Delivering on the RNA Revolution - August 2021 - Investors | Avidity ...
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Delivering on the RNA Revolution August 2021
Forward Looking Statements
We caution the reader that this presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than
statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy,
the anticipated timing, costs, design and conduct of our ongoing and planned preclinical studies and planned clinical trials, research and development plans, timing
and likelihood of success, prospective products, product approvals, plans and objectives of management for future operations, and future results of anticipated
product development efforts, are forward-looking statements. In some cases, the reader can identify forward-looking statements by terms such as “may,” “will,”
“should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative
of these terms or other similar expressions. The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of our plans
will be achieved. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in our business, including, without
limitation: we are early in our development efforts and all of our development programs are in the preclinical or discovery stage; our approach to the discovery and
development of product candidates based on our AOC platform is unproven, and we do not know whether we will be able to develop any products of commercial
value; the success of our preclinical studies and clinical trials for our product candidates; the results of preclinical studies and early clinical trials are not necessarily
predictive of future results; potential delays in the commencement, enrollment and completion of clinical trials; our dependence on third parties in connection with
preclinical testing and product manufacturing; disruption to our operations from the COVID-19 pandemic; unexpected adverse side effects or inadequate efficacy of
our product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; regulatory
developments in the United States and foreign countries, including acceptance of INDs and similar foreign regulatory submissions and our proposed design of
future clinical trials; our ability to obtain and maintain intellectual property protection for our product candidates and proprietary technologies; we may use our capital
resources sooner than we expect; and other risks described in our filings with the SEC, including under the heading “Risk Factors” in our Form 10-K for the year
ending on December 31, 2020, filed with the SEC on March 15, 2021, and any subsequent filings with the SEC. The reader is cautioned not to place undue reliance
on these forward-looking statements, which speak only as of the date hereof, and except as required by applicable law, we do not plan to publicly update or revise
any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. All forward-
looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about
our industry. This data involves a number of assumptions and limitations, and the reader is cautioned not to give undue weight to such estimates. In addition,
projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high
degree of uncertainty and risk. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent
parties and by us.
2
Our Vision
To profoundly improve
people’s lives by
revolutionizing the
delivery of RNA
therapeutics
Luke
Living with DM1
3
Delivering on Our Vision
DISRUPTIVE & BROAD ADVANCING & EXPANDING AGILE & DIVERSE
PLATFORM PIPELINE COMPANY
• Committed to delivering a • Progressing robust pipeline in • Leveraging expertise in clinical
new class of RNA therapies muscle and commercial execution
• Demonstrated preclinical • AOC 1001 cleared to proceed • Assembling an experienced
proof of concept in multiple with Phase 1/2 MARINATM trial; team in rare & RNA therapies
tissues FDA granted orphan drug
designation • Building an integrated and
• Broadening to other tissues diverse company in service of
& cell types through • Anticipated clinical trials for our patients
partnerships & internal both AOC 1044 for DMD and
discovery our AOC FSHD program in
2022
4
AOCs - A Powerful Potential New Class of Drugs
Utilizing decades of proven science in an effort to deliver the power of oligonucleotides
• Designed to combine the proven and safe technologies of
approved monoclonal antibodies and oligonucleotides
Specificity of targeting with mAbs
Potency & precision of oligonucleotides
mAb Targets tissues with durable agents
OLIGO
• Designed to deliver to tissues previously untreatable with RNA
therapeutics
• Focused first on muscle, broadening to other tissues (i.e.
cardiac) and cell types (i.e. B Cells)
ANTIBODY
OLIGONUCLEOTIDE
CONJUGATE (AOC) • Readily scalable with many experienced manufacturers
5
Advancing our Muscle Disease Franchise of AOCs
DISCOVERY /
PROGRAM / INDICATION TARGET LEAD OPTIMIZATION IND ENABLING PHASE 1/2
MUSCLE DISORDERS
AOC 1001:
DMPK
Myotonic Dystrophy Type 1 (DM1)
AOC FSHD Program:
Facioscapulohumeral Muscular DUX4 Clinical trial initiations planned for 2022
Dystrophy (FSHD)
AOC 1044:
Exon 44
Duchenne Muscular Dystrophy Clinical trial initiations planned for 2022
Dystrophin
(DMD)
Exon 51
Dystrophin
Next AOC DMD Programs
Exon 45
Dystrophin
AOC Muscle Atrophy:
MuRF1
Muscle Atrophy*
AOC Pompe Disease:
GYS1
Pompe Disease
* Opportunity for a rare disease indication 6
Engineering AOCs:
Following the Data
• AOCs: Designed to deliver RNA
therapies
mAb
• AOC 1001: First AOC clinical program
• Delivering Next: Potential applications
for AOCs in rare muscle diseases…and OLIGO
beyond
7
Our AOC™ Platform A Potential New Class of RNA Therapeutics
Engineering an
AOC Therapeutic
Designed to combine the mAb
potency and precision of
oligonucleotide therapies with mAb OLIGO
OLIGO
the specificity of mAbs
MONOCLONAL ANTIBODY
OLIGONUCLEOTIDE OLIGONUCLEOTIDE
ANTIBODIES THERAPIES CONJUGATE (AOC)
9
Following the Data: Choosing a mAb to Expand Delivery
Beyond the Liver
• We followed the data to select the delivery moiety
Plasma
Cyno 2 PK in a • Experiments showed that mAbs are superior
Non-Human
Plasma PK Primate • Monoclonal antibodies (mAbs) are a proven technology
100
Fab siRNA
Fab-SSB (6(6mg/kg)
mg/kg)
that have been in use for 30 years. Approved mAbs offer:
% of injected dose
10
• Chronic therapies with well-established safety profiles
mAb siRNA(6(6mg/kg)
mAb-SSB mg/kg)
in plasma
1
• High specificity and affinity
0.1
0.01
• Long half-lives
0.001 • We designed our mAbs in an effort to ensure:
0.0001
0 1 2 3 7 • Specific epitope binding to not compete with
time (days) transferrin
• Antibody is effector function null
• Placement of the oligo itself on the antibody
10Following the Data: Engineering the Linker
Our Linkers are Optimized for Stability and Durability
AOCs with Different Linkers at 0.5 mg/kg
in Mouse • In addition to engineering our linker,
we optimize several other key
aspects including:
• sites of conjugation
• the ratio of oligonucleotides to
antibodies
11Following the Data: Choosing the Oligonucleotide
siRNA was a deliberate choice
Target mRNA Expression
in Gastrocnemius*
• Selected siRNAs for activity and specificity and
designed them to withstand lysosomal enzymes
% Relative mRNA Expression
100 • siRNAs are well characterized. Approved siRNA drugs
have shown:
(myostatin)
• Attractive safety profiles with no known
50
thrombocytopenia, liver or renal toxicity
• Potency in the nanomolar range
0 • Sustained activity in both the cytoplasm and the
1 14 28 44 57 nucleus
Days
• Readily reproducible with many
Modification 1
Modification 2
experienced manufacturers
Modification 3
• Leveraging this approach across the pipeline in different
*Target is myostatin, or MSTN in mouse tissue and cell types
12Optimizing the Specificity of our AOCs
Targeting the RNA with the Right Oligonucleotide
RNA DEGRADATION RNA SPLICING
Reducing the expression of a Correction of aberrant processing
disease-related RNA with of RNAs with splice modifying
siRNAs oligonucleotides
SINGLE STRAND
DOUBLE STRAND THERAPEUTIC
THERAPEUTIC
RISC
siRNA
mRNA
S P L I C E M O D U L AT I O N
We use oligonucleotides that are tailored to modulate a given
disease process
13Following the Data: Each Component was Engineered in an
Effort to Deliver the Optimal AOC for the Target
AOC DATA-DRIVEN COMPONENT
OUR ENGINEERING IMPACT
COMPONENTS CHARACTERISTICS
Approved mAbs offer: • Designed through engineering to be effector
Monoclonal • Well-established safety profiles function null
antibody • High specificity and affinity • Epitope selection designed for optimal
• Long half-lives activity
• Enhanced for durability
• Known linker • Engineered sites of conjugation
Linker
• Applicable to multiple oligo modalities • Optimized ratio of oligonucleotides to
antibodies
Approved siRNA drugs have shown:
• Attractive safety profiles - no known
• Engineered to withstand lysosomal enzymes
thrombocytopenia, liver or renal toxicity
siRNA • Selected and modified to diminish off-target
• Potency in the nanomolar range
effects
• Sustained activity in the cytoplasm and
nucleus
14Engineering AOCs:
Following the Data
• AOCs: Designed to deliver RNA
therapies
mAb
• AOC 1001: First AOC clinical program
• Delivering Next: Potential applications for
AOCs in rare muscle diseases…and OLIGO
beyond
15AOC 1001 for Myotonic Dystrophy Type 1 (DM1) Program “Some days I don’t have the energy to take another step.” Karin, Living with DM1
DM1, Caused by a Toxic Gain-of-Function mRNA, is
Well Suited to an siRNA Approach
MECHANISM OF DISEASE THERAPEUTIC APPROACH
(CUG) n
DMPK AOC 1001 MBNL MBNL
mRNA mRNA
MBNL
Splicing Splicing
MBNL
C
U
G
Errors C
U
G
MBNL
X
Errors
MBNL
Mutant DMPK mRNA Mutant DMPK mRNA
X
Knock down of DMPK
• Trinucleotide expansion in DMPK mRNA sequesters an RNA • Allows MBNL to be released to perform its natural
splicing protein MBNL (Muscleblind like) in nuclear foci. function to aid in splicing key mRNAs in muscle
• Sequestration of MBNL leads to RNA splicing errors in multiple • Improves the splice patterns, muscle function and
muscle-related RNAs and induces DM1 disease reverses the course of DM1 disease. Splice patterns
manifestations. can serve as biomarkers.
17The AOC 1001 siRNA Showed Activity in the Nucleus and
Cytoplasm and Reduced Nuclear Foci in Patient-Derived
Muscle Cells
DM1 Patient Cells Reduction of Nuclear Foci Containing
Control
Mutant DMPK mRNA
140
siDMPK.19
120
5
DMPK expression %
Mock treatment
of mock treatment
100 1 nM siRNA
4
Foci per nucleus
3 nM siRNA
80 10 nM siRNA
3
60
40
2
20 1
0
0
C t l i N l Wh l ll
Cytoplasmic Nuclear Whole cell siDMPK.19
fraction fraction extract
Nuclear and Cytoplasmic DMPK mRNA Levels in DM1
Patient-Derived Muscle Cells; Data: N=2 mean with range
18The AOC 1001 siRNA (siDMPK.19) Produced a 56%
Improvement in Splicing in DM1 Myotubes
Treatment Signature
(100 Splicing Events)
1.25
1.00
Splicing Signature Score
0.75
0.50
56.5%
0.25 Splicing derangement
comparing DM1 to
Splicing control myotubes
0.00 correction
after siRNA
-0.25
treatment
-0.50
-0.75
-1.00 9
9
k
k
.1
.1
oc
oc
PK
PK
M
M
M
M
D
D
Control Myotubes DM1 Myotubes
19Durable ~75% Reduction of DMPK mRNA Observed in Monkey
Skeletal Muscles After a Single Dose of 2mg/kg of siDMPK.19
100
Quadriceps Gastrocnemius
% DMPK mRNA Expression in
75
Cynomolgus Monkey
50
25
0
0 4 8 12
Time (weeks)
20The AOC 1001 siRNA Reduced DMPK mRNA in a Wide
Range of Skeletal Muscle at Nanomolar Concentrations
DMPK Expression in Skeletal Muscle and GI Tissue After a Single i.v. Dose in Monkey
66mg/kg
mg/kg(4(4weeks
weekspost-dose)
post-dose) 22 mg/kg weeks post-dose)
mg/kg (12 weeks post-dose)
21Plasma Profiles Demonstrated No Neutralizing
Antibodies to AOC 1001 in Monkey
100
[siRNA] in Plasma (uM)
10
15 mg/kg
mg/kg
1 5 mg/kg
mg/kg
0.1
1.5
1.5mg/kg
mg/kg
0.01
0.001
0.0001 Study Termination
0.00001
0 20 40 60
Time (day)
• No accumulation with • No change in peak levels or • Plasma half-life at 5
repeated dosing (Q3W) slopes with repeated dosing, mg/kg ~ 24hrs
indicating an absence of
neutralizing antibodies
22AOC 1001 Reduced Muscle DMPK mRNA in Concentration
Responsive Manner in Non-human Primates
NHP Study 6 Day 21 or 28 Post Dosing
70
siDMPK.19 Concentration
in Skeletal Muscle (nM)
60
50
EC50AOC 1001 Toxicology Results Support Entry into the Clinic
Summary of IND-enabling 13-week toxicology studies:
• No dose limiting toxicity • No treatment-related • NOAELs were identified at the
observed in monkey at the histopathologic toxicity highest doses tested in monkey
highest dose tested observed in monkey in which pharmacology was
essentially saturated
• No observed platelet or renal • No changes observed in safety
toxicity pharmacology parameters • Safety results were similar in
(cardiac, respiratory and mice
neurological)
24AOC 1001 Produced >80% Reductions of DMPK mRNA in
Skeletal Muscle at 13 Weeks of Treatment in Monkey
No adverse effects associated with DMPK mRNA reduction
150
DMPK mRNA Levels
Vehicle
(% Control)
100
AOC 1001 (low)
AOC 1001 (mid)
50
AOC 1001 (high)
25
0
Gastroc LD VL Diaphragm Intercostal L.Ventricle
Skeletal MuscleSkeletal Cardiac Muscle Cardiac
Muscle Muscle
LD = Latissimus Dorsi, VL = Vastus Lateralis
• > 80% DMPK mRNA reduction • DMPK mRNA reductions
observed at all AOC 1001 dose observed in left ventricle and
levels across multiple skeletal diaphragm of >75%
muscle tissue
25AOC 1001 Has Been
Engineered to Optimize
Potential Therapeutic Profile
Delivered RNA product candidate to skeletal DELIVERING ON DM1
muscle in vivo
Reduced target mRNA in a broad range of APPROACHING THE CLINIC
muscles in a dose dependent manner in vivo
EC50s in muscle biopsies were in the nM
range Cleared to proceed with
Activity after a single dose continued for Phase 1/2 MARINA trial
months in vivo
Favorable toxicology results that support
clinical development plans FDA granted Orphan Drug
US Patent No. 10,881,743 for AOC 1001 Designation
issued in January 2021
26MARINATM: A Phase 1/2 Clinical Trial to Evaluate AOC 1001 in Adult Patients with DM1
Myotonic Dystrophy Type 1 (DM1): Disease Overview
>40,000 0
PEOPLE WITH DM1 IN THE US APPROVED THERAPIES
• DM1 is a complex disease with symptoms that present
with high variability from patient to patient
• Monogenic, autosomal dominant, progressive disease
that primarily affects muscle: skeletal, cardiac & smooth
• Increases in severity from generation to generation
• Significant impact on quality of life
Loraine,
• Shortened life-expectancy Kristl & Zen
Living with DM1
28DM1 is a Progressive Neuromuscular Disease with
Multiple Organ Involvement
SKELETAL MUSCLE Myotonia, Weakness, Wasting, Pain
CARDIOVASCULAR SYSTEM Arrhythmias, Conduction Blocks
GASTROINTESTINAL TRACK Dysphagia, Dyspepsia, Constipation, Diarrhea
RESPIRATORY SYSTEM Respiratory Muscle Weakness, Aspiration, Sleep Apnea
CENTRAL NERVOUS SYSTEM Hypersomnia, Executive Dysfunction, Emotional, and Social Difficulties
EYE Particulate cataracts
29
References: Thomas 2018, Comprehensive Physiology; Wenninger, 2018Avidity is Collaborating on a Large Natural History
Study (NHS) in DM1 called END-DM1
• END-DM1 is a non-interventional NHS that will advance the understanding of disease
progression in DM1 patients
• END-DM1 is designed and run by the Myotonic Dystrophy Clinical Research Network
(DMCRN)
• 700 patients with DM1 will be enrolled at multiple sites in the US and Europe
Avidity is one of several sponsoring organizations
30Partnering with the DM1 Community to Develop Patient
Reported Outcome (PRO) Measure
Myotonic Dystrophy Type 1 Neuromuscular Severity Measure (DM1-NSM)
• DM1-NSM specifically designed for use in clinical trials of DM1 treatments
• Validation in Phase 1/2 MARINA trial
• Gaining valuable input directly from patients to better understand patients’
experience with DM1
• Collaborating with Myotonic Dystrophy Foundation & key opinion leaders
31MARINATM: A Phase 1/2 Study to Evaluate the Safety, Tolerability,
Pharmacokinetics, and Pharmacodynamics of Single and Multiple
Doses of AOC 1001 Administered Intravenously to Adult DM1
Patients
32Trial Objectives
Primary Objective Secondary Objectives Key Exploratory Objectives
• Safety and tolerability of • Pharmacokinetics • Measures of clinical activity:
single and multiple doses
• Pharmacodynamics • Mobility
(DMPK mRNA knockdown) • Muscle strength
• Spliceopathy • Muscle function
• Patient-reported outcomes (PRO)
• Quality of life
33Trial of AOC 1001 in Adults with DM1
Patient Population: Part A
Single Dose (N=8) 1mg/kg*
N = ~44; Ages 18-65 (1 Cohort)
3:1 RANDOMIZATION
(AOC 1001:Placebo)
Dosing:
2mg/kg (N=12) OPEN
Single and multi-doses Part B LABEL
administered via an Multi-Ascending Dose (N=36) 4mg/kg (N = 12) EXTENSION
intravenous (IV) infusion; (3 Cohorts) STUDY
Multidose quarterly with 8mg/kg (N = 12)
booster after 6 weeks;
Placebo
Biopsies in all cohorts
Treatment and observation duration = 6 months;
patients have the option to roll into the OLE study at the end of each cohort
*Dose listed for all cohorts is siRNA component of AOC 1001
34Dosing Regimen
Quarterly Dosing
Part A
Single IV Dose:
Dosing Open Label Extension Study
AOC 1001 or placebo
Schedule
6 Months
Booster Quarterly Dosing
Part B
Multiple IV Dose:
Dosing Open Label Extension Study
AOC 1001 or placebo
Schedule
Multidose cohort treated quarterly with booster after 6 weeks
35Trial Summary
• Evaluating safety and tolerability in adults with DM1 to identify dose
for future studies
• 1 single dose cohort and 3 multi-dose cohorts
• Patients have the option to roll over into open label extension (OLE) study
• Key secondary endpoints focused on DMPK knockdown and spliceopathy biomarkers
• Exploratory endpoints on measures of clinical activity, PRO and quality of life
• Quarterly maintenance dosing regimen
• Designed in collaboration with patients, advocates and key
physicians in the field
• Participating academic sites from DMCRN and END-DM1
36Engineering AOCs:
Following the Data
• AOCs: Designed to deliver RNA
therapies
mAb
• AOC 1001: First AOC clinical program
• Delivering Next: Potential applications
for AOCs in rare muscle OLIGO
diseases…and beyond
37Advancing our Muscle Disease Franchise of AOCs
DISCOVERY /
PROGRAM / INDICATION TARGET LEAD OPTIMIZATION IND ENABLING PHASE 1/2
MUSCLE DISORDERS
AOC 1001:
DMPK
Myotonic Dystrophy Type 1 (DM1)
AOC FSHD Program:
Facioscapulohumeral Muscular DUX4 Clinical trial initiations planned for 2022
Dystrophy (FSHD)
AOC 1044:
Exon 44
Duchenne Muscular Dystrophy Clinical trial initiations planned for 2022
Dystrophin
(DMD)
Exon 51
Dystrophin
Next AOC DMD Programs
Exon 45
Dystrophin
AOC Muscle Atrophy:
MuRF1
Muscle Atrophy*
AOC Pompe Disease:
GYS1
Pompe Disease
* Opportunity for a rare disease indication 38AOCs Engineered to Use Receptor Mediated Uptake for a
Range of Tissue and Cell Types In Vivo
LIVER SKELETAL MUSCLE CARDIAC IMMUNOLOGY IMMUNO-ONCOLOGY
39Engineering AOCs:
Following the Data
AOCs are designed to deliver RNA therapies
with specificity, potency and precision
AOCs are the result of years of in-house
engineering
AOCs are designed to exploit the well mAb
characterized safety and efficacy profiles of
approved mAbs and siRNA drugs
AOC 1001 – first AOC clinical program
Advancing and expanding AOC pipeline – OLIGO
Progressed AOC 1044 and AOC FSHD program
into IND-Enabling Studies
Focused today on rare disease with potential for
much broader application
40Delivering on the RNA
Revolution
DELIVERING NEXT
AOC 1001 cleared to proceed
with Phase 1/2 MARINA trial
AOC FSHD program & AOC 1044
for DMD anticipated to enter the
clinic in 2022
Pursuing preclinical proof of
Luke concept in additional skeletal
Living with DM1
muscle and other tissues
41Facioscapulohumeral Muscular Dystrophy (FSHD) Program “Living with FSHD feels like an imprisonment in your own body.” Amy, Living with FSHD
FSHD Disease Overview
AFFECTS
~16,000 - 38,000 ~1 in 20,000 0
PEOPLE IN THE US INDIVIDUALS IN THE US APPROVED THERAPIES
• FSHD is one of the most common forms of muscular dystrophy
characterized by progressive skeletal muscle loss; initial signs appear in the
face, shoulders, arms and trunk
• The disease is caused by the abnormal expression of DUX4 (double
homeobox 4), a gene involved in embryonic development but not typically
expressed in adults
43FSHD is Caused by Aberrant Expression of DUX4 Gene
After Birth
HEALTHY DISEASE
DUX4 is located on human D4Z4 is open and expressed in
chromosome 4, in the D4Z4 region FSHD muscles
X DUX4
D4Z4 REPEATS Shortened D4Z4 Repeats
• DUX4 is normally only expressed • DUX4 creates changes in gene
during embryonic development expression that result in muscle
degeneration
• DUX4 gene is repressed in healthy
muscles • Inappropriate DUX4 expression in
muscles results in FSHD
44Our AOC is Designed to Treat the Underlying Cause of FSHD
DISEASE
DUX4
Shortened D4Z4 Repeats • Our AOC FSHD silences DUX4
expression to inhibit the
expression of toxic downstream
genes to a more normal state
siRNA-mediated
DUX4 silencing
X
Reduced expression
of toxic DUX4-induced genes
45Potent Reductions in DUX4 Target Gene Expression
Observed in Muscle Cells with Lead siRNA Candidates
FSHD Composite
• Reduction in gene expression in vitro of
a composite of 4 known biomarkers in
cells from patients with FSHD
• Similar results were observed across a
range of cells from patients
• Lead siRNA candidates showed high
potency, with IC50FSHD Program Summary
Aberrant expression of DUX4 well
established as cause of FSHD DELIVERING ON FSHD
Mouse model with human DUX4 gene PRECLINICAL STUDIES
available ONGOING
AOC FSHD reduced expression of key
DUX4 biomarkers in FSHD patient Planned regulatory filing to
myotubes support initiation of a
Natural history study planned clinical trial in 2022
47Duchenne Muscular Dystrophy (DMD) Program Three programs advancing toward the clinic
Duchenne Muscular Dystrophy: Disease Overview
~10,000 - 15,000 SIMILAR PREVALENCE APPROVED THERAPIES
HAVE NOT ESTABLISHED
DMD BOYS IN THE US ESTIMATES FOR EUROPE A CLINICAL BENEFIT
• DMD is a monogenic, X-linked, recessive,
neuromuscular disease 14.0% Exon 51
Exon 45
Exon 44
• Caused by mutations in the DMD gene, which 35.6%
9.0%
encodes for the protein “dystrophin”
• Lack of functional dystrophin leads to stress and 7.1%
tears of muscle cell membranes, resulting in
muscle cell death and the progressive loss of
10.1%
2.0%
2.7%
muscle function 3.6%
3.8%
4.6%
7.5%
Exons 44, 51 and 45 represent ~30% of the
total mutations observed amenable to skipping
49AOC Treatment Increased Exon Skipping > 50-fold
Compared to an Unconjugated Oligo in DMD Model
• mdx mouse model of DMD 50
• Single injection of 8 mg/kg of
(Skipped vs total DMD mRNA)
40
phosphorodiamidate morpholino
% DMD Exon23 Skipping
oligomer (PMO)
30
• Vehicle = PBS
• PMO = Dystrophin (DMD) exon 23 20
skipping PMO
10
• AOC = TfR1 mAb + DMD exon 23
skipping PMO
0
• Exon skipping was measured 14 days Vehicle PMO AOC
post dose
50Exon Skipping with a TfR1 mAb AOC or Control mAb AOC
80
TfR1.mAb AOC 1.9 mg/kg
TfR1.mAb AOC 3.3 mg/kg
% Skipping Efficiency
60
TfR1.mAb AOC 5.7 mg/kg
(skipped/total)
TfR1.mAb AOC 8.5 mg/kg
TfR1.mAb AOC 10 mg/kg
40
Control.mAb AOC 10 mg/kg
20
Data provides us with a framework
for establishing target
0 concentration in clinical trials
0 50 100 150
Tissue PMO conc (nM)
The PMO conjugated to a non-targeting mAb (black square) allowed for uptake into muscle,
but skipping was substantially less compared to the TfR1 targeted AOC
51Dystrophin Exon 44-Skipping Lead Candidates
Substantial skipping of Exon 44 of dystrophin observed in human
primary myocytes when incubated with two lead development
80 candidates
44 Seq 5
60
% Exon 44 Skipping
44 Seq 7
(skipped/total)
40
20
0
0.0 0.5 1.0 1.5
Concentration (uM)
52DMD Program Summary
Skipping of exons in relevant disease
models DELIVERING ON DMD
Long duration of action THREE PROGRAMS
ADVANCING TOWARD
Specificity of the target exon
THE CLINIC
Effective delivery of PMO
Planned regulatory filing
Well-established and scalable
methods for manufacturing to support initiation of a
clinical trial for AOC
Potential for DMD mutations beyond 1044 in 2022
exons 44, 51 and 45
53Building for the Future
Experienced Leadership with Significant RNA
Therapeutic Expertise
Management Team
Sarah Boyce Art Levin, PhD Jae Kim, MD, FACC W. Michael Flanagan, PhD
President & CEO CSO CMO CTO
Michael MacLean John Wallen III, PhD, JD Joseph Baroldi Teresa McCarthy
CFO General Counsel COO CHRO
Board of Directors
Troy Wilson, PhD, JD Carsten Boess Edward Kaye, MD Jean Kim
Chairman & Avidity Founder, Board Member CEO & Director, Board Member
CEO of Kura Oncology Stoke Therapeutics
Noreen Henig, MD Roderick Wong, MD Tamar Thompson Sarah Boyce
Chief Medical Officer, Managing Partner, VP, Govt. Affairs and Policy, President & CEO,
Kezar Life Sciences RTW Investments Alexion Pharmaceuticals Avidity
55Partnering Strategy to Accelerate and Expand the Utility of
AOCs Outside of Rare Diseases
NEW TISSUES
IMMUNOLOGY CARDIAC MUSCLE
Plan to add additional leading
partners to accelerate and
expand the utility of AOCs in
Collaboration focused on
Research collaboration focused tissues and cell types beyond
immunology and other select
on cardiac disease skeletal muscle
indications, but not muscle
diseases
$405M
Potential milestone payments
per target, plus mid-single to
low double-digit tiered royalties
56Q1 2021 – Financial Results
In millions
Q121 Q420 Q120 Q121 vs Q420 Q121 vs Q120
(unaudited)
Collaboration Revenue $2.7 $2.1 $1.3 $0.6 $1.4
R&D expenses 20.6 13.6 5.5 7.0 15.1
G&A expenses 5.9 4.8 2.0 1.1 3.9
Total operating expenses 26.5 18.4 7.5 8.1 19.0
Loss from operations (23.8) (16.3) (6.2) (7.5) (17.6)
Other income (expense) 0.0 0.0 0.1 0.0 (0.1)
Net loss ($23.8) ($16.3) ($6.1) ($7.5) ($17.7)
In millions ∆ ∆
Q121 Q420
(unaudited) 2Q19 2Q20 vs 1Q20 2Q20 vs 2Q19
Cash, cash equivalents and
$307.9 $328.1
marketable securities
Strong cash position of $279.5M* as of June 30th as we move toward the clinic with AOC 1001
*Unaudited and preliminary estimate 57You can also read
