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Immunic Therapeutics Positive Data from Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis NASDAQ: IMUX | April 30, 2025
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Cautionary Note Regarding Forward-Looking Statements This presentation contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These include statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Immunic undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. We use words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, risks relating to strategy, future operations, future financial position, future revenue, projected expenses, availability and terms of necessary financing, prospects, plans and objectives of management. Risks and uncertainties that may cause actual results to differ materially from those expressed or implied in any forward-looking statement include, but are not limited to: Immunic’s development programs and the targeted diseases; the potential for Immunic’s development programs to safely and effectively target and treat the diseases mentioned herein; preclinical and clinical data for Immunic’s development programs; the impact of future preclinical and clinical data on Immunic’s product candidates; the timing of the availability of data from Immunic’s clinical trials; the availability or efficacy of Immunic’s potential treatment options that may be supported by trial data discussed herein; the timing of current and future clinical trials and anticipated clinical milestones; Immunic’s ability to protect its intellectual property position; Immunic’s plans to research, develop and commercialize its current and future product candidates; the timing of any planned investigational new drug application or new drug application; the development and commercial potential of any product candidates of the company; expectations regarding potential market size; developments and projections relating to Immunic’s competitors and industry; the clinical utility, potential benefits and market acceptance of Immunic’s product candidates; Immunic’s commercialization, marketing and manufacturing capabilities and strategy; Immunic’s ability to successfully collaborate with existing collaborators or enter into new collaboration agreements, and to fulfill its obligations under any such collaboration agreements; Immunic’s ability to identify additional products or product candidates with significant commercial potential; the impact of government laws, regulations and tariffs; the COVID-19 pandemic; impacts of the conflicts in Ukraine – Russia and the Middle East; Immunic’s listing on The Nasdaq Global Select Market; expectations regarding the capitalization, resources and ownership structure of the company; the executive andboard structure of the company; Immunic’s estimates regarding future revenue, expenses, capital requirements and need for additional financing, including the ability to satisfy the minimum average price and trading volume conditions required to receive funding in tranche 2 and 3 of the January 2024 private placement; the nature, strategy and focus of the company and further updates with respect thereto; and the other risks set forth in the company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission. Forward-looking statements included in this presentation are based on information available to Immunic as of the date of this presentation. Immunic does not undertake any obligation to update such forward-looking statements except as required by applicable law. | © Immunic, Inc. | Apr/30/20252
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Today’s Speakers Positive Data from Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis | © Immunic, Inc. | Apr/30/20253 Jason Tardio President & Chief Operating Officer Andreas Muehler, MD, MBA Chief Medical Officer Daniel Vitt, PhD Chief Executive Officer Jessica Breu Vice President Investor Relations & Communications
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Study met primary and key secondary endpoints Open-label extension ongoing 2021 2022 2023 2024 2025 2026 20272019 2020 Vidofludimus Calcium: Clinical Trials Overview in Multiple Sclerosis (MS) | © Immunic, Inc. | Apr/30/20254 CDW: confirmed disability worsening;PPMS: primary progressive multiple sclerosis; naSPMS: non-active secondary progressive multiple sclerosis Today EMPhASIS Phase 2 RELAPSING MS Actively recruiting, n=1050 patients planned ENSURE-1 Phase 3 Q2/2026 Completion (expected) RELAPSING MS Actively recruiting, n=1050 patients planned ENSURE-2 Phase 3 H2/2026 Completion (expected) PROGRESSIVE MS Reduced CDW in PPMS and naSPMS CALLIPER Phase 2 RELAPSING- REMITTING MS Open-label extension ongoing
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Vidofludimus Calcium in Progressive Multiple Sclerosis Phase 2 CALLIPER Trial
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Vidofludimus Calcium Has the Potential to be the First and Only Oral DMT Approved for Both Relapsing and Progressive MS | © Immunic, Inc. | Apr/30/20256 DMT: disease-modifying therapy; MS: multiple sclerosis; RRMS: relapsing-remitting MS; SPMS: secondary progressive MS; aSPMS: active SPMS; MRI: magnetic resonance imaging; Nurr1: nuclear receptor-related 1; DHODH: dihydroorotate dehydrogenase Relapsing MS (RMS) Progressive MS (PMS) DHODH Inhibition Nurr1 Activation Relapses and focal inflammation Smoldering disease and neurodegeneration Non-Active SPMS
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Regardless of the Subtype, the Outcome of Every Patient Journey in Multiple Sclerosis Is Physical and/or Cognitive Disability | © Immunic, Inc. | Apr/30/20257 While over 15 anti-inflammatory treatments exist for relapsing multiple sclerosis, there is no therapy available that directly impacts the neurodegeneration driving disability progression 1.0 101.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1.0 No disability, minimal signs of MS 3.0 Moderate disability in one system, or mild disability in up to four systems. No impairment to walking 5.0 Disability severe enough to impair full daily activities, able to walk without aid for 200m 6.0 Requires a walking aid, cane, crutch, etc. – to walk 100m 7.5 Unable to take more than a few steps. Restricted to wheelchair 9.0 Confined to bed, can still communicate and eat 10 Death by MS
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Objectives of the Exploratory Phase 2 CALLIPER Trial Why Did Immunic Conduct the Exploratory CALLIPER Trial in Patients With Progressive Multiple Sclerosis? | © Immunic, Inc. | Apr/30/20258 Scientific: Does vidofludimus calcium show signs of direct neuroprotection in multiple sclerosis via its mechanism of Nurr1 activation? Clinical: Can vidofludimus calcium make a clinically meaningful impact in progressive multiple sclerosis patients? o Can it reduce disability worsening? o Are other clinical datapoints impacted? o Is the safety and tolerability profile favorable as in previous studies? Commercial: Which progressive multiple sclerosis indications should be further pursued with vidofludimus calcium in confirmatory trials?
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CALLIPER: Phase 2 Clinical Trial in Progressive Multiple Sclerosis NCT05054140 | © Immunic, Inc. | Apr/30/20259 EoMT: end of main treatment period, either at Week 120 or when last enrolled patient reached Week 72 R: randomization; D: day; W: week; EoMT: end of main treatment period; MRI: magnetic resonance imaging; PPMS: primary progressive multiple sclerosis; SPMS: secondary progressive multiple sclerosis; EDSS: Expanded Disability Status Scale; QD: quaque die = once-daily Screening Period Main Treatment Period (Blinded) 45 mg IMU-838 (N=235) Placebo (N=232) R D1 W24D-28 to -3 D-8 to-1 W72W48 Visits every 12 weeks MRI every 24 weeks EoMT+ up tp 120 Weeks Main Analysis Multicenter, Randomized, Double- Blind, Placebo-Controlled Phase 2 Trial ▪ 467 adult patients, aged 18 to 65 years, enrolled at more than 70 sites in North America, Western, Central and Eastern Europe – PPMS or SPMS diagnosis ( revised McDonald criteria 2017) – EDSS score at screening between 3.0 to 6.5 – No relapse in last 24 months before randomization – Evidence of disability progression ▪ Randomization to 45 mg vidofludimus calcium or placebo QD ▪ Blinded main treatment period up to 120 weeks ▪ Optional, approximately 8-year, open-label extension period 45 mg IMU-838 Coordinating Investigator: Robert J. Fox, M.D., Cleveland Clinic Extension (Open-Label) Interim Biomarker Analysis
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Baseline and Patient Characteristics Top-Line Data Phase 2 CALLIPER Trial
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N=152 32.5% N=268 57.4% N=47 10.1% Primary progressive MS Non-active secondary progressive MS Active secondary progressive MS Baseline Patient Characteristics Total (N=467) Age [years], median (min-max) 51.0 (21-65) Gender (n and % female) 302 (64.7%) Race (n and % White) 460 (98.7%) BMI [kg/m˄2], median (min-max) 25.0 [15.8 – 46.6] SDMT [points], median (min-max) 35.0 [0-180] EDSS at Visit 1, median (min-max) 5.5 [2.5-6.5] MS relapses during last 24 months, median (min-max) 0.0 [0-0] Gd+ lesions at baseline MRI (%) 16.3% Progressive Disease Subtypes Baseline Characteristics CALLIPER: Patient Demographics and Baseline Characteristics Total Study Population of 467 Enrolled Patients | © Immunic, Inc. | Apr/30/202511 Baseline characteristics init ially assessed by the investigators when patients entered screening based on history. These data summarize the disease subtype as assessed by the invest igator at the time of randomization. A small number of patients changed their subtype (in particular from non -active to active disease) due to events during the screening period. Definition non -active SPMS (according to CALLIPER protocol): no evidence of relapse i n the last 24 mont hs before randomization, AND patients showing no evidence of Gd+ MRI lesions in t he brain or spinal cord in the last 12 mont hs; definition non -relapsing SPMS: no evidence of relapse in the last 24 months before randomization / BMI: body mass index; SDMT: Symbol Digit Modalities Test; ED SS: Expanded Disability Status Scale; Gd+: gadolinium -enhancing; MRI: magnetic resonance imaging T otal N=467
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Clinical Endpoints Top-Line Data Phase 2 CALLIPER Trial
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Vidofludimus Calcium Showed Substantial Reduction of 24wCDW-EDSS Events
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Vidofludimus Calcium Reduced Relative Risk of 24wCDW in Overall Study Population and Subtypes Compared to Placebo | © Immunic, Inc. | Apr/30/202514 Based on intent-to-treat population (ITT), patients are analyzed as randomized; 24wCDW: 24-week confirmed disability worsening;naSPMS: non-active secondary progressive multiple sclerosis; PPMS: primary progressive multiple sclerosis 24-week confirmed disability worsening based on EDSS scale (24wCDW), total of 85 events in the intent-to-treat population of CALLIPER trial Data displayed for the reduction of risk of occurrence of 24wCDW events, percentages refer to the rate of 24wCDW in each of the treatment arms per disease subtype. Disease subtype as per investigator diagnosis at screening. Proportion of Patients With 24wCDW Events Overall CALLIPER Patient Population (N=467) PPMS (N=152) naSPMS (N=268) Vidofludimus Calcium 16.2% 19.5% 14.1% Placebo 20.3% 28.0% 16.5% Relative Risk Ratio for 24wCDW 0.80 0.70 0.85 Relative Risk Reduction for 24wCDW 20% 30% 15%
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Comparison CALLIPER Versus ORATORIO Trials in PPMS Population | © Immunic, Inc. | Apr/30/202515 * Clinical Review Report: Ocrelizumab (Ocrevus): (Hoffmann-La Roche Limited): Indication: Management of adult patients with early primary progressive multiple sclerosis as defined by disease duration and level of disability, in conjunction with imaging features characteristic of inflammatory activity [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 May. Results. Available from: https://www.ncbi.nlm.nih.gov/books/NBK533357/ PPMS: primary progressive multiple sclerosis; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing lesions found onT1-weighted MRI images; MRI: magnetic resonance imaging; 24wCDW: 24-week confirmed disability worsening ORATORIO* CALLIPER (N=732) (N=152) Mean Age (Years) 44.6 47.4 Female (N,%) 361 (49.3%) 93 (61.1%) EDSS - Mean 4.7 4.9 EDSS - Median 4.5 4.5 Gd+ Lesions at Baseline MRI (N,%) 26.6% 17.8% Relative Risk Reduction of 24wCDW, Active Over Placebo 25% 30%
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Vidofludimus Calcium Reduced Relative Risk of 24wCDW Events in Patients Without Gd+ Lesions at Baseline | © Immunic, Inc. | Apr/30/202516 Reduction of 24wCDW Events by 29% in Patients With Highest Need 24wCDW: 24-week confirmed disability worsening; Gd+: gadolinium-enhancing; EDSS: Expanded Disability Status Scale; Nurr1: nuclear receptor-related 1 Proportion and number of patients without Gd+ lesions at baseline with 24wCDW EDSS in vidofludimus calcium group (N=197) compared to placebo (N=194) % of patients with 24wCDW of the total number in the respective treatment group 14.2% 20.1% Vidofludimus Calcium Placebo ▪ 391 of 467 patients had no Gd+ lesions at baseline ▪ In this group, vidofludimus calcium reduced 24wCDW events by 29%, with relative risk ratio of RR=0.71 ▪ Precisely the patients who were largely shown to not benefit from current anti - inflammatory therapies ▪ Underlines neuroprotective effect of Nurr1 activation by vidofludimus calcium n=28 n=39 29% Relative Risk Reduction n=28 n=39
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Clinically meaningful risk reduction of confirmed disability worsening of 20% in overall PMS population and even more prominent 30% reduction in PPMS population CALLIPER successfully demonstrated the neuroprotective potential of vidofludimus calcium in PMS patients
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Magnetic Resonance Imaging (MRI) Endpoints Top-Line Data Phase 2 CALLIPER Trial
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Brain Atrophy Endpoints Consistently Demonstrated Beneficial Effect of Vidofludimus Calcium Compared to Placebo | © Immunic, Inc. | Apr/30/202519 [1] Moccia M et al., Multiple Sclerosis JournalVolume 23, Issue 12, October 2017 [2] Azevedo CJ et al., Ann Neurol. 2018 Feb;83(2):223-234 [3] Azevedo CJ et al., Ann Neurol 2018 Jan 12; [e-pub] [4] Cao Y et al., Neuropsychol Rev 2021 [5] Mes aros S et al., AJNR Am J Neuroradiol 2011;32:1016–1020 [6] Schoonheim MM et al., Mult Scler 2021:13524585211008743 MRI: magnetic resonance imaging; LS: least square; PBVC = percent brain volume change (using the Siena method); intent-to-treat population (all patients are analyzed as randomized) For the calculation of least square means, patients with a valid baseline MRI are considered. Miss ing values are calculated based on the analysis set. Estimates are obtained from a random intercept, random slope mixed model, accounting for treatment effect and stratified by the randomization strata (disease type and bas eline EDSS score). Convergence and positive estimated G matrix was achieved with an Autoregressive Order One (AR(1)) covariance matrix. The annualized rate of PBVC is th e population slope within treatment group as change from baseline. The effect es timate of the treatment difference is equivalentto the difference between annualized rates. For the primary estimand, data collected up to 30 days after the ons et date of a post-baseline relapse or between the start and 30 days after the end of any res cue medication intake were s et tomiss ing. Data after treatment discontinuation was included in the analysis. ▪ Modest benefit on exploratory primary MRI endpoint: decreased annualized rate of whole brain atrophy: 5% improvement of vidofludimus calcium compared to placebo at 24 months ▪ Substantially reduced annualized rate of thalamic brain volume loss by 20% in patients with PMS compared to placebo at 24 months − Change in thalamus volume is more sensitive MRI atrophy measure in PMS[1,2,3] − Thalamic atrophy is prevalent in PMS[4,5] and data have shown strong associations between thalamic atrophy and clinical disability progression[6]-1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 0 6 12 18 24 Change in LS Mean from Baseline Months Change in Thalamus Volume - All Patients Vidofludimus calcium Placebo -1 -0.8 -0.6 -0.4 -0.2 0 6 12 18 24 Change in LS Mean from Baseline Months Change in Whole Brain Volume - All Patients Re-Baselined at 6 Months Vidofludimus calcium Placebo
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Vidofludimus Calcium Substantially Lowered Volume of New/Enlarging T2 Lesions Compared to Placebo | © Immunic, Inc. | Apr/30/202520 T2 lesion load: volume of lesions on T2 -weighted magnet ic resonance images; intent -to-treat population (all patients are analyze d as randomized) Estimates obtained from a random intercept, random slope mixed model, accounting for treatment effect and stratified by the r andomization strata (disease type and baseline EDSS score). The population slope within treatment group as change from baseline. For the primary estimand , data collected up to 30 days aft er the onset dat e of a post-baseline relapse or between the st art and 30 days after the end of any rescue medication intake w ere set to missing. Data after t reatment discontinuation was included in the analysis. ▪ Change of T2 lesion volume (cm³) gets steadily worse compared to baseline in placebo patients while remaining stable in vidofludimus calcium patients ▪ Volume change different between arms at every time point in the study Percent Change Vidofludimus Calcium -0.22% Placebo +2.97% Benefit Vidofludimus Calcium Over Placebo at Month 24 3.19% 2.97% -0.22% PlaceboVidofludimus Calcium
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Safety and Tolerability Top-Line Data Phase 2 CALLIPER Trial
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▪ No new safety signals identified ▪ Occurrence of TEAEs and SAEs with similar frequency in both treatment arms Top-Line Data Confirmed Favorable Safety and Tolerability Profile of Vidofludimus Calcium Observed in Previous Clinical Trials | © Immunic, Inc. | Apr/30/202522 TEAE: treatment-emergent adverse event; SAE: serious adverse event Safety Population contains any patient who received at least 1 dose of study drug, Vidofludimus calcium (N=235), Placebo (N=232), Total (N=467). All other SAE not listed had only single occurrences in the CALLIPER trial. Number of Patients With Any TEAE and SAE Vidofludimus Calcium N=235 Placebo N=233 Any TEAE, n(%) 163 (69.4) 159 (68.5) Any SAE n(%) 19 (8.1) 15 (6.5) Vidofludimus Calcium Placebo Total Urinary tract infection 161 152 313 Upper respiratory infection 57 49 106 Headache 16 42 58 Back pain 11 24 35 Fall 15 17 32 Five Most Common TEAE Events Most Common SAE Events (all SAE with total incidence >1) Vidofludimus Calcium Placebo Total Pyelonephritis 1 1 2 Femoral neck fracture 0 2 2 Femur fracture 0 2 2 Vertigo 2 0 2
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Commercial Background Top-Line Data Phase 2 CALLIPER Trial
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Huge Unmet Medical Need Exists in PPMS, An Underdiagnosed and Tougher to Treat Patient Population | © Immunic, Inc. | Apr/30/202524 PPMS: primary progressive multiple sclerosis; RMS: relapsing multiple sclerosis / Gross HJ, Watson C. NeuropsychiatrDis Treat. 2017;13:1349–1357; National Multiple Sclerosis Society website: https://www.nationalmssociety.org/understanding-ms/what-is-ms/types-of-ms/primary-progressive-ms; Patient numbers sourced via internal Immunic analysis and 2024 Multiple Sclerosis Landscape and Forecast report by Decision Resources Group Part of Clarivate; EU5 countries: France, Germany, Italy, Spain, and United Kingdom ▪ PPMS, which affects 10-15% of people diagnosed with MS , is characterized by a steady worsening of neurological function from the beginning of the disease, without distinct relapses or periods of remission ▪ Compared with RMS, PPMS is clinically associated with greater symptom severity and functional impairment, higher rates of unemployment and hospitalization, greater economic burden, and a more substantial impact on health-related quality of life ▪ ~120,000 patients diagnosed (US & EU5), of which only ~54,000 (45%) are currently treated by disease-modifying therapies ▪ Underdiagnosed and undertreated, due to lack of safe, effective and convenient treatments (only one approved therapy)
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Even With an Approved Therapy, Neurologists Still Identify New DMTs to Treat PPMS as an Area of High Unmet Need in MS | © Immunic, Inc. | Apr/30/202525 DMT: disease-modifying therapy; PPMS: primary progressive multiple sclerosis; SPMS: secondary progressive MS; aSPMS: active SPMS; RRMS: relapsing-remitting MS; PIRA: progression independent of relapse activity / Spherix Global Insights Realtime Dynamic Multiple Sclerosis report Q3 2024; quotes provided by participating neurologists “Always room for improved efficacy, particularly for primary progressive MS without safety/tolerability concerns.” “I would say that treatment of progressive MS is the biggest challenge. I don’t think there are any good treatments for secondary or primary progressive MS.” “We need a safe and effective oral treatment for PPMS.” 0% 10% 20% 30% 40% 50% 60% 70% 80% New DMTs for RRMS New DMTs for aSPMS New DMTs for naSPMS New DMTs for PPMS New products to treat PIRA MS Treating Neurologists (n=100) High Level of Unmet Needs for New DMTs % of respondents selecting high (8-10 on a 10-point scale)
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Currently Approved Therapy Does Not Address PPMS Patient Needs | © Immunic, Inc. | Apr/30/202526 PPMS: primary progressive multiple sclerosis / Garg H, Bush S, GappmaierE. Int J MS Care. 2016 Mar-Apr;18(2):71-7; Safety Monitoring of Disease-Modifying Therapies in Multiple Sclerosis: https://practicalneurology.com/diseases-diagnoses/ms-immune-disorders/safety- monitoring-of-disease-modifying-therapies-in-multiple-sclerosis/32085/#:~:text=Anti%2DCD20%20therapies%20require%20baseline%20CBC%20with%20differential,planning%20because%20of%20prolonged%20intervals%20between%20dosing Non-immunosuppressant mode of action: ▪ B-cell depletion significantly reduces the body's immune response, making patients more susceptible to various infections, including opportunistic ones.This is a major concern, particularly in PPMS where the disease course is progressive and immune system function is already potentially compromised. ▪ Vaccine responses are significantly blunted in patients on B-cell depleting therapies, adding to concerns with an age-dependent decreased immune response. Convenience: ▪ Patients with PPMS may experience difficulties with mobility and fatigue, making it hard to travel to and from infusion appointments. Lack of complex monitoring: ▪ Safety monitoring for anti-CD20 therapy involvesregular monitoring of immunoglobulin levels, vigilance for infusion reactions, and ongoing surveillance for potential opportunistic infections, particularly those associated with hypogammaglobulinemia.Routine laboratory monitoring includes CBC, CD19 count, IgG, IgM and HCG in women of childbearing age.
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Global Market for PPMS Treatment Estimated to Be $6+ Billion But Less Than Half of All Diagnosed Patients Are Treated Today | © Immunic, Inc. | Apr/30/202527 PPMS: primary progressive multiple sclerosis; DMT: disease-modifying therapy; K: thousand; B: billion / Patient and market size numbers sourced via internal Immunic analysis and 2024 Multiple Sclerosis Landscape and Forecast report by Decision Resources Group Part of Clarivate; EU5 countries: France, Germany, Italy, Spain, and United Kingdom; TD Cowen Therapeutic Categories Outlook Comprehensive Study – Multiple Sclerosis October 2024 ~120K diagnosed PPMS patients in the US & EU5 45% of diagnosed PPMS patients are currently on a DMT ~$2.7B in PPMS sales for the only approved product Total global market for PPMS estimated to be $6B+ and expected to grow with the approval and increased availability of new medicines
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Vidofludimus Calcium: Derisked Near-Term Opportunity With $3-7 Billion Peak Potential | © Immunic, Inc. | Apr/30/202528 Patient and market size numbers sourced via internal Immunic analysis and 2024 Multiple Sclerosis Landscape and Forecast report by Decision Resources Group Part of Clarivate RMS: relapsing MS; naSPMS: non-active secondary progressive MS; PPMS: primary progressive MS; Gd+: gadolinium-enhancing; CDW: confirmed disability worsening; K: thousand; B: billion Clinical Evidence Eligible Population Next Milestones Status Indication Potential Peak Sales RMS Phase 3 76% reduction in new Gd+ lesions (Phase 2) ~900K Phase 3 completion expected 2026 $1-2B naSPMS Phase 3-ready 15% relative risk reduction in 24-week CDW (Phase 2) ~175K End of phase 2 meeting with regulators TBD $1-2B PPMS Phase 3-ready 30% relative risk reduction in 24-week CDW (Phase 2) ~120K End of phase 2 meeting with regulators TBD $2-3B
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Designed to Combine the Best of Two Worlds: Neuroprotection and Relapse Prevention First-in-class, dual mode of action approach designed to address the full spectrum of disease: ▪ Nurr1 activation provides direct neuroprotective effects ▪ DHODH inhibition is associated with anti-inflammatory effects Oral DMT category: Aims for best-in-class benefit / risk profile by combining strong efficacy with safety, tolerability, and once-daily convenience No first-dose or on-treatment monitoring makes it an easy start or switch to therapy No anticipated black box warnings or serious infection risk (e.g., PML, malignancies, etc.) Vidofludimus Calcium Has the Potential to Transform the Oral Multiple Sclerosis DMT Market | © Immunic, Inc. | Apr/30/202529 DMT: disease-modifying therapy; Nurr1: nuclear receptor-related 1; DHODH: dihydroorotate dehydrogenase; PML: progressive multifocal leukoencephalopathy [1] Based on Immunic internal market research If approved, peak sales potential for vidofludimus calcium of $3-7 billion[1]
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Conclusions and Outlook Top-Line Data Phase 2 CALLIPER Trial
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“We are delighted about the phase 2 CALLIPER results showing that vidofludimus calcium outperformed historic trials in PPMS regarding numerical reduction of disability progression events.”
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CALLIPER Data Paves Way for Potential Registrational Study in PPMS | © Immunic, Inc. | Apr/30/202532 Data Impressively Confirms Main Objectives of this Exploratory Phase 2 Clinical Trial Achieved unprecedented proof of concept, in particular, regarding the key medical and future phase 3 endpoint of confirmed disability progression – not only for primary progressive multiple sclerosis but also for non-active secondary progressive multiple sclerosis Vidofludimus calcium addresses a $6+ billion market in PPMS, alone, where currently only one therapy is approved Results to be discussed with healthcare authorities to determine appropriate next steps for vidofludimus calcium in progressive multiple sclerosis, including potential application for breakthrough designation Market size numbers sourced via internal Immunic analysis
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Q&A Session Top-Line Data Phase 2 CALLIPER Trial
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Summary Top-Line Data Phase 2 CALLIPER Trial
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Positive Data from Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis | © Immunic, Inc. | Apr/30/202535 Reduced relative risk of 24wCDW by 20% in overall study population; even more prominent 30% reduction in high unmet need population of PPMS Remarkable 29% reduction of disability worsening in patients without baseline inflammatory lesions in overall study population Confirmed favorable safety and tolerability observed in previous clinical trials; no new safety signals identified Underlines Nurr1 activation as new mode of action for preventing neurodegeneration in MS and substantiates impact on disability accumulation by both PIRA and RAW As of April 2025, more than 375 patients continue to be treated in open-label extension phase of CALLIPER trial Further de-risks ongoing phase 3 ENSURE program with potential to offer relapsing MS patients an oral, safe and neuroprotective treatment early in the disease
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Study met primary and key secondary endpoints Open-label extension ongoing 2021 2022 2023 2024 2025 2026 20272019 2020 Vidofludimus Calcium: Clinical Trials Overview in Multiple Sclerosis (MS) | © Immunic, Inc. | Apr/30/202536 CDW: confirmed disability worsening;PPMS: primary progressive multiple sclerosis; naSPMS: non-active secondary progressive multiple sclerosis Today EMPhASIS Phase 2 RELAPSING MS Actively recruiting, n=1050 patients planned ENSURE-1 Phase 3 Q2/2026 Completion (expected) RELAPSING MS Actively recruiting, n=1050 patients planned ENSURE-2 Phase 3 H2/2026 Completion (expected) PROGRESSIVE MS Reduced CDW in PPMS and naSPMS CALLIPER Phase 2 RELAPSING- REMITTING MS Open-label extension ongoing
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Thank You! | © Immunic, Inc. | Apr/30/202537 Immunic, Inc. 1200 Avenue of the Americas New York City, NY 10036 USA Immunic AG Lochhamer Schlag 21 82166 Gräfelfing(Munich) Germany Immunic Australia Pty. Ltd. Melbourne Australia Jessica Breu Vice President Investor Relations & Communications Phone: +1-332-255-9819 Email: ir@imux.com Web: www.imux.com
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Back-up Top-Line Data Phase 2 CALLIPER Trial
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Large Proportion of Patients With Non-Active Disease as Compared to Historical Studies | © Immunic, Inc. | Apr/30/202539 PMS: progressive multiple sclerosis; PPMS: primary PMS; naSPMS: non-active secondary PMS; aSPMS: active secondary PMS; nrSPMS: non-relapsing secondary PMS; Gd+: gadolinium-enhancing *Fox R.J., Bar-Or A., TraboulseeA. et al., Presented at: 2024 ECTRIMS; September 18-20; Copenhagen, Denmark. Abstract 4027 **Kappos L. et al., EXPAND Clinical Investigators. Lancet. 2018 Mar 31;391(10127):1263-1273 ***Clinical Review Report: Ocrelizumab (Ocrevus): (Hoffmann-La Roche Limited): Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 May. Results. Available from: https://www.ncbi.nlm.nih.gov/books/NBK533357/ CALLIPER PPMS ORATORIO PPMS*** CALLIPER naSPMS EXPAND a/naSPMS** HERCULES nrSPMS* Gd+ at Screening 17.8% 22.4% 6.8% 21% 12.6% On-Study Relapses 3.3% (5/152) 16% 7.1% (19/268) 19% Not reported Relapses Within 24 Months Prior to Study Entry 0% 0% 0% 64% 0%
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Comparison of Patient Characteristics for CALLIPER Trial Versus ORATORIO Trial in the PPMS Population | © Immunic, Inc. | Apr/30/202540 * Clinical Review Report: Ocrelizumab (Ocrevus): (Hoffmann-La Roche Limited): Indication: Management of adult patients with early primary progressive multiple sclerosis as defined by disease duration and level of disability, in conjunction with imaging features characteristic of inflammatory activity [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 May. Results. Available from: https://www.ncbi.nlm.nih.gov/books/NBK533357/ PPMS: primary progressive multiple sclerosis; VidoCa: vidofludimus calcium; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing lesions found on T1-weighted MRI images; MRI: magnetic resonance imaging ORATORIO* CALLIPER Ocrelizimab Placebo Vidofludimus Calcium Placebo (N=488) (N=244) (N=77) (N=75) Mean Age (Years) 44.7 44.4 47.3 45.3 Female (N,%) 237 (48.6%) 124 (50.8%) 51 (66.2%) 42 (56.0%) EDSS - Mean 4.7 4.7 4.9 4.9 EDSS - Median 4.5 4.5 4.5 4.5 Gd+ Lesions at Baseline MRI (N,%) 27.5% 24.7% 15.6% 20.0%
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Comparison Patient Characteristics for CALLIPER Trial Versus Other Studies in the Non-Active/Non-Relapsing SPMS Population | © Immunic, Inc. | Apr/30/202541 * Fox R.J., Bar-Or A., TraboulseeA. et al., Presented at: 2024 ECTRIMS; September 18-20; Copenhagen, Denmark. Abstract 4027 SPMS: secondary progressive multiple sclerosis; VidoCa: vidofludimus calcium; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing lesions found on T1-weighted MRI images; MRI: magnetic resonance imaging HERCULES 3* CALLIPER Tolebrutinib Placebo Vidofludimus Calcium Placebo (N=754) (N=377) (N=135) (N=133) Mean Age (Years) 48.9 48.9 51.3 50.9 Female (N,%) 454 (60.2%) 242 (64.2%) 85 (63.0%) 93 (69.9%) EDSS - Mean 5.49 5.59 5.35 5.35 EDSS - Median 6.0 6.0 6.0 6.0 Gd+ Lesions at Baseline MRI (%) 12.5% 13.1% 7.4% 6.0%
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Vidofludimus Calcium Reduced Relative Risk of 24wCDW in Overall Study Population and Subtypes Compared to Placebo | © Immunic, Inc. | Apr/30/202542 Based on intent-to-treat population (ITT), patients are analyzed as randomized; 24wCDW: 24-week confirmed disability worsening;naSPMS: non-active secondary progressive multiple sclerosis; PPMS: primary progressive multiple sclerosis 24-week confirmed disability worsening based on EDSS scale (24wCDW), total of 85 events in the intent-to-treat population of CALLIPER trial Data displayed for the reduction of risk of occurrence of 24wCDW events, percentages refer to the rate of 24wCDW in each of the treatment arms per disease subtype. Disease subtype as per investigator diagnosis at screening. Proportion of Patients With 24wCDW Events Overall CALLIPER Patient Population PPMS naSPMS Vidofludimus Calcium 16.2% (38/235) 19.5% (15/77) 14.1% (19/135) Placebo 20.3% (47/232) 28.0% (21/75) 16.5% (22/133) Relative Risk Ratio for 24wCDW 0.80 0.70 0.85 Relative Risk Reduction for 24wCDW 20% 30% 15%
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Relative Risk Reduction of 24wCDW Events Shows Similar Performance in Various Non-Active Patient Subpopulations | © Immunic, Inc. | Apr/30/202543 Based on intent-to-treat population (ITT), patients are analyzed as randomized; 24wCDW: 24-week confirmed dis ability worsening;naSPMS: non-active secondary progress ive multiple sclerosis; PPMS: primary progressive multiple s clerosis 24-week confirmed dis ability worsening based on EDSS scale (24wCDW), total of 85 events in the intent-to-treat population of CALLIPE R trial. Data displayed for the reduction of risk of occurrence of 24wCDW events, percentages refer to the rate of 24wCDW in each of the treatment arms per disease subtype. Disease subtype as per investigator diagnosis at screening. Non-active disease: no study relapses, no Gd+ lesions at baseline or during study, no new or enlarging T2 lesions during s tudy. No Gd+ lesions at baseline: in addition to no relapses in 24 months prior to s tudy entry (as required by inclus ion criteria).Non-relapsing population: no on-study relaps es, in addition to no relapses in 24 months prior to study entry (as required by inclusion criteria) Proportion of Patients With 24wCDW Events Overall CALLIPER Patient Population Non-Active Disease No Gd+ Lesions at Baseline Non-Relapsing Population Vidofludimus Calcium 16.2% (38/235) 12.1% (15/124) 14.2% (28/197) 14.4% (32/222) Placebo 20.3% (47/232) 16.2% (18/111) 20.1% (39/194) 17.4% (38/218) Relative Risk Ratio for 24wCDW 0.80 0.75 0.71 0.83 Relative Risk Reduction for 24wCDW 20% 27% 29% 17% Provides Further Evidence for the Potential Neuroprotective Effects of Vidofludimus Calcium
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Vidofludimus Calcium Reduces Gadolinium-Enhancing Lesions During Study Period | © Immunic, Inc. | Apr/30/202544 ITT = intent-to-treat analysis set; Gd+ = gadolinium-enhancing (in magnetic resonance imaging examinations); PPMS = primary progressive multiple sclerosis; SPMS = secondary progressive multiple sclerosis; a: active; na: non-active; N = total number of patients in the treatment group and analysis set; n = number of patients in the corresponding category and treatment group Percentages for subcategories of Disease Type are calculated based on total number of patients in the corresponding disease type and treatment group. Disease subtypes are based on investigator diagnosis at screening visit. Number of Patients with Gd+ Lesions Overall CALLIPER Study Population PPMS a/naSPMS Vidofludimus Calcium 6.4% 5.2% 7.0% Placebo 10.8% 12.0% 10.2% Relative Risk Ratio 0.59 0.43 0.69 Relative Risk Reduction 41% 57% 31%