Summary of Avidity Biosciences FY Conference Call Industry Overview - The focus of the conference was on muscular dystrophies, particularly Duchenne Muscular Dystrophy (DMD) and Facioscapulohumeral Muscular Dystrophy (FSHD) [1][24] - DMD is a multibillion-dollar market projected to grow to $3 billion by 2033 [1] - Other muscular dystrophies like DM1 and FSHD currently lack approved therapies, but promising treatments are in development [1] Key Points on DMD Treatments - Current DMD treatments include first-generation PMO exon-skipping therapies, new gene therapies, and steroids, but significant unmet needs remain, especially for non-ambulatory patients [2][3] - The FDA's approval of the first PMO exon-skipping therapy is seen as a watershed moment that opened investment in the DMD space [3][4] - The approval set a low regulatory bar, leading to increased investment and development of new therapies [3][5] - New technologies, such as Antibody Oligonucleotide Conjugates (AOCs), are being developed to improve dystrophin production and functional benefits [9][10] Clinical Data and Efficacy - AOCs have shown promising results, with 40% exon skipping and a 25% increase in dystrophin levels [10][11] - Creatine kinase (CK) levels, a measure of muscle damage, have returned to normal for many patients, indicating functional improvement [11][14] - The FDA's low bar for approval has allowed for a variety of therapies to enter the market, but safety and efficacy remain critical [16][19] Gene Therapy Insights - Sarepta Therapeutics' Elevidys gene therapy faced scrutiny but initially showed strong uptake due to the unmet need in DMD [16] - Avidity's approach focuses on optimizing the gene therapy construct and manufacturing processes to improve safety and efficacy [18][19] - The company has developed a microdystrophin that closely resembles natural dystrophin, aiming for higher expression and longer half-life [17][18] FSHD Developments - FSHD is characterized by the aberrant expression of the DUX4 transcription factor, which is toxic to muscle cells [26][27] - Avidity is using AOC technology to deliver silencing RNA to inhibit DUX4 expression, showing early signs of clinical benefit [27][30] - The identification of a circulating biomarker (C-DUX) for DUX4 may facilitate accelerated approval processes [29][32] Market Dynamics and Future Outlook - The DMD market is expected to see multiple effective therapies, with opportunities for various players due to the large unmet need [41][42] - The potential for combination therapies is highlighted, with patients and physicians open to using multiple modalities for better outcomes [47][48] - The FDA's accelerated approval pathway is anticipated to remain in place to encourage ongoing innovation in the muscular dystrophy space [49] Conclusion - The conference highlighted the significant advancements in genetic medicine for muscular dystrophies, the importance of regulatory pathways, and the potential for new therapies to address unmet needs in DMD and FSHD [1][41][49]

Core Insights - Avidity Biosciences, Inc. will present late-breaking oral and poster presentations at the 30th Annual International Congress of the World Muscle Society (WMS) from October 7-11, 2025, in Vienna, Austria [1][2] - The data to be presented will build on positive findings from September 2025, showing reversal of disease progression and significant improvement in functional measures for Duchenne muscular dystrophy (DMD) patients treated with delpacibart zotadirsen (del-zota) [2][7] - Del-zota is still investigational and has not received FDA approval, with its safety and efficacy yet to be established [2][5] Presentation Details - Oral presentation by Kevin M. Flanigan, M.D., scheduled for October 11, 2025, focusing on functional and patient-reported outcomes in DMD patients [7] - Poster presentation by Aravindhan Veerapandiyan, M.D., on October 8, 2025, highlighting increased dystrophin and improved muscle integrity markers in DMD patients [7] Company Overview - Avidity Biosciences is focused on developing a new class of RNA therapeutics known as Antibody Oligonucleotide Conjugates (AOCs), aiming to improve treatment for rare muscle diseases [5] - The company has demonstrated successful targeted delivery of RNA into muscle and is advancing clinical programs for myotonic dystrophy type 1, Duchenne muscular dystrophy, and facioscapulohumeral muscular dystrophy [5] - Avidity is also expanding its pipeline to include precision cardiology candidates and programs in cardiology and immunology through partnerships [5]

Core Insights - Avidity Biosciences is positioned to lead in rare neuromuscular diseases with significant milestones expected in 2025, including the first BLA submission for its AOC platform [1][2] - The company has a strong financial position with approximately $1.5 billion in cash as of the end of 2024, enabling continued development and commercialization efforts [2][14] - Avidity is preparing for three potential product launches for Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and facioscapulohumeral muscular dystrophy (FSHD) starting in 2026 [1][4] Clinical Programs - Avidity's del-zota for DMD44 is on track for a BLA submission by the end of 2025, with positive initial data showing a 25% increase in near full-length dystrophin production [4][10] - The EXPLORE44-OLE study has completed enrollment, and data from both the EXPLORE44 and EXPLORE44-OLE studies will support the BLA submission [4][3] - Del-desiran for DM1 is progressing with the completion of enrollment in the Phase 3 HARBOR trial expected by mid-2025, and the FDA has granted breakthrough therapy designation for this candidate [4][10] Financial Performance - For the fourth quarter of 2024, Avidity reported a net loss of $102.3 million, compared to a net loss of $60.4 million in the fourth quarter of 2023 [14][16] - Research and development expenses increased to $95.6 million in Q4 2024 from $52.8 million in Q4 2023, driven by advancements in clinical programs [14][16] - Collaboration revenues for Q4 2024 were $3.0 million, up from $2.2 million in Q4 2023, primarily from partnerships with Bristol Myers Squibb and Eli Lilly [14][16] Strategic Initiatives - Avidity is expanding its global commercial infrastructure and team to support upcoming product launches and enhance its AOC technology [2][4] - The company is also broadening its pipeline into precision cardiology, with two new candidates for PRKAG2 syndrome and PLN cardiomyopathy [10][11] - Avidity's proprietary AOC platform aims to revolutionize RNA therapeutics by combining the specificity of monoclonal antibodies with oligonucleotide therapies [11]