#1DEL Corporate Presentation DAVID GILJOHANN, CEO NASDAQ: XCUR exicure 2021 g#2Cautionary Note Regarding Forward Looking Statement 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 expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements other than statements of historical fact in this presentation are forward looking including, but not limited to, statements regarding future operations, financial results and the financial condition of Exicure, Inc. ("Exicure" or the "Company"); the Company's cash runway; the Company's business strategy, including the development of product candidates based on its proprietary SNA technology; the initiation, timing, progress, scope and results of the Company's preclinical studies, clinical trials and research and development programs; its plans for development of cavrotolimod (AST-008), including its Phase 1b/2 clinical trial; the timing, availability and presentation of preclinical, clinical and regulatory developments; the potential benefits of the Company's product candidates; the development and the commercial potential, growth potential and market opportunity for the Company's product candidates, if approved, and the drivers, timing, impact and results thereof; potential and future results of current and planned collaborations; and the timing or likelihood of regulatory filings and approvals. Forward- looking statements are based on management's current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the risk that the COVID-19 pandemic and the associated containment efforts may have a material adverse impact on the Company's business, operations and financial results; the Company's preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; unexpected safety or efficacy data observed during preclinical or clinical studies; the failure of the data from the Company's preclinical trials to be indicative in human trials; clinical site activation rates or clinical trial enrollment rates that are lower than expected; the cost, timing and results of clinical trials; changes in the regulatory environment; unexpected litigation or other disputes; the ability of the Company to protect its intellectual property rights; and the actual funding required to develop and commercialize the Company's product candidates and operate the Company. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in the Company's most recent Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the Securities and Exchange Commission. The forward-looking statements in this presentation speak only as of the date of this presentation, and the Company undertakes no obligation to update these forward-looking statements, unless required by law. exicure | 2#3The Exicure Difference PLATFORM Better Uptake, Greater Stability 3-D architecture drives better uptake and greater stability Preclinically demonstrated local delivery in CNS, eye, Gl tract, liver, lung, skin Mechanism-agnostic: antisense, siRNA, TLR9 modulation, splice-switching THERAPEUTICS Growing Development Pipeline RARE DISEASE FORMS NEURO Friedreich's Ataxia SCN9A- Neuropathic Pain CLN3- Battens Disease PARTNERSHIPS IMMUNO- ONCOLOGY CAVRO Phase 2- MCC, CSCC, Melanoma DERMATOLOGY abbvie Allergan + DERMELIX BIOTHERAPEUTICS Potential for additional partners VALUE XCUR (NASDAQ) MARKET CAP ~$190M 2/1/21 CASH $94M 9/30/20 POTENTIAL MILESTONE PAYMENTS AbbVie/Allergan up to $725M (2 programs underway) Dermelix up to $166M/program (up to 6 programs) CASH RUNWAY INTO 2022 exicure | 3#4Our Broad Therapeutic Opportunity SNA technology allows nucleic acids to be delivered to local sites throughout the body, expanding the potential application of nucleic acid therapeutics SNA Technology Early efforts of nucleic acid therapeutics industry focused on the liver # NEUROLOGY IMMUNO- ONCOLOGY DERMATOLOGY OPHTHALMOLOGY GI TRACT LUNG Near-Term Therapeutic Focus LIVER exicure |#5Spherical Nucleic Acids: A Proprietary Technology Platform L Synthetic Nucleic Acid Therapeutics + Benign Lipid Nanoparticle Scaffold Dense, Radial Arrangements of Synthetic Nucleic Acids SNA (Spherical Nucleic Acids) Multiple Therapeutic Modalities SNA ANTISENSE siRNA TLR9 ACTIVATION SPLICE- SWITCHING and Local Site Delivery Throughout the Body CNS EYE SKIN GI TRACT LUNG exicure | 5#6Consistent History of Execution PROGRESSING THE PIPELINE 2017 Cavro P1 in healthy subjects ● brooks 2018 Cavro P1 complete XCUR17 P1 complete NEW 30,000 FT² FACILITY Brooks ● Neuro ● 2019 ● GROWING THE FACILITIES expansion Cavro P1b/2 Allergan partnership ~30 MEMBERS (2019) 2020 ● Cavro P2 ● XCUR-FXN selected TEAM EXPANSION ~60 MEMBERS (2020) David Giljohann, PhD CEO Timothy Walbert illumina V valneva Chairman NORTHWESTERN UNIVERSITY AUGMENTING THE TEAM Jeffrey Cleland, PhD HARVARD UNIVERSITY MANAGEMENT Chad Mirkin, PhD Co-founder Matthias Schroff, PhD COO BOARD MOLOGEN AG Orpheris VAXIMM David Walt, PhD HORIZON PHARMA Bali Muralidhar, BM BCh, PhD Momenta™ AuraSense VERSARTIS Doug Feltner, MD CMO abbvie James Sulat Bosun Hau Quanterix Pfizer avegis NORTHWESTERN UNIVERSITY MFEINBERG SCHOOL OF MEDICINE exicure | 6#7Nucleic Acid Therapeutics Come of Age Over $42B Total Market Cap Dicerna™ ProQR arrowhead pharmaceuticals Small Molecules WAVE™ LIFE SCIENCES neubase CHECKMATE IONIS PHARMACEUTICALS AVIDITY BIOSCIENCES PHARMACEUTICALS STOKE THERAPEUTICS THERAPEUTICS IDERA Protein-based Antibodies 11 Approved drugs and Engineered Cellular Therapies >40 Drugs in late stage clinical development $2.9B Drug Revenues in 2019 SPINRAZA (nusinersen) 12mg/5 mL EXONDYS 51 (eteplirsen) Injection injection onpattro (patisiran) i complexnjection 10mg/5mL KYNAMRO (mipomersen sodium) injection 200mg/ml DEFITELIO (defibotide sodium Immuno-oncology CAR-T VYONDYS 53 (golodirsen) Injection OXLUMO™ (lumasiran)/5ml GIVLAARIⓇ (givosiran) injection for subcutaneous use 189 mg/mL injection Tegsedi (inotersen) injection VILTEPSO waylivra (volanesorsen) injection 285 mg/1.5 mL Nucleic Acid Therapeutics exicure | 7#8Uniquely Positioned in the Competitive Landscape for Nucleic Acid Therapeutics Agnostic TECHNOLOGY/ MODALITY Specialized SNA exicure Earlier siRNA Dicerna arrowhead pharmaceuticals AVIDITY Dicerna Antisense/Splice neubase Dyne ST KE THERAPEUTICS WAVE LIFE SCIENCES TLR-9 CHECKMATE IDERA PHARMACEUTICALS MATURITY ProQR wy (Company, Clinical Stage) IONIS Later PHARMACEUTICALS exicure | 8#9SNAS Differentiated from Conventional Linear Oligos Differentiated Uptake Cell surface SNA Binding Scavenger receptor SNA enters cells via ubiquitous scavenger receptors exicure SNAS VS Others Linear Oligos The Benefits 1 HIGH CELL UPTAKE Without encapsulation or chemical modifications 2 ENHANCED STABILITY Extended therapeutic half-life in cells 3 EXTRA-HEPATIC DELIVERY Shown in humans and mice exicure | 9#10Exicure is Advancing a Deep Pipeline NEUROLOGY XCUR-FXN CLN3 SCN9A Discovery Programs IMMUNO-ONCOLOGY DERMATOLOGY CAVROTOLIMOD (TLR9 AGONIST) XCUR17 (ANTI-IL17RA) Undisclosed Target Undisclosed Target 1) In combination with checkpoint inhibitors ACA FRIEDREICH'S ATAXIA BATTEN DISEASE NEUROPATHIC PAIN ALS, SCAS, ANGELMAN'S MERKEL CELL CARCINOMA¹ CUTANEOUS SQUAMOUS CELL CARCINOMA¹ INFLAMMATORY DISORDERS HAIR LOSS DISORDERS NETHERTON SYNDROME DISCOVERY PRECLINICAL DEV IND-enabling PHASE 1 abbvie DERMELIX BIOTHERAPEUTICS PHASE 2 exicure | 10#11Differentiated Platform Enables Rapid Progress in Advancing Neuroscience Therapeutics Differentiated Nucleic Acid Therapeutics Rapidly Advancing Neuroscience Pipeline Outstanding R&D Capabilities - - - ● Enable dramatically higher cellular uptake of oligonucleotides in vitro Achieve desired PD effects in vivo at substantially lower oligonucleotide doses Broad CNS distribution and longer persistence in the CNS compared to linear oligonucleotides (rodent & non-human primates) SNA platform clinically de-risked ● XCUR-FXN for Friedreich's Ataxia entered IND-enabling stage in 4Q'20 Deep pipeline of SNA therapeutics advancing for neurodegenerative disorders • Hired CMO Doug Feltner (2020) from AveXis to lead clinical development ~60 employees, ~50 in R&D + high-throughput oligonucleotide discovery platform exicure | 11#12Rapid Progress in Advancing SNA Programs in Neuroscience 1889 XCUR-FXN in IND-Enabling Studies for FA Rapid Clinical De-Risking Based on Increasing Frataxin Levels in CSF Two Additional CNS Programs Moving into Preclinical Studies SCN9A - Validated Pain Target CLN3 - PoC for Eye Disorders SCAS Batten Disease ALS Angelman Friedreich's Ataxia Deep CNS Discovery Pipeline SNA Therapeutics with Differentiating CNS Biodistribution and Persistence Further Active Programs Against Validated, Sought-After Targets exicure | 12#13Extensive Proof of Concept in Neurological Disorders Biogen IONIS Spinraza Ⓡ (nusinersen) Commercially available linear oligo therapeutic to treat spinal muscular atrophy (SMA) Survival data presented at 2018 Annual Cure SMA Conference 100 80 60 40 20 0 0 PROOF OF CONCEPT (MICE) 20 Control 40 60 80 Days Survival 100 120 exicure SNA 2x levels of healthy, full-length SMN2 mRNA and protein in SMA patient fibroblasts 4x longer survival vs. nusinersen and mitigated nusinersen toxicity exicure | 13#14SNAS Show Higher Persistence in Brain and Lower Clearance Through Kidneys 0 Hours Nusinersen Alone Nusinersen + SNA Rat Distribution Study 24 Hours Nusinersen Alone Nusinersen + SNA Nusinersen alone Clearance into kidneys and spleen Nusinersen Alone 7 Days Nusinersen + SNA Our SNA Persistence in spinal cord and brain Highest levels of drug present in CNS (50 SUV) Drug still present in CNS (0.5 SUV) exicure | 14