Exicure, Inc. · NASDAQ:XCUR

Exicure — Investor Presentation (April 2021)

39 slides from Exicure's investor presentation, Apr 9, 2021

  1. Slide 1: Corporate Overview April 9, 2021

    Corporate Overview April 9, 2021

  2. Slide 2: Cautionary Note Regarding Forward Looking Statements

    ©2021 Exicure, Inc.® All Rights Reserved. Cautionary Note Regarding Forward Looking Statements 2 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "expect," "plan," "may," "will," and similar

  3. Slide 3: Exicure Snapshot

    ©2021 Exicure, Inc.® All Rights Reserved. Exicure Snapshot 3 • Clinical-stage biotechnology company developing therapeutics for genetic disorders based on our proprietary Spherical Nucleic Acid (SNA™) technology • In CNS, differentiated from conventional oligonucleotides by increased cellular uptake

  4. Slide 4: SNAs are the Next Generation of Oligonucleotide Therapeutics

    ©2021 Exicure, Inc.® All Rights Reserved. Spherical Nucleic Acids (SNAs) are the Next Generation of Oligonucleotide Therapeutics 4 • Entered IND-enabling studies in 4Q20 • IND filing anticipated by end of 2021 • Potential for early target engagement read-out in FIH via CSF frataxin levels Friedreich

  5. Slide 5: 3-Dimensional Architecture Drives Receptor-Mediated Uptake

    ©2021 Exicure, Inc.® All Rights Reserved. 3-Dimensional Architecture Drives Receptor-Mediated Uptake 5 1) Compos ition: 1,2-dioleoyl -sn-glycero-3-phosphocholine (DOPC) liposome; DOPC is in the FDA-approved drug DepoDur®, a morphine sulfate extended-release liposome injection for lumbar epidural adm

  6. Slide 6: Established and Proven Management Team

    ©2021 Exicure, Inc.® All Rights Reserved. 6 David A. Giljohann Chief Executive Officer Matthias Schroff Chief Operating Officer Douglas Feltner Chief Medical Officer Tim Walbert Chairman David Walt Jeffrey L. ClelandJames Sulat Bali Muralidhar Bosun Hau Elizabeth Garofalo Andrew Sassine Chad Mirkin

  7. Slide 7: SNA Is a Highly Differentiated and Versatile Platform

    ©2021 Exicure, Inc.® All Rights Reserved. Increased SNA potency results in greater efficacy at same dose SNA Benefits Drive Superior In Vivo Efficacy SNA Is a Highly Differentiated and Versatile Platform 7 Multi-Targeting Capability Cell-specific delivery of defined ratios of oligonucleotides 2 1 3

  8. Slide 8: Differentiation in Neuroscience

    Differentiation in Neuroscience

  9. Slide 9: Three Drivers of Superior SNA Efficacy in Neuroscience

    ©2021 Exicure, Inc.® All Rights Reserved. Three Drivers of Superior SNA Efficacy in Neuroscience 9 21 3 Higher Cell Uptake, Leading to Higher Potency at Same Dose Higher Persistence in the CNS, Leading to Prolonged Efficacy Broad CNS Penetration and Uptake in all Neuronal Subtypes SNA Linear SNA wit

  10. Slide 10: Exicure Continues to Focus its Pipeline and Invest Into Neuroscience

    ©2021 Exicure, Inc.® All Rights Reserved. Exicure Continues to Focus its Pipeline and Invest Into Neuroscience 10 DISCOVERY PRECLINICAL DEV PHASE 1 PHASE 2 NEUROSCIENCE XCUR-FXN FRIEDREICH’S ATAXIA SCN9A NEUROPATHIC PAIN CLN3 BATTEN DISEASE Discovery Programs ALS, SCAs, ANGELMAN’S IMMUNO-ONCOLOGY CA

  11. Slide 11: SNA-Nusinersen Outperforms Linear Nusinersen in Mouse Models

    ©2021 Exicure, Inc.® All Rights Reserved. SNA-Nusinersen Outperforms Linear Nusinersen in Mouse Models 11 Days Survival Note: Survival data presented at 2018 Annual Cure SMA Conference; Nusinersen curve (red) in line with published Ionis data for single dose administration in SMA mice (Hua et al., 2

  12. Slide 12: SNA Efficacy is Driven by Longer CNS Persistence

    ©2021 Exicure, Inc.® All Rights Reserved. SNA Efficacy is Driven by Longer CNS Persistence 12 0 Hours Nusinersen Alone SNA-Nusinersen 24 Hours Nusinersen Alone SNA-Nusinersen 7 Days Nusinersen Alone SNA-Nusinersen Rat Distribution Study Highest levels of drug present in CNS (50 SUV) Drug still prese

  13. Slide 13: SNA Persistence Translates to Non-Human Primates

    ©2021 Exicure, Inc.® All Rights Reserved. 13 • Broad distribution throughout the CNS • Strong SNA signals in the cerebellum, a region particularly important for FA, as well as midbrain, hippocampus and occipital lobe • Strong SNA persistence with >50% of day 1 signal remaining after 14 days 124I-lab

  14. Slide 14: Friedreich's Ataxia (FA): Progressive Neurological Disorder

    ©2021 Exicure, Inc.® All Rights Reserved. • Degenerative, debilitating, life-shortening, neuromuscular disorder causing loss of coordination (ataxia) in arms and legs • Monogenic disorder: FXN mutations result in reduced levels of frataxin • Leads to progressive childhood disability and early death

  15. Slide 15: CNS Manifestations of FA Have the Most Significant Impact on Function

    ©2021 Exicure, Inc.® All Rights Reserved. For Patients, CNS Manifestations of FA Have the Most Significant Impact on Function and Quality of Life 15 Data from FARA’s FA PFDD Meeting, June 2, 2017, N = 136; graphical illustration adapted from FARA version presented on Jan 7, 2021 0. 25. 50. 75. 100.

  16. Slide 16: Reduced Frataxin Expression Causes Neuronal Dysfunction in FA

    ©2021 Exicure, Inc.® All Rights Reserved. Reduced Frataxin Expression Due to Expanded GAA Repeats Causes Neuronal Dysfunction in Friedreich’s Ataxia 16 Friedreich’s Ataxia Affects: -Cerebellum -Dorsal Root Ganglia Neuronal Dysfunction DNA Reduced FXN ProteinReduced FXN mRNA Expanded GAA Repeats (~70

  17. Slide 17: Residual Frataxin Levels in FA Support Oligonucleotide Approach

    ©2021 Exicure, Inc.® All Rights Reserved. Residual Frataxin Levels in Friedreich’s Ataxia (FA) Support Oligonucleotide Approach 17 Frataxin Levels in Blood From FA Patients vs. Controls Conclusions • Patients with FA have substantial residual frataxin • Residual frataxin levels support Exicure’s pro

  18. Slide 18: XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation

    ©2021 Exicure, Inc.® All Rights Reserved. 18 XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation Increased Frataxin Production DNA mRNA Mitochondrion Enzyme Degradation of Natural Antisense Transcript Cytoplasm Cytoplasm mRNA Stabilization XCUR-FXN (bi-specific SNA) Nucleus Carries two

  19. Slide 19: XCUR-FXN Dose-Dependently Upregulates Frataxin Protein and mRNA

    ©2021 Exicure, Inc.® All Rights Reserved. XCUR-FXN Dose-Dependently Upregulates Frataxin Protein and mRNA 19 • Consistent in vitro activity in FA-patient derived induced neurons and fibroblasts and biodistribution observed with SNA reporter gene constructs suggests attractive candidate for progressi

  20. Slide 20: XCUR-FXN Increases Mitochondrial Frataxin and Activity

    ©2021 Exicure, Inc.® All Rights Reserved. 0 30 60 90 120 F ra ta x in P ro te in (% N o n D is e a s e C o n tr o l) XCUR-FXN Increases Mitochondrial Frataxtin and Activity 20 1) SDH - succinate dehydrogenase • XCUR-FXN returns frataxin levels to non-diseased level in mitochondria, the target cellul

  21. Slide 21: Magnitude of In Vivo Frataxin Upregulation Indicates Possibility for Disease Resolution

    ©2021 Exicure, Inc.® All Rights Reserved. 21 Magnitude of In Vivo Frataxin Upregulation by the Components of XCUR-FXN Indicates Possibility for Disease Resolution in Patients Frataxin Protein Measured Across Brain and Cord Regions at 2 Dose Levels in Pook800J FA Mouse Model • The highest fold change

  22. Slide 22: SNAs Distribute Into Deep Brain Regions Critical for FA Pathology

    ©2021 Exicure, Inc.® All Rights Reserved. 22 SNAs Distribute Into Deep Brain Regions Critical for FA Pathology In Situ Hybridization of SNA in the Brain (Rat)1 via ICM dosing 1) Rats received single ICM dose of 415 µg (~2 mg/kg) MALAT1-targeting oligonucleotide in SNA format. Rats were sacrificed fo

  23. Slide 23: XCUR-FXN: Rapid Path Forward to Clinical Validation

    ©2021 Exicure, Inc.® All Rights Reserved. XCUR-FXN: Rapid Path Forward to Clinical Validation 23 • IND filing expected at end of 2021, initiate Phase 1b First-in-Human study in Friedreich’s Ataxia (FA) patients in H1, 2022 • Robust and scalable platform GMP manufacturing process in place - Exicure h

  24. Slide 24: Pharmacodynamic Endpoints for Phase 1b

    ©2021 Exicure, Inc.® All Rights Reserved. Pharmacodynamic Endpoints for Phase 1b Selected to Provide Robust Data Package to Assess Effects of XCUR-FXN in Patients 24 Neuroimaging CSF / Serum Biomarkers PD Marker Significance of Change Frataxin protein (in CSF) Target engagement by XCUR- FXN in most

  25. Slide 25: FA Competition: Late-Stage Programs do not Address the Genetic Cause

    ©2021 Exicure, Inc.® All Rights Reserved. FA Competition: Late-Stage Programs do not Address the Genetic Cause of FA; Early-Stage Programs Unlikely to Sufficiently Reach CNS 25 Program Vatiquinone Omaveloxolone Leriglitazone CTI-1601 FA GeneTAC AAV Gene Therapies MOA Oxidative stress reduction Oxida

  26. Slide 26: Deep Neuroscience Pipeline

    exicure’ Deep Neuroscience Pipeline

  27. Slide 27: Nav1.7: a Validated Pain Target Ideally Suited to SNA Platform

    ©2021 Exicure, Inc.® All Rights Reserved. Nav1.7: a Validated Pain Target is Ideally Suited to Exicure’s SNA Platform Due to SNA Selectivity and Biodistribution Profile 27 Oligonucleotide Selectivity vs Small Molecules (SMs) 2 • Past small molecules required unbound plasma concentrations substantial

  28. Slide 28: Potent CLN3 Splice Modulating SNAs for Batten Disease

    ©2021 Exicure, Inc.® All Rights Reserved. Potent CLN3 Splice Modulating SNAs for Treatment of Both the CNS and Ocular Disease Manifestations of CLN3 Batten Disease 28 Establishing PoC for Eye Disease3 • SNA target engagement (splice switching) observed with eGFP reporter construct in mouse retina an

  29. Slide 29: Oncology Differentiated TLR9 Agonist in P2 for Solid Tumors

    Oncology Differentiated TLR9 Agonist in P2 for Solid Tumors

  30. Slide 30: SNAs Are Ideal for TLR9 Activation

    ©2021 Exicure, Inc.® All Rights Reserved. SNAs Are Ideal for TLR9 Activation • Toll like receptor 9 (TLR9) agonism can produce the desired pharmacodynamics • TLR9 is found in the endosome of cells – SNAs are colocalized in the endosome after internalization into cells • The SNAs are coated externall

  31. Slide 31: Phase 1b Summary of Cavrotolimod Clinical Findings

    ©2021 Exicure, Inc.® All Rights Reserved. Phase 1b Summary of Cavrotolimod Clinical Findings Clinically meaningful overall response rate ORR 21% (all doses; 1 CR, 3 PR) ORR 33% (highest and Phase 2 dose; 2 PR) Systemic (abscopal) effects Regression in distant and regional lesions Proof of concept in

  32. Slide 32: Response in Refractory Melanoma Patient With Progression on Anti-PD-1

    ©2021 Exicure, Inc.® All Rights Reserved. Effects on Both Lesions Injected Non-injected Response in Refractory Melanoma Patient With Progression on Anti-PD-1 at Enrollment 76-year-old man with melanoma 32 Lesions at Baseline Response to Cavrotolimod + Pembrolizumab at 12 Weeks

  33. Slide 33: Phase 1b: Tumor Regression in Distant, Noninjected Lesions

    ©2021 Exicure, Inc.® All Rights Reserved. Phase 1b: Tumor Regression in Distant, Noninjected Lesions 33 PD CRPDPR Overall Response CSCC MCCMelanomaMCC -33% R face -20% R lung -33% L neck -36% R axillary LN -34% R axillary LN -50% L axillary LN -47% L abdomen -29% L abdomen -100% L leg -100% L leg CS

  34. Slide 34: Cavrotolimod Phase 2 Expansion Stage: Enrollment Commenced

    ©2021 Exicure, Inc.® All Rights Reserved. Merkel Cell Carcinoma N = up to 29 1 Enroll 10 cavro at RP2D and pembro per label N=10 Enroll 19 cavro at RP2D and pembro per label N=29 ≥ 1 partial response or complete response Cutaneous Squamous Cell Carcinoma N = up to 29 2 Enroll 6 cavro at RP2D and cem

  35. Slide 35: Broad Applicability of the SNA Platform

    Broad Applicability of the SNA Platform Applications in Eye, Lung, GI, Dermatology

  36. Slide 36: Preclinical Data Supports Additional Therapeutic Settings

    ©2021 Exicure, Inc.® All Rights Reserved. Ophthalmology OLIGO ALONE OUR SNA Distribution after 24 hours GI Lung DistributionAnti-TNFα SNA Increases Survival in TNBS-induced Colitis Mouse Model Our SNA High levels of oligonucleotide in the eye Oligo Very low levels in the eye Our SNA High levels of o

  37. Slide 37: Exicure + Allergan: Active Collaboration for Hair Loss Disorders

    ©2021 Exicure, Inc.® All Rights Reserved. Exicure + Allergan: Active Collaboration for Hair Loss Disorders • $25MM upfront • Up to $50M in option/IND- enabling payments • Up to $195M in development and regulatory milestones • Up to $530MM in commercial milestones • Tiered royalties of mid single-dig

  38. Slide 38: Exicure Deliverables 2021/2022

    ©2021 Exicure, Inc.® All Rights Reserved. Exicure Deliverables 2021/2022 38 Q1, 2021 Q2-Q3, 2021 Q4, 2021 H1, 2022 • XCUR-FXN in IND- enabling studies • SCN9A and CLN3 move into in vivo studies • SCN9A and CLN3 in vivo target engagement • MALAT1 target engagement in NHPs (platform) • IND filing for

  39. Slide 39: ex§cure’ <5

    ex§cure’ <5

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