Myotonia

- Preclinical data show ARO-DM1 reduces muscular DMPK expression and corrects spliceopathies, which could lead to improved muscle strength and function PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc., Inc. (NASDAQ: ARWR) announced today that it has dosed the first subjects in a Phase 1/2a double-blinded, placebo-controlled, dose-escalating study (NCT06138743) to evaluate single and multiple ascending doses of ARO-DM1, the company’s investigational RNA interference (RNAi) therapeutic, in up to 48 subjects with type 1 myotonic dystrophy (DM1). DM1 is the most common adult-onset muscular dystrophy. Patients with DM1 have muscle weakness and wasting, myotonia, cataracts, and often develop cardiac conduction abnormalities. Additionally, patients may become physically disabled and have a shortened life span. There is currently no approved disease-modifying therapy for DM1. Treatments have focused on symptomatic management, including physical therapy, exercise, ankle-foot orthoses, and assistive devices, such as wheelchairs. ARO-DM1 is designed to reduce expression of the dystrophia myotonica protein kinase (DMPK) gene in the muscle. Pathogenesis of DM1 is driven by an expanded CUG trinucleotide repeat in the 3’-untranslated region of DMPK transcripts. These abnormal transcripts cause mis-regulated splicing, known as spliceopathy, for certain messenger RNAs which are directly linked to the clinical manifestations of DM1. Preclinical data recently presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference showed that in nonhuman primates, ARO-DM1 achieved greater than 80% silencing of DMPK in skeletal muscle, which was maintained for longer than 85 days. In a mouse model of DM1 harboring a pathogenic DMPK transgene, a modified species-specific version of ARO-DM1 (S-ARO-DM1) decreased the DMPK-CUG expression and corrected the spliceopathies. Presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on X (formerly Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.

- Positive Initial Clinical Data from ACHIEVE Trial in DM1 Patients and DELIVER Trial in DMD Patients Demonstrated Proof-of-Concept, Validating the Promise of the FORCE™ Platform and Targeted Delivery to Muscle - - Strengthened Balance Sheet with $345 Million Public Offering Extending Projected Cash Runway Through 2025 - WALTHAM, Mass., March 05, 2024 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today reported financial results for the fourth quarter and full year 2023 and recent business highlights. “We’ve had an exciting start to 2024 highlighted by Dyne’s first clinical data demonstrating proof-of-concept in our DM1 and DMD programs that validated the promise of the FORCE™ platform in developing targeted therapeutics for people living with rare muscle diseases. We were thrilled to see dose-dependent results in our ACHIEVE trial in DM1 as well as meaningful improvement in myotonia at the lowest dose, and in our DELIVER trial to exceed the level of dystrophin production reported for the standard of care for DMD exon 51 with a fraction of the dose. The strength of these data formed the foundation of the $345 million offering we completed in January 2024, which has extended our projected cash runway through 2025,” said Joshua Brumm, president and chief executive officer of Dyne. “In 2024, we are focused on leveraging the favorable safety profiles for both DYNE-101 and DYNE-251 and the adaptive nature of our ACHIEVE and DELIVER trials to optimize dose and dose regimen. We plan to provide an update from both trials in the second half of 2024, including reporting data from multiple, higher dose cohorts. We also continue to pursue expedited regulatory pathways as part of our commitment to move with a sense of urgency to deliver potentially transformative therapies for the DM1 and Duchenne communities.” Highlights from Clinical Programs Phase 1/2 ACHIEVE Trial of DYNE-101 in DM1 In January 2024, Dyne reported initial clinical data from the Phase 1/2 ACHIEVE trial of DYNE-101 in adult patients with myotonic dystrophy type 1 (DM1). The initial efficacy assessment was based on data from 32 patients enrolled in the randomized, placebo-controlled multiple ascending dose (MAD) portion of the trial, including 6-month data from the 1.8 mg/kg (approximate ASO dose) cohort and 3-month data from the 3.4 mg/kg Q4W cohort. DYNE-101 demonstrated a dose-dependent splicing correction as well as an increase in muscle delivery and DMPK knockdown. Patients treated with 1.8 mg/kg Q4W of DYNE-101 also experienced functional improvement in myotonia as measured by video hand opening time (vHOT) and overall improvement in the Myotonic Dystrophy Health Index (MDHI) patient reported outcome, including the fatigue subscale, suggesting potential benefit in the central nervous system.Safety and tolerability data were based on 45 patients enrolled through the 5.4 mg/kg Q8W cohort of the MAD portion. DYNE-101 demonstrated a favorable safety profile as of the data cutoff date1. The ACHIEVE trial is fully enrolled through the 5.4 mg/kg Q8W cohort and is currently enrolling participants in the 6.8 mg/kg Q8W cohort. Phase 1/2 DELIVER Trial of DYNE-251 in DMD In January 2024, Dyne reported initial clinical data from the Phase 1/2 DELIVER trial of DYNE-251 in Duchenne muscular dystrophy (DMD). The initial efficacy assessment was based on 6-month data from 6 male patients with DMD amenable to exon 51 skipping enrolled in the 5 mg/kg (approximate PMO dose) cohort of the randomized, placebo-controlled MAD portion of the trial. Once every 4-week administration of DYNE-251 reached levels of dystrophin expression, exon skipping and percent dystrophin positive fibers that exceeded levels reported in a clinical trial for the current weekly standard of care for DMD exon 51, eteplirsen, at 6 months2 with a 24-fold lower total PMO dose.Safety and tolerability data were based on 37 patients enrolled through the 20 mg/kg cohort of the MAD portion. DYNE-251 demonstrated a favorable safety profile as of the data cutoff date1. The DELIVER trial is fully enrolled through the 20 mg/kg Q4W cohort and is currently enrolling participants in the 40 mg/kg Q8W cohort. Other Business Highlights In January 2024, Dyne completed an underwritten public offering of 19,722,500 shares of its common stock at a public offering price of $17.50 per share, which included 2,572,500 shares issued upon the exercise in full by the underwriters of their option to purchase additional shares of common stock in the offering. The gross proceeds to Dyne from the offering were approximately $345.1 million, before deducting underwriting discounts and commissions and offering expenses payable by Dyne. Upcoming Events & Key 2024 Milestones Initial data from ACHIEVE and DELIVER reported in January 2024 will be featured in oral presentations at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference on March 6, 2024. Dyne anticipates reporting data from multiple, higher dose cohorts from both the ACHIEVE and the DELIVER trials in the second half of 2024 with the goal of initiating registrational cohorts by the end of 2024. Fourth Quarter and Full Year 2023 Financial Results Cash position: Cash, cash equivalents and marketable securities were $123.1 million as of December 31, 2023. In January 2024, the Company completed an underwritten public offering of 19,722,500 shares of its common stock for net proceeds of approximately $323.9 million. The Company expects that its cash, cash equivalents and marketable securities as of December 31, 2023, together with the net proceeds from the January 2024 underwritten public offering, will be sufficient to fund its operations through 2025. Research and development (R&D) expenses: R&D expenses were $58.8 million and $33.2 million for the quarters ended December 31, 2023 and 2022, respectively. R&D expenses were $210.8 million and $142.8 million for the years ended December 31, 2023 and 2022, respectively. General and administrative (G&A) expenses: G&A expenses were $8.8 million and $7.0 million for the quarters ended December 31, 2023 and 2022, respectively. G&A expenses were $31.4 million and $28.2 million for the years ended December 31, 2023 and 2022, respectively. Net loss: Net loss for the quarter ended December 31, 2023 was $66.6 million, or $1.09 per basic and diluted share. This compares with a net loss of $38.8 million, or $0.74 per basic and diluted share, for the quarter ended December 31, 2022. Net loss for the year ended December 31, 2023 was $235.9 million, or $3.95 per basic and diluted share. This compares with a net loss of $168.1 million, or $3.23 per basic and diluted share, for the year ended December 31, 2022. About Dyne Therapeutics Dyne Therapeutics is a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases. With its proprietary FORCE™ platform, Dyne is developing modern oligonucleotide therapeutics that are designed to overcome limitations in delivery to muscle tissue. Dyne has a broad pipeline for serious muscle diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and a preclinical program for facioscapulohumeral muscular dystrophy (FSHD). For more information, please visit https://www.dyne-tx.com, and follow us on X, LinkedIn and Facebook. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Dyne’s strategy, future operations, prospects and plans, objectives of management, the potential of the FORCE platform, the trial design of the DYNE-101 and DYNE-251 clinical trials, the anticipated timelines for reporting data from the DYNE-101 and DYNE-251 clinical trials and initiating registrational cohorts, plans to optimize dose and dose regimen for DYNE-101 and DYNE-251 and the sufficiency of Dyne’s cash resources for the period anticipated, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Dyne may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Dyne’s ability to initiate and enroll patients in clinical trials; whether results from preclinical studies and initial data from early clinical trials will be predictive of the final results of the clinical trials or future trials; whether Dyne’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Dyne’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-K and in subsequent filings Dyne may make with the SEC. In addition, the forward-looking statements included in this press release represent Dyne’s views as of the date of this press release. Dyne anticipates that subsequent events and developments will cause its views to change. However, while Dyne may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Dyne’s views as of any date subsequent to the date of this press release. 1. Safety data as of December 6, 20232. No head-to-head trials have been conducted comparing DYNE-251 to eteplirsen. Eteplirsen data may not be directly comparable due to differences in trial protocols, dosing regimens and patient populations. Accordingly, these cross-trial comparisons may not be reliable. Eteplirsen data from J Neuromuscul Dis. 2021; 8(6): 989–1001 Dyne Therapeutics, Inc. Condensed Consolidated Statement of Operations (in thousands, except share and per share data) Three Months Ended Year Ended December 31, December 31, 2023 2022 2023 2022 Operating expenses: Research and development$58,843 $33,191 $210,762 $142,760 General and administrative 8,846 6,955 31,400 28,202 Total operating expenses 67,689 40,146 242,162 170,962 Loss from operations (67,689) (40,146) (242,162) (170,962)Other (expense) income, net 1,050 1,319 6,225 2,863 Net loss$(66,639) $(38,827) $(235,937) $(168,099)Net loss per share, basic and diluted$(1.09) $(0.74) $(3.95) $(3.23)Weighted average common shares outstanding, basic and diluted 61,393,409 52,817,413 59,683,851 51,976,343 Dyne Therapeutics, Inc. Condensed Consolidated Balance Sheet Data (in thousands) December 31, 2023 2022 Assets Cash, cash equivalents and marketable securities $123,100 $256,012 Other assets 41,982 50,313 Total Assets $165,082 $306,325 Liabilities and Stockholders’ Equity Liabilities 73,790 53,961 Stockholders' equity 91,292 252,364 Total liabilities and stockholders' equity $165,082 $306,325 Contacts: InvestorsAmy Reillyareilly@dyne-tx.com 857-341-1203 MediaStacy Nartkersnartker@dyne-tx.com 781-317-1938

Avidity accelerates global Phase 3 HARBOR™ study initiation to Q2 2024 following regulatory agreement on study design; primary endpoint is video hand opening time (vHOT) and secondary endpoints include muscle strength and activities of daily living Delpacibart etedesiran (AOC 1001) demonstrated consistent and durable improvements in myotonia, muscle strength and activities of daily living in people with DM1 in long-term data from MARINA-OLE™ Delpacibart etedesiran (AOC 1001) data from MARINA-OLE showed reversal of disease progression in multiple functional measures in people living with DM1 compared to END-DM1 natural history data Avidity to host Volume 8 of investor and analyst event series via webcast March 4, 2024, at 8:00 a.m. ET SAN DIEGO, March 4, 2024 /PRNewswire/ -- Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced new positive long-term AOC 1001 data from the MARINA open-label extension (MARINA-OLE™) trial showing reversal of disease progression in people living with myotonic dystrophy type 1 (DM1) across multiple endpoints including vHOT, muscle strength and activities of daily living when compared to END-DM1 natural history data. These endpoints are the same key endpoints that will be used in the global Phase 3 HARBOR™ trial for people living with DM1. The primary endpoint in the Phase 3 HARBOR trial is video hand opening time (vHOT), and key secondary endpoints include muscle strength as measured by hand grip strength and quantitative muscle testing (QMT) total score, and activities of daily living as measured by DM1-Activ. Avidity is accelerating the global Phase 3 HARBOR trial initiation to the second quarter of 2024. Avidity also announced delpacibart etedesiran as the approved international nonproprietary name of AOC 1001, abbreviated as del-desiran. Del-desiran (AOC 1001) is an investigational treatment designed to address the root cause of DM1, an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies. "The long-term data from the MARINA-OLE study demonstrating that del-desiran improved measures of disease progression in DM1 patients compared to natural history data is remarkable," said John W. Day, MD, PhD, Professor of Neurology and Pediatrics, and Director, Division of Neuromuscular Medicine, Stanford University School of Medicine, an investigator of the MARINA® and MARINA-OLE trials. "The favorable long-term safety data and consistent, durable improvement in myotonia, muscle strength and patient-reported outcomes measures show the potential of del-desiran to make a meaningful difference in the lives of DM1 patients. I am very encouraged by the prospect of del-desiran as a potential treatment for DM1." "Initiating our global pivotal study for del-desiran in the coming months is a significant step forward in bringing a much-needed treatment to people living with DM1 as quickly as possible. We are pleased that the agreed upon functional endpoints in the Phase 3 HARBOR study are the same endpoints in which del-desiran has demonstrated consistent and durable improvements in the MARINA studies," said Sarah Boyce, president and chief executive officer at Avidity. "Thank you to the DM1 community, in particular - the participants, their families, the investigators and their teams - for their support, dedication and commitment to the MARINA program. The depth and breadth of del-desiran data that we have gathered from these studies offer hope for people living with DM1, a devastating rare disease for which there are no treatment options available." Data Presented at 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 3-6 MARINA-OLE™ is an open-label, multi-center trial to evaluate the safety, tolerability, PK, PD, and efficacy of del-desiran (AOC 1001) in participants that were enrolled in the randomized, placebo-controlled, Phase 1/2 MARINA® clinical trial. Participants enrolled in the MARINA-OLE study receive quarterly doses of del-desiran (AOC 1001) regardless of whether they received active treatment or placebo in the MARINA study. All 37 participants that completed the MARINA trial remain on del-desiran (AOC 1001) in the MARINA-OLE trial. Long-term efficacy data presented were assessed from 12 participants on 4 mg/kg del-desiran (AOC 1001) in the MARINA-OLE study. The endpoints used in the MARINA-OLE measure important aspects of the disease and correspond to those utilized in the ongoing END-DM1 natural history study. The long-term data from the MARINA-OLE trial are being presented in a poster session at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference being held March 3-6, 2024, in Orlando, Florida and can also be found on Avidity's website on the Publications page. MARINA-OLE data compared to END-DM1 natural history data For the first time new data were reported from END-DM1, a natural history study to establish biomarkers and clinical endpoints in DM1 by understanding the progression of myotonic dystrophy. Long-term del-desiran (AOC 1001) data from the MARINA-OLE study show reversal of disease progression in people living with DM1 across multiple endpoints including myotonia, muscle strength and patient reported activities of daily living compared to a matched END-DM1 natural history study population over one year. Avidity is grateful to the END-DM1 team for their partnership over the years and for their approval and permission to share this analysis from the study. Del-desiran long-term efficacy data from MARINA-OLE In the MARINA-OLE study, del-desiran (AOC 1001) 4 mg/kg provided consistent and durable improvements in the following: Myotonia (video hand opening time, or vHOT) Multiple measures of strength: Hand grip Quantitative Muscle Testing (QMT) total score which includes hand grip; elbow extension and elbow flexion; knee extension and knee flexion, and ankle dorsiflexion DM1-Activ, a patient reported outcome (PRO) that measures activities of daily living (e.g., taking a shower, visiting family or friends, and walking up stairs) Del-desiran safety and tolerability data from MARINA-OLE With over 265 infusions totaling 61.1 patient-years of exposure, del-desiran (AOC 1001) continues to demonstrate favorable safety and tolerability. In the MARINA-OLE study of del-desiran (AOC 1001): All related adverse events (AE) were mild or moderate The most common related AEs reported in 2 or more participants in the MARINA-OLE were nausea and headache There were no study drug related SAEs There have been no discontinuations in the MARINA-OLE study Video Webcast Information The company is hosting Volume 8 of its investor and analyst event series on March 4, 2024, beginning at 8:00 a.m. ET to discuss new positive long-term del-desiran (AOC 1001) data from the MARINA-OLE™ trial in people living with DM1. The virtual event will be available via a live video webcast and can be accessed here or from the "Events and Presentations" page in the "Investors" section of Avidity's website. A replay of the webcast will be archived on Avidity's website following the event. About the Phase 1/2 MARINA® Trial The MARINA® trial was a randomized, double-blind, placebo-controlled, Phase 1/2 clinical trial that enrolled 38 adults with DM1. The primary objective of this study was to evaluate the safety and tolerability of single and multiple ascending doses of del-desiran (AOC 1001) administered intravenously. The MARINA trial assessed the activity of del-desiran (AOC 1001) across key biomarkers, including spliceopathy, an important biomarker for DM1, and knockdown of DMPK mRNA. Though the Phase 1/2 trial was not powered to assess functional benefit, it explored the clinical activity of del-desiran (AOC 1001) in multiple measures of muscle function including myotonia, muscle strength, measures of mobility as well as patient reported outcomes and quality of life measures. Patients had the option to enroll in MARINA-OLE™, an open-label extension study, at the end of the post-treatment period. For more information on this study click here or visit and search for NCT05027269. About the Phase 2 MARINA-OLE™ Study MARINA-OLE™ is an open-label, multi-center trial designed to evaluate the long-term safety and tolerability of del-desiran (AOC 1001) in participants with DM1 who were previously enrolled in the MARINA® Phase 1/2 trial. This trial will continue to evaluate the safety, tolerability, PK, PD, and efficacy of del-desiran (AOC 1001) in participants enrolled in the randomized, placebo-controlled, Phase 1/2 MARINA clinical trial. Participants enrolled in the MARINA-OLE study receive quarterly doses of del-desiran (AOC 1001) regardless of whether they received active treatment or placebo in the MARINA study. The total duration of active treatment with del-desiran (AOC 1001) in the MARINA-OLE study is approximately 24 months. Once patients have completed active treatment, there will be a nine-month safety follow-up period. Avidity may extend active treatment beyond 24 months at a future timepoint. For more information on this study click here or visit and search for NCT05479981. About Del-desiran (AOC 1001) Del-desiran (AOC 1001), Avidity's lead product candidate utilizing its AOC platform, is designed to address the root cause of DM1 by reducing levels of a disease-related mRNA called DMPK. Del-desiran (AOC 1001) consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA. In preclinical studies, del-desiran (AOC 1001) successfully delivered siRNAs to muscle cells, resulting in durable, dose-dependent reductions of DMPK RNA across a broad range of muscles including skeletal, cardiac, and smooth muscles. Del-desiran (AOC 1001) is currently in Phase 1/2 development with the completed MARINA® trial and the ongoing MARINA-OLE™ trial in adults with DM1. The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have granted Orphan Designation for del-desiran (AOC 1001) and the FDA has granted del-desiran (AOC 1001) Fast Track Designation. About Myotonic Dystrophy Type 1 Myotonic dystrophy type 1 (DM1) is an underrecognized, progressive and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation and age of onset, however all forms of DM1 are associated with high levels of disease burden and may cause premature mortality. DM1 primarily affects skeletal and cardiac muscle, however patients can suffer from a constellation of manifestations including myotonia and muscle weakness, respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. Currently, there are no approved treatments for people living with DM1. About Avidity Avidity Biosciences, Inc.'s mission is to profoundly improve people's lives by delivering a new class of RNA therapeutics - Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through internal discovery efforts and key partnerships. Avidity is headquartered in San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit and engage with us on LinkedIn and X (formerly Twitter). Forward-Looking Statements Avidity cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the characterization of safety, tolerability and long-term efficacy data associated with delpacibart etedesiran (del-desiran, or AOC 1001) from the MARINA-OLE™ study; the impact of such data on the advancement of del-desiran; a global pivotal Phase 3 trial for del-desiran, the timing of its initiation and key endpoints to be used therein; regulatory agreement regarding a Phase 3 trial for del-desiran; expectations related to the MARINA-OLE study and del-desiran; timelines for active treatment and safety follow-up in MARINA-OLE; data from the END-DM1 study and its importance to the assessment of del-desiran; the potential of Avidity's product candidates to treat rare diseases and Avidity's efforts to bring them to people suffering from applicable diseases; the potential of AOCs to target a range of different cells and tissues beyond the liver, and to treat cardiac and immunological diseases; and Avidity's plans to expand its AOC platform and to invest in its pipeline programs. This press release also contains estimates and other statistical data made by independent parties and by us. This data involves a number of assumptions and limitations, and the reader is cautioned not to give undue weight to such estimates. The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of these plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Avidity's business, including, without limitation: Avidity may not be able to resolve the partial clinical hold related to the serious adverse event which occurred in the Phase 1/2 MARINA trial, which may result in delays in the clinical development of del-desiran; additional participant data related to del-desiran that continues to become available may be inconsistent with the data produced as of the date hereof, and further analysis of existing data and analysis of new data may lead to conclusions different from those established as of the date hereof; unexpected adverse side effects to, or inadequate efficacy of, Avidity's product candidates that may delay or limit their development, regulatory approval and/or commercialization, or may result in additional clinical holds which may not be timely lifted, recalls or product liability claims; Avidity is early in its development efforts; Avidity's approach to the discovery and development of product candidates based on its AOC platform is unproven, and the company does not know whether it will be able to develop any products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of preclinical studies or clinical trials; Avidity's dependence on third parties in connection with preclinical and clinical testing and product manufacturing; regulatory developments in the United States and foreign countries; and other risks described in Avidity's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, filed with the Securities and Exchange Commission (SEC) on February 28, 2024, and in subsequent filings with the SEC. Avidity cautions readers not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that arise after the date hereof. 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. Investor Contact: Geoffrey Grande, CFA (619) 837-5014 [email protected] Media Contact: Navjot Rai (619) 837-5016 [email protected] SOURCE Avidity Biosciences, Inc.