Summary of Avidity Biosciences Conference Call Company and Industry Overview - **Company**: Avidity Biosciences (NasdaqGM:RNA) - **Acquirer**: Novartis - **Industry**: Biotechnology, specifically focusing on RNA therapeutics and neuromuscular diseases Key Points and Arguments 1. **Acquisition Details**: Novartis proposes to acquire Avidity Biosciences for $72 per share, representing a 46% premium over Avidity's closing price on October 24, 2025 [4][25] 2. **Strategic Fit**: The acquisition is seen as a strong strategic fit for Novartis, enhancing its presence in neuromuscular diseases and expanding its RNA technology platform [4][6] 3. **Growth Potential**: The acquisition is expected to improve Novartis's medium and long-term growth profile, raising its CAGR from 5% to 6% for 2024 to 2029 [10][32] 4. **Late-Stage Assets**: Novartis will acquire three late-stage assets from Avidity, which are anticipated to unlock multiple near-term multibillion-dollar opportunities with launches expected before 2030 [8][32] 5. **Pipeline Overview**: The acquisition includes a preclinical neuromuscular pipeline and a platform for extrahepatic delivery of xRNAs, which is crucial for targeting RNA therapeutics beyond the liver [5][11] 6. **Disease Focus**: The focus is on high unmet needs in neuromuscular diseases, specifically targeting conditions like DM1 (myotonic dystrophy type 1) and FSHD (facioscapulohumeral muscular dystrophy) [7][20] 7. **Regulatory Designations**: Delbisiran for DM1 has received FDA orphan drug designation, FastTrack designation, and breakthrough therapy designation, indicating its potential as a transformative therapy [14][20] 8. **Market Potential**: The combined patient population for DM1 and FSHD is estimated to be between 125,000 and 167,000, with significant potential for market capture due to the lack of approved therapies [12][20] 9. **Financial Impact**: The total transaction value is estimated at $12 billion, with an enterprise value of $11 billion at the expected closing date in the first half of 2026 [25][32] 10. **Long-Term Outlook**: The assets acquired are expected to contribute significantly to Novartis's growth through the 2040s, with no loss of exclusivity (LOE) expected before 2042 [8][32] Additional Important Content 1. **Technology Platform**: Avidity's AOCs™ platform allows for targeted delivery of RNA therapeutics to muscle tissues, which is a significant advancement in the field [11][49] 2. **Clinical Trials**: The Phase 1-2 studies for Delbisiran and Delbrac have shown promising results, with significant improvements in patient-reported outcomes and biomarkers [17][21] 3. **Commercial Strategy**: Novartis plans to leverage its existing commercial capabilities in neuromuscular diseases to drive rapid uptake of the new therapies [28][30] 4. **Cost Synergies**: While cost synergies from the merger may be limited, Novartis expects to achieve productivity improvements and maintain a strong balance sheet [63][71] 5. **Regulatory Strategy**: Novartis aims to approach the FDA for accelerated approval based on compelling biomarker data from ongoing studies [72][73] This summary encapsulates the key points discussed during the conference call regarding the acquisition of Avidity Biosciences by Novartis, highlighting the strategic rationale, growth potential, and the expected impact on Novartis's portfolio and market position.

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]

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]

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]