Immunic, Inc. · NASDAQ:IMUX
Immunic — Investor Day (September 2024)
85 slides from Immunic's investor day presentation, Sep 10, 2024
Slide 1: Immunic Therapeutics Multiple Sclerosis R&D Day
Immunic Therapeutics Multiple Sclerosis R&D Day NASDAQ: IMUX | September 10, 2024 | New York City
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 saf e harbor within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securitie
Slide 3: Welcome and Introductions
01 Multiple Sclerosis R&D Day Welcome and Introductions
Slide 4: Speakers: Immunic's Multiple Sclerosis R&D Day
Speakers: Immunic’s Multiple Sclerosis R&D Day Immunic Speakers Featured Experts Daniel Vitt, PhD Francesca Montarolo, PhD Co-Founder Neuroscience Institute Cavalieri Ottolenghi (NICO) Chief Executive Officer and University of Turin, Italy Hella Kohlhof, PhD Amit Bar-Or, MD, FRCPC Co-Founder Departm
Slide 5: Agenda: Immunic's Multiple Sclerosis R&D Day
Agenda: Immunic’s Multiple Sclerosis R&D Day Vidofludimus Calcium’s Profile and Positioning as a Potentially Groundbreaking Multiple Sclerosis Therapy Relevance of Neuroprotection and 01 10:30 – 10:35 Welcome and Introductions 05 11:45 – 12:10 Preventing Disability Worsening for MS Patients Featured
Slide 6: Clinical-Stage Biopharmaceutical Company
CLINICAL-STAGE Innovative pipeline: BIOPHARMACEUTICAL First-in-class oral drugs with unique modes of actions for multiple COMPANY (NASDAQ: IMUX) sclerosis and gastrointestinal diseases Dedicated to improving the lives of patients with chronic inflammatory and autoimmune diseases Experienced leadersh
Slide 7: Advanced Clinical Pipeline
Advanced Clinical Pipeline Well Differentiated Programs in Various Phases of Clinical Development Program Preclinical Phase 1 Phase 2 Phase 3 Key Program Updates ✓ Phase 2 EMPhASIS trial in relapsing-remitting MS successfully completed Relapsing Multiple Sclerosis (RMS) – ENSURE-1 and ENSURE-2 Trial
Slide 8: Multiple Sclerosis is a Lifelong Neurodegenerative Disease
Multiple Sclerosis is a Lifelong Neurodegenerative Disease Lifelong Disease Therapeutic Goal: Requiring Decades of Therapy Increase Independence ▪ ~2.9 million people affected worldwide[1] ▪ Key unmet need: prevention or slowing of long-term ▪ ~1 million people affected in US[1] disability worsening
Slide 9: The Unmet Medical Needs in Multiple Sclerosis
The Unmet Medical Needs in Multiple Sclerosis Despite Being on Efficient Relapse-Targeting Therapies, Majority of Patients Still Experiences Goals for New Disability Worsening[1] Multiple Sclerosis Treatments 50% ▪ Developing a new therapy offering: of DMT-treated − Neuroprotective effects and effec
Slide 10: Vidofludimus Calcium Aims to Redefine the Oral MS Treatment Landscape
Vidofludimus Calcium Aims to Redefine the Oral Multiple Sclerosis Treatment Landscape Combines the best of two worlds: neuroprotection and relapse prevention ▪ Positive phase 2 data in relapsing-remitting multiple sclerosis ▪ Hints to slowing down disability worsening ▪ Positive biomarker data from
Slide 11: Vidofludimus Calcium: Clinical Trials Overview in MS
Vidofludimus Calcium: Clinical Trials Overview in Multiple Sclerosis (MS) H2/2026 ENSURE-2 RELAPSING MS Phase 3 Actively recruiting, n=1050 patients planned Completion (expected) Q2/2026 ENSURE-1 RELAPSING MS Phase 3 Actively recruiting, n=1050 patients planned Completion (expected) April 2025 CALLI
Slide 12: The Commercial Opportunity
02 Multiple Sclerosis R&D Day The Commercial Opportunity
Slide 13: Vidofludimus Calcium Has the Potential to Transform the Oral MS DMT Market
Vidofludimus Calcium Has the Potential to Transform the Oral Multiple Sclerosis DMT Market Anticipated Profile 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 wi
Slide 14: ~1.3 Million People Worldwide Diagnosed with Multiple Sclerosis
~1.3 Million People Worldwide Diagnosed with Multiple Sclerosis Across Three Distinct Indication Categories Relapsing MS Non-Relapsing SPMS Primary Progressive MS ▪ Relapses and MRI lesions dominate Relapses have stopped, but disability Disability worsening without relapses from clinical course (RRM
Slide 15: A Heterogenous Disease Where One Size Does Not Fit All
A Heterogenous Disease Where One Size Does Not Fit All The primary goals of MS treatment While broad patterns in treatment There is no “one size fits all” are to reduce disease activity, exist, all DMTs have a clinical role, treatment protocol and HCPs delay disability progression, and and DMT use i
Slide 16: Clinicians Still Prefer a Tailored Approach for Each Patient
Clinicians Still Prefer a Tailored Approach for Each Patient Individually Approach to Creating a Treatment Plan for MS Patients % of respondents I tailor my approach for each patient 41% individually 59% I typically prefer to use a DMT escalation approach (starting with a safer agent and 24% switchi
Slide 17: A Large and Growing Global Market Where Multiple Blockbusters Coexist
A Large and Growing Global Market Where Multiple Blockbusters Coexist Many brands are generating in excess of $1 billion in global annual sales in 2023[1] $20 billion market today growing 4% y/y [2] Major market sales of MS therapies($ billion) Ocrevus® $7.2 billion 35 Kesimpta® $2.2 billion 30 Tysa
Slide 18: Oral DMTs Will Continue to Play a Big Role as Important Treatment Options
Oral DMTs Will Continue to Play a Big Role as Important Treatment Options Global Market Share by Drug Class 2022 vs. 2032[1] While the anti-CD20 class of therapies continues to grow, the oral class still captures 31% over 1/3 of the global market 39% 38% ▪ Data supports that 42% of patients prefer 4
Slide 19: Unmet Needs Still Exist for New Products to Address Disability Accumulation
Unmet Needs Still Exist for New Products to Address Disability Accumulation and Progressive Disease “I would say that treatment of progressive MS is the biggest “Finding an oral drug that is challenge. I don’t think efficacious but has little to there are any good no side effects.” treatments for se
Slide 20: The Ideal Agent Would Work Across the Disease Continuum
The Ideal Agent Would Work Across the Disease Continuum Addressing Relapses, MRI Activity, RAW and PIRA Newer data shows that half of the disability accumulation in relapsing MS foca comes from PIRA and is contributed to l inf lam the underlying “invisible disability ma tio accumulation” or “smolder
Slide 21: Vidofludimus Calcium Has the Potential to Offer a Superior Benefit / Risk Balance
Vidofludimus Calcium Has the Potential to Offer a Superior Benefit / Risk Balance Benefit Risk Relapses Safety MRI activity Tolerability Disability (RAW) Convenience Disability (PIRA) Burden of use MRI: magnetic resonance imaging; RAW: relapse-associated worsening; PIRA: progression independent of r
Slide 22: Multiple MS Patient Segments Could Benefit from Vidofludimus Calcium
Multiple MS Patient Segments Could Benefit from Vidofludimus Calcium Older patients where Newly diagnosed patients immunosuppression is a concern Patients switching therapies due to disability Untreated patients worsening Patients switching Patients with progressive therapies due to tolerability dis
Slide 23: Phase 3 Pipeline of Oral DMTs in Both RMS and PMS
Phase 3 Pipeline of Oral DMTs in Both RMS and PMS: Vidofludimus Calcium Is the Only Non-BTKi Nurr1 Activator / DHODH Inhibitor BTK Inhibitor Vidofludimus Calcium RELAPSING MS (ENSURE-1 & ENSURE-2) Tolebrutinib | Phase 3 RELAPSING MS (GEMINI 1 & GEMINI 2) Phase 3 & Phase 2 Completion expected 2026 Da
Slide 24: Derisked Near-Term Opportunity with $2-6 Billion Peak Potential
Vidofludimus Calcium: Derisked Near-Term Opportunity with $2-6 Billion Peak Potential RMS nrSPMS PPMS Indication Phase 3 Phase 2 Phase 2 Status 76% reduction in 20.1% reduction in serum NfL compared 18.8% reduction in serum NfL compared Clinical new Gd+ lesions (Phase 2) to placebo in nrSPMS patient
Slide 25: Relevance of Nurr1 as an Emerging Neurodegenerative Target
03 Multiple Sclerosis R&D Day Relevance of Nurr1 as an Emerging Neurodegenerative Target
Slide 26: Vidofludimus Calcium Addresses Smoldering Neurodegeneration
Vidofludimus Calcium Addresses Smoldering Neurodegeneration First-in-Class Nurr1 Activator, Targeting Improvement of Physical and Mental Ability of Multiple Sclerosis Patients Nurr1 Activator DHODH Inhibitor ▪ Direct and indirect ▪ Selectively targets hyperactive neuroprotective effects immune cells
Slide 27: Nurr1 Is a Nuclear Receptor Involved in Neuroprotection
Nurr1 Is a Nuclear Receptor Involved in Neuroprotection Nurr1 is expressed in different cells relevant for neuroprotection microglia astrocyte neuron Nurr1 activation prevents microglia/ Nurr1 activation mediates neuronal survival astrocyte-driven neurotoxicity in the brain Nurr1 activation in motor
Slide 28: Francesca Montarolo, PhD
Francesca Montarolo, PhD Senior Post-Doc Researcher, Neuroscience Institute Cavalieri Ottolenghi (NICO) and University of Turin, Italy Biologist, Leading MS and Nurr1 Target Expert ▪ Expert in neuroscience, cell biology and immunology ▪ PhD in experimental neuroscience from University of Turin, Ital
Slide 29: Francesca Montarolo, PhD
Featured Expert Francesca Montarolo, PhD Biologist, leading MS and Nurr1 target expert Neuroscience Institute Cavalieri Ottolenghi (NICO) and University of Turin, Italy
Slide 30: Q&A Session with Francesca Montarolo, PhD
Multiple Sclerosis R&D Day Q&A Session with Francesca Montarolo, PhD
Slide 31: Vidofludimus Calcium Activates the Neuroprotective Transcription Factor Nurr1
Vidofludimus Calcium Activates the Known Neuroprotective Transcription Factor Nurr1 (NR4A2) at Nanomolar Concentrations Direct binding of vidofludimus calcium to Nurr1 confirmed by using an ITC method with Kd of 700 nM Vidofludimus calcium binds to and strongly activates Nurr1 activity with nM value
Slide 32: Nurr1 Is a Nuclear Receptor Involved in Neuroprotection
Nurr1 Is a Nuclear Receptor Involved in Neuroprotection Vietor et al., Journal of Medicinal Chemistry 2023 66 (9), 6391-6402; Schiro et al., 2022, Frontiers in Neurology, adapted from Willems S, Merk D. J Med Chem. 2022;65(14):9548-9563; illustrations created in BioRender.com Nurr1: nuclear receptor
Slide 33: Nurr1 Is a Nuclear Receptor Involved in Neuroprotection
Nurr1 Is a Nuclear Receptor Involved in Neuroprotection Nurr1 is expressed in different cells relevant for neuroprotection Nurr1 activation by vidofludimus calcium leads to induction of primary target genes in these cells N2A cell HMC3 1.4 * 1.3 1.2 Relative mVMAT2 1.1 1.0 0.9 0.8 0.7 0.7 0.0 0 0.1
Slide 34: Vidofludimus Calcium Reduces Microglia Activation
Vidofludimus Calcium Reduces Microglia Activation ▪ Nurr1 can prevent antigen-induced activation of microglia and subsequent production of pro-inflammatory cytokines in the brain. In our experiment, vidofludimus calcium (#1260) attenuated LPS-stimulated IL-6, TNF⍺ and IFNγ production in human HMC3 m
Slide 35: Vidofludimus Calcium Improves Neuronal Survival
Vidofludimus Calcium Improves Neuronal Survival Protective Effects Already Present at 1 µM Concentrations in Human and Murine Cell Systems ▪ Vidofludimus calcium dose dependently improves ▪ Vidofludimus calcium improves neuronal survival after survival of murine neuronal cells after apoptosis apopto
Slide 36: High Dose Demonstrated Activity in Murine EAE Model 1/2
High Dose of Vidofludimus Calcium Demonstrated Activity in Murine EAE Model 1/2 Dose dependent reduction of Primary Nurr1 target genes are regulated in clinical score in EAE mouse model brain and spinal cord ▪ TH – brain Tyrosine Hydroxylase ▪ SOD – spinal cord protects against ROS Brain Spinal Cord
Slide 37: Vidofludimus Calcium Induces Nurr1 Effects In Vivo, EAE Model 2/2
Vidofludimus Calcium Induces Nurr1 Effects In Vivo, EAE Model 2/2 Brain-derived neurotrophic factor (BDNF) plays Neurofilament light chain (NfL) is a neuronal protein an important role in neuronal survival and associated with neurodegeneration and neuroaxonal growth and is is a direct target of Nurr
Slide 38: Activity in Murine EAE Model Supported by Histological Improvement
Activity of Vidofludimus Calcium in Murine EAE Model is Supported by Histological Improvement in Spinal Cord ▪ Improving myelination status ▪ Reducing microglia activation ▪ Reducing axonal injury 8 50 8 * % of IBA1+ area 40 6 % of APP+ area 6 % of MBP+ area 30 p=0.05 4 4 20 p=0.05 10 2 2 0 0 Vehicl
Slide 39: Vidofludimus Calcium Specifically Targets Highly Metabolically Activated Immune Cells
Vidofludimus Calcium Specifically Targets Highly Metabolically Activated Immune Cells – Acting on Focal Inflammation in MS Hyperactive/High-Affinity Immune Cells Vehicle Vidofludimus Calcium are Specifically Dependent on DHODH 104 104 0.53% 0.25% MFI 108 MFI 37 103 103 ▪ High metabolic turnover in h
Slide 40: DHODH Inhibition Provides Broad-Spectrum Antiviral Activity
Vidofludimus Calcium: DHODH Inhibition Provides Broad- Spectrum Antiviral Activity Against Different Pathogenic Viruses Inhibits Epstein-Barr Virus (EBV) Showed Dose-Dependent Decreased Number of Opportu- Replication and Reactivation Inhibition of EBV Reactivation nistic SARS-CoV-2 Infections By tar
Slide 41: Vidofludimus Calcium: General Effects on MS Disease Processes
Vidofludimus Calcium: General Effects on MS Disease Processes 2 3 Improving the survival of neurons Targeting metabolically active in a neurotoxic environment immune cells involved in MS Nurr1 Activation Neuronal apoptosis DHODH Inhibition 1 Reducing the activation of microglia (which are a Microgli
Slide 42: Takeaways: Mode of Action and Preclinical
Takeaways: Mode of Action and Preclinical Vidofludimus Calcium Has the Potential to Address the Unmet Medical Needs in Progressive and Relapsing MS ▪ Reducing neurodegeneration − Directly by improving survival and function of neurons − Indirectly by reducing the neurotoxic activity of activated micr
Slide 43: Ongoing Phase 3 ENSURE Program in Relapsing Multiple Sclerosis
04 Multiple Sclerosis R&D Day Ongoing Phase 3 ENSURE Program of Vidofludimus Calcium in Relapsing Multiple Sclerosis
Slide 44: EMPhASIS: Completed Phase 2 Trial in Relapsing-Remitting MS
EMPhASIS: Completed Phase 2 Trial in Relapsing-Remitting MS NCT03846219 Trial Met Key Efficacy and Safety Endpoints ▪ Randomized 268 patients in 36 centers across four Coordinating Investigator European countries ▪ Vidofludimus calcium showed strong activity in relapsing- Robert J. Fox, M.D. Clevela
Slide 45: EMPhASIS: Strong Reduction of MRI Lesion Activity
EMPhASIS: Strong Reduction of MRI Lesion Activity Primary Endpoint Hit With High Statistical Significance, Pooled Cohorts 1 & 2 Reduction in Cumulative CUA Lesions up to Week 24 Reduction in Gd+ Lesions up to Week 24 0 0 0 7 0 5 0 -13% -10 4.5 -10 6 -20 4 -20 5 -30 3.5 -30 4 -40 3 -40 -50 2.5 -50 3
Slide 46: ENSURE: Ongoing Pivotal Phase 3 Trials in Relapsing MS
ENSURE: Ongoing Pivotal Phase 3 Trials in Relapsing MS NCT05134441 & NCT05201638 Two Multicenter, Randomized, Double-Blind Phase 3 Trials ▪ Approximately 1,050 patients in each trial Coordinating Investigator ▪ More than 100 sites in the United States, Latin America, Central and Eastern Europe, and
Slide 47: ENSURE: General Phase 3 Study Design in RMS
ENSURE: General Phase 3 Study Design in RMS Main Treatment Period Open-Label Extension Period (Optional) Screening Period 72 Weeks (Blinded) Up to 8 Years (Unblinded) 30 mg IMU-838 EoMT R 30 mg IMU-838 EoT EoS Placebo EoMT Screening exam Visits every 12 weeks Visits every 24/48 weeks D0 W24 W48 W72
Slide 48: ENSURE: Powering Assumptions and Interim Analysis
ENSURE: Powering Assumptions and Interim Analysis Event-Based Interim Analysis Sample Size Calculation ▪ Planned after approximately half of the ▪ Primary endpoint for both trials is time events have occurred in the double- to first relapse up to 72 weeks blind treatment periods ▪ The events require
Slide 49: Unrivaled Safety and Tolerability Profile Observed in Multiple Clinical Trials
Unrivaled Safety and Tolerability Profile Observed for Vidofludimus Calcium in Multiple Clinical Trials ▪ Safety profile similar to placebo: no general safety ▪ Drug exposure tested in more than 1,800 human subjects and signals observed in clinical trials so far patients, to date ▪ No increased rate
Slide 50: Takeaways: Relapsing Multiple Sclerosis
Takeaways: Relapsing Multiple Sclerosis Vidofludimus Calcium Aims to Redefine the Oral Multiple Sclerosis Treatment Landscape ▪ Combines the best of two worlds: neuroprotection and relapse prevention ▪ Easy to use: once-daily oral tablet ▪ Easy initiation: No complex screening requirements for docto
Slide 51: Relevance of Neuroprotection and Preventing Disability Worsening for MS Patients
05 Multiple Sclerosis R&D Day Relevance of Neuroprotection and Preventing Disability Worsening for Multiple Sclerosis Patients
Slide 52: Vidofludimus Calcium Showed Blood NfL Response Across Active and Non-Active Progressive Disease
Vidofludimus Calcium Showed Blood NfL Response Across Active and Non-Active Progressive Disease Phase 2 EMPhASIS Phase 2 CALLIPER Siponimod Phase 3 EXPAND RRMS Overall PMS PPMS n-aSPMS aSPMS Overall SPMS Without With Without With Population Population Gd+ Gd+ relapses relapses N= 64 N=102 N=32 N=62
Slide 53: Amit Bar-Or, MD, FRCPC
Amit Bar-Or, MD, FRCPC Most Eminent Neuroimmunologist and MS Clinical Expert from UPenn Medicine ▪ Studied medicine at McGill University in Montreal ▪ Former Professor in the Department of Neurology and Neurosurgery at the Montreal Neurological Institute and Hospital, McGill University ▪ Neurology r
Slide 54: Highlights of Dr. Bar-Or's Research Focus
Highlights of Dr. Bar-Or's Research Focus Relapsing MS ▪ Since 2022, it has been known that EBV infection is “a necessary precondition for developing Multiple Sclerosis”[1] − Dr. Bar-Or's research focus: Similar to other autoimmune diseases, MS will arise from a disbalance of proinflammatory and ant
Slide 55: Amit Bar-Or, MD, FRCPC
Featured Expert Amit Bar-Or, MD, FRCPC Clinician and scientist, one of the leading neuroimmunologists in MS Melissa and Paul Anderson Distinguished Chair Director, Center for Neuroinflammation and Experimental Therapeutics Chief, Multiple Sclerosis Division, Department of Neurology Perelman School o
Slide 56: Q&A Session with Amit Bar-Or, MD, FRCPC
Multiple Sclerosis R&D Day Q&A Session with Amit Bar-Or, MD, FRCPC
Slide 57: Ongoing Phase 2 CALLIPER Trial in Progressive Multiple Sclerosis
06 Multiple Sclerosis R&D Day Ongoing Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis
Slide 58: EMPhASIS: Completed Phase 2 Trial in Relapsing-Remitting MS
EMPhASIS: Completed Phase 2 Trial in Relapsing-Remitting MS NCT03846219 Trial Met Key Efficacy and Safety Endpoints ▪ Randomized 268 patients in 36 centers across four Coordinating Investigator European countries ▪ Vidofludimus calcium showed strong activity in relapsing- Robert J. Fox, M.D. Clevela
Slide 59: Neurofilaments Are Neuronal Proteins Released Upon Axonal Injury
Neurofilaments Are Neuronal Proteins Released Upon Axonal Injury Measurable in Blood Cross-Disease Neurologic Biomarker for Neurodegenerative Diseases ▪ Neurofilaments are highly specific neuronal proteins that, upon neuroaxonal injury, are degraded into peptides, shed to the cerebrospinal fluid (CS
Slide 60: EMPhASIS: Reduction of Serum NfL Concentrations Observed
EMPhASIS: Reduction of Serum NfL Concentrations Observed Versus Placebo After 24 Weeks, Pooled Cohorts 1 & 2 50% Vidofludimus calcium showed a remarkable reduction in NfL levels in all active doses tested compared with placebo ▪ The relative change of serum NfL versus placebo -9% is proportional to
Slide 61: EMPhASIS: 12-Week Confirmed Disease Worsening After 2 Years
EMPhASIS: 12-Week Confirmed Disease Worsening After 2 Years Interim Analysis Open-Label Extension Period Compared to Select Historical Trials RRMS patients with 12-week (3-months) confirmed disability worsening after 2 Years (96 Weeks) (% of patients at risk) 20% 15% 15.0% KM estimates 13.6% 12.4% 1
Slide 62: CALLIPER: Ongoing Phase 2 Trial in Progressive MS
CALLIPER: Ongoing Phase 2 Trial in Progressive MS NCT05054140 Multicenter, Randomized, Double-Blind, Screening Period Main Treatment Period (Blinded) Placebo-Controlled Phase 2 Trial Maximum 120 Weeks ▪ 467 patients enrolled at more than 70 sites in North America, Western, Main Central and Eastern E
Slide 63: CALLIPER: Patient Demographics and Baseline Characteristics
CALLIPER: Patient Demographics and Baseline Characteristics Total Study Population of 467 Enrolled Patients Progressive Disease Subtypes Baseline Characteristics Baseline Patient Characteristics Total (N=467) N=37 7.9% Age [years], median (min-max) 51.0 (21-65) N=152 Gender (n and % female) 302 (64.
Slide 64: PPMS Patients Treated with Ocrelizumab with Lower NfL Had Lower Risk
PPMS Patients Treated with Ocrelizumab That Achieved Lower Levels of NfL Had a Lower Risk for Future Disability Ocrelizumab ORATORIO Study in PPMS as Historical Comparison ▪ Blood NfL levels re-baselined at Week 48, an optimized cut-off was created between high (H) and low (L) NfL levels ▪ Patients
Slide 65: Historical Comparison: Ocrelizumab Reduced Blood NfL Levels in ORATORIO
Historical Comparison: Ocrelizumab, the Only Approved Drug for PPMS, Reduced Blood NfL Levels in the ORATORIO Study ORATORIO Showed a 12.4 % Delta for 24-Week Serum NfL Levels for Ocrelizumab Versus Placebo ▪ Blood NfL levels (geometric mean and 95% CI, top) and relative change from baseline (% redu
Slide 66: Interim Analysis of the Phase 2 CALLIPER Trial
Interim Analysis of the Phase 2 CALLIPER Trial Prospectively Planned Interim Biomarker Analysis ▪ Preplanned interim analysis − Group-level data − Entire study and individual treatment assignments remained blinded ▪ Evaluation of biomarkers ▪ Included 203 progressive MS patients with baseline and 24
Slide 67: CALLIPER: Change in Serum NfL Overall PMS Population
CALLIPER: Change in Serum NfL Overall PMS Population Post-Hoc Statistical Analysis of Change from Baseline to Week 24 Total Interim Analysis Population (24-Week Completer) N=102 (45 mg IMU-838), N=101 (Placebo) Nominal Change in NfL from BL to W24 Post-Hoc Statistical Analysis: Δ +2.705 ng/L (Placeb
Slide 68: Improvements in Serum NfL Consistent Across PMS Population and Subtypes
Improvements in Serum NfL for Vidofludimus Calcium Consistent Throughout the Overall PMS Population and All Subtypes Mean Change to Week 24 as Compared to Placebo in % of Baseline Overall PMS Population PPMS n-aSPMS aSPMS 10% N=102 (IMU-838) N=32 (IMU-838) N=62 (IMU-838) N=8 (IMU-838) N=101 (Placebo
Slide 69: CALLIPER: Serum NfL Improvements With/Without Disease or MRI Activity
CALLIPER: Improvements in Serum NfL for Vidofludimus Calcium in Patients With/Without Disease or MRI Activity Change to Week 24 as Compared to Placebo in % of Baseline 10% Overall PMS Population aPMS n-aPMS aMRI n-aMRI N=102 (IMU-838) N=27 (IMU-838) N=75 (IMU-838) N=26 (IMU-838) N=76 (IMU-838) N=101
Slide 70: NfL Reduction Compares Favorably with Other MS Therapies
NfL Reduction Compares Favorably with Other MS Therapies CALLIPER Interim Data Compared to Select Historical Trials Vidofludimus Ocrelizumab Vidofludimus Siponimod Vidofludimus Siponimod PPMS PPMS n-aSPMS n-aSPMS aSPMS aSPMS (CALLIPER) (ORATORIO) (CALLIPER) (EXPAND) (CALLIPER) (EXPAND) 10% N=32 (IMU
Slide 71: Positive Interim Biomarker Data in Progressive Multiple Sclerosis
Positive Interim Biomarker Data of Vidofludimus Calcium in Progressive Multiple Sclerosis Biomarker evidence that vidofludimus calcium’s activity extends beyond the previously observed anti-inflammatory effects, thereby further reinforcing its neuroprotective potential Vidofludimus calcium aiming to
Slide 72: Takeaways: Progressive Multiple Sclerosis
Takeaways: Progressive Multiple Sclerosis Leveraging Nurr1 in a Population Without Focal Inflammatory Disease ▪ CALLIPER interim analysis showed biomarker evidence for activity of vidofludimus calcium in both SPMS and PPMS and in both active and non-active forms of PMS – Such biomarker pattern diffe
Slide 73: Potential of Vidofludimus Calcium to Prevent Long-Term Fatigue
Potential of Vidofludimus Calcium to Prevent Long-Term Fatigue
Slide 74: MS Fatigue Affects Lifestyle But Is Often Invisible to Others
MS Fatigue Affects Lifestyle But Is Often Invisible to Others ▪ Almost everyone who lives with MS will experience fatigue − Around 80% of people with MS experience fatigue at some point during the course of the disease ▪ Fatigue in MS can be physical, mental or a combination of both − Feeling of con
Slide 75: Publication on T-Cell Receptor Repertoire in MS Patients
Publication on T-Cell Receptor Repertoire in MS Patients: Broader EBV-Specific CD8 TCR Repertoire in MS Blood Discovery cohort ▪ More unique EBV-specific CD8 TCR sequences (T cells) in MS blood ▪ Effect size: – discovery + 2.2 – validation + 2.1 – MS twin + 1.6 Validation cohort MS twin cohort Ref:
Slide 76: EBV Virus Shedding in Saliva as Indicator for Lytic Infection
EBV Virus Shedding in Saliva as Indicator for Lytic (Active) Infection Teriflunomide (Another DHODH Inhibitor) Lytic EBV Activity in an MS Population Decreases Lytic EBV Activity Number of Overall Proportion of Patients with Samples With EBV Shedding Proportion of Samples, % Studies Patients with EB
Slide 77: Detectable EBV Reactivation in Post-COVID Syndrome and Persistent Fatigue
Detectable EBV Reactivation in Post-COVID Syndrome More Prevalent in Patients Suffering from Persistent Fatigue ▪ No detectable SARS-CoV-2 RNA in throat washings or stool samples EBV Antibodies of any study participants[1] in Serum ▪ No significant differences in anti- EBV antibodies between Long- C
Slide 78: Potential Contribution to Prevention of Long-Term Fatigue
Potential Contribution of Vidofludimus Calcium to Prevention of Long-Term Fatigue, One of the Most Common Post-COVID Symptoms EBV Reactivation Thought to CALVID-1 Trial: Proportion of Drive Fatigue in MS and Post- Patients With Fatigue at Study COVID Syndrome (PCS)[1] Completion[2,3] ▪ Vidofludimus
Slide 79: RAPID_REVIVE: Phase 2 Trial in Patients with Post COVID Syndrome
RAPID_REVIVE: Investigator-Sponsored Phase 2 Trial of Vidofludimus Calcium in Patients with Post COVID Syndrome* Potential Read-Through to Multiple Sclerosis Development Program ▪ In addition to post COVID readouts, designed to deliver data on Coordinating Investigator activity of vidofludimus calci
Slide 80: Upcoming Milestones for Vidofludimus Calcium in Multiple Sclerosis
07 Multiple Sclerosis R&D Day Upcoming Milestones for Vidofludimus Calcium in Multiple Sclerosis
Slide 81: Outlook: Poster Presentations at the Upcoming 40th Congress of ECTRIMS
Outlook: Immunic’s Poster Presentations at the Visit Booth #60 Upcoming 40th Congress of ECTRIMS Serum Neurofilament Changes in Progressive MS: Exploring the Potential of Vidofludimus Calcium to Reduce Fatigue Exploring the Impact of Vidofludimus Calcium by Age and in Multiple Sclerosis by Preventin
Slide 82: Vidofludimus Calcium in Multiple Sclerosis
Vidofludimus Calcium in Multiple Sclerosis Consistent and Differentiated Results to Date Support Straightforward Path Towards Potential Regulatory Approvals EMPhASIS: CALLIPER: CALLIPER: RMS NDA Positive phase 2 RRMS data demonstrating Positive phase 2 PMS PMS top-line data Submission statistically
Slide 83: Aimed to Go Above and Beyond Current Care to Address Patients' Needs
Vidofludimus Calcium Aimed to Go Above and Beyond Current Care to Comprehensively Address Patients’ Needs Targeted to Elevate the Standard of Care for Was hältst du von der Option? Multiple Sclerosis Patients Targeted to Elevate Once-daily, oral Uniquely matched to the multi-faceted neuro- Seeks to
Slide 84: Q&A Session
08 Multiple Sclerosis R&D Day Q&A Session
Slide 85: Thank You!
Thank You! Immunic, Inc. Immunic AG 1200 Avenue of the Americas Lochhamer Schlag 21 New York City, NY 10036 82166 Gräfelfing (Munich) USA Germany Jessica Breu Vice President Investor Relations & Communications Immunic Australia Pty. Ltd. Melbourne Phone: +49-89-2080477-09 Australia Email: ir@imux.co