Myotonia

- Presentations Will Feature Recent Clinical Data From DYNE-251 and DYNE-101 as Well as Preclinical Data in FSHD and Pompe Disease - WALTHAM, Mass., Oct. 09, 2024 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today announced that previously reported clinical and preclinical data across its pipeline will be featured in poster presentations at the 29th Annual Congress of the World Muscle Society, held virtually and in Prague, Czech Republic, October 8-12, 2024. The presentations highlight the promise of the FORCE™ platform to deliver targeted therapeutics to address neuromuscular diseases. “The full breadth and versatility of our FORCE platform is on display at this year’s World Muscle Society Congress, with presentations covering both of our co-lead clinical programs in DM1 and DMD, along with preclinical work in FSHD and Pompe disease,” said John Cox, president and chief executive officer of Dyne. “We’ve observed targeted delivery with the FORCE platform showing broad distribution to key tissues like skeletal, cardiac, smooth muscle and the CNS – which has the potential to transform the lives of individuals living with these diseases.” Poster Highlights The Phase 1/2 DELIVER trial evaluating DYNE-251 in males with Duchenne muscular dystrophy (DMD) mutations amenable to exon 51 skipping includes 6-month biomarker and functional data from patients enrolled in the 20 mg/kg (approximate PMO dose) cohort and 12-month functional data from the 10 mg/kg cohort. DYNE-251 demonstrated dose dependent exon skipping and dystrophin expression and improvement in multiple functional endpoints in both cohorts. Patients treated with 20 mg/kg of DYNE-251 Q4W had a mean absolute dystrophin expression of 3.7% of normal (unadjusted for muscle content) and when adjusting for muscle content, it reached 8.7%. Importantly, treatment with DYNE-251 resulted in meaningful improvements in Stride Velocity 95th Centile (SV95C), a digital objective outcome measure of ambulatory performance in a patient’s normal daily environment. The change from baseline in SV95C met the published minimal clinically important difference as defined by the European Medicines Agency (0.1 m/sec) at 6 months for both the 10 and 20 mg/kg cohorts (approximately 0.2 m/sec change from baseline for both cohorts).The Phase 1/2 ACHIEVE trial evaluating DYNE-101 in adult participants with myotonic dystrophy type 1 (DM1) includes 12-month data from the 1.8 mg/kg Q4W (approximate ASO dose) cohort, 6-month data from the 3.4 mg/kg Q4W cohort, and 3-month data from the 5.4 mg/kg Q8W cohort. DYNE-101 demonstrated robust muscle delivery and dose-dependent, consistent splicing correction while also showing improvement in myotonia, muscle strength, and timed function tests and in the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-ACTIVc) and the Myotonic Dystrophy Health Index (MDHI) patient reported outcomes. Patients in the 5.4 mg/kg Q8W cohort had a 27% mean splicing correction from baseline across a broad, 22-gene panel at 3 months, with all participants demonstrating splicing correction.Both DYNE-251 and DYNE-101 have demonstrated favorable safety profiles. 1 2Preclinical data for DYNE-302 in facioscapulohumeral muscular dystrophy (FSHD), demonstrated robust and durable DUX4 suppression and functional benefit in an innovative hTfR1/iFLExD mouse model developed by Dyne. In hTfR1/iFLExD mice, a single intravenous dose of DYNE-302 resulted in dose-dependent and robust reduction of the DUX4 transcriptome (D4T) that lasted up to three months, with benefit on muscle structure and function.Preclinical data in a Pompe disease model demonstrated the potential of the FORCE platform to deliver enzyme replacement therapy to cardiac and skeletal muscle and the central nervous system (CNS), potentially expanding the modularity of the platform beyond oligonucleotides. Presentation Information Title: Initial Data from the DELIVER Trial of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 SkippingDate/Time: October 9, 2024, 2:30 p.m. CEST/8:30 a.m. ETPresenter: Liesbeth De Waele, M.D., Ph.D., Pediatric Neurologist at University Hospital Leuven, Belgium Title: Initial Data from the ACHIEVE Trial of DYNE-101 in Adults with Myotonic Dystrophy Type 1 (DM1)Date/Time: October 9, 2024, 2:30 p.m. CEST/8:30 a.m. ETPresenter: Joost Kools, M.D., Neuromuscular Department at Radboud University Medical Center, Netherlands Title: The FORCE™ Platform Achieves Robust and Durable DUX4 Suppression and Improves Muscle Function in Facioscapulohumeral Muscular Dystrophy Mouse ModelDate/Time: October 9, 2024, 5:15 p.m. CEST/11:15 a.m. ETPresenter: Tyler Picariello, Ph.D., Director, Neuromuscular Research, Dyne Therapeutics Title: The FORCE™ Platform Enables Tfr1-mediated Delivery of Enzyme Replacement Therapy to Muscle and Central Nervous System, Resolving Pompe Pathology in MiceDate/Time: October 11, 2024, 3:45 p.m. CEST/ 9:45 a.m. ETPresenter: Tyler Picariello, Ph.D., Director, Neuromuscular Research, Dyne Therapeutics The presentations will be available in the Scientific Publications & Presentations section of Dyne’s website following the session. Additionally, a symposium titled “Potential of the FORCE™ Platform to Address Unmet Needs in Rare Neuromuscular Diseases” will be held on October 10 at 8:15 a.m. CEST/ 2:15 a.m. ET. About the FORCE™ Platform The proprietary FORCE™ platform drives Dyne’s efforts to develop targeted, modern oligonucleotide innovative therapeutics with the potential to be life-transforming for patients with serious muscle diseases. Dyne designed the FORCE platform using its deep knowledge of muscle biology and oligonucleotide therapeutics to overcome the current limitations in delivery to muscle tissue with the goal of stopping or reversing disease progression. The FORCE platform leverages the importance of transferrin receptor 1 (TfR1) in muscle biology as the foundation for its novel approach. TfR1, which is highly expressed on the surface of muscle cells, is required for iron transport into muscle cells. Dyne links therapeutic payloads to its TfR1-binding fragment antibody (Fab) to develop targeted therapeutics for muscle diseases. About Dyne Therapeutics Dyne Therapeutics is a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases. With its proprietary FORCE™ platform, Dyne is developing modern oligonucleotide therapeutics that are designed to overcome limitations in delivery to muscle tissue. Dyne has a broad pipeline for serious muscle diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and preclinical programs for facioscapulohumeral muscular dystrophy (FSHD). For more information, please visit https://www.dyne-tx.com/, and follow us on X, LinkedIn and Facebook. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Dyne’s strategy, future operations, prospects and plans, objectives of management, the potential of the FORCE platform, the potential of DYNE-101, DYNE-251 and DYNE-302, expectations regarding the timing and outcome of interactions with global regulatory authorities, and plans to provide future updates on pipeline programs, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Dyne may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Dyne’s ability to enroll patients in clinical trials; whether results from preclinical studies and initial data from early clinical trials will be predictive of the final results of the clinical trials or future trials; uncertainties as to the FDA’s and other regulatory authorities’ interpretation of the data from Dyne's clinical trials and acceptance of Dyne's clinical programs and the regulatory approval process; whether Dyne’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Dyne’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-Q and in subsequent filings Dyne may make with the SEC. In addition, the forward-looking statements included in this press release represent Dyne’s views as of the date of this press release. Dyne anticipates that subsequent events and developments will cause its views to change. However, while Dyne may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Dyne’s views as of any date subsequent to the date of this press release. Safety data as of August 21, 2024Safety data as of August 20, 2024 Contacts: InvestorsAmy Reillyareilly@dyne-tx.com 857-341-1203 MediaStacy Nartkersnartker@dyne-tx.com 781-317-1938

Earlier this year, Avidity started a pivotal Phase III HARBOR trial evaluating del-desiran inpatients with DM1. Image credit: JHVEPhoto /Shutterstock. The US Food and Drug Administration (FDA) has lifted the partial clinical hold on Avidity Biosciences ’ investigational drug, delpacibart etedesiran (del-desiran). In 2022, the US regulatory agency placed a partial hold after a report of a serious adverse event in a newly enrolled patient in the Phase I/II MARINA trial (NCT05027269), which evaluated del-desiran in patients myotonic dystrophy type 1 (DM1). The company did not disclose the details of the adverse event and the US FDA eased the partial clinical hold the following year, allowing the company to recruit new patients. The clinical hold has not slowed down Avidity’s efforts to advance the clinical development of del-desiran in DM1. Earlier this year, Avidity started a pivotal placebo-controlled Phase III HARBOR trial (NCT06411288). The study is expected to enrol 150 participants with DM1 who will be assessed over 54 weeks. The trial’s primary endpoint is the improvement of myotonia over 30 weeks, measured using video Hand Opening Time (vHOT), the average time to extend the right third and first digits. The study’s secondary endpoints also include the functional assessment of myotonia across 30 weeks, including hand grip strength, quantitative muscle testing composite score and Myotonic Dystrophy Type 1 activity and participation scale c. Del-desiran is an antibody oligonucleotide conjugate (AOC) made up of a monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a small interfering RNA (siRNA) targeting myotonic dystrophy protein kinase (DMPK) mRNA, responsible for producing DMPF protein. If approved, GlobalData expects del-desiran to pull in over $1.2bn in sales by 2030. See Also: BMS receives FDA approval for Opdivo to treat NSCLC Novaliq and Laboratoires Théa announce EC approval for dry eye disease therapy GlobalData is the parent company of Pharmaceutical Technology . mRNA vaccines were instrumental during the Covid-19 pandemic. Since then, there has been increased interest in mRNA therapies beyond the vaccines. GlobalData forecasts the mRNA non-vaccine therapeutics field to reach $2bn by 2028. DM1 is a genetic disorder caused by a triplet-repeat in the DMPK gene. It primarily affects skeletal and cardiac muscle causing muscle weakness and wasting leading to respiratory problems, and cardiac abnormalities. There are no approved treatments for DM1 and management is mostly aimed at symptomatic treatment. Another therapy in development for treating DM1 is AMO Pharma’s AMO-02 (tideglusib). The therapy is an irreversible inhibitor of glycogen synthase kinase 3 (GSK-3), it has the potential to disrupt the RNA repeats that cause congenital DM1. In May, AMO announced plans to start a Phase III trial for AMO-02 in DM1 patients.

SAN DIEGO, Oct. 3, 2024 /PRNewswire/ -- Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced that the U.S. Food and Drug Administration (FDA) has removed the partial clinical hold on delpacibart etedesiran (del-desiran/AOC 1001), an investigational treatment designed to address the root cause of myotonic dystrophy type 1 (DM1). Del-desiran is being evaluated in the ongoing Phase 3 HARBOR™ trial in patients with DM1, an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies. Del-desiran has received Breakthrough Therapy, Orphan Drug and Fast Track designations by the FDA and Orphan designation by the European Medicines Agency (EMA). About Del-desiran (AOC 1001) Del-desiran (AOC 1001), Avidity's lead product candidate utilizing its AOC platform, is designed to address the root cause of DM1 by reducing levels of a disease-related mRNA called DMPK. Del-desiran consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA. Del-desiran is currently being assessed in the global Phase 3 HARBOR™ trial and in the ongoing MARINA-OLE™ trial in people with DM1. Long-term data from the MARINA-OLE trial showed reversal of disease progression in people living with DM1 across multiple endpoints including video hand opening time (vHOT) as a measure of hand function and myotonia, muscle strength and activities of daily living when compared to END-DM1 natural history data. Del-desiran has received Breakthrough Therapy, Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA) and Orphan designation by the European Medicines Agency (EMA). About Myotonic Dystrophy Type 1 Myotonic dystrophy type 1 (DM1) is an underrecognized, autosomal dominantly inherited, progressive and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation and age of onset, however all forms of DM1 are associated with high levels of disease burden and may cause premature mortality. DM1 primarily affects skeletal and cardiac muscle, however patients can suffer from a constellation of manifestations including myotonia and muscle weakness, respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. Currently, there are no approved treatments for people living with DM1. About Avidity  Avidity Biosciences, Inc.'s mission is to profoundly improve people's lives by delivering a new class of RNA therapeutics - Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through internal discovery efforts and key partnerships. Avidity is headquartered in San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit and engage with us on LinkedIn and X. Forward-Looking Statements Avidity cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the advancement of del-desiran™ and the timing thereof; the characterization of data associated with del-desiran™, and the impact of such data on its advancement; the design, goals, timelines and expectations related to the global Phase 3 HARBOR™ trial of del-desiran; and Avidity's platform, planned operations and programs. The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of these plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Avidity's business and beyond its control, including, without limitation: preliminary results of a clinical trial are not necessarily indicative of final results; further analysis of existing clinical data and analysis of new data may lead to conclusions different from those established as of the respective data cutoff dates in Avidity's clinical trials, and such data may not meet Avidity's expectations; unexpected adverse side effects to, or inadequate efficacy of, Avidity's product candidates that may delay or limit their development, regulatory approval and/or commercialization; the FDA lifting the partial clinical hold related to del-desiran does not foreclose the possibility of additional issues of safety related to del-desiran; later developments with the FDA and other global regulators that could be inconsistent with the feedback received to date regarding Avidity's clinical trials; Avidity's approach to the discovery and development of product candidates based on its AOC™ platform is unproven; potential delays in the commencement, enrollment, data readouts and completion of preclinical studies or clinical trials; Avidity's dependence on third parties in connection with preclinical and clinical testing and product manufacturing; legislative, judicial and regulatory developments in the United States and foreign countries; Avidity could exhaust its available capital resources sooner than it currently expects; and other risks described in Avidity's Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and subsequent filings with the SEC. Avidity cautions readers not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that arise after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investor Contact: Mike MacLean (619) 837-5014 [email protected] Media Contact: Navjot Rai (619) 837-5016 [email protected] SOURCE Avidity Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED