Myotonic Dystrophy

- Recently presented data demonstrated sustained functional improvement with DYNE-251 treatment through 18 months - - Data from the fully enrolled DELIVER registrational expansion cohort is planned for late 2025 - April 24, 2025 -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage company focused on advancing life-transforming therapeutics for people living with genetically driven neuromuscular diseases, today announced that the European Commission (EC) has granted orphan drug designation for DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD). DYNE-251 is being evaluated in the Phase 1/2 DELIVER global clinical trial in individuals with DMD who are amenable to exon 51 skipping. Long-term clinical data from the ongoing DELIVER trial of DYNE-251 that demonstrated unprecedented and sustained functional improvement at the selected registrational dose were presented in March at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference. Functional assessments in the DELIVER trial include Stride Velocity 95th Centile (SV95C), an objective digital outcome that is accepted as a primary endpoint for DMD clinical trials in Europe. “Our recent long-term DELIVER trial results demonstrated clinically relevant and sustained functional improvement through 18 months, including as assessed by SV95C, which may support a strong rationale for regulatory approval in Europe,” said Doug Kerr, MD, PhD, chief medical officer of Dyne. “We are pleased that the EC has granted orphan drug designation to DYNE-251, reinforcing our belief that our next-generation exon 51 skipping investigational therapy for DMD may be able to bring clinically meaningful functional improvement to those living with this devastating disease. With full enrollment of the registrational expansion cohort in the DELIVER trial complete, we look forward to sharing data from this cohort in late 2025 and the potential to move forward with our first regulatory submissions in early 2026.” The EC grants orphan drug designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare, life-threatening or chronically debilitating diseases or conditions that affect fewer than five in 10,000 people in the European Union (EU). Orphan designation provides companies with certain benefits, including reduced regulatory fees, clinical protocol assistance, research grants and the potential for up to 10 years of market exclusivity in the EU if approved. DYNE-251 was also granted U.S. Food and Drug Administration (FDA) orphan drug and rare pediatric disease designations in March 2023. Key Milestones for the DELIVER Trial Dyne continues to pursue expedited approval pathways globally for DYNE-251 in patients with DMD who are amenable to exon 51 skipping. Dyne has fully enrolled the registrational expansion cohort of 32 patients as part of the DELIVER trial. Data from this cohort are planned for late 2025. Dyne anticipates filing a Biologics License Application (BLA) submission for US accelerated approval in early 2026. DELIVER is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial evaluating the safety, tolerability and efficacy of DYNE-251 in patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. The multiple ascending dose (MAD) portion of the study resulted in the selection of a registrational dose and regimen of 20 mg/kg every four weeks. A registrational expansion cohort to support potential regulatory submissions for expediated approvals, including accelerated approval in the U.S., is fully enrolled. The primary endpoint for this cohort is the change from baseline in dystrophin protein levels as measured by Western blot. For more information on the DELIVER trial, visit clinicaltrials.gov (NCT05524883) and euclinicaltrials.eu (2023-510351-31-00). DYNE-251 is an investigational therapeutic being evaluated in the Phase 1/2 global DELIVER clinical trial for people living with DMD who are amenable to exon 51 skipping. DYNE-251 consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a fragment antibody (Fab) that binds to the transferrin receptor 1 (TfR1), which is highly expressed on muscle. It is designed to enable targeted muscle tissue delivery and promote exon skipping in the nucleus, allowing muscle cells to create internally shortened, near full-length dystrophin protein, with the goal of stopping or reversing disease progression. DYNE-251 has been granted fast track, orphan drug and rare pediatric disease designations by the U.S. Food and Drug Administration for the treatment of DMD mutations amenable to exon 51 skipping. In addition to DYNE-251, Dyne is building a global DMD franchise and has preclinical programs targeting other exons, including 53, 45 and 44. DMD is a rare disease caused by mutations in the gene that encodes for dystrophin, a protein critical for the normal function of muscle cells. These mutations, the majority of which are deletions, result in the lack of dystrophin protein and progressive loss of muscle function. DMD occurs primarily in males and affects an estimated 12,000 to 15,000 individuals in the U.S. and 25,000 in Europe. Loss of strength and function typically first appears in pre-school age boys and worsens as they age. As the disease progresses, the severity of damage to skeletal and cardiac muscle often results in patients experiencing total loss of ambulation by their early teenage years and includes worsening cardiac and respiratory symptoms and loss of upper body function by the later teens. There is no cure for DMD, and currently approved therapies provide limited benefit. Dyne Therapeutics is discovering and advancing innovative life-transforming therapeutics for people living with genetically driven neuromuscular diseases. Leveraging the modularity of its FORCE™ platform, Dyne is developing targeted therapeutics that deliver to muscle and the central nervous system (CNS). Dyne has a broad pipeline for neuromuscular diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD), and preclinical programs for facioscapulohumeral muscular dystrophy (FSHD) and Pompe disease. 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Vertex is pulling back on its genetic medicine research, ending all work related to adeno-associated viruses, or AAVs — the viral vectors commonly used to deliver gene therapies into the body, the company confirmed to Endpoints News . The cuts impact Vertex’s collaborations with at least two biotech startups: the AAV design company Affinia Therapeutics and tRNA therapy company Tevard Biosciences, which uses AAVs. It also calls into question Vertex’s work on CRISPR therapies for genetic muscle diseases. Several bigger pharmaceutical companies, including Biogen , Pfizer , Roche and Takeda , have cut or pared back on AAV gene therapy research in recent years. And several gene therapy biotech companies have trimmed their pipelines and staff as private and public investors sour on the field. This change of fortune was seemingly unimaginable a few years ago. AAV technology ushered in a new era of gene therapy investment and led to several commercial products for diseases, including Roche’s Luxturna for childhood blindness, Sarepta Therapeutics’ Elevidys for Duchenne muscular dystrophy, and Novartis’ Zolgensma for an otherwise fatal neurodegenerative condition in infants. But a panoply of challenges — including costly manufacturing, multimillion-dollar drug prices, slow progress in improving targeted delivery and lingering safety issues — has raised questions about the future of AAV medicines. Vertex did not have any AAV gene therapies in clinical development, despite work on the technology stretching back to at least 2019 when it acquired Exonics Therapeutics for its early-stage CRISPR therapies for two muscle diseases: Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). Exonics relied on AAV vectors to deliver its therapies to muscles. Vertex has shared few updates on the program since its acquisition. The approach was essentially a permanent version of the commercial exon-skipping therapies for DMD, meaning it wouldn’t fully restore the dystrophin protein that’s broken in people with the disease. A Chinese biotech called HuidaGene has developed a similar CRISPR therapy and has already treated two boys, Endpoints reported last month . The first patient had modest improvement in his walking ability three months after the treatment. It is unknown why Vertex’s own CRISPR therapy has seemingly lagged behind. It is possible that the company is holding out for a more curative approach. It may also have been spooked by multiple deaths in people who received the high doses of AAV needed to reach the body’s many muscles, including two from Pfizer’s experimental therapy , one from Sarepta’s approved drug and one from a custom CRISPR therapy . Heather Nichols, a spokesperson for Vertex, confirmed that the company has discontinued its AAV work, but in an email said that the company’s “commitment to cell and genetic therapies remains strong” and that other investments in DMD and DM1 continue. The company declined to provide further comment on its AAV cuts or make an executive available for an interview. The need for better AAVs, ones that could deliver more of the therapy at lower doses, has been clear for years. Vertex struck a partnership with Affinia in 2020 worth up to $1.6 billion for access to the startup’s viral vectors designed to better target the muscles for treating DMD and DM1 and target the lungs to treat cystic fibrosis, the disease responsible for most of the company’s $11 billion revenue last year. Affinia CEO Rick Modi told Endpoints in an email that his company regained the rights to its muscle-targeting viruses from Vertex in March. He said the earlier work on cystic fibrosis ended in 2022 and rights to those programs were returned then. The startup is currently focused on finishing preclinical studies and designing a clinical trial for its lead candidate, for a heart condition called BAG3 dilated cardiomyopathy. Modi said that Affinia received “the maximum amount of milestone payments” for the research phase of its DMD and DM1 collaboration with Vertex, but he wouldn’t specify the amount. He added that Affinia is looking to license its newly-regained muscle capsids to other companies. Vertex’s step back from AAVs also impacts Tevard Biosciences. The small startup, which is housed in Eli Lilly’s genetics-focused research center that opened in Boston last summer, struck a four-year partnership with Vertex in February 2023 to develop a new class of genetic medicines known as tRNA therapies. In nature, tRNA molecules are part of the machinery that cells use to translate genetic code into proteins. Tevard is one of a few companies developing synthetic versions of these molecules to help skip over genetic mutations that prevent cells from making fully functional proteins. Tevard believes its approach could help restore the vital dystrophin protein missing from the muscles of the 15% of people with DMD whose disease is caused by so-called nonsense mutations. While some companies are trying to package tRNA therapies in lipid nanoparticles, those delivery vessels are not readily taken up by the body’s many muscles, so Tevard planned to use AAVs to deliver its treatment. “We were doing great. The collaboration was going great. But in December, we were informed that they were realigning priorities, and multiple programs were being terminated, including this one,” Tevard CEO Daniel Fischer told Endpoints in an interview. “Two weeks ago, we got the rights back to this program.” Other tRNA companies have also struggled, including HC Bioscience, which shut down in March after “challenges in targeted delivery,” Endpoints previously reported . Fischer said the fate of the DMD program will depend on whether Tevard can find another drugmaker to partner with or raise enough money to move it forward on its own. The company is planning to present data showing that the DMD therapy works in mice at the upcoming American Society of Gene & Cell Therapy meeting later this month.

Phase 2 biomarker trial in FECD patients anticipated to begin in the second half of 2025CARLSBAD, Calif., May 01, 2025 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc. (Nasdaq: DSGN), a clinical-stage biotechnology company developing treatments for serious degenerative genetic diseases, today announced favorable data from a Phase 1 single- and multiple-ascending dose (SAD/MAD) trial of DT-168 in healthy volunteers, which will be presented on May 2, 2025 at Eyecelerator @ Park City 2025, an event backed by the American Academy of Ophthalmology highlighting industry advancements and innovative new products disrupting eye care. DT-168 is a novel GeneTAC® small molecule, formulated as an eye drop, that is designed to selectively target and reduce the expression of the mutant TCF4 gene that causes corneal endothelial cell dysfunction leading to Fuchs endothelial corneal dystrophy (FECD). “DT-168 represents a differentiated opportunity for FECD, a disease with millions of patients facing progressive vision loss and no approved disease modifying therapies,” said Pratik Shah, Ph.D., chairperson and chief executive officer of Design Therapeutics. “Leveraging a convenient eye drop formulation, DT-168 is designed to address the underlying genetic cause of FECD by targeting the repeat expansion that drives disease progression. We are excited to initiate the Phase 2 proof-of-concept trial later this year as we advance what has the potential to be the first disease-modifying medicine for a large, underserved patient population.” Design completed a Phase 1, double-masked, placebo-controlled, randomized, SAD/MAD trial to evaluate the safety, tolerability and systemic pharmacokinetics (PK) of DT-168 ophthalmic solution. Twenty-four healthy volunteers received either placebo or single- and multiple-ascending doses of DT-168 eye drops twice daily for seven days (up to a maximum dose of two 0.5% drops twice-daily). DT-168 eye drops were well-tolerated in all participants.There were no serious adverse events, no ocular adverse events (AEs) and no treatment discontinuations due to AEs in the trial. All observed AEs were deemed not related to DT-168 by the trial investigator.As expected, PK analysis demonstrated systemic exposure below the limit of quantitation for all participants across all timepoints and all dose groups. In parallel with the Phase 1 trial, Design conducted reference range studies which showed consistently different splicing in the corneal endothelium between unaffected eye donors and surgical samples from mutant TCF4 FECD patients, supporting the potential for corneal endothelium RNA biomarkers as a clinical proof-of-concept measure of drug activity. Phase 2 Biomarker Trial of DT-168 in Patients with FECD Based on these findings, Design plans to conduct a Phase 2 biomarker trial of DT-168 to evaluate safety, tolerability, and corneal endothelium biomarkers in patients with FECD. The trial will enroll FECD patients with the TCF4 mutation who are scheduled for corneal transplant surgery. Patients will receive 0.5% DT-168 eye drops twice-daily for approximately 4 weeks or more before corneal transplant surgery. Following surgery, tissues from the treated eyes of FECD patients will undergo testing to assess corneal endothelium RNA biomarkers, including the abnormal splicing of genes known as spliceopathy. Design plans to initiate the DT-168 Phase 2 biomarker trial in the second half of 2025, with data anticipated in 2026. About Design TherapeuticsDesign Therapeutics is a clinical-stage biotechnology company developing a new class of therapies based on its platform of GeneTAC® gene targeted chimera small molecules. The company’s GeneTAC® molecules are designed to either dial up or dial down the expression of a specific disease-causing gene to address the underlying cause of disease. In addition to its GeneTAC® programs, DT-216P2, in development for patients with Friedreich ataxia, and DT-168, for Fuchs endothelial corneal dystrophy, the company is advancing programs in myotonic dystrophy type-1 and Huntington’s disease. Discovery efforts are underway for multiple genomic medicines. For more information, please visit designtx.com. Forward-Looking StatementsStatements in this press release that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to DT-168’s ability to target the repeat expansion that leads to FECD; the opportunity and potential for DT-168 to be the first disease-modifying treatment for FECD; the potential utility of corneal endothelium biomarkers in clinical development; the planned initiation and trial design and data result of Design’s Phase 2 biomarker trial of DT-168 and the timing thereof; Design's ability to advance its pipeline of GeneTAC® small molecules and create long-term value; and the capabilities and potential advantages of Design’s pipeline of GeneTAC® small molecules. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “designed to,” “anticipates,” “capable of,” “on track to,” “plans to,” “expects,” “estimate,” “intends,” “will,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Design’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the acceptance of INDs by the FDA or similar applications by foreign regulatory agencies for the conduct of planned clinical trials of our product candidates and our proposed design of future clinical trials; pursuing a biomarker-driven clinical development strategy carries increased risks as there are currently a limited number of approved biomarker-specific therapies; nonclinical development activities and results of nonclinical studies; conducting a clinical trial and patient enrollment, which are affected by many factors, and any difficulties or delays encountered with such clinical trial or patient enrollment may delay or otherwise adversely affect Design’s clinical development plans; the process of discovering and developing therapies that are safe and effective for use as human therapeutics and operating as a development stage company; undesirable side effects or other undesirable properties, which could cause Design or regulatory authorities to suspend or discontinue clinical trials and thereby delay or prevent Design’s product candidates’ development or regulatory approval; Design’s ability to develop, initiate or complete nonclinical studies and clinical trials for its product candidates; whether promising early research or clinical trials will demonstrate safety and/or efficacy in later nonclinical studies or clinical trials; changes in Design’s plans to develop its product candidates; reliance on third parties to successfully conduct clinical trials and nonclinical studies; competitive products, which may make any products we develop or seek to develop obsolete or noncompetitive; Design’s reliance on key third parties, including contract manufacturers and contract research organizations; Design’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; Design’s ability to obtain and maintain intellectual property protection for its product candidates; Design’s ability to recruit and retain key scientific or management personnel; and market conditions. For a more detailed discussion of these and other factors, please refer to Design’s filings with the Securities and Exchange Commission (SEC), including under the “Risk Factors” heading of Design’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, as filed with the SEC on March 10, 2025. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Design undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law. Contact:Renee LeckTHRUST Strategic Communicationsrenee@thrustsc.com