Corporate Presentation - DAVID GILJOHANN, CEO NASDAQ: XCUR - Jan 07
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Jan
07
2021
Corporate Presentation
DAVID GILJOHANN, CEO
NASDAQ: XCUR
Cautionary 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.
2
The Exicure Difference
PLATFORM THERAPEUTICS VALUE
Better Uptake, Greater Stability Growing Development Pipeline XCUR (NASDAQ)
RARE DISEASE FORMS MARKET CAP CASH
IMMUNO-
3-D architecture drives NEURO ONCOLOGY
better uptake Friedreich’s Ataxia ~$175M $94M
CAVRO 1/5/21 9/30/20
and greater stability SCN9A- Neuropathic Pain
Phase 2- MCC,
CLN3- Battens Disease
CSCC, Melanoma
PARTNERSHIPS POTENTIAL MILESTONE PAYMENTS
Preclinically demonstrated
local delivery in CNS, eye, GI tract, AbbVie/Allergan Dermelix
DERMATOLOGY
liver, lung, skin up to up to
$725M $166M/program
(2 programs underway) (up to 6 programs)
Mechanism-agnostic:
antisense, siRNA, TLR9 modulation,
splice-switching Potential for additional partners CASH RUNWAY INTO 2022
3
NEUROLOGY
Our Broad Near-Term
Therapeutic IMMUNO-
ONCOLOGY
Therapeutic
SNA Focus
Opportunity Technology DERMATOLOGY
SNA technology allows
nucleic acids to be OPHTHALMOLOGY
delivered to local sites
throughout the body, GI TRACT
Early efforts of nucleic
expanding the potential acid therapeutics
application of nucleic industry focused on the
LUNG
liver
acid therapeutics
LIVER
4
Spherical Nucleic Acids: A Proprietary Technology Platform
Multiple Local Site Delivery
Therapeutic Modalities Throughout the Body
Dense, Radial
Arrangements of
Synthetic Nucleic Acids
ANTISENSE
CNS
Synthetic Nucleic EYE
Acid Therapeutics
SKIN
siRNA GI TRACT
and LUNG
SNA
SNA
(Spherical Nucleic TLR9
Acids) ACTIVATION
Benign Lipid SPLICE-
Nanoparticle Scaffold SWITCHING
5
Consistent History of Execution
PROGRESSING THE PIPELINE AUGMENTING THE TEAM
MANAGEMENT
2017 2018 2019 2020
David Giljohann, PhD Matthias Schroff, PhD Doug Feltner, MD
CEO COO CMO
• Cavro P1 • Cavro P1 • Neuro • Cavro P2
in healthy complete expansion • XCUR-FXN BOARD
subjects • XCUR17 P1 • Cavro P1b/2 selected
complete • Allergan
partnership
GROWING THE FACILITIES Timothy Walbert
Chairman
Chad Mirkin, PhD
Co-founder
David Walt,
PhD
James Sulat
NEW 30,000 FT2 FACILITY TEAM EXPANSION
~30 ~60 Jeffrey Cleland, Bali Muralidhar, Bosun Hau
PhD BM BCh, PhD
MEMBERS MEMBERS
(2019) (2020)
6
Nucleic Acid Therapeutics Come of Age
Over $36B Total Market Cap $2.9B Drug Revenues in 2019
11 >40
and Drugs in late
Approved
stage clinical
drugs
development
Small Protein-based Engineered Cellular Immuno-oncology Nucleic Acid
Molecules Antibodies Therapies CAR-T Therapeutics
7
Uniquely Positioned in the Competitive Landscape for
Nucleic Acid Therapeutics
SNA
Agnostic
TECHNOLOGY/
MODALITY
siRNA
Specialized
Antisense/Splice
TLR-9
Earlier MATURITY Later
(Company, Clinical Stage)
8
SNAs Differentiated from Conventional Linear Oligos
The Benefits
Differentiated Uptake 1
HIGH CELL UPTAKE
SNA
Others
Without encapsulation or
SNAs Linear Oligos chemical modifications
2
Binding ENHANCED STABILITY
VS
Extended therapeutic half-life
Cell surface in cells
Scavenger receptor
3
EXTRA-HEPATIC DELIVERY
SNA enters cells via ubiquitous
scavenger receptors Shown in humans
and mice
9
Exicure is Advancing a Deep Pipeline
DISCOVERY PRECLINICAL DEV PHASE 1 PHASE 2
NEUROLOGY
XCUR-FXN FRIEDREICH’S ATAXIA IND-enabling
CLN3 BATTEN DISEASE
SCN9A NEUROPATHIC PAIN
Discovery Programs ALS, SCAs, ANGELMAN’S
IMMUNO-ONCOLOGY
MERKEL CELL CARCINOMA1
CAVROTOLIMOD
(TLR9 AGONIST) CUTANEOUS SQUAMOUS
CELL CARCINOMA1
DERMATOLOGY
XCUR17 (ANTI-IL17RA) INFLAMMATORY DISORDERS
Undisclosed Target HAIR LOSS DISORDERS
Undisclosed Target NETHERTON SYNDROME
1) In combination with checkpoint inhibitors
10Differentiated 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 distribution and longer persistence in the CNS compared to linear
oligonucleotides (rodent & non-human primates)
– SNA platform clinically de-risked
Rapidly Advancing • XCUR-FXN for Friedreich’s Ataxia entered IND-enabling stage in 4Q’20
Neuroscience Pipeline • Deep pipeline of SNA therapeutics advancing for neurodegenerative disorders
• Hired CMO Doug Feltner (2020) from AveXis to lead clinical development
Outstanding
R&D Capabilities • ~60 employees, ~50 in R&D + high-throughput oligonucleotide discovery platform
11Rapid Progress in Advancing SNA Programs in Neuroscience
SCAs ALS
Batten Disease Angelman
Friedreich’s Ataxia
XCUR-FXN Two Additional CNS Deep CNS Discovery
in IND-Enabling Programs Moving into Pipeline
Studies for FA Preclinical Studies Further Active Programs
Rapid Clinical De-Risking SCN9A – Validated Pain Target Against Validated,
Based on Increasing Frataxin CLN3 – PoC for Eye Disorders Sought-After Targets
Levels in CSF
SNA Therapeutics with Differentiating CNS Biodistribution and Persistence
12Extensive Proof of Concept in Neurological Disorders
Spinraza® PROOF OF CONCEPT (MICE)
SNA
(nusinersen)
100
2x
Survival probability (%)
80 levels of healthy, full-length
SMN2 mRNA and protein in
Commercially available
SMA patient fibroblasts
linear oligo 60
therapeutic to treat
spinal muscular atrophy 40
(SMA) 4x
20 longer survival vs. nusinersen
and
Control
0 mitigated nusinersen toxicity
0 20 40 60 80 100 120
DaysDays
Survival
Survival data presented at 2018 Annual Cure SMA Conference 13SNAs Show Higher Persistence in Brain and Lower Clearance
Through Kidneys
Rat Distribution Study
0 Hours 24 Hours 7 Days
Highest levels
of drug present in
CNS (50 SUV)
Drug still
present in CNS
(0.5 SUV)
Nusinersen Nusinersen Nusinersen Nusinersen Nusinersen Nusinersen
Alone + SNA Alone + SNA Alone + SNA
Nusinersen alone Our SNA
Clearance into kidneys and spleen Persistence in spinal cord and brain
14SNA Penetration to Central Nervous System
Non-Human Primate Biodistribution Study
1 Hour 24 Hours 4 Days 7 Days 14 Days
Nusinersen
Alone
Highest levels Rapid clearance
of drug present in
Nusinersen CNS (50 SUV)
through kidney; poor
persistence in CNS
Our SNA
Persistence in spinal
Drug still
cord for weeks;
Our SNA present in CNS clearance through liver
(intact nanoparticles)
(0.5 SUV)
15SNAs Distribute Widely Throughout the Brain
Non-Human Primate Biodistribution Models
1 Hour 24 Hours 4 Days 7 Days 14 Days
Nusinersen
Highest levels
Alone
of drug present in
Rapid uptake,
Nusinersen CNS (5 SUV) but poor persistence
in brain
Our SNA
Extremely high levels
Drug still of drug in brain for
Our SNA present in CNS weeks
(0.2 SUV)
16Exicure SNAs Distribute to CNS Regions, Cell Types and Subcellular
Compartments Critical for Modulating Neurodegenerative Diseases
Occipital Lobe
Cortex
CYTOPLASM
Neurons
Thalamus
Midbrain NUCLEUS
Astrocytes
Hippocampus
Brainstem Microglia
Corticospinal Tracts
SNA
Blood Vessels
Cerebellum
Dorsal Root Ganglia
Lymphatic Vessels
Friedrich’s Ataxia Batten Disease Pain
17SNAs Reach Areas of the Brain Critical in Neurodegeneration
Nusinersen-SNA Brain Distribution (Mouse) Conclusions
• Confirms broad CNS distribution of
Medial
previous studies
• Demonstrates SNAs distribute to all
regions of the brain, including the
cortex (Batten), cerebellum (FA,
Batten) and thalamus (Batten)
• Laminar patterning suggests prominent
uptake by neurons
Lateral
• Similar results after intrathecal (IT) /
intra-cisterna magna (ICM) / intra-
cerebroventricular (ICV) administration
• Grey, black shading/dots represent ASO; areas with complete lack of ASO would appear white
• Single intrathecal dose of Cy5-labeled nusinersen-SNA (1.5 mg/kg) in 8-week old mice
• Mice sacrificed 14 days post administration
• Images are representative sagittal (left) and coronal (right) sections (5 µm)
18SNAs Distribute Across Key Cell Types in the CNS, incl. Neurons
Immunohistochemistry of SNA-Nusinersen in the CNS (Mouse)1 Conclusions
• Strong uptake in CNS cell types critical
to neurodegenerative disease, incl.
neurons, astrocytes and microglia
• Some uptake to lymph & blood
vessels
• Suggestive of SNAs’ ability to reach
deep brain regions and enter neurons
• Neuronal uptake important to
White arrows indicate
colocalization of
address neuronal dysfunction, the
SNA-Cy5 signal with hallmark of Friedreich’s Ataxia
cell type-specific IHC pathology
1) Representative images of fluorescent IHC from hypothalamus of ICV group. LYVE1 staining from choroid
plexus/meninges. Part of same Cy5-labeling experiment as described before. Similar results after IT / ICM
administration
19Significant Unmet Need in Rare Neurological Disorders
TARGET-RICH SIGNIFICANT THE EXICURE
ENVIRONMENT UNMET NEED DIFFERENCE
Diseases with genetically validated Additional
targets known, but few disease Rare Neurological Disorders Higher potency and longer
modifying therapies exist persistence in animal models
Spinocerebellar Angelman
Ataxia Syndrome suggest potential advantages
Batten Disease Huntington’s
Not readily addressable by Ataxia
ALS
↓ Frequency of dosing and
traditional therapeutic modalities Telangiectasia
↑ Therapeutic Activity
20NEUROLOGY
XCUR-FXN for
Friedreich's Multi-
targeting SNA
IMMUNO-
ONCOLOGY
SNA
Ataxia Technology DERMATOLOGY
• Genetic disorder with no
FDA approved therapies
OPHTHALMOLOGY
• 13,000 patients in the
US and EU5 countries GAA- NAT-
Targeting Targeting
GI TRACT
FXN- LUNG
Potential to address Targeting
many genetic
neurological disorders LIVER
21XCUR-FXN Leverages Multi-Targeting Approach for FXN Upregulation
Degradation of Natural mRNA
XCUR-FXN 1 2
Antisense Transcript Binding
(bi-specific SNA)
DNA Enzyme Mitochondrion
1 2
mRNA
Carries two distinct Increased FXN mRNA Increased
oligonucleotides Frataxin
Production
Cytoplasm Nucleus Cytoplasm
XCUR-FXN degrades a natural antisense transcript 1 and binds to the FXN mRNA 2 , increasing production of
the FXN mRNA and enabling more frataxin protein to be made per mRNA molecule.
22Friedreich’s Ataxia: A Progressive Neurodegenerative Disorder
RARE, LIFE SHORTENING DISORDER OUR APPROACH
Genetically Well Defined: Use genetically targeted SNA
Target
Caused by expansion of GAA triplet in 1st intron therapy to remove FXN
root cause
of frataxin (FXN) gene transcription blockage and
vs. symptoms
increase FXN levels
Neuromuscular
Diagnosed decline
in childhood
Collaboration
Loss of with
independence
Wheelchair bound
after 10-15 years
Intrathecal injection
Mid 30s Survival
Rapid
IND-enabling studies Progress
No Approved Therapies initiated in late 2020
23XCUR-FXN Dose-Dependently Upregulates Frataxin Protein and
FXN mRNA
Neurons (iPSC-derived) from FA Patients Fibroblasts from FA Patients
XCUR-FXN (bi-specific) XCUR-FXN (bi-specific)
160
(% Non Disease Control)
140 100
(% Non Disease Control)
Frataxin Protein
120
80
100
FXN mRNA
80 60
60 40
40
20
20
0 0
Non Disease Untreated 9x 3x 1x Non Disease Untreated 9x 3x 1x
Control Control
Friedreich’s Ataxia (FA) Friedreich’s Ataxia (FA)
• Consistent in vitro activity in FA-patient derived induced neurons and fibroblasts and biodistribution observed with SNA
reporter gene constructs suggests attractive candidate for progression into IND-enabling studies
• All experiments are conducted with unassisted free uptake, without the use of transfection agents or electroporation,
suggesting high translatability to in vivo studies
Key experimental conditions: (left) Frataxin protein study: N = 3 biological replicates, incubation time = 96 hours, days in vitro at time of experiment = 18 days; (right) FXN
mRNA study: N = 3 biological replicates, incubation time = 72 hours, hours in vitro at time of experiment = 24 hours; (both) Cell line 541/420 GAA 24Rapid Path to Clinical Validation for XCUR-FXN
• IND filing expected end of 2021 to initiate Phase 1b MAD study in FA patients in2022
• Robust and scalable platform GMP manufacturing process in place
• Phase 1b goal: Demonstrate safety of multiple ascending doses in FA patients and inform P2/3 dose
selection
• Translational biomarkers, incl. brain imaging and FXN expression in CSF to provide fast read-out for
target engagement and PD effects
• Exploratory endpoints to measure clinical outcomes (ratings scales, etc.) in preparation for pivotal trial
• P1b trial design and site selection in close collaboration with FARA
25NEUROLOGY
Targeting Pain Antisense
oligonucleotides
IMMUNO-
ONCOLOGY
SNA
with SNAs targeting SCN9A
Technology DERMATOLOGY
• Targeting SCN9A, a
genetically validated
OPHTHALMOLOGY
target for potential pain
management
• We have identified SNAs GI TRACT
that silence SCN9A
Expression by >95%
LUNG
LIVER
26NaV1.7, a Validated Pain Target, is Ideally Suited to Our SNA
Platform Due to SNA Selectivity and Biodistribution Profile
1 Human Genetic Validation 2 Oligonucleotide Selectivity 3 SNA Distribute to DRGs
vs Small Molecules (SMs)
SCN9A (IT) Spinal cord (dorsal view) Cy5
Cervical Thoracic
Gain-of-Function Mutations Severe Illustrative Example of Nav1.7
Channel Activation
Pain Selectivity Profile for Small Rostral Caudal
Molecule Inhibitor (Xenon/
Genentech; Bankar et al., (IT) Spinal cord (transverse view)
Dorsal Root
2018) Ganglia
(IT) Spinal cord (lateral view)
SCN9A Dorsal Root
Dorsal Root
Ganglia
Loss-of-Function Mutations Ganglia
Lack of
Caudal
Pain Rostral
Small Molecule Inhibitor of NaV1.7 (nM) *arrowhead indicates level of transverse section
• NaV1.7 is a trans-membrane sodium channel • Past small molecules required unbound • Intrathecal SNA achieves in vivo delivery
key for pain signal transduction to the brain plasma concentrations substantially above to dorsal root ganglion (DRG) neurons, the
the IC50 to sufficiently inhibit NaV1.7 in DRGs key cell type expressing NaV1.7 and which
• Gain-of-function mutations lead to severe mediates transmission of peripheral pain
pain conditions such as inherited • Maintaining selectivity over NaV family
members challenging at these concentrations signals to the brain
erythromelalgia and small fiber neuropathy
• Loss-of-function mutations lead to • Knockdown via SNAs is exquisitely selective,
congenital insensitivity to pain with SNA screening hits not exhibiting
homology with other NaV family members
27NEUROLOGY
SNAs for Splice-switching
oligonucleotides
IMMUNO-
ONCOLOGY
SNA
Batten disease Technology
targeting CLN3
DERMATOLOGY
• Juvenile Batten Disease is a
Severe Monogenic (CLN3)
OPHTHALMOLOGY
Disease
• We have identified SNAs that
increase CLN3 by >3x GI TRACT
LUNG
LIVER
28Juvenile Batten Disease is a Severe Monogenic (CLN3) Disease
• Monogenic, autosomal recessive lysosomal storage disorder
• Estimated prevalence (US): ~7001
• Caused by mutations in the CLN3 gene resulting in battenin deficiency
– Vast majority (>95%) of patients harbor ~1.02-kb deletion of exons 7 and 82,3 on at least one allele
• Leads to childhood blindness, pediatric dementia syndrome (behavioral and mood problems,
intellectual decline), motor impairment, and early death2,4
• No approved therapies; no disease-modifying treatments available
4-7 years 6-10 years 10 years 20 -30 years
Onset of vision Onset of pediatric Onset of Death
loss with dementia epilepsy
progression to syndrome
legal blindness
within 2 years
0 5 10 20 30
Age
1) Exicure interviews with leading Batten Disease clinicians and patient organizations; 2) Williams R. NCL incidence and prevalence data. In: Mole S, Williams R, Goebel H, eds. The Neuronal Ceroid
Lipofuscinoses: Batten Disease. ed. Oxford: Oxford University Press; 2011; 3) Munroe 1997; 4) Ostergaard 2016, Jarvela 1997 29SNA Target Engagement in Mouse Eye and Optic Nerve After Intravitreal
Injection Supports Pursuit of Ocular Manifestations
Target Engagement in Mouse Eye & Optic Nerve Conclusions
(eGFP Reporter Gene)
• Target engagement
Optic
demonstrated for splice-
Oligonucleotide nerve modulating oligonucleotides
(via Cy5) in eye (retina) and optic nerve
with eGFP reporter construct
Injected Eye
(same mode of action used in
our CLN3 program)
Target Engagement Hair
• Co-localization of
(via eGFP under markers for oligonucleotide
splice modulator (Cy5) and target engagement
control) (eGFP)
following intravitreal injection
Uninjected Eye Injected Eye
Note: Mouse hair naturally emitting at same
wavelength, does not reflect eGFP activation
• Support pursuit of ocular
Frontal brain section diseases or disease
Experimental design: 250 μM SNA, D15 post-dose, sectioned at 50 μm (Ex:640 nm, Em:680/13 nm & Ex:470 nm, Em:511/20 nm). Uninjected eye as negative control. manifestations, e.g. in Batten
30NEUROLOGY
IMMUNO-
TLR-9 agonist
oligos ONCOLOGY
SNA
Cavrotolimod Technology DERMATOLOGY
• Targeting Merkel cell
carcinoma and
OPHTHALMOLOGY
cutaneous squamous
cell carcinoma
GI TRACT
LUNG
LIVER
31SNAs Are Ideal for TLR9 Activation
SNA
Scavenger
Receptors
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
Endosome
after internalization into cells
TLR9s
The SNAs are coated externally with
oligonucleotides allowing for facile
interaction with TLR9
SNAs have high cellular uptake,
driving potency
IL-12 IP-10 Activated Activated
NK cell T cell
32Phase 1b Summary
Clinically meaningful overall
response rate Durable response Systemic effects
ORR 21% (all doses) 16 months to date and ongoing in Regression in distant and regional
all 4 responders [1 CR, 3 PR] lesions
ORR 33% (highest
and Phase 2 dose) 6+ months in all 4 responders
Proof of concept in largely Pharmacodynamic profile
Safe and well tolerated
refractory population corroborating efficacy
Progressive disease on Increased serum No treatment-related serious AEs
prior anti-PD-1: 85% cytokines/chemokines or grade 4 AEs
Two or more lines of Increased activation Most common AEs are flu-like
systemic therapy: 65% of immune cells symptoms, injection site reactions,
expected from mechanism of action
Increased tumor infiltration
by immune cells Support highest dose (32 mg) in
Phase 2
CR = complete response, PR = partial response 33Response in Refractory Melanoma Patient with Progression on
Anti-PD-1 at Enrollment
RESPONSE TO CAVROTOLIMOD +
LESIONS AT BASELINE PEMBROLIZUMAB AT 12 WEEKS
Effects on both lesions
Non-injected
Injected
76-year-old man with melanoma 34Decreased Target Tumor Diameter Observed in 37% of Patients
Target Tumor Response: Sum of Injected and Noninjected Lesions
100%
Target Lesion Diameters (%)
Change from Baseline in
Mel CSCC MCC Mel Mel Mel MCC
0%
MCC HSNCC Mel Mel Mel MCC MCC LMS Mel Mel
-100%
Figure excludes 3 patients who did not have post-treatment CT scan assessment 35Cavrotolimod Phase 2 Expansion Stage: Enrollment Commenced
Phase 2 Expansion Design Objectives/Timing
• Determine the safety
Enroll 10 ≥ 1 partial Enroll 19 and preliminary efficacy
Merkel Cell response of AST-008 plus CPI
cavro at RP2D cavro at RP2D
1 Carcinoma or
N = up to 29
and pembro per label complete and pembro per label • Pursuing orphan drug
N=10 response N=29 designation
• Potential for trial to be
registrational in early
2021
Enroll 6 ≥ 1 partial Enroll 19
Cutaneous Exploratory cohorts
cavro at RP2D response cavro at RP2D
Squamous Cell
2 and cemiplimab per label or and cemiplimab underway in Melanoma
Carcinoma (If safe, enroll additional 4) complete per label
N = up to 29 response
and with SC dosing
N=10 N=29
Cavro: cavrotolimod; pembro: pembrolizumab; RP2D: recommended Phase 2 dose; CPI: checkpoint inhibitor 36SNA Technology NEUROLOGY
NHP biodistribution study showed
SNA accumulation and persistence
Has Broad SNA
in brain
Partnership Technology IMMUNO-
ONCOLOGY
AST-008 in Phase 1b/2 clinical
development for solid tumors
Opportunities
Partnerships with
DERMATOLOGY Allergan and Dermelix
Enhanced distribution & persistence
OPHTHALMOLOGY in retinal layers vs. linear oligos after
intravitreal injection in rabbits
Partnership
Efforts Demonstrated activity through
GI TRACT oral gavage in IBD mouse models
Demonstrated target
LUNG engagement and activity in mice
with nebulized SNA formulation
37Nucleic Acid Therapeutic Space Ripe for Partnership
Example Partnership
COMPANY PARTNER AREA UPFRONT TARGETS STAGE
$400MM1;
2019 Opth, CNS, liver $400MM2
30 Discovery
Cardiomet, $100MM1;
2018 $100MM2
10+ Discovery
neurology, pain
$375MM1;
2018 Neurology $625MM2
Unknown Discovery
$110MM1;
2018 CNS $60MM2
9 Phase 1
~$10MM per target for a typical discovery stage partnership
Opth = ophthalmology; CNS = central nervous system;
Cardiomet = cardiometabolic
1. Upfront payment made in cash
2. Equity purchase associated with partnership 38Compelling Pre-clinical Data Provides Rationale for
Partnering/Expansion
OPHTHALMOLOGY GI LUNG
Anti-TNFα SNA increases animal survival in
OLIGO ALONE OUR SNA TNBS-induced colitis mouse model Distribution in lung
Distribution after 24 hours
Oligo Our SNA Our SNA
High levels
Very low High levels
Our SNA of oligonucleotide
levels of oligonucleotide
Increase in the lung in just
in the eye in the eye
survival 2 hours
39Exicure + Allergan: A Hair Loss Disorder Collaboration
THE PARTNERSHIP THE ECONOMICS
• Discover and develop two SNA- • $25MM upfront
based treatments for hair loss
disorders
• Up to $50M in option/IND-
enabling payments
• Initiated November, 2019
• Up to $195M in development and
• Exicure responsible for discovery regulatory milestones
costs prior to option exercise by
Allergan; Allergan responsible
• Up to $530MM in commercial
milestones
afterwards
• Tiered royalties of mid single-digit
to mid-teen percentage
40GROWTH
Well Positioned Potential for robust and growing
pipeline and partnerships
for Success CAPITALIZATION
Well-capitalized with cash
runway into 2022
PARTNERSHIPS
2 current – with opportunity
for many more
CLINIC
Driven drugs into the clinic:
One Phase 2; Four Phase 1’s
MANUFACTURING
Scaled up manufacturing of
our SNA technology
THERAPEUTIC AREA
Expanding scope of diseases addressable
with nucleic acid therapies
41Jan
07
2021
Corporate Presentation
DAVID GILJOHANN, CEO
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