, /PRNewswire/ -- Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCsâ"¢) to profoundly improve people's lives, today announced that it will deliver late-breaking oral and poster presentations at the 30th Annual International Congress of the World Muscle Society (WMS), to be held October 7-11, 2025, in Vienna, Austria. The data to be presented at WMS will reinforce and build on the posit ...

Summary of Wave Life Sciences FY Conference Call Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Industry**: RNA therapeutics, focusing on oligonucleotides and genomic medicine [2][3] Core Points and Arguments INHIBIN-E Obesity Program - **Program Type**: siRNA, GALAX siRNA program targeting obesity [4] - **Mechanism**: INHIBIN-E is a liver-expressed dimer that regulates lipolysis by binding to ALK7 on fat cells, acting as a brake on fat breakdown [5] - **Clinical Evidence**: Carriers of loss-of-function variants show healthier cardiometabolic profiles, including lower abdominal obesity and triglycerides [4] - **Differentiation**: Unlike GLP-1 agonists that focus on appetite regulation, INHIBIN-E directly targets fat cells, potentially leading to fat loss without affecting muscle [6][17] - **Preclinical Data**: Comparable weight loss to semaglutide, with a focus on fat loss, particularly visceral fat [6][8] - **Dosing**: Potential for once or twice a year dosing based on preclinical data [6] - **Current Status**: Phase one trial focusing on safety, tolerability, and target engagement, with upcoming data releases for different dosing cohorts [12][14] Alpha-1 Antitrypsin Deficiency (AATD) Program - **Disease Overview**: A rare disease affecting lung and liver, with current treatments limited to protein replacement and liver transplantation [27] - **Mechanism**: RNA editing approach to correct mutations at the RNA level, producing healthy M protein [28] - **Clinical Data**: Achieved significant conversion from C to M protein, with a 65% decrease in C protein levels and increases in M protein [30] - **Unique Finding**: Observed endogenous regulation of AAT levels, demonstrating the potential for better patient response during inflammatory events [31][33] DMD (Duchenne Muscular Dystrophy) Program - **Program Type**: Exon-skipping therapy for exon 53, targeting about 10% of DMD patients [58] - **Clinical Data**: High and consistent levels of dystrophin observed, with significant improvements in muscle pathology and clinical measures [59][61] - **Differentiation**: Unique stereochemistry and PN chemistry allow for better drug delivery and efficacy compared to competitors [62][63] Huntington's Disease Program - **Program Type**: Allele-selective ASO targeting the mutant Huntington allele while sparing the wild-type protein [70] - **Clinical Data**: Achieved a 46% knockdown of mutant Huntington with no effect on wild-type, correlating with slowing of caudate atrophy [74] - **Regulatory Discussions**: Engaging with regulators for potential accelerated approval based on observed endpoints [74] Emerging Pipeline and Future Directions - **PLMP3 Program**: Targeting liver disease with a large patient population, aiming for clinical trials in 2026 [54][55] - **Broader Applications**: Exploring RNA editing for extrahepatic diseases, with promising preclinical data [56] Important but Overlooked Content - **Competitive Landscape**: Comparison with competitors in the siRNA space, highlighting differences in dosing frequency and weight loss efficacy [24] - **Regulatory Pathway**: Plans to engage with regulators for AATD and other programs, indicating a proactive approach to market entry [50][51] - **Market Potential**: Emphasis on the large unmet need in obesity and liver diseases, positioning Wave Life Sciences for significant market opportunities [10][54] Upcoming Milestones - **Near-term Catalysts**: Data readouts for INHIBIN-E and AATD programs expected in Q4 and Q1, respectively [75]

Key Takeaways CRISPR Therapeutics and Sirius start a phase II study of SRSD107 in thromboembolic disorders.SRSD107 targets Factor XI to prevent venous thromboembolism in knee arthroplasty patients.The collaboration expands CRISPR Therapeutics' pipeline into RNA therapeutics beyond gene therapies.CRISPR Therapeutics (CRSP) , along with privately held biotech, Sirius Therapeutics, announced the dosing of the first patient in a phase II study evaluating SRSD107, a next-generation, long-acting siRNA therapy for ...

Del-zota Clinical Trial Results - Del-zota demonstrated unprecedented functional improvement on all key measures at one year across EXPLORE44® & EXPLORE44-OLE[18] - Creatine kinase (CK) levels rapidly reduced by >80% compared to baseline and sustained at near normal levels[41] - 50% of participants had CK levels within normal range at 1 year of treatment[41] - Dystrophin increase to up to 58% of normal[36] Safety and Tolerability - Del-zota continues to demonstrate favorable long-term safety and tolerability[27] - In EXPLORE44-OLE, 85% of participants experienced any adverse event (AE), 26% related to the study drug[27] - Serious adverse events occurred in 8% of participants, with 3% related to the study drug[27] - 3% of participants discontinued treatment due to adverse events[27] Regulatory and Commercialization - The company is on track for BLA submission by year end 2025 and launch in 2026[18] - The company is aligned on path for accelerated approval in the U S for DMD44, which affects approximately 900 people in the U S[14, 17]

Core Insights - Avidity Biosciences announced positive data from the EXPLORE44 and EXPLORE44-OLE trials, showing unprecedented improvements in multiple functional measures for Duchenne muscular dystrophy (DMD) patients treated with del-zota [1][3][4] - The company is on track to submit a Biologics License Application (BLA) to the FDA by the end of 2025 for accelerated approval of del-zota [1][6] Clinical Trial Results - Participants treated with del-zota showed a 25% increase in normal dystrophin production and a reduction of creatine kinase (CK) levels by over 80% compared to baseline, maintained near normal levels for up to 16 months [3][4] - Functional improvements included: - 4-Stair Climb (4SC): Improved by 2.1 seconds compared to a decline of 2.7 seconds in the natural history group [4] - 10-Meter Walk/Run Test (10mWRT): Improved by 0.7 seconds compared to a decline of 1.5 seconds in the natural history group [4] - Time to Rise from Floor (TTR): Improved by 3.2 seconds compared to a decline of 1.6 seconds in the natural history group [4] - Performance of Upper Limb (PUL): Improved by 1.5 points compared to a decline of 0.7 points in the natural history group [12] Safety Profile - Del-zota demonstrated a favorable long-term safety and tolerability profile, with most treatment-emergent adverse events being mild or moderate [5] - Common adverse events included upper respiratory tract symptoms, diarrhea, falls, back pain, and headaches [5] Future Plans - Avidity is preparing for a confirmatory study to support full global approval of del-zota [6] - The company plans to present additional data from the EXPLORE44 program at upcoming scientific congresses [1]

Core Insights - Avidity Biosciences' shares have increased by 36% in the past month due to reports of Novartis' interest in acquiring the company, although discussions are still in early stages with no guarantees of a deal [1][7] - Avidity is a clinical-stage biotech focused on RNA therapeutics, with key programs targeting rare muscular diseases and expanding into precision cardiology [2][3] - Year-to-date, Avidity's shares have surged by 59%, significantly outperforming the industry average growth of 4% [6] Company Overview - Avidity Biosciences is developing RNA therapeutics for conditions such as myotonic dystrophy type 1, facioscapulohumeral muscular dystrophy, and Duchenne muscular dystrophy [2] - The company has established partnerships with major pharmaceutical companies like Bristol Myers and Eli Lilly to develop therapies for cardiovascular and immunology indications [3] Market Context - Novartis is reportedly interested in acquiring Avidity to mitigate potential revenue losses from generic competition affecting its top-selling drugs, such as Entresto, Gleevec, and Diovan [7][8] - The acquisition would enhance Novartis' pipeline in rare muscular diseases and strengthen its position in the cardiovascular market [8]

-- 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 ...

Core Insights - Avidity Biosciences has received Breakthrough Therapy designation from the FDA for delpacibart zotadirsen (del-zota) aimed at treating Duchenne muscular dystrophy (DMD) in patients with mutations suitable for exon 44 skipping [1][4][7] - The company is on track for a Biologics License Application (BLA) submission by the end of 2025, with ongoing preparations for a potential U.S. launch of del-zota following FDA approval [5][4] - Del-zota is currently in the Phase 2 EXPLORE44 Open-Label Extension trial, building on positive results from the Phase 1/2 trial that showed significant improvements in biomarkers related to DMD [2][4][10] Company Overview - Avidity Biosciences focuses on developing a new class of RNA therapeutics known as Antibody Oligonucleotide Conjugates (AOCs™) [13] - The company aims to address rare neuromuscular diseases, including DMD, myotonic dystrophy type 1 (DM1), and facioscapulohumeral muscular dystrophy (FSHD) [13] - Avidity's proprietary AOC platform allows for targeted delivery of RNA into muscle tissue, which is a significant advancement in the field of RNA therapeutics [13] Product Development - Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to specifically skip exon 44 of the dystrophin gene, facilitating the production of near-full length dystrophin [3][12] - The Phase 1/2 EXPLORE44 trial demonstrated statistically significant increases in exon skipping and dystrophin production, along with a reduction in creatine kinase levels to near normal [4][12] - The ongoing EXPLORE44-OLE study will evaluate the long-term safety and efficacy of del-zota, with a total treatment duration of approximately 24 months [9][10] Regulatory Designations - In addition to Breakthrough Therapy designation, del-zota has received Orphan designation, Rare Pediatric Disease designation, and Fast Track designation from the FDA [7][12] - These designations highlight the drug's potential to significantly improve treatment options for patients with DMD, a condition with a high unmet medical need [11][6]

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]