Slides
Page 1
1 43rd Annual J.P . Morgan Healthcare Conference Sarah Boyce President and Chief Executive Officer NASDAQ: RNA | aviditybio.com January 14, 2025
Page 2
2 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, design, goals and conduct of our ongoing and planned preclinical studies and clinical trials; the timing of release of data from our ongoing clinical prog rams; 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), delpacibart braxlosiran (del-brax) and delpacibart zotadirsen (del-zota); our plans to submit a BLA for del-zota and the timing thereof; the status of our three current clinical programs as potentially registrational; the ability for our product candidates to achieve accelerated approval; planned marketing applications for del-desiran in the U.S. and European Union and the timing thereof; our plans for potential product launches and commercialization; safety and tolerability of our product candidates; efficacy or functional data demonstrated by our product candidates; our next generation technology and plans for our precision cardiology programs; our plans regarding our DMD franchise; the potential of the AOC platform and specific product candidates; the regulatory expectations and pathways of our product candidates; the status and potential of our product candidates; the ability of our product candidates to treat rare diseases; timing and likelihood of success; pr oduct approvals; and plans and objectives of management for future 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 materially from those set forth in this presentatio n due to the risks and uncertainties inherent in our business based and factors beyond our control, including, without limitation: requests for data by the FDA or other regulatory authorities may result in significant additional expense and timing delays; data delivered to the FDA may not be satisfactory to the FDA and may not support BLA submissions or accelerated approvals; 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 a nd 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, regula tory 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; even if approve d, we may not be able to execute on our planned product launches; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; potential delays in t he 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 pro duct 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 f orm new collaborations; regulatory developments in the United States and foreign countries; Fast Track or Breakthrough Designation by the FDA may not lead to a faster development or regulatory revie w 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 req uired 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, p rojections, 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. Forward-Looking Statements
Page 3
3 OUR VISION To profoundly improve people’s lives by revolutionizing the delivery of RNA therapeutics Luke Living with DM1
Page 4
OUR VISION To profoundly improve people’s lives by revolutionizing the delivery of RNA therapeutics Loraine, Kristl and Zen Living with DM1, and Lora ine’s husband, Kevin
Page 5
5 Three Programs Moving to Commercialization Lee Living with DMD, and his mother, Ginne Jeannine Living with DM1 Russell Living with FSHD Del-desiran in DM1 • ~80,000 patients in U.S. and E.U. • On track to be the first globally approved drug for DM1 Del-brax in FSHD • ~45,000-87,000 patients in U.S. and E.U. • On track to be the first globally approved drug for FSHD Del-zota in DMD44 • ~900 patients in U.S. • Aligned on path for accelerated approval in the U.S.
Page 6
6 Consistent and Reproducible Results Across 3 Rare Neuromuscular Programs Product Candidate Functional Improvement Agreed Regulatory Path Registrational Program Ongoing Confirmatory trial design underway Expected Q2 2025 Del-zota Duchenne Muscular Dystrophy (DMD44) Del-desiran Myotonic Dystrophy Type 1 (DM1) Del-brax Facioscapulohumeral Muscular Dystrophy (FSHD) Safety, tolerability, delivery to muscle and target engagement demonstrated across all programs
Page 7
Del-zota in DMD44 Lee Living with DMD, and his mother, Ginne
Page 8
8 Del-zota: 25% Increase in Dystrophin Production and Profound Reduction in Creatine Kinase Seen in DMD44 Patients Data presented as of August 2024. 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 Increase of 25% of Normal in Dystrophin Production Creatine Kinase Levels Decrease to Near Normal Del-zota 25% increase * placebo del-zota 5 mg/kg Dystrophin (%normal) Baseline 4 Months Baseline 4 Months 0 10 20 30 40 12000 8000 4000 0 0 30 120 Study Day Placebo Del–zota (5 mg/kg) Upper Limit of Normal Creatine Kinase (U/L) 60 90 Statistically Significant Robust Exon Skipping Statistically Significant Dystrophin Production Profound & Sustained Reduction in Creatine Kinase Favorable Safety and Tolerability Unsurpassed Delivery to Muscle
Page 9
9 Significant and Sustained Reductions in Creatine Kinase in All Treated Groups Data presented as of November 2024. Mean +/- SEM. N=3 (Placebo), N=7 (del-zota). Dose expressed as PMO component. Del-zota 12000 8000 4000 0 600 120 180 240 Study Day Creatine Kinase (U/L) Placebo Del–zota (5 mg/kg)Del–zota (5 mg/kg)
Page 10
10 First of Three: Del-zota U.S. Launch Launch Preparations Del-zota sets the foundation for sequential neuromuscular launches 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 Del-zota
Page 11
Del-desiran in DM1 Jeannine Living with DM1
Page 12
12 Del-desiran: First to Show Reversal of Disease Progression in Patients with DM1 Data presented at 2024 Muscular Dystrophy Association Clinical & Scientific Conference. Thanks to END-DM1 physicians for reviewing and approving use of this Avidity analysis; END-DM1 subpopulation matched to MARINA® (n ~ 60) In MARINA-OLE data 4 mg/kg, n=12 for vHOT, QMT composite, hand grip; n=11 for DM1-Activ PPN = Percent predicted normal; CNTL= percentile; Error bars = SEM (standard error of the mean) Del-desiran MARINA-OLE data reverses disease progression compared to similar patients in END-DM1 natural history study DM1-Activ (CNTL) Hand Grip (PPN) QMT Composite (PPN) vHOT (sec) -4 -2 0 2 4 86420-2-4-6-8 4 2 0 -2 -4 ImprovingDeclining END-DM1 Natural History (1 year) Significant DMPK Knockdown Reversal of Disease Progression Signs of Functional Improvement Favorable Safety and Tolerability
Page 13
13 END-DM1 Natural History (1 year) Del-desiran: First to Show Reversal of Disease Progression in Patients with DM1 Del-desiran MARINA-OLE data reverses disease progression compared to similar patients in END-DM1 natural history study DM1-Activ (CNTL) Hand Grip (PPN) QMT Composite (PPN) vHOT (sec) -4 -2 0 2 4 86420-2-4-6-8 4 2 0 -2 -4 ImprovingDeclining 4 mg/kg Q13W (1 year) Significant DMPK Knockdown Reversal of Disease Progression Signs of Functional Improvement Favorable Safety and Tolerability Data presented at 2024 Muscular Dystrophy Association Clinical & Scientific Conference. Thanks to END-DM1 physicians for reviewing and approving use of this Avidity analysis; END-DM1 subpopulation matched to MARINA® (n ~ 60) In MARINA-OLE data 4 mg/kg, n=12 for vHOT, QMT composite, hand grip; n=11 for DM1-Activ PPN = Percent predicted normal; CNTL= percentile; Error bars = SEM (standard error of the mean)
Page 14
14 Advancing Del-desiran Towards Regulatory Approvals HARBOR Phase 3 Ongoing On track to complete enrollment in mid-2025 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 Del-desiran
Page 15
Del-brax in FSHD Russell Living with FSHD
Page 16
16 Del-brax: First to Target the Underlying Cause of FSHD Data presented as of October 2024. *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 Mean +/- SEM. Del-brax Meaningful reduction in novel DUX-4 regulated biomarker Significant reduction in creatine kinase biomarker Trends of Functional Improvement and Reported Outcome Study Month % Change From Baseline % Change From Baseline 20 0 -20 -40 -60 0 1 2 3 4 5 6 Placebo del-brax 2 mg/kg* del-brax 4 mg/kg** Dose Study Month 20 0 -20 -40 -60 0 1 2 3 4 5 6 Placebo del-brax 2 mg/kg* del-brax 4 mg/kg** Reductions in DUX4 Regulated Genes Novel DUX4 Biomarker Provides Path to Potential Accelerated Approval Trends of Functional Improvement and Reported Outcome Favorable Safety and Tolerability
Page 17
17 Dual Pathways to Rapidly Deliver Del-brax to Patients U.S. Accelerated Approval Pathway Global Phase 3 Trial for Full Approval Completion of enrollment of the FORTITUDETM biomarker cohort in Q2 2025 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 Initiation of a global, potentially registrational trial in Q2 2025 Del-brax
Page 18
OUR VISION To profoundly improve people’s lives by revolutionizing the delivery of RNA therapeutics Amy, Living with FSHD Amy Living with FSHD
Page 19
19 Expanding in Rare Neuromuscular and Entering Precision Cardiology PROGRAM / INDICATION TARGET PRECLINICAL PHASE 1/2 REGISTRATIONAL COMMERCIAL Duchenne Muscular Dystrophy (DMD) Exon 44 Myotonic Dystrophy Type 1 (DM1) DMPK Facioscapulohumeral Muscular Dystrophy (FSHD) DUX4 DMD Exon 45 Exon 45 Additional DMD Programs Undisclosed Rare Neuromuscular Undisclosed PLN Cardiomyopathy PLN PRKAG2 Syndrome PRKAG2 Del-desiranTM Del-zotaTM AOC 1045 AOC 1072 Del-braxTM AOC 1086
Page 20
20 AOC Precision Cardiology: Transforming Genetic Cardiomyopathy Treatment TARGETED siRNA DELIVERY TO CARDIAC MUSCLE GENETIC MUTATIONS IN THE HEART PRECISION CARDIOLOGY Robust siRNA delivery to heart muscle Target knockdown with potent reduction in cardiac mRNA Well-tolerated with no effect on ECG parameters in NHP
Page 21
21 Indicates modifications Leading Innovations in Delivery of RNA Therapeutics Next-generation technology is being incorporated into current and planned programs AOC mAb OLIGO siRNA Modification siRNA Modification & Antibody Engineering Today Tomorrow Future
Page 22
Delivering on our Vision: Executing in 2025
Page 23
23 Preparations to Launch Three Drugs Well Underway Leader in the Rare Neuromuscular Space All-Star Rare Disease Team Community Engagement • Building a synergistic franchise to tap into multiple patient populations with a significant unmet need • Experienced rare disease leadership team in place to execute patient- centric product launches • Leveraging established relationships with patients, clinicians, and others to execute our rapid go-to-market strategy
Page 24
24 Experienced Leadership Team to Deliver a New Class of RNA Therapeutics Sarah Boyce President & CEO Steve Hughes, MD Chief Medical Officer Eric Mosbrooker Chief Commercial Officer John B. Moriarty, Jr, J.D. Chief Legal Officer & Company Secretary Teresa McCarthy Chief Human Resources Officer Michael MacLean Chief Financial Officer W. Michael Flanagan, PhD Chief Scientific Officer Kat Lange Chief Business Officer Charles Calderaro III Chief Technical Officer Kath Gallagher Chief Program Officer
Page 25
25 Avidity 2025 Catalysts: Realizing Our Vision Program Catalyst Q1 Q2 Q3 Q4 Del-zota EXPLORE44TM topline data EXPLORE44-OLETM topline data BLA submission for accelerated approval Del-desiran Additional data analyses from Phase 1/2 MARINA® trial Phase 3 HARBORTM trial enrollment completion MARINA-OLETM trial update including long-term 4 mg/kg and safety data Del-brax Regulatory alignment on global Phase 3 trial design Alignment with FDA on potential accelerated approval path for ongoing FORTITUDETM biomarker cohort FORTITUDETM biomarker cohort enrollment completion Topline data from FORTITUDETM trial Initiation of global, potentially registrational trial in FSHD