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

The results from the phase 2 CALLIPER trial in PMS were also selected for the Best of ECTRIMS 2025 slide deck. (PRNewswire) - "Consistent 24-week confirmed disability worsening (24wCDW) outcomes were observed across disability endpoints, patient populations and subgroups (including the overall population and in PPMS and naSPMS), and those without baseline inflammatory gadolinium-enhancing (Gd+) lesions during magnetic resonance imaging (MRI). Newly available data regarding 24-week confirmed disability improvement (24wCDI) demonstrated a greater than two-fold probability for vidofludimus calcium over placebo, statistically significant in the overall PMS population, with consistent trends across subtypes. These findings support clinically measurable neuroprotective effects consistent with vidofludimus calcium's Nurr1 activation mechanism and de-risk a potential phase 3 program, as 24wCDW is an accepted regulatory endpoint to demonstrate clinical benefit in PMS."

P2 data • Multiple Sclerosis

Long-term data from the phase 2 EMPhASIS OLE period... (PRNewswire) - "...reinforced vidofludimus calcium's robust efficacy signals and favorable safety and tolerability profile, demonstrating that it was well-tolerated for treatment durations of up to 5.5 years in patients with RRMS. Among 182 patients remaining on therapy as of January 14, 2025, cumulative exposure totaled ~952 treatment years with an annualized discontinuation rate of only ~6.4%. Most adverse events were mild, with low rates of renal and liver-related events, and no new safety signals observed. Serious adverse events were infrequent, and none were deemed related to treatment."

P2 data • Multiple Sclerosis

Anticipated Clinical Milestones (PRNewswire) - "Vidofludimus calcium in MS: Top-line data from the twin phase 3 ENSURE-1 and ENSURE-2 trials in RMS is expected by the end of 2026; IMU-856: The company is preparing for further clinical testing of IMU-856, the orally available and systemically acting small molecule modulator that targets Sirtuin 6 (SIRT6), contingent on financing, licensing or partnering."

New trial • P3 data: top line • Immunology • Multiple Sclerosis

Immunic CEO talks BIO-Europe 2025, MS trials… (Proactiveinvestors) - "The conversation centred on the progress of its lead asset vidofludimus calcium, particularly its ongoing ENSURE Phase 3 trials for relapsing multiple sclerosis, which are fully enrolled and expected to report data at the end of 2026."

P3 data • Multiple Sclerosis

The Construction and Characterization of an Infectious Clone of the Asian Genotype Chikungunya Virus from Yunnan, China. (PubMed, Trop Med Infect Dis) - "The study also found that two DHODH inhibitors, ML390 and vidofludimus, could effectively inhibit CHIKV replication in vitro. The infectious clone created in this study provides a useful tool for studying the recently prevalent Asian-type strain in China, supporting the subsequent development of prevention and treatment methods."

Journal • Chikungunya

Efficacy and Safety of Vidofludimus Calcium, a novel Nurr1 activator and DHODH inhibitor, in Primary Progressive Multiple Sclerosis (PPMS): Subpopulation Data from the Phase 2 CALLIPER Trial (ECTRIMS 2025) - P2 | "The PPMS population of CALLIPER study showed evidence suggestive of clinical activity in reducing disability progression that should be further investigated in a Phase 3 trial. The observed treatment effect was maintained in the subgroup of PPMS patients without Gd+ at baseline which supports clinically measurable neuroprotective effects of vidofludimus calcium, presumably due to the Nurr1 activation mechanism. Disclousure of interest: R.J. Fox reports personal consulting fees from Astoria Biologica, Biogen, Bristol Myers Squibb, Cognito, EMD Serono, Galvani, Immunic, INmune Bio, Kiniksa, Novartis, Sanofi, Siemens, and TG Therapeutics and has served on advisory committees for AB Science, Biogen, Immunic, Novartis, and Sanofi, and received clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi."

Clinical • Late-breaking abstract • P2 data • CNS Disorders • Inflammation • Multiple Sclerosis • NR4A2

Update on the assessment of long-term safety and tolerability of vidofludimus calcium in patients with relapsing-remitting multiple sclerosis up to 5.5 years: the open-label extension period of the phase 2 trial (EMPhASIS) study (ECTRIMS 2025) - P2 | "The EMPhASIS OLE period is characterized by a low discontinuation rate as well as by low rates of TEAEs and SAEs. No new safety signal emerged during treatment durations up to 5.5 years. Overall, this analysis suggests a favorable safety and tolerability profile in long-term treatment with VidoCa."

Clinical • P2 data • Back Pain • Breast Cancer • CNS Disorders • Hepatology • Infectious Disease • Melanoma • Multiple Sclerosis • Musculoskeletal Pain • Solid Tumor • Thrombosis • NR4A2

144-Week Analysis of the Confirmed Disability Worsening Events from the Open-Label Treatment Extension of the Phase 2 EMPhASIS Study of Vidofludimus Calcium in Patients with Relapsing-Remitting Multiple Sclerosis (ECTRIMS 2025) - "In this long-term open-label phase of EMPhASIS, patients treated with VidoCa had a low rate of confirmed disability worsening events. Most remaining events observed were classified as relapse-associated worsening."

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

Potential Neuroprotective Activity by Vidofludimus Calcium in In Vivo Models of Multiple Sclerosis (ECTRIMS 2025) - "These data show that VidoCa ameliorates EAE and suggest that VidoCa also activates Nurr1 in vivo, further supporting its potential to enhance neuroprotection."

Preclinical • CNS Disorders • Immunology • Multiple Sclerosis • APP • BDNF • CSF2 • IFNG • IL17A • MBP • NEFL • NR4A2 • Plasma NfL

Efficacy and Safety of Vidofludimus Calcium, a novel Nurr1 activator and DHODH inhibitor, in Progressive Multiple Sclerosis: Data from the Phase 2 CALLIPER Trial (ECTRIMS 2025) - P2 | "The CALLIPER trial assesses the effect of vidofludimus calcium on imaging and clinical measures in progressive MS. The results will provide initial insights into the activity and safety of vidofludimus calcium in this difficult-to-treat population."

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

CALLIPER Subpopulation Data Support Therapeutic Effect of Vidofludimus Calcium in Primary Progressive MS (NeurologyLive) - "Among a cohort of 467 participants, the double-blind, placebo-controlled trial enrolled 152 patients with PPMS, aged 18 to 65 years, with baseline Expanded Disability Status Scale (EDSS) score of 3.0 to 6.5. For those with PPMS, the difference of least square mean (ΔLSM, all re-baselined at 6 months) of the annualized rate for percent brain volume change (PBVC), the study’s primary end point, was 0.04 (VidoCa: LSM, –0.78; placebo; –0.82; P >.03)....These findings were presented as late-breaking data at the 2025...ECTRIMS Congress..."

P2 data • Multiple Sclerosis

Immunic talks vidofludimus calcium…at ECTRIMS 2025 (Proactiveinvestors) - "Tardio explained that Immunic is showcasing one oral and four poster presentations, including late-breaking data from the Phase 2 CALLIPER study in progressive multiple sclerosis....Looking ahead, Immunic plans end-of-Phase 2 discussions with both the FDA and EMA before moving toward a potential Phase 3 program in progressive MS. Top-line data from the ENSURE-1 and -2 studies in relapsing MS are expected by the end of 2026."

Clinical data • Late-breaking abstract • New P3 trial • Multiple Sclerosis

Vidofludimus calcium shows potential neuroprotective effects in an in vivo multiple sclerosis model by Nurr1 modulation (EAN 2025) - "These data indicate that VidoCa potentially enhances neuroprotection in vivo by activating Nurr1."

Preclinical • CNS Disorders • Immunology • Multiple Sclerosis • Solid Tumor • APP • BDNF • MBP • NEFL • NR4A2 • Plasma NfL

Immunic Receives Notice of Allowance for United States Patent Protecting Vidofludimus Calcium's Dose Strengths in Progressive Multiple Sclerosis (PRNewswire) - "...received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for patent application 18/529,946...Specifically, the resulting patent covers dose strengths associated with lead asset, vidofludimus calcium (IMU-838), and other salt forms as well as free acid forms, at a daily dose of about 10 mg to 45 mg....The patent is expected to provide protection into 2041, and potential Patent Term Extension may offer additional market exclusivity in the United States."

Patent • Multiple Sclerosis

Immunic…announced that it has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for patent application 18/529,946, entitled, "Treatment of multiple sclerosis comprising DHODH inhibitors" (PRNewswire) - "Specifically, the resulting patent covers dose strengths associated with lead asset, vidofludimus calcium (IMU-838), and other salt forms as well as free acid forms, at a daily dose of about 10 mg to 45 mg, for the treatment of progressive multiple sclerosis (PMS)....The patent is expected to provide protection into 2041, and potential Patent Term Extension may offer additional market exclusivity in the United States."

Patent • Multiple Sclerosis

Immunic to Participate in Investor and Scientific Conferences in September (PRNewswire) - "September 24-26: 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)....Data on Immunic's orally available lead-asse...vidofludimus calcium (IMU-838) will be presented in an oral presentation and four poster presentations, including one late-breaking poster."

P2 data • Preclinical • Multiple Sclerosis

Randomized adaptive assessment of post COVID syndrome treatments (RAPID): a study protocol for a multicenter, randomized, controlled adaptive platform trial of treatment options for Post Covid Syndrome (PCS) on patients physical function including the first intervention specific appendix RAPID_REVIVE (reducing inflammatory activity in patients with PCS). (PubMed, Trials) - "PCS is a major problem for global health care and the identification of treatment options is urgently needed. Currently, PCS patients are in a situation without evidence-based treatment options, and quality of life, and often mental health are significantly impaired. The purpose of RAPID is to establish an adaptive platform trial protocol which will concert and quicken clinical trials to evaluate the efficacy and safety of different potential treatments for PCS with the aim to expand the very limited evidence base for the treatment of PCS."

Clinical protocol • Journal • CNS Disorders • Fatigue • Infectious Disease • Mental Retardation • Novel Coronavirus Disease • Psychiatry • Respiratory Diseases

Inhibition of pyrimidine de novo synthesis fosters Treg cells and reduces diabetes development in models of Type 1 Diabetes. (PubMed, Mol Metab) - "We demonstrate that restricting pyrimidine de novo synthesis by next-generation DHODH inhibition is a strategy to interfere with autoimmune activation while fostering Tregs."

Journal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Carboxylic Acid Bioisosteres Boost Nurr1 Agonist Selectivity. (PubMed, J Med Chem) - "Among them, the clinically studied dihydroorotate dehydrogenase (DHODH) inhibitor vidofludimus was found to exhibit strong Nurr1 agonism...We explored bioisosteric replacement of the drug's carboxylate motif and succeeded in boosting selectivity for Nurr1 over DHODH to >100-fold. Dopaminergic neural cells treated with the optimized tetrazole-based Nurr1 agonist revealed induction of genes involved in neuroprotection and neuronal health, supporting the potential of Nurr1 activation in neurodegenerative diseases."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease • NR4A2

Immunic Reports New, Positive Long-Term Open-Label Extension Data From Phase 2 EMPhASIS Trial of Vidofludimus Calcium in Relapsing-Remitting Multiple Sclerosis (PRNewswire) - P2 | N=268 | EMPhASIS (NCT03846219) | Sponsor: Immunic AG | "The data at week 144 showed that 92.3% of patients remained free of 12-week CDW, and 92.7% free of 24-week CDW. A total of 29 CDW events were confirmed at 12 weeks following the trigger event through week 144. Of these, 44.8% were associated with relapse-associated worsening (RAW), while only 13.8% were associated with progression independent of relapse activity (PIRA). Additionally, the cumulative data available from the EMPhASIS OLE period, thus far, further reinforces the favorable safety and tolerability profile of vidofludimus calcium, showing low discontinuation rates and low rates of treatment-emergent and serious adverse events. Importantly, no new safety signals have emerged during treatment durations up to 5.5 years."

P2 data • Multiple Sclerosis

Additional Data Available from Phase 2 CALLIPER Trial in Progressive Multiple Sclerosis (PMS) (PRNewswire) - P2 | N=450 | CALLIPER (NCT05054140) | Sponsor: Immunic AG | "In the overall PMS patient population (n=467), vidofludimus calcium demonstrated a clinically meaningful reduction of the hazard ratio (HR) for 24wCDW by 24% compared to placebo (HR 0.76). Further analyses by disease subtype showed that vidofludimus calcium was associated with a 33% reduction in 24wCDW in the primary progressive multiple sclerosis (PPMS) study population (n=152) compared to placebo (HR 0.67), a 19% reduction in the non-active secondary progressive multiple sclerosis (naSPMS) study population (n=268) compared to placebo (HR 0.81), and a 34% reduction in the active secondary progressive multiple sclerosis (aSPMS) study population (n=47) compared to placebo (HR 0.66)."

P2 data • Multiple Sclerosis

Immunic Announces Completion of Enrollment for Both Phase 3 ENSURE Trials in Relapsing MS… (PRNewswire) - "Immunic, Inc...announced the completion of enrollment for both phase 3 ENSURE trials of lead asset, nuclear receptor-related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), in patients with relapsing multiple sclerosis...The ENSURE program comprises two identical multicenter, randomized, double-blind phase 3 trials designed to evaluate the efficacy, safety and tolerability of vidofludimus calcium versus placebo in RMS patients. Each of the trials, titled ENSURE-1 and ENSURE-2, enrolled adult patients with active RMS at more than 100 sites in 15 countries, including the United States, India and countries in the Middle East and North Africa (MENA) region, Latin America, and Central and Eastern Europe."

Enrollment closed • Multiple Sclerosis

Immunic releases June conference schedule (Proactiveinvestors) - "CEO Dr. Daniel Vitt will present at the Jefferies Healthcare Conference on June 5 in New York. Company representatives will also attend the RSC Symposium in Denmark, UBS Life Sciences Conference in London, BIO International Convention in Boston, EAN Congress in Helsinki, and the ABI Conference in Cambridge. Presentations and data will cover preclinical and clinical advances for vidofludimus calcium (IMU-838)."

Clinical • Preclinical • Multiple Sclerosis

Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design. (PubMed, Commun Chem) - "Structure-guided ligand design using these insights resulted in an optimized Nurr1 agonist with substantially enhanced potency and binding affinity. Our results provide a structural and molecular basis for Nurr1 activation by a synthetic agonist which was lacking for rational ligand design."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease • NR4A2

Immunic to Participate in Scientific and Industry Conferences in May (PRNewswire) - "May 3-6: Digestive Disease Week (DDW). Two abstracts discussing Immunic's phase 1/1b clinical trial of IMU-856, an orally available and systemically acting small molecule modulator that targets SIRT6 (Sirtuin 6), in patients with celiac disease, have been accepted for poster presentations at this conference in San Diego, CA....May 28-31: Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting 2025. Members of Immunic's management, medical and preclinical teams will attend this meeting in Phoenix, AZ. The team will be available throughout the event at booth #911. Additionally, preclinical data highlighting lead asset, nuclear receptor-related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), will be presented in a poster presentation."

P1 data • Preclinical • Celiac Disease • Multiple Sclerosis