Eyevinal (ibudilast) / Kyorin, University of Colorado, MediciNova - LARVOL DELTA

Late Breaking Abstract - Combining an iPSC-derived pulmonary fibrosis onset model with a deep generative neural network for drug discovery (ERS 2026) - "These included drugs already being used in clinical practice (PDE4 inhibitors) and drugs newly identified by UNAGI (HDAC inhibitor belinostat, PDE4 inhibitors cilomilast, ibudilast). In vitro experiments using iAT2 cells to validate candidate treatments are currently underway. This study is the first to combine novel human preclinical iPSC models of pulmonary fibrosis with novel generative neural networks approaches to identify novel insights in drug discovery."

Late-breaking abstract • Immunology • Pulmonary Disease • Respiratory Diseases • COL1A1 • ROBO2

Phase 1b/2a study evaluating the combination of MN-166 (ibudilast) and temozolomide in patients with newly diagnosed and recurrent glioblastoma (GBM). (ASCO 2024) - P1/2 | "This study met its primary endpoint for rGBM, as the combination of ibudilast and TMZ was associated with a higher PFS-6 rate than historical controls. CD3 expression was a good predictor for tumor progression at 5 months in patients with rGBM. Encouraging preclinical studies suggest enhanced efficacy of ibudilast in GBM when combined to immune checkpoint blockade agents."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD74

Pharmacological targeting of neuronal calcium sensor proteins: Neuroprotective potential of ibudilast | Poster Board #1034 (ACS-Fall 2026) - "In neuroblastoma cells treated with the chemotherapeutic drug paclitaxel, co-treatment with ibudilast inhibited calpain-mediated degradation of neuronal calcium sensor 1 (NCS1), a neuronal calcium sensor protein, and preserved calcium signaling. We also plan to apply steady state anisotropy to monitor the interaction of these proteins with their cellular partners e.g., presenilin, D2R receptor, Kv4 channel protein in presence and absence of ibudilast. In conclusion, all these findings will shed light on the neuroprotection mechanism of ibudalist in calcium signaling pathway."

Alzheimer's Disease • Autism Spectrum Disorder • Bipolar Disorder • CNS Disorders • Genetic Disorders • Huntington's Disease • Metabolic Disorders • Movement Disorders • Nephrology • Neuroblastoma • Parkinson's Disease • Solid Tumor • NCS1

Downstream regulatory element antagonist modulator, a potential target for ibudilast | Poster Board #1239 (ACS-Fall 2026) - "Molecular docking studies further revealed the presence of several potential binding sites with the binding side located within EF-hand 4 and helix 10 demonstrating the highest docking score. in both the N-terminal and C-terminal domains of the protein."

Alzheimer's Disease • CNS Disorders • Huntington's Disease • Movement Disorders

Synergistic modulation of cAMP and cGMP rescues hemin-induced plasma membrane fragmentation. (PubMed, J Biol Chem) - "We found that pharmacological modulation of these pathways via NO donors (DEA/NO), soluble guanylyl cyclase (sGC) stimulators (riociguat) or IP receptor agonists (PGE1), and phosphodiesterase (PDE) inhibitors (PDE-5 inhibitor: sildenafil, PDE-3 inhibitor: ibudilast), phosphorylate the downstream vasodilator-stimulated phosphoprotein (VASP) and inhibit hemin-induced platelet activation and degranulation. In comparison, the PGE1-induced cAMP synthesis was enhanced in the presence of hemin. In conclusion, high concentrations of hemin change the cGMP and cAMP synthesis induced by their associated stimulators, while promoting plasma membrane destruction, which can be significantly inhibited by the simultaneous administration of riociguat DEA/NO and PGE1."

Journal • Thrombosis

MediciNova…announced that the target enrollment of 200 patients has been achieved in the SEANOBI-ALS study (Scalable Expanded Access with Analysis of Neurofilament and Other Biomarkers in ALS ; NCT06743776) evaluating MN‑166 (ibudilast) in patients with amyotrophic lateral sclerosis (ALS) (GlobeNewswire) - "Active participants in the SEANOBI-ALS study remain on-track with treatment and protocol-specified follow-ups. Final patient follow-ups are projected to conclude in early 2027, triggering the data analysis phase to support upcoming scientific presentations and peer-reviewed publications by an academic lead investigator."

Trial status • Amyotrophic Lateral Sclerosis

MIF-CD74 Signaling Defines a Brain-Specific Immune Vulnerability in Metastasis and Neurologic Disease. (PubMed, Cancer Res) - "The MIF-CD74 inhibitor, ibudilast, suppresses brain metastatic tumor growth in mouse models and shows efficacy across patient-derived organotypic cultures from multiple tumor origins. Extending beyond cancer, CD74+ brain macrophages are also observed in other neurologic pathologies, highlighting shared, pan-disease microenvironmental programs mediated by CD74+ macrophages across diverse brain disorders. See related article by Alvaro-Espinosa et al., p. 3249."

Journal • Brain Cancer • CNS Disorders • Oncology • Solid Tumor • CD74 • MIF

MediciNova CEO Provides Shareholder Update (StockTitan.net) - "Phase 2 MN-001-NATG-202 trial reached last patient last visit; top-line data expected Q3 2026. SEANOBI ALS expanded-access program for MN-166 activated at 12 U.S. sites with 100 of 200 patients enrolled....Company highlights anticipated end-2026 topline data catalyst for COMBAT ALS Phase 2b/3 registration trial."

Clinical data • Enrollment status • Amyotrophic Lateral Sclerosis • Hypertriglyceridemia • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Can Repurposed Ibudilast Mitigate Fibromyalgia Pain? (EAN 2026) - No abstract available

Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

SEA-NOBI-ALS Expanded Access Program Of Ibudilast (MN-166) (ENCALS 2026) - "The SEA NOBI ALS program introduces a novel model that integrates expanded access with rigorous biomarker collection, decentralized trial conduct, and multi omic profiling. This approach aims to generate generalizable real world evidence on ibudilast while establishing a scalable, ethically robust, and patient centered framework for future ALS research."

Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • Plasma NfL

Ibudilast Modulates Neuroinflammation, Oxidative Stress, And Cognition In An Alzheimer'S Disease Rat Model (AAIC 2026) - No abstract available

Oxidative stress • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation

Metabolomic Signatures of Brain Atrophy and Ibudilast Response in Progressive Multiple Sclerosis. (PubMed, medRxiv) - "We further demonstrated that ibudilast treatment was associated with longitudinal changes in specific metabolites, linking metabolic pathways to both disease progression and therapeutic response.Implications of all the available evidence: These findings support circulating metabolomic signatures as potential markers of brain atrophy in MS. Metabolomics may provide a scalable approach to identify individuals at risk of progressive brain tissue loss and to inform future mechanistic and therapeutic investigations targeting metabolic pathways involved in disability progression."

Clinical • Journal • Cardiovascular • CNS Disorders • Metabolic Disorders • Multiple Sclerosis

MediciNova Receives Notice of Allowance for New Patent Covering Use of MN-166 in Combination with Anti-PD-1 Immune Checkpoint Inhibitor for Glioblastoma Treatment (GlobeNewswire) - "Once issued, this patent is expected to expire no earlier than September 2042. The allowed claims cover not only the combination of ibudilast with multiple anti-PD-1 antibodies, but also a broad range of treatment conditions, including duration of administration, dosing frequency, route of administration, dose levels, and dosing schedules."

Patent • Glioblastoma

A Metabolomics-Derived Body Mass Index Identifies Heterogeneity In Neurodegeneration Among Individuals with Progressive Multiple Sclerosis (CMSC 2026) - "Objectives: We assessed whether metabolic BMI excess (i.e., worse metabolic health than indicated by BMI) is more strongly associated with brain atrophy than BMI and whether these associations are modified by ibudilast, a potential modulator of glucose and lipid metabolism... ∆MetBMI captures metabolic vulnerability beyond conventional BMI and identifies MS subgroups with accelerated neurodegeneration. Our findings may provide novel insights into risk stratification and therapeutic evaluation in progressive MS."

Clinical • Heterogeneity • CNS Disorders • Multiple Sclerosis

Macrophage migration inhibitory factor in autoimmune diseases: Translation at last? (AUTO 2026) - "Despite these advances, translation to clinical application remains in early clinical stages with the exception of the semi specific inhibitors of MIF tautomerasic activity of MIF ibudilast that is being repurposed for patients with multiple sclerosis...Ongoing efforts to refine MIF modulation, improve inhibitor specificity, and validate biomarkers are critical to realize MIF-directed therapies in autoimmune disease management. This body of work suggests that MIF inhibition may finally bridge mechanistic insight and clinical intervention in autoimmunity."

CNS Disorders • Diabetes • Immunology • Metabolic Disorders • Multiple Sclerosis • Type 1 Diabetes Mellitus • CD74 • CXCR2 • MIF

Neuroinflammatory and Synaptic Roles of Glial Cells in Autism Spectrum Disorder. (PubMed, CNS Neurol Disord Drug Targets) - "Interventions to correct glial dysfunction-e.g., anti-inflammatory medication (e.g., minocycline, ibudilast), gene therapy, and stem cell therapy-are investigated for their potential to restore glia to normal and diminish ASD symptoms. Understanding glial-neuronal communication mechanisms and their role in neuroinflammation offers a hopeful future for accurate, target-specific treatment. Advances in the elucidation of these processes will foretell an enormous increase in therapeutic efficacy and quality of life for individuals with ASD."

IO biomarker • Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Gene Therapies • Genetic Disorders • Inflammation • Psychiatry • Solid Tumor • IL6

New Peer‑Reviewed Study Reveals Actionable Immune–Microenvironment Target in Brain Metastasis; Medicinova Advances Clinical Translation (Business Insider) - "The study further demonstrates that ibudilast can effectively block MIF–CD74 signaling, reverse pro‑metastatic immune reprogramming, and suppress brain metastasis growth in preclinical systems. In addition, transcriptomic analyses define predictive biomarker signatures associated with treatment response, reinforcing the potential for patient stratification in future clinical studies. The findings suggest translational potential for MN-166 (ibudilast), the company’s leading product, in future therapeutic strategies for brain metastasis within neuro-oncology...MediciNova plans to collaborate with Dr. Valiente and CNIO on future clinical research aimed at patients with solid tumors having brain metastases."

Preclinical • CNS Tumor

Ibudilast and dipyridamole ameliorate murine γ-herpesvirus 68-induced acute hepatitis following airway infection. (PubMed, Virus Genes) - "Dipyridamole exhibited in vitro antiviral activity, and both agents effectively ameliorated MHV68-induced hepatitis in vivo. These findings highlight their therapeutic potential for acute hepatitis associated with extrahepatic viral infections, including EBV-associated disease."

Journal • Preclinical • Epstein-Barr Virus Infections • Hepatitis C • Infectious Disease • Inflammation

Effect of MN-166 (ibudilast) on acute respiratory failure prevention in hospitalized participants with COVID-19: a randomized, double-blind, placebo-controlled phase 2 study. (PubMed, BMC Pulm Med) - No abstract available

Clinical • Journal • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

MIF-Induced CD74+ Microglia and Macrophages Promote Progression of Brain Metastasis and are Clinically Relevant Across Central Nervous System Disorders. (PubMed, Cancer Res) - "The brain-penetrant drug ibudilast, which prevents the binding of MIF to CD74, decreased brain metastasis in experimental models in vivo and in patient-derived organotypic cultures ex vivo in a primary tumor-agnostic manner. These findings suggest that MIF/CD74-induced reprogramming of myeloid cells in brain disorders is a vulnerability that could be exploited therapeutically against brain metastases, and possibly other brain disorders."

Journal • Alzheimer's Disease • Brain Cancer • CNS Disorders • Glioma • Multiple Sclerosis • Oncology • Solid Tumor • CD74 • IFNG

Targeting autoimmunity: Phosphodiesterase inhibitors as immunomodulators-a review of current insights and future direction. (PubMed, Autoimmun Rev) - "Emerging PDE-targeted agents, including ibudilast and the PDE4B-selective inhibitor nerandomilast, combine immunomodulatory and antifibrotic properties. These compounds have demonstrated clinical benefit and improved tolerability in patients with progressive fibrotic lung disease, highlighting the therapeutic potential of isoform-selective PDE inhibition. Collectively, targeting the NO-cGMP-cAMP signaling axis provides a unifying mechanistic framework for the treatment of vascular, immune, and fibrotic manifestations of rheumatic disease, positioning PDE inhibition as an emerging pillar of modern translational rheumatology."

Journal • Review • Cardiovascular • CNS Disorders • Dermatology • Fibrosis • Hypertension • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Psoriasis • Psoriatic Arthritis • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Seronegative Spondyloarthropathies

Screening of probiotics for promoting mineral absorption based on in vitro fermentation and cell models. (PubMed, Front Microbiol) - "Strains L. paracasei PC-01, B. lactis Ca360, L. plantarum Fe-01, B. lactis MN16620, and L. brevis MN14440 exhibited pronounced acid-producing ability, indicated by markedly decreased fermentation broth pH values...Comprehensive analysis indicated that strain B. lactis Ca360 demonstrated the most prominent effect in promoting calcium, iron, and zinc absorption, likely through mechanisms involving acid production-induced pH reduction and phytate hydrolysis facilitation. This study provides systematic verification of the integrated mechanisms by which probiotics promote mineral absorption and offers both theoretical support and strain resources for the development of targeted probiotics aimed at improving mineral bioavailability."

Journal • Preclinical

COMBAT-ALS: Evaluation of MN-166 (Ibudilast) for 12 Months Followed by an Open-label Extension for 6 Months in Patients With ALS (clinicaltrials.gov) - P2/3 | N=234 | Active, not recruiting | Sponsor: MediciNova | Trial completion date: Dec 2026 ➔ Apr 2028 | Trial primary completion date: Dec 2025 ➔ Apr 2027

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Repurposed Systemic Pharmacologic Agents in Chronic Pain: Emerging Mechanistic and Clinical Insights. (PubMed, J Clin Med) - "This narrative review examines the mechanistic and emerging clinical evidence describing how systemically administered pharmacological agents interact with pathways implicated in chronic pain, focusing on glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, metformin, statins, minocycline, ibudilast, low-dose naltrexone, beta-blockers, and cannabinoids. The mechanisms reviewed include glial activation, cytokine signaling, oxidative stress, mitochondrial dysfunction, ion channel sensitization, and autonomic imbalance. The use of these systemic agents may provide additional treatment options for patients with chronic neuropathic, centralized, or mixed pain states who have limited response to conventional therapies, although current clinical evidence remains preliminary."

Journal • Review • Cardiovascular • Inflammation • Metabolic Disorders • Pain

Synergistic Enhancement of Peripheral Nerve Regeneration via Ibudilast-Primed Three-Dimensional Spheroid Culture of Human Adipose-Derived Stem Cells. (PubMed, Pharmaceuticals (Basel)) - "Notably, conditioned media from these primed spheroids significantly accelerated HSwCs migration and induced robust upregulation of myelination-related genes (specifically PMP22 and EGR2), with trophic effects sustained for up to 72 h. Ibudilast-primed 3D spheroids synergistically amplify the neuroregenerative secretome of ADSCs. By utilizing a repurposed, safe small molecule to overcome functional variability and maximize potency without genetic manipulation, this strategy represents a highly translatable candidate for peripheral nerve repair."

Journal • IGF1