Slide 1: Changing Paradigms: IMU-856 Celiac Disease Clinical Phase 1b Results
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements 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 pub
Slide 3: Today's Highlights
Today’s Highlights 3. | © immunic, inc. | May/04/2023 Positive Phase 1b Results of IMU-856 in Celiac Disease Regeneration and protection of the gut wall proven for the first time in patients, establishing a new concept for healthy gut in gastrointestinal disorders Consistent clinical benefit seen ac
Slide 4: IMU-856 could become a game changer in the way we treat gastrointestinal diseases
IMU-856 could become a game changer in the way we treat gastrointestinal diseases.
Slide 5: Once-Daily, Oral IMU-856 Aims to Regenerate the Gut Wall and Barrier Function
Once-Daily, Oral IMU-856 Aims to Regenerate the Gut Wall and Barrier Function by a New Epigenetic Mechanism Damaged Gut Wall Healthy Gut Wall Bowel lumen Bowel lumen IMU-856: antigens, microbiome, nutrients antigens, microbiome, nutrients . . = Epigenetic modulator aimed to regenerate gut wall and K
Slide 6: Enhances the Natural Regenerative Process in the Gut
IMU-856 Enhances the Natural Regenerative Process in the Gut 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 rene
Slide 7: IMU-856 is a completely new approach for the treatment of gastrointestinal diseases
IMU-856 is a completely new approach for the treatment of gastrointestinal diseases by restoring a healthy gut by renewal of the gut wall.
Slide 8: First Proof-of-Concept for Gastrointestinal Disorders in Celiac Disease
First Proof-of-Concept for Gastrointestinal Disorders in Celiac Disease Celiac Disease is a Serious Life-Long Disease Celiac disease is a multifactorial, complex autoimmune disease caused by an immune reaction against a degradation product of gluten and is strongly associated with specific HLA oe gl
Slide 9: Addresses Two Key Pathological Aspects of Celiac Disease
IMU-856 Addresses Two Key Pathological Aspects of Celiac Disease IMU-856 Mode of Action Orally available and systemically acting small molecule modulator that targets a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium Celiac Dise
Slide 10: Celiac Disease Currently Has No Adequate Treatment Options
Celiac Disease Currently Has No Adequate Treatment Options = Two million patients diagnosed with celiac disease in the , _ -_ . (1,2) 10 mg of gluten is the total limit for all US; more than one million more undiagnosed! foods combined for the entire day. = Most studies report between 24% and 47%“!
Slide 11: Shows Positive Effects in Main Four Dimensions of Clinical Outcome
IMU-856 Shows Positive Effects in Main Four Dimensions of Clinical Outcome in Celiac Disease Patients IMU-856 reduces/reverses gluten-induced symptoms reported by patients IMU-856 effectively reduces gluten-induced intestinal damage, as measured by villous height Improve Patients’ Symptoms pee Enhan
Slide 12: Trial Design
THERAPEUTICS Trial Design Phase 1b Clinical Trial of IMU-856
Slide 13: Trial Design Phase 1b Clinical Trial of IMU-856
Trial Design Phase 1 Clinical Trial of IMU-856 PART C Evaluation of patients with celiac disease receiving 28-day treatment of IMU-856 or placebo = Planned dosing completed: 80 and 160 mg QD of IMU-856 = 43 patients with celiac disease enrolled (IMU-856: N=29) = Provided proof-of-concept of IMU-856’
Slide 14: Phase 1b Clinical Trial of IMU-856 in Celiac Disease
Phase 1b Clinical Trial of IMU-856 in Celiac Disease Designed as a Gluten Challenge Trial Flow Chart of Part C in Celiac Disease Proof-of-Concept Study = Part C planned to include a well-controlled celiac disease patient population = 100% seronegative patients (indicating absence of ongoing substant
Slide 15: Patients Per Treatment Group
Patients Per Treatment Group Randomized/Completed N=43/35 Placebo 80 mg IMU-856 Assigned/Completed 160 mg IMU-856 Assigned/Completed Assigned/Completed N=14/11 N=15/13 N=14/11 Day 14 BL/Day 29 Day14 BL/Day 29 BL/Day 29 IL-2; N=14 EGD; N=11 IL-2; N=12 EGD; N=13 EGD; N=11 Reasons for Early Termination
Slide 16: Distribution of Q-MARSH Histology Score at Baseline
Distribution of Q-MARSH Histology Score at Baseline Approximately 60% of IMU-856 Treated Patients Already in FDA Required Phase 2/3 Population Category IMU-856 80mg _ | IMU-856 160mg All Active All Placebo = Inclusion criteria representing well-controlled (N=14) (N=15) (N=29) (N=14) celiac disease:
Slide 17: Protects Gut Architecture
THERAPEUTICS Protects Gut Architecture Phase 1b Clinical Trial of IMU-856
Slide 18: Histological Hallmarks of Celiac Disease
Histological Hallmarks of Celiac Disease Well-Controlled Celiac Disease |B | Ongoing Active Celiac Disease (OACD) = Villi with normal appearance = Villous height:Crypt depth ratio decreases Kambo) etal, Clinical and Transitional Gasroenterology (2017) e116 18 | © Immunic, inc. | May/04/2023 Immunic
Slide 19: Protects Villous Height as Compared to Placebo
IMU-856 Protects Villous Height as Compared to Placebo Absolute changein villous height (um) between Baseline and Day 29 Day 1-28: Treatment IMU-856/placebo to) Day 14-28: Gluten challenge with 6 g/daily -10 -20 = § alr 2 g 0. = Substantial protection for IMU-856 treatment groups as é compared to pl
Slide 20: Individual Patient Data for Changes in Villous Height
Individual Patient Data for Changes in Villous Height Dose-Dependent Shift in Histological Protection From Placebo to 160 mg of IMU-856 Relative change from Baseline in villous height SHNODII III O REP > Oy oe @ Subject Im IMU856 80mg jq IMU-856 160mg jy Placebo cual patient, Disease AnaysieSet: N=3
Slide 21: Staging of Celiac Disease: Q-Marsh Histological Scores
Staging of Celiac Disease: Q-Marsh Histological Scores Schematic Depiction of Marsh-Oberhuber Grades Healthy mucosa Little malabsorption No villous atrophy Little crypt hyperplasia Increased IELs ‘Adapted from Adelman etal, Am JGastroenterol2018, 113:339-347 TEL intraepithelial ymphocytes,CelD- celi
Slide 22: Shows Signal Preventing Histological Damage (Q-Marsh)
IMU-856 Shows Signal Preventing Histological Damage (Q-Marsh) Change in Q-MARSH between Baseline and Day 29 Deterioration/improvement defined as at least a decrease/increase of 1 category in Q-MARSH score on Day 29 as compared to Baseline Deterioration Improvement 100% 100% o% % eo wx 2 é 70% 63.696
Slide 23: Improves Patients' Symptoms
THERAPEUTICS Improves Patients’ Symptoms Phase 1b Clinical Trial of IMU-856
Slide 24: Treated Patients Have Fewer Symptoms After First Day of Gluten Challenge
IMU-856 Treated Patients Have Fewer Symptoms After First Day of Gluten Challenge Than Placebo Patients (on Day 14) Mean change in symptoms from last day before gluten challenge to first day of gluten challenge 1 0.9 Mean 0.8 Mean 0.8 Mean 0.8 sD 1.2 sD 1.1 sD14 2 08 Q 07 Mean 0.6 fat SD 1.0 2 06 Mea
Slide 25: Treated Patients Recover From Bloating Symptoms
IMU-856 Treated Patients Recover From Bloating Symptoms on Continued Treatment During Gluten Challenge Bloating: Mean change from Day 13 to Day 14 Bloating: Mean change from Day 14 to Day 29 Mean group change in CDSD score 2° o 8 & Az 6B 38 bo swioqdwiAs Jamed “06 Mean-0.5 08 SD 1.0 a Placebo mAll A
Slide 26: Treated Patients Recover From Tiredness Symptoms
IMU-856 Treated Patients Recover From Tiredness Symptoms on Continued Treatment During Gluten Challenge Tiredness: Mean change from Day 13 to Day 14 Tiredness: Mean change from Day 14 to Day 29 zl Mean 0.8 SD 1.1 Mean group change in CDSD score ° o 8 6 2 g swoqduiAs Jama4 0.4 Mean-0.3 sD 0.8 -0.6 0.
Slide 27: Biomarker Response
THERAPEUTICS Biomarker Response Phase 1b Clinical Trial of IMU-856
Slide 28: Dampens Acute IL-2 Immune Response on First Day of Gluten Challenge
IMU-856 Dampens Acute IL-2 Immune Response on First Day of Gluten Challenge Mean absolute change and maximum change in serum IL-2 (in pg/mL) from pre-gluten to 4 hours post- gluten on first day of gluten challenge Luminex® Test System SIMOA® Test System Max 274.3 Max 35.7 IMU-856 dampens gluten-indu
Slide 29: Shows Signal for Improving Citrulline
IMU-856 Shows Signal for Improving Citrulline Biomarker Reflecting the Health Status and Function of Enterocytes Mean change from Baseline to Day 14 Mean change from Baseline to Day 29 See - Citrulline is a non-essential amino 8 Wen acid that is mainly produced by the SD5.9 enterocyte and, hence, th
Slide 30: Enhances Nutrient Absorption
THERAPEUTICS Enhances Nutrient Absorption Phase 1b Clinical Trial of IMU-856
Slide 31: Shows Enhanced Uptake of Vitamin B12
IMU-856 Shows Enhanced Uptake of Vitamin B12 Mean change from Baseline to Day 29 in vitamin B12 (pmol/L) 80 60 40 Mean 45.8 SD 94.4 20 Serum vitamin B12 (pmol/L) -20 Mean -31.0 SD 68.8 40 Placebo (N=11) MIMU-856 80mg(N=11) ml IMU-856 160 mg (N=13) SD: standard deviation 31 | © Immunic, inc. | May/04
Slide 32: Shows Enhanced Uptake of Zinc
IMU-856 Shows Enhanced Uptake of Zinc Mean change from Baseline to Day 29 in zinc (mol/L) 0.8 Mean 0.9 SD 2.1 0.2 Mean SD 1. ° Serum zine (umo/L} Mean -0.9 08 SD 2.1 Placebo (N=11) MIMU-856 80mg(N=11) ml IMU-856 160 mg (N=13) SD: standard deviation 32 | © Immunic, inc. | May/04/2023 © Immunic
Slide 33: Shows Amelioration of Gluten-Induced Iron Malabsorption - Ferritin Levels
IMU-856 Shows Amelioration of Gluten-Induced Iron Malabsorption — Ferritin Levels Mean Change from Baseline to Day 29 in Ferritin (ug/L) Mean -11.4 SD 20.2 Serum ferritin (ug/L) “a2 Mean -40.3 $037.9 Placebo (N=11) MIMU-856 80mg(N=11) ml IMU-856 160 mg (N=13) SD: standard deviation 33 | © Immunic, i
Slide 34: Shows Improvement in Red Blood Cell Function as a Consequence of Improved Iron Absorption
IMU-856 Shows Improvement in Red Blood Cell Function as a Consequence of Improved Iron Absorption Mean Change from Baseline to Day 29 in MCHC (g/L) MCHC is a measure of the 4 concentration of hemoglobin as in red blood cells. g Since hemoglobin is the 5 2 molecule to which oxygen 5 2 attaches, MCHCi
Slide 35: Shows Positive Effects in Main Four Dimensions of Clinical Outcome
IMU-856 Shows Positive Effects in Main Four Dimensions of Clinical Outcome in Celiac Disease Patients IMU-856 reduces/reverses gluten-induced symptoms reported by patients IMU-856 effectively reduces gluten-induced intestinal damage, as measured by villous height Improve Patients’ Symptoms pee Enhan
Slide 36: Safety and Pharmacokinetics
Safety and Pharmacokinetics Phase 1b Clinical Trial of IMU-856
Slide 37: Overall Summary of Treatment Emergent Adverse Events
Overall Summary of Treatment Emergent Adverse Events Treatment Category IMU-856 80 mg _| IMU-856 160 mg All Placebo (N=14) (N=15) 26 (89.7) Subjects with mild TEAEs, n (96) 13 (92.9) 11 (73.3) 24 (82.8) 9 (64.3) Subjects with moderate TEAEs, n (%) 6 (42.9) 6 (40) 12 (41.4) 4 (28.6) Subjects with sev
Slide 38: Disease-Related TEAEs Associated With High Number of Ongoing Active Celiac Disease Patients
Disease-Related TEAEs Associated With High Number of Ongoing Active Celiac Disease Patients in IMU-856 Treatment Group TEAEs regularly associated with celiac disease and occurring in more than 10 % of all subjects Number of subjects (%) [number of TEAEs reported] (SEB IMU-856 80 mg | IMU-856 160 mg
Slide 39: No Change in Neutrophils as Compared to Placebo
No Change in Neutrophils as Compared to Placebo rq Laboratory Values Over Time Eee Individual Laboratory Values Hematology — Neutrophils Hematology — Neutrophils 39 | © Immunic, inc. | May/04/2023 & Immunic
Slide 40: No Hy's Law Cases
No Hy’s Law Cases Bilirubin vs. ALT Showed Eee Bilirubin vs. AST Showed No Evidence of DILI Potential No Evidence of DILI Potential ALT: Alanine Aminotansferase; AST Aspartate Aminotransferase; DIL ruginduced ler injury; BIL Bilirubin; ULN: Upper Limitof Normal 40 | © immunic, inc. | May/04/2023 © I
Slide 41: No Clinically Relevant Changes of QTcF Interval
No Clinically Relevant Changes of QTcF Interval 12-Lead ECGs Over Time =e Individual 12-Lead ECGs Ky QTcF Interval Ee QITcF Interval nim ns sas ” se j ‘ oe i i nis ms _— é " , hart ws FCG: electrocardiogram; QTeF Fridercs's correction formula for QT interval 41 | © immunic, inc. | May/04/2023 © Immu
Slide 42: Pharmacokinetics: Trough Levels After Multiple Dosing
Pharmacokinetics: Trough Levels After Multiple Dosing IMU-856 mean trough levels (ng/mL) 200 Day 8 =z 180 ay E Val = ved IMU-856 80mg _ | IMU-856 160 mg = 140 (Mean) 120 G 5 100 ea 354.5 765.6 § (ng/mL) & 80 ———— a) E 60 Tmax 19 15 = 40 (hr) : : s 20 Fo AUC ote 1568 3613 (hr*ng/mL) Day1 Day8 Day 14
Slide 43: Shows Positive Effects in Main Four Dimensions of Clinical Outcome
IMU-856 Shows Positive Effects in Main Four Dimensions of Clinical Outcome in Celiac Disease Patients © immunic, inc. May Final phase 1b celiac disease data consistently shows beneficial effects for IMU-856 over placebo: = Prevents histological damage = Consistent benefits on symptoms over placebo =
Slide 44: Intestinal Barrier Function is a Therapeutic Target Beyond Celiac Disease
Intestinal Barrier Function is a Therapeutic Target Beyond Celiac Disease Compromised intestinal barrier function has been associated not only with celiac disease but with a number of disease states, both intestinal and systemic Crohn’s disease: low bowel permeability has better ~~ Ser 2] probabilit
Slide 45: Could Elevate the Standard-of-Care Across Multiple Gastrointestinal Diseases
IMU-856 Could Elevate the Standard-of-Care Across Multiple Gastrointestinal Diseases With Histologic Damage Ulcerative Colitis “1 million patients in US Crohn’s Disease “1 million patients in US Celiac Disease >2 million patients in US = Major unmet need, ‘h no drug treatment options available 45 |
Slide 46: Could Become a Game Changer for the Treatment of Gastrointestinal Disorders
IMU-856 Could Become a Game Changer for the Treatment of Gastrointestinal Disorders IMU-856 is poised to be a potential paradigm shift in how to treat gastrointestinal diseases. Dozens of endpoints were investigated in this small exploratory trial and all demonstrated that IMU-856 has a beneficial e
Slide 47: Q&A Session
THERAPEUTICS Q&A Session Phase 1b Clinical Trial of IMU-856
Slide 48: Thank You!
Thank You! Immunic, Inc. 1200 Avenue of the Americas iyctorier scBiag’i New York City, NY 10036 nae a ven ‘ork City, 82166 Grafelfing (Munich) Germany Jessica Breu Head of IR & Communications & Phone: +49-89-2080477-09 ©@ Email: ir@imux.com Immunic Australia Pty. Ltd. Melbourne Australia ® Web: www.
Slide 49: Appendix
THERAPEUTICS Appendix Phase 1b Clinical Trial of IMU-856
Slide 50: Pathophysiology of Malabsorption in Celiac Disease
Pathophysiology of Malabsorption in Celiac Disease = The small intestine measures approximately 6 min length = The surface area of the small intestine is significantly enhanced by the presence of villi and microvilli by up to 600-fold = One of the main functions of villiis to absorb nutrients from t
Slide 51: Patient Demographics
Patient Demographics IMU-856 80 mg IMU-856 160 mg All Active All Placebo Parameter (N=14) (N=15) (N=29) (N=14) Mean age (years) 43.1 40.9 42.0 43.4 Female N (%) 8 (57.1) 10 (66.7) 18 (62.1) 11 (78.6) White 14 (100) 15 (100) 29 (100) 14 (100) Race N (%) Other (¢) (¢) ie) te) Mean height (cm) 173.86 1
Slide 52: Villous Height Results Stratified by Baseline Disease Severity
Villous Height Results Stratified by Baseline Disease Severity Baseline Disease Baseline Disease Severity by Baseline Mean Absolute Mean Relative|channe Severity Treatment Arm Nul Villous Height"! Change to Day 29 pon 2 (QMarsh) (Marsh) (in um) (in um) v Placebo pooled 383.6 -56.6 -14.4% Q-Marsh Sco
Slide 53: Shows Signal Preventing Histological Damage During Two-Week, 6 g Gluten Challenge (Vh:Cd)
IMU-856 Shows Signal Preventing Histological Damage During Two-Week, 6 g Gluten Challenge (Vh:Cd) Absolute change in Vh:Cd between Baseline and Day 29 IMU-856 80 mg IMU-856 160 mg All Active All Placebo (N=11) (N=13) (N=24) (N=11) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Absolute Change Vh:Cd -0.19 (
Slide 54: Patient Reported Outcomes: Celiac Disease Symptom Diary (CDSD)
Patient Reported Outcomes: Celiac Disease Symptom Diary (CDSD) CDSD Version 2.1° Description = The CDSD is a daily patient reported outcome measurement assessing the presence or absence of a broad range of symptoms typical for celiac disease = Phase 1b trial of IMU-856: — On Day 1: CDSD Questionnair
Slide 55: Shows Signal Protecting Against Acute Gluten-Induced Symptoms
IMU-856 Shows Signal Protecting Against Acute Gluten-Induced Symptoms on First Day of Gluten Challenge Mean change from last day before gluten challenge to first day of gluten challenge IMU-856 80 mg IMU-856 160 mg All Active All Placebo Symptom (N=13) (N=13) (N=26) (N=12) Mean (SD) Mean (SD) Mean (
Slide 56: Shows Signal Protecting Against Chronic Gluten-Induced Symptoms
IMU-856 Shows Signal Protecting Against Chronic Gluten-Induced Symptoms Mean change from Day 13 to Day 14 Mean change from Day 14 to Day 29 N Bloating Tiredness N Bloating Tiredness Mean (SD) Mean (SD) Mean (SD) Mean (SD) IMU-856 80 mg 13 0.3 (0.85) 0.2 (0.60) 9 -0.4 (1.01) -0.1 (0.33) IMU-856 160 m
Slide 57: Patient Reported Outcomes: Impact Of Celiac Disease Symptom Questionnaire (ICDSQ)
Patient Reported Outcomes: Impact Of Celiac Disease Symptom Questionnaire (ICDSQ°) Description Questionnaire is assessed weekly and suggested as complement to the Celiac Disease Symptom Diary (CDSD)!#): Schedule of assessment phase 1b trial of IMU-856: — Baseline (Day 1) — Visit 2 (day 8) — Visit 3
Slide 58: Ameliorates Negative Gluten-Induced Impact on Daily Activities
IMU-856 Ameliorates Negative Gluten-Induced Impact on Daily Activities Daily Activities, Mean Change Baseline to Day 14 Day 14 to Day 22 Day 14 to Day 29 Mean Change Mean Change Mean Change N N N Mean (SD) Mean (SD) Mean (SD) IMU-856 80 mg 14 0.089 (0.362) 11 0.091 (0.573) 10 0.000 (0.425) IMU-856 1
Slide 59: Non-Inferior to Placebo Regarding Negative Gluten-Induced Impact on Social Activities
IMU-856 Non-Inferior to Placebo Regarding Negative Gluten- Induced Impact on Social Activities Social Activities, Mean Change Baseline to Day 14 Day 14 to Day 22 Day 14 to Day 29 N Mean Change N Mean Change N Mean Change Mean (SD) Mean (SD) Mean (SD) IMU-856 80 mg 14 -0.095 (0.275) 11 0.182 (0.721)
Slide 60: Ameliorates Negative Gluten-Induced Impact on Emotional Well-Being
IMU-856 Ameliorates Negative Gluten-Induced Impact on Emotional Well-Being Emotional Well-Being, Mean Change Baseline to Day 14 Day 14 to Day 22 Day 14 to Day 29 Mean Change Mean Change Mean Change N Mean (SD) N Mean (SD) N Mean (SD) IMU-856 80 mg 14 -0.014 (0.183) 11 0.105 (0.294) 9 -0.044 (0.088)
Slide 61: Ameliorates Negative Gluten-Induced Impact on Physical Activities
IMU-856 Ameliorates Negative Gluten-Induced Impact on Physical Activities Physical Activities, Mean Change Baseline to Day 14 Day 14 to Day 22 Day 14 to Day 29 Mean Change Mean Change Mean Change N N N Mean (SD) Mean (SD) Mean (SD) IMU-856 80 mg 14 0.11 (0.289) 11 -0.09 (0.302) 9 -0.11 (0.333) IMU-8