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]

Core Insights - Wave Life Sciences Ltd. has appointed Dr. Christopher Wright as Chief Medical Officer to lead the clinical development of its RNA medicines pipeline [1][2] - Dr. Wright brings extensive experience in global development, having worked with regulatory agencies in both the US and EU, and has a strong track record in drug development for various diseases [2][3] - The company has a robust therapeutic pipeline and has delivered positive clinical datasets over the past year, indicating the potential of its RNA medicines [4] Company Overview - Wave Life Sciences is a biotechnology company focused on RNA medicines, utilizing its PRISM platform to address both rare and common disorders [5] - The company's RNA-targeting modalities include editing, splicing, RNA interference, and antisense silencing, providing a comprehensive toolkit for disease treatment [5] - Wave's pipeline includes clinical programs for Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington's disease, and obesity, along with several preclinical programs [5] Leadership Background - Dr. Wright has held significant roles in various biotechnology companies, including CMO at Ring Therapeutics and AavantiBio, and has experience in leading global development functions [2][3] - He has a strong academic background, having served as a board-certified neurologist and Associate Professor of Neurology at Harvard Medical School [3] Equity Grant - In connection with his appointment, Dr. Wright received a share option to purchase 300,000 ordinary shares of Wave, with an exercise price of $5.94 per share, vesting over four years [4]

Company Overview - TransCode Therapeutics, Inc. is a clinical-stage oncology company focused on developing RNA-targeted therapeutics for cancer treatment [1][4] - The company aims to combat metastatic disease through the intelligent design and effective delivery of RNA therapeutics using its proprietary TTX nanoparticle platform [4] Key Appointment - Dr. Phillip D. Zamore has been appointed to the Scientific Advisory Board of TransCode Therapeutics [1] - Dr. Zamore is recognized for his pioneering work in RNA interference (RNAi) and co-founded Alnylam Pharmaceuticals, which developed the first FDA-approved RNAi drug [1][6] Research Contributions - Dr. Zamore's research has advanced the understanding of non-coding RNA and its implications in health and disease, particularly in the processing of microRNAs [2] - His contributions have earned him recognition from prestigious institutions, including the National Academy of Sciences and the National Academy of Medicine [2] Strategic Vision - The company emphasizes the importance of Dr. Zamore's expertise in RNA biology to enhance its pipeline of RNA-targeted cancer therapies [3] - Dr. Zamore expressed enthusiasm for contributing to the development of effective RNA-based treatments for cancer patients [3] Product Focus - TransCode's lead therapeutic candidate, TTX-MC138, targets metastatic tumors that overexpress microRNA-10b, a biomarker associated with metastasis [4] - The company has a portfolio of first-in-class RNA therapeutic candidates aimed at overcoming RNA delivery challenges to access novel genetic targets for various cancers [4]

Core Viewpoint - TransCode Therapeutics is advancing its Phase 1a clinical trial for TTX-MC138, a novel RNA therapeutic aimed at treating metastatic cancers, with positive safety and pharmacokinetic data supporting further development [1][3][5]. Group 1: Clinical Trial Progress - The third patient in Cohort 4 has received the initial dose of TTX-MC138, with all cohorts having at least three patients dosed [1]. - A total of 15 patients have been treated across four dose levels (0.8 mg/kg to 4.8 mg/kg), with no significant safety or dose-limiting toxicities reported [2][8]. - Ten patients remain on study, receiving doses every 28 days, with two patients showing stable disease after seven doses over approximately seven months [2][8]. Group 2: Safety and Efficacy Data - Preliminary pharmacokinetic (PK) and pharmacodynamic (PD) analyses indicate a predictable dose-response relationship, with evidence of miR-10b target engagement at 24 hours post-infusion [2][4][8]. - The observed tolerability profile supports the advancement of the trial into the Phase 1b dose expansion stage to further evaluate safety and potential anti-tumor activity [3]. Group 3: About TTX-MC138 - TTX-MC138 is designed to inhibit microRNA-10b, which is implicated in the progression of many metastatic cancers, and has shown promising delivery and activity in preclinical studies [4][7]. - The drug candidate has demonstrated a broad therapeutic window, suggesting potential for effective treatment of metastatic tumors [4]. Group 4: Trial Design - The Phase 1 clinical trial is a multicenter, open-label study aimed at evaluating the safety and tolerability of TTX-MC138 in patients with various metastatic solid cancers [5]. - The trial consists of an initial dose-escalation stage followed by a dose-expansion stage to further assess safety, tolerability, and anti-tumor activity [5].

Core Insights - TransCode Therapeutics is advancing its Phase 1a clinical trial of TTX-MC138, a first-in-class therapeutic candidate targeting microRNA-10b, which is believed to play a significant role in metastatic cancer progression [1][4][7] - The trial has treated 13 patients with doses ranging from 0.8 mg/kg to 4.8 mg/kg, with no significant safety issues reported [1][8] - Preliminary pharmacokinetic (PK) and pharmacodynamic (PD) data indicate a favorable profile for TTX-MC138, supporting its progression to the Phase 1b trial [2][3] Company Overview - TransCode Therapeutics focuses on RNA therapeutics for treating metastatic diseases, utilizing its proprietary TTX nanoparticle platform [7] - The lead candidate, TTX-MC138, aims to inhibit microRNA-10b, a biomarker associated with metastasis [7] Clinical Trial Details - The Phase 1 clinical trial is designed as a multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety and tolerability of TTX-MC138 in patients with various metastatic solid cancers [5] - The trial consists of an initial dose-escalation stage followed by a dose-expansion stage, with the primary objective of assessing safety and tolerability [5] Treatment Progress - Eight patients are currently receiving ongoing treatment, with two patients demonstrating stable disease after seven months of treatment [2][8] - The trial has shown a predictable dose-response relationship in PK data, with evidence of target engagement for miR-10b in 5 out of 6 patients analyzed [2][8]

Core Insights - TransCode Therapeutics has initiated treatment for the first patient in Cohort 4 of its Phase I clinical trial for TTX-MC138, a therapeutic candidate targeting microRNA-10b, which is associated with metastatic cancer [1][3] - The trial has shown no significant safety or dose-limiting toxicities among the ten patients treated so far, with seven remaining on study for continued treatment [2][8] - The ongoing analysis of pharmacokinetic and pharmacodynamic data suggests that TTX-MC138 aligns with preclinical results, indicating a promising safety profile [2][4] Company Overview - TransCode Therapeutics is focused on developing RNA therapeutics to treat metastatic diseases, utilizing its proprietary TTX nanoparticle platform [7] - TTX-MC138 is the lead candidate designed to inhibit microRNA-10b, which is believed to drive metastatic disease [4][7] - The company aims to address challenges in RNA delivery to unlock therapeutic access to various genetic targets relevant for cancer treatment [9] Clinical Trial Details - The Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study aimed at evaluating the safety and tolerability of TTX-MC138 in patients with metastatic solid cancers [5] - The trial consists of an initial dose-escalation phase followed by a dose-expansion phase, with the primary objective of assessing safety and tolerability [5] - Cohort 4's treatment is expected to provide insights for dose expansion and initial evidence of clinical activity as the trial progresses [3][5]