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

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

RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine (clinicaltrials.gov) - P2/3 | N=460 | Completed | Sponsor: University Health Network, Toronto | Suspended ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Plasma Metabolomic Signatures of Neurodegeneration and Ibudilast Response in Progressive Multiple Sclerosis (ACTRIMS Forum 2026) - "Distinct lipid and xenobiotic metabolic networks were associated with progressive MS outcomes, and ibudilast was associated with several metabolites in neuroprotective directions. Metabolomics may provide prognostic and pharmacodynamic biomarkers for progressive MS."

CNS Disorders • Metabolic Disorders • Multiple Sclerosis

Reductions in cigarette and cannabis use during a randomized clinical trial for alcohol use disorder. (PubMed, Alcohol Alcohol) - "Individuals enrolled in an RCT for AUD were able to reduce their cigarette and cannabis use without being prompted to, and these changes were significantly associated with changes in DPDD. These findings emphasize the importance of evaluating co-occurring substance use in AUD clinical trials, given that significant changes in cigarette and cannabis use behaviors may occur even when not directly targeted."

Clinical • Journal • Addiction (Opioid and Alcohol)

Direct Trifluoromethylation and Chlorodifluoromethylation Enabled by the Reaction of Reformatsky Reagent with YlideFluor. (PubMed, J Org Chem) - "This reaction proceeds under mild conditions and exhibits a broad functional group tolerance. The utility of this protocol was demonstrated through the synthesis of trifluoromethylated derivatives of two pharmaceutical agents, donepezil and ibudilast."

Journal

MN‑166 (ibudilast) is also being evaluated in the COMBAT‑ALS Phase 2b/3 trial, a randomized, placebo‑controlled study assessing MN‑166’s efficacy and safety in ALS (GlobeNewswire) - "The study includes a 12‑month double‑blind period followed by a 6‑month open‑label extension, with 234 patients enrolled in the U.S. and Canada. Top‑line results are expected by the end of 2026."

P2/3 data • Amyotrophic Lateral Sclerosis

MediciNova…announced that as of the end of January 2026, 12 sites in the US are activated and 100 patients have been enrolled in the SEANOBI study…representing 50% of the planned 200-enrollment, evaluating MN‑166 (ibudilast) in patients with amyotrophic lateral sclerosis (ALS) (GlobeNewswire) - "The NIH‑funded SEANOBI Expanded‑Access Program (EAP), supported by a $22 million NINDS grant under ACT for ALS, is designed to offer MN-166 (ibudilast) treatment access to individuals living with ALS who are not eligible to participate in ongoing randomized clinical trials."

Trial status • Amyotrophic Lateral Sclerosis

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

MIF inhibition attenuates proliferative vitreoretinopathy pathogenesis and protects the eye in preclinical model. (PubMed, Biomed Pharmacother) - "Most importantly, in a rabbit model of PVR, intravitreal ibudilast significantly slowed disease progression, protecting eyes from advancing to higher disease grades. These findings establish MIF as a likely target for PVR treatment and position ibudilast as a promising candidate with high translational potential."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • MIF • TGFB1

Pilot Study of the Effect of Ibudilast on Neuroinflammation in Methamphetamine Users (clinicaltrials.gov) - P2 | N=176 | Completed | Sponsor: VA Office of Research and Development | Recruiting ➔ Completed | N=120 ➔ 176 | Trial completion date: Jun 2026 ➔ Oct 2025

Enrollment change • Trial completion • Trial completion date • Inflammation

Evaluation of cortical pathology in primary-progressive multiple sclerosis: a post hoc analysis of the SPRINT-MS trial. (PubMed, BMJ Neurol Open) - P2 | "Ibudilast treatment was found to slow progression of whole brain and cortical atrophy, but the effect of ibudilast on CLs is unknown...Its protective effect on cortical thinning is more prominent with greater CL formation. NCT01982942."

Journal • Retrospective data • CNS Disorders • Multiple Sclerosis

MediciNova Announces Completion of Patient Enrollment Evaluating MN-166 (ibudilast) in the Prevention of Chemotherapy-induced Peripheral Neuropathy (GlobeNewswire) - "This study, an investigator-initiated clinical trial led by Dr. Janette Vardy and Dr. Haryana Dhillon, is evaluating MN-166 (ibudilast) for the prevention of chemotherapy-induced peripheral neuropathy in patients with metastatic colorectal cancer. A total of 100 patients have been randomized across two treatment arms at 11 clinical sites in Australia. Patient recruitment is now officially closed....While the exact study completion date is not yet determined, we anticipate that top-line data may be available later in 2026."

Enrollment closed • P2 data • Colorectal Cancer

Phosphodiesterase Inhibition Increases Striatal GDNF and Protects Against Preclinical Parkinsonism. (PubMed, J Neurochem) - "In a chronic MPTP mouse model of PD, Ibudilast treatment conferred significant neuroprotection, as evidenced by preservation of tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra, attenuation of TH+ fiber loss in the striatum, and mitigation of striatal dopamine depletion. Given its established clinical use and favorable safety profile, these findings support further investigation of Ibudilast as a potential disease-modifying therapy in PD."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

MediciNova Announces Update and Basic Characteristic Randomized Patients’ of Phase 2/3 Clinical Trial of MN-166 (Ibudilast) in ALS (COMBAT-ALS Clinical Trial) Presented at the 36th International Symposium on ALS/MND (GlobeNewswire) - "Baseline Characteristics: Total randomized patients: 234 (Female: 86 [36.8%], Male: 148 [63.2%]); Mean age at screening: 60.6 years; Racial distribution: Caucasian (90.2%), Asian (5.1%), African American (1.3%), Native Hawaiian or Other Pacific Islander (0.4%), American Indian or Alaskan Native (0.4%), Other (2.6%); ALS onset type: Upper limb (46.2%), Lower limb (32.5%), Bulbar (20.9%), Unknown (0.4%); Mean ALSFRS-R score at screening: 40.6; Mean disease duration from first symptom: 12.5 months...'We anticipate top-line data by the end of 2026...'"

P2/3 data • Trial status • Amyotrophic Lateral Sclerosis

Effect of Ibudilast vs Placebo on GFAP and Contactin levels in a phase 2 clinical trial in progressive multiple sclerosis. (PubMed, Neurol Open Access) - P2 | "We found that although ibudilast treatment previously was associated with positive effects on MRI measures of MS disease, it didn't affect GFAP or contactin. The generalizability of these findings regarding the utility of GFAP or contactin as a treatment response biomarker in progressive MS requires further study.Registered on ClinicalTrials.gov: NCT01982942."

Journal • P2 data • CNS Disorders • Multiple Sclerosis • CNTN • GFAP

Associations Between Baseline C-Reactive Protein Levels and Drinking and Craving Outcomes in a Clinical Trial of a Neuroimmune Modulator for Alcohol Use Disorder [WITHDRAWN] (Neuroscience 2025) - "This study is a secondary analysis of a recently completed 12-week randomized controlled trial testing ibudilast (IBUD), a phosphodiesterase inhibitor with anti-inflammatory properties, as a treatment for AUD...Among high-CRP individuals, IBUD was associated with greater reductions in craving over the trial compared to placebo, while craving outcomes were similar across medication conditions among low-CRP individuals. These findings suggest that IBUD, a neuroimmune modulator, may be more effective for individuals with high baseline levels of inflammation, particularly in reducing craving, while the effects on drinking varied across phases of the trial."

Clinical • Addiction (Opioid and Alcohol) • CNS Disorders • CRP

COMBAT-ALS phase 2b/3 trial of MN-166 (ibudilast) in ALS: trial update and baseline characteristics (ALS-MND 2025) - P2, P2/3 | "Participants are allowed to be on riluzole and edaravone and other approved ALS treatments. This update summarizes the current status and baseline characteristics of currently enrolled participants in the COMBAT-ALS trial. The demographic and clinical profile of the enrolled population is consistent with those reported in other Phase 2 and Phase 3 ALS trials, supporting the generalizability of the study findings."

P2/3 data • P2b data • MIF

MediciNova Wins Contract Research and Development Innovation Award at 2025 BioTech Breakthrough Awards (GlobeNewswire) - "MediciNova earned this recognition for its innovative work advancing MN-166 (ibudilast), the company’s lead small molecule drug candidate, currently in development for several neurological diseases, including amyotrophic lateral sclerosis (ALS), one of the fatal neurodegenerative diseases."

Commercial • Amyotrophic Lateral Sclerosis

Repurposing immunomodulatory drugs targeting microglia for amyotrophic lateral sclerosis. (PubMed, Brain Res) - "Compounds such as ibudilast, fingolimod, and modafinil have shown encouraging initial clinical results, whereas others were well-tolerated but underpowered or failed to demonstrate efficacy. New candidates, such as azithromycin, naltrexone, montelukast, doxycycline, tofacitinib, quercetin, belinostat, and several kinase inhibitors, have demonstrated positive preclinical results, supporting their advancement toward clinical evaluation...To realize this potential, future studies must include larger cohorts, assess effects across disease stages and patient subgroups, and examine sex differences. This is essential to address patient heterogeneity and improve personalized treatment in ALS."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

Exploring Ferroptosis-Related Genes in Depression: Insights Into Molecular Mechanisms and Potential Therapies. (PubMed, Int J Gen Med) - "We identified five potential small-molecule compounds (VX-702, gossypol, atomoxetine, TWS-119, and ibudilast) that may target these ferroptosis-related pathways...This study provides evidence supporting the involvement of ferroptosis-related mechanisms in depression and proposes a integrative treatment strategy combining targeted molecular interventions with TCM approaches. The findings offer new perspectives for developing therapeutic interventions, particularly for treatment-resistant depression."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry

Bioinformatics-based screening and validation of ferroptosis-related genes in sepsis and type 2 diabetes mellitus. (PubMed, Exp Biol Med (Maywood)) - "Echinacea and Ibudilast were predicted to possess the greatest preclinical potential among them. This study provides a deeper insight into the shared pathogenesis of sepsis and T2DM, highlighting the pivotal role of ferroptosis in the development and progression of this comorbidity. Our findings offer preliminary insights into the sepsis-T2DM comorbidity, highlighting ferroptosis as a potential key pathological mechanism and identifying candidate targets for future therapeutic exploration."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Septic Shock • Type 2 Diabetes Mellitus • CDC25B • CNPY2 • FBXO31 • GNRP • NCOA4