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Immunic Therapeutics Developing Selective Oral Therapies in Immunology NASDAQ: IMUX | November 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. | November 20252
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Large commercial opportunity: $3-7 billion peak sales potential for vidofludimus calcium in MS Financials: Cash balance of $35.1 million as of September 30, 2025 Experienced leadership team: Successfully developed and commercialized multiple medicines Positive MS phase 2 data sets: Underline neuroprotective effect of Nurr1 activation by vidofludimus calcium Innovative pipeline: First-in-class oral drugs with unique modes of actions for multiple sclerosis and gastrointestinal diseases LATE-STAGE BIOTECHNOLOGY COMPANY (NASDAQ: IMUX) Dedicated to improving the lives of patients with chronic inflammatory and autoimmune diseases
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Leadership Team Company is Led by an Experienced Management Team | © Immunic, Inc. | November 20254 Andreas Muehler , MD, MBA Chief Medical Officer Hella Kohlhof, PhD Chief Scientific Officer Jason Tardio, MBA President & Chief Operating Officer Daniel Vitt, PhD Chief Executive Officer Glenn Whaley, CPA Chief Financial Officer Patrick Walsh Chief Business Officer Inderpal Singh General Counsel Werner Gladdines Chief Development Officer Duane Nash, MD, JD, MBA Executive Chairman
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Advanced Clinical Pipeline Well Differentiated Programs in Various Phases of Clinical Development | © Immunic, Inc. | November 20255 Program Preclinical Phase 1 Phase 2 Phase 3 Key Program Updates Vidofludimus Calcium (IMU-838)* ✓ Phase 2 EMPhASIS trial in RRMS successfully completed, significantly reduced brain lesions, encouraging results in reducing disability worsening ✓ Interim analysis of ENSURE program completed, IDMC recommendation to continue trials as planned, both ENSURE trials fully enrolled ✓ CALLIPER trial successfully completed, substantial reductions in disability worsening ✓ Phase 2 CALDOSE -1 trial in UC completed, effective in 50 weeks maintenance phase ▪ Top-line data for both ENSURE trials expected by end of 2026 Relapsing Multiple Sclerosis (RMS) – ENSURE-1 and ENSURE-2 Trials Progressive Multiple Sclerosis (PMS) – CALLIPER Trial Ulcerative Colitis (UC) – CALDOSE-1 Trial IMU-856 ✓ Phase 1/1b trial in healthy volunteers and celiac disease completed, first proof -of-concept in celiac disease ✓ Dose-dependent increase of endogenous GLP -1 in post hoc analysis of phase 1b trial in celiac disease ▪ Further clinical testing in preparation Celiac Disease and other Gastrointestinal Disorders IMU-381 Gastrointestinal Diseases Ongoing In preparation or plannedCompleted RRMS: relapsing-remitting multiple sclerosis; IDMC: Independent Data Monitoring Committee; GLP-1: glucagon-like peptide-1 *Additional investigator-sponsored phase 2 RAPID_REVIVE trial of vidofludimus calcium in post COVID syndrome ongoing, sponsored by University Hospital Frankfurt
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Targeted to Elevate the Standard of Care for the Full Spectrum of Multiple Sclerosis Patients Vidofludimus Calcium in Multiple Sclerosis (MS)
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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. | November 20257 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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Regardless of the Subtype, the Outcome of Every Patient Journey in Multiple Sclerosis Is Physical and/or Cognitive Disability | © Immunic, Inc. | November 20258 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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“Invisible” Disability Progression Over Time Requires a Neuroprotective Mode of Action Approach | © Immunic, Inc. | November 20259 One stage model of MS [1]: ▪ All patients exhibit progressive components from disease onset ▪ Can be overlapped by relapsing components in the early phases To address this, new treatments should: ▪ Have a significant impact on relapses and focal MRI activity ▪ Reduce RAW ▪ Tackle processes responsible for smoldering MS/PIRA Graphic adapted from Kretzschmar A., Symposium MSVirtual2020 / 8th Joint ACTRIMS-ECTRIMS Meeting and REVIEW article, Front. Immunol., 29 November 2023, Sec. Multiple Sclerosis and Neuroimmunology, Volume 14 – 2023 [1] Scalfari A. Mult Scler. 2021 Jun;27(7):1002-1004 / MRI: magnetic resonance imaging; Nurr1: nuclear receptor-related 1; DHODH: dihydroorotate dehydrogenase; MS: multiple sclerosis Relapses & MRI lesions / focal inflammation (RAW) Smoldering disease and neurodegeneration (PIRA) Disability Time focal inflammation PIRA (progression independent of relapse activity) RAW (relapse-associated worsening) DHODH inhibition Nurr1 activation
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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. | November 202510 DMT: disease-modifying therapy; MS: multiple sclerosis; RRMS: relapsing-remitting MS; SPMS: secondary progressive MS; aSPMS: active SPMS; MRI: magnetic resonance imaging; DHODH: dihydroorotate dehydrogenase; Nurr1: nuclear receptor-related 1; RAW: relapse-associated worsening; PIRA: progression independent of relapse activity Relapsing MS (RMS) Progressive MS (PMS) DHODH Inhibition Nurr1 Activation Relapses and focal inflammation (RAW) Smoldering disease and neurodegeneration (PIRA) Non-Active SPMS
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A Large and Growing Global Market Where Multiple Blockbusters Coexist | © Immunic, Inc. | November 202511 [1] Company public filings [2] Sales numbers in G7 countries (US, UK, Canada, Japan, Germany, France, Italy) in USD billion; Multiple Sclerosis Landscape and Forecast by Decision Resources Group Part of Clarivate 0 5 10 15 20 25 30 35 2024 2025 2026 2027 2028 2029 2030 2031 2032 $20 billion market today growing 4% y/y [2] Major market sales of MS therapies($ billion) United States Many brands are generating in excess of $1 billion in global annual sales in 2024[1] Ocrevus® $7.6 billion Kesimpta® $3.2 billion Tysabri® $1.7 billion Tecfidera® & Vumerity® $1.6 billion Mavenclad® $1.15 billion Avonex® & Plegridy® $968 million Rebif® $626 million Gilenya® $552 million Aubagio® $379 million Briumvi® $310 million
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Oral DMTs Will Continue to Play a Big Role as Important Treatment Options | © Immunic, Inc. | November 202512 While anti-CD20 class of therapies continues to grow, oral class still expected to capture over 1/3 of the global market ▪ 42% of patients prefer oral medicines [2] ▪ Early-line reliance on injectable therapies will continue to wane as the market shifts to using oral therapies earlier ▪ 15% of patients with PPMS and 25% of patients with non-active SPMS received oral treatments (off label) [3] Global Market Share by Drug Class 2022 vs. 2032[1] 39% 21% 9% 31% 38% 7% 13% 42% 2022 2032 Orals Injectables Infusions [1] Sales numbers in G7 countries (US, UK, Canada, Japan, Germany, France, Italy) in USD billion; 2024 Multiple Sclerosis Landscape and Forecast by Decision Resources Group Part of Clarivate. [2] Jonker MF, et al. Med Decis Making. 2020 Feb;40(2):198-211 [3] Watson C, et al. Neurol Ther. 2023 Dec;12(6):1961-1979 / DMT: disease-modifying therapy; CD20: B lymphocyte cell-surface molecule; SPMS: secondary progressive MS; PPMS: primary progressive MS Anti-CD20
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Multiple MS Patient Segments Could Benefit from Vidofludimus Calcium | © Immunic, Inc. | November 202513 MS: multiple sclerosis; naSPMS: non-active secondary progressive MS; PPMS: primary progressive MS Patients switching therapies due to progression Untreated patients Newly diagnosed patients Older patients where immuno- suppression is a concern Patients with progressive disease (naSPMS & PPMS) Patients switching off anti-CD20 therapies due to safety concerns
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Vidofludimus Calcium: Derisked Near-Term Opportunity With $3-7 Billion Peak Potential | © Immunic, Inc. | November 202514 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 Patients Treated Status Indication Potential Peak Sales RMS Phase 3 78% reduction of new Gd+ lesions (Phase 2) ~900K ~525K $1-2B naSPMS Phase 3-ready 19% reduction of 24-week CDW (Phase 2) ~175K ~65K $1-2B PPMS Phase 3-ready 31% reduction of 24-week CDW (Phase 2) ~120K ~54K $2-3B
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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. | November 202515 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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First-in-Class, Potent Nurr1 Activator and Selective DHODH Inhibitor Vidofludimus Calcium in Multiple Sclerosis (MS)
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First-in-Class Nurr1 Activator ▪ Direct and indirect neuroprotective effects ▪ Involved in protecting relevant neurons from cell death ▪ Known effects reducing activation of microglia and astrocytes ▪ Effect independent from focal inflammation Selective DHODH Inhibitor ▪ Selectively targets hyperactive immune cells ▪ Selective anti-inflammatory effects, reducing focal inflammation, magnetic resonance imaging lesions and relapses ▪ Broad-spectrum antiviral effects prevent reactivation of EBV and could stop cross reactive immune responses First-in-Class Nurr1 Activator, Targeting Improvement of Physicaland Mental Ability of Multiple Sclerosis Patients Vidofludimus Calcium Addresses Smoldering Neurodegeneration 17 Nurr1: nuclear receptor-related 1; DHODH: dihydroorotate dehydrogenase; EBV: Epstein-Barr virus | © Immunic, Inc. | November 2025
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Gene Expression Regulation Improves Neuronal Survival Vidofludimus Calcium Activates Nurr1, Shown to Increase Neuronal Survival | © Immunic, Inc. | November 202518 [1] Vietor et al., Journal of Medicinal Chemistry2023 66 (9), 6391-6402 The related research project was funded by the German Federal Ministry of Education and Research under the grant number 03INT607AA; Structure: Zhao, M.et.al. (2022)Proc Natl Acad Sci USA 119; [2] Sun, Zuoming. City of Hope. 2023, unpublished [3] Unpublished data: Sun lab, City of Hope, Duarte; 2023/ Nurr1: nuclear receptor-related 1; DNA: deoxyribonucleic acid; VMAT2: vesicular monoamine transporter 2; DMSO: dimethyl sulfoxide; TNF: tumor necrosis factor Nurr1 is a transcription factor binding to DNA[1] Vidofludimus calcium binds to and strongly activates Nurr1 activity with nM values Vidofludimus calcium induces a > 2-fold induction of target gene expression of VMAT2 at 30 nM concentration[2] Vidofludimus calcium improves neuronal survival via Nurr1 activation[3] Nurr1 Binding Relative hVMAT2 Vidofludimus Calcium [µM] Human microglia cells (HMC3) 1 100 N2A cells Improved neuronal survival (%) Vidofludimus Calcium [µM]: TNFα + CHX
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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. | November 202519 CDW: confirmed disability worsening;PPMS: primary progressive multiple sclerosis; naSPMS: non-active secondary progressive multiple sclerosis Today EMPhASIS Phase 2 RELAPSING MS Fully enrolled, n=1121 patients ENSURE-1 Phase 3 RELAPSING MS Fully enrolled, n=1100 patients ENSURE-2 Phase 3 Top-Line Data Expected End of 2026 for both ENSURE trials PROGRESSIVE MS Reduced CDW in PPMS and naSPMS CALLIPER Phase 2 RELAPSING- REMITTING MS Open-label extension ongoing
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Development in Relapsing Multiple Sclerosis (RMS) Vidofludimus Calcium in Multiple Sclerosis (MS)
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Goals for New Relapsing Multiple Sclerosis Treatments Vidofludimus Calcium Could be the First Treatment Option for Relapsing MS Fulfilling the Current Unmet Needs of Patients | © Immunic, Inc. | November 202521 ▪ Developing a new therapy offering: − Neuroprotection and effect on progression independent of relapse activity (PIRA) − Excellent safety and tolerability − Easy to use, convenient oral administration without complex screening requirements ▪ Developing a new therapy for newly diagnosed patients and as an excellent switch opportunity Unmet Medical Need High Low Low Progression Independent of Relapse Activity (PIRA) Relapse Associated Worsening (RAW) High Currently approved therapies, mainly targeting relapses
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EMPhASIS: Completed Phase 2 Trial in Relapsing-Remitting MS NCT03846219 | © Immunic, Inc. | November 202522 MS: multiple sclerosis; QD: quaque die = once-daily; MRI: magnetic resonance imaging; NfL: neurofilament light chain Coordinating Investigator Robert J. Fox, M.D. Cleveland Clinic Trial Met Key Efficacy and Safety Endpoints ▪ Randomized 268 patients in 36 centers across four European countries ▪ Vidofludimus calcium showed strong activity in relapsing- remitting MS population − Primary and key secondary endpoints met with high statistical significance: strong reduction of MRI lesion activity − Reduced serum NfL concentrations − Signal in preventing confirmed disability worsening ▪ Vidofludimus calcium’s safety profile was similar to placebo − No general safety signals observed − Low discontinuation rates, considerably lower than placebo Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Trial ▪ Blinded main treatment period of 24 weeks ▪ Cohort 1: 30 and 45 mg or placebo QD ▪ Cohort 2: 10 mg or placebo QD ▪ Extended treatment period of up to 9.5 years ongoing to observe long-term safety is ongoing
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EMPhASIS: Strong Reduction of MRI Lesion Activity Primary Endpoint Hit With High Statistical Significance, Pooled Cohorts 1 & 2 | © Immunic, Inc. | November 202523 As Cohort 2 only allowed MRI machines of 1.5T, pooled data of Cohorts 1 & 2 only include patients that were evaluated at MRI field strength of 1.5 T es la. Modified full analysis set C1/C2 (N10 = 47, N30 = 65, N45 = 66, NPBO C1 = 59, NPBO C2 = 12) Data displayed are as adjusted mean values. Estimates are adj usted for baseline volume of T2 lesions and baseline number of Gd+ lesions (0, >=1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first investigational medicinal product (IMP) dose to date of last MRI assessment with non-miss ing values is used as offset term / RRMS: relapsing-remitting multiple sclerosis; MRI: magnetic resonance imaging; CUA: cumulative unique active, Gd+: gadolinium-enhancing Reduction in Cumulative CUA Lesions up to Week 24 Reduction in Gd+ Lesions up to Week 24 0 0 -76% -71% -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 3 4 5 6 7 Placebo 10 mg IMU-838 30 mg IMU-838 45 mg IMU-838 Cumulative CUA Lesions Lesion Reduction in % 0 -13% -78% -74% -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Placebo 10 mg IMU-838 30 mg IMU-838 45 mg IMU-838 Cumulative Gd+ Lesions Lesion Reduction in % Primary and key secondary endpoints of cumulative number of new CUA lesions up to week 24 met with high statistical significa nce (primary 45 mg vs. placebo: p = 0.0002 / key secondary 30 mg vs. placebo: p < 0.0001)
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EMPhASIS: Reduction of Serum NfL Concentrations Observed Versus Placebo After 24 Weeks, Pooled Cohorts 1 & 2 | © Immunic, Inc. | November 202524 Vidofludimus calcium showed remarkable reduction in NfL levels in all active doses tested compared with placebo ▪ Clear dose-response relationship in NfL reduction ▪ Higher doses expected to show stronger neuroprotective effects Displayed are median values of differences between percentage change of serum neurofilament light chain concentration (Hodges-Lehmann estimation), treatment vs. placebo Data shows 10 mg versus placebo for Cohort 2 and 30/45 mg versus placebo for Cohort 1; NfL: neurofilament light chain 50% -50% -18% -26% -9% 30 mg IMU-838 45 mg IMU-83810 mg IMU-838
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EMPhASIS: Reduced Confirmed Disability Worsening Events End of 24-Week Blinded Treatment Period | © Immunic, Inc. | November 202525 ▪ Signal in preventing 12-week and 24-week confirmed disability worsening events as compared to placebo ▪ Confirmatory data will be obtained in phase 3 ENSURE clinical program CDW: confirmed disability worsening; EDSS: Expanded Disability Status Scale Only disability worsenings with a trigger point during the 24 -wek blinded treatment period are considered. The EDSS increases during the blinded treatment phase were subsequently confirmed during open -label extension phase of t he trial. Pat ients at risk in this analysis are 187 for vidofludimu s calcium (pooling 10, 30 and 45 mg data) and 81 for placebo. The trigger event is an EDSS progression defined as an increase in t he EDSS compared to Baseline of at least 1.5 poi nts if Baseline EDSS = 0, of at least 1.0 points if Baseline EDSS of 1 -5, or of at least 0.5 points if Baseline EDSS ≥ 5.5 12-week CDW: The confirmat ion event is at least 77 days after the trigger event. At the confirmation event and each assessment b etween trigger and possible confirmation event, EDSS must be at least as high as at the trigger event. 24-week CDW is are defined analogously, the only difference being the time interval between t rigger event and confirmation visit , which is at least 161 days. Full analysis set pooled cohorts 1&2 (N10 = 47, N30 = 71, N45 = 69, NPBO C1 = 69, NPBO C2 = 12) 1.6% 3.7% 1.6% 3.7% 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% 3.5% 4.0% Vidofludimus Calcium Placebo CDW Events at the End of the 24 -Week Blinded Treatment Period 12-Week CDW 24-Week CDW
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EMPhASIS: Low Rates of Confirmed Disability Worsening Events Open-Label Extension Period, 196 Patients Reaching 144 Weeks of Treatment | © Immunic, Inc. | November 202526 ▪ At week 144, 92.3 % of patients remained free of 12-week CDW ▪ 29 CDW events confirmed at 12 weeks following trigger event through week 144 ▪ Of these, 13 events (44.8%) defined as relapse-associated worsening (RAW), while only 4 (13.8%) as progression independent of relapse activity (PIRA) ▪ Low discontinuation rate with 196 out of 254 patients reaching 144 weeks of OLE treatment ▪ More than 180 patients still in the OLE phase of the EMPhASIS trial* ▪ Vidofludimus calcium continued to demonstrate favorable safety and tolerability profile CDW: confirmed disability worsening; OLE: open-label extension; * as of January 2025 100.0% 98.0% 97.2% 94.6% 93.3% 93.3% 92.3% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 24 48 72 96 120 144 % Patients Free of 12wCDW Events Weeks of Open -Label Extension Treatment Proportion of patients free of 12-week confirmed disability worsening after up to 144 weeks of open-label extension vidofludimus calcium treatment
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5.8% 12.4% at 108 weeks 15.0% KM estimates 9.1% 10.9% KM estimates 10.1% at 108 weeks 13.6% 0% 5% 10% 15% 20% EMPhASIS: 12-Week Confirmed Disease Worsening After 2 Years Interim Analysis Open-Label Extension Period Compared to Select Historical Trials | © Immunic, Inc. | November 202527 The trigger event is any EDSS progression during the open-label extension (OLE) period defined as an increase in the EDSS compared to start of the OLE period (Baseline) of at least 1.5 points if Baseline EDSS = 0, of at least 1.0 points if Baseline EDSSof 1-5, or of at least 0.5 points if Baseline EDSS ≥ 5.5. Patients with RRMS at risk in this EMPhASIS analysis are 158 at 96 weeks. Data cut-off was Oct 16, 2022. This includes all patients randomized to either placebo or any dose of vidofludimus calcium during the 24-week blinded treatment period and then continued with open-label treatment with either 30 mg or 45 mg vidofludimus calcium. Survival rates and times estimated by the Kaplan-Meier method. 95% CI for rates based on Greenwood's formula.; 12-week CDW: The confirmation event is at least 77 daysafter the trigger event. At the confirmation event and each assessment between trigger and possible confirmation event, EDSS must be atleast as high as at the trigger event.; 24-week CDW is are defined analogously, the only difference being the time interval between trigger event and confirmation visit, which is at least 161 days.; KM: graphical estimates from published Kaplan-Meier curves; EDSS: Expanded Disability Status Scale; RRMS: relapsing-remitting multiple sclerosis. All trials performed in RRMS. Vidofludimus Calcium: Immunic data; OPTIMUM: Kappos et al. 2021; ASCLEPIOS: Hauser et al. 2020; OPERA: Hauser et al. 2017 RRMS patients with 12-week (3-months) confirmed disability worsening after 2 Years (96 Weeks) (% of patients at risk) Vidofludimus Calcium Interferon-1aOcrevus® Ponvory®Kesimpta® ASCLEPIOSOPERA OPERAOPTIMUMEMPhASIS Aubagio® OPTIMUM ASCLEPIOS
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Vidofludimus Calcium: Unrivaled Safety and Tolerability Profile Observed in Multiple Clinical Trials | © Immunic, Inc. | November 202528 PML: progressive multifocal leukoencephalopathy ▪ Safety profile similar to placebo: no general safety signals observed in clinical trials so far ▪ No increased rates of diarrhea, neutropenia, or alopecia ▪ No increased rates of infections and infestations or hematology values ▪ Drug exposure tested in approximately 2,700 human subjects and patients, to date, with data available up to 5.5 years ▪ Low rates of adverse events ▪ No signals for hepatotoxicity or elevations of liver enzymes and no Hy’s law cases observed to date PML risk Increased number of infections Vaccination limitations Gastrointestinal toxicities, incl. diarrhea Cardiovascular risks, incl. blood pressure Lymphopenia Neutropenia Risk of liver injury Increased risk of cancer Macular edema Vidofludimus Calcium ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ Favorable profile Vidofludimus Calcium’s Safety Profile to Date is Unique
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EMPhASIS: Vidofludimus Calcium Well-Tolerated With Adverse Events Similar to Placebo | © Immunic, Inc. | November 202529 The observed adverse events were generally mild in nature. There were very few adverse events with medium and high incidence rate. Safety & Tolerability Endpoints Placebo Vidofludimus Calcium 30 mg Vidofludimus Calcium 45 mg Any treatment -emergent adverse event 44% 45% 41% Treatment-emergent adverse events occurring in >5% of total patients by preferred term Headache 6% 4% 6% Nasopharyngitis 4% 4% 7% Treatment-emergent adverse events occurring in 2% -5% of total patients by preferred term Upper respiratory tract infection 4% 3% 0% Viral respiratory tract infection 4% 0% 3% Treatment-emergent adverse events occurring in >1 to <2% of total patients by preferred term Back pain 3% 1% 0% ALT increase 3% 1% 0% Influenza 3% 0% 1% Liver enzymes elevated 1% 1% 3% Nausea 1% 1% 3% Bronchitis 1% 0% 3% Alopecia 0% 4% 1% Fatigue 0% 3% 3% Rash 0% 3% 3% Cystitis 0% 1% 4% Treatment-emergent adverse events by severity Mild 33% 41% 30% Moderate 12% 16% 23% Severe 1% 0% 0% Series adverse events 1% 3% 0% Treatment discontinuation for any reason 7% 3% 6% Treatment-emergent adverse events leading to treatment discontinuation 4% 0% 3%
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Reflected in Low Discontinuation Rates for Vidofludimus Calcium-Treated RRMS Patients, Considerably Lower Than Placebo* EMPhASIS: Patients Feel Well-Treated With Vidofludimus Calcium | © Immunic, Inc. | November 202530 *The table summarizes the data on treatment/study discontinuation rates of the commercial dose in phase 2 trials of RRMS drugs. If the commercial dose was not included in the phase 2 trials, the dose closest to the commercial dose was shown. This high-level comparison is provided for illustrative purposes only, is based on publicly available data and does not purport to be a comprehensive comparison or depiction of the other trials. Larger data sets than presented in this presentation are publicly available for certain of the compounds included on this slide. Please note that these results are taken from placebo-controlled trials, and these medications have not been tested in head-to-head assessments. [1] Comi et al. Ann Neurol. 2001;49(3):290-297 [2] O'Connor et al. Neurology. 2006;66(6):894-900 [3] Kappos et al. Lancet. 2008;372(9648):1463-1472 [4] Kappos et al. N Engl J Med. 2006;355(11):1124-1140 [5] Cohen JA, Arnold DL, Comi G, et al. Lancet Neurol. 2016;15(4):373- 381; QD: quaque die = once-daily; TID: ter in die = three times daily; RRMS: relapsing-remitting multiple sclerosis Vidofludimus Calcium Glatiramer Acetate [1] Aubagio® [2] Tecfidera® [3] Gilenya® [4] Zeposia® [5] Administration Oral Injectable Oral Oral Oral Oral Daily Dose 30 mg QD 20 mg QD 14 mg QD 240 mg TID 1.25 mg QD 1 mg QD Treatment Period 24 weeks 9 months 36 weeks 24 weeks 6 months 24 weeks Active Treatment 2.8% 5.9% 19.3% 15.6% 5.4% 2.3% Placebo 7.2% 5.8% 6.6% 9.2% 6.5% 3.4%
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ENSURE: Ongoing Pivotal Phase 3 Trials in Relapsing MS NCT05134441 & NCT05201638 | © Immunic, Inc. | November 202531 [1] Lublin FD, et al. Neurology. 2014;83(3):278-286 MS: multiple sclerosis; EDSS: Expanded Disability Status Scale; QD: quaque die = once-daily IDMC: Independent Data Monitoring Committee; N: number of patients Coordinating Investigator Robert J. Fox, M.D. Cleveland Clinic Two Multicenter, Randomized, Double-Blind Phase 3 Trials ▪ More than 100 sites in 15 countries in each trial, including the United States, India, Middle East and North Africa, Latin America, Central and Eastern Europe ▪ Randomization to 30 mg vidofludimus calcium or placebo QD ▪ Positive interim analysis: Unblinded IDMC recommended continuing trial without changes, including no need for a potential upsizing ▪ Enrollment completed: 1,121 patients in ENSURE-1; 1,100 patients in ENSURE-2 ▪ T op-line data for both ENSURE trials expected by end of 2026 Included Patient Population: Relapsing Forms of MS ▪ Adult patients aged 18 to 55 years ▪ Established diagnosis of MS (revised McDonald criteria 2017) ▪ Confirmed relapsing MS (1996 Lublin criteria[1]) ▪ Active disease as defined by Lublin 2014 ▪ EDSS score at screening between 0 to 5.5 ENSURE-1: Vidofludimus Calcium vs. Placebo ENSURE-2: Vidofludimus Calcium vs. Placebo Primary Endpoint: Time to First Relapse Primary Endpoint: Time to First Relapse Pooled Secondary Endpoints Including Confirmed Disability Progression Placebo Vidofludimus CalciumN=525 N=525 72 Weeks Placebo Vidofludimus CalciumN=525 N=525 72 Weeks
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Development in Progressive Multiple Sclerosis (PMS) Vidofludimus Calcium in Multiple Sclerosis (MS)
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Huge Unmet Medical Need Exists in PPMS, An Underdiagnosed and Tougher to Treat Patient Population | © Immunic, Inc. | November 202533 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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CALLIPER: Phase 2 Clinical Trial in Progressive Multiple Sclerosis NCT05054140 | © Immunic, Inc. | November 202534 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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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) 24.85 [14.0 - 46.6] SDMT [points], median (min-max) 40 [8-80] EDSS at Visit 1, median (min-max) 5.5 [2.5-6.5] MS relapses during last 24 months, median (min-max) 0.0 [0-1] Gd+ lesions at baseline MRI (%) 16.3% Treatment duration, median 589 days Progressive Disease Subtypes Baseline Characteristics CALLIPER: Patient Demographics and Baseline Characteristics Total Study Population of 467 Enrolled Patients | © Immunic, Inc. | November 202535 Baseline characteristics initially assess ed by the investigators when patients entered s creening based on history. These datasummarize the disease subtype as as sessed per diagnosis at screening visit 1. A small number of patients changed their subtype (in particular from non-active to active disease) due to events during the s creening period. Definition non-active SPMS (according to CALLIPE R protocol): no evidence of relapse in the last 24 months before randomization, AND patients s howing no evidence of Gd+ MRI les ions in the brain or spinal cord in the last 12 months; definition non-relapsing SPMS: no evidence of relapse in the last 24 months before randomization / BMI: body mass index; SDMT: Symbol Digit Modalities Test; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing; M RI: magnetic resonance imaging; N: number of patients evaluated T otal N=467
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Clinically meaningful risk reduction of confirmed disability worsening of 24% in overall PMS population and even more prominent 31% reduction in PPMS population CALLIPER successfully demonstrated the neuroprotective potential of vidofludimus calcium in PMS patients
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CALLIPER: Vidofludimus Calcium Reduced Time to 24wCDW in Overall Study Population and All Subtypes Compared to Placebo | © Immunic, Inc. | November 202537 24wCDW: 24-week confirmed dis ability worsening; tt: time to; PPMS: primary progressive multiple sclerosis; naSPMS: non-active secondary progress ive multiple sclerosis; aSPMS: active secondary progress ive multiple sclerosis; HR: hazard ratio; CI: confidence interval / Intent-to-treat population (ITT); patients analyzed as randomized; dis eas e s ubtype as per diagnosis at s creening; presented is 24wCDW with applied imputation for participants who discontinued the double-blind main treatment period due to disease progression and who already achieved 12-week CDW confirmation; 24wCDW is defined as patients with worsening inEDSS sus tained over at least 22 weeks (154 days ) Overall CALLIPER Patient Population (N=467) PPMS (N=152) naSPMS (N=268) aSPMS (N=47) HR (Kaplan Meier) 0.762 0.687 0.808 0.644 95 % CI [0.479; 1.210] [0.330; 1.430] [0.418, 1.564] [0.143, 2.892] p-value 0.249 0.315 0.527 0.566 Risk Reduction of tt24wCDW 23.8% 31.3% 19.2% 33.6%
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CALLIPER: Vidofludimus Calcium Significantly Reduced EDSS Increase from Baseline Compared to Placebo EDSS: expanded disability status scale; MMRM: mixed models for repeated measure; LS: least square MMRMs analysis: For the calculation of LS means based on the MMRM, patients with baseline and at least one-post baseline visit are considered. Missing values are calculated based on the analysis set. Estimates are adjusted for stratification factors used at baseline randomization (disease type and baseline EDSS value). 2-sided p-value is presented. Error bars show the standard error of the LSMean. Data are based on group level analysis for overall CALLIPER population, total N= 467, vidofludimus calcium N=235, placebo N=232 | © Immunic, Inc. | November 202538 ▪ Patients treated with vidofludimus calcium showed only minimal worsening of EDSS LS mean from baseline ▪ Placebo treated cohort showed steady increase in LS mean of EDSS ▪ Difference significant starting at week 60 -0.05 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0 12 24 36 48 60 72 84 96 108 120 LS Mean of EDSS Weeks MMRM Analysis (All Patients): Change from Baseline in EDSS Score Vidofludimus Calcium Placebo * * * ** * * Statistically significant (p<0.05) ** Statistically significant (p<0.01) *
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Comparison CALLIPER Versus ORATORIO Trials in PPMS Population | © Immunic, Inc. | November 202539 * Clinical Review Report: Ocrelizumab (Ocrevus): (Hoffmann-La Roche Limited): Indication: Management of adult patients with early primary progressive multiple scleros is as defined by disease duration and level of disability, in conjunction with imaging features characteris tic 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 s clerosis; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing lesions found on T1-weighted MRI images; MRI: magnetic resonance imaging; tt24wCDW: time to 24-week confirmed dis ability worsening; N: number ofpatients evaluated 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 Time to 24wCDW Active Over Placebo 25% 31%
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Hazard Ratio Analysis 3-Months Confirmed Disability Worsening Phase 3 Ocrelizumab ORATORIO Study | © Immunic, Inc. | November 202540 EMA Clinical Review PPMS: primary progressive multiple sclerosis; MRI: magnetic resonance imaging; CDW: confirmed disability worsening; Gd+: gadolinium-enhancing Reduction of 12-week confirmed disability events seems to be largely driven by patients with active disease (MRI lesions) and young age (labeled as “early PPMS with signs of active disease”) Hazard Ratio 12-Week CDW Patient age ≤ 45 years and Gd+ lesions at baseline 0.52 Overall study outcome (all patients) 0.76 Patients without Gd+ lesions during study 0.84 Patient age >45 years 0.91 Patient age >45 years and without Gd+ lesions during study 0.93 During the scientific assessment the Applicant modified the indication to 'early PPMS', and better reflect the results of the performed trial. Younger age was correlated with more MRI activity. It seems that younger patients with T1 Gd-enhancing lesions at baseline have a better treatment effect. This supports an indication in early PPMS early with imaging features characteristic of inflammatory disease. EMA Medical Reviewer Comment:
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CALLIPER: Vidofludimus Calcium Substantially Reduced 24wCDW in Patients Without Gd+ Lesions at Baseline | © Immunic, Inc. | November 202541 24wCDW: 24-week confirmed dis ability worsening based on the EDSS (expanded disability status scale) score; tt: time to; Gd+: gadolinium-enhancing; HR: hazard ratio; CI: confidence interval; RRR: relative risk reduction; disease subtype as per diagnosis at screening visit 1 24wCDW is defined as patients with worsening in EDSS s ustained for at least 22 weeks (154 days) given the visit window +-7 days. Confirmed disability progression event status was imputed for participants who completed the trial, met the criteria for confirmed dis ability progression s ustained for at least 12 weeks, and continued to meet the criteria for disability progression according to the EDSS score through the final trial as sessment but did not reach the 24-week confirmation vis it. Total of 73 events for 24wCDW based on EDSS, 70 events observed and 3 events imputed after 12-week confirmation before end of study (performed as sensitivity analysis). Time to 24wCDW With No Evidence of Gd+ Lesions at Baseline Group Number of Patients HR 95 % CI p-value RRR tt24wCDW All Patients 391 0.663 [0.394, 1.115] 0.121 33.7% PPMS 125 0.656 [0.294; 1.464] 0.303 34.4% naSPMS 250 0.702 [0.346, 1.422] 0.326 29.8% ▪ Precisely the patients who were largely shown to not benefit from current anti-inflammatory therapies ▪ These clinical effects underlines neuroprotective effect of Nurr1 activation by vidofludimus calcium
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CALLIPER: Vidofludimus Calcium Demonstrated Statistically Significant 24-Week Confirmed Disability Improvement | © Immunic, Inc. | November 202542 MS: multiple sclerosis; PPMS: primary progressive MS, naSPMS: non-active secondary progressive MS; aSPMS: active secondary progressive MS; nrSPMS: non-relapsing secondary progressive MS; 24wCDI: 24-week confirmed disability improvement; 6mCDI: 6-months confirmed disability improvement; EDSS: Expanded Disability Status Scale / Disability improvement in the CALLIPER study is defined as an increase of the EDSS score compared to BL of at least 1.0 point for patients with a BL EDSS score ≤5.5 or an increase of ≥0.5 point if EDSS at entry is >5.5. The event is counted as 24wCDI if the improvement is sustained over at least 24 week. ▪ Patients treated with vidofludimus calcium showed approximately 2-fold increase in 24wCDI event numbers over placebo ▪ Consistent effects across subtypes, with clearest signal in PPMS subtype 24wCDI Events Vidofludimus Calcium Placebo Hazard Ratio [95% CI] p-value CALLIPER Overall Population 19/235 (8.1%) 8/232 (3.4%) 2.441 [1.068; 5.581] 0.034* PPMS 8/77 (10.4%) 3/75 (4.0%) 2.823 [0.747;10.672] 0.126 naSPMS 9/135 (6.7%) 5/133 (3.8%) 1.813 [0.607; 5.414] 0.286
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| © Immunic, Inc. | November 202543 TEAE: treatment-emergent adverse event; SAE: serious adverse event; N: number of patients; n: number of events Safety Population contains any patient who received at least one dose of study drug, vidofludimuscalcium (N=235), placebo (N=232), total (N=467). All other SAE not listed had only single occurrences in the CALLIPER trial. N (%) of Patients Vidofludimus Calcium N=235 Placebo N=232 Any TEAE, n(%) 163 (69.4%) 159 (68.5%) Any SAE, n(%) 19 (8.1%) 15 (6.5%) n of Events Vidofludimus Calcium Placebo T otal 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) n of Events Vidofludimus Calcium Placebo T otal Pyelonephritis 1 1 2 Femoral neck fracture 0 2 2 Femur fracture 0 2 2 Vertigo 2 0 2 Number of Patients With Any TEAE and SAE CALLIPER: Top-Line Data Confirmed Favorable Safety and Tolerability Profile of Vidofludimus Calcium Observed in Previous Clinical Trials ▪ No new safety signals identified ▪ Occurrence of TEAEs and SAEs with similar frequency in both treatment arms
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CALLIPER: Liver Enzyme Elevations No Evidence of Increased Rates of Liver Enzyme Elevations | © Immunic, Inc. | November 202544 ULN: upper limit of normal reference range Tables depict number of patients with any increase fulfilling the criteria at any point during the double-blind treatment (main treatment period). Hy‘s Lase cases are defined as liver enzyme elevation of greater than 3xULN with concurrent elevation of serum total bilirubin greater than 2xULN. Vidofludimus Calcium (n=235) Placebo (n=232) ALT>3xULN 7 (3.0%) 6 (2.6%) ALT>5xULN 2 (0.9%) 4 (1.7%) ALT>10xULN 1 (0.4%) 4 (1.7%) ALT>20xULN 1 (0.4%) 1 (0.4%) Hy's Law Cases 0 0 Vidofludimus Calcium (n=235) Placebo (n=232) AST>3xULN 5 (2.2%) 5 (2.2%) AST>5xULN 1 (0.4%) 5 (2.2%) AST>10xULN 1 (0.4%) 1 (0.4%) AST>20xULN 1 (0.4%) 1 (0.4%) Hy's Law Cases 0 0 Elevations of Alanine Aminotransferase (ALT) Elevations of Aspartate Aminotransferase (AST)
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Positive Data from Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis | © Immunic, Inc. | November 202545 Clinically meaningful risk reduction of 24wCDW by 24% in overall study population; even more prominent 31% reduction in high unmet need population of PPMS Remarkable 34% reduction of 24wCDW 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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Inhibits Epstein-Barr Virus (EBV) Replication and Reactivation Showed Dose-Dependent Inhibition of EBV Reactivation Decreased Number of Opportu- nistic SARS-CoV-2 Infections Vidofludimus Calcium: DHODH Inhibition Provides Broad- Spectrum Antiviral Activity Against Different Pathogenic Viruses | © Immunic, Inc. | November 202546 Left: Eur J Clin Invest. 2020;50:e13366 / middle: Marschall et al., Poster ECTRIMS 2021 / right: Immunic data; DHODH: dihydroorotate dehydrogenase; RNA: ribonucleic acid; DNA: deoxyribonucleic acid; EC50: half-maximal effective concentration; EBV: Epstein-Barr virus; hIgG: human immunoglobulin G; SARS-CoV-2: severe acute respiratory syndrome coronavirus; COVID-19: coronavirus disease 2019; RRMS: relapsing-remitting multiple sclerosis By targeting the host cell metabolism, vidofludimus calcium has shown to be active against different RNA and DNA viruses in vitro ▪ Shows antiviral activity with EC50 values in single digit μM range ▪ Including strong anti-EBV activity Anti-Akata-BX1-EBV-GFP stimulated with hIgG Vidofludimus calcium showed interesting hints for clinical anti-SARS-CoV-2 activity in the phase 2 EMPhASIS trial in RRMS ▪ Number of reported COVID-19 cases Cohort 2: 17.0% 8.5% 33.0% 25.0% 0% 5% 10% 15% 20% 25% 30% 35% Any Infection COVID-19 10 mg Vidofludimus Calcium Placebo
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Multi-Layered Intellectual Property (IP) Strategy Approach Exclusivity for Vidofludimus Expected up to 2044 in the US | © Immunic, Inc. | November 202547 ▪ Multi-layered IP strategy approach with 10 independent patent families to effectively protect vidofludimus (free acid and salts) with Orange Book listable patents up to 2044 in the US, or even beyond ▪ Main IP value driver is a smart two-fold approach to protect vidofludimus via composition-of-matter patents on the one hand and indication as well as method-of-treatment patents on the other hand, supplemented by additional layers of protection such as dose strength and formulation patents ▪ Two main pillars are: − Calcium salt and calcium polymorph patent covering the stable, crystalline polymorphic form, which is the only polymorph in the developed drug product − Broad dosing regimens patent directed to the safety and label relevant dosing regimen of vidofludimus in all (salt) forms; this titration scheme was part of every safety testing and therefore this regimens patent cannot be avoided
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Vidofludimus Calcium in Multiple Sclerosis Consistent and Differentiated Results to Date Support Straightforward Path Towards Potential Regulatory Approvals | © Immunic, Inc. | November 202548 Although we currently believe that each of these goals is achievable, they are each dependent on numerous factors, most of which are not under our direct control and can be difficult to predict. We plan to periodically review this assessment and provide updates of material changes as appropriate. / MS: multiple sclerosis; RRMS: relapsing-remitting MS; RMS: relapsing MS; PMS: progressive MS; NfL: neurofilament light chain 2020 2021 2022 2023 2024 2025 2026 2027 EMPhASIS: Positive phase 2 RRMS data demonstrating statistically significant effect on lesion control and relapse prevention, with clear impact on serum NfL Aug 2020 Nov 2022 EMPhASIS: Positive RRMS open-label extension data demonstrating signal for improvement in confirmed disability worsening CALLIPER: Positive phase 2 PMS interim data showing clear impact on serum NfL in all subtypes and subpopulations Oct 2023 Oct 2024 ENSURE: Positive phase 3 RMS interim analysis; IDMC recommendation to continue trials as planned CALLIPER: Positive phase 2 PMS data showing substantial reductions in disability worsening Apr 2025 Potential RMS NDA Submission 2027 End of 2026 ENSURE: Top-line data expected for both ENSURE trials
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Restoring a Healthy Gut through Renewal of the Bowel Wall IMU-856
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IMU-856 Targets Physiological Intestinal Epithelial Regeneration and Restoration of Gut Cell Function | © Immunic, Inc. | November 202550 ▪ Innovative oral therapeutic approach potentially applicable to a broad range of gastrointestinaldisorders ▪ Targets physiological intestinal epithelial regeneration, including gut hormon-producing cells ▪ Designed to strengthen gut wall integrity and function without immunosuppression
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| © Immunic, Inc. | November 202551 IMU-856: ▪ First-in-class modulator of sirtuin 6 (SIRT6), targets physiological intestinal epithelial regeneration and restoration of barrier function ▪ Provides protection and enhances transport of nutrients ▪ This new approach avoids immunosuppression Damaged Gut Wall antigens, microbiome, nutrients Lamina propria / immune system Healthy Gut Wall Bowel lumen Lamina propria / immune system IMU-856 antigens, microbiome, nutrients Bowel lumen Once-Daily, Oral IMU-856 Aims to Regenerate the Gut Wall and Barrier Function by a New Innovative Targeted Mechanism
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SIRT6 Target IsHighly Expressed in Gut Epithelial Cells | © Immunic, Inc. | November 202552 Left: https://www.proteinatlas.org/ / Right: Peterson, L., Artis, D. Nat Rev Immunol14, 141–153 (2014) SIRT: sirtuin; mRNA: messenger ribonucleic acid; nTPM: normalized transcript per million Highest mRNA Expressions in Paneth Cells, Enterocytes, Goblet Cells and Enteroendocrine Cells such as L -Cells
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IMU-856 Enhances the Natural Regenerative Process in the Gut | © Immunic, Inc. | November 202553 Adapted from Mamis K et al., Proc. R. Soc. B. 290:20231020 (2023) Asymmetric cell division renews stem cells and regenerates the gut wall Gut wall renewal is a normal physiological process 1. Regeneration begins in the crypts, where intestinal stem cells are located 2. Stem cells undergo asymmetric division thereby producing fully differentiated epithelial gut cells and renewing intestinal stem cells 3. These new epithelial cells are renewing the lining of crypts and villi to maintain healthy gut and proper intestinal barrier IMU-856 is an epigenetic regulator which enhances this natural tissue renewal phenotype
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Demonstrated Clinical Proof-of-Concept in a Phase 1b Clinical Trial IMU-856 in Celiac Disease
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Celiac Disease Currently Has No Adequate Treatment Options | © Immunic, Inc. | November 202555 [1] Singh et al., Clinical Gastroenterology and Hepatology 2018;16:823 –836 [2] Choung et al., Mayo Clin Proc. 2016 Dec 5:S0025 -6196(16)30634 -6 [3] Lebwohl et al., Aliment Pharmacol Ther. 2014 March ; 39(5): 488–495 [4] Lanzini et al., Aliment Pharmacol Ther. 2009; 29(12):1299 –308 [5] Ciacci et al., Digestion. 2002; 66(3):178 –85 [6] Selby et al., Scand J Gastroenterol. 1999; 34( 9):909–14 [7] Rubio -Tapia et al., Am J Gastroenterol. 2010; 105(6):1412 –20 [8] Sharkey et al., Aliment Pharmacol Ther. 2013; 38(10):1278 –91 [9]: https:// nationalceliac.org /celiac -disease-questions/understanding -gluten-levels/ (text and picture) ▪ Two million patients diagnosed with celiac disease in the US; more than one million more undiagnosed[1,2] ▪ Most studies report between 24% and 47%[3-8] of patients with signs and symptoms of ongoing active celiac disease (OACD) despite a gluten-free diet, most likely due to continuous (inadvertent) gluten exposure ▪ Only established therapeutic option is a life-long strict adherence to a gluten-free diet[9], which involves complete avoidance of proteins from wheat, barley, and rye ▪ Gluten challenge is an accepted concept for clinical trials in celiac disease How much is 10 mg of gluten? A 350th piece of bread Just a crumb! Like a pin-point of flour 10 mg of gluten is the total limit for all foods combined for the entire day.
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IMU-856 Demonstrated Clinical Proof-of-Concept in a Phase 1b Clinical Trial in Celiac Disease | © Immunic, Inc. | November 202556 Proof-of-Concept Study Designed as a Gluten Challenge Trial QD: quaque die = once-daily; EGD: esophagogastroduodenoscopy Flow Chart of Phase 1b Clinical Trial in Celiac Disease ▪ Celiac disease used as disease model to provide clinical proof-of-activity of IMU-856 in a 28-day trial setting ▪ Designed to explore effects of gluten challenge in a celiac disease patient population ▪ Dosing: 80 and 160 mg QD of IMU-856, or placebo ▪ 43 patients enrolled (IMU-856: N=29) ▪ Assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of IMU-856 ▪ Proof-of-concept: measured histological changes, blood biomarkers of epithelial mass, nutrient uptake and disease-related symptoms Day 1-28: Treatment IMU-856/placebo Day 14-28: Gluten challenge with 6 g/daily Baseline: EGD with biopsy Day 14: Citrulline Day 29: EGD with biopsy Citrulline Celiac Disease Symptom Diary (CDSD) and other patient reported outcomes Biomarker and nutrition absorption marker
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Mean -60.3 SD 52.2 Mean -20.9 SD 34.8 Mean -22.5 SD 51.1 -70 -60 -50 -40 -30 -20 -10 0 Placebo (N=11) IMU-856 80 mg (N=11) IMU-856 160 mg (N=13) IMU-856 Protected Against Gluten-Induced Decrease in Villous Height as Compared to Placebo | © Immunic, Inc. | November 202557 * Wilcoxon Two-Sample Test comparisonbetween pooled IMU-856 groups and placebo, performed as post-hoc exploratory statistical analysis Disease Analysis Set: N=35/43 included in histology analysis set. 8 patients not included in this analysis due to early termination. Gluten Challenge for 15 days with 6 g daily. Central pathology laboratory: Jilab Inc. Tampere, Finland EGD: esophagogastroduodenoscopy; SD: standard deviation Absolute change in villous height (μm) between Baseline and Day 29 Villous height (µm) Day 1-28: Treatment IMU-856/placebo Day 14-28: Gluten challenge with 6 g/daily Baseline: EGD with biopsy Visit 6 / Day 29: EGD with biopsy p=0.04* ▪ Substantial protection for IMU-856 treatment groups as compared to placebo ▪ Reached statistical significance* for this objective readout which is known to be relevant to influence future medical complications of celiac disease ▪ Assessed by central pathology laboratory and blinded pathology reader
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Vitamin B12 Zinc IMU-856 Improved Uptake ofActively Transported Essential Nutrients Vitamin B12 and Zinc | © Immunic, Inc. | November 202558 SD: standard deviation Mean -31.0 SD 68.8 Mean 45.8 SD 94.4 Mean 74.2 SD 99.9 -40 -20 0 20 40 60 80 Mean change from Baseline to Day 29 in vitamin B12 (pmol/L) Placebo (N=11) IMU-856 80 mg (N=11) IMU-856 160 mg (N=13) Serum vitamin B12 (pmol/L) Mean -0.9 SD 2.1 Mean 0.3 SD 1.4 Mean 0.9 SD 2.1 -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1 Mean change from Baseline to Day 29 in zinc (µmol/L) Placebo (N=11) IMU-856 80 mg (N=11) IMU-856 160 mg (N=13) Serum zinc (µmo/L)
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Dose-Dependent Increase of GLP-1 in Patients IMU-856: Additional Pharmacological Effect
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Intestinal Production of GLP-1 Mediates Effects on Body Weight | © Immunic, Inc. | November 202560 GLP-1: Glucagon-Like Peptide-1 Left: Review Zheng, Z., Zong, Y., Ma, Y.et al. Sig TransductTarget Ther 9, 234 (2024); right: JakubowskaA, Roux CWL, Viljoen A. Endocrinol Metab (Seoul). 2024 Feb;39(1):12-22 Main Physiologic Effects of GLP-1 ▪ Peptide hormone generated through enzymatic breakdown of proglucagon ▪ Endocrine hormone, secreted by enteroendocrine L-cells located in the distal jejunum, ileum, and colon in response to nutrient ingestion and neuroendocrine stimulation ▪ Typical physiological increase in GLP-1 levels in healthy humans after a meal is 2-3 times ▪ GLP-1 increase leads to slow gut motility, lower food intake, increase satiety and induce insulin secretion
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6-Months In Vivo Study Phase 1b Clinical Trial of IMU-856 IMU-856: Effects on Body Weight in Preclinical Experiment and on Blood GLP-1 Levels in Celiac Disease Clinical Trial | © Immunic, Inc. | November 202561 [1] according to ICH M3(R2) [2] Wistar Han rats / GLP-1: glucagon-like peptide-1; GLP: Good Laboratory Practice; QD: quaque die = once-daily; ICH: International Council for Harmonisationof Technical Requirements for Pharmaceuticals for Human Use ▪ Regulated GLP study[1] to support clinical development ▪ Daily oral treatment of rats [2] for 6 months ▪ Dosing: 0 (vehicle), 10, 25, 75 mg/kg/day of IMU -856 ▪ Weekly body weight measurement ▪ Designed to explore effects of gluten challenge in a celiac disease patient population ▪ Total of 43 patients enrolled (IMU-856: N=29) ▪ Dosing: 80 and 160 mg QD of IMU -856, or placebo ▪ Double-blind treatment period of 28 days, 13 days without and 15 days with 6 g daily gluten challenge ▪ Patients measured post hoc for plasma GLP -1 concentrations Day 1-28: Treatment IMU-856/placebo Day 14-28: Gluten challenge with 6 g/daily Baseline GLP-1 Day 14 GLP-1 Day 29 GLP-1 Daily for 6 months: Treatment IMU-856/vehicle control Baseline Body weight Weekly: Body weight measurement
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In a 6-Months In Vivo Study, IMU-856 Dose-Dependently Reduced Weight Gain | © Immunic, Inc. | November 202562 Reduced body weight gain observed in 6-month toxicology study. Rats were 7-8 weeks old at study start and were expected to gain weight over the course of the study. Data show less weight gain in IMU-856 treated animals in connection with reduced food consumption. 10 mg/kg -18 % 25 mg/kg -23 % 75 mg/kg -40 % Reduction of weight gain in % compared to vehicle control IMU-856 reduced body weight gain in a dose-dependent fashion up to -40 % compared to vehicle control ▪ Dose-dependent effect on body weight gain ▪ Linked to reduced food consumption ▪ Effect in both males and females ▪ No effect on general health condition
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| © Immunic, Inc. | November 202563 Confirmation of Effects as Part of Phase 1b Clinical Trial: IMU-856 Dose-Dependently Increased GLP-1 in Celiac Disease Patients 28-day phase 1b clinical trial of IMU-856 in celiac disease ▪ Patients measured for plasma GLP-1 concentrations: N=11 (placebo), N=13 (80 mg IMU-856), N=13 (160 mg IMU-856) ▪ Baseline: Day 1, N=37 over all arms ▪ Day 14: before start of challenge, N=36 ▪ Day 29: after last treatment on Day 28, N=32 ▪ Morning baseline levels under fasting conditions ▪ Dose-dependent increase of endogenous GLP-1 levels of up to 2.5 times versus placebo control ▪ Typical physiological increase in GLP-1 levels in healthy humans after a meal is also 2-3 times Statistics: two-sided Mann-Whitney U, treatment vs. placebo at Day 14 and Day 29 / GLP-1: glucagon-like peptide-1; BL: baseline 100% 100% 100% 108.9% 160.1% *, p = 0.047 158.7% 95.8% 161.7% *, p = 0.014 247.7% **, p = 0.003 0% 50% 100% 150% 200% 250% 300% Placebo 80 mg IMU-856 160 mg IMU-856 GLP-1 Plasma Concentration Median % Change from Baseline to Day 14 and Day 29 BL Day 14 Day 29 BL Day 14 Day 29 BL Day 14 Day 29
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Main Secretory Epithelial Cells of the Small Intestine and Colon Epithelium All Have Been Shown to Express SIRT6 Target | © Immunic, Inc. | November 202564 Meyer AR, Brown ME, McGrath PS, Dempsey PJ. Cell Mol Gastroenterol Hepatol. 2022;13(3):843-856 / SIRT: sirtuin Crypt Villus Produce and release a protective mucus layer, with the main component of this mucus being a protein called mucin Secret gastrointestinal hormones: such as gastric inhibitory peptide (GIP), glucagon-like peptides (GLP-1 and GLP-2), cholecystokinin (CCK), ghrelin, neurotensin, serotonin (5- hydroxy-tryptamine or 5-HT), and peptide YY (PYY) Secrete antimicrobial peptides and proteins, most notably defensins
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SIRT6 Targeting Approach IMU-856 Incretin Mimetics GLP-1, GLP-2, GIP IMU-856: A Novel Mechanism Offering Potential to Go Beyond Existing GLP-1, GLP-2, GIP Mimetics | © Immunic, Inc. | November 202565 SIRT: sirtuin; GLP: glucagon-like peptide; GIP: glucose-dependent insulin-tropic polypeptide ▪ Functional improvement of enteroendocrine and other epithelial cells through increasing physiologic cell regeneration in gut wall ▪ Secretion of the physiological GLP-1 protein and possible increase of secretion of multiple incretins (currently being investigated) ▪ Improvement of gut barrier and functionality in general ▪ Oral administration, small molecule ▪ Providing synthetic peptides that mimic the natural hormones secreted by enteroendocrine cells ▪ Targets one or two target incretins only (at this point) ▪ Injectable, peptide
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Obesity Market Expected to Reach More Than $170 Billion Globally by 2031[1] | © Immunic, Inc. | November 202566 [1] GlobalDataPharma DECODED, Feb. 11th 2025 “Obesity: Seven-Market Drug Forecast and Market Analysis – Update” [2] https://www.who.int/news-room/fact- sheets/detail/obesity-and-overweight#:~:text=In%202022%2C%202.5%20billion%20adults%20aged%2018%20years%20and%20older,1990%20to%2020%25%20in%202022 [3] https://data.worldobesity.org/economic-impact-new/countries/US.pdf Unmet Needs Still Exist to Address This Growing Medical Challenge ▪ Obesity and overweight are among the fastest growing and most prevalent chronic human conditions in the world affecting ~2.5 billion adults worldwide [2] ▪ The economic impact of obesity and overweight in the United States is estimated to be $706 billion, increasing to $2.6 trillion by 2060 [3] ▪ GLP-1 receptor agonist class has revolutionized obesity treatment but there are still unmet needs for novel mode of actions , oral administration, increased tolerability and greater efficacy ▪ Current drugs in development are mainly peptidomimetics – with challenges in oral administration
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Summary Immunic Therapeutics
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Summary: Vidofludimus Calcium Is a Derisked Near-Term Opportunity Innovative clinical pipeline: First-in-class oral drugs with unique modes of actions for multiple sclerosis and gastrointestinal diseases in various phases of clinical development Relapsing MS opportunity is meaningful and de -risked: Oral category going to remain a large portion of overall MS market; peak sales potential for vidofludimus calcium of $1-2 billion Currently available oral therapies have limitations in benefit/risk profile; there is need for improvement Vidofludimus calcium has the potential to address these shortcomings and transform the oral MS DMT market ENSURE program: Two identical phase 3 clinical trials, designed to achieve potential regulatory approval of vidofludimus calcium in relapsing MS in a low-risk study design; top-line data for both ENSURE trials expected by end of 2026 Progressive MS provides tremendous upside opportunity: High unmet medical need market: No approved therapies for non-active SPMS; one approved therapy for PPMS (infusion) Peak sales potential for vidofludimus calcium of $3-5 billion across respective indications Phase 2 CALLIPER trial successfully demonstrated neuroprotective potential of vidofludimus calcium in progressive MS patients Results to be discussed with healthcare authorities to determine appropriate next steps Financials: Cash position: $35.1 million (as of September 30, 2025), shares outstanding: 120,284,724 (as of November 11, 2025)
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Thank You! 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 | © Immunic, Inc. | November 202569