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Slide 2: Cautionary Note Regarding Forward-Looking Statements
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 216 of the Securities
Slide 3: Multiple Clinical Data Readouts for All Three Development Programs Expected Throughout 2022
Multiple Clinical Data Readouts for All Three Development Programs Expected Throughout 2022 = Completed or ongoing 3 Program _| Target Preclinical Phase 1 Phase 2 Phase 3 Key Milestones RMS interim analysis planned after approx. half of the events occurred PMS interim analysis planned after half of
Slide 4: Treatment Compliance and Persistence are Important Considerations
Treatment Compliance and Persistence are Important Considerations for Life-Long Diseases such as Multiple Sclerosis (MS) MS Disease Course!) Preclinical | Relapsing-remitting tt ft tit t it Clinical disability MRI activity Secondary progressive phase Brain volume asia - i i lx? years >|<— 10-15 year
Slide 5: Treatment Escalation Remains the Typical Approach for Patients With RRMS
Treatment Escalation Remains the Typical Approach for Patients With Relapsing-Remitting Multiple Sclerosis (RRMS) Treatments escalated due to: 1. Long time-course of Escalation (Switch)!22] disease " = Switch most often driven by 2. Lack of efficacy Base Therapy (Initiation) either — Relapse(s) . no
Slide 6: Vidofludimus Calcium is Targeted to Address Unmet Needs
Vidofludimus Calcium is Targeted to Address Unmet Needs From Both the Patient and Healthcare Provider Perspective Intended Value for Neurologist Intended Value for Patient = Clear therapeutic benefits . — Reduction of relapses and MRI lesions — Prevent and/or delay disability worsening — Confirmed r
Slide 7: Off-Target Effects: Kinase Inhibition by Teriflunomide
Off-Target Effects: Kinase Inhibition by Teriflunomide Teriflunomide trough level Teriflunomide is not purely selective for DHODH, it also PIM inhibits kinases such as Aurora A PDGFR, Aurora A, FYN, LCK, JAK3, PIM and EGFR JAK3 SS > c 2 = Most common adverse tek Ll ee events of EGFR inhibitors: FYN
Slide 8: Traditional Thinking About MS Medications (Simplified)
Traditional Thinking About MS Medications (Simplified) Relapsing MS (RMS) Progressive MS (PMS) Disease Drivers Mainly driven by autoimmune-triggered inflammation The exact mechanism of disability accumulation without relapse or ongoing MRI activity is currently unknown Assumed that PMS is driven by
Slide 9: Relapse-Associated Versus Relapse-Independent Disability Worsening
Relapse-Associated Versus Relapse-Independent Disability Worsening Neuroprotective Mechanisms Are of Importance for Both, RMS and PMS RAW PIRA Meta-Analysis of Novartis MS Trials (Relapse-Associated (Progression Independent of Containing Data From ~35,000 Patients Worsening) Relapse Activity) = With
Slide 10: Emerging Data Support a Change in Thinking About What is Driving Long-Term Patient Outcomes
Emerging Data Support a Change in Thinking About What is Driving Long-Term Patient Outcomes in Relapsing and Progressive MS = It has long been believed that the relapse- independent disability worsening process (“smoldering disease”) occurs even in absence of relapse activity. = New data validates t
Slide 11: Clinical Objectives for Vidofludimus Calcium in MS
Clinical Objectives for Vidofludimus Calcium in MS Focusing on Key Strengths of Medication Related to Long-Term Patient Outcome = Obtain approval: Relapse activity is an approvable endpoint in RMS — Phase 3 ENSURE program in RMS is designed to provide a straightforward path to potential regulatory a
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Slide 13: EMPhASIS: Phase 2 Study Overview in RRMS
EMPhASIS: Phase 2 Study Overview in RRMS NCT03846219 Included Patient Population: 5) RRMS With Relevant Disease Activity = Male or female ( 18 > age < 55) P Coordinating Investigator = RRMS diagnosis (Revised McDonald criteria 2017) = Evidence of disease activity based on relapse and MRI criteria =
Slide 14: EMPhASIS: Phase 2 Trial in RRMS
EMPHASIS: Phase 2 Trial in RRMS Patient Cohorts and Treatment Groups Investigated Randomized, double-blind, placebo-controlled, multi-center Phase 2 trial assessing the effect of vidofludimus calcium on disease activity, as measured by magnetic resonance imaging (MRI), as well as safety and tolerabi
Slide 15: EMPhASIS: Phase 2 Trial in RRMS
EMPHASIS: Phase 2 Trial in RRMS Patient Population for Pooled MRI Analysis over Both Cohorts TE IMU-838 |] IMU-838 | IMU-838 | Placebo 45mg | 30mg | 10mg | C1+C2 C1+ C2 OLE N=69 N=71 | N=47 | N=81 Ss 1st 66 65 47 71 ran aN =_ _ 45 mg IMU-838 30 mg IMU-838 10 mg IMU-838 Placebo C1 + C2 aT 3 6 0 10 N=
Slide 16: EMPhASIS: Phase 2 Trial Design in RRMS
EMPhASIS: Phase 2 Trial Design in RRMS Extended Treatment Period (Optional) 30mg IMU-838 =I 45 mg IMU-838 a ia cI 10 mg IMU-838 =I Placebo Open-Label Treatment (30 mg or 45 mg) End Of Main Treatment BL W6 W12 wis ‘cecohort; BL: baseline; W = week 16 | ©immunic, inc. | May/10/2022 & Immunic
Slide 17: EMPhASIS: Schedule of MRI Examinations
EMPhASIS: Schedule of MRI Examinations hw | Timeline of MRI Visits Primary Endpoint To evaluate the efficacy of vidofludimus calcium as compared to placebo based on the cumulative number of new combined unique active lesions at Week 24 |@| Combined Unique Active (CUA) Lesions Baseline Week 12 Sum of
Slide 18: EMPhASIS: Phase 2 Trial in RRMS
EMPhASIS: Phase 2 Trial in RRMS Patient Disposition in Main Period Discontinued N=5 mpleted Week 24 N=64 Not Treated Discontinued N=1 N=3 Randomized Patients Completed Week 24 Discontinued N=4 N=68 Discontinued Completed Week 24 N=65 N=1 Completed Week 24 N=11 Not Treated Discontinued N=2 *Note: aN
Slide 19: EMPhASIS: Objectives of Cohort 2
© Objectives EMPhASIS: Objectives of Cohort 2 Endpoints = Obtain more efficacy and safety data for vidofludimus calcium in patients with RRMS = Allow pharmacodynamic modelling of dose response = Confirm lowest effective doses for relapsing and progressive MS The endpoints analyzed include: = Cumulat
Slide 20: Main result: Reduction of MRI Lesions Supports 30 mg as Phase 3 Dose
Main result: Reduction of MRI Lesions Supports 30 mg as Phase 3 Dose (Pooled Cohorts 1 & 2) Reduction in Cumulative CUA Lesions up to Week 24 meee -71% Placebo 3OmgiMU-838 45 mg IMU-838 10 mg IMU-838 mm Cumulative CUA Lesions. ~®=Lesion Reduction in% Reduction in Gd+ Lesions up to Week 24 Q ° 5 ° “1
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Slide 22: Dose-Response Reduction of MRI Lesions
Dose-Response Reduction of MRI Lesions Mean Numbers of CumCUA®! at W24 Mean Numbers of Gd+ at W24 10 7 Subjects treated 6 with 30 and 45 mg 5 of vidofludimus a < jf S =) J calcium, on Ba i (bl 3 = averagel”!, = al experienced less 8 MRI lesions than eo, those on 10 mg IMU-838 or 4 lacebo. l i o Plac
Slide 23: Reduction of CumCUA and Gd+ Lesions by Vidofludimus Calcium
Reduction of CumCUA and Gd+ Lesions by Vidofludimus Calcium Across All Doses of Cohorts 1 & 2 of EMPhASIS Trial Reduction in CumCUA Lesions 0% 0% oF NeoORaaA -71% Placebo 10 mg IMU-83830 mg IMU-83845 mg IMU-838 mm Cum CUA Lesions Cum CUA Lesions and Reduction Compared to Placebo —e Lesion Reduction
Slide 24: Dose-Dependent Reduction of CumCUA Lesions by IMU-838
Dose-Dependent Reduction of CumCUA Lesions by IMU-838 Across All Doses of Cohorts 1 & 2 of EMPhASIS Trial 7 0 ' 0% 6 58 = -10 -20 5 -320 4 -40 3 50 2 LP 14 -60 a -10 “71% 0 -80 -76% Placebo 10 mgIMU-838 30 mgIMU-838. 45 mg IMU-838 10 mg IMU-838 30 mg IMU-838 45 mg IMU-838 wm CumCUA Lesions 1m CumCUA
Slide 25: Dose-Dependent Reduction of Gd+ Lesions by IMU-838
Dose-Dependent Reduction of Gd+ Lesions by IMU-838 Across All Doses of Cohorts 1 & 2 of EMPhASIS Trial 5 0 46 45 -10 A 13% a -20 35 -30 3 -40 25 -50 2 -60 15 _ 1 : -70 “74% Os L “0 -78% 0 -90 Placebo 10mg IMU-838 30 mgIMU-838 45 mg IMU-838 10 mg IMU-838 30 mg IMU-838 45 mg IMU-838 m1 Gd+ Lesions tm
Slide 26: Dose-Response Relationship Regarding Reduction of MRI Lesions
Dose-Response Relationship Regarding Reduction of MRI Lesions Across All Vidofludimus Calcium Doses of Cohorts 1 & 2 of EMPhASIS Trial Treatment Group | Mean(95%Cl) ss nue Treatment Group Mean (95% Cl) 8 eee 10 mg IMU-838 5.9) 0% 10 mg IMU-838 4.0 13% 30 mg IMU-838 1.4 76% 30 mg IMU-838 1.0 78% 45 m
Slide 27: Highly Significant MRI Lesion Suppression
Highly Significant MRI Lesion Suppression Compares Favorably to Other First-Line and Oral Base Medications Commercially Available in RRMS* Vidofludimus | Vidofludimus | Glatiramer |. gmiqei| _Dimethyl neato? || eerie Calcium Calcium Acetatel] Fumaratel*] Administration Oral Oral Injectable Oral Oral
Slide 28: Relationship Between Trough Levels of Vidofludimus And Number of CumCUA/Gd+ Lesions
Relationship Between Trough Levels of Vidofludimus And Number of CumCUA/Gd+ Lesions at Week 24 Plasma Trough Levels of IMU-838 [g/mL] Cumulative CUA Lesions and Trough Levels Gd+ Lesions and Trough Levels up to up to Week 24 Week 24 a . a z Treatment 6.074 g/mL 6.074 ug/mt gant een ast ard Quartile
Slide 29: Annualized Relapse Rates for Active Treatment Group and Placebo
Annualized Relapse Rates for Active Treatment Group and Placebo Relapse Lowering Effect Signal Despite Short Follow-Up Period of 24 Weeks 1.00 a rf Treatment a Mean ARR = Group [95% cl] 2 075 s 10 m 47 028 3 a s 30mg Zt 038 3 ose 45mg 3 047 3 Placebo ai 052 g S & 2 025 The Cox regressionanalysis for
Slide 30: Relative Change of Serum NfL Concentrations Versus Placebo
Relative Change of Serum NfL Concentrations Versus Placebo After 24 Weeks (Cohorts 1&2) 50% The relative change of serum neurofilament light chain versus placebo is proportional to vidofludimus calcium dose. = May reflect increasing trough -9% levels and related improved effects of vidofludimus calc
Slide 31: Longitudinal Change of EDSS and Unconfirmed EDSS Progressions
Longitudinal Change of EDSS and Unconfirmed EDSS Progressions (Cohorts 1 & 2) Change of EDSS From Baseline to Week 24 28 28 a 27 oo 26 = 25 24 Baseline Week 12 Week 24 10 mgIMU-838 =mm3O mg IMU-838 MMS mg |IMU-338 eMMPlacebo Displayedre mean values combined datafor Cohort and 2 patients EDSS: Ecpand
Slide 32: Dose-Response Relationship of Longitudinal Change in EDSS
Dose-Response Relationship of Longitudinal Change in EDSS (Cohorts 1 & 2) Change of EDSS From Baseline to Week 24 Neuroprotective effects on EDSS seem to start at a low dose of » a 10 me of IMU-838. 27, ——————— This low, 10 mg dose of IMU-838 26 _——— performs similarly well regarding os change in ED
Slide 33: Neurofilament Light Chain in Serum at Week 24
Neurofilament Light Chain in Serum at Week 24 A Promising Signal of Neuroprotective Activity Median of % of Change of Serum Neurofilament from pase eras Competed rh iiaceea Arobust and dose-linear decrease in serum 10 . 5 neurofilament light chain provides a 5 ing signal of neuroprotective activity
Slide 34: Relative Change of Serum Neurofilament from Baseline to Week 24
Relative Change of Serum Neurofilament from Baseline to Week 24 (Cohorts 1 & 2) 50% The relative change of serum _ neurofilament light chain versus placebo is proportional to vidofludimus calcium dose. = May reflect increasing trough levels and related improved -9% effects of vidofludimus calcium =
Slide 35: Conclusions Cohort 2
Conclusions Cohort 2 Regarding Efficacy Doses of 30 and 45 mg of vidofludimus calcium showed compelling anti-inflammatory effects (with 65-78% reduction in CUA and Gd+ lesions) and other signs of clinical activity, while the 10 mg dose has shown no or minimal effects on MRI lesions. This confirms th
Slide 36: Vidofludimus Calcium: DHODH Inhibition Provides Broad-Spectrum Antiviral Activity
Vidofludimus Calcium: DHODH Inhibition Provides Broad- Virus Mutations are Not Expected to Have Any Impact on Vidofludimus Calcium’s Activity Spectrum Antiviral Activity Against Different Pathogenic Viruses Antiviral Activity With EC., Values in Single Digit WM Range In general, viruses rely on the
Slide 37: Clinical Data of Vidofludimus Calcium in the COVID-19 Context
Clinical Data of Vidofludimus Calcium in the COVID-19 Context Treatment With Vidofludimus Calcium Does Not Interfere with Antibody Development During SARS-CoV-2 Infection Treatment With Vidofludimus Calcium Decreases the Number of Opportunistic COVID-19 Infections IMU-838 Day6 Day 14 Day 28 Placebo
Slide 38: Link of Epstein-Barr Virus (EBV) Infection and Onset of MS
Link of Epstein-Barr Virus (EBV) Infection and Onset of MS Fig 3. EBV infection precedes. a levation of sNfL before the onset Try ee EV incon Neve, Tacos ative of 1 EB poem spo ner con ‘of MS. (A) Box plots of si levels before, around, and after the time of EBV infection, *P < 005, two sided multiva
Slide 39: New Data Provide New Insights Into Potential MS Therapies
New Data Provide New Insights Into Potential MS Therapies Based on Epstein-Barr Virus (EBV) Antiviral Effects EBV infection has been linked to MS epidemiologically, but its pathological role remains unclear. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBN
Slide 40: Epstein-Barr Virus (EBV) Virus Shedding in Saliva as Indicator for Lytic Infection
Epstein-Barr Virus (EBV) Virus Shedding in Saliva as Indicator for Lytic (Active) Infection Lytic EBV Activityin an MS Population Teriflunomide Decreases Lytic EBV Activity Number of Proportion of Patients % Samples With EBV Shedding* . Overall Patients with EBV Virus 3 Studies with EBV Shavhhie O58
Slide 41: Epstein-Barr Virus (EBV) Antibody Titers are Higher in MRI-Active Patients
Epstein-Barr Virus (EBV) Antibody Titers are Higher in MRI-Active Patients 41. | ©immunic, inc. | Mi lo) is 2 te) 2 = 2 a Ww ps<0.001 | 791 295 ~ ee 2 iw) Ratio of EBNA1:VCA IgG Ny So J 2 o be ° r p<0.001 3.8 aa EBNA-1 Gd-ve EBNA-1 Gd +ve Subjects with non-active/active MRI 2009,732):32-38 nglobulin
Slide 42: Vidofludimus Calcium: Potent Anti-Epstein-Barr Virus (EBV) Activity
Vidofludimus Calcium: Potent Anti-Epstein-Barr Virus (EBV) Activity Demonstrated in Cell-Culture-Based Systems Anti-Akata-BX1-EBV-GFP Stimulated With higG 110- 100- : a Z 90. 2 80. 5 Vidofludimus calcium showed concentration- § 0 dependent anti-EBV = 50- 7 activity at concentrations of Fa 40. a 3.3-
Slide 43: Summary of DHODH-Related Antiviral Effects and Anti-EBV Activity
Summary of DHODH-Related Antiviral Effects and Anti-Epstein- Barr Virus (EBV) Activity = Vidofludimus as a DHODH inhibitor is known to have broad-spectrum antiviral effects — Clinical proof of antiviral effects demonstrated in a trial in moderate COVID-19 patients — Preclinical models also documente
Slide 44: Vidofludimus Calcium is Targeted to Improve Long-Term Clinical Outcomes
Vidofludimus Calcium is Targeted to Improve Long-Term Clinical Outcomes for Patients with All Forms of MS Anti-Inflammatory Effects v Selectively targets hyperactive immune cells v Reduces MRI lesions v Reduces relapses Y Mechanism already shown to reduce brain atrophy MRI: magnetic resonance imagin
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Slide 46: Reasons and Rate for Treatment Discontinuations Due to Adverse Events and SAE
Reasons and Rate for Treatment Discontinuations Due to Adverse Events and SAE (Cohort 1&2) aa iscontinuations: ig totreatment Treatment Discontinuation Before 2 Iver enaymiewARUOTS Week 24 (all dosed patients until end N=1 cervix carcinoma of blinded treatment slhematurie Placebo 7.4% 6/81 | | Noeve
Slide 47: Most Common Treatment-Emergent Adverse Events
Most Common Treatment-Emergent Adverse Events Adverse Events Present in More Than 1% of Study Population There were very few adverse events with medium and high incidence rate Tog UES ESTATE ng MOSS Fiesebotca ial Tomber Tomber Timber Number Tumoer numoer| of | eatents | nomoer] of | eatents | numbe
Slide 48: Treatment-Emergent Adverse Events
Treatment-Emergent Adverse Events No Increase in Infections and Infestations (Cohort 1&2) Rate of Infections and Infestations C1+ C2 = Rate of Infections and Infestations ae Z mg IMU mgiMU- foe lacebo C1+ 10mgimu-s38 | 30mgiwu-838 | 45 mgiMU-838 nee Placebo C1sc2 30 Kot Kot Kot Kot Kot N N N N N pt
Slide 49: Clinical Data of Vidofludimus Calcium in the COVID-19 Context
Clinical Data of Vidofludimus Calcium in the COVID-19 Context Treatment Does Not Interfere With Antibody Opportunistic COVID-19 Infections Development During SARS-CoV-2 Infection Treatment Tends to Decrease the Number of IMU-838 (10 mg QD) Placebo Day 6 Day 14 Day 28 IgA IgG IgA IgG IgA IgG Any Infe
Slide 50: EMPhASIS Trial Liver Events
EMPHASIS Trial Liver Events No Increase in the Rate of Liver Enzyme Elevations (Cohort 1&2) Rate of Liver Enzyme Elevations in % of Patients ; j liver enzyme _ elevations 3 above certain thresholds were as prevalent in placebo Very few cases of increases of alanine ae as in the vidofludimus aminotra
Slide 51: Hy's Law Assessment of Liver Events
Hy’s Law Assessment of Liver Events No Signal for Drug-Induced Liver Injury Observed for Vidofludimus Calcium Peak Alanine- Aminotransferase Peak Aspartate- Aminotransferase Cohort 1 Hy's law plot of allpatientsfrom Cohort 1 and Cohort 2Safety analysis set C1/C2 (N1O=47,N30=71,N@5=69, NFBOC1=63, NPB
Slide 52: Hematology Analysis: Lymphocyte and Neutrophile Counts
Hematology Analysis: Lymphocyte and Neutrophile Counts No Change in Hematology from Baseline to Week 24 Lyme sb ES at esp abs 10694) hi i ee Lymphocytes, Neutrophiles Counts (10° | placebo | 10mg | 30mg | 45mg | Placebo} 10mg | 30mg | 45mg cells/t) aso | 180 | 189 | 127 | aos | 390 | sa: | 426 Basel
Slide 53: Conclusions Regarding Safety
Conclusions Regarding Safety = The administration of vidofludimus calcium in this trial was observed to be well-tolerated, thereby providing further evidence of a favorable safety profile of vidofludimus calcium in the RRMS patient population. — Safety profile is similar to placebo group = Very low
Slide 54: Vidofludimus Calcium's Safety and Tolerability Profile to Date is Unique
Vidofludimus Calcium’s Sa Unique fety and Tolerability Profile to Date is Vidofludimus (a1 Calcium! Teriflunomide’™ Dimethyl Fumarate”! Cladribine! fa Fingolimod!) Siponimod!®) Ponesimod”! Ozanimod!® PML Risk Increased Number of Infections Vaccination Limitations Gastrointestinal Toxicities, Incl. D
Slide 55: Summary
Summary Vidofludimus Calcium Seems to Provide Anti-Inflammatory and Direct Neuroprotective Effects as well as Anti-EBV Effects to Progressive Multiple Sclerosis Patients Vidofludimus calcium showed compelling anti-inflammatory effects and clinical activity regarding inhibition of MRI lesions that ar
Slide 56: Phase 3 and Approval Strategy in MS
Phase 3 and Approval Strategy in MS Phase 3 ENSURE Program in RMS Phase 2 CALLIPER Trial in PMS = Two identical pivotal trials in RMS patients * Phase 2 trial in PMS patients = Goal: Demonstrate vidofludimus calcium’s potential for neuroprotective activity = Dosage: 45 mg vidofludimus calcium QD ® C
Slide 57: Thank You!
Thank You! Immunic AG Immunic, Inc. Grafelfing near Munich 1200 Avenue of the Americas Germany New York City, NY 10036 USA ee = Immunic Research GmbH === A Weinberg Campus Halle (Saale) Germany Immunic Australia Pty. Ltd. “Melbourne Australia 57 | ©immunic, inc. | May/10/2022