Exicure, Inc. · NASDAQ:XCUR
Exicure — Investor Day (January 2021)
72 slides from Exicure's investor day presentation, Jan 7, 2021
Slide 1: Building a Leading Platform in Neurology
exicure Building a Leading Platform in Neurology Neuroscience R&D Day 2021 January 7, 2021
Slide 2: Cautionary Note Regarding Forward Looking Statements
Cautionary Note Regarding Forward Looking Statements 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 expre
Slide 3: Today's Speakers
Today’s Speakers 28 oO David Giljohann, PhD Matthias Schroff, PhD Doug Feltner, MD Susan Perlman, MD Exicure Exicure Exicure UCLA CEO coo CMO Clinical Prof. of Neurology bs XN Bart Anderson, PhD Grant Corbett, PhD Jennifer Farmer, MS, CGC Exicure Exicure FARA Director, R&D Head, Neuroscience Researc
Slide 4: External Speaker Introductions
External Speaker Introductions ex}cure Susan L. Perlman, MD UCLA Clinical Prof. of Neurology * Clinical Professor, Dep. of Neurology, UCLA * Director of Clinical Trials, UCLA Neurogenetics program * Director, Ataxia Clinic, UCLA Neurogenetics program * Medical Research Advisory Board, National Ataxi
Slide 5: External Speaker Introductions
External Speaker Introductions Jennifer Farmer, MS, CGC FARA CEO * CEO, Friedreich’s Ataxia Research Alliance (FARA) * >15 years of active engagement on behalf of FA patients * Led FARA’s efforts to establish clinical research infrastructure and clinical trial readiness and grow research grant budge
Slide 6: Disclosures
Disclosures * Susan L. Perlman, MD - Dr. Perlman receives compensation for serving on Exicure’s Scientific Advisory Board. - Dr. Perlman has worked with Biogen, Biohaven, Cadent, Celavie, Erydel, Horizon, IntraBio, Reata, Retrotope, PTC, Sanofi, Seelos, Steminent, Uniqure, and Takeda Pharmaceutical
Slide 7: Program Agenda
Program Agenda Exicure Platform Friedreich’s Ataxia SNA Therapeutics for Neurology Pipeline David Giljohann Susan Perlman Friedreich’s Ataxia Progress | | Bart Anderson Matthias Schroff uf 2 3 4 5 6 7 8 SNA Differentiation FARA & Exicure Path to Clinical Q&A Session for Neuroscience Partnership Vali
Slide 8: Exicure Platform for CNS Disorders
exicure Exicure Platform for CNS Disorders David Giljohann, PhD — CEO
Slide 9: Differentiated Platform Enables Rapid Progress in Advancing Neuroscience Therapeutics
Differentiated Platform Enables Rapid Progress in Advancing Neuroscience Therapeutics - Enable dramatically higher cellular uptake of oligonucleotides in vitro - Achieve desired PD effects in vivo at substantially lower oligonucleotide doses Differentiated Nucleic Acid Therapeutics - Broad CNS distr
Slide 10: Spherical Nucleic Acids (SNAs) Are Dense, Radial Arrangements of Oligonucleotides
Spherical Nucleic Acids (SNAs) Are Dense, Radial Arrangements of Oligonucleotides Ideally Suited for Creating Therapeutics Synthetic Oligonucleotides zs + Compatible with virtually all oligonucleotide classes/chemistries (e.g. ASOs, siRNA, TLRs) + Maximum sequence length ~80 nucleotides ol. Benign L
Slide 11: SNAs Exhibit Higher Cellular Uptake vs Linear Oligonucleotides
SNAs Exhibit Higher Cellular Uptake vs Linear Oligonucleotides The Benefits Differentiated Uptake wy d uf Without the need for transfection reagents 2 ENHANCED STABILITY Extended therapeutic half-life in cells 3 EXTRA-HEPATIC DELIVERY Shown in humans, NHPs, minipigs, rats and mice a Linear Oligos ex
Slide 12: Higher Cellular Uptake Translates to Lower IC50 in Neurons
Higher Cellular Uptake Translates to Lower IC. in Neurons Higher Cellular Uptake into Neurons (In Vitro) Linear SNA * Similar results for spinal motor neurons, medium spiny neurons, cortical astrocytes Human i * Free uptake experiments, not Glutamatergic employing transfection agents or Cortical ele
Slide 13: SNA Platform - Next Generation Oligonucleotide Therapeutics
SNA Platform - Next Generation Oligonucleotide Therapeutics Full Spectrum T_ Oligonucleotide Platform ———— RNase-mediated Vie Knockdown 3 Increased Gene Expression Access targets and diseases inaccessible by traditional methods exicure
Slide 14: SNA Platform - Next Generation Oligonucleotide Therapeutics
SNA Platform - Next Generation Oligonucleotide Therapeutics Full Spectrum Enhanced Cellular Oligonucleotide Platform Delivery ° RNase-mediated SMA Mouse Model 7, Knockdown | — [7 & SNA 2 Nusinersen B 60. Increased Gene 3 g Expression = 40 g Nusinersen § 20. or sles °y wa 6 8 100 120 a switchi Switch
Slide 15: SNA Platform - Next Generation Oligonucleotide Therapeutics
SNA Platform - Next Generation Oligonucleotide Therapeutics Full Spectrum T_ Oligonucleotide Platform RNase-mediated N12 Knockdown Increased Gene Expression Access targets and diseases inaccessible by traditional methods exicure Survival Probability (9%) Enhanced Cellular Multi-Targeting Delivery ~~
Slide 16: SNA Platform - Next Generation Oligonucleotide Therapeutics
SNA Platform - Next Generation Oligonucleotide Therapeutics Full Spectrum Enhanced Cellular Multi-Targeting Oligonucleotide Platform Delivery Capability o ‘ivase-mediated SMA Mouse Model Oligo vs N77 Knockdown _ 1007 Target A sal g SNA 2 Nusinersen 2 Oligo vs Increased Gene 3 g Target 8 Expression =
Slide 17: Advancing a Deep Pipeline for Attractive Neuroscience Targets
Advancing a Deep Pipeline for Attractive Neuroscience Targets NEUROLOGY XCUR-FXN SCN9SA CLN3 Discovery Programs IMMUNO-ONCOLOGY CAVROTOLIMOD (TLR9 AGONIST) DERMATOLOGY XCUR17 (ANTI-IL17RA) Undisclosed Target Undisclosed Target Ar My 3j Bok rn FRIEDREICH’S ATAXIA IND ing NEUROPATHIC PAIN BATTEN DISEA
Slide 18: Rapid Progress in Advancing SNA Programs in Neuroscience
Rapid Progress in Advancing SNA Programs in Neuroscience exicure ih Om XCUR-FXN Two Additional CNS in IND-Enabling Programs Moving into Studies for FA Preclinical Studies Rapid Clinical De-Risking SCN9A — Validated Pain Target Based on Increasing Frataxin CLN3 — PoC for Eye Disorders Levels in CSF m
Slide 19: SNA Differentiation for Neuroscience
exicure SNA Differentiation for Neuroscience Grant Corbett, PhD —- Head, Neuroscience Research
Slide 20: SNA-Nusinersen Outperforms Linear Nusinersen in Mice
SNA-Nusinersen Outperforms Linear Nusinersen in Mice a * * Biogen IONIS exicure i C) Spinraza’ PROOF OF CONCEPT (MICE) SNA (nusinersen) 2x levels of healthy, full-length SMN2 mRNA and protein in Commercially available SMA patient fibroblasts linear oligonucleotide therapeutic to treat spinal muscula
Slide 21: Three Drivers of Differentiated SNA Activity in the CNS
Three Drivers of Differentiated SNA Activity in the CNS Higher cell uptake, Higher persistence in the Broad CNS penetration leading to higher CNS, leading to and uptake in all potency at same dose prolonged efficacy neuronal subtypes exicure 2a
Slide 22: Increased SNA Uptake Leads to Higher Potency at Same Dose
@ Increased SNA Uptake Leads to Higher Potency at Same Dose SNA-Nusinersen Linear Nusinersen Oo (Exicure data) (Literature) © Observed FLSMN «=m Predicted FL SMN 3 Observed A7 SMN Predicted A7 SMN © Observed FL SMN* Predicted FL SMN A. Observed A7 SMN'= = = Predicted A7 SMN 7.0: 25 50 C30 = 0.9 ugla
Slide 23: SNA Efficacy is Driven by Longer CNS Persistence
@ SNA Efficacy is Driven by Longer CNS Persistence Ne ex}cure 0 Hours Rat Distribution Study 24 Hours Nusinersen Alone SNA-Nusinersen 7 Days Highest levels of drug present in CNS (50 SUV) Drug still present in CNS Nusinerse (0.5 SUV) Nusinersen sNA-Nusinersen Alone * SNA-Nusinersen Persistence in sp
Slide 24: SNA Shows Broad and Persistent CNS Distribution in NHPs
@@ SNA Shows Broad and Persistent CNS Distribution in NHPs SNA: lusinersen ex}cure Non-Human Primate Biodistribution Study 1 Hour 24 Hours 4 Days 7 Days 14 Days Highest levels of drug present in brain (5 SUV) Brain persistence of drug for weeks following intrathecal Drug still dosing present in brai
Slide 25: Exicure SNAs Distribute to CNS Regions, Cell Types, and Subcellular Compartments
Exicure SNAs Distribute to CNS Regions, Cell Types, and Subcellular Compartments Critical for Modulating Neurodegenerative Diseases Cortex ult } _ CYTOPLAS Thalamus es 1th ~ Midbrain strocytes Hippocampus “yo \ : -- Brainstem Microglia -- Corticospinal Tracts SS Blood Vessels Cerebellum _.. Dorsal R
Slide 26: SNAs Reach Areas of the Brain Critical in Neurodegeneration
SNAs Reach Areas of the Brain Critical in Neurodegeneration SNA-Nusinersen Brain Distribution (Mouse) Medial Lateral Grey, black shading/dots represent ASO; areas with complete lack of ASO appear white Single intrathecal dose of CyS-labeled SNA-nusinersen (1.5 mg/kg) in 8-week-old mice Mice sacrific
Slide 27: SNAs Reach Areas of the Spinal Cord Critical in Neurodegeneration
SNAs Reach Areas of the Spinal Cord Critical in Neurodegeneration SNA-Nusinersen Spinal Cord Distribution (Mouse) Conclusions (IT) Spinal cord (dorsal view) Cervical, | Thoracic * Confirms SNA distribution throughout spinal cord and dorsal root ganglia (DRGs) at multiple levels rostral to the inject
Slide 28: CNS Biodistribution of SNAs Translates to Non-Human Primates
CNS Biodistribution of SNAs Translates to Non-Human Primates - Relative Biodistribution in the CNS (NHP)? Conclusions — * 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 * Stron
Slide 29: SNAs Distribute Across Key Cell Types in the CNS
SNAs Distribute Across Key Cell Types in the CNS Immunohistochemistry of SNA-Nusinersen in the CNS (Mouse)? Neufons:« Microglia Lymphatic Endothelial Gells Blood Vessels’ White arrows indicate colocalization of SNA-Cy5 signal with cell type-specific IHC pe images of fluorescent INC from hypothslamus
Slide 30: SNAs Distribute Broadly in the Brain and Show Nuclear Uptake
SNAs Distribute Broadly in the Brain and Show Nuclear Uptake i In Situ Hybridization of MALAT1-Targeting SNA in the Brain (Rat)* 7 Conclusions ——q Full Brain * Broad and persistent brain distribution of SNAs in rat — Consistent with mouse Cy5-studies * Co-localization of anti-MALAT1 oligonucleotides
Slide 31: Friedreich's Ataxia
exicure Friedreich’s Ataxia Susan Perlman, MD — Clinical Prof. of Neurology, UCLA
Slide 32: Friedreich's Ataxia (FA) — Progressive Neurological Disorder
Friedreich’s Ataxia (FA) — Progressive Neurological Disorder * 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 disabili
Slide 33: FA Results in Rapid Neurological Deterioration and Early Mortality
FA Results in Rapid Neurological Deterioration and Early Mortality Time to Wheelchair-Dependence! Early Mortality? 10 i oe Late-Onset FA _ 2 1 - Very Late-Onset FA‘ g a 4 “Classic” Early-Onset FAS W ¢ 1 _—— ly: S 25 = f 5 20 s Nore Late-Onset Median Time 2 18 & < to wheelchair: ~23 yrs & 10 = oad ‘
Slide 34: Reduced Frataxin Expression Due To Expanded GAA Repeats Cause Neuronal Dysfunction
Reduced Frataxin Expression Due To Expanded GAA Repeats Cause Neuronal Dysfunction in Friedreich’s Ataxia f— NEURON — fp cns —— 4 NUCLEUS ~ Friedreich’s DNA Mitochondrial . y ‘i Ataxia \ ( — Affects: eens ip e ‘ ~ * Dorsal Root Expanded GAA Ganglia Repeats (~70-1000+) “NY ) {. ee . iw? — oun? a Redu
Slide 35: Residual Frataxin Levels in FA Support Oligonucleotide Approach
Residual Frataxin Levels in FA Support Oligonucleotide Approach Frataxin Levels in Blood from FA Patients vs Controls = 150 p<oa0 z i x e > x__p<0.001 32) i : ge s g x 3 Ter “ 3 Sail 28 g E I £ "Oo ‘Control (n=67) Came (n=143)_cFRDA (n=248) LOFA(n=35) — pFROA (n=12) CERDA = Classic, typieal onset FA
Slide 36: Frataxin Levels Are Closely Tied to Disease Outcomes in FA
Frataxin Levels Are Closely Tied to Disease Outcomes in FA GAA Repeat Number? GAA Repeat Number Highly Highly Correlated with Frataxin Levels? Correlated with Disease Outcomes?4 : . 1-075 c ? 2 3 so j 0s xe . AgeofOnset 40 Frataxin gE ~ @ 2d Protein 3 7 = ist A Cr) ‘ 10 Boz oe ees ° ‘ ° 200 400 600
Slide 37: Modified Friedreich's Ataxia Rating Scale (mFARS) is a Validated, Approvable Endpoint
Modified Friedreich’s Ataxia Rating Scale (mFARS) is a Validated, Approvable Endpoint for Measuring Impact on Disease Progression * The “modified FARS” (mFARS) is the clinical rating scale used as the primary outcome measure in most contemporary clinical studies in Friedreich’s Ataxia * =mFARS score
Slide 38: Raising Frataxin Levels is Expected to Improve mFARS Score
Raising Frataxin Levels is Expected to Improve mFARS Score Frataxin mRNA Levels are the Key Increasing Frataxin mRNA Levels with Determinant for Predicting mFARS Variability Substantial Expected Effect Size 159 150. 93 93 5 Severe Severe Disease Disease 8 a) Effect of a 21% § § ap increased FXN 3 2
Slide 39: FARA & Exicure Partnership
exicure FARA & Exicure Partnership Jennifer Farmer, MS, CGC — CEO, FARA
Slide 40: FARA's Collaborative Approach and Impact
FARA’s Collaborative Approach and Impact G FARA’s Mission My To marshal and focus the resources and relationships needed to treat and cure FA Guiding Principles Collaboration and partnership, not isolation and confrontation (Academia, Industry and Government) ? g Our Strategic Pillars Attracting and
Slide 41: FARA Supports and De-risks R&D by Leveraging our Expertise, Network, and Domain Resources
FARA Supports and De-risks R&D by Leveraging our Expertise, Network, and Domain Resources Grant funding Patient registry / recruitment A adv y in post phase 2/3 ‘eval Access to academic experts & Trial design advice m FARA’s value eareairetters Eueiding cupnort / patient costs Serve on FDA advisory
Slide 42: The CNS Symptoms of FA Have the Most Significant Impact on Function and Quality of Life
The CNS Symptoms of FA Have the Most Significant Impact on Function and Quality of Life Which of the Following FA-Related Health Concerns Which FA Symptoms Most Impact Your Daily Do You Have Currently? Quality of Life? 100 100 g #9 2 a 5 G @ eS = 0 & 0 re ‘o S 40 So 0 2 5 = go = 2 £20 & é a 0 i) Woa
Slide 43: A Natural History Study to Track Brain and Spinal Cord Changes (TRACK-FA)
A Natural History Study to Track Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA) * Brings together an international consortium of academic, industry and patient advocacy partners to accelerate the drug development through identification of biomarkers and endpoints in t
Slide 44: SNA Therapeutics for Friedreich's Ataxia
exicure SNA Therapeutics for Friedreich’s Ataxia Bart Anderson, PhD — Director, R&D
Slide 45: FA is an Attractive, Rational Indication Choice for Exicure
FA is an Attractive, Rational Indication Choice for Exicure Well-defined, monogenic disease of the CNS Intrathecal administration of SNAs will address key neurological disease manifestations - Leverages differentiated SNA biodistribution and persistence in the CNS SNA technology allows for a synergi
Slide 46: XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation
XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation e Degradation of Natural e mRNA Antisense Transcript 11 Stabilization | Mitochondrion Enzyme Increased Frataxin Carries two distinct mRNA Increased FXN mRNA = Production oligonucleotides Cytoplasm @e) Cytoplasm We believe XCUR-FXN incr
Slide 47: Exicure SNAs Demonstrate Highest Reported FXN mRNA Upregulation
Exicure SNAs Demonstrate Highest Reported FXN mRNA Upregulation In System Without Transfection Agents Deep Pool of Screening Hits for Increasing FXN mRNA (In Vitro — Transfection-Free, at 370 nM) 300 Gi Multi-targeting SNAs @ Mono-targeting SNAs s 2 8 200 € 5 x g Z 100 € 2 z 0 Candidate SNAs * 2-3x
Slide 48: XCUR-FXN Dose-Dependently Upregulates Frataxin Protein & mRNA
XCUR-FXN Dose-Dependently Upregulates Frataxin Protein & mRNA T Neurons (iPSC-derived) from FA Patients 7 —— Fibroblasts from FA Patients —7T = sai = 100 g = §§ 3° £3 100 2% £8 £8 9 aa 23 ae ie 2 a as § Zz, «= = 20 20 = o o Untreated 370nM 1111nM 3333nM. Untreated 370 nM 1111nM 3333nM a a XCUR-FXN C
Slide 49: XCUR-FXN Increases Mitochondrial Frataxin and Activity
XCUR-FXN Increases Mitochondrial Frataxtin and Activity Frataxin Protein Levels in Mitochondria Mitochondrial Activity (Isolated from Induced Neurons) (Isolated from Induced Neurons) D untreated @ untreated 120 XCUR-FXN (500 nM) @ XCUR-FXN (500 nM) 2. - 35 100 e = ce 25 a zS go ag 29 a 23 z3 © co 29
Slide 50: Path to Clinical Validation
exicure Path to Clinical Validation Doug Feltner, MD — Chief Medical Officer
Slide 51: Rapid Path to Clinical Validation
Rapid Path to Clinical Validation * IND filing expected end of 2021 to initiate Phase 1b First-in-Human study in FA patients in 2022 * Robust and scalable platform GMP manufacturing process in place - Exicure has previously successfully scaled up 3 SNA programs for clinical trials in oncology and in
Slide 52: Phase 1b to Provide Important De-risking PK/PD Results
Phase 1b to Provide Important De-risking PK/PD Results Pharmacokinetics Pharmacodynamic Indicators Frataxin Expression Clinical Improvement XCUR-FXN Oligonucleotide Levels Clinical and Functional Serum Biomarkers of Hi Rating Scales Neuronal Damage Neuro-Imaging Robust Set of PK/PD Measures in Phase
Slide 53: Pharmacodynamic Endpoints for Phase 1b Selected to Provide Robust Data Package
Pharmacodynamic Endpoints for Phase 1b Selected to Provide Robust Data Package to Assess Effects of XCUR-FXN in Patients Neuroimaging r CSF / Serum Biomarkers PD Marker Significance of Change PD Marker Significance of Change Quantitative susceptibility Decrease in iron Frataxin protein (in ‘Target e
Slide 54: Neurology Pipeline Expansion
exicure Neurology Pipeline Expansion Matthias Schroff, PhD — Chief Operating Officer
Slide 55: Advancing a Deep Pipeline for Attractive Neuroscience Targets
Advancing a Deep Pipeline for Attractive Neuroscience Targets SCN9A for Neuropathic Pain and CLN3 for Batten Disease Slated to Enter Preclinical Characterization in 1Q21 Exicure CNS Portfolio Program Indication Approach SCNSA Neuropathic Pain Knockdown es CLN3 Batten Disease Splice Modulation | SCA3
Slide 56: SCN9A (Encoding Protein Nav1.7)
exicure SCN9A (Encoding Protein Nav1.7) Matthias Schroff, PhD — Chief Operating Officer
Slide 57: Nav1.7, a Validated Pain Target, is Ideally Suited to Exicure's SNA Platform
Na,1.7, a Validated Pain Target, is Ideally Suited to Exicure’s SNA Platform Due to SNA Selectivity and Biodistribution Profile (1) Human Genetic Validation SCNIA Gain-of-Function Mutations ‘sess SCN9A Loss-of-Function Mutations ae Pain + Na,1.7 isa trans-membrane sodium channel key for pain signal
Slide 58: Nav1.7, a Validated Pain Target, is Ideally Suited to Exicure's SNA Platform
Na,1.7, a Validated Pain Target, is Ideally Suited to Exicure’s SNA Platform Due to SNA Selectivity and Biodistribution Profile (1) Human Genetic Validation SCN9A Gain-of-Function Mutations Severe SCN9A Loss-of-Function Mutations ae Pain + Na,1.7 is a trans-membrane sodium channel key for pain signa
Slide 59: Nav1.7, a Validated Pain Target, is Ideally Suited to Exicure's SNA Platform
Na,1.7, a Validated Pain Target, is Ideally Suited to Exicure’s SNA Platform Due to SNA Selectivity and Biodistribution Profile (1) Human Genetic Validation SCNIA Gain-of-Function Mutations ‘sess SCN9A Loss-of-Function Mutations incicol ae Pain + Na,1.7 is a trans-membrane sodium channel key for pai
Slide 60: We Have Identified Multiple SNAs That Dose-Dependently Silence SCN9A Expression by >95%
We Have Identified Multiple SNAs That Dose-Dependently Silence SCNIA Expression by >95% Dose-Dependent SCN9A Knockdown with SNAs In Vitro* 220 nM 660 nM 2000 nM 6000 nM SCN9A mRNA (% Untreated) SNAL SNA2 SNA3 SNA4_ SNAS SNAG =SNA7_ = SNA8_—SNAQ SCN9A Knockdown in Rat DRG Neurons 100% 80% 60% 40% SCN
Slide 61: CLN3 Batten Disease
exicure CLN3 Batten Disease Matthias Schroff, PhD — Chief Operating Officer
Slide 62: Juvenile Batten Disease is a Severe Monogenic (CLN3) Disease
Juvenile Batten Disease is a Severe Monogenic (CLN3) Disease * Monogenic, autosomal recessive lysosomal storage disorder * Estimated prevalence (US): ~700! * Caused by mutations in the CLN3 gene resulting in battenin deficiency - Vast majority (>95%) of patients harbor 1.02-kb deletion of exons 7 an
Slide 63: Mutations in CLN3 Cause a Lysosome Storage Defect with Debilitating Ocular and CNS Effects
Mutations in CLN3 Cause a Lysosome Storage Defect with Debilitating Ocular and CNS Effects CLN3 Molecular Neuron & Clinical [Deletion | i Effects 7 [~ ——e —h [~~ Manifestations ~ | oss Lack of membrane- bound battenin leads'to . lysosome storage — disorder Epilepsy (seizures); Neuronal & progressive
Slide 64: Our SNA is Designed to Create a Stable and Functional CLN3 Variant
Our SNA is Designed to Create a Stable and Functional CLN3 Variant exicure Exicure Approach to CLN3 SNA-mediated \Y Splice Switching “reer SHRLCHSTE- Expression of Functional CLN3 Variant Normal Lysosomal Disposal & Clearance Exicure’s splice-modulating SNAs are designed to correct the CLN3 open rea
Slide 65: We have Identified SNAs that Potently Modulate CLN3 Splicing
We have Identified SNAs that Potently Modulate CLN3 Splicing Exicure CLN3 Splice Modulating SNAs Increase Stable CLN3 An+78 Transcript WCLN3 478 CLN3 An+78 (Mutation) —(Splice-corrected) 100% zg CLN3 BS 80% Batten Se Patient ER ee line 1 55 ee CLN3 = 20% Batten 3 Patient 0% Line 2 PD YG? 9 GOH GP GP
Slide 66: Increase in Functional CLN3 Variant Translates into Increased Levels of Total CLN3 mRNA
Increase in Functional CLN3 Variant Translates into Increased Levels of Total CLN3 mRNA rs” Average Increase In Total CLN3 mRNA Transcript! at 5 uM? — +| 300 ; ATT SNA1 SNA2 SNA3 SNA4 SNAS SNA6 SNA7 SNA8 SNA9 SNAI0 SNA11 SNA12 SNA13 SNAI4 SNAI5 CLN3 mRNA (% Untreated) 8 Our SNAs dose-dependently cor
Slide 67: SNA Target Engagement in Mouse Eye and Optic Nerve After Intravitreal Injection
SNA Target Engagement in Mouse Eye and Optic Nerve After Intravitreal Injection Supports Pursuit of Ocular Manifestations Target Engagement in Mouse Eye & Optic Nerve Oligonucleotide (via Cy5) Target Engagement (via eGFP under splice modulator control) ex}cure (eGFP Reporter Gene) Frontal brain sect
Slide 68: Potent CLN3 Splice Modulating SNAs for Treatment of Both CNS and Ocular Disease Manifestations
Potent CLN3 Splice Modulating SNAs for Treatment of Both the CNS and Ocular Disease Manifestations of CLN3 Batten Disease Commercially Attractive Indication 0 in US and EU + ~50% of US patients already known by KOLs * High unmet need supports attractive pricing for a clinically meaningful therapy +
Slide 69: Closing Remarks
Closing Remarks exijcure
Slide 70: Rapid Progress in Advancing SNA Programs in Neuroscience
Rapid Progress in Advancing SNA Programs in Neuroscience exicure ih Om XCUR-FXN Two Additional CNS in IND-Enabling Programs Moving into Studies for FA Preclinical Studies Rapid Clinical De-Risking SCN9A — Validated Pain Target Based on Increasing Frataxin CLN3 — PoC for Eye Disorders Levels in CSF m
Slide 71: Thank you
exicure Thank yous
Slide 72: Q&A
Q&A exijcure