Immunic, Inc. · NASDAQ:IMUX
Immunic — Technical Presentation (July 2021)
55 slides from Immunic's technical presentation, Jul 12, 2021
Slide 1: Immunic Therapeutics: IMU-935 Preclinical and Clinical Development Update
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: IMU-935: Preclinical and Clinical Development Update
) IMU-935: Preclinical and Clinical Development Update Introduction and Oral IL-17 Landscape 06 | IMU-935: Preclinical Anti-Cancer Activity Background Target RORyt 03 | Scientific Expert: Zuoming Sun, Ph.D., City of Hope 08 | Q&A CRPC IMU-935: Planned Phase 1 Study in CRPC Q&A RORyt Summary IMU-935:
Slide 4: Development Pipeline
Development Pipe Program | Indication Target Preclinical Phase 1 Phase 2 Phase 3 Imu-838 Relapsing-Remitting Multiple Sclerosis Progressive Multiple Sclerosis, Ulcerative Colitis Crohn's Disease DHODH | Primary Sclerosing Cholangitis IMU-935, Psoriasis Castration-Resistant Prostate Cancer RORyt Guil
Slide 5: Introduction and Oral IL-17 Landscape
Slide 6: Autoimmune Diseases and IMU-935
Autoimmune Diseases and IMU-935 . 2 : Unmet Need in Psoriasis Care IL-17 in Autoimmune Diseases = Autoimmune diseases affect millions of patients worldwide! = Th17/IL-17/RORyt axis plays an important role in auto immunity-related diseases!) * Antibodies targeting this axis corroborate IL-17’s role i
Slide 7: Current Landscape of Oral IL-17 Inhibitors
Current Landscape of Oral IL-17 Inhibitors" Product Developer Mode of Action Administration | indications Development Stage 81730357 Boehringer ingelheim | RORytinverse agonist | Orel Plaque psoriasis and psoriaticarthritis. | Phase 2 Cedirogant AbbVie RORyt inverse agonist | Orel Plaque psoriasis P
Slide 8: Background Target RORyt
Slide 9: Main Functions of RORyt
Main Functions of RORyt s Co) Differentiation 1: | pL ES The differentiation towards Th17 cells is inhibited by IMU-935 ay ob aha | The production of IL-17A and Cytokine He, A | BA 11-176 is inhibited by IMU-935 Production Ft Se IFN-y xox The physiological maturation of T cells within _ the thymus i
Slide 10: IMU-935 Has Been Observed to be Potent in Human Cells
IMU-935 Has Been Observed to be Potent in Human Cells Effect of IMU-935 in Stimulated Human PBMC at Nanomolar Concentrations IC59(uM) IL-I7A 0.005 IL-A7F 0.004 IFNy 0.003 IL-la and b no inhibition 1L-4,5,6,8 no inhibition RORy (MST) 0.024 RORY (cellular, reporter assay) 0.020 DHODH 0.240 Th17 differ
Slide 11: Inhibition of Th17 Differentiation and IL-17 Production
Inhibition of Th17 Differentiation and IL-17 Production Th17 Differentiation— Murine Primary Thymocytes IL-17F Expression — Human Primary PBMCs Eee ao ECyg= 2.0 1M E 5 70 EZ 100 ECgo = 5.8 7M 5 = 00 BE ® S750: SE 50 ° 1C50 (134.7 nM) - ge 40 S ga EC50 E 5 30 z 5 SE 20. = 234 250: i i - E690 T_T T_T
Slide 12: IMU-935 Potently Inhibited Cytokine Release in Ex Vivo Stimulated Human Skin Punches
IMU-935 Potently Inhibited Cytokine Release in Ex Vivo Stimulated Human Skin Punches Cytokine Inhibition in Inflamed Human Skin Model i gMicsr pesT/y WtZE Wez2 . y | x . 85" | 210] a i . +. g Pa | r ge a a v , "S UBO) Ceses " UOF i es Maa IMU-935 is TI 3 Tr 3 Try TP a c PET PEGE PEPE geda OO eee $2
Slide 13: Human Graft-Versus-Host Disease and GVHD Mouse Model
Human Graft-Versus-Host Disease and GVHD Mouse Model [2] Human Graft-Versus-Host Disease = Graft-versus-host disease (GvHD) is an immune condition that occurs after transplant procedures when immune cells from the donor (graft cells) attack the recipient patient host's tissues i td = The disease is
Slide 14: Activity of IMU-935 on GVHD is Due to a Reduction of Circulating Human T Lymphocytes
Activity of IMU-935 on GVHD is Due to a Reduction of Circulating Human T Lymphocytes IMU-935 reduced circulating human CD45 cells IMU-935 reduced microscopic pathology findings in the (CD4* and CD8* T cells) colon, typical for GVHD -————— nes ned 8000; 1 Architecture, Crypt Epithelial 100.0 * cary H
Slide 15: Challenge: RORyt Inhibition and Risk For T Cell Lymphomas
Challenge: RORyt Inhibition and Risk For T Cell Lymphomas = In several publications, knock-out of RORyt was shown to correlate with a potential risk of T cell lymphomas = Guntermann et al.!] have shown that some small molecule inhibitors developed by Novartis and GSK show thymic aberrations = Due to
Slide 16: In Contrast to Full Knock-Out, RORyt Functions Can be Uncoupled
In Contrast to Full Knock-Out, RORyt Functions Can be Uncoupled!#) Mutation Seo Variable Contribution L93A Mutation in RORC Leads to Selective TH17 Inhibition of Protein Sequences to Different Phenotypes ALA scan of Hinge region and DED c-terminal region resulted in 193A exchange relevant for select
Slide 17: Inhibition of RORyt-Dependent Th17 But Not Thymocyte Function by IMU-935
Slide 18: Potential Issue With RORyt Inhibitors: Lymphoma
Potential Issue With RORyt Inhibitors: Lymphoma wa Prevent Th17-dependent autoimmunity IN Interfere with thymocyte development which leads to thymic lymphoma RORyt inhibitors Is it possible to have a RORyt inhibitor specifically targeting Th17 but not thymocytes? Hy:
Slide 19: IMU-935 Inhibits Th17 Differentiation in a Dose Dependent Manner
1175 ——__»> IMU-935 Inhibits Th17 Differentiation ina Dose Dependent Manner at-935 (Socks Differentiation ay | Nua In vitro Th17 differentiation “NO ™N : ont g = = Re RORY -MU-835 (500nHt) iw ° = 10 { 155) ] 105 58] | 108 er) 8 30 —E 2 i iy; 3 + 3 wo oa a Siem é od 10 4 101 = S i = 10 2 10] 10 | a 2
Slide 20: IMU-935 Modulates RORy-Related Gene Expression Under Th17 Differentiation Conditions
IMU-935 Modulates RORy-Related Gene Expression Under Th17 Differentiation Conditions Downregulated Upregulated genes genes by IMU-935 by IMU-935 8 7 v 6 a ° D4 7 18 12 «6 0 6 Loge FC (IMU-935 vs Veh) Volcano plot showing DEGs by IMU-935
Slide 21: Repression of Typical Th17 Genes by IMU-935
Repression of Typical Th17 Genes by IMU-935 Murine primary thymocytes, Th17 differentiation condition, 500 nM IMU-935 (CPD#1) Wize mm We3r Mee 10. Relative mRNA = Relative mRNA Relative mRNA - Relative mRNA 0. a 0. pa RORyr: = IMUS3s RORyr: - Musa RORyr: -_IMU-S35 RORyr = IMUS3 ROR! ORV! RoRve RORY
Slide 22: IMU-935 Blocks Th17 Differentiation and Modifies Gene Expression Profiles
IMU-935 Blocks Th17 Differentiation and Modifies Gene Expression Profiles ThI7 cell Rory Rory = Rory AUN IMU-935 x Th17 cell differentiation “of gene's total counts IE 10 20 20 Similar gene expression pattern for Th17 signature genes in RORyt knockout and wild type cells treated with IMU-935
Slide 23: IMU-935 Attenuates RORyt Genome-Wide DNA-Binding in Th17 Cells
IMU-935 Attenuates RORyt Genome-Wide DNA-Binding in Th17 Cells TSS plot Rory RORY RORYt~~IMU-935 ‘TSS plot: a common visualization method fo obtain a global evaluation of enrichment around the transcription startsite (TSS) RORyt protein binds to ~3000 gene| loci in murine cells under Th17 differenti
Slide 24: IMU-935 Attenuates RORyt DNA-Binding and Inhibits Expression of Genes Critical for Th17 Cells
IMU-935 Attenuates RORyt DNA-Binding and Inhibits Expression of Genes Critical for Th17 Cells Chip-seq RNA-seq (th17) (th17) gs eg & es e ize wf g || oo Sf we & |] ize § |] coe i € war 3 |] nes = |}smaas = |] Roa 16ra Neoat + Neda (orrOE 20 2 40 4 8 2 IMU-935 leads to reduced binding of This decreas
Slide 25: IMU-935 Blocks Th17 Differentiation - What Happens With Thymocytes?
IMU-935 Blocks Th17 Differentiation -— What Happens With Thymocytes? IMU-935 a ThI7 cell differentiation ? OS) cps’ Thymocyte development () 7 —@ : O- es L Areptois req Cityof it fea
Slide 26: IMU-935 Does Not Impact Survival Signals During Thymocyte Maturation
IMU-935 Does Not Impact Survival Signals During Thymocyte Maturation = RORyt provides a survival signal during thymocyte = Deletion of RORyt by knockout reduces the maturation by upregulating the anti-apoptotic gene survival/viability of thymocytes, whereas blocking Bcl-XL RORyt by IMU-935 does not
Slide 27: IMU-935 Does Not Impact Production of CD4+/CD8+ Cells During Thymocyte Maturation
IMU-935 Does Not Impact Production of CD4*/CD8* Cells During Thymocyte Maturation = RORyt promotes the differentiation of ISP into DP cells = Deletion of RORyt by knockout reduces the number of DP cells, whereas blocking RORyt by IMU-935 does not Thymocyte development towards double positive (DP) CD
Slide 28: IMU-935 Does Not Induce Thymocyte Apoptosis
% Thymocyte (relative to % viable cells in vehicle) 120: 100: IMU-935 Does Not Induce Thymocyte Apoptosis = In contrast to IMU-935, comparator compounds have a negative impact on thymocyte viability and therefore bear the T cell malfunction and risk of lymphoma. pH By 30 36 : & Vehicle 3% IM105035 >
Slide 29: IMU-935 Blocks Th17 Differentiation But Allows Normal Thymocyte Maturation: Gene Expression Profiles
IMU-935 Blocks Th17 Differentiation But Allows Normal Thymocyte Maturation: Gene Expression Profiles Thymocytes Th17 cell ° wow fo RoR = RORY ERNE cakn2a oid IMU-935 o Me. x, 2 cass? < cos 8 yes. 3 Th17 cell differentiation ‘Thymocyte development (e) z ed 5 cas e 1L-6, TOF. a7 Papi _| § SS — asp e P
Slide 30: Summary: RORyt Has Two Critical Functions
RORyt has two critical functions: > Th17 cells = Generation of Th17 cells that mediate autoimmune diseases > Thymocytes = Thymocyte development by regulating survival and proliferation Challenge: = Deletion of RORyt gene or RORYt inhibitors may increase the potential risk of lymphoma Summary Differe
Slide 31: Q&A RORyt
Slide 32: Clinical Development Status
Slide 33: Phase 1 Clinical Trial of IMU-935: Design and Status
Phase 1 Clinical Trial of IMU-935: Design and Status PART A part B part C Evaluation of Evaluation of Evaluation of single ascending doses (SAD) multiple ascending doses (MAD) moderate-to-severe psoriasis = = patients receiving 28-day Healthy volunteers Healthy volunteers randomized treatment of eit
Slide 34: Adaptive Transition from Part A (SAD) to Part B (MAD)
Adaptive Transition from Part A (SAD) to Part B (MAD) Fasted Part B Cohorts of N=8 Active (6) : Placebo (2) 34 | ©immunic, inc. | Jul/12/2021 Immunic THERAPEUTICS
Slide 35: Phase 1 Clinical Trial: Interim SAD Pharmacokinetic Results
Phase 1 Clinical Trial: Interim SAD Pharmacokinetic Results New Formulation With Dose-Linear AUC 8 6 IMU-935 Mean Plasma Concentration Ing/mL] Preliminary data AUC: area underthe cur;h: hours C.. maximum (peal plasmadrug concentration; T.:timeto reschmaximum (peak) plasma concentration; AUC. areaund
Slide 36: Phase 1 Clinical Trial: Interim SAD Pharmacokinetic Results
Phase 1 Clinical Trial: Interim SAD Pharmacokinetic Results Comparison of Lipid-Based and New Formulation IMU-935 Concentration Time Profiles (Log-Linear Scale) 100 IMU-935 Mean Plasma Concentration Preliminary data 24. -e-Cohort 3 (100mg) —*-Cohort 3N (100mg) 36 Time [hours] 48 72 Comparable Pharma
Slide 37: Phase 1 Clinical Trial: Interim Blinded SAD Safety Results
Phase 1 Clinical Trial: Interim Blinded SAD Safety Results Blinded Safety Data Does Not Indicate Safety Signals Number (%) of Subjects With TEAES [Number of TEAEs Reported] Imu-935 Imu-935 Imu-935 Imu-935 100mg 3N 200mg 4N 300mg 5N 400mg 6N (N=7) (N=8) (N=8) (N=8) 7 (100%) 6 (75%) 4 (50%) 7 (88%) [a
Slide 38: Phase 1 Clinical Trial: Interim Blinded SAD Safety Results
Phase 1 Clinical Trial: Interim Blinded SAD Safety Results Related Adverse Events by Incidence Number (%) of Subjects With Related TEAEs Occurring in2 2 Subjects [Number of TEAEs Reported] IMu-935 IMu-935 IMu-935 IMu-935 100mg 3N 200mg 4N 300mgSN 400mg 6N lMedDRA Preferred Term N=”) (N8) (N8) (Ns) c
Slide 39: Phase 1 Clinical Trial: Part C in Psoriasis Patients
Phase 1 Clinical Trial: Part C in Psoriasis Patients Study Design = Double-blind, placebo-controlled dose escalation study to evaluate safety, tolerability, pharmacodynamics and exploratory efficacy of IMU-935 in patients with moderate-to-severe psoriasis = Psoriasis patients will receive 28 days of
Slide 40: Phase 1 Clinical Trial: Part C in Psoriasis Patients
Phase 1 Clinical Trial: Part C in Psoriasis Patients 1h Eligibility Criteria Key Objectives/Endpoints = Age 18 to 65 years (inclusive) Primary: = Diagnosis of chronic plaque-type psoriasis for * Safety and tolerability at least 6 months: Secondary: — PASI score 2 10, or PASI score < 10 and DLAI * Tr
Slide 41: Preclinical Anti-Cancer Activity
Slide 42: Prostate Cancer: Introduction & Definitions
Prostate Cancer Introduction & Definitions = Metastatic prostate cancer has spread to the bone, distant lymph nodes or other parts of the body. = Evidence of disease progression while being treated with androgen deprivation therapy (ADT) and having castrate levels of serum testosterone (<50 ng/dL) i
Slide 43: Standard of Care in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Standard of Care in Metastatic Castration-Resistant Prostate Cancer (mCRPC) ESMO Guidelines i = Abiraterone or enzalutamide is recommended for asymptomatic/ mildly ‘ete survellance symptomatic men with chemotherapy-naive mCRPC 2 nenschat doetzal f F Lozaly aces Noodjnant ADT +o R= = Docetaxel is rec
Slide 44: Resistance Formation as a Key Challenge in CRPC
Resistance Formation as a Key Challenge in CRPC In patients, prostate cancer usually can be controlled for Published in final edited form as: multiple years Nat Med. 2016 May ; 22(5): 488-496. doi: 10.1038/nm.4070. However, mutations can arise which make prostate cancer cell clones insensitive to RO
Slide 45: IMU-935 As Treatment Option in CRPC: Synergistic Effects by Targeting RORy and RORyt
IMU-935 As Treatment Option in Castration-Resistant Prostate Cancer — Synergistic Effects by Targeting RORy and RORyt Inhibition of IL-17 by RORyt Regulation Inhibition of RORy Differentiation of MDSCs = The androgen-receptor mutant = |L-17 contributes to the formation, = |L-17 mediates the inductio
Slide 46: IMU-935 Demonstrated RORy-Dependent Effects in CRPC Cells
IMU-935 Demonstrated RORy-Dependent Effects in CRPC Cells IMU-935 Has Been Shown to Repress Expression of Mutated AR mRNA Relative AR.V7 expression protein Relative A.V protein levels Mutant AR-V7 mas0sea5 | sRz2H rary IMU-935 Potently Inhibited Proliferation of Different Prostate Cell Lines 72h, 2d
Slide 47: Planned Phase 1 Study in Castration-Resistant Prostate Cancer (CRPC)
Slide 48: Johann Sebastian de Bono, M.D., Ph.D.
9) Johann Sebastian de Bono, M.D., Ph.D. The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust “IMU-935 possesses a unique mechanism of action which may prove transformative in its ability to effectively treat a range of underserved diseases. Preclinical studies have shown that
Slide 49: Phase 1 Clinical Trial of IMU-935 in CRPC
Phase 1 Clinical Trial of IMU-935 in CRPC Study Design = Open-label dose escalation trial to evaluate safety, tolerability, anti-tumor activity, and pharmacokinetics of IMU-935 in patients with progressive, metastatic castration-resistant prostate cancer = Dose escalation follows a Bayesian optimal
Slide 50: Phase 1 Clinical Trial of IMU-935 in CRPC
Phase 1 Clinical Trial of IMU-935 in CRPC Study Design Dose Escalation Cohort Dose Escalation Cohort Dose 2 Dose Escalation Cohort Dose 1 Dose 3 Atleast 6 butno more than 9 patients will enter each dose escalation cohort Study Scheme Day-28 Day-1 Main analysis Main Treatment (3 Cycles of 28 Days Eac
Slide 51: Phase 1 Clinical Trial of IMU-935 in CRPC
Phase 1 Clinical Trial of IMU-935 in CRPC 1h Eligibility Criteria Key Objectives/Endpoints = Age > 18 years Primary: ® Histologically or cytologically confirmed = Dose-limiting toxicity adenocarcinoma of the prostate = Recommended phase 2 dose (RP2D) = Progressive disease according to PCWG3 Secondar
Slide 52: Q&A CRPC
Slide 53: Summary
Slide 54: IMU-935: An Emerging Oral IL-17 Inhibitor
IMU-935: An Emerging Oral IL-17 Inhibitor = |MU-935 has been observed to be a potent RORyt inhibitor with an IC, on IL-17A and IL-17F inhibition of < 5 nM = |MU-935 demonstrated a selective effect of inhibition of Th17 differentiation while maintaining physiological function of thymocyte maturation
Slide 55: Thank You!
Thank You! Head of IR & Communications Phone: +49-89-2080477-09 Email: ir@imux.com w.imux.com 55 | ©immunic, nc. | Jul/12/2021 Immunic, Inc. 1200 Avenue of the Americas Immunic AG New York City, NY 10036 Gréfelfing (Munich) USA Germany Immunic Research GmbH Weinberg Campus Halle (Saale) Germany Immu