Dyne Therapeutics, Inc. operates as a clinical-stage neuromuscular disease company.
The company is focused on discovering and advancing innovative life-transforming therapeutics for people living with genetically driven neuromuscular diseases. Leveraging the modularity of its FORCE platform, it is developing targeted therapeutics designed to overcome limitations in delivery to muscle tissue and the central nervous system (CNS). The company's proprietary FORCE platform therapeutics consist of a...
Dyne Therapeutics, Inc. operates as a clinical-stage neuromuscular disease company.
The company is focused on discovering and advancing innovative life-transforming therapeutics for people living with genetically driven neuromuscular diseases. Leveraging the modularity of its FORCE platform, it is developing targeted therapeutics designed to overcome limitations in delivery to muscle tissue and the central nervous system (CNS). The company's proprietary FORCE platform therapeutics consist of a payload that it rationally designs to target the genetic basis of the disease it seeks to treat, a linker, and an antigen-binding fragment, or Fab, that it attaches to the payload using the linker. With its FORCE platform, the company has the flexibility to deploy different classes of payloads (such as oligonucleotides and enzymes) with specific mechanisms of action that modify target functions. The company leverages this modularity to focus on neuromuscular diseases with high unmet need, with etiologic targets, and with clear translational potential from preclinical disease models to well-defined clinical development and regulatory pathways.
Using its FORCE platform, the company is assembling a broad portfolio of product candidates, including product candidates being developed for myotonic dystrophy type 1 or (DM1), Duchenne muscular dystrophy (DMD), facioscapulohumeral dystrophy (FSHD), and Pompe disease. In addition, the company plans to expand its portfolio through development efforts focused on rare skeletal muscle diseases, as well as cardiac and metabolic muscle diseases, including some with larger patient populations, and diseases involving the CNS. The company has identified product candidates for each of its DM1, DMD, FSHD, and Pompe programs that are in varying stages of preclinical and clinical development.
The company’s product candidate DYNE-101 is being evaluated in ACHIEVE, an ongoing Phase 1/2 global clinical trial in patients with DM1. ACHIEVE, which is designed to be a registrational trial, consists of a 24-week multiple ascending dose, or MAD, randomized, placebo-controlled period, a 24-week open-label extension, or OLE, a 96-week long-term extension, and a registrational expansion cohort.
In January 2025, the company announced the completion of the MAD portion of the trial and the company’s plans to initiate a registrational expansion cohort to support submission for Accelerated Approval in the U.S. The company plans to complete enrollment of the registrational expansion cohort in mid-2025 with data from this cohort in the first half of 2026 and potential submission for the U.S. Accelerated Approval in the first half of 2026.
The company's product candidate DYNE-251 is being evaluated in DELIVER, an ongoing Phase 1/2 global clinical trial in patients with Duchenne muscular dystrophy (DMD) who have mutations amenable to exon 51 skipping. DELIVER, which is designed to be a registrational trial, consists of a 24-week multi-ascending dose (MAD), randomized, placebo-controlled period, a 24-week open-label extension (OLE), a 192-week long-term extension, and a registrational expansion cohort. In September 2024, the company announced the completion of the MAD portion of the trial, and in November 2024, it announced the initiation of the registrational expansion cohort to support submission for Accelerated Approval in the U.S. The company plans to complete enrollment of the registrational expansion cohort in the first quarter of 2025, with data from this cohort expected in late 2025 and potential submission for the U.S. Accelerated Approval in early 2026.
Approach
The company has designed the company’s proprietary FORCE platform using the company’s deep knowledge of muscle biology. The company’s therapeutics consist of three essential components: a proprietary Fab, a linker and a payload that the company attaches to its Fab using the linker. The company engineered its proprietary Fab to bind to Transferrin receptor 1, or TfR1, to enable targeted delivery to skeletal, cardiac and smooth muscle, and TfR1 binding may also enable delivery to the CNS. The company connects the proprietary Fab to the therapeutic payload with a linker. The company selected the linker for its DM1, DMD and FSHD product candidates based on its clinically validated safety and efficacy in approved products, its serum stability and its ability to release the therapeutic payload within the muscle cell. For the company’s Pompe product candidate, the company selected a linker that effectively connects to the GAA enzyme payload. The company attaches the Fab and linker to a therapeutic payload that can be an antisense oligonucleotide, or ASO, a small interfering RNA, or siRNA, a phosphorodiamidate morpholino oligomer, or PMO, a small molecule, or a large molecule, such as an enzyme, that the company rationally selects to target the genetic basis of disease to potentially stop or reverse disease progression. The company uses the same Fab for its product candidates which enables modularity of the platform.
While some therapeutics have been approved for the treatment of neuromuscular diseases, the development of these therapeutics have been limited by challenges in the delivery of the payload to the tissue or area of the CNS that requires therapy. To overcome these limitations, the company’s FORCE platform utilizes the importance of TfR1, which is highly expressed on the surface of muscle cells, as the foundation of the company’s novel approach of linking therapeutic payloads to the company’s TfR1-binding Fab to deliver targeted therapeutics for muscle diseases. The mechanism of FORCE delivery is designed to utilize the natural biology of TfR1. The company does not use membrane destabilizing agents to enter the cell or to escape the endosome. As a result, FORCE displays a distinct pharmacokinetic and pharmacodynamic profile, with the potential for a wide therapeutic index.
The company has demonstrated proof-of-concept of its FORCE platform in the company’s ACHIEVE and DELIVER clinical trials, as well as in multiple in vitro and in vivo studies. In murine and non-human primate, or NHP, studies, the company has delivered ASOs and PMOs to genetic targets within muscle tissue and observed durable, disease-modifying, functional benefit in preclinical models of disease. In ACHIEVE, DYNE-101 has demonstrated robust splicing correction and DMPK knockdown while also showing improvement across multiple clinical measures, including myotonia, strength, timed function tests, and patient reported outcomes, including measurements of the CNS manifestations of DM1. In DELIVER, DYNE-251 has demonstrated best-in-class levels of dystrophin expression, exon skipping and percent dystrophin positive fibers while also showing improvement across multiple clinical measures, including strength and time function tests.
Proprietary antibody (Fab)
The company’s proprietary Fab is engineered to bind to TfR1 to enable targeted delivery of nucleic acids and other molecules to skeletal, cardiac and smooth muscle. A Fab is the region of an antibody that binds to antigens. The company selected a Fab antibody over monoclonal antibodies, or mAbs, due to its potential significant advantages when targeting TfR1 to enable muscle delivery, including enhanced tissue penetration, increased tolerability due to lower protein load and reduced risk of immune system activation due to the lack of the Fc domain, the portion of an antibody that interacts with the immune system, on the Fab. To identify the proprietary Fab the company uses in its product candidates, the company generated and screened proprietary antibodies for selectivity to TfR1 in order to enhance muscle specificity and for binding to TfR1 without interfering with the receptor’s function of transporting iron into cells. Binding to TfR1 may also enable delivery to the CNS.
Linker
The role of the linker is to connect, or conjugate, the Fab and the therapeutic payload, such as oligonucleotide or enzyme. As a result, it is critical that the linker maintain stability in serum and provide release kinetics that favor sufficient payload accumulation in the targeted muscle cell. For the company’s DM1, DMD and FSHD product candidates, the company has selected the Val-Cit linker based on its clinically validated safety and efficacy in approved products, its serum stability and its endosomal release attributes. Serum stability is necessary to enable systemic intravenous administration, stability of the conjugated oligonucleotide in the bloodstream, delivery to muscle tissue and internalization of the therapeutic payload in the muscle cells. In preclinical studies, the company’s Val-Cit linker facilitated precise conjugation of multiple types of payloads to the company’s proprietary Fabs, including ASOs, siRNAs, and PMOs. For the company’s Pompe product candidate, the company selected a linker that effectively connects to the GAA enzyme payload. This broad flexibility enables the company to rationally select the appropriate type of payload to address the genetic basis of each muscle disease. Additionally, the company’s linker and conjugation chemistry allow the company to optimize the ratio of payload molecules attached to each Fab for each type of payload. The company’s linker and conjugation chemistry will enable the company to rapidly design, produce and screen molecules to enable new muscle disease programs.
Optimized Payload
With the company’s FORCE platform, the company has the flexibility to deploy different types of therapeutic payloads with specific mechanisms of action that modify target functions. Using this modularity, the company rationally selects the therapeutic payload for each program to match the biology of the target, with the aim of addressing the genetic basis of disease and stopping or reversing disease progression. For instance, in the company’s DM1 program, where the genetic driver of DM1 is mutant DMPK pre-mRNA located in the nucleus, the company has determined to use an ASO because ASOs have advantages in degrading RNA in the nucleus when compared to siRNAs. In the case of the company’s DMD program, the company is utilizing an exon skipping PMO payload with the goal of enhancing dystrophin expression. For the company’s FSHD program, the company is utilizing a siRNA payload designed to reduce DUX4 expression. For the company’s Pompe program, the company is utilizing enzyme replacement therapy to address the deficiency of the lysosomal enzyme, acid alpha glucosidase, or GAA, the genetic basis of Pompe.
Strategy
The key elements of the company’s strategy are to advance its co-lead product candidates for DM1 and DMD through development and to commercialization to offer meaningful benefit to patients; progress its FSHD program to the clinic with the goal of ultimately offering a therapeutic for a disease with no approved treatments; establish a DMD franchise by expanding its DMD program to reach additional DMD patient populations; expand its pipeline to additional product candidates and indications to fully exploit the potential of its proprietary FORCE platform; selectively enter into strategic collaborations to maximize the value of its pipeline and its proprietary FORCE platform; and build a sustainable leadership position in muscle diseases with a deep connection to patients, caregivers, the research community and physicians.
Portfolio
The company is creating a pipeline of product candidates and programs to address diseases with high unmet need and etiologic targets. Its initial focus is on DM1, DMD, FSHD, and Pompe disease, with potential pipeline expansion opportunities in additional rare skeletal muscle diseases, as well as cardiac and metabolic muscle diseases and diseases involving the CNS. In selecting diseases to target with its FORCE platform, the company seeks diseases with clear translational potential from preclinical disease models to well-defined clinical development and regulatory pathways, and where it believes that it would be able to commercialize any products that it develops and are approved with an efficient, targeted sales force. The company has global commercial rights to all of its programs.
Myotonic dystrophy type 1 (DM1)
The company is developing its product candidate, DYNE-101, to address the genetic basis of DM1 by targeting the toxic nuclear DMPK RNA that causes the disease. DYNE-101 consists of the company's proprietary Fab conjugated with a clinically validated linker to an antisense oligonucleotide (ASO) and is designed to reduce the accumulation of DMPK pre-mRNA in the nucleus, release splicing proteins, and potentially stop or reverse disease progression. In in vitro and in vivo preclinical studies supporting its DM1 program, the company has observed a reduction in nuclear foci and toxic nuclear DMPK RNA, correction of splicing changes, reversal of myotonia (a neuromuscular condition in which the relaxation of a muscle is impaired), and enhanced muscle distribution. DYNE-101 is being evaluated in the ACHIEVE trial, a Phase 1/2 global clinical trial of adult patients with DM1. ACHIEVE, which is designed to be a registrational trial, consists of a 24-week multi-ascending dose (MAD) randomized, placebo-controlled period, a 24-week open-label extension (OLE), a 96-week long-term extension, and a registrational expansion cohort. In January 2025, the company announced the completion of the MAD portion of the trial, its plans to initiate a registrational expansion cohort to support submission for the U.S. Accelerated Approval, and the selection of the 6.8 mg/kg Q8W dose to be evaluated in the registrational expansion cohort. The company also reported 6-month clinical data from the 6.8 mg/kg Q8W cohort of the MAD portion of the trial, including data on safety, tolerability, splicing, DMPK knockdown, and multiple clinical measures, including myotonia as measured by video hand opening time (vHOT), muscle strength, timed function tests, and patient-reported outcomes, including those measuring the CNS manifestations of DM1. At the 6.8 mg/kg Q8W dose, DYNE-101 resulted in significant splicing correction at three months compared to baseline, which was associated with improvement in multiple functional endpoints, beginning at three months and continuing at six months.
DM1 is a monogenic, autosomal dominant, progressive disease that primarily affects skeletal, cardiac and smooth muscles. DM1 patients can suffer from various manifestations of the disease, including myotonia, muscle weakness, cardiac arrhythmias, respiratory problems, fatigue, cardiac abnormalities, gastrointestinal, or GI, complications, early cataracts and cognitive and behavioral impairment.
DM1 is caused by an abnormal expansion in a region of the DMPK gene. Specifically, DM1 is caused by an increase in the number of CTG triplet repeats found in the 3’ non-coding region of the DMPK gene. The number of repeats ranges from up to approximately 35 in healthy individuals to many thousands in DM1 patients. The higher-than-normal number of triplet repeats form large hairpin loops that entrap the DMPK pre-mRNA in the nucleus and impart toxic activity, referred to as a toxic gain-of-function mutation. The mutant DMPK pre-mRNA sequesters in the nucleus, forming nuclear foci that bind splicing proteins. This inhibits the ability of splicing proteins to perform their normal function in the nucleus of guiding pre-mRNA processing of gene transcripts from many other genes. As a result, multiple pre-mRNAs that encode key proteins are mis-spliced. This mis-splicing in the nucleus results in the translation of atypical proteins which ultimately cause the clinical presentation of DM1. When nuclear DMPK levels are reduced, the nuclear foci that bind splicing proteins are diminished, releasing splicing proteins, allowing normal mRNA processing and translation of normal proteins, and potentially stopping or reversing disease progression.
The company is advancing its own efforts to better characterize the actual DM1 patient population through a natural history study that it is sponsoring. Based on age of onset and severity of symptoms, DM1 is typically categorized into four overlapping phenotypes: late-onset, classical (adult-onset), childhood, and congenital (cDM1).
The company’s program is designed to address the genetic basis of DM1 by targeting the toxic nuclear DMPK RNA that is the cause of the disease. The company’s product candidate, DYNE-101, consists of its proprietary Fab targeting TfR1 conjugated to an ASO to reduce the levels of mutant DMPK RNA in the nucleus, thereby releasing splicing proteins, allowing normal mRNA processing and translation of normal proteins, and potentially stopping or reversing disease progression. The ASO is a gapmer oligonucleotide that is designed to translocate to the nucleus, bind its complementary sequence on the DMPK RNA, recruit RNAseH1 to degrade DMPK RNA and thus reduce toxic nuclear DMPK RNA. The company has chosen to develop its product candidate with an ASO because single-stranded ASOs preferentially target nuclear RNAs, which is essential for degradation of toxic nuclear DMPK RNA. DYNE-101 has been awarded orphan drug designation for the treatment of DM1 by both the European Medicines Agency, or EMA, and the U.S. Food and Drug Administration, or FDA, and the FDA also awarded it fast track designation for the treatment of DM1.
Preclinical Data
The company has conducted extensive preclinical studies supporting the development of DYNE-101 in multiple preclinical disease models. In in vitro and in vivo preclinical studies, it observed a reduction of nuclear foci, correction of splicing and reversal of myotonia in disease models, reduction of toxic human nuclear DMPK in a hTfR1/DMSXL DM1 mouse model developed by the company. In NHPs, DYNE-101 demonstrated a favorable safety profile and achieved enhanced muscle distribution as evidenced by a reduction in wild-type DMPK RNA.
Phase 1/2 ACHIEVE Clinical Trial of DYNE-101 in DM1
DYNE-101 is being evaluated in the ACHIEVE trial, a global Phase 1/2 clinical trial consisting of a 24-week MAD, randomized, placebo-controlled period, a 24-week OLE, a 96-week long-term extension, and a registrational expansion cohort. The primary endpoints of the MAD portion of the trial were safety and tolerability; with secondary endpoints of pharmacokinetics and pharmacodynamics, including change from baseline in splicing as measured by the composite alternative splicing index, or CASI-22, as well as multiple measures of muscle strength and function and patient-reported outcomes, including the Myotonic Dystrophy Health Index, or MDHI. In the MAD portion of the ACHIEVE trial, patients were randomized to receive DYNE-101 or placebo intravenously every four weeks or every eight weeks for 24 weeks, depending on cohort. Patient cohorts were dosed from 1.8 mg/kg to 6.8 mg/kg (approximate ASO dose). Following the MAD placebo-controlled period, patients transition to DYNE-101 treatment in the OLE portion of the trial and in the long-term extension.
In January 2025, the company announced the completion of the multi-ascending dose (MAD) portion of the trial, its plans to initiate a registrational expansion cohort to support submission for the U.S. Accelerated Approval, and the selection of the 6.8 mg/kg Q8W dose to be evaluated in the registrational expansion cohort. The company plans to enroll up to 48 patients in the registrational expansion cohort, and the primary endpoint for this cohort will be mean splicing correction at 3 months as measured by CASI-22, supported by clinically meaningful measures of muscle strength and function as secondary endpoints.
Duchenne muscular dystrophy (DMD)
The company is developing product candidates under its DMD program to address the genetic basis of Duchenne muscular dystrophy (DMD) by delivering a phosphorodiamidate morpholino oligomer (PMO) to muscle tissue to promote the skipping of specific DMD exons in the nucleus, allowing muscle cells to create a more complete, functional dystrophin protein and potentially stop or reverse disease progression. In in vitro and in vivo preclinical studies, the company's PMOs, when conjugated to a Fab targeting transferrin receptor 1 (TfR1), have shown increased exon skipping, increased dystrophin expression, reduced muscle damage, and increased muscle function. The company is seeking to build a global DMD franchise by initially focusing on the development of its product candidate DYNE-251 for patients with mutations amenable to skipping exon 51, to be followed by the development of product candidates for patients with mutations amenable to skipping other exons, including exon 53, 45, and 44. DYNE-251 is being evaluated in the DELIVER trial, a Phase 1/2 global clinical trial in males with mutations amenable to skipping exon 51. The DELIVER trial consists of a 24-week multi-ascending dose (MAD) randomized, placebo-controlled period, a 24-week open-label extension, a 192-week long-term extension, and a registrational expansion cohort with the potential to support Accelerated Approval in the U.S. In September 2024, the company reported positive data from the MAD portion of the DELIVER trial, including data on safety, tolerability, and dystrophin expression. In November 2024, the company announced that it has begun enrolling a 20 mg/kg Q4W (approximate PMO dose) registrational expansion cohort of 32 participants as part of the DELIVER trial.
The company's DMD program is designed to address the genetic basis of Duchenne muscular dystrophy (DMD) by promoting the skipping of specific DMD exons in the nucleus, allowing muscle cells to create a more complete, functional dystrophin protein. Under its DMD program, the company is developing product candidates that incorporate its proprietary Fab targeting transferrin receptor 1 (TfR1) conjugated to a phosphorodiamidate morpholino oligomer (PMO) designed to promote the skipping of specific DMD exons in the nucleus. Existing clinical data generated by others supports the benefits of utilizing a single-stranded antisense oligonucleotide (ASO) or PMO to skip the faulty exon in the nucleus of DMD patient cells. The company plans to develop its program candidates for DMD with a PMO, initially for exon 51, and in the future for other exon mutations, including exons 53, 45, and 44.
DYNE-251
The company is evaluating DYNE-251 in the Phase 1/2 global DELIVER clinical trial for people living with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. DYNE-251 consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a Fab that binds to transferrin receptor 1 (TfR1). DYNE-251 has been awarded fast track, orphan drug, and rare pediatric disease designations by the FDA for the treatment of DMD mutations amenable to exon 51 skipping.
Preclinical Data
The company has conducted multiple in vitro and in vivo preclinical studies of its FORCE platform in Duchenne muscular dystrophy (DMD) that have shown increased exon skipping, increased dystrophin expression, reduced muscle damage, and increased muscle function.
In studies in the mdx mouse DMD model, a validated and widely accepted mouse model in DMD which has a mutation in exon 23, the company observed that single intravenous doses of an exon 23-targeting PMO conjugated to a Fab targeting TfR1 which the company refers to as FORCE-M23D, achieved robust, durable exon skipping in cardiac and skeletal muscles after a single dose. In NHPs, DYNE-251 demonstrated a favorable safety profile and achieved robust exon skipping, especially in the heart and diaphragm muscles which weaken over time leading to mortality in people living with DMD.
Phase 1/2 DELIVER Clinical Trial of DYNE-251 in DMD
DYNE-251 is being evaluated in the DELIVER trial, a Phase 1/2 global clinical trial consisting of a 24-week MAD randomized, placebo-controlled period, a 24-week OLE, and a 192-week long-term extension, and a registrational expansion cohort. The trial, which is designed to be registrational, is enrolling ambulant and non-ambulant males with DMD who are ages 4 to 16 and have mutations amenable to exon 51 skipping. The primary endpoints of the MAD portion were safety, tolerability and change from baseline in dystrophin levels as measured by Western blot. Additional endpoints in the MAD portion of the trial included pharmacokinetics and change from baseline in exon 51 skipping levels, muscle tissue percent dystrophin positive fibers, multiple assessments of muscle function, including North Star Ambulatory Assessment, or NSAA, score, Stride Velocity 95th Centile and certain timed functional tests.
In September 2024, the company announced the completion of the MAD portion and positive clinical data from the DELIVER trial. The efficacy assessment of the DYNE-251 DELIVER trial reported in September 2024 was based on 6-month biomarker and functional data from eight male participants enrolled in the 20 mg/kg (approximate PMO dose) cohort who were randomized to receive DYNE-251 or placebo once every four weeks and 12-month functional data from six male participants who were randomized in the 10 mg/kg (approximate PMO dose) cohort.
The company has begun enrolling a 20 mg/kg Q4W (approximate PMO dose) registrational expansion cohort of approximately 32 participants as part of the DELIVER trial. It continues to pursue accelerated approval in the U.S. based on dystrophin as a surrogate endpoint. The company plans to complete enrollment of the registrational expansion cohort in the first quarter of 2025, with data from this cohort expected in late 2025 and potential submission for the U.S. Accelerated Approval in early 2026. The company is also pursuing expedited approval pathways globally for DYNE-251.
Facioscapulohumeral Dystrophy (FSHD)
The company is developing DYNE-302 to address the genetic basis of facioscapulohumeral muscular dystrophy (FSHD) by reducing DUX4 expression in muscle tissue. In June 2024, the company announced new preclinical data for DYNE-302, its product candidate for FSHD, demonstrating robust and durable DUX4 suppression and functional benefit in a mouse model. The company generated these data using an innovative hTfR1/iFLExD mouse model that it developed, which expresses TfR1 and enables tunable DUX4 induction in skeletal muscle. In hTfR1/iFLExD mice, a single intravenous dose of DYNE-302 resulted in a dose-dependent and robust reduction of the DUX4 transcriptome that lasted up to three months, with benefits on muscle structure and function. DYNE-302 also demonstrated high in vitro potency in FSHD patient-derived myotubes. The company is progressing DYNE-302 through investigational new drug (IND) or clinical trial application (CTA)-enabling studies.
Pompe Disease
The company is developing DYNE-401 to deliver an enzyme replacement therapy to address the deficiency of the lysosomal enzyme, GAA, that causes Pompe disease. It engineered FORCE-GAA by leveraging the FORCE platform and evaluated efficacy in vivo using hTfR1/6Neo mice, which were developed by crossing the well-established 6Neo mouse model of Pompe with mice expressing human transferrin receptor 1. Using this approach, intravenous (IV) administration cleared glycogen in muscle and the central nervous system (CNS) and normalized lysosomal size in hTfR1/6Neo mice. This approach reduced serum neurofilament light chain, a biomarker of axonal injury, providing evidence of benefit in the CNS and displayed superior dose potency compared to GAA alone. Additional data with this approach supported the potential for monthly dosing, which is less frequent than approved enzyme replacement therapies for Pompe.
The company intends to expand its FORCE portfolio by pursuing programs in additional indications, including rare skeletal muscle diseases, as well as cardiac and metabolic muscle diseases and diseases involving the CNS. By rationally selecting therapeutic payloads to conjugate with its proprietary Fab and linker, the company plans to develop product candidates to address the genetic basis of additional muscle diseases. For example, it plans to prioritize antisense oligonucleotides (ASOs) for indications driven by nuclear genetic targets and small interfering RNAs (siRNAs) for indications driven by cytoplasmic targets. The company has completed screening and identified potent ASO and siRNA payloads against a number of cardiac and metabolic targets.
The company has demonstrated in preclinical studies that its FORCE platform achieved delivery to the central nervous system (CNS). Intravenous (IV) administration of the FORCE conjugate, its proprietary Fab antibody conjugated to an antisense oligonucleotide (ASO), achieved delivery to the CNS via transferrin receptor 1 (TfR1) in both non-human primates (NHPs) and its hTfR1/DMSXL mouse model. The hTfR1/DMSXL model, developed by the company, expresses human TfR1 and carries a human DMPK gene with more than 1,000 CTG repeats, representing a severe DM1 phenotype. In these studies, the FORCE conjugate was generally well tolerated. In NHPs, the FORCE conjugate achieved superior delivery compared to unconjugated ASO when both were administered intravenously. Additionally, IV administration of FORCE in the company's preclinical studies showed broader distribution throughout the brain compared to intrathecal administration of unconjugated ASO. The FORCE conjugate was also delivered to the brain of hTfR1/DMSXL mice and demonstrated robust knockdown of toxic human nuclear DMPK RNA and foci reduction in hTfR1/DMSXL mice.
Intellectual Property
As of December 31, 2024, the company owned 60 patent application families related to its business, consisted of eight U.S. provisional patent applications, 36 issued U.S. patents, 48 pending U.S. non-provisional patent applications, six pending Patent Cooperation Treaty (PCT) patent applications, and 411 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, Hong Kong, India, Israel, Japan, South Korea, Mexico, New Zealand, Singapore, and South Africa, along with three granted foreign patents. The company exclusively licensed one patent family, which consists of three issued U.S. patents, two pending U.S. patent applications, and one issued European patent that has been validated in Belgium, Switzerland, Germany, Denmark, Spain, France, the United Kingdom, Ireland, Italy, the Netherlands, and Sweden.
The company's owned and licensed patent estate covers various aspects of its programs and technology, including its FORCE platform, proprietary antibodies, oligonucleotide conjugates, enzyme conjugates, methods of treatment, and aspects of manufacturing. Any U.S. or foreign patents issued from national stage filings of its PCT patent applications and any U.S. patents issued from non-provisional applications that it may file in connection with its provisional patent applications would be scheduled to expire on various dates from 2039 through 2045, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity, and other governmental fees.
FORCE Platform
With regard to its FORCE platform, as of December 31, 2024, the company owned three issued U.S. patents, nine pending U.S. non-provisional patent applications, and 67 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, Hong Kong, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These applications relate to various aspects of the FORCE platform, including proprietary antibodies, oligonucleotide conjugates, enzyme conjugates, methods of manufacture, and methods of treatment. The three issued U.S. patents are expected to expire in 2042 without taking into account any possible patent term extensions. Any patents issued from these applications are expected to expire from 2039 to 2042; however, patent term extension may be available.
DM1 Program
With regard to the company’s DM1 program, as of December 31, 2024, it owned three pending U.S. provisional patent applications, 16 issued U.S. patents, ten pending U.S. non-provisional patent applications, two granted foreign patents, and 99 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, Hong Kong, India, Israel, Japan, South Korea, Mexico, New Zealand, Singapore, and South Africa. These applications relate to composition of matter and methods of treating disease involving its FORCE platform in the context of DM1. The 16 issued U.S. patents are expected to expire in 2039, 2042 and 2043 without taking into account any possible patent term extensions. The two granted foreign patents are expected to expire in 2039 without taking into account any possible patent term extensions.
Any additional patents issued from these applications are expected to expire from 2039 to 2045; however, patent term extension may be available.
DMD Programs (exons 51, 53, 44, 45, and other)
With regard to its DMD programs, as of December 31, 2024, the company owned two pending PCT patent applications, 20 issued U.S. patents, 15 pending U.S. non-provisional patent applications, three granted foreign patents, and 147 pending foreign patent applications in Australia, Brazil, China, Canada, Europe, Eurasia, Hong Kong, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These patent filings relate to the composition of matter and methods of treating disease involving the company's FORCE platform in the context of DMD. The 20 issued U.S. patents are expected to expire in 2039 and 2042 without taking into account any possible patent term extensions. The three granted foreign patents are expected to expire in 2039 without taking into account any possible patent term extensions. Any additional patents issued from these applications are expected to expire in 2039 and from 2041 to 2044; however, patent term extension may be available.
FSHD Program
With regard to its FSHD program, as of December 31, 2024, the company owned two pending PCT patent applications, 12 issued U.S. patents, two pending U.S. provisional patent applications, five pending U.S. non-provisional patent applications, two granted foreign patents, and 58 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, Hong Kong, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These patent filings relate to the composition of matter and methods of treating disease involving the company's FORCE platform in the context of FSHD. The 12 issued U.S. patents are expected to expire in 2039 and 2042 without taking into account any possible patent term extensions. The two granted foreign patents are expected to expire in 2039 without taking into account any possible patent term extensions. Any additional patents issued from these applications are expected to expire in 2039 and from 2041 to 2045; however, patent term extension may be available. The company also in-licenses a patent family from the University of Mons (UMONS), comprising two pending U.S. patent applications. Any patents issued from these applications are expected to expire in 2031; however, patent term extension may be available.
Pompe Program
With regard to its Pompe program, as of December 31, 2024, the company owned one pending U.S. provisional patent application and seven pending foreign patent applications in Canada, China, Europe, Eurasia, Israel, Japan, South Korea, and South Africa. These patent filings relate to the composition of matter and methods of treating disease involving the company's FORCE platform in the context of Pompe disease. Any patents issued from these applications are expected to expire in 2039 and 2045; however, patent term extension may be available.
Discovery Programs
With regard to its discovery programs, as of December 31, 2024, the company owned one pending PCT patent application, three pending U.S. non-provisional patent applications, and nine pending foreign patent applications in China, Canada, Europe, and Japan. These applications relate to the composition of matter and methods of treating disease involving the company's FORCE platform in the context of a variety of additional rare skeletal muscle diseases, as well as cardiac and metabolic muscle diseases and diseases involving the CNS. Any patents issued from these applications are expected to expire in 2039, 2041, and 2042; however, patent term extension may be available.
License Agreement with the University of Mons
In April 2020, the company entered into a license agreement with UMONS, or the UMONS Agreement, pursuant to which UMONS granted to the company an exclusive, worldwide license to certain patents and patent applications related to oligonucleotides for the company’s FSHD program and a non-exclusive, worldwide license to existing, related know-how. Each of the issued patents licensed to the company under the UMONS Agreement is scheduled to expire in 2031. The licenses under the UMONS Agreement confer on the company the right to research, develop and commercialize products, which the company refers to as licensed products, and to practice processes, in each case, covered by the licensed patents and existing, related know-how.
Under the UMONS Agreement, the company is obligated to use commercially reasonable efforts to develop at least one licensed product, and to the extent regulatory approval is obtained in such jurisdictions, to commercialize at least one licensed product in the United States and the United Kingdom or a member country of the European Union.
Government Regulation
FDA regulations allow access to investigational products under an IND by the company or the treating physician for treatment purposes on a case-by-case basis for: individual patients (single-patient IND applications for treatment in emergency settings and non-emergency settings); intermediate-size patient populations; and larger populations for use of the investigational product under a treatment protocol or treatment IND application. The company’s third-party manufacturers are required to manufacture any product candidates it develops under current Good Manufacturing Practice, or cGMP, requirements and other applicable laws and regulations.
History
Dyne Therapeutics, Inc. was founded in 2017. The company was incorporated in 2017.
