Nezglyal (leriglitazone) / Minoryx - LARVOL DELTA

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

Interim Results from the NEXUS Open-Label Phase 2 Study on the Safety and Efficacy of Leriglitazone in the Treatment of Childhood Cerebral Adrenoleukodystrophy (AAN 2023) - P2 | "Leriglitazone was well tolerated, continuation criteria were met, and disease arrest or stabilization was demonstrated radiologically, clinically and via plasma biomarkers. LS changes were similar to those attained with HSCT-based therapies. Enrolment is ongoing."

Clinical • Late-breaking abstract • P2 data • Bone Marrow Transplantation • CNS Disorders • Genetic Disorders • Transplantation • MMP9 • NEFL

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

New P3 trial • Genetic Disorders

Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate. (PubMed, Int J Mol Sci) - "Leriglitazone is a novel, blood-brain barrier (BBB)-penetrant PPARγ agonist that is being developed to treat CNS diseases. Here, we review the main roles of PPARγ in physiology and pathophysiology in the CNS, describe the mechanism of action of PPARγ agonists, and discuss the evidence supporting the use of leriglitazone to treat CNS diseases."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Immunology • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Vascular Neurology

PPAR Gamma Agonist Leriglitazone Recovers Alterations Due to Pank2-Deficiency in hiPS-Derived Astrocytes. (PubMed, Pharmaceutics) - "The treatment with leriglitazone did not affect the differentiation of the neuronal precursor cells into astrocytes, and it improved the viability of PKAN cells and their respiratory activity, while diminishing the iron accumulation similarly or even better than CoA. The data suggest that leriglitazone is well tolerated in this cellular model and could be considered a beneficial therapeutic approach in the treatment of PKAN."

Journal • CNS Disorders • Metabolic Disorders

Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2-3 trial. (PubMed, Lancet Neurol) - P2/3 | "The primary endpoint was not met, but leriglitazone was generally well tolerated and rates of adverse events were in line with the expected safety profile for this drug class. The finding that cerebral adrenoleukodystrophy, a life-threatening event for patients with adrenomyeloneuropathy, occurred only in patients in the placebo group supports further investigation of whether leriglitazone might slow the progression of cerebral adrenoleukodystrophy."

Journal • P2/3 data • CNS Disorders • Genetic Disorders • Pain

Leriglitazone: frustration and hope in adrenoleukodystrophy. (PubMed, Lancet Neurol) - No abstract available

Journal • 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 | Recruiting | Sponsor: Minoryx Therapeutics, S.L. | Trial completion date: Feb 2021 ➔ Dec 2023 | Trial primary completion date: Nov 2020 ➔ Dec 2023

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Genetic Disorders • Pediatrics • Transplantation