltrials.gov) - P2 | N=13 | Active, not recruiting | Sponsor: Minoryx Therapeutics, S.L. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bone Marrow Transplantation • Genetic Disorders • Pediatrics • Transplantation

MITOCHONDRIAL MODULATION WITH LERIGLITAZONE AS A POTENTIAL TREATMENT FOR RETT SYNDROME. (EPNS 2023) - "Our studies confirm mitochondrial modulation through Leriglitazone as a potential treatment for Rett syndrome along with other diseases with mitochondrial implication, constituting the pre-clinical evidence introductory to a clinical trial."

CNS Disorders • Developmental Disorders • Epilepsy • Metabolic Disorders • Movement Disorders • Psychiatry