Summary of AVIDITY Biosciences Conference Call Company Overview - **Company**: AVIDITY Biosciences - **Focus**: Development of RNA therapeutics targeting muscle diseases, with three late-stage programs: Dalzosia (DMD), Delbrex (FSHD), and Daldistarone (myotonic dystrophy) [4][5][10] Core Points and Arguments Vision and Strategy - AVIDITY aims to revolutionize the RNA space and significantly impact patients' lives, with a focus on muscle diseases [3][4] - The company is on track to file its first Biologics License Application (BLA) for Dalzosia by the end of the year [4][17] Drug Development Progress - **Dalzosia**: Targeting boys and young men with DMD amenable to exon 44 skipping; enrollment completed, with data readout expected in Q2 next year [4][12] - **Delbrex**: For FSHD, with alignment on primary endpoint for accelerated approval; data readout also expected in Q2 next year [4][12][54] - **Daldistarone**: For myotonic dystrophy, with a focus on significant unmet medical needs [4][48] Delivery Mechanism - AVIDITY's platform allows for high delivery of RNA therapeutics to muscle tissue, achieving 3-5 times higher delivery compared to other methods [7][8][40] - The use of antibody oligonucleotide conjugates (AOCs) targets the transferrin receptor, enhancing muscle delivery [6][7] Market Potential and Commercialization - Anticipated rapid uptake for Dalzosia, with approximately 900 boys and young men in the US eligible for treatment [27] - The company has established a commercial infrastructure, including patient services and payer engagement teams, to support drug launches [22][49] Regulatory Environment - Positive interactions with the FDA, with no significant impact from leadership changes; the same division reviews all three programs, ensuring consistency [20][21] - Plans for BLA submissions for FSHD and myotonic dystrophy in the second half of next year [57] Additional Important Insights - The company is preparing for potential acquisition interest due to the value of its upcoming drug launches, with two drugs expected to be multi-billion dollar opportunities [10][11] - The myotonic dystrophy patient population is estimated at 40,000 in the US, with around 10,000 already diagnosed, indicating a significant market opportunity [45][46] - AVIDITY has secured a global commercial supply agreement with Lonza for manufacturing, ensuring readiness for market demand [49] Conclusion AVIDITY Biosciences is positioned for significant growth with its innovative RNA therapeutics targeting high-need muscle diseases. The company is on track for multiple drug launches, backed by a strong regulatory strategy and a well-prepared commercial infrastructure.

Key Takeaways Avidity shares jumped 36% after reports that Novartis is interested in acquiring the biotech.FT noted talks are in early stages with no guarantee of a deal and other suitors may emerge.Avidity develops RNA therapies for rare muscular diseases and has major pharma partnerships.Shares of Avidity Biosciences (RNA) have soared 36% in the past month, all thanks to a report issued by the Financial Times (FT), which stated that pharma giant Novartis (NVS) is interested in acquiring the company.Per th ...

Core Viewpoint - Novartis plans to acquire Avidity Biosciences, a leader in the AOC field with a market value of nearly $6 billion, to strengthen its pipeline in the rare disease treatment sector [3]. Group 1: Market Dynamics - The small nucleic acid drugs, including siRNA, ASO, and miRNA, are designed to regulate gene expression for disease treatment, offering breakthrough therapies for genetic, rare, and chronic diseases [4]. - Novartis faces a "patent cliff" with several blockbuster drugs, including Entresto, set to lose patent protection between 2025 and 2030, necessitating the acquisition of new pipeline assets to ensure future growth [5]. - Major pharmaceutical companies, including Sanofi, Pfizer, and Eli Lilly, have been actively acquiring and partnering in the small nucleic acid drug space to capture the potential market [6]. Group 2: AOC Development and Commercialization - AOC (Antibody-Oligonucleotide Conjugates) represents an innovative delivery method for small nucleic acid drugs, combining the targeting ability of monoclonal antibodies with the gene regulation capabilities of oligonucleotides [10]. - Avidity Biosciences is a leading player in the AOC field, with three pipelines in Phase III clinical trials, including a drug for Duchenne Muscular Dystrophy (DMD) that has shown promising results [12]. - The commercialization of AOC drugs is expected to accelerate, with several biotech companies entering late-stage clinical trials, aiming for market entry around 2026-2027 [11]. Group 3: Investment and Policy Support - The Chinese government continues to support the development of RNA and small nucleic acid drugs through funding initiatives aimed at overcoming core bottlenecks in drug creation [14]. - Recent financing activities in the small nucleic acid drug sector indicate growing interest and investment, with several companies securing significant funding [17]. - Novartis's acquisition of Avidity, if completed, would mark a significant milestone in the global AOC drug market, highlighting the increasing focus on innovative therapies [15].

Investment Rating - The report indicates a strong interest in the small nucleic acid drug sector, particularly through acquisitions and partnerships, highlighting the potential for significant growth in this area [3][5][15]. Core Insights - Novartis is focusing on expanding its pipeline in rare disease treatments by acquiring Avidity Biosciences, a leader in the Antibody-Oligonucleotide Conjugates (AOC) field, which is valued at nearly $6 billion [3][11]. - The small nucleic acid drugs, including siRNA, ASO, and miRNA, are gaining traction due to their ability to target traditionally "undruggable" disease-causing genes, offering breakthrough treatment options for genetic, rare, and chronic diseases [4][9]. - The report emphasizes the importance of delivery technologies for small nucleic acid drugs, particularly the need for effective delivery systems to target tissues outside the liver, as 90% of disease-causing genes are expressed in non-liver tissues [8][9]. Summary by Sections Acquisition and Market Dynamics - Novartis has been actively acquiring companies to fill the pipeline gap created by upcoming patent expirations of key drugs, such as Entresto, which is projected to generate $7.822 billion in sales in 2024 [5][6]. - The report outlines several significant acquisitions in the small nucleic acid space, including Novartis's $9.7 billion acquisition of The Medicines Company and a $1.7 billion deal for Regulus Therapeutics [6][12]. Delivery Technology and Challenges - The report discusses the challenges faced by small nucleic acid drugs in terms of delivery, particularly the degradation by nucleases and the difficulty in penetrating the blood-brain barrier [7][8]. - Innovations in delivery systems, such as the FALCON platform by DTx Pharma, are highlighted as crucial for advancing the application of RNA therapies beyond liver-targeted treatments [8][10]. Competitive Landscape - The competitive landscape is characterized by major pharmaceutical companies, including Sanofi, Pfizer, and Eli Lilly, making significant investments in small nucleic acid drug technologies to capture the emerging market [6][10]. - Avidity Biosciences is noted as a key player with multiple clinical-stage AOC pipelines, including a breakthrough therapy for Duchenne Muscular Dystrophy [12][13]. Regulatory and Funding Environment - The report mentions supportive policies from the Chinese government aimed at promoting RNA and small nucleic acid drug development, including funding initiatives for innovative research [14][15]. - Recent financing activities in the small nucleic acid drug sector indicate growing investor interest, with several companies securing substantial funding to advance their research and development efforts [16].

高盛最新研报以"2Q25EPS更新"为主题，其中重点对Amylyx(AMLX.US)、CG Oncology(CGON.US)、硕 迪生物(GPCR.US)、Ideaya生物科学(IDYA.US)等生物科技公司进行逐一拆解，结论是：运营数据大体 符合预期，投资逻辑无需大改，但个别公司因现金流或临床节点微调目标价。 Amylyx：开启药物商业化尝试 公司二季度运营费用约4,300万美元，略高于市场共识的4,100万美元和高盛原估的4,000万美元，差异主 要来自研发费用，2,700万美元对预期2,200万～2,500万美元区间，销售费用则与市场持平。 投资者仍紧盯减重术后低血糖(PBH)三期临床试验：管理层重申2025年完成入组、2026年上半年读出数 据、2027年有望上市，潜在可及患者约16万人。公司已悄悄启动商业化热身，包括锁定核心内分泌中 心、试水定价，若对标近期罕见内分泌新药，高盛目前"10万美元/年"的定价假设仍有上行空间。 管线方面，进行性核上性麻痹(PSP)二期临床将在三季度揭盲，公司设定了"PSP评分量表延缓≥20%"的 高门槛;Wolfram综合征三期设计正与FDA沟通，今年会有更新;ALS ...

PART I – FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (unaudited)](index=3&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(unaudited)) This section presents unaudited condensed consolidated financial statements, including balance sheets, statements of operations, equity, cash flows, and detailed notes [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section provides a summary of the company's financial position at specific dates Condensed Consolidated Balance Sheet Highlights (in thousands) | Metric | June 30, 2025 | December 31, 2024 | | :-------------------------- | :------------ | :---------------- | | Cash and cash equivalents | $243,907 | $219,868 | | Marketable securities | $939,237 | $1,281,629 | | Total current assets | $1,250,560 | $1,542,290 | | Total assets | $1,368,926 | $1,563,895 | | Total current liabilities | $135,061 | $98,018 | | Total liabilities | $176,262 | $138,936 | | Total stockholders' equity | $1,192,664 | $1,424,959 | - Total assets decreased by **$195.0 million** from December 31, 2024, to June 30, 2025, primarily due to a reduction in marketable securities[11](index=11&type=chunk) - Total liabilities increased by **$37.3 million**, while total stockholders' equity decreased by **$232.3 million** during the six-month period[11](index=11&type=chunk) [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This section details the company's revenues, expenses, and net loss over specific periods Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands, except per share data) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Collaboration revenue | $3,847 | $2,045 | $5,420 | $5,588 | | Research and development expenses | $138,125 | $63,940 | $237,615 | $130,772 | | General and administrative expenses | $36,864 | $20,731 | $70,464 | $34,629 | | Loss from operations | $(171,142) | $(82,626) | $(302,659) | $(159,813) | | Interest income | $14,478 | $11,949 | $30,657 | $20,382 | | Net loss | $(157,315) | $(70,793) | $(273,088) | $(139,648) | | Net loss per share, basic and diluted | $(1.21) | $(0.65) | $(2.11) | $(1.44) | | Weighted-average shares outstanding | 129,622 | 106,928 | 129,428 | 97,070 | - Net loss significantly increased for both the three-month period (from **$(70.8 million)** to **$(157.3 million)**) and the six-month period (from **$(139.6 million)** to **$(273.1 million)**) year-over-year[12](index=12&type=chunk) - Research and development expenses more than doubled for both periods, driving the increased net loss[12](index=12&type=chunk) [Condensed Consolidated Statements of Stockholders' Equity](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This section outlines changes in the company's equity, including common stock and accumulated deficit Changes in Stockholders' Equity (in thousands) | Metric | December 31, 2024 | March 31, 2025 | June 30, 2025 | | :-------------------------------- | :---------------- | :------------- | :------------ | | Common Stock Shares | 119,893 | 120,512 | 120,778 | | Additional Paid-in Capital | $2,315,111 | $2,334,784 | $2,357,029 | | Accumulated Other Comprehensive Income | $2,902 | $2,766 | $1,777 | | Accumulated Deficit | $(893,066) | $(1,008,839) | $(1,166,154) | | Total Stockholders' Equity | $1,424,959 | $1,328,723 | $1,192,664 | - Total stockholders' equity decreased by **$232.3 million** from December 31, 2024, to June 30, 2025, primarily due to the accumulated net loss[15](index=15&type=chunk) - Additional paid-in capital increased due to stock option exercises, ESPP, and stock-based compensation[15](index=15&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section presents the company's cash inflows and outflows from operating, investing, and financing activities Condensed Consolidated Statements of Cash Flows (in thousands, Six Months Ended June 30) | Activity | 2025 | 2024 | | :------------------------------------------ | :--------- | :--------- | | Net cash used in operating activities | $(324,495) | $(135,384) | | Net cash provided by (used in) investing activities | $342,673 | $(307,616) | | Net cash provided by financing activities | $5,710 | $836,169 | | Net increase in cash, cash equivalents and restricted cash | $24,042 | $393,169 | | Cash, cash equivalents and restricted cash at end of period | $246,705 | $578,546 | - Net cash used in operating activities increased significantly from **$135.4 million** in 2024 to **$324.5 million** in 2025[20](index=20&type=chunk) - Investing activities shifted from using **$307.6 million** in 2024 to providing **$342.7 million** in 2025, primarily due to proceeds from maturities of marketable securities[20](index=20&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=9&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed explanations and disclosures for the unaudited condensed consolidated financial statements [1. Description of Business and Basis of Presentation](index=9&type=section&id=1.%20Description%20of%20Business%20and%20Basis%20of%20Presentation) This note describes the company's biopharmaceutical business and the basis for financial statement presentation - Avidity Biosciences is a biopharmaceutical company developing Antibody Oligonucleotide Conjugates (AOCs) to target the root cause of previously untreatable diseases[22](index=22&type=chunk) - As of June 30, 2025, the company had an accumulated deficit of **$1.2 billion** and cash, cash equivalents, and marketable securities of **$1.2 billion**[23](index=23&type=chunk) - Existing cash, cash equivalents, and marketable securities are believed to be sufficient to fund operations for at least 12 months from the Form 10-Q filing date[24](index=24&type=chunk) [2. Summary of Significant Accounting Policies](index=10&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) This note outlines the key accounting policies used in preparing the condensed consolidated financial statements - No significant changes to accounting policies occurred during the six months ended June 30, 2025[29](index=29&type=chunk) - The company is evaluating the impact of new FASB ASUs 2023-09 (Income Tax Disclosures) and 2024-03 (Expense Disaggregation Disclosures) on its financial statements[33](index=33&type=chunk)[34](index=34&type=chunk) Common Stock Equivalent Securities Not Included in Diluted Net Loss Per Share (in thousands) | Security Type | June 30, 2025 | June 30, 2024 | | :-------------------------------- | :------------ | :------------ | | Common stock options | 14,394 | 12,728 | | Restricted stock units | 2,812 | 1,526 | | Performance stock units | 810 | 562 | | ESPP shares pending issuance | 3 | 4 | | **Total** | **18,019** | **14,820** | [3. Fair Value Measurements](index=11&type=section&id=3.%20Fair%20Value%20Measurements) This note details the fair value measurements of financial instruments, primarily marketable securities Fair Value Measurements of Marketable Securities (in thousands, as of June 30, 2025) | Asset Type | Total | Level 1 (Quoted Prices) | Level 2 (Other Observable Inputs) | Level 3 (Unobservable Inputs) | | :----------------------- | :------ | :---------------------- | :-------------------------- | :------------------------ | | U.S. Treasury securities | $939,237 | $939,237 | $0 | $0 | - All marketable securities are measured at fair value using Level 1 inputs, indicating readily available quoted prices in active markets[35](index=35&type=chunk) [4. Marketable Securities](index=11&type=section&id=4.%20Marketable%20Securities) This note provides information on the company's marketable securities, including their fair value and maturity Marketable Securities (in thousands, as of June 30, 2025) | Maturity | Amortized Cost | Unrealized Gains | Unrealized Losses | Estimated Fair Value | | :--------------- | :------------- | :--------------- | :---------------- | :------------------- | | U.S. Treasury securities (1 year or less) | $753,666 | $1,350 | $(94) | $754,922 | | U.S. Treasury securities (1-2 years) | $183,924 | $435 | $(44) | $184,315 | | **Total** | **$937,590** | **$1,785** | **$(138)** | **$939,237** | - Unrealized losses on marketable securities are primarily due to interest rate increases, not credit quality, and no allowance for credit losses was recorded[37](index=37&type=chunk) - The company does not intend to sell these investments before maturity and expects to recover their amortized cost bases[37](index=37&type=chunk) [5. Collaboration, License and Research Agreements](index=12&type=section&id=5.%20Collaboration,%20License%20and%20Research%20Agreements) This note details revenue and deferred revenue from collaboration, license, and research agreements Collaboration Revenue (in thousands) | Agreement | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Bristol Myers Squibb Company (BMS) | $3,847 | $2,045 | $5,420 | $4,500 | | Eli Lilly and Company (Lilly) | $0 | $0 | $0 | $1,100 | | **Total Collaboration Revenue** | **$3,847** | **$2,045** | **$5,420** | **$5,600** | - Revenue from the BMS Collaboration Agreement increased for both the three and six months ended June 30, 2025[39](index=39&type=chunk) - Deferred revenue related to collaboration agreements decreased from **$58.9 million** at December 31, 2024, to **$53.5 million** at June 30, 2025[41](index=41&type=chunk) [6. Composition of Certain Consolidated Financial Statement Items](index=13&type=section&id=6.%20Composition%20of%20Certain%20Consolidated%20Financial%20Statement%20Items) This note provides a breakdown of specific balance sheet items, including prepaid assets and other current assets Prepaid and Other Current Assets (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :-------------------------- | :------------ | :---------------- | | Prepaid assets | $15,976 | $12,571 | | Interest receivable | $8,540 | $9,447 | | Other current assets | $42,900 | $18,775 | | **Total** | **$67,416** | **$40,793** | - Other current assets increased significantly, including reimbursable tenant improvements rising from **$7.1 million** to **$31.1 million**[42](index=42&type=chunk) - The company recorded approximately **$87.0 million** in nonrefundable reservation fees with a Contract Manufacturing Organization (CMO) for future production batches (2026-2028)[44](index=44&type=chunk) [7. Commitments and Contingencies](index=14&type=section&id=7.%20Commitments%20and%20Contingencies) This note discloses the company's future lease commitments and any material litigation matters - The company has future lease commitments of approximately **$80.0 million** for its corporate headquarters sublease (payments starting Q3 2025) and **$53.7 million** for an amended sublease for an adjacent building (payments starting April 2026)[46](index=46&type=chunk)[47](index=47&type=chunk) - A **$2.5 million** letter of credit is maintained for the benefit of the sublandlord[48](index=48&type=chunk) - No material litigation matters are currently outstanding for which liabilities have been accrued[49](index=49&type=chunk) [8. Stockholders' Equity](index=15&type=section&id=8.%20Stockholders'%20Equity) This note details changes in stockholders' equity and stock-based compensation expenses Stock-Based Compensation Expense (in thousands) | Expense Type | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $9,490 | $6,529 | $18,609 | $12,266 | | General and administrative | $8,169 | $6,283 | $16,786 | $10,852 | | **Total** | **$17,659** | **$12,812** | **$35,395** | **$23,118** | - Unrecognized compensation cost as of June 30, 2025, includes **$121.0 million** for time-based options, **$68.0 million** for restricted stock units, and **$34.2 million** for performance stock units[51](index=51&type=chunk) - The company issued 92,348 shares under the Employee Stock Purchase Plan (ESPP) during the six months ended June 30, 2025[52](index=52&type=chunk) [9. Segment Information](index=16&type=section&id=9.%20Segment%20Information) This note confirms the company operates as a single segment and provides related financial information - The company operates as a single operating and reportable segment[54](index=54&type=chunk) - The Chief Executive Officer (CODM) uses consolidated net loss to assess performance and allocate resources[54](index=54&type=chunk) Cash, Cash Equivalents and Marketable Securities (in thousands) | Date | Amount | | :----------- | :--------- | | June 30, 2025 | $1,183,144 | | December 31, 2024 | $1,501,497 | [10. Subsequent Events](index=16&type=section&id=10.%20Subsequent%20Events) This note discloses significant events that occurred after the reporting period, including stock sales and new agreements - From July 1, 2025, through August 7, 2025, the company sold 5,646,583 shares of common stock, generating **$185.5 million** in net proceeds[56](index=56&type=chunk) - On August 1, 2025, the company entered into a commercial manufacturing agreement with a CMO, incurring approximately **$620.0 million** in future unconditional purchase obligations from 2026 through 2028[57](index=57&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=16&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's financial condition, operational results, biopharmaceutical pipeline progress, and liquidity [Overview](index=17&type=section&id=Overview) This overview highlights the company's biopharmaceutical focus, clinical trial progress, and strategic advancements - Avidity Biosciences is a biopharmaceutical company developing Antibody Oligonucleotide Conjugates (AOCs) for rare diseases, with three programs in potentially registrational trials[60](index=60&type=chunk) - The company is expanding into precision cardiology with two wholly-owned development candidates: AOC 1072 (PRKAG2 Syndrome) and AOC 1086 (PLN cardiomyopathy)[76](index=76&type=chunk) - Avidity is building global commercial infrastructure for potential product launches for DMD, DM1, and FSHD starting in 2026[77](index=77&type=chunk) [Delpacibart zotadirsen (del-zota) for the treatment of DMD44](index=18&type=section&id=Delpacibart%20zotadirsen%20(del-zota)%20for%20the%20treatment%20of%20DMD44) This section details del-zota's development for DMD44, including clinical trials and FDA Breakthrough Therapy designation - Del-zota, for Duchenne muscular dystrophy (DMD44), is in Phase 2 development (EXPLORE44-OLE™ study) and received FDA Breakthrough Therapy designation in July 2025[60](index=60&type=chunk)[61](index=61&type=chunk)[62](index=62&type=chunk) - Positive top-line data from the Phase 1/2 EXPLORE44 trial showed statistically significant improvements across key biomarkers and favorable safety[63](index=63&type=chunk) - The company plans to submit its first Biologics License Application (BLA) for del-zota at year-end 2025, using data from EXPLORE44 and EXPLORE44-OLE studies[63](index=63&type=chunk)[67](index=67&type=chunk) [Delpacibart etedesiran (del-desiran) for the treatment of myotonic dystrophy type 1 (DM1)](index=18&type=section&id=Delpacibart%20etedesiran%20(del-desiran)%20for%20the%20treatment%20of%20myotonic%20dystrophy%20type%201%20(DM1)) This section details del-desiran's development for DM1, including the HARBOR trial and anticipated data - Del-desiran, for myotonic dystrophy type 1 (DM1), is in the global Phase 3 HARBOR™ trial, with enrollment completed in July 2025[60](index=60&type=chunk)[64](index=64&type=chunk)[66](index=66&type=chunk) - Data from the MARINA-OLE™ trial showed reversal of disease progression across multiple endpoints, including hand function and muscle strength[64](index=64&type=chunk) - Topline data from the HARBOR study is anticipated in the second quarter of 2026, with marketing application submissions expected to start in the second half of 2026[72](index=72&type=chunk) [Delpacibart braxlosiran (del-brax) for the treatment of facioscapulohumeral muscular dystrophy (FSHD)](index=19&type=section&id=Delpacibart%20braxlosiran%20(del-brax)%20for%20the%20treatment%20of%20facioscapulohumeral%20muscular%20dystrophy%20(FSHD)) This section details del-brax's development for FSHD, including registrational trials and regulatory pathways - Del-brax, for facioscapulohumeral muscular dystrophy (FSHD), is in the registrational FORTITUDE biomarker cohort, Phase 2 FORTITUDE-OLE™, and Phase 3 FORTITUDE-3™ trials[60](index=60&type=chunk)[68](index=68&type=chunk) - FDA has aligned on accelerated and full approval pathways for del-brax, with positive topline Phase 1/2 FORTITUDE data showing consistent improvement in functional mobility, muscle strength, and rapid reduction in biomarkers[69](index=69&type=chunk)[73](index=73&type=chunk) - The company plans to submit a BLA for accelerated approval in the second half of 2026, supported by data from FORTITUDE trials[69](index=69&type=chunk) [Company Advancements](index=20&type=section&id=Company%20Advancements) This section highlights pipeline expansion into precision cardiology and commercial infrastructure development - Avidity is expanding its AOC pipeline beyond rare neuromuscular disorders into precision cardiology, with candidates AOC 1072 and AOC 1086[76](index=76&type=chunk) - The company is developing a global commercial infrastructure in preparation for potential product launches for DMD, DM1, and FSHD starting in 2026[77](index=77&type=chunk) - Since inception, the company has incurred operating losses, with a net loss of **$273.1 million** for the six months ended June 30, 2025, and an accumulated deficit of **$1.2 billion**[79](index=79&type=chunk) [Components of Results of Operations](index=21&type=section&id=Components%20of%20Results%20of%20Operations) This section explains the key components of the company's revenue and expenses, and their expected trends - Revenue is derived from license and research collaboration agreements; no product sales revenue is expected until regulatory approval[83](index=83&type=chunk)[84](index=84&type=chunk) - Research and development expenses are expected to increase significantly due to ongoing preclinical studies and clinical trials, including external and internal costs[87](index=87&type=chunk)[89](index=89&type=chunk) - General and administrative expenses are also projected to increase to support expanded R&D activities, commercial readiness, and corporate functions[92](index=92&type=chunk) [Results of Operations (Comparison of the Three and Six Months Ended June 30, 2025 and 2024)](index=23&type=section&id=Results%20of%20Operations%20(Comparison%20of%20the%20Three%20and%20Six%20Months%20Ended%20June%2030,%202025%20and%202024)) This section analyzes the company's financial performance for the three and six months ended June 30, 2025 and 2024 Key Financial Results (in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Revenue | $3,847 | $2,045 | $5,420 | $5,588 | | Research and development expenses | $138,125 | $63,940 | $237,615 | $130,772 | | General and administrative expenses | $36,864 | $20,731 | $70,464 | $34,629 | | Other income | $13,827 | $11,833 | $29,571 | $20,165 | - Research and development expenses increased by **$74.2 million** (three months) and **$106.8 million** (six months) year-over-year, driven by clinical trial progression, manufacturing costs, and personnel[97](index=97&type=chunk) - General and administrative expenses increased by **$16.1 million** (three months) and **$35.8 million** (six months) due to higher personnel costs and professional fees[98](index=98&type=chunk) [Liquidity and Capital Resources](index=24&type=section&id=Liquidity%20and%20Capital%20Resources) This section discusses the company's cash position, capital requirements, and future funding strategies - As of June 30, 2025, the company had **$1.2 billion** in cash, cash equivalents, and marketable securities, expected to fund operations for at least 12 months[103](index=103&type=chunk) - Future capital requirements are substantial and will depend on the progress of product candidates, manufacturing, regulatory outcomes, and commercialization efforts[104](index=104&type=chunk)[105](index=105&type=chunk) - The company plans to finance future cash needs through equity offerings, debt financings, or collaborations, as product sales revenue is not anticipated in the immediate term[104](index=104&type=chunk) [Critical Accounting Estimates](index=27&type=section&id=Critical%20Accounting%20Estimates) This section addresses the company's critical accounting estimates and any material changes - No material changes to critical accounting estimates were reported as of June 30, 2025, compared to the annual report on Form 10-K for the year ended December 31, 2024[111](index=111&type=chunk) [Contractual Obligations and Commitments](index=27&type=section&id=Contractual%20Obligations%20and%20Commitments) This section outlines the company's significant contractual obligations and commitments - The company has aggregate future lease commitments of approximately **$80.0 million** for its corporate headquarters sublease and **$53.7 million** for an amended sublease for an adjacent building[112](index=112&type=chunk) - No other material changes to contractual obligations were reported as of June 30, 2025, outside the ordinary course of business[112](index=112&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=27&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section states no material changes in market risk as of June 30, 2025, compared to prior annual report disclosures - No material changes in market risk were reported as of June 30, 2025, compared to the disclosures in the annual report on Form 10-K for the year ended December 31, 2024[114](index=114&type=chunk) [Item 4. Controls and Procedures](index=27&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls were effective as of June 30, 2025, with no material changes in internal control - Management concluded that the company's disclosure controls and procedures were effective at the reasonable assurance level as of June 30, 2025[116](index=116&type=chunk) - There have been no material changes in internal control over financial reporting during the quarter ended June 30, 2025[117](index=117&type=chunk) PART II – OTHER INFORMATION [Item 1. Legal Proceedings](index=28&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings - The company is not currently subject to any material legal proceedings[119](index=119&type=chunk) [Item 1A. Risk Factors](index=28&type=section&id=Item%201A.%20Risk%20Factors) This section states no material changes to risk factors previously disclosed in the annual report on Form 10-K - No material changes to the risk factors set forth in the annual report on Form 10-K for the year ended December 31, 2024, were reported[120](index=120&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=28&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales or issuer repurchases of equity securities during the period - No unregistered sales of equity securities occurred during the period[121](index=121&type=chunk) - No issuer repurchases of equity securities occurred during the period[122](index=122&type=chunk) [Item 3. Defaults Upon Senior Securities](index=28&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is not applicable to the company - This item is not applicable[123](index=123&type=chunk) [Item 4. Mine Safety Disclosures](index=28&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - This item is not applicable[124](index=124&type=chunk) [Item 5. Other Information](index=28&type=section&id=Item%205.%20Other%20Information) The Chief Human Resources Officer adopted a Rule 10b5-1 trading arrangement during the quarter - Teresa McCarthy, Chief Human Resources Officer, adopted a Rule 10b5-1 trading arrangement on April 11, 2025, to sell 120,000 shares by July 31, 2026[126](index=126&type=chunk) [Item 6. Exhibits](index=29&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the Form 10-Q, including corporate governance documents and certifications - Exhibits include Amended and Restated Certificate of Incorporation, Bylaws, Form of Common Stock Certificate, Form of Pre-Funded Warrant, CEO/CFO Certifications (31.1, 31.2, 32.1, 32.2), and Inline XBRL documents[127](index=127&type=chunk) SIGNATURES This section contains the official signatures of the company's executive officers, certifying the report - The report was signed on August 7, 2025, by Sarah Boyce, President, Chief Executive Officer and Director, and Michael F. MacLean, Chief Financial Officer[131](index=131&type=chunk)

Planned del-zota BLA submission at year end 2025 for DMD44 on track to be Avidity's first BLA submission On track for three potential BLA submissions over a 12-month period Strong balance sheet and cash runway to mid-2027 enabling global commercial launch readiness; first potential commercial launch in U.S. in 2026 SAN DIEGO, August 7, 2025 /PRNewswire/-- Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleoti ...

Core Viewpoint - Avidity Biosciences is experiencing significant market interest due to potential acquisition talks with Novartis, leading to a notable increase in its stock price by 26% [3][4]. Group 1: Company Overview - Avidity Biosciences focuses on developing Antibody Oligonucleotide Conjugates (AOCs) for rare diseases, with a current market capitalization of $5.8 billion [4]. - The company has a strong cash position of approximately $1.4 billion, providing funding into mid-2027 [7]. - Avidity is advancing three AOCs in clinical development, targeting Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy Type 1 (DM1), and Facioscapulohumeral Muscular Dystrophy (FSHD) [26][39]. Group 2: Clinical Development and Pipeline - Avidity's lead therapy, del-zota, for DMD has received breakthrough therapy designation from the FDA and is expected to submit a Biologics License Application (BLA) by the end of 2025 [5][7]. - The company is preparing for three planned BLA submissions within 12 months, with ongoing registrational trials [7]. - Avidity's AOC platform has successfully delivered RNA to muscle tissue, marking a significant advancement in RNA therapy [7][39]. Group 3: Recent Developments and Collaborations - Avidity recently entered a collaboration with Bristol Myers Squibb (BMS) for the development of up to five cardiovascular targets, with potential payments totaling $2.3 billion [18][19]. - The collaboration includes an upfront payment of $100 million and milestone payments based on development progress [19]. - Avidity's stock surged by 40% following the announcement of this partnership, reflecting strong market confidence in its pipeline and strategic direction [18][19].

Core Viewpoint - Novartis is reportedly proposing to acquire Avidity Biosciences Inc. to expand its pharmaceutical pipeline, leading to a significant increase of over 24% in Avidity's stock price [1]. Company Overview - Avidity Biosciences, Inc. (NASDAQ: RNA) is a biopharmaceutical company focused on developing a new class of RNA therapies known as Antibody Oligonucleotide Conjugates (AOC™) [3][12]. - The company has received Breakthrough Therapy designation from the FDA for its drug delpacibart zotadirsen (del-zota), aimed at treating Duchenne Muscular Dystrophy (DMD) patients with exon 44 skipping mutations [3][6]. Drug Development and Clinical Trials - Del-zota is currently being evaluated in the Phase 2 EXPLORE44-OLE trial, which is an open-label extension study for DMD patients [4][8]. - The Phase 1/2 EXPLORE44 trial demonstrated significant improvements in biomarkers, including increased dystrophin production and decreased creatine kinase levels, indicating a favorable safety profile [4][11]. - Avidity plans to submit a Biologics License Application (BLA) for del-zota by the end of 2025, with commercial preparations underway for a potential U.S. launch [4][6]. Disease Context - Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder characterized by progressive muscle degeneration due to the absence of dystrophin, leading to severe muscle weakness and a significantly reduced lifespan [9]. - DMD primarily affects males, with an incidence of approximately 1 in every 3,500 to 5,000 male births globally [9]. Technology and Innovation - Avidity's AOC platform combines the specificity of monoclonal antibodies with the precision of oligonucleotide therapies, enabling targeted delivery of RNA to muscle tissues [12]. - The company is advancing clinical development projects for three rare neuromuscular diseases: DM1, DMD, and FSHD, while also exploring candidates for rare genetic cardiomyopathies [12].

-- Topline data readout from HARBOR study anticipated in Q2 2026 -- -- Marketing application submissions for del-desiran including in U.S., EU and Japan anticipated to start in H2 2026; on track to potentially be the first globally approved drug for DM1-- -- On track to share updates from ongoing MARINA-OLE™ trial of del-desiran including long-term 4 mg/kg efficacy and safety data in Q4 2025 -- SAN DIEGO, July 28, 2025 /PRNewswire/ -- Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company comm ...