Dyne Therapeutics Stock

Dyne Therapeutics, Inc. operates as a clinical-stage muscle disease company.

The company is advancing innovative life-transforming therapeutics for people living with genetically driven diseases. It is utilizing its proprietary FORCE platform to overcome the current limitations of muscle tissue delivery and advance modern oligonucleotide therapeutics for muscle diseases. The company’s proprietary FORCE platform therapeutics consist of an oligonucleotide payload that the company rationally designs to target the genetic basis of the disease it is seeking to treat, a clinically validated linker and an antigen-binding fragment, or Fab, that the company attaches to the payload using the linker. With its FORCE platform, the company has the flexibility to deploy different types of oligonucleotide payloads with specific mechanisms of action that modify target functions. The company leverages this modularity to focus on muscle 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 the company’s FORCE platform, it is assembling a broad portfolio of muscle disease therapeutics, including the company’s programs in myotonic dystrophy type 1, or DM1, Duchenne muscular dystrophy, or DMD, and facioscapulohumeral dystrophy, or FSHD. 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. The company has identified product candidates for each of its DM1, DMD and FSHD programs that are in varying stages of preclinical and clinical development.

For the company’s product candidate DYNE-101, in September 2022 the company began enrollment in ACHIEVE, an ongoing Phase 1/2 global clinical trial in adult 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 and a 96-week long-term extension. The company anticipates reporting initial data on safety, tolerability and splicing from the MAD portion of the trial in the second half of 2023.

For the company’s product candidate DYNE-251, in August 2022 the company began enrollment in DELIVER, an ongoing Phase 1/2 global clinical trial in males with DMD who have mutations amenable to exon 51 skipping therapy. DELIVER, which is designed to be a registrational trial, consists of a 24-week MAD randomized, placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The company anticipates reporting initial data on safety, tolerability and dystrophin from the MAD portion of the trial in the second half of 2023.

In September 2022, the company was re prioritizing its focus and resources on the company’s clinical programs, DYNE-101 for DM1 and DYNE-251 for DMD. As a result, the company announced the deferral of the Investigational New Drug, or IND, application submission for the company’s product candidate DYNE-301 for FSHD that the company had originally targeted for the second half of 2022. The company plans to provide an update on the FSHD program by the end of 2023.

Strategy

The key elements of the company’s strategy are to advance its co-lead programs in DM1 and DMD to clinical proof-of-concept and approval 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 the company’s DMD program to reach additional DMD patient populations; expand its pipeline of therapeutics for muscle diseases to fully exploit the potential of its proprietary FORCE platform; selectively enter into strategic collaborations to maximize the value of its pipeline and the company’s 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 with etiologic targets. Its initial focus is on DM1, DMD and FSHD with potential pipeline expansion opportunities in additional rare skeletal muscle diseases, as well as cardiac and metabolic muscle diseases. 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 the company would be able to commercialize any products that it develops and is 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 its linker to an 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 the company’s DM1 program, it has observed a reduction in nuclear foci and toxic nuclear DMPK RNA, correction of splicing changes, reversal of myotonia, which is a neuromuscular condition in which the relaxation of a muscle is impaired, and enhanced muscle distribution. In 2022, the company submitted regulatory filings and received subsequent clearances in multiple countries outside of the United States for DYNE-101. 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 MAD randomized, placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The company anticipates reporting initial data from the MAD placebo-controlled portion of the ACHIEVE trial on safety, tolerability and splicing in the second half of 2023.

The company is advancing its own efforts to better characterize the actual DM1 patient population through a natural history study that the company is sponsoring. The introduction of new therapies for DM1 will cause the diagnosis rate to improve, resulting in an increase in the overall prevalence estimates for the disease.

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 linked 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.

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, the company 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, as well as enhanced muscle distribution. These data support the potential for its oligonucleotide therapy to be a disease-modifying therapy for patients with DM1.

The company has developed an innovative hTfR1/DMSXL mouse model designed to evaluate pharmacodynamics and accelerate the advancement of its DM1 program. The company also evaluated DYNE-101 in non-human primates.

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 open-label extension and a 96-week long-term extension. The trial, which is designed to be registrational, is expected to enroll approximately 64 adult patients with DM1 who are 18 to 49 years of age. Following the placebo-controlled period, patients transition to DYNE-101 treatment in the open-label portion of the trial and in the long-term extension. The company anticipates reporting initial data on safety, tolerability and splicing from the MAD portion of the trial in the second half of 2023.

Duchenne Muscular Dystrophy (DMD)

The company is developing program candidates under its DMD program to address the genetic basis of DMD by delivering a 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 to potentially stop or reverse disease progression. In in vitro and in vivo preclinical studies, the company’s PMOs when conjugated to a Fab targeting 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 therapeutics for patients with mutations amenable to skipping other exons, including Exon 53, 45 and 44.

In 2022, the company submitted regulatory filings and received subsequent clearances in multiple countries, including the United States, for DYNE-251. 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 MAD randomized, placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The company anticipates reporting initial data on safety, tolerability and dystrophin from the MAD portion of the trial are anticipated in the second half of 2023. In October 2022, the U.S. Food and Drug Administration granted Fast Track designation for DYNE-251.

The company’s DMD program is designed to address the genetic basis of DMD by promoting the skipping of specific DMD exons in the nucleus, allowing muscle cells to create more complete, functional dystrophin protein.

Under the company’s DMD program, it is developing program candidates that incorporate the company’s proprietary Fab targeting TfR1 conjugated to a PMO designed to promote the skipping of specific DMD exons in the nucleus. 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.

The company has conducted multiple in vitro and in vivo preclinical studies of its FORCE platform in DMD that have shown increased exon skipping, increased dystrophin expression, reduced muscle damage and increased muscle function. These data support the potential for DYNE-251 to be a disease-modifying therapy for patients with DMD amenable to skipping Exon 51. The company also evaluated the safety and tolerability of DYNE-251 in a GLP toxicology study.

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 open-label extension and a 96-week long-term extension. Following the placebo-controlled period, patients transition to DYNE-251 treatment in the open-label portion of the trial and in the long-term extension. The company anticipates reporting initial data on safety, tolerability and dystrophin from the MAD portion of the trial are anticipated in the second half of 2023.

The company is seeking to build a global DMD franchise by initially focusing on the development of DYNE-251 in patients with mutations amenable to skipping Exon 51, to be followed by the development of therapeutics for patients with mutations amenable to skipping other exons, including Exons 53, 45 and 44.

Facioscapulohumeral Dystrophy (FSHD)

The company is developing its product candidate, DYNE-301 to address the genetic basis of FSHD by reducing DUX4 expression in muscle tissue. The company exclusively licensed from the University of Mons, or UMONS, intellectual property covering multiple ASOs that have been shown to potently target DUX4 in preclinical studies. DYNE-301, consists of the company’s proprietary Fab conjugated with its linker to an ASO that is designed to address the genetic basis of FSHD by reducing DUX4 expression in muscle tissue. The company generated proof-of-concept data showing that DYNE-301 reduced expression of key DUX4 biomarkers in FSHD patient myotubes, a type of muscle cell. The company continues to evaluate the optimal approach to target DUX4 and translate its preclinical work to a tractable clinical development pathway. The company plans to provide an update on the FSHD program by the end of 2023.

The company generated proof-of-concept data showing that DYNE-301 reduced expression of key DUX4 biomarkers in FSHD patient myotubes.

In September 2022, the company was prioritizing its focus and resources on its clinical programs, DYNE-101 for DM1 and DYNE-251 for DMD. As a result, the company announced the deferral of the IND application submission for DYNE-301 for FSHD that the company had originally targeted for the second half of 2022. The company plans to provide an update on the FSHD program by the end of 2023.

Discovery Programs

The company intends to expand its FORCE portfolio by pursuing programs in additional indications, including additional rare skeletal muscle diseases, as well as cardiac and metabolic muscle diseases. By rationally selecting therapeutic payloads to conjugate with the company’s proprietary Fab and linker, the company plans to develop product candidates to address the genetic basis of additional muscle diseases. In selecting these payloads, the company plans to prioritize ASOs for indications driven by nuclear genetic targets and 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 may selectively establish strategic collaborations for certain of these programs where the company could benefit from the resources or capabilities of other biopharmaceutical companies. The company may also seek strategic collaborations where the company can utilize its FORCE platform to enhance delivery of third-party payloads to muscle tissue.

In addition to the company’s muscle disease portfolio, there is an opportunity to leverage its TfR1 antibody expertise to develop novel antibodies that cross the blood-brain barrier and deliver therapeutics to CNS tissue through systemic intravenous administration. These antibodies will likely have different characteristics, such as TfR1 affinity, than the antibodies the company has optimized for muscle delivery.

Intellectual Property

As of December 31, 2022, the company owned 57 patent application families related to its business, consisted of 15 U.S. provisional patent applications, eight issued U.S. patents, 32 pending U.S. non-provisional patent applications, 24 pending Patent Cooperation Treaty, or PCT, patent applications, and 132 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa; and the company exclusively licensed one patent family, consisted of two 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 the company’s programs and technology, including its FORCE platform, proprietary antibodies, oligonucleotide conjugates, methods of treatment and aspects of manufacturing. Any U.S. or foreign patents issued from national stage filings of the company’s PCT patent applications and any U.S. patents issued from non-provisional applications the company may file in connection with its provisional patent applications would be scheduled to expire on various dates from 2039 through 2043, 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 the company’s FORCE platform, as of December 31, 2022, the company owned four pending PCT patent applications, eight pending U.S. non-provisional patent applications, and 32 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These applications relate to various aspects of the company’s FORCE platform, including proprietary antibodies, oligonucleotide conjugates, methods of manufacture and methods of treatment. 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, 2022, the company owned two pending PCT patent applications, four pending U.S. provisional patent applications, two issued U.S. patents, five pending U.S. non-provisional patent applications, and 25 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These applications relate to composition of matter and methods of treating disease involving the company’s FORCE platform in the context of DM1. The two issued U.S. 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 2043, however, patent term extension may be available.

DMD Programs (Exons 51, 53, 44, 45, and Other)

With regard to the company’s DMD programs, as of December 31, 2022, the company owned nine pending PCT patent applications, three pending U.S. provisional patent applications, five issued U.S. patents, four pending U.S. non-provisional patent applications, and 25 pending foreign patent applications in Australia, Brazil, China, Canada, Europe, Eurasia, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These patent filings relate to composition of matter and methods of treating disease involving the company’s FORCE platform in the context of DMD. The five issued U.S. 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, 2041, 2042 and 2043; however, patent term extension may be available.

FSHD Program

With regard to the company’s FSHD Program, as of December 31, 2022, the company owned two pending PCT patent applications, four issued U.S. patents, six pending U.S. non-provisional patent applications, and 25 pending foreign patent applications in Australia, Brazil, Canada, China, Europe, Eurasia, India, Israel, Japan, South Korea, Mexico, Singapore, and South Africa. These patent filings relate to composition of matter and methods of treating disease involving the company’s FORCE platform in the context of FSHD. The four issued U.S. 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, 2041, 2042 and 2043; however, patent term extension may be available. The company also in-licenses a patent family from UMONS consisted of two 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 issued patents expire in 2031; however, a patent term extension may be available.

Discovery Programs

With regard to the company’s discovery programs, as of December 31, 2022, the company owned one pending PCT patent application, three pending U.S. non-provisional patent applications, and five pending foreign patent applications in China, Canada, Europe and Japan. These applications relate to 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. 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.

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.

History

Dyne Therapeutics, Inc. was founded in 2017. The company was incorporated under the laws of the state of Delaware in 2017.