Sarepta Therapeutics Stock

Sarepta Therapeutics, Inc. operates as a commercial-stage biopharmaceutical company.

The company focuses on helping patients through the discovery and development of unique RNA-targeted therapeutics, gene therapy and other genetic therapeutic modalities for the treatment of rare diseases. Applying the company’s proprietary, highly-differentiated and innovative technologies, and through collaborations with its strategic partners, it has developed multiple approved products for the treatment of Duchenne muscular dystrophy (Duchenne) and is developing potential therapeutic candidates for a broad range of diseases and disorders, including Duchenne, Limb-girdle muscular dystrophies (LGMDs) and other neuromuscular and central nervous system (CNS) related disorders.

Commercial Products

As of December 31, 2022, the company had developed and commercialized the following approved products for the treatment of Duchenne:

EXONDYS 51 (eteplirsen) Injection (EXONDYS 51) is indicated for the treatment of Duchenne in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 51 skipping. EXONDYS 51 uses the company’s phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene.

VYONDYS 53 (golodirsen) Injection (VYONDYS 53) is indicated for the treatment of Duchenne in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. VYONDYS 53 uses the company’s PMO chemistry and exon-skipping technology to skip exon 53 of the dystrophin gene.

AMONDYS 45 (casimersen) Injection (AMONDYS 45) is indicated for the treatment of Duchenne in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping. AMONDYS 45 uses the company’s PMO chemistry and exon-skipping technology to skip exon 45 of the dystrophin gene.

Technology and Platforms

As part of its multifaceted approach to Duchenne, the company is developing gene therapy technologies to treat Duchenne. The company is clinically developing a product candidate, SRP-9001 that aims to express a smaller but still functional version of dystrophin. The company uses a unique adeno-associated virus (AAV) vector called AAVrh.74 to transport the transgene – the genetic material that will make the protein of interest – to the target cells. A unique, engineered dystrophin is used because naturally-occurring dystrophin is too large to fit in an AAV.

The company is also developing gene therapy programs for various forms of limb-girdle muscular dystrophies (LGMDs). The company’s most advanced LGMD product candidate, SRP-9003, is designed to transfer a gene that codes for and restores beta-sarcoglycan protein with the goal of restoring the dystrophin associated protein complex. SRP-9003 utilizes the AAVrh.74 vector, the same vector used in SRP-9001.

The company’s pipeline includes more than 40 programs at various stages of discovery, pre-clinical and clinical development, reflecting its aspiration to apply its multifaceted approach and expertise in precision genetic medicine to make a profound difference in the lives of patients suffering from rare diseases.

Strategy

The key elements of the company’s strategy include continuing to build its gene therapy engine, including developing gene therapy product candidates, operationalizing its manufacturing strategy and furthering its commercial capabilities in preparation for potential regulatory approvals; advancing its RNA technologies (e.g., phosphorodiamidate morpholino oligomer (PMO) and PPMO), launching potential approved products and supporting commercialization of approved products; investing in next-generation precision medicine through internal research, strategic partnerships, collaborations and other potential opportunities; and continuing to nurture its culture, which is based on strong patient focus, bias to action, a self-starter mentality, smart and appropriate risk-taking and high ethics.

Commercial Products

EXONDYS 51: The company launched its first commercial product, EXONDYS 51, in 2016. EXONDYS 51 is indicated for the treatment of Duchenne in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 51 skipping. EXONDYS 51 uses the company’s PMO chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. PMO-based compounds are synthetic compounds that bind to complementary sequences of RNA by standard Watson-Crick nucleobase pairing.

EXONDYS 51 targets the most frequent series of mutations that cause Duchenne. Approximately 13% of Duchenne patients are amenable to exon 51 skipping.

VYONDYS 53: The company launched VYONDYS 53 in 2019. VYONDYS 53 is indicated for the treatment of Duchenne in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. VYONDYS 53 uses the company’s PMO chemistry and exon-skipping technology to skip exon 53 of the dystrophin gene. VYONDYS 53 has the potential to treat up to 8% of Duchenne patients who are amenable to exon 53 skipping.

AMONDYS 45: The company launched AMONDYS 45 in the first quarter of 2021. AMONDYS 45 is indicated for the treatment of Duchenne in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping. AMONDYS 45 uses the company’s PMO chemistry and exon-skipping technology to skip exon 45 of the dystrophin gene. AMONDYS 45 has the potential to treat up to 8% of Duchenne patients who are amenable to exon 45 skipping.

The company is conducting various clinical trials for EXONDYS 51, VYONDYS 53 AND AMONDYS 45, including studies that are required to comply with its post-marketing FDA requirements and commitments to verify and describe the clinical benefit of the three products.

Pipeline – Key Programs

SRP-5051 (Duchenne PPMO (cell-penetrating peptide-conjugated PMO) program) uses the company’s next-generation chemistry platform, PPMO, and its exon-skipping technology to skip exon 51 of the dystrophin gene. The PPMO technology features covalent attachment of a cell-penetrating peptide to a PMO with the goal of enhanced delivery into the cell. In pre-clinical research, the company’s proprietary class of PPMO compounds demonstrated an increase in dystrophin production and a more durable response compared to PMO.

In 2019, the company commenced a multiple ascending dose study for the treatment of Duchenne with SRP-5051 in patients who are amenable to exon 51 skipping (Study 5051-201). In December 2020 and May 2021, the company announced results from Part A of Study 5051-201. The company initiated Part B of Study 5051-201 in the fourth quarter of 2021 and is enrolling. In August 2022, the FDA lifted the clinical hold placed on Study 5051-201 following a serious adverse event of hypomagnesemia.

SRP-9001 (Duchenne gene therapy program) aims to express a smaller but still functional version of dystrophin.

In the fourth quarter of 2017, an investigational new drug (IND) application for SRP-9001 was cleared by the FDA, and a Phase 1/2a clinical trial in individuals with Duchenne was initiated (Study 101). In October 2018, Nationwide Children’s Hospital (Nationwide) presented results from Study 101 in four individuals with Duchenne enrolled in the trial. In March 2019, the company presented nine-month functional and creatine kinase (CK) data from baseline from these four individuals, and twelve-month CK data from baseline from one of these individuals. In the fourth quarter of 2018, the company commenced a randomized, double-blind, placebo-controlled trial of SRP-9001 with the goal to establish the functional benefits of SRP-9001 protein expression (Study 102). In January 2021, the company released top-line results for Part 1 of Study 102 (the 48-week assessment of the 41 participants) and interim expression results from Part 2 of Study 102 (the crossover phase). The company announced topline results for Part 2 of Study 102 in January 2022. In May 2021, the company announced 12-week expression and safety results from the first 11 participants enrolled in Study 103, an open-label study evaluating the safety and expression of commercially representative material for SRP-9001 (Study 103). In October 2021, the company announced functional data from the first 11 patients and tolerability data for all 32 patients enrolled in Study 103. The company also initiated its pivotal trial of SRP-9001 for the treatment of Duchenne (Study 301) in October 2021 and expects the data read out in the fourth quarter of 2023. In July 2022, the company announced additional data from Study 102 and Study 103.

In September 2022, the company announced that it submitted a biologics license application (BLA) seeking accelerated approval of SRP-9001 for the treatment of ambulant individuals with Duchenne muscular dystrophy (Duchenne). In November 2022, the FDA accepted for filing and granted priority review for the BLA for SRP-9001 with an anticipated regulatory action date of May 29, 2023.

SRP-9003 (LGMD, gene therapy program): The company is developing gene therapy programs for various types of LGMDs. The company’s LGMD programs use the AAVrh.74 vector, the same vector used in its SRP-9001 gene therapy program, to transfect a restorative gene. The most advanced of the company’s LGMD product candidates, SRP-9003, aims to treat LGMD2E, also known as beta-sarcoglycanopathy, a severe and debilitating form of LGMD characterized by progressive muscle fiber loss, inflammation and muscle fiber replacement with fat and fibrotic tissue. SRP-9003 is designed to transfect a gene that codes for and restores beta-sarcoglycan protein with the goal of restoring the dystrophin associated protein complex. SRP-9003 has generated positive pre-clinical safety and efficacy data utilizing the AAVrh.74 vector.

A Phase 1/2a trial of SRP-9003 commenced in the fourth quarter of 2018. In February 2019, the company announced two-month biopsy data from the first three-patient cohort dosed in the SRP-9003 trial, and in October 2019, the company announced nine-month functional data from these three patients. In June 2020, the company announced safety and expression results from three clinical trial participants in the high-dose cohort measured at 60 days, and one-year functional data from three clinical trial participants in the low-dose cohort. In September 2020, the company announced six-month functional data from three clinical trial participants in the in the high-dose cohort, and eighteen-month functional data from three clinical trial participants in the low-dose cohort. The company also announced one-year functional data in the high-dose cohort and two-year functional data in the low-dose cohort in March 2021. In March 2022, the company announced 36-month functional data from three clinical trial participants in the low-dose cohort and 24-month functional data from two clinical trial participants in the high-dose cohort.

Manufacturing, Supply and Distribution

The company’s gene therapy manufacturing capabilities have been greatly enhanced through partnerships with Thermo Fisher Scientific Inc. (Thermo), Catalent, Inc. (Catalent) and Aldevron LLC (Aldevron).

Manufacturers and suppliers of the company’s commercial products and product candidates are subject to the FDA’s current GMP (Good Manufacturing Practices) (cGMP) requirements and other rules and regulations prescribed by foreign regulatory authorities. The company depends on its third-party partners for continued compliance with cGMP requirements and applicable foreign standards.

Material Agreements

F. Hoffman-La Roche Ltd

License, Collaboration, and Option Agreement

On December 21, 2019, the company entered into a license, collaboration, and option agreement (the Collaboration Agreement) with F. Hoffman-La Roche Ltd (Roche) pursuant to which it granted Roche an exclusive license under certain of its intellectual property rights to develop, manufacture, and commercialize SRP-9001 in all countries outside of the U.S. The company retained all rights to SRP-9001 in the U.S. The company intends to manufacture and supply all clinical and, upon approval in the relevant market, commercial supply of SRP-9001.

Roche Options and Negotiation Rights

Pursuant to the Collaboration Agreement, the company granted Roche an exclusive option to obtain an exclusive license to develop, manufacture and commercialize the following products outside of the U.S. certain exon-skipping products that target the dystrophin gene to induce exon skipping, including eteplirsen, golodirsen, casimersen and SRP-5051; certain gene therapy products other than SRP-9001 that encode and directly express dystrophin or a derivative thereof; and certain gene-editing products that modify, repair, or activate an endogenous dysfunctional dystrophin gene.

Myonexus Therapeutics Inc.

On May 3, 2018, the company purchased from Myonexus Therapeutics Inc. (Myonexus), a privately-held Delaware corporation.

BioMarin Pharmaceutical Inc.

License Agreement

On July 17, 2017, the company executed a license agreement (as amended on April 14, 2019 and November 17, 2021, the License Agreement) with BioMarin Leiden Holding BV, BioMarin Nederlands BV and BioMarin Technologies BV (collectively, BioMarin), pursuant to which BioMarin granted it a royalty-bearing, worldwide license under patent rights (Licensed Patents) and know-how (Licensed Know-How) controlled by BioMarin with respect to BioMarin’s Duchenne program, which are potentially necessary or useful for the treatment of Duchenne, to practice and exploit the Licensed Patents and Licensed Know-How in all fields of use and for all purposes, including to develop and commercialize antisense oligonucleotide products that target one or more exons of the dystrophin gene to induce exon skipping, including eteplirsen, golodirsen and casimersen (collectively, the Products).

University of Western Australia

In April 2013, the company entered into an agreement with UWA under which an existing exclusive license agreement between the two parties was amended and restated and, in June 2016, the company entered into the first amendment to the license agreement (the UWA License Agreement). The UWA License Agreement grants the company specific rights to compounds for the treatment of Duchenne by inducing exon skipping. EXONDYS 51, VYONDYS 53 and AMONDYS 45 fall under the scope of the license agreement.

Key Patents and Regulatory Exclusivities

The company’s products, product candidates and its technologies are primarily protected by composition of matter and methods of use patents and patent applications. A summary of granted composition of matter and/or methods of use patents that the company solely owns or controls (or in the case of BioMarin/AZL patents, control with BioMarin), which cover its products in the U.S. and Europe.

Platform Technologies

The company separately owns patents and patent applications in the U.S. and in major foreign markets that cover its proprietary PMO-based platform technologies (e.g., PPMO) relevant to its products. These patents, and patent applications, if granted, expire through at least 2038, such expiration dates not accounting for any patent term extension, supplemental protection certificate or pediatric extensions that may be available.

Trademarks

The company typically files trademark applications and pursue their registration in the U.S., Europe and other markets in which it anticipates using such trademarks. The company is the owner of multiple federal trademark registrations in the U.S. including, but not limited to, Sarepta, Sarepta Therapeutics, the double-helix logo, EXONDYS, EXONDYS 51, the EXONDYS 51 Logo, VYONDYS, VYONDYS 53, the VYONDYS 53 Logo, AMONDYS, AMONDYS 45, and the AMONDYS 45 Logo. In addition, the company has multiple pending trademark applications and registrations in the U.S. and in major foreign markets.

Competition

The company faces competition in the field of Duchenne by third parties who are developing or who had once developed exon skipping product candidates, such as Wave (notably for exons 51 and 53), Nippon Shinyaku (notably for exon 44 and exon 53, for which it has received FDA approval for its product Viltepso (viltolarsen)), Daiichi (notably for exon 45), Dyne Therapeutics pursuing antibody-oligonucleotide conjugates for exons 44, 45, 51, and 53, Avidity Biosciences pursuing antibody-oligonucleotide conjugates for exons 44, 45 and 51, PepGen (notably for exon 51) and BioMarin (BMN-351 for exon 51); gene therapies, such as Pfizer and Solid (in partnership with Ultragenyx), and Regenxbio; gene editing, including CRISPR/Cas 9 approaches, such as Exonics Therapeutics (acquired by Vertex Pharmaceuticals), CRISPR Therapeutics, Editas Medicine, Beam Therapeutics Inc. (in partnership with Pfizer) and Precision Biosciences (in partnership with Eli Lilly); other disease modifying approaches, such as PTC Therapeutics, which has a small molecule candidate, ataluren, that targets nonsense mutations; and other approaches that may be palliative in nature or potentially complementary with its products and product candidates and that are or were once being developed by Santhera, Catabasis, Fibrogen, ReveraGen, Capricor Therapeutics (in partnership with Nippon Shinyaku), BioPhytis, Mallinckrodt, Antisense Therapeutics, Italfarmco, Dystrogen and Edgewise Therapeutics.

Government Regulation

To obtain the U.S. Food and Drug Administration (FDA) approval of a product candidate, the company must, among other things, submit clinical data providing substantial evidence of safety and efficacy of the product for its intended use, as well as detailed information on product composition, its manufacture and controls and proposed labeling. In addition to regulations enforced by the FDA and foreign authorities relating to the clinical development and marketing of products, the company are or may become subject to regulation under the Occupational Safety and Health Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential future foreign, federal, state and local laws and regulations.

History

Sarepta Therapeutics, Inc. was founded in 1980. The company was incorporated in the state of Oregon in 1980 and reincorporated in the state of Delaware in 2013.