Delivering on the RNA Revolution

January 13, 2025

NASDAQ: RNA | [Link]

1
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 fact contained in this
presentation are forward-looking statements. Forward-looking statements include, but are not limited to, statements regarding: our business strategy; the anticipated timing, costs, design, goals and
conduct of our ongoing and planned preclinical studies and clinical trials; the timing of release of data from our ongoing clinical programs and the announcement of new programs; the timing of
additional cohorts to existing clinical trials, including dosage levels and other details thereof; the characterization of data and results from preclinical studies and clinical trials and conclusions drawn
therefrom; research and development plans; plans and projected timelines for delpacibart etedesiran (del-desiran, formerly AOC 1001), delpacibart braxlosiran (del-brax, formerly AOC 1020) and
delpacibart zotadirsen (del-zota, formerly AOC 1044); safety and tolerability profiles of our product candidates; efficacy or functional data demonstrated by our product candidates; our plans regarding
our DMD franchise; the potential of the AOC platform and specific product candidates; the ability of our AOC platform to develop precision cardiology therapeutics; the ability for AOC 1086 to target PLN
cardiomyopathy, for AOC 1072 to target PRKAG2 Syndrome, and our ability to target additional genetic cardiac conditions; our ability to deliver siRNA to the heart; the design and capabilities of AOC
1086 and AOC 1072; the regulatory pathways of our product candidates; the design and capabilities of our next generation technology innovations; the status and potential of our product candidates as
first-in-class and/or best-in-class; the possibility of accelerated approval for del-brax and del-zota; our plans and timing for a BLA submission for del-zota; the status of certain clinical trials and cohorts as
potentially registrational; dosage levels to be administered in our clinical trials; enrollment in our clinical trials and the timing of completion; the ability of our product candidates to treat rare diseases;
timing and likelihood of success; product approvals; plans and objectives of management for future operations; collaborations with third parties and expected benefits therefrom; and our cash position
and our ability to fund our planned operations. 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 based on factors beyond our control, including, without limitation: the results of preclinical studies and early clinical trials are not necessarily predictive of future results; preclinical data
may not support IND filing or approval; our next-generation technology innovations may not produce results of commercial value; requests for data by the FDA or other regulatory authorities may result
in significant additional expense and timing delays; data delivered to the regulators may not be satisfactory, or support a successful BLA submission or registration; additional participant data related
to our product candidates that continues to become available may be inconsistent with the data produced as of the most recent respective date cutoffs, and further analysis of existing data and analysis
of new data may lead to conclusions different from those established as of such date cutoffs; unexpected adverse side effects or inadequate efficacy of our product candidates may delay or limit their
development, regulatory approval and/or commercialization, or may result in clinical holds, recalls or product liability claims; we are early in our development efforts; 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; potential delays in the
commencement, enrollment and completion of clinical trials, or of designations conferred by regulatory authorities; our dependence on third parties in connection with preclinical and clinical testing and
product manufacturing; we may not realize the expected benefits of our collaborations with third parties, our existing collaborations may terminate earlier than expected or we may not be able to form
new collaborations; 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; Fast Track or Breakthrough Designation by the FDA may not lead to a faster development or regulatory review or approval process; our ability to obtain and maintain intellectual property
protection for our product candidates and proprietary technologies; we may exhaust our capital resources sooner than we expect and fail to raise additional needed funds; and other risks
described under the heading “Risk Factors” in our Form 10-K for the year ended December 31, 2023, filed with the SEC on February 28, 2024, and in 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. 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. This
presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior
to registration or qualification under the securities laws of any such state or jurisdiction.

2
 OUR VISION

To profoundly improve
people’s lives by
revolutionizing
the delivery of
RNA therapeutics

Luke
Living with DM1 3
Key to Our Success: Proprietary AOC Platform

Combining the specificity mAb

of mAbs with the precision
of oligonucleotide therapies mAb OLIGO
OLIGO

MONOCLONAL OLIGONUCLEOTIDE ANTIBODY OLIGONUCLEOTIDE

ANTIBODIES THERAPIES CONJUGATE (AOC)

AOC platform advantages:

 Ability to target new tissue and cell types beyond the liver
 Flexibility to select and deploy the most potent oligonucleotides (e.g., siRNAs, PMOs)
 Maximizes therapeutic durability, enabling infrequent dosing
 Readily reproducible and scalable

4
Delivering on our vision

• AOC platform delivered first-ever successful delivery of RNA to muscle and showed this
PROVEN consistently across our three registrational rare neuromuscular programs
P L AT F O R M • We are expanding the reach of the AOC platform to precision cardiology and next-
generation technology innovations

• Committed to advancing innovative science and building a global commercial

A L L - S TA R R A R E company
DISEASE TEAM • Experienced rare disease leadership team in place to execute patient-centric
product launches

• Preparations to build a synergistic neuromuscular commercial franchise well

POSITIONED underway as we advance three potentially registrational clinical trials
TO E XECUTE
• Solid cash position of ~$1.6 billion¹ provides funding into mid-2027

¹ As of Sept 30, 2024

5
Three Programs Moving to Commercialization

Del-zota in DMD44
Lee • ~900 patients in U.S.
Living with DMD,
and his mother, Ginne • Aligned on path for accelerated approval in the U.S.

Del-desiran in DM1
Jeannine • ~80,000 patients in U.S. and E.U.
Living with DM1
• On track to be the first globally approved drug for DM1

Del-brax in FSHD
Russell • ~45,000-87,000 patients in U.S. and E.U.
Living with FSHD
• On track to be the first globally approved drug for FSHD

6
Delivered Consistent and Reproducible Results Across
Three Rare Neuromuscular Programs

Functional Agreed Registrational

Product Candidate Improvement Regulatory Path Program Ongoing

Del-zota Confirmatory trial

Duchenne Muscular design underway
Dystrophy (DMD44)

Del-desiran
Myotonic Dystrophy
Type 1 (DM1)

Del-brax Expected
Facioscapulohumeral Q2 2025
Muscular Dystrophy (FSHD)

Safety, tolerability, delivery to muscle and target engagement demonstrated across all programs

7
 Pipeline Expanding in Rare Neuromuscular and
Entering Precision Cardiology
PROGRAM / INDICATION TARGET PRECLINICAL PHASE 1/2 REGISTRATIONAL COMMERCIAL

Duchenne Muscular Dystrophy

Exon 44 Del-zotaTM
(DMD)

Myotonic Dystrophy Type 1 (DM1) DMPK Del-desiranTM

Facioscapulohumeral Muscular
DUX4 Del-braxTM
Dystrophy (FSHD)

DMD Exon 45 Exon 45 AOC 1045

Additional DMD Programs Undisclosed

Rare Neuromuscular Undisclosed

PLN Cardiomyopathy PLN AOC 1086

PRKAG2 Syndrome PRKAG2 AOC 1072

8
Continuing to Innovate on our Proven Platform
First-ever company to successfully demonstrate targeted delivery of RNA to muscle

Past 30 Years AOC PoC Shown Today Beyond

in Human

RNA Therapeutics
Skeletal
Muscle
Immunology
mAb
OLIGO

Precision Next-Gen
Focused Cardiology
on delivery to the Other
AOC
liver or local delivery Indications

9
Leading Innovations in Delivery of RNA Therapeutics

Today Tomorrow Future

mAb
OLIGO

AOC
siRNA siRNA Modification &
Modification Antibody Engineering

Next-generation technology is being incorporated into current and planned programs

Indicates modifications
10
Avidity 2025 Catalysts: Realizing Our Vision
Program Catalyst Q1 Q2 Q3 Q4
EXPLORE44TM topline data

Del-zota EXPLORE44-OLETM topline data

BLA submission for accelerated approval

Additional data analyses from Phase 1/2 MARINA® trial

Del-desiran Phase 3 HARBORTM trial enrollment completion

MARINA-OLETM trial update including long-term 4 mg/kg and safety data

Regulatory alignment on global Phase 3 trial design

Alignment with FDA on potential accelerated approval path for ongoing

FORTITUDETM biomarker cohort
Del-brax
FORTITUDETM biomarker cohort enrollment completion

Topline data from FORTITUDETM trial

Initiation of global, potentially registrational trial in FSHD

11
The Experience to Deliver a New Class of RNA Therapeutics
AVIDITY LEADERSHIP TEAM

Sarah Boyce Steve Hughes, MD W. Michael Flanagan, PhD Michael MacLean Kath Gallagher
President & CEO Chief Medical Officer Chief Scientific Officer Chief Financial Officer Chief Program Officer

Eric Mosbrooker John B. Moriarty, Jr, J.D. Teresa McCarthy Charles Calderaro III Kat Lange
Chief Commercial Officer Chief Legal Officer & Company Chief Human Resources Officer Chief Technical Officer Chief Business Officer
Secretary

BOARD OF DIRECTORS

Troy Wilson, PhD, JD Noreen Henig, MD Jean Kim Tamar Thompson

Chairman & Avidity Founder, Board Member Board Member VP, Govt. Affairs and Policy,
CEO of Kura Oncology Alexion Pharmaceuticals
Carsten Boess Edward Kaye, MD Simona Skerjanec Sarah Boyce Art Levin, PhD
Board Member CEO & Director, Board Member President & CEO, Board Member
Stoke Therapeutics Avidity Biosciences
12
 Nathan,
Living with DMD, and
his father, Brad

Del-zota for Duchenne Muscular

Dystrophy (DMD) exon 44

“My advice to any other family dealing with this is

to take it day by day, do as much research as
possible, and connect with others. I hope that
someday there will be a cure for DMD, and no other
family will have to go through this”
— Brad, Nathan’s Father, DMD Advocate
DMD: Hereditary Disorder Causing Progressive, Debilitating Muscle
Damage and Significantly Reduced Life Expectancy

~10,000 - 15,000 ~900

DMD Advocates
Lee, living with DMD, and Ginne, his mother

PEOPLE WITH DMD IN THE US PEOPLE WITH DMD44 IN THE US

SIMILAR PREVALENCE IN EUROPE

• Monogenic, X-linked, recessive condition characterized by progressive

muscle damage and weakness
• Primarily affects males, loss of ambulation by teenage years
• Significantly reduces life expectancy
• Caused by mutations in the DMD gene, which encodes for the dystrophin
protein
• ~ 7% of DMD skip-amenable patients have mutations amenable to exon 44
skipping (DMD44)
• ~900 patients with DMD44 in US
• Del-zota: designed to specifically skip exon 44 of dystrophin gene to enable
dystrophin production

14
Del-zota Produces Near Full-Length Dystrophin

Naturally occurring dystrophin

R R R R R R R R R R R R R R R
N H1 R1 R2 R3 H2 R4 R5 R6 R7 R8 R9 H3 H4 CR CT
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Representative dystrophin produced by del-zota

R R R R R R R R R R R R R R
N H1 R1 R2 R3 H2 R4 R5 R6 R7 R8 R9 H3 H4 CR CT
10 11 12 13 14 15 16 17 19 20 21 22 23 24

Micro-dystrophin produced by gene therapies

R
N H1 R1 R2 R3 H2 H4 CR
24

15
 Accelerated approval pathway available for del-zota

Part A: Healthy Volunteers Part B: Participants with DMD amenable to exon 44 skipping

A
3:1 Randomization

Healthy Volunteer Cohorts

Del-zota: Placebo

B1 5.0 mg/kg

B2 10.0 mg/kg

7.5-month treatment and observation

Dose – dose listed is PMO Initiation of next dose level cohort

• EXPLORE44 enrollment complete; dose-escalation to 20 mg/kg not necessary

• Plan to enroll additional patients in the EXPLORE44 Open-Label Extension study
• Planned BLA submission year end 2025

16
Del-zota: Favorable Safety and Tolerability in DMD44 Patients

Most treatment emergent adverse

Subjects with ≥ 1 TEAE Placebo 5.0 mg/kg 10 mg/kg events (TEAEs) were mild or moderate
n (%) N=7 N=9 N=9
• No related AE occurred in >2
Any AE 4 (57%) 8 (89%) 4 (44%) participants
Related to study drug 0 2 (22%) 1 (11%) • 1 participant discontinued due to
serious AE of anaphylaxis
Serious AE (SAE) 0 1 (11%) 0
• 1 participant discontinued due to
AE leading to study moderate infusion related reaction
0 2 (22%) 0
discontinuation
• No symptomatic hemoglobin changes,
AE leading to death 0 0 0 hypomagnesemia or renal events

Data from EXPLORE44TM as of 25 July 2024

17
Del-zota: First of Multiple AOCs in DMD Franchise
Data support expediting advancement of additional exon-skipping candidates

Unsurpassed Delivery to Statistically Significant Statistically Significant Profound Decrease in

Muscle Robust Exon Skipping Dystrophin Production Creatine Kinase Biomarker

• Consistent delivery of • 37% increase in exon 44 • Increase of 25% of • Creatine kinase levels
PMO of 200 nM in skipping normal in dystrophin reduced to near normal
skeletal muscle production with greater than 80%
• Up to 66% increase in
reduction compared to
• Once again, reinforcing exon 44 skipping • Restored total
baseline
the disruptive and broad dystrophin up to 54% of
potential of our AOC normal
platform

18
Del-zota: Increase of 25% of Normal in Dystrophin Production
Significantly restored total dystrophin up to 54% of normal

Dystrophin (% normal)
40
* Healthy

30

Dystrophin
20
25%
32%
increase
10 25% increase
on del-zota

7%
0
Baseline 4 Month Baseline 4 Month
DMD
placebo del-zota
5 mg/kg
Dystrophin protein determined in biceps brachii muscle biopsy at 1 month post 3rd dose by Western Blot. Data
normalized to myosin heavy chain. Mean +/- SEM. N=3 (Placebo), N=7 (del-zota). Dose expressed as PMO component.
*p<0.05 by Wilcoxon test 19
 Del-zota

Significant and Sustained Reductions in Creatine Kinase in All Treated Groups

12000

8000
Kinase (U/L)
Creatine

4000

0
0 60 120 180 240
Study Day
Placebo Del–zota (5 mg/kg) Del–zota (5 mg/kg)

Data presented as of November 2024. Mean +/- SEM. N=3 (Placebo), N=7 (del-zota). Dose expressed as PMO component.
20
First of Three: Del-zota U.S. Launch

Alignment on Regulatory Path

Accelerated Approval path open for
del-zota – anticipate BLA filing at year end
2025
Commercial Launch in U.S.
Team in place to execute go-to-
market strategy
Launch Preparations
Del-zota sets the foundation for
sequential neuromuscular launches

21
Del-desiran for Myotonic Dystrophy
Type 1 (DM1)

“Some days I don’t have the energy

to take another step.”
— Karin, living with DM1
DM1: Significant Patient Burden and Unmet Need

~80,000 0
PEOPLE WITH DM1 IN THE US & EU APPROVED THERAPIES

• Underrecognized, progressive & often fatal neuromuscular

disease that primarily affects skeletal, cardiac & smooth muscle

• Increases in severity from generation to generation

• Significant impact on quality of life

• Del-desiran is designed to address root cause of DM1

Loraine,
• On track to be the first globally approved drug for DM1 Kristl & Zen
Living with DM1

23
 Del-desiran Designed to Address Underlying Cause of Myotonic
Dystrophy by Liberating Free MBNL

*
2.5
Video Hand Opening
PBO (n=8)
Time (vHOT)

(fold change from baseline)

2.0 1 mg/kg (n=5)
Del-desiran 2 mg/kg (n=8)

[MBNL]inf
4 mg/kg (n=9) MYOTONIA
1.5

1.0 Hand Grip Quantitative

MBNL Muscle Testing

0.5 STRENGTH

MBNL sequestered by Del-desiran (AOC 1001) *Del-desiran (AOC 1001) DM1-Activ

CUG repeats of mutant treatment Reduced mutant Leads to Dose-dependent ACTIVITIES OF
DMPK DMPK increase in MBNL DAILY LIVING

#Data shown as mean and standard error. Fold change is calculated per subject as post-treatment relative to baseline;
*P<0.05, unpaired t-test 24
Wagner, SD, et al. PLOS Genet. 2016;12(9):e1006316
 Phase 1/2 MARINA® and MARINA-OLE Trial Design

Dose Booster

Del-desiran, n=6
A (N=8) 1 mg/kg

All Participants Receive

(Del-desiran: Placebo)

Placebo, n=2
3:1 Randomization

2 mg/kg

Del-desiran
Del-desiran, n=9
B1 (N=12) 2 mg/kg
Placebo, n=3

4 mg/kg
Del-desiran, n=13
B2 (N=18) 4 mg/kg
Placebo, n=5

• In MARINA, one participant receiving 4 mg/kg del-desiran discontinued treatment due to SAE
• All eligible participants (N=37) have enrolled in the MARINA-OLE

Dose listed is siRNA. The diagram for the MARINA-OLE trial includes the first 12 of the 24 months with quarterly dosing.
‡Booster dose was only given to participants who were in Cohort A1 and placebo B1/B2.
SAE: serious adverse event; siRNA: small interfering ribonucleic acid.
25
 Favorable Long-term Safety and Tolerability
Over 340 infusions of del-desiran totaling ~80 patient-years of exposure

MARINA-OLETM Number (%)

with AE
Subjects with ≥ 1 AE N=37 • All 37 participants enrolled remain
on study
Any AE 37 (100%)
• All related AEs were mild or
moderate
AE related to study drug 11 (29.7%)
• Most common related AE reported in
Unrelated serious AE (SAE) 7 (18.9%) >2 participants:
• Nausea
SAE related to study drug 0
• No discontinuations
AE leading to treatment
discontinuation
0 • No study drug related SAEs; unrelated
SAEs are consistent with DM1
AE leading to death 0

As of August 2024, AE data from MARINA-OLE and exposure data from MARINA and MARINA-OLE.
SAEs considered unrelated to treatment included obstructive pancreatitis, rectal perforation, vomiting, basal cell carcinoma, invasive ductal
breast carcinoma, atrial fibrillation, chest pain, and cholelithiasis. The unrelated SAEs are either consistent with DM1 or commonly seen in
clinical trials 26
MARINA-OLE Data Summary
Potential of del-desiran to be a transformational therapy for DM1 patients

• Del-desiran 4 mg/kg END-DM1 Natural History (1 year)

4 mg/kg Q13W (1 year)
• Demonstrated favorable long-term
safety and tolerability
• Showed reversal of disease
progression in MARINA® and
MARINA-OLE compared to END-
DM1 natural history data
• Provided consistent and durable
improvements in multiple clinical
endpoints
• Global Phase 3 HARBOR trial
initiated

Data as of August 2024

27
 Global Phase 3 Study Underway

• Phase 3 HARBORTM Study Ongoing

• FDA, EMA and other global regulatory authorities in agreement on study design
• HARBORTM study designed for efficiency and speed of execution

1:1 del-desiran 4 mg/kg Q8W HARBOR

Randomization Open Label
(N=150) Placebo Extension Trial

PRIMARY ANALYSIS: 30 weeks

Duration of Placebo Controlled Study: 54 weeks

HARBOR trial enrollment to be completed mid-2025

28
 Phase 3 Trial: Design and Objectives
Optimized for efficiency and speed of execution

Key Secondary
Pivotal Study Design Primary Endpoint
Endpoints

• 4 mg/kg every 8 weeks; first dose of 2 mg/kg Video Hand Opening Hand Grip Quantitative
Time (vHOT) Muscle Testing
• N=150; Ages 16+
• 1:1 randomization
• Primary analysis at Week 30; Placebo-control STRENGTH
out to week 54
MYOTONIA
• Participants eligible to roll-over into​ an open DM1-Activ
label extension ACTIVITIES OF
• ~40 global sites DAILY LIVING

29
Advancing Del-desiran Towards Regulatory Approvals

Regulatory Path is Known

Aligned with global regulators on the
registrational path for full approval Commercial Launch
First global launch, including
U.S. and E.U.
Significant activities currently
underway
HARBOR Phase 3 Ongoing
On track to complete enrollment in
mid-2025

30
Del-brax for Facioscapulohumeral
Muscular Dystrophy (FSHD)

“Living with FSHD feels like an

imprisonment in your own body.”
— Amy, Living with FSHD
Facioscapulohumeral Muscular Dystrophy (FSHD)
Rare, hereditary disorder causing relentless loss of muscle function and progressive disability

~45,000 - 87,000 0
PEOPLE WITH FSHD IN THE US & EU APPROVED THERAPIES

• One of the most common forms of muscular dystrophy, FSHD causes

progressive muscle weakness, pain, fatigue and disability
• Onset typically occurs in teenage or early adult years
• Steady loss of independence and ability to care for oneself
• 20% of patients become wheelchair dependent
• Autosomal dominant - multiple generations can be affected
• 20-30% arise from spontaneous mutations
• Del-brax: designed to address root cause of FSHD by directly targeting
double homeobox 4 (DUX4)
Russell
• On track to be the first globally approved drug for FSHD Living with FSHD

32
Del-brax: Targets DUX4, the Root Cause of FSHD
Targets aberrant expression of DUX4 mRNA for destruction
FSHD disease pathology1,2 Del-brax Therapeutic Hypothesis

1 Lemmers RJLF, et al. Science 329:1650–1653 (2010)

2 Snider L, et al. PLoS Genet. 2010;6(10):e1001181;
33
 Ongoing Biomarker Cohort Provides Path to
Potential Accelerated Approval
2:1 Del-brax 2 mg/kg | Every 6 weeks FORTITUDETM
Randomization Open Label
(N=48) Placebo Extension Trial

BIOMARKER ANALYSIS: 4 months

FUNCTIONAL ANALYSIS: 6, 9, 12 month

Duration of Placebo Controlled Study: 52 weeks

Primary and Secondary Objectives Key Exploratory Objectives

• Change in DUX4-regulated gene expression in muscle • Measures of clinical activity
biopsies (Cohort C) • Muscle strength, function and composition (MRI)
• Change in a circulating biomarker of FSHD disease biology • Patient and Clinician reported outcomes
(Cohort C)
• Changes in creatine kinase

FORTITUDE biomarker cohort enrollment to be complete Q2 2025

34
Del-brax: Favorable Safety and Tolerability

OLE All 39 patients enrolled remain in

Subjects with ≥ 1 AE Placebo 2 mg/kg* 4 mg/kg** (2 mg/kg)
n (%) N=13 N=8 N=18 N=7 FORTITUDE or FORTITUDE-OLE
Any AE 12 (92.3%) 8 (100%) 18 (100%) 1 (14.3%) • No serious adverse events (AE), no severe AE
• No discontinuations
Related to study drug 3 (23.1%) 6 (75%) 10 (55.6%) 1 (14.3%)
• All AEs were mild or moderate
Severe AE 0 0 0 0
• Most common related AE occurring in >2
Serious AE (SAE) 0 0 0 0 participants:
AE leading to study • Fatigue
0 0 0 0
discontinuation • Hemoglobin decreased/anemia
AE leading to death 0 0 0 0
As of September 2024, data from FORTITUDE; At time of the safety cut, 7 participants were in the OLE

*Participants receive a first dose of 1mg/kg and then receive the 2mg/kg dose for the remainder of the study
**Participants receive 4mg/kg at all doses
35
Del-brax: Transforming the Treatment of FSHD
​First-in-class and best-in-clas​s: greater than 50% reduction in DUX4 regulated genes

Unprecedented & Consistent Signs of Functional Favorable Safety and

Reduction in DUX4 Regulated Improvement and Reported Tolerability
Genes Outcomes
• Greater than 50% reduction across • Improved muscle strength • All adverse events (AEs) were mild
multiple DUX4 gene panels or moderate
• Increased reachable workspace
• All treated participants showed compared to placebo and natural • No serious AEs, No severe AEs
reductions greater than 20% history study
• No discontinuations
• Reduction of a newly-identified • Positive patient and clinician
DUX4 circulating biomarker & reported outcomes
creatine kinase

36
Del-brax Shows Consistent >50% Reductions in DUX4-regulated Genes as
Measured by Multiple Gene Panels

Avidity Panel 1 ReDUX4 Panel 2 41-Gene Panel 3

(% Change from Baseline)

(% Change from Baseline)

(% Change from Baseline)

0 0 0

-25 -25 -25

DUX4 score*

DUX4 score*

DUX4 score*
-50 -50 -50
53% 53% 60%
-75 -75 -75

-100 -100 -100

PBO del-brax
AOC 1020 PBO del-brax
AOC 1020 PBO del-brax
AOC 1020
(1 & 2 mg/kg) (1 & 2 mg/kg) (1 & 2 mg/kg)
2 mg/kg
(12 #
mg/kg) 22 mg/kg
(12mg/kg ##
mg/kg) 2 mg/kg
(12 #
mg/kg)

1 Avidity 4-Gene panel (LEUTX, TRIM43, MBD3L2, KHDC1L; Reference genes: TBP, STATA5)
2 ReDUX4 6-Gene panel (CCNA1, ZSCAN4, MBD3L2, KHDC1L, SLC34A2, PRAMEF6); Tawil, R. et al., Lancet Neurol 23:477
(2024)
3 Van den Heuvel, A. et al., Scientific Reports 12:1426 (2022)

* DUX4 score in MRI informed muscle biopsy were determined utilizing qPCR (Avidity panel) or RNASeq (ReDux and 41-
Gene). DUX4 score calculated as cumulative expression of each gene and data presented as change at 4M treatment
relative to cohort normalized baseline. Mean +/- SEM, N=7 del-brax, N=4 PBO. One participant in treated group did not
receive post-treatment biopsy.
37
#Doses were 1 mg/kg (D1), 2 mg/kg (D43 and D92) with biopsy 1 month after 3rd dose.
Del-brax Improved Muscle Strength in Both Upper and Lower Limb

Placebo
del-brax 2 mg/kg*
QMT

-10 -5 0 5

Shoulder Abductor

-20 -10 0 10

Ankle Dorsiflexion

-40 -20 0 20

Declining Improving

Change from Baseline to Month 4 (Mean ± SEM) Percent Predicted Normal

QMT by hand-held device
Total composite score: shoulder abductors, shoulder external rotators, elbow flexors, elbow extensors, knee flexor, knee extensor and ankle dorsiflexion
* Participants receive a first dose of 1mg/kg and then receive the 2mg/kg dose for the remainder of the study
38
Novel DUX4-Regulated Circulating Biomarker
Potential accelerated approval endpoint

Multi-year Discovery Process

Novel DUX4-Regulated Circulating Biomarker
FSHD & Healthy Biopsies Potential Accelerated Approval Endpoint
• Significantly elevated in patients with FSHD as
compared to healthy individuals

Plasma from FSHD & • Allows rapid and continuous monitoring of how
Healthy Volunteers participants are responding to del-brax
• Non-invasive, patient-friendly
• Guides selection of dose regimen
Advisors & Disease
Expertise • Alignment on a potential accelerated approval path
using this biomarker in Q2 2025

39
DUX-4 Regulated Biomarker and Creatine Kinase Biomarker Levels
Confirm Del-brax Dose and Dose Regimen
Del-brax 2 mg/kg to be dosed every six weeks in the FORTITUDE biomarker cohort

Novel DUX4-regulated biomarker Creatine kinase biomarker

Dose

*del-brax dosed 1mg/kg D1, 2 mg/kg D43 D92 and D183

**del-brax dosed 4mg/kg at all doses
Timecourse of circulating biomarker at baseline and several timepoints post dose
N=13 for placebo, 8 for 2 mg/kg, 18 for 4 mg/kg 40
Mean +/- SEM.
Dual Pathways to Rapidly Deliver Del-brax to Patients

Completion of enrollment of the FORTITUDETM biomarker cohort in Q2 2025

U.S. Accelerated
Approval Pathway
Alignment with FDA on potential accelerated approval path for the
ongoing FORTITUDETM biomarker cohort in Q2 2025

Regulatory alignment on a global Phase 3 trial design in Q2 2025

Global Phase 3
Trial for
Full Approval
Initiation of a global, potentially registrational trial in Q2 2025

41
 Precision Cardiology:
Transforming Genetic
Cardiomyopathy Treatment

42
 The Perfect Pair: Our AOC Technology and Precision Cardiology
HEART DISEASE is #1 cause of death globally*
PRECISION CARDIOLOGY targets an underlying disease-causing genetic mutation in the heart muscle

AOC

TARGETED siRNA GENETIC

PRECISION
DELIVERY TO MUTATIONS
CARDIOLOGY
CARDIAC MUSCLE IN THE HEART

Robust siRNA delivery to Target knockdown with potent Well-tolerated with no effect
heart muscle reduction in cardiac mRNA on ECG parameters in NHP

*World Health Organization

43
Precision Cardiology Development Candidates Targeting PLN and
PRKAG2
Advancing new class of targeted RNA therapeutics to address rare genetic cardiomyopathies

AOC 1086 AOC 1072

PLN Cardiomyopathy PRKAG2 Syndrome
(Phospholamban) (Protein Kinase AMP-activated non-catalytic subunit Gamma 2)

Robust siRNA delivery to Target knockdown with potent Well-tolerated with no effect on
heart muscle reduction in cardiac mRNA ECG parameters in NHP

44
 PLN Cardiomyopathy: Hereditary Disease Resulting in Dilated and
Arrhythmogenic Cardiomyopathy

~2,000-4,000 0
PEOPLE LIVING WITH PLN APPROVED DISEASE-
CARDIOMYOPATHY (US and CANADA) MODIFYING THERAPIES

• Autosomal dominant, progressive cardiac disease characterized

by dilated and/or arrhythmogenic cardiomyopathy
• Increased risk for sudden cardiac arrest and heart failure,
even in younger people
• Caused by a mutation (R14del) in PLN gene which results
in accumulation of protein aggregates which cause
cardiomyocyte death
• AOC 1086 is designed to target and degrade PLN mRNA to
eliminate protein aggregates

45
AOC 1086 Demonstrates Robust siRNA Cardiac Delivery
in Non-Human Primates (NHP)

siRNA concentration
in NHP heart
DELIVERY
100

siRNA concentration in TARGET

NHP heart (nM) ENGAGEMENT

nM
10

TOLERABILITY
1
AOC 1086

Single dose of AOC 1086 at 3mg/kg (of siRNA) with evaluation 28 days post-dose

Mean +SD, n=2

46
AOC 1086 Demonstrates Target Knockdown with Potent Reduction
in Cardiac PLN mRNA and Protein in NHP

Target mRNA reduction Target protein reduction

in NHP heart in NHP heart
125 DELIVERY
100
(% of Control)

PLN Pentamer
PLN mRNA

75
TARGET
50 ENGAGEMENT
25
PLN Monomer
0 TOLERABILITY
Control AOC 1086 Control AOC 1086

Single dose of AOC 1086 at 3mg/kg (of siRNA) with evaluation 28 days post-dose

Mean +SD, n=2/group

47
AOC 1086 PLN Inhibition Well-Tolerated With No Effect on
Electrocardiogram (ECG) Parameters in NHP
No effect on ECG parameters for
evaluating cardiac changes
Tolerability

QTc interval in NHP PR interval in NHP DELIVERY

400 80

300 60 TARGET

milliseconds
milliseconds

ENGAGEMENT
200 40

20
100 TOLERABILITY

0 0
Control AOC 1086 Control AOC 1086

Single dose of AOC 1086 at 3mg/kg (of siRNA) with evaluation 28 days post-dose

Mean +SD, n=2/group

48
 PRKAG2 Syndrome: Hereditary Disease Causing Hypertrophic
Cardiomyopathy and Wolff-Parkinson-White Syndrome

~1,000-2,000 0
PEOPLE LIVING WITH PRKAG2 SYNDROME APPROVED DISEASE-
(US and CANADA) MODIFYING THERAPIES

• Autosomal dominant, progressive cardiac disease characterized by

hypertrophic cardiomyopathy, arrhythmia and heart failure
• Increased risk of sudden cardiac arrest
• Caused by mutations on PRKAG2 gene which result in increased
AMP Kinase (AMPK) activity which causes accumulation cardiac
glycogen
• AOC 1072 is designed to target and degrade PRKAG2 mRNA to
restore normal AMPK activity and reduce glycogen accumulation

49
AOC 1072 Demonstrates Robust siRNA Cardiac Delivery in NHP

siRNA concentration
in NHP heart
100 DELIVERY

siRNA concentration in TARGET

NHP heart (nM)
nM
10 ENGAGEMENT

TOLERABILITY
1
AOC 1072

Single dose of AOC 1072 at 3mg/kg (of siRNA) with evaluation 28 days post-dose

Mean +SD, n=3

50
AOC 1072 Demonstrates Target Knockdown with Potent
Reduction in Cardiac PRKAG2 mRNA and Protein in NHP

Target mRNA reduction Target protein reduction

in NHP heart in NHP heart
150 DELIVERY
(% change of control)

125
PRKAG2 mRNA

100
75 TARGET
ENGAGEMENT
50
25
0 TOLERABILITY
Control AOC 1072 Control AOC 1072

Single dose of AOC 1072 at 3mg/kg (of siRNA) with evaluation 28 days post-dose

Mean +SD, n=2 for the control group and n=3 for the AOC 1072 group
51
AOC 1072 PRKAG2 Inhibition Well-Tolerated With No Effect on
Electrocardiogram (ECG) Parameters in NHP

No effect on ECG parameters for evaluating cardiac changes

QTc Interval in NHP PR Interval in NHP DELIVERY

500 80

400
60 TARGET
milliseconds

milliseconds
300 ENGAGEMENT
40
200
20 TOLERABILITY
100

0 0
Control AOC 1072 Control AOC 1072

Single dose of AOC 1072 at 3mg/kg (of siRNA) with evaluation 28 days post-dose

n=2 for the control group and n=3 for the AOC 1072 group
52
Avidity Next-Generation Innovations
Innovation Drives Our Industry-leading RNA Platform Technology

Leading RNA Delivery Technology Innovations

Delivery ligands Improved delivery

ANTIBODY
Ab Peptide Lipids
Increased
durability

siRNA Modifications
siRNA Patient
convenience

54
Next-Gen siRNA Modifications Provide Greater Than 4-Fold
Increase in Delivery to Muscle in Mice
siRNA Modification Improved Delivery

siRNA Tissue Concentration

6

Fold Increase
4

0
AOC Next Gen

Indicates modifications

Single dose of 0.75 mg/kg siRNA equivalent; Day 28; n = 4

55
Next-Gen siRNA Modifications Show Sustained Target Inhibition for
3 Months in Mice; Potential for Convenient Less Frequent Dosing
siRNA Modification Increased Durability

Improved Patient Convenience

Indicates modifications

Single dose of 0.75 mg/kg of siRNA equivalent; n = 4

56
siRNA and Antibody Innovations Lead to >30-Fold Increase in
siRNA Delivery to Skeletal Muscle in Non-Human Primates (NHP)
siRNA Modification & Improved Delivery
Antibody Engineering

Indicates modifications

Single dose of 1.0 mg/kg siRNA equivalent; Day 29, n = 3

57
Expanding Use of AOCs Beyond Skeletal Muscle
Industry-leading partners validate broad potential of AOC platform; including precision cardiology
and immunology

PRECISION CARDIOLOGY IMMUNOLOGY

Global licensing & research collaboration focused on Global licensing & research collaboration focused on
up to five cardiovascular indications immunology and other select indications
Expansion of our Bristol Myers Squibb/MyoKardia
Up to $405M
single target research arrangement
Potential milestone payments per target, plus mid-
$100M up-front plus potential for ~$2.2B single to low double-digit tiered royalties
$60M upfront payment
$40M equity investment at a 40% premium
Up to ~$1.35B in R&D milestone payments, up to
~$825 million in commercial milestone payments
and tiered royalties on net sales

58
Solid Cash Position – Funded into mid 2027
Q3 2024 financial results

In millions Q324 Q224 Q323 Q324 vs Q224 Q324 vs Q323

Collaboration revenue $2.3 $2.0 $2.8 $0.3 ($0.5)

R&D expenses 77.2 63.9 47.7 13.3 29.5
G&A expenses 23.2 20.7 13.7 2.5 9.5
Total operating expenses 100.4 84.6 61.4 15.8 39.0
Loss from operations (98.1) (82.6) (58.6) (15.5) (39.5)
Other income/expenses, net 17.7 11.8 6.2 5.9 11.5
Net loss ($80.4) ($70.8) ($52.4) ($9.6) ($28.0)

In millions Q324 Q224 ∆ ∆

2Q19 2Q20 vs 1Q20 2Q20 vs 2Q19
Cash, cash equivalents and
$1,588.6 $1,299.0
marketable securities

Solid cash position with ~$1.6 billion providing funding into mid 2027
Building out global commercial infrastructure as we advance three potentially registrational clinical trials for del-desiran, del-brax and
del-zota – executing on other DMD and precision cardiology programs

59