vidofludimus (IMU-838) / 4SC, Immunic - LARVOL DELTA

Immunic to host virtual relapsing MS R&D Day on September 9 (Proactiveinvestors) - "The company plans to discuss vidofludimus calcium, also known as IMU-838, its investigational oral small-molecule therapy for relapsing MS. Immunic is evaluating the treatment in the ENSURE Phase 3 program, with topline data expected by the end of the year."

P3 data: top line • Immunology • Multiple Sclerosis

Anticipated Clinical Milestones:…Vidofludimus Calcium in Progressive MS (PRNewswire) - "The planned initiation of a Phase 3 program in progressive MS remains on track for later this year."

New P3 trial • Multiple Sclerosis

Anticipated Clinical Milestones: Vidofludimus Calcium in Relapsing MS (PRNewswire) - "Top-line data from the twin Phase 3 ENSURE-1 and ENSURE-2 trials remains on track and is expected to be available by the end of 2026. If positive, Immunic plans to submit a New Drug Application (NDA) in the United States in mid-2027, with a targeted potential regulatory approval date in 2028."

FDA approval • FDA filing • P3 data: top line • Multiple Sclerosis

Vidofludimus calcium for the treatment of multiple sclerosis: development rationale, mechanism of action, and early trial data. (PubMed, Expert Opin Investig Drugs) - "Completed studies indicate that vidofludimus calcium was generally well tolerated. In light of current unmet treatment needs, results from ongoing phase 3 trials are awaited with interest."

Journal • Review • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • NR4A2

Development of a Brain-Penetrant Nurr1 Agonist Tool. (PubMed, ChemMedChem) - "Here, we employed the scaffold of the dihydroorotate dehydrogenase (DHODH) inhibitor and strong Nurr1 activator vidofludimus to develop a descendant with a high brain-to-blood ratio. Scaffold-hopping from cyclopentene to thiophene, enhanced fluorination, and replacement of the carboxylic acid by an amide provided a highly potent, selective, and brain-penetrant Nurr1 agonist to study the effects of Nurr1 activation in the central nervous system (CNS)."

Journal • CNS Disorders • NR4A2

Evaluation of the potent and selective dihydroorotate dehydrogenase inhibitor PTC844 for use in immune-mediated diseases (EULAR 2026) - "PTC844 is a novel, orally administered, small molecule that has demonstrated uniquely potent and selective inhibition of DHODH compared with in-class compounds both approved and under development to treat immune-mediated disease (teriflunomide, the teriflunomide prodrug leflunomide and vidofludimus)...In the xGvHD mouse model, the median survival time (MST) with PTC844 was 76 days compared with 36 days without treatment, demonstrating better survival than cyclosporine, Janus kinase inhibitors or prednisolone...In a rabbit model of arthritis, PTC844 reduced swelling by 58% at Day 40 compared with the group without treatment, a similar reduction to that observed with methotrexate...Inhibition of DHODH in vivo resulted in elevations in DHO levels, which allowed identification of DHO levels associated with efficacy in preclinical studies. Conclusions Preclinical findings support further testing of PTC844 in immune-mediated disease."

CNS Disorders • Graft versus Host Disease • Immunology • Inflammatory Arthritis • Lupus • Multiple Sclerosis • Solid Tumor

DHODH Inhibitors Based on the Vidofludimus Scaffold Containing Carboxylic Acid Bioisosteres Exert a Superior Broad-Spectrum Antiviral Activity. (PubMed, J Med Chem) - "Selectivity indices exceeded 50,000, highlighting the therapeutic potential of this target. These findings identify this compound class as a promising starting point for host-directed antivirals (HDAs), as well as for pandemic preparedness and applications in other disease areas."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Novel Unified Statistical Analyses for Confirmed Disability Changes In Multiple Sclerosis for Capturing Possible Neuroprotective Effects (CMSC 2026) - "Vidofludimus calcium (VidoCa) is a direct activator of Nurr1 and selective inhibitor of dihydroorotate dehydrogenase (DHODH)... These three novel statistical frameworks provide uniqueassessments of confirmed disability changes (CDC) in MS, with specific utility for therapies exhibiting neuroprotective properties such as VidoCa. Adoption of these frameworks may improve statistical power in clinical trials and inform future therapeutic developments for MS."

Late-breaking abstract • CNS Disorders • Multiple Sclerosis • NR4A2

Effect of Vidofludimus Calcium, a Direct Nurr1 Activator and Selective DHODH Inhibitor, on Patient-Reported Outcomes (PRO) In Progressive MS: Data from Phase 2 Calliper Trial (CMSC 2026) - "The data show that treatment with VidoCa had no apparent negative effects on depressive or suicidal thoughts as compared with placebo. While subjective assessment of treatment effectiveness was numerically higher for VidoCa as compared to placebo, the subjective side effect score was no different between treatment arms. This analysis informs a favorable patient-reported profile for VidoCa."

Clinical • P2 data • Patient reported outcomes • CNS Disorders • Multiple Sclerosis • Suicidal Ideation • NR4A2

Safety and Tolerability of Vidofludimus Calcium, a Direct Nurr1 Activator and Selective DHODH Inhibitor: Data from Phase 2 Calliper Trial (CMSC 2026) - "Overall, the safety experience from the CALLIPER study indicate similar rates and types of adverse events in vidofludimus calcium-treated MS patients as with placebo, which is similar to what was seen in previous trials. These observations confirm the favorable safety profile of vidofludimus calcium."

Clinical • P2 data • Back Pain • CNS Disorders • Multiple Sclerosis • Musculoskeletal Pain • NR4A2

Immunic…announced the presentation of…two additional posters highlighting additional data from its phase 2 CALLIPER trial evaluating lead asset, nuclear receptor-related 1 (Nurr1) activator, vidofludimus calcium (IMU-838) in patients with progressive multiple sclerosis (PMS) at the 2026 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting (PRNewswire) - "Analyses using a mixed model repeated measures (MMRM) approach showed that changes in PHQ-9 scores were similar between vidofludimus calcium and placebo across all assessed timepoints, including weeks 48, 72 and 120. At week 48, PHQ-9 scores numerically improved in both groups (vidofludimus calcium: -0.786 vs. placebo: -0.347), with a similar pattern observed at week 72 (vidofludimus calcium: -0.568 vs. placebo: -0.609) and week 120 (vidofludimus calcium: -1.777 vs. placebo: -0.525).....The overall incidence of treatment-emergent adverse events (TEAEs) was comparable between vidofludimus calcium (69.4%) and placebo (68.5%). The most commonly reported events, including urinary tract infection, headache and back pain, occurred at similar or lower rates in the vidofludimus calcium arm compared to placebo."

Adverse events • P2 data • Multiple Sclerosis

Anticipated Clinical Milestones: Vidofludimus calcium in MS (PRNewswire) - "Top-line data from the twin phase 3 ENSURE-1 and ENSURE-2 trials in RMS is expected by the end of 2026. Subsequently, Immunic plans to submit an NDA in the United States in mid-2027, with a targeted potential regulatory approval date in 2028. Initiation of a phase 3 clinical program in PPMS is expected later this year and is estimated to take approximately 3.5 to 4 years to complete."

FDA approval • FDA filing • New P3 trial • P3 data: top line • Multiple Sclerosis

Immunic to present MS data, meet investors at May conferences (Proactiveinvestors) - "At the CMSC Annual Meeting in Charlotte, the company will present three posters, including a late-breaking analysis on disability changes in multiple sclerosis, and data from its Phase 2 CALLIPER trial evaluating vidofludimus calcium."

Clinical data • Late-breaking abstract • P2 data • Multiple Sclerosis

P1-IMU-838-DDI-BCRP: A study investigating the effect of curcumin on the absorption and elimination of IMU 838, a new compound that may potentially be used in the treatment of multiple sclerosis, and the effect of IMU 838 on the absorption and elimination of rosuvastatin. (clinicaltrialsregister.eu) - P1 | N=28 | Completed | Sponsor: Immunic AG | Recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Immunic to Participate in Scientific and Medical Conferences in April (PRNewswire) - "April 14-16: 8th Annual Neuroimmunology Drug Development Summit. Hella Kohlhof, Ph.D., Chief Scientific Officer of Immunic, will give a presentation highlighting lead asset, nuclear receptor-related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), at this conference in Boston."

Clinical • Multiple Sclerosis

P1-IMU-838-DDI-COC: A Phase 1, drug-drug interaction trial of IMU-838 with oral contraceptives in women (clinicaltrialsregister.eu) - P1 | N=26 | Not yet recruiting | Sponsor: Immunic AG

New P1 trial • CNS Disorders • Multiple Sclerosis

Immunic, Inc…announced that the European Patent Office (EPO) has granted a key European patent, EP3713554, directed to label-relevant dosing regimens of lead asset, nuclear receptor-related 1 (Nurr1) activator, vidofludimus calcium (IMU-838). (PRNewswire) - "The patent is expected to provide protection for vidofludimus calcium in Europe into 2038, and may be eligible for a Supplementary Protection Certificate (SPC), which could extend market exclusivity potentially into 2043....The claims broadly protect vidofludimus and its salt, solvate and free acid forms, in all label-relevant dosing regimens. This protection extends beyond a specific salt form, meaning that even alternative salts or forms will fall within the scope of the patent if used according to the label."

Patent • Multiple Sclerosis

P1-IMU-838-DDI-BCRP: A study investigating the effect of curcumin on the absorption and elimination of IMU 838, a new compound that may potentially be used in the treatment of multiple sclerosis, and the effect of IMU 838 on the absorption and elimination of rosuvastatin. (clinicaltrialsregister.eu) - P1 | N=28 | Recruiting | Sponsor: Immunic AG

New P1 trial • CNS Disorders • Multiple Sclerosis

MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS) (clinicaltrials.gov) - P2 | N=195 | Recruiting | Sponsor: Immunic AG

New P2 trial • CNS Disorders • Multiple Sclerosis

MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS) (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: Immunic AG | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2030 ➔ Dec 2029 | Trial primary completion date: Nov 2020 ➔ May 2020

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

P1-IMU838DDI-CYP2C8: A Phase 1, Single-Center, Open-Label, Fixed-Sequence, 2-Part Study to Assess the Pharmacokinetics of IMU-838 Administered Alone and in Combination with Multiple Doses of Gemfibrozil as CYP2C8 Inhibitor, or Rifampicin as CYP2C8 Inducer, in Healthy Subjects (clinicaltrialsregister.eu) - P1 | N=24 | Active, not recruiting | Sponsor: Immunic AG | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

ENSURE-2: Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis (clinicaltrials.gov) - P3 | N=1100 | Active, not recruiting | Sponsor: Immunic AG | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2032 ➔ Oct 2033 | Trial primary completion date: Oct 2024 ➔ Nov 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

ENSURE-1: Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis (clinicaltrials.gov) - P3 | N=1121 | Active, not recruiting | Sponsor: Immunic AG | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2032 ➔ Sep 2033 | Trial primary completion date: Sep 2024 ➔ Nov 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Immunic Announces Oversubscribed Private Placement of up to USD 400 Million to Accelerate Transformation into Commercial-Stage Company (PRNewswire) - "Expected to Fund Completion of Phase 3 ENSURE Trials in Relapsing Multiple Sclerosis, Initiation of Phase 3 Trial in Primary Progressive Multiple Sclerosis, and Transition into a Commercial Organization...Completion of the ongoing phase 3 ENSURE clinical trials of vidofludimus calcium in relapsing multiple sclerosis (RMS): Top-line data continues to be expected by the end of 2026. Subsequently, Immunic plans to submit a New Drug Application (NDA) in the United States in mid-2027, with a targeted potential regulatory approval date in 2028....Immunic is working towards initiation of a phase 3 clinical program, which is expected later this year and estimated to take approximately 3.5 to 4 years to complete."

FDA approval • FDA filing • Financing • New P3 trial • P3 data: top line • Immunology • Multiple Sclerosis

Effect of Vidofludimus Calcium, a Novel Nurr1 Activator and Selective DHODH Inhibitor, on MRI Outcomes in Progressive Multiple Sclerosis: Data from the Phase 2 CALLIPER Trial (ACTRIMS Forum 2026) - "These MRI results show that VidoCa reduces the MRI hallmarks of acute-focal (Gd+ lesions, T2 lesion load) and chronic-compartmentalized (SEL) inflammation in a progressive MS patient population."

P2 data • CNS Disorders • Inflammation • Multiple Sclerosis • NR4A2