Full Press Release Details
Virtual Investor & Analyst Event
Series - Volume 6: AOC 1001 MARINATM Phase 1/2 Trial Preliminary Data Assessment Exhibit 99.1
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 facts contained in this presentation, including, but not limited to,
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 clinical trials, research and development plans,
plans and projected timelines for AOC 1001, AOC 1020 and AOC 1044; 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 may not be able to resolve the partial clinical hold, and the analysis related to the underlying cause of the
serious adverse event may result in delays in the MARINA study or an inability to compete the study; the Phase 1/2 MARINA trial results are based on a preliminary analysis of interim data available as of the data cutoffs, and the interim results do
not predict the final results of the trial, and one or more of the safety or biomarker results may materially change following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues, as and if
additional patients enroll in the trial and as more patient data become available, any of which may materially alter the findings and conclusions from our preliminary analysis; 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 and many 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 and clinical testing and product manufacturing; disruption to our operations from the COVID-19 pandemic; the war in Ukraine; 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,
2021, filed with the SEC on March 1, 2022, 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.
Our Vision To profoundly improve
people's lives by revolutionizing the delivery of RNA therapeutics Luke Living with DM1
Delivering on Our Vision Progressing
robust pipeline in muscle; 3 programs in clinical development in approx. a year AOC 1001* Phase 1/2 MARINATM trial and MARINA-OLETM ongoing AOC 1020 for FSHD in Phase 1/2 FORTITUDETM trial AOC 1044 for DMD in Phase 1/2 EXPLORE44TM trial
Leveraging expertise in clinical and commercial execution Assembling an experienced team in rare & RNA therapies Building an integrated and diverse company in service of our patients DISRUPTIVE & BROAD PLATFORM ADVANCING & EXPANDING
PIPELINE AGILE & DIVERSE COMPANY Committed to delivering a new class of RNA therapies Advancing three AOCs in clinical development; two siRNAs and first PMO Broadening to other tissues & cell types through partnerships & internal
discovery *Sept. 2022, FDA placed a partial clinical hold on new participant enrollment. All current participants may continue in their current dosing cohort. All participants in MARINA may roll over into the MARINA-OLE where they will receive AOC
1001 as planned. Avidity is working to resolve the partial clinical hold as quickly as possible.
Delivering on 2022 Goals Three programs
in three distinct rare diseases in clinical development DM1: AOC 1001* MARINATM Successfully completed preliminary assessment Top-line data and program updates planned for 2023 FSHD: AOC 1020 FORTITUDETM DMD: AOC 1044 EXPLORE44TM IND cleared; trial
initiation underway Preliminary assessment in approximately half of participants in 1H 2024 IND cleared; trial initiation underway Results from healthy volunteers in 2H 2023 Overall program planned for potential Accelerated Approval *Sept. 2022, FDA
placed a partial clinical hold on new participant enrollment. All current participants may continue in their current dosing cohort. All participants in MARINA may roll over into the MARINA-OLE where they will receive AOC 1001 as planned. Avidity is
working to resolve the partial clinical hold as quickly as possible.
Goals for the Day AOC 1001 Preliminary
Data Assessment Living with DM1 Disruptive and Broad AOC Platform Answer your questions mAb OLIGO AOC 1001
Delivery to Muscle AOCs Deliver to
Muscle - Revolutionary Advancement for the Field of RNA Therapeutics MARINA Primary Endpoint; Phase 1/2 trial ongoing First-ever successful targeted delivery of RNA to muscle - reinforces disruptive and broad potential of the AOC
platform DMPK Reduction 100% of treated participants had a DMPK reduction 45% mean DMPK reduction in treated participants Impact on Disease Mechanism 16% splicing improvement across 22 gene panel 31% improvement in key set of muscle-specific genes
Safety & Tolerability Early Signs of Clinical Activity Myotonia improvement in early responders
Steve Hughes, M.D. Chief Medical
Officer Sarah Boyce President and CEO Art Levin, Ph.D. Chief Scientific Officer Mike Flanagan, Ph.D. Chief Technical Officer AOC 1001 MARINATM Phase 1/2 Trial Preliminary Data Assessment Avidity Management Team Members Nicholas E. Johnson, M.D.,
M.Sci., FAAN Virginia Commonwealth University
Agenda Sarah Boyce, President & CEO
Steve Hughes, M.D., CMO Mike Flanagan, Ph.D., CTO Nicholas E. Johnson, M.D., M.Sci., FAAN Virginia Commonwealth University Art Levin, Ph.D., CSO Avidity Management Dr. Nicholas Johnson, VCU Kath Gallagher, SVP, Communications & IR (Moderator)
Sarah Boyce, President & CEO Welcome & Introduction MARINATM: AOC 1001 Phase 1/2 Preliminary Data Assessment Living with Myotonic Dystrophy Type 1 Broad Utility & Power of the Platform Q&A Session Closing Remarks
Steve Hughes, M.D., Chief Medical
Officer MARINA: A Phase 1/2 Clinical Trial to Evaluate AOC 1001 in Adult Patients with DM1
0 APPROVED THERAPIES Myotonic
Dystrophy Type 1 (DM1): Disease Overview >40,000 PEOPLE WITH DM1 IN THE US 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 Shortened life-expectancy Loraine, Kristl & Zen Living with DM1
DM1 is Caused by a Toxic
Gain-of-Function mRNA and is Well Suited to an siRNA Approach Mutant DMPK mRNA Splicing Errors in Target mRNAs Potential Therapeutic Approach Reduces mRNA Splicing Errors AOC 1001 Oligonucleotide binds DMPK mRNA Mechanism of Disease MBNL Release
Reduce Nuclear Foci Knock Down of DMPK MBNL Sequestration in Nuclear Foci DMPK mRNA MBNL (Muscleblind-like) X CUG CUG Trinucleotide expansion in DMPK mRNA sequesters an RNA splicing protein MBNL (Muscleblind-like) in nuclear foci Sequestration of
MBNL leads to RNA splicing errors in multiple muscle-related RNAs and induces DM1 disease manifestations Allows MBNL to be released to perform its natural function to aid in splicing key mRNAs in muscle Improves the splice patterns and muscle
function. Splice patterns can serve as biomarkers
IND AOC 1001's Compelling
Preclinical Package Safety and Tolerability Delivery to Muscle Impact on Disease Mechanism Favorable toxicology profile in Non-Human Primates (NHPs) Duration and delivery shown in wide range of muscles in multiple preclinical models DMPK Reduction
75% reduction in NHPs Splicing Improvement in patient-derived muscle cells
N = ~44 Ages 18-65 (3:1
randomization) Part A receives single IV dose Part B receives multi-ascending IV doses Quarterly doses - 1 booster after first 6 weeks 6-month treatment and observation duration MARINATM and MARINA-OLETM Allow for Both Short- and Long-term Data
Collection to Support AOC 1001* N = ~44 Ages 18-65 All participants receive AOC 1001 Quarterly doses - 1 booster after first 6 weeks 24-month treatment and 9-month observation duration A B3 B2 B1 All Participants Receive AOC 1001 2 mg/kg 2 mg/kg 4
mg/kg 8 mg/kg 3:1 Randomization (AOC 1001:Placebo) A B1 B2 B3 4 mg/kg 2 mg/kg 1 mg/kg 8 mg/kg Dose Booster Dose listed is siRNA *Sept. 2022, FDA placed a partial clinical hold on new participant enrollment. All current participants may continue in
their current dosing cohort. Avidity is working to resolve the partial clinical hold as quickly as possible.
N = ~44 Ages 18-65 (3:1
randomization) Part A receives single IV dose Part B receives multi-ascending IV doses Quarterly doses - 1 booster after first 6 weeks 6-month treatment and observation duration MARINATM and MARINA-OLETM Allow for Both Short- and Long-term Data
Collection to Support AOC 1001* N = ~44 Ages 18-65 All participants receive AOC 1001 Quarterly doses - 1 booster after first 6 weeks 24-month treatment and 9-month observation duration A B3 B2 B1 All Participants Receive AOC 1001 2 mg/kg 2 mg/kg 4
mg/kg 8 mg/kg 3:1 Randomization (AOC 1001:Placebo) A B1 B2 B3 4 mg/kg 2 mg/kg 1 mg/kg 8 mg/kg Dose Booster Dose listed is siRNA *Sept. 2022, FDA placed a partial clinical hold on new participant enrollment. All current participants may continue in
their current dosing cohort. Avidity is working closely to resolve the partial clinical hold as quickly as possible.
Early Data from MARINA Mid-Point at
6 weeks post 1 or 2 doses of AOC 1001 3:1 Randomization (AOC 1001:Placebo) Dose Booster Dose listed is siRNA Biopsy A 1 mg/kg Day 43 Day 92 BL B1 2 mg/kg Day 92 Day 183 BL Biopsy 1 mg/kg (n=8 Participants) 2mg/kg (n=12 Participants) Baseline Day 43
Baseline Day 92 DMPK 6 Active 2 Placebo 5* Active 2 Placebo 9 Active 3 Placebo 9 Active 3 Placebo Splicing 8** Active 3 Placebo *One participant in the 1mg/kg cohort had insufficient tissue for analysis **Due to timing, one splicing
sample from the 2mg/kg cohort will be evaluated in the next batch analysis Safety includes all cohorts (including 4mg/kg) with a data cutoff of November 17th NOTE: Day 92 biopsy in 2mg/kg cohort taken prior to third dose of AOC 1001 Data at 3
Months: n=19 participants* 1mg/kg Cohort (n=5 active participants) 2mg/kg Cohort (n=9 active participants) Pooled placebo (n=5 participants)
MARINATM is on a partial clinical
hold for new participant enrollment The partial hold is in response to a serious adverse event (SAE) reported in a single participant in the 4mg/kg cohort. No similar events observed in other participants in either MARINA or the MARINA-OLE
Avidity working to conclude the investigation of the SAE Participants already in MARINA or the MARINA open label extension (MARINA-OLETM) continue to receive either AOC 1001 or placebo 38 participants enrolled in MARINA; to date, 100% of
participants who completed MARINA have chosen to roll into the MARINA-OLE Anticipate sharing an update on the partial hold by the end of the first quarter in 2023 Plan to disclose more information on the SAE at that time MARINA top-line data
anticipated in 2023 Update* *Current as of December 13, 2022.
Baseline Demographics* Generally
Well Matched Between Cohorts Mean (Range) or Number of subjects Cohort A1 (1 mg/kg) N=8 Cohort B1 (2 mg/kg) N=12 Age 37.9 (21-64) 38.8 (18-60) Sex Male: 2 / Female: 6 Male: 1 / Female: 11 BMI 22.0 (16.1-29.2) 25.0
(17.5-32.0) Mean CTG repeat length (range) 504 (150-725) 707 (150-1250) Baseline Splicing (composite of 22 splicing events; higher number is more severe) 74 (38-96) 72 (39-105) *Preliminary Results Based on Live, Unlocked Clinical Database
- Numbers Subject to Change Cohort A and B1 Enrolled Participants with Mild-Moderate Disease Severity
Generally Favorable Safety and
Tolerability Subjects with 1 AE n (%) Placebo n=10 1mg/kg n=6 2mg/kg n=9 4mg/kg n=13 Total AOC 1001 N=28 Any AE 8 (80%) 6 (100%) 9 (100%) 12 (92%) 27 (96%) Related to study drug 2 (20%) 1 (17%) 3 (33%) 10 (77%) 14 (50%) Serious AE (SAE) 0 0
1 (11%) 1 (8%) 2 (7%) AE leading to study discontinuation 0 0 0 0 0 AE leading to death 0 0 0 0 0 17-Nov-2022 data cutoff. MARINA data only presented Preliminary Results Based on Live, Unlocked Clinical Database - Numbers Subject to
Generally Favorable Safety and
Tolerability Subjects with 1 AE n (%) Placebo n=10 1mg/kg n=6 2mg/kg n=9 4mg/kg n=13 Total AOC 1001 N=28 Any AE 8 (80%) 6 (100%) 9 (100%) 12 (92%) 27 (96%) Related to study drug 2 (20%) 1 (17%) 3 (33%) 10 (77%) 14 (50%) Serious AE (SAE) 0 0
1 (11%) 1 (8%) 2 (7%) AE leading to study discontinuation 0 0 0 0 0 AE leading to death 0 0 0 0 0 17-Nov-2022 data cutoff. MARINA data only presented Preliminary Results Based on Live, Unlocked Clinical Database - Numbers Subject to Change
Majority of treatment emergent adverse events (AEs) were mild or moderate The most common in the study were COVID-19 (16%) and headache (16%) Other AEs include: Infusion related reactions Reductions in hemoglobin Elevations in ASTs or ALTs No
changes in bilirubin No thrombocytopenia and no renal impairment reported 2 Serious Adverse Events (SAEs) 1 SAE in the 4mg/kg cohort resulted in a partial clinical hold 1 unrelated SAE in reaction to opioid pain medication after an elective
Summary DM1 underrecognized,
progressive and often fatal neuromuscular disease with a high unmet need and no approved therapies Data presented today is an early mid-point look at MARINA 6 weeks post 1 or 2 doses of AOC 1001 Baseline demographics generally well matched between
cohorts Generally favorable safety and tolerability profile Anticipate update on MARINA partial hold by the end of Q1 2023 Plan to disclose more information on the SAE at that time MARINA top-line data anticipated in 2023
Delivering on the AOC Platform and
Impacting the Underlying Disease Mechanism of DM1 W. Michael Flanagan, Ph.D., Chief Technical Officer