Slide 1: Corporate Overview
Corporate Overview August 5th, 2021 Exhibit 99.1
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 simila
Slide 3: Exicure Snapshot
© 2021 Exicure, Inc. All Rights Reserved. | Exicure Snapshot 3 • Developing therapeutics for genetic disorders based on proprietary Spherical Nucleic Acid (SNA™) platform • SNAs enable differentiated oligonucleotides ideal for CNS applications: – Increased cellular uptake: Higher Potency at Same Dos
Slide 4: Key Value Inflections Across Platform & Programs in 2021 & 2022
© 2021 Exicure, Inc. All Rights Reserved. | Key Value Inflections Across Platform & Programs in 2021 & 2022 Q2 2021 • Rat dose-range finder for XCUR-FXN • Commencement of GLP tox studies for XCUR-FXN • In vivo PoC (eye) for CLN3 program for Batten Disease Q3-4 2021 • Neuroscience collaboration with
Slide 5: Spherical Nucleic Acids are the Next Generation of Oligonucleotide Therapeutics
© 2021 Exicure, Inc. All Rights Reserved. | Spherical Nucleic Acids (SNAs™) are the Next Generation of Oligonucleotide Therapeutics 5 • 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 Friedre
Slide 6: SNA 3D Architecture Drives Receptor-Mediated Uptake Into Cells
© 2021 Exicure, Inc. All Rights Reserved. | SNA 3D Architecture Drives Receptor-Mediated Uptake Into Cells 6 Synthetic Oligonucleotides Benign Lipid Nanoparticle Scaffold1 SNA Spherical Nucleic Acid • Compatible with virtually all oligonucleotide classes/chemistries (e.g. ASOs, siRNA, TLRs) • Maximu
Slide 7: Established and Proven Management Team
© 2021 Exicure, Inc. All Rights Reserved. | Established and Proven Management Team 7 David A. Giljohann Chief Executive Officer Matthias Schroff Chief Operating Officer Douglas Feltner Chief Medical Officer Tim Walbert Chairman Jeffrey L. ClelandJames SulatBali Muralidhar Bosun Hau Elizabeth Garofal
Slide 8: SNAs are a Highly Differentiated and Versatile Platform for Drug Development
© 2021 Exicure, Inc. All Rights Reserved. | SNAs are a Highly Differentiated and Versatile Platform for Drug Development 8 Increased SNA potency results in greater efficacy at same dose SNA Benefits Drive Superior In Vivo Efficacy Multi-Targeting Capability Cell-specific delivery of defined ratios o
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 1 Higher Cell Uptake, Leading to Higher Potency at Same Dose 2 Broad CNS Penetration and Uptake in all Neuronal Subtypes SNA Linear SNA with 3x lower IC50 (141 nM) vs. linear oligonucleotides (464 nM
Slide 10: Exicure Continues to Focus its Pipeline and Invest in Neuroscience
© 2021 Exicure, Inc. All Rights Reserved. | Exicure Continues to Focus its Pipeline and Invest in Neuroscience DISCOVERY PRECLINICAL DEV PHASE 1 PHASE 2 NEUROSCIENCE XCUR-FXN Friedreich’s Ataxia SCN9A Neuropathic Pain CLN3 Batten Disease Undisclosed Huntington’s Disease Undisclosed Angelman Syndrome
Slide 11: SNA Differentiation in Neuroscience
SNA Differentiation in Neuroscience
Slide 12: SNA-Nusinersen Outperforms Linear Nusinersen in Mouse Models
© 2021 Exicure, Inc. All Rights Reserved. | SNA-Nusinersen Outperforms Linear Nusinersen in Mouse Models 12 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.,
Slide 13: SNA Efficacy is Driven by Longer CNS Persistence
© 2021 Exicure, Inc. All Rights Reserved. | SNA Efficacy is Driven by Longer CNS Persistence 13 0 Hours Nusinersen Alone SNA- Nusinersen 24 Hours Nusinersen Alone SNA- Nusinersen 7 Days Nusinersen Alone SNA- Nusinersen Highest levels of drug present in CNS (50 SUV) Drug still present in CNS (0.5 SUV
Slide 14: SNA Persistence Translates to Non-Human Primates
© 2021 Exicure, Inc. All Rights Reserved. | SNA Persistence Translates to Non-Human Primates (IT Dosing) 14 • 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 persist
Slide 15: XCUR-FXN: Friedreich's Ataxia
XCUR-FXN: Friedreich’s Ataxia
Slide 16: Friedreich's Ataxia is a Progressive Neurological Disorder
© 2021 Exicure, Inc. All Rights Reserved. | Friedreich’s Ataxia (FA) is a Progressive Neurological Disorder 16 • Degenerative, debilitating, life-shortening, neuromuscular disorder causing loss of coordination (ataxia) in arms and legs • Monogenic disorder: FXN mutations result in reduced levels of
Slide 17: Reduced Frataxin Expression Due To Expanded GAA Repeats Cause Neuronal Dysfunction
© 2021 Exicure, Inc. All Rights Reserved. | Reduced Frataxin Expression Due To Expanded GAA Repeats Cause Neuronal Dysfunction in FA 17 Friedreich’s Ataxia Key CNS Tissues: • Cerebellum • Dorsal Root Ganglia Neuronal Dysfunction & Death DNA Reduced FXN ProteinReduced FXN mRNA GAAGAAGAAGAAGAAGA … Mit
Slide 18: Neurodegeneration Drives All Components of the mFARS Rating Scale
© 2021 Exicure, Inc. All Rights Reserved. | Neurodegeneration Drives All Components of the mFARS Rating Scale, the Validated Registrational Endpoint for FA 18 1) Bürk, K., Cerebellum & Ataxias, 2017 2) Puccio, et al., Rev Neurol, 2014; Parkinson et al., J Neurochem, 2013 3) mFARS used as the primary
Slide 19: CNS Manifestations of FA Have the Most Significant Impact on Function
© 2021 Exicure, Inc. All Rights Reserved. | 0 20 40 60 80 100 Pe rc en t o f P at ie nt s For Patients, the CNS Manifestations of FA Have the Most Significant Impact on Function and Quality of Life 19 CNS Manifestations “CNS manifestations of FA are the most significant in terms of function and qual
Slide 20: Increased Frataxin Levels Expected to Slow or Stop Disease Progression
© 2021 Exicure, Inc. All Rights Reserved. | Increased Frataxin Levels Elicited by Oligonucleotides Expected to Slow or Stop Disease Progression 20 Frataxin Levels in Blood from FA Patients vs Controls • Patients with FA have substantial residual frataxin • Residual frataxin levels support Exicure’s
Slide 21: XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation
© 2021 Exicure, Inc. All Rights Reserved. | Cytoplasm XCUR-FXN (bi-specific SNA) Carries two distinct oligonucleotides ( )1 2 1 2 XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation 21 DNA mRNA CytoplasmNucleus Degradation of Natural Antisense Transcript 1 1 Increased Frataxin Productio
Slide 22: XCUR-FXN Dose-Dependently Upregulates Frataxin Protein and Restores Mitochondrial Function
© 2021 Exicure, Inc. All Rights Reserved. | Increased Mitochondrial Frataxin Levels2 • XCUR-FXN restores protein levels to non- disease controls in mitochondria, the main target cellular compartment of FA XCUR-FXN Dose-Dependently Upregulates Frataxin Protein and Restores Mitochondrial Function in I
Slide 23: Magnitude of In Vivo Frataxin Upregulation by Components of XCUR-FXN
© 2021 Exicure, Inc. All Rights Reserved. | Magnitude of In Vivo Frataxin Upregulation by the Components of XCUR-FXN Showed Possibility for Disease Resolution in Patients 23 • The highest fold changes (2-3x) are observed in the cerebellum and across all DRG regions, the areas with highest known dise
Slide 24: SNA Oligonucleotides Observed in Cytoplasm and Nucleus of Neurons in Deep Cerebellum
© 2021 Exicure, Inc. All Rights Reserved. | SNA Oligonucleotides Observed in Both the Cytoplasm and Nucleus of Neurons in the Deep Cerebellum 24 In Situ Hybridization of SNA in the Brain (Rat)1 via ICM dosing • Co-localization of anti-MALAT1 oligonucleotides with nuclei suggests nuclear uptake of SN
Slide 25: Rat Dose Range Finder Results for XCUR-FXN Show No Related Adverse Findings
© 2021 Exicure, Inc. All Rights Reserved. | Rat Dose Range Finder Results for XCUR-FXN Show No Test Article- Related Adverse Findings 25 • XCUR-FXN was overall well tolerated at all dose levels in this study • No adverse, test article-related histopathologic findings at any of the 3 dose levels eval
Slide 26: FA Competition: Late-Stage Programs Do Not Address the Genetic Cause of FA
© 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 26 Program Omaveloxolone Vatiquinone Leriglitazone CTI-1601 XCUR-FXN FA GeneTAC AAV Gene Therapies MoA Oxidative stress redu
Slide 27: Rapid Path to Clinical Validation for XCUR-FXN
© 2021 Exicure, Inc. All Rights Reserved. | Rapid Path to Clinical Validation for XCUR-FXN 27 • IND filing expected end of 2021 to initiate Phase 1b First-in-Human study in FA patients in H1 '22 • Phase 1b goals: Demonstrate safety and characterize PK of multiple ascending doses in FA patients and i
Slide 28: 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 28 PD Marker Significance of Change Frataxin protein (in CSF) Target engagement by XCUR-FXN in most proximal compartment Neurofilament
Slide 29: Deep Neuroscience Pipeline
Deep Neuroscience Pipeline
Slide 30: Nav1.7, a Validated Pain Target, is Ideally Suited to SNA Platform
© 2021 Exicure, Inc. All Rights Reserved. | Small Molecule Inhibitor of Nav1.7 (nM) C ha nn el A ct iv at io n • Past small molecules required unbound plasma concentrations substantially above the IC50 to sufficiently inhibit Nav1.7 in DRGs • Due to small selectivity margins, SMs failed to reach tar
Slide 31: 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 31 • SNAs restore CLN3 mRNA expression to wild-type level in retina of Batten disease mouse model • Supports pursuit of ocular manifes
Slide 32: Cavrotolimod Differentiated TLR9 Agonist in P1b/2 for Solid Tumors
Cavrotolimod Differentiated TLR9 Agonist in P1b/2 for Solid Tumors
Slide 33: SNAs Are Ideal for TLR9 Activation
© 2021 Exicure, Inc. All Rights Reserved. | SNAs Are Ideal for TLR9 Activation 33 • 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 exte
Slide 34: Cavrotolimod Phase 2 Expansion Stage Design
© 2021 Exicure, Inc. All Rights Reserved. | Cavrotolimod Phase 2 Expansion Stage 34 Merkel Cell Carcinoma (MCC) 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 Carcino
Slide 35: Phase 1b/2 Summary of Cavrotolimod Clinical Findings
© 2021 Exicure, Inc. All Rights Reserved. | Phase 1b/2 Summary of Cavrotolimod Clinical Findings 35 Clinically meaningful overall response rate Confirmed ORR 21% in all evaluable MCC patients in P1b/2 (3 out of 14; 2 P1b and 1 P2) P2 CSCC and exploratory cohorts continuing enrollment and data accrua
Slide 36: Phase 1b/2 MCC: Regression of Noninjected Regional & Distant Lesions
© 2021 Exicure, Inc. All Rights Reserved. | Phase 1b/2 MCC: Regression of Noninjected Regional & Distant Lesions 36 CR**PR*Overall Response (RECIST v1.1) P1b Stage -36% R axillary LN † -34% R axillary LN -50% L axillary LN † -100% L leg -100% L leg * Patient progressing on anti-PD-1 therapy at the t
Slide 37: MCC Patient with Overall Complete Response by RECIST v1.1
© 2021 Exicure, Inc. All Rights Reserved. | Phase 2 MCC Patient with Overall Complete Response by RECIST v1.1 37 Baseline Week 36 Overall Response (RECIST v1.1) - Complete Response #1 - Injected Target Lesion Right wrist 20 mm 0 mm #2 - Injected Target Lesion Right lower arm 53 mm 0 mm #3 - Noninjec
Slide 38: Existing Partnerships & Near-Term Value Inflections
Existing Partnerships & Near-Term Value Inflections
Slide 39: Exicure & AbbVie: Active Collaboration for Hair Loss Disorders
© 2021 Exicure, Inc. All Rights Reserved. | Exicure & Abbvie: Active Collaboration for Hair Loss Disorders 39 • $25M upfront • Up to $50M in option/IND- enabling payments • Up to $195M in development and regulatory milestones • Up to $530M in commercial milestones • Tiered royalties of mid single-di
Slide 40: Ipsen Neuroscience Collaboration for Huntington's and Angelman's
© 2021 Exicure, Inc. All Rights Reserved. | Ipsen Neuroscience Collaboration for Huntington’s and Angelman’s 40 • $1B+ total deal value • $20M cash upfront • Up to $10M in preclinical milestones • Up to $50M in option exercise payments • Up to $180M in development and regulatory milestones • Up to $
Slide 41: Key Value Inflections Across Platform & Programs in 2021 & 2022
© 2021 Exicure, Inc. All Rights Reserved. | Key Value Inflections Across Platform & Programs in 2021 & 2022 Q2 2021 • Rat dose-range finder for XCUR-FXN • Commencement of GLP tox studies for XCUR-FXN • In vivo PoC (eye) for CLN3 program for Batten Disease Q3-4 2021 • Neuroscience collaboration with
Slide 42: exbcure’
exbcure’ www.exicuretx.com