Core Insights - Avidity Biosciences announced FDA alignment on accelerated and full approval pathways for delpacibart braxlosiran (del-brax) in facioscapulohumeral muscular dystrophy (FSHD) [1] - The company will present two oral and one poster presentations at the 32nd Annual FSHD Society International Research Congress in Amsterdam on June 12-13, 2025 [1][2] - Key presentations will include topline data from the FORTITUDE trial and characterization of a novel DUX4-regulated circulating biomarker [1][6] Company Overview - Avidity Biosciences focuses on delivering a new class of RNA therapeutics known as Antibody Oligonucleotide Conjugates (AOCs™) [4] - The company aims to revolutionize RNA therapy by combining the specificity of monoclonal antibodies with the precision of oligonucleotide therapies [4] - Avidity is advancing clinical development programs for three rare neuromuscular diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD), and facioscapulohumeral muscular dystrophy (FSHD) [4] Upcoming Presentations - Jeffrey M. Statland, M.D. will present topline data from the dose escalation cohorts of the FORTITUDE trial on June 13, 2025 [6] - Stephen Tapscott, M.D., Ph.D. will present findings on a DUX4-regulated circulating biomarker on June 12, 2025 [6] - A poster presentation is also scheduled for June 12, 2025 [6]

Summary of Avidity Biosciences Conference Call Company and Industry Overview - **Company**: Avidity Biosciences - **Industry**: RNA therapeutics, specifically targeting Facioscapulohumeral Muscular Dystrophy (FSHD) Key Points and Arguments 1. **FDA Confirmation**: Avidity has received confirmation from the FDA regarding the accelerated approval pathway for their DELBRAX program targeting FSHD, which is significant for the FSHD community [5][6][68] 2. **Clinical Study Updates**: The company is presenting twelve-month top-line data from the FORTITUDE study and has initiated a global confirmatory Phase III study named FORWARD [6][8][68] 3. **Primary Endpoint**: The primary endpoint for the FORTITUDE biomarker study is the reduction of circulating biomarkers, specifically CDAS [5][6][68] 4. **Patient Impact**: The presentation highlighted the profound impact of FSHD on patients' lives, emphasizing the urgency of developing effective treatments [4][70] 5. **Study Design**: The FORTITUDE study is a double-blind, placebo-controlled trial with a one-year duration, focusing on safety and pharmacokinetics, while the FORWARD study will last eighteen months [10][58][62] 6. **Safety Profile**: DELBRAX has shown a favorable long-term safety profile, with no serious adverse events related to the study drug reported [13][14] 7. **Biomarker Significance**: The circulating biomarker CDUX is significantly elevated in FSHD patients and is linked to disease progression. DELBRAX treatment led to rapid reductions in CDUX levels [42][43][55] 8. **Patient Reported Outcomes**: Improvements in strength, mobility, and quality of life were reported by patients treated with DELBRAX, indicating its potential effectiveness [38][39][55] 9. **Regulatory Pathway**: The FDA has provided written confirmation that an accelerated approval path is open, with CDUX as the primary endpoint for the FORTITUDE biomarker cohort [56][68] 10. **Commercial Strategy**: Avidity is building its commercial organization in preparation for three successive product launches in the same therapeutic area, which is expected to enhance operational efficiency [85][86] Additional Important Content - **Patient Testimonials**: Personal stories from patients highlighted the importance of preserving function and improving quality of life, showcasing the emotional and physical benefits of the treatment [39][70] - **Future Directions**: The company plans to leverage the insights gained from the ongoing studies to refine their approach and ensure robust data for regulatory submissions [60][66][92] - **Community Engagement**: Avidity emphasizes the importance of engaging with the FSHD community and addressing their needs through effective treatment options [70][94] This summary encapsulates the critical updates and insights shared during the conference call, focusing on the advancements in Avidity Biosciences' DELBRAX program and its implications for patients with FSHD.

Del-brax Development and Regulatory Pathway - FDA has confirmed an accelerated approval pathway for delpacibart braxlosiran (del-brax) in the US [8] - The primary endpoint for accelerated approval is the reduction in the circulating biomarker cDUX [10, 59, 76] - A global confirmatory Phase 3 FORWARD trial has been initiated with 200 participants in a 1:1 randomized, double-blind, placebo-controlled design [10, 79] - The company anticipates topline data from the biomarker cohort of the FORTITUDE trial in Q2 2026 and a BLA submission in H2 2026 [10, 74] - The confirmatory Phase 3 FORWARD trial is designed to support full approval, with approximately 45 global sites [80, 83] FORTITUDE Trial Data - 12-month topline data from the FORTITUDE trial showed improved functional mobility in del-brax treated participants compared to placebo, as measured by 10MWRT and TUG [35, 39, 57] - Participants treated with del-brax also demonstrated improved muscle strength measured by QMT and improved upper limb function measured by RWS compared to placebo [42, 44, 57] - Del-brax showed a favorable long-term safety and tolerability profile in the FORTITUDE trial and its open-label extension (OLE) [10, 19, 57] - Over 60% of patients express that slowing or stopping the loss of muscle function would be the most meaningful outcome [30] cDUX Biomarker - cDUX is elevated 6- to 9-fold in people living with FSHD compared to healthy volunteers [59] - Del-brax treatment resulted in rapid and statistically significant reductions in cDUX and creatine kinase (CK) levels [59, 64]

Core Insights - Avidity Biosciences announced positive topline data from the Phase 1/2 FORTITUDE™ program for delpacibart braxlosiran (del-brax) in treating Facioscapulohumeral Muscular Dystrophy (FSHD), showing improvements in function, strength, and patient-reported outcomes compared to placebo [1][3][6] - The company plans to submit a Biologics License Application (BLA) for accelerated approval in the second half of 2026 [1][3] - Del-brax is the first investigational therapy targeting the underlying cause of FSHD by directly addressing the DUX4 gene, with no approved therapies currently available for this condition [2][13] Group 1: Clinical Data and Results - The FORTITUDE™ trial included a randomized, placebo-controlled, double-blind study evaluating 39 participants on doses of 2 mg/kg or 4 mg/kg of del-brax over 12 months [5][10] - Results indicated consistent improvements in functional mobility and muscle strength, as measured by the 10-Meter Walk-Run test, Timed Up and Go, and quantitative muscle testing [6][9] - Significant reductions in biomarkers such as KHDC1L and creatine kinase were observed, indicating muscle damage [6][7] Group 2: Safety and Regulatory Pathway - Del-brax demonstrated favorable long-term safety and tolerability, with most adverse events being mild or moderate, and no serious adverse events reported [7][9] - The U.S. FDA has opened the accelerated approval regulatory pathway for del-brax, and a global Phase 3 FORWARD™ study has been initiated [3][4] Group 3: Future Developments - The ongoing biomarker cohort of the FORTITUDE trial aims to assess the impact of del-brax on KHDC1L levels, with topline data expected in Q2 2026 [7][11] - Avidity is advancing its clinical development pipeline, focusing on RNA therapeutics through its proprietary Antibody Oligonucleotide Conjugates (AOCs™) platform [16]

Avidity Biosciences Conference Call Summary Company Overview - **Company**: Avidity Biosciences - **Industry**: Biotechnology, specifically RNA therapeutics Key Points and Arguments FDA Interactions - Avidity has not experienced any changes in interactions with the FDA despite recent staffing changes within the agency, maintaining consistent communication over several years on three different programs [5][6][7] - The company emphasizes the importance of advocacy for the biotech ecosystem to ensure the FDA remains a premier review agency [6][7] Intellectual Property and Manufacturing - Avidity's intellectual property (IP) is primarily based in the US, covering all three of its drugs and aspects of its technology [8] - The company aims to manufacture drugs in the US for the US market, Europe for Europe, and has established a supply chain to eliminate redundancies [9] Product Pipeline and Development - Avidity is focused on revolutionizing the RNA space, with late-stage development in three programs targeting myotonic dystrophy, FSHD, and exon skipping [11] - The company plans to file its first Biologics License Application (BLA) for Del Zotia by the end of the year [11] - Enrollment for the HARVEST study in myotonic dystrophy is on track to complete by mid-year [12] FSHD Program - Avidity is the only company with a drug in development for FSHD, with ongoing discussions with the FDA regarding accelerated approval pathways [13][14] - The company has seen significant interest in FSHD due to its large patient population, comparable in size to cystic fibrosis [15] Clinical Data and Efficacy - Preliminary data from the FORTITUDE study shows over 50% reductions in DUX4 regulated genes and over 25% changes in circulating biomarkers, indicating significant muscle health improvements [17][18] - The company has chosen a lower dose of 2 mg/kg for its accelerated approval pathway based on safety and efficacy data [24][25] Unmet Medical Need - FSHD is described as a devastating disease with a high unmet medical need, justifying the use of the Accelerated Approval Pathway [33] - Patient testimonials highlight the severe impact of FSHD on daily life, emphasizing the need for effective treatments [35][38] Myotonic Dystrophy Program - Avidity's myotonic dystrophy program is in phase three, with an update expected in Q4 of this year [44] - The company has aligned with global regulators on study design, which supports both efficacy and safety for potential approval [51] Competitive Landscape - Avidity is aware of competitors in the DM1 space but emphasizes its rigorous approach to drug development and the importance of demonstrating functional changes to payers [56][58] Additional Important Content - The company is focused on ensuring that its drugs can be reimbursed effectively, which is a critical aspect of its phase three study designs [52] - Avidity's commitment to patient engagement is evident through its patient advisory council, which informs clinical trial design [35] This summary encapsulates the key insights from the Avidity Biosciences conference call, highlighting the company's strategic direction, product pipeline, and the critical unmet needs in the diseases it targets.

Company Performance - Avidity Biosciences reported a quarterly loss of $0.90 per share, slightly worse than the Zacks Consensus Estimate of a loss of $0.88, and compared to a loss of $0.79 per share a year ago, indicating a negative earnings surprise of -2.27% [1] - The company posted revenues of $1.57 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 46.68%, and down from $3.54 million in the same quarter last year [2] - Over the last four quarters, Avidity has surpassed consensus EPS estimates three times, but has only topped consensus revenue estimates once [2] Market Comparison - Avidity Biosciences shares have declined approximately 10% since the beginning of the year, while the S&P 500 has seen a decline of -4.3% [3] Future Outlook - The current consensus EPS estimate for the upcoming quarter is -$0.86 on revenues of $2.1 million, and for the current fiscal year, it is -$3.90 on revenues of $9.25 million [7] - The estimate revisions trend for Avidity Biosciences is currently favorable, leading to a Zacks Rank 2 (Buy) for the stock, suggesting it is expected to outperform the market in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Avidity belongs, is currently in the top 33% of over 250 Zacks industries, indicating a positive outlook for stocks within this sector [8]

Financial Performance - The company reported net losses of $322.3 million and $212.2 million for the years ended December 31, 2024 and 2023, respectively, with an accumulated deficit of $1.0 billion as of March 31, 2025[81][82]. - Revenue for the three months ended March 31, 2025, was $1.573 million, a decrease of $1.970 million compared to the same period in 2024[96][97]. - The company has not generated any revenue from product sales since its inception in 2012 and plans to finance future needs through equity offerings and collaborations[80][83]. - Other income increased by $7.4 million for the three months ended March 31, 2025, due to higher interest income from marketable securities and cash[101]. - The company reported a net increase in cash, cash equivalents, and restricted cash of $34.3 million in Q1 2025, down from $286.3 million in Q1 2024, reflecting a decrease of $251.9 million[108]. Cash and Funding - The company has approximately $1.4 billion in cash, cash equivalents, and marketable securities as of March 31, 2025, expected to fund operations for at least 12 months[83]. - The company had cash, cash equivalents, and marketable securities of $1.4 billion as of March 31, 2025, sufficient to fund operations for at least 12 months[105]. - Net cash used in operating activities increased to $124.8 million for Q1 2025 from $70.4 million in Q1 2024, primarily due to higher research and development costs[109]. - Net cash provided by investing activities was $157.2 million in Q1 2025, driven by $330.2 million from maturities of marketable securities, offset by $169.3 million in purchases of marketable securities[110]. - Net cash provided by financing activities decreased significantly to $1.9 million in Q1 2025 from $389.4 million in Q1 2024, which included $244.2 million from common stock sales[111]. - The company terminated the 2022 Sales Agreement in August 2024 and entered into a new agreement allowing for the sale of up to $400 million in common stock[102][103]. Research and Development - Del-desiran is currently in Phase 3 development with the global HARBOR trial, involving approximately 150 participants aged 16 and older[70]. - The Phase 1/2 EXPLORE44 trial for del-zota demonstrated statistically significant improvements across key biomarkers, with a selected dose of 5 mg/kg every six weeks for future studies[72][74]. - Enrollment in the FORTITUDE trial for del-brax has been completed with a total of 51 participants, assessing safety and potential accelerated approval[76]. - The company plans to submit its first Biologics License Application (BLA) for del-zota by the end of 2025[74]. - Del-desiran has been granted Breakthrough Therapy designation by the FDA for the treatment of DM1, and all three programs have received Orphan Designation[67]. - The ongoing MARINA-OLE trial for del-desiran is expected to provide long-term safety data in Q4 2025[73]. - The company is advancing its AOC pipeline to develop treatments for rare diseases, including two candidates targeting rare genetic cardiomyopathies[78]. - The company anticipates ongoing increases in research and development expenses as it advances preclinical and clinical programs[89]. - Research and development expenses increased by $32.7 million to $99.490 million for the three months ended March 31, 2025, primarily due to increased external costs and higher personnel costs[99]. Expenses - General and administrative expenses rose by $19.7 million to $33.600 million for the three months ended March 31, 2025, mainly due to higher personnel costs and professional fees[100]. - The increase in cash used in operations is attributed to rising general and administrative expenses alongside research and development costs[109]. Collaborations and Agreements - The company entered into a collaboration with Bristol Myers Squibb, receiving approximately $100 million upfront, including $60 million in cash and $40 million from the purchase of common stock[84]. - The company is eligible for up to $1.35 billion in R&D milestone payments and $825 million in commercial milestone payments under the BMS Agreements[84]. Market and Risk - As of March 31, 2025, there have been no material changes in market risk compared to the previous year[115]. - The company continues to evaluate critical accounting estimates, with no material changes reported as of March 31, 2025[112]. - The company has not disclosed any new strategies or market expansions in the current report[115].

Financial Performance - Avidity reported a cash balance of approximately $1.4 billion as of March 31, 2025, supporting its late-stage clinical programs and commercial launch preparations[5]. - Collaboration revenues for Q1 2025 were $1.6 million, down from $3.5 million in Q1 2024, primarily due to the absence of revenue recognition from a prior year partnership[5]. - The net loss for Q1 2025 was $115.8 million, compared to a net loss of $68.9 million in Q1 2024, with a net loss per share of $0.90[13]. - Total operating expenses for Q1 2025 were $133.1 million, significantly higher than $80.7 million in Q1 2024[13]. Research and Development - Research and development expenses increased to $99.5 million in Q1 2025, compared to $66.8 million in Q1 2024, driven by advancements in del-desiran, del-brax, and del-zota[6]. - Avidity plans to submit its first Biologics License Application (BLA) for del-zota by the end of 2025, following positive topline data from the EXPLORE44 trial[2]. - The company is on track to share key regulatory updates for del-brax in Q2 2025, including a potential accelerated approval path in the U.S.[2]. - Enrollment for the ongoing Phase 3 HARBOR trial for del-desiran is expected to be completed by mid-2025, with marketing application submissions planned starting in 2026[3]. - Avidity completed enrollment for the FORTITUDE biomarker cohort for del-brax with 51 participants, ahead of original guidance[3]. Administrative Expenses - General and administrative expenses rose to $33.6 million in Q1 2025, up from $13.9 million in Q1 2024, mainly due to higher personnel costs[6].

Company Overview - Avidity Biosciences, Inc. (RNA) shares increased by 11.3% to close at $29.77, following a period of 6.4% loss over the past four weeks, indicating a significant turnaround in investor sentiment [1][2] Clinical Pipeline - The surge in stock price is attributed to positive investor sentiment regarding Avidity's rare diseases pipeline, with three investigational candidates currently in mid to late-stage clinical studies for different muscle disease indications [2] Financial Expectations - The company is expected to report a quarterly loss of $0.88 per share, reflecting an 11.4% year-over-year decline, with revenues projected at $2.95 million, down 16.7% from the previous year [3] - The consensus EPS estimate for the quarter has remained unchanged over the last 30 days, suggesting that stock price movements may not sustain without trends in earnings estimate revisions [4] Industry Context - Avidity Biosciences operates within the Zacks Medical - Biomedical and Genetics industry, where another company, Mirum Pharmaceuticals, Inc. (MIRM), closed 2.2% higher at $45, but has seen a -2.6% return over the past month [4] - Mirum Pharmaceuticals' consensus EPS estimate has changed by -3.2% over the past month to -$0.37, representing a 31.5% increase compared to the previous year's EPS [5]

Core Insights - Avidity Biosciences has completed enrollment in the FORTITUDE biomarker cohort for delpacibart braxlosiran (del-brax), targeting accelerated approval for treating facioscapulohumeral muscular dystrophy (FSHD) [1][2] - The company plans to present topline data from the FORTITUDE trial in Q2 2025, with regulatory alignment anticipated for a global Phase 3 trial [1][6] - Del-brax aims to be the first approved therapy for FSHD, a rare disease affecting approximately 45,000 to 87,000 individuals in the U.S. and EU [2][10] Company Overview - Avidity Biosciences focuses on RNA therapeutics, specifically Antibody Oligonucleotide Conjugates (AOCs™), to address rare neuromuscular diseases [11] - The company is advancing clinical programs for multiple conditions, including myotonic dystrophy type 1 and Duchenne muscular dystrophy, alongside FSHD [11] Clinical Trial Details - The FORTITUDE trial is a Phase 1/2 randomized, placebo-controlled study evaluating del-brax in 90 participants with FSHD [3] - The trial assesses safety, tolerability, pharmacokinetics, and pharmacodynamics, using biomarkers like DUX4-regulated genes and MRI measures [3][4] - The ongoing biomarker cohort evaluates del-brax at a dose of 2 mg/kg every six weeks for 12 months, focusing on changes in DUX4-regulated gene expression [5] Efficacy and Safety Data - Initial data from the 2 mg/kg dose of del-brax show over 50% reductions in DUX4-regulated genes, alongside trends of functional improvement and favorable safety [2][9] - The trial's design includes three dose cohorts, with the 2 mg/kg every six weeks identified for future studies [4] Future Plans - Avidity aims to share additional data and key milestones from the del-brax program in Q2 2025, including regulatory updates and topline results [2][6]