We are a commercial-stage biopharmaceutical company focused 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.
−Removed: Applying our proprietary, highly-differentiated and innovative technologies, and through collaborations with our strategic partners, we are developing potential therapeutic candidates for a broad range of diseases and disorders, including Duchenne muscular dystrophy (“DMD”), Limb-girdle muscular dystrophies (“LGMDs”), Mucopolysaccharidosis type IIIA (“MPS IIIA”) and other neuromuscular and central nervous system (“CNS”) related disorders.
+Added: Applying our proprietary, highly-differentiated and innovative technologies, and through collaborations with our strategic partners, we are developing potential therapeutic candidates for a broad range of diseases and disorders, including Duchenne muscular dystrophy (“DMD”), Limb-girdle muscular dystrophies (“LGMDs”) and other neuromuscular and central nervous system (“CNS”) related disorders.
Our first commercial product, EXONDYS 51 (eteplirsen) Injection (“EXONDYS 51”), was granted accelerated approval by the U.S.
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VYONDYS 53 uses our PMO chemistry and exon-skipping technology to skip exon 53 of the dystrophin gene.
−Removed: In addition to our commercial-stage products, we have a PMO-based product candidate in clinical development that is designed to treat those patients with DMD who have genetic mutations amenable to skipping exon 45 of the DMD gene (SRP-4045) (casimersen).
−Removed: In January 2020, we commenced our rolling submission of a New Drug Application (“NDA”) to the FDA seeking accelerated approval for casimersen.
−Removed: We also have other PMO-based product candidates in discovery and preclinical development that are designed to skip other exons of the DMD gene.
+Added: Our third commercial product, AMONDYS 45 (casimersen) Injection (“AMONDYS 45”), was granted accelerated approval by the FDA on February 25, 2021.
+Added: AMONDYS 45 is indicated for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.
+Added: AMONDYS 45 uses our PMO chemistry and exon-skipping technology to skip exon 45 of the dystrophin gene.
Exon skipping is intended to promote the production of an internally truncated but functional dystrophin protein.
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Our most advanced PPMO product candidate is SRP-5051, which is designed to treat DMD in patients with genetic mutations amenable to exon 51 skipping.
−Removed: In 2017, we commenced a first-in-human, single ascending dose, Phase 1 clinical trial for this product candidate.
−Removed: In 2019, we commenced a multiple ascending dose study for the treatment of DMD with SRP-5051 in patients who are amenable to exon 51 skipping, and we expect to have safety and dosing insights for this study by the middle of 2020.
As part of our multifaceted approach to DMD, we are also developing gene therapy technologies to treat DMD.
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Micro-dystrophin is used because naturally-occurring dystrophin is too large to fit in an AAV.
−Removed: On October 3, 2018, Nationwide Children’s Hospital (“Nationwide”) presented positive results from a Phase 1/2a clinical trial testing SRP-9001 in four individuals with DMD enrolled in the trial.
−Removed: On March 25, 2019, we 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.
−Removed: In the fourth quarter of 2018, we commenced a randomized, double-blind, placebo-controlled trial with the goal to establish the functional benefits of micro-dystrophin expression.
−Removed: We have dosed all 41 participants in that trial and have begun dosing participants in the crossover phase of the study.
−Removed: We plan to commence a trial evaluating SRP-9001 using commercial supply in the middle of 2020, pending regulatory feedback.
−Removed: We are also develop ing gene therapy programs for various forms of LGMDs.
+Added: We are also developing gene therapy programs for various forms of LGMDs.
Our 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.
−Removed: We commenced a Phase 1/2a trial of SRP-9 0 03 in the fourth quarter of 2018 .
−Removed: O n February 27, 2019, we announced positive two-month biopsy data from the first three-patient cohort dosed in the SRP-90 0 3 trial and on October 4, 2019, we announced positive nine-month functional data from these three patients .
−Removed: We have recently dosed one additional cohort of three patients at a higher dose per the study protocol .
−Removed: We expect to have the results from the second cohort and to make a dose selection in the third quarter of 2020 .
Our pipeline includes more than 40 programs at various stages of discovery, pre-clinical and clinical development, reflecting our aspiration to apply our multifaceted approach and expertise in precision genetic medicine to make a profound difference in the lives of patients suffering from rare diseases.
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Currently, there are no available treatment options for LGMDs.
−Removed: MPS IIIA is a rare inherited neurodegenerative lysosomal storage disorder characterized by intractable behavioral problems and developmental regression resulting in early death.
−Removed: It is caused by mutations in the SGSH gene, which encodes an enzyme called Heparan-N-sulfamidase necessary for heparan sulfate (“HS”) recycling in cells.
−Removed: The disrupted lysosomal degradation and resulting storage of HS and glycolipids such as gangliosides leads to severe neurodegeneration.
−Removed: MPS IIIA affects approximately 1 in 100,000 individuals and is inherited in an autosomal recessive pattern.
−Removed: There are currently no treatment options for patients.
−Removed: CMT is a group of hereditary, degenerative nerve diseases that are caused by mutations in genes that produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath.
+Added: Charcot-Marie-tooth Disease, or CMT is a group of hereditary, degenerative nerve diseases that are caused by mutations in genes that produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath.
CMT can cause degeneration of motor skills, resulting in muscle weakness, and limiting patients’ ability to walk or use their hands, and in some cases, can cause degeneration of sensory nerves, resulting in a reduced ability to feel heat, cold, and pain.
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Thus, PMOs use a fundamentally different mechanism from other RNA-targeted technologies.
−Removed: We are in the process of conducting various EXONDYS 51 clinical trials, including studies that are required to comply with our post-marketing FDA requirements/commitments to verify and describe the clinical benefit of EXONDYS 51.
EXONDYS 51 targets the most frequent series of mutations that cause DMD.
Approximately 13% of DMD patients are amenable to exon 51 skipping.
−Removed: For the years ended December 31, 2019, 2018, and 2017, the Company recorded net revenue of $380.7 million, $301.0 million, and $154.6 million, respectively, related to the sale of EXONDYS 51.
+Added: We are in the process of conducting various EXONDYS 51 clinical trials, including studies that are required to comply with our post-marketing FDA requirements/commitments to verify and describe the clinical benefit of EXONDYS 51.
VYONDYS 53 , our second commercial product, approved by the FDA on December 12, 2019, is indicated for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.
VYONDYS 53 uses our PMO chemistry and exon-skipping technology to skip exon 53 of the dystrophin gene.
+Added: VYONDYS 53 has the potential to offer treatment to up to 8% of DMD patients who are amenable to exon 53 skipping.
We are in the process of conducting various VYONDYS 53 clinical trials, including studies that are required to comply with our post-marketing FDA requirements/commitments to verify and describe the clinical benefit of VYONDYS 53.
−Removed: VYONDYS 53 targets the second most frequent series of mutations that cause DMD.
−Removed: Up to 8% of DMD patients are amenable to exon 53 skipping.
−Removed: As of December 31, 2019, we had commenced shipment of VYONDYS 53 but revenue from VYONDYS 53 was immaterial.
+Added: AMONDYS 45 , our third commercial product, approved by the FDA on February 25, 2021, is indicated for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.
+Added: AMONDYS 45 uses our PMO chemistry and exon-skipping technology to skip exon 45 of the dystrophin gene.
+Added: AMONDYS 45 has the potential to offer treatment to up to 8% of DMD patients who are amenable to exon 45 skipping.
+Added: We are in the process of conducting various AMONDYS 45 clinical trials, including studies that are required to comply with our post-marketing FDA requirements/commitments to verify and describe the clinical benefit of AMONDYS 45.
+Added: For the years ended December 31, 2020, 2019, and 2018, the Company recorded net revenue of $455.9 million, $380.8 million, and $301.0 million, respectively, related to the sale of our products.
Our Pipeline – Key Programs
−Removed: Casimersen (SRP-4045) uses our PMO chemistry and exon-skipping technology to skip exon 45 of the DMD gene.
−Removed: Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or “skipping”, of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping.
−Removed: We are enrolling and dosing patients in ESSENCE (4045-301), our Phase 3 placebo controlled confirmatory trial in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 or 53 skipping using casimersen and golodirsen, respectively.
−Removed: On March 28, 2019, we announced results from our interim analysis of muscle biopsy endpoints comparing casimersen treatment to placebo in the ESSENCE study.
−Removed: In January 2020, we commenced a rolling submission of an NDA to the FDA seeking accelerated approval for casimersen .
SRP-5051 uses our next-generation chemistry platform, PPMO, and our exon-skipping technology to skip exon 51 of the dystrophin gene.
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In the fourth quarter of 2017, we commenced a first-in-human, single ascending dose, trial for the treatment of DMD using SRP-5051 in patients who are amenable to exon 51 skipping.
−Removed: In 2019, we commenced a multiple ascending dose study for the treatment of DMD with SRP-5051 in patients who are amenable to exon 51 skipping, and we expect to have safety and dosing insights by the middle of 2020.
+Added: In 2019, we commenced a multiple ascending dose study for the treatment of DMD with SRP-5051 in patients who are amenable to exon 51 skipping (“Study 5051-201”).
+Added: In December 2020, we announced an interim analysis on clinical results from the 10 mg/kg and 20 mg/kg dose cohorts of Part A of Study 5051-201.
+Added: We expect to announce results from the next cohort of Part A of Study 5051-201 at 30 mg/kg in the second quarter of 2021.
SRP-9001 (DMD, micro-dystrophin gene therapy program) , aims to express micro-dystrophin – a smaller but still functional version of dystrophin.
A unique, engineered micro-dystrophin is used because naturally-occurring dystrophin is too large to fit in an AAV vector.
−Removed: SRP-9001 employs the AAVrh .
−Removed: 74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle without promiscuously crossing the blood brain barrier, which we believe makes it a strong candidate to treat peripheral neuromuscular diseases.
+Added: SRP-9001 employs the AAVrh.74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle without promiscuously crossing the blood brain barrier, which we believe makes it a strong candidate to treat peripheral neuromuscular diseases.
An MHCK7 promoter was chosen for its ability to robustly express in the heart, which is critically important for patients with DMD, who typically die from pulmonary or cardiac complications.
Lastly, the transgene was designed to maintain spectrin-like repeats 2 and 3, which has been reported to be critical to maintaining muscle force.
−Removed: In the fourth quarter of 2017, an investigational new drug (“IND”) application for the micro-dystrophin gene therapy program was cleared by the FDA, and a Phase 1/2a clinical trial in individuals with DMD was initiated.
−Removed: On October 3, 2018, Nationwide presented what we believe to be positive updated results from the Phase 1/2a clinical trial in four individuals with DMD enrolled in the trial.
−Removed: On March 25, 2019, we presented nine-month functional and CK data from baseline from these four individuals, and twelve-month CK data from baseline from one of these individuals.
−Removed: In the fourth quarter of 2018, we commenced a randomized, double-blind, placebo-controlled trial of SRP-9001 with the goal to establish the functional benefits of micro-dystrophin expressions.
−Removed: We have dosed all 41 participants in that trial and have begun dosing participants in the crossover phase of the study.
−Removed: We plan to commence a trial evaluating SRP-9001 using commercial supply in the middle of 2020, pending regulatory feedback.
+Added: In the fourth quarter of 2017, an investigational new drug (“ IND ”) application for the micro-dystrophin gene therapy program was cleared by the FDA, and a Phase 1/2a clinical trial in individuals with DMD was initiated (Study 10 1 ) .
+Added: I n October 2018, Nationwide Children’s Hospital (“Nationwide”) presented updated results from Study 10 1 in four individuals with DMD enrolled in the trial.
+Added: I n March 2019, we presented nine -month functional and CK data from baseline from these four individuals, and twelve -month CK data from baseline from one of these individuals.
+Added: In the fourth quarter of 2018, we commenced a randomized, double-blind, placebo-controlled trial of SRP-9001 with the goal to establish the functional benefits of micro-dystrophin expressions (Study 102) .
+Added: We dosed all 4 1 participants in that trial and have begun dosing participants i n the crossover phase of the study .
+Added: In January 2021, we 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 ) .
+Added: We expect additional results from Part 2 of Study 102 in the first quarter of 202 2 .
+Added: We commenced dosing in Study 103, an open-label study evaluating the safety and expression of commercially representative material for SRP-9001, and expect to report biomarker and safety results from Study 103 in the second quarter of 2021.
SRP-9003 (LGMD, gene therapy program) .
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A Phase 1/2a trial of SRP-9003 was commenced in the fourth quarter of 2018.
−Removed: On February 27, 2019, we announced positive two-month biopsy data from the first three-patient cohort dosed in the SRP-9003 trial, and on October 4, 2019, we announced positive nine-month functional data from these three patients.
−Removed: We have recently dosed one additional cohort of three patients at a higher dose per the study protocol.
−Removed: We expect to have the results from the second cohort and make a dose selection in the third quarter of 2020.
−Removed: LYS-SAF 302 .
−Removed: We are collaborating with Lysogene S.A.
−Removed: (“Lysogene”) to develop a gene therapy, LYS-SAF302, to treat MPS IIIA.
−Removed: LYS-SAF302 is an AAV-mediated gene therapy, the goal of which is to replace the faulty N-sulfoglucosamine sulfohydrolase (“SGSH”) gene with a healthy copy of the gene.
−Removed: LYS-SAF302 employs the AAVrh.10 virus, chosen for its ability to target the CNS.
−Removed: Proof-of-concept was established in MPS IIIA pre-clinical models demonstrating strong expression, broad distribution, and the ability of the compound to correct lysosomal storage defects by producing the missing enzyme.
−Removed: Lysogene is conducting a global Phase 2/3 clinical trial of LYS-SAF302 (AAVance), aiming at evaluating the effectiveness of a one-time delivery of an AAVrh.10 virus carrying the N-SGSH gene.
−Removed: We expect to complete dosing in this trial in the first half of 2020.
+Added: In February 2019, we announced two-month biopsy data from the first three-patient cohort dosed in the SRP-9003 trial, and in October 2019, we announced nine-month functional data from these three patients.
+Added: In June 2020, we 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 high-dose cohort, and eighteen-month functional data from three clinical trial participants in the low-dose cohort.
+Added: We expect to complete GMP runs for SRP-9003 in 2021.
+Added: We also expect to seek FDA confirmation to initiate our pivotal trial in 2021.
The chart below summarizes the status of our programs, including those with our strategic partners:
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All of our CMO partners have extensive technical expertise, GMP experience and experience manufacturing our specific technology.
−Removed: For our commercial DMD program, we have commenced work with our existing manufacturers to increase product capacity from mid-scale to large-scale.
+Added: For our commercial DMD program, we have worked with our existing manufacturers to increase product capacity from mid-scale to large-scale.
While there are a limited number of companies that can produce raw materials and APIs in the quantities and with the quality and purity that we require for our commercial products, based on our diligence to date, we believe our current network of manufacturing partners are able to fulfill these requirements, and are capable of expanding capacity as needed.
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through a limited network of home infusion specialty pharmacy providers that deliver the medication to patients and a specialty distributor that distributes our products to hospitals and hospital outpatient clinics.
−Removed: With respect to the pre-commercial distribution of our products to patients outside of the U.S., we have contracted with third party distributors and service providers to distribute our products in certain countries through our ex-U.S.
−Removed: early access programs (“EAP”).
+Added: With respect to the pre-commercial distribution of our products to patients outside of the U.S., we have contracted with third party distributors and service providers to distribute our products in certain countries through our EAPs.
We plan to continue building out our network for commercial distribution in jurisdictions in which our products are approved.
−Removed: Our gene therapy manufacturing capabilities have been greatly enhanced through partnerships with Brammer Bio LLC, which has recently been acquired by Thermo Fisher Scientific Inc.
−Removed: (“Brammer”), Paragon Bioservices, Inc., which has recently been acquired by Catalent, Inc.
−Removed: (“Paragon”) and Aldevron LLC (“Aldevron”).
+Added: Our gene therapy manufacturing capabilities have been greatly enhanced through partnerships with Thermo Fisher Scientific Inc.
+Added: (“Thermo”), Catalent, Inc.
+Added: (“Catalent”) and Aldevron LLC (“Aldevron”).
We have adopted a hybrid development and manufacturing strategy in which we are building internal manufacturing expertise relative to all aspects of AAV-based manufacturing, including gene therapy and gene editing supply, while closely partnering with first-in-class manufacturing partners to expedite development and commercialization of our gene therapy programs.
−Removed: We expect that our partnerships with Brammer and Paragon will support our clinical and commercial manufacturing capacity for our micro-dystrophin DMD gene therapy programs and LGMD programs, while also acting as a manufacturing platform for potential future gene therapy programs.
+Added: We expect that our partnerships with Thermo and Catalent will support our clinical and commercial manufacturing capacity for our micro-dystrophin DMD gene therapy programs and LGMD programs, while also acting as a manufacturing platform for potential future gene therapy programs.
The collaboration integrates process development, clinical production and testing, and commercial manufacturing.
−Removed: Aldevron is expected to provide GMP-grade plasmid for our SRP-9001 micro-dystrophin DMD gene therapy program and LGMD programs, as well as plasmid source material for future gene therapy programs, such as CMT, MPS IIIA and other neuromuscular and CNS related disorders.
+Added: Aldevron is expected to provide GMP-grade plasmid for our SRP-9001 micro-dystrophin DMD gene therapy program and LGMD programs, as well as plasmid source material for future gene therapy programs, such as CMT and other neuromuscular and CNS related disorders.
Manufacturers and suppliers of our commercial products and product candidates are subject to the FDA’s current GMP (“cGMP”) requirements and other rules and regulations prescribed by foreign regulatory authorities.
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We retained all rights to SRP-9001 in the U.S.
+Added: The transaction closed on February 14, 2020.
Also, under the terms of the Collaboration Agreement, Roche granted us a license to use certain of its intellectual property rights to perform development activities worldwide under a joint global development plan , commercialize SRP-9001 in the U .
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under intellectual property rights developed by Roche under the Collaboration Agreement .
−Removed: We intend to manufacture and supply all clinical and commercial supply of SRP-9001.
+Added: We intend to manufacture and supply all clinical and, upon approval in the relevant market, commercial supply of SRP-9001.
Roche Options and Negotiation Rights
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Subject to certain exceptions, the parties will share the costs of the development activities under such joint global development plan.
−Removed: Roche will perform all development activities set forth in a territory-specific development plan for SRP-9001, including additional activities not set forth in the joint global development plan that are specifically directed to obtaining and maintaining regulatory approvals for SRP-9001 outside of the U.S.
+Added: Roche will have sole responsibility to perform all development activities set forth in a territory-specific development plan for SRP-9001, including additional activities not set forth in the joint global development plan that are specifically directed to obtaining and maintaining regulatory approvals for SRP-9001 outside of the U.S.
Roche will be solely responsible for costs arising from the territory-specific development plan for SRP-9001.
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Financial Terms
−Removed: In February 2020, Roche and Roche Finance Ltd, an affiliate of Roche (“Roche Finance”), together paid us an up-front payment of $1.2 billion, comprised of $750.0 million in cash from Roche and approximately $400.0 million from Roche Finance in exchange for 2,522,227 shares of our common stock, priced at $158.59 per share under the Stock Purchase Agreement described below.
+Added: In consideration for the rights that we granted and for prepaid funding for development activities, in February 2020, Roche and Roche Finance Ltd, an affiliate of Roche (“Roche Finance”), together paid us an up-front payment of approximately $1.2 billion, comprised of $750.0 million in cash from Roche and approximately $400.0 million from Roche Finance in exchange for 2,522,227 shares of our common stock, priced at $158.59 per share under the Stock Purchase Agreement described below.
Additionally, we are eligible to receive up to $1.7 billion in regulatory and sales milestone payments with respect to SRP-9001.
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Stock Purchase Agreement
−Removed: On December 21, 2019, pursuant to the Collaboration Agreement, we entered into a Stock Purchase Agreement with Roche Finance (the “Stock Purchase Agreement”) pursuant to which, in February 2020, we issued and sold 2,522,227 shares (the “Shares”) of common stock to Roche Finance in a private placement for an aggregate purchase price of approximately $400.0 million, or $158.59 per share.
−Removed: The Shares are subject to lock-up restrictions, which, without our prior approval, prohibit Roche Finance from selling the Shares for a period of 180 days after the closing of the Share issuance.
+Added: On December 21, 2019, pursuant to the Collaboration Agreement, we entered into a Stock Purchase Agreement with Roche Finance (the “Stock Purchase Agreement”) pursuant to which, in February 2020, we issued and sold 2,522,227 shares (the “Shares”) of common stock to Roche Finance in a private placement for an aggregate purchase price of approximately $400.0 million, or $158.59 per share, with a fair value of $316.3 million.
The Stock Purchase Agreement contains other customary terms and conditions, including mutual representations, warranties, and covenants.
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License Agreement
−Removed: On July 17, 2017, we executed a License Agreement (as amended on April 14, 2019, the “License Agreement”) with BioMarin Leiden Holding BV, BioMarin Nederlands BV and BioMarin Technologies BV (collectively, “BioMarin”), pursuant to which BioMarin granted us a royalty-bearing, worldwide license under patent rights (“Licensed Patents”) and know-how (“Licensed Know-How”) controlled by BioMarin with respect to BioMarin’s DMD program, which are potentially necessary or useful for the treatment of DMD, 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 and golodirsen (collectively, the “Products”).
+Added: On July 17, 2017, we executed a License Agreement (as amended on April 14, 2019, the “License Agreement”) with BioMarin Leiden Holding BV, BioMarin Nederlands BV and BioMarin Technologies BV (collectively, “BioMarin”), pursuant to which BioMarin granted us a royalty-bearing, worldwide license under patent rights (“Licensed Patents”) and know-how (“Licensed Know-How”) controlled by BioMarin with respect to BioMarin’s DMD program, which are potentially necessary or useful for the treatment of DMD, 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”).
The license granted by BioMarin is exclusive, even as to BioMarin, with respect to the Licensed Patents, and is non-exclusive with respect to Licensed Know-How.
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Under the terms of the License Agreement, we were required to pay BioMarin an up - front payment of $15 .0 million, and BioMarin is eligible to receive up to $20 .0 million from us per dystrophin gene exon (other than exon 51) targeted by one or more Products in specified regulatory milestones, as well as an additional $10 .0 million milestone, payable following the regulatory approval of eteplirsen by the EMA .
−Removed: BioMarin is also eligible to receive $15 .0 million from us upon the achievement of $650 .0 million in sales, as well as royalties segmented by specified geographic markets, in some jurisdictions dependent on the existence of a patent, ranging from four (4) to eight (8) percentages of net sales on a product-by-product and country-by-country basis.
−Removed: Milestones and royalties are payable with respect to eteplirsen (an exon 51 skipping Product), golodirsen (an exon 53 skipping Product), casimersen (an exon 45 skipping Product) and other Products.
+Added: BioMarin is also eligible to receive $15 .0 million from us upon the achievement of $650 .0 million in sales of Products , as well as royalties segmented by specified geographic markets, in some jurisdictions dependent on the existence of a patent, ranging from four (4) to eight (8) percentages of net sales on a product-by-product and country-by-country basis.
+Added: Milestones and royalties are payable with respect to eteplirsen (an exon 51 skipping Product), golodirsen (an exon 53 skipping Product), casimersen (an exon 45 skipping Product) and potentially other Products.
For eteplirsen, golodirsen and casimersen, the royalty term will expire upon March 31, 2024 in the U.S., upon December 31, 2024 in the EU and no later than December 31, 2024 in other countries provided certain conditions are met.
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The UWA License Agreement grants us specific rights to compounds for the treatment of DMD by inducing exon skipping.
−Removed: EXONDYS 51, VYONDYS 53 and casimersen fall under the scope of the license agreement.
−Removed: Under the UWA License Agreement, we are required to make payments of up to $6.0 million in the aggregate to UWA based on the successful achievement of certain development and regulatory milestones relating to EXONDYS 51, VYONDYS 53 and up to four additional product candidates.
−Removed: As of December 31, 2019, $2.7 million of the $6.0 million development and regulatory milestone payments has been made.
+Added: EXONDYS 51, VYONDYS 53 and AMONDYS 45 fall under the scope of the license agreement.
+Added: Under the UWA License Agreement, we are required to make payments of up to $6.0 million in the aggregate to UWA based on the successful achievement of certain development and regulatory milestones relating to EXONDYS 51, VYONDYS 53, AMONDYS 45 and up to three additional product candidates.
+Added: As of December 31, 2020, $3.7 million of the $6.0 million development and regulatory milestone payments had been made.
We are also obligated to make payments to UWA of up to $20.0 million upon the achievement of certain sales milestones.
Additionally, we are required to pay a low-single-digit percentage royalty on net sales of products covered by issued patents licensed from UWA during the term of the UWA License Agreement.
−Removed: However, we have the option to purchase future royalties up-front for a one-time payment to UWA of $23.0 million.
Currently, the latest date on which an issued patent covered by the UWA License Agreement expires is November 2030 (excluding any patent term extension, supplemental protection certificate or pediatric extensions that may be available);
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In addition, in December 2016, we entered into an exclusive option agreement with Nationwide to acquire exclusive rights to their micro-dystrophin gene therapy program as well as a sponsored research agreement to conduct pre-IND research and conduct the first clinical trial with the lead micro-dystrophin gene therapy.
−Removed: In October 2018, we exercised our exclusive license option and an option under the sponsored research agreement and entered into an exclusive license agreement with Nationwide to acquire exclusive rights to its micro-dystrophin gene therapy program.
+Added: In October 2018, we exercised our exclusive license option and an option under the sponsored research agreement and entered into an exclusive license agreement with Nationwide to acquire exclusive rights to its micro-dystrophin gene therapy program, which provides us with exclusive rights to commercialize SRP-9001.
Furthermore, in October 2018, we entered into an exclusive option agreement with Nationwide with respect to exclusive rights to its NT-3 gene therapy program for the treatment of certain CMT neuropathy subtypes, including CMT Type 1A.
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The option agreement contains pre-determined economic terms for the exclusive license to be entered into upon us exercising our option.
−Removed: In October 2018, we entered into a license and collaboration agreement with Lysogene, a gene therapy company focused on the treatment of orphan diseases of the CNS, for the development of a gene therapy, LYS-SAF302, to treat MPS IIIA.
−Removed: Concomitantly, we also entered into an option with Lysogene to acquire an exclusive license to an additional CNS-targeted gene therapy candidate.
−Removed: Lysogene is responsible for completion of the pivotal trial for LYS-SAF302.
−Removed: We have exclusive commercial rights to LYS-SAF302 and exclusive option rights for the additional CNS-targeted gene therapy program in the U.S.
−Removed: and all territories outside of Europe, and Lysogene will retain exclusive commercial rights to each program in Europe.
−Removed: We will be responsible for global manufacturing of LYS-SAF302 and will supply Lysogene for its territory.
−Removed: If all milestones are met, we may be required to pay up to $130.8 million in development and commercial milestones and tiered royalties upon commercialization.
Duke University
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Patent and Trademark Office ( “ USPTO ” ) during prosecution of a patent application.
−Removed: We actively strive to maximize the potential for patent protection for our products and product candidates in accordance with the law.
+Added: We actively strive to maximize the potential for patent protection for our product s and product candidates in accordance with the law.
Key Patents & Regulatory Exclusivities
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June 28, 2025
+Added: US 10,781,451
United States
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United States
+Added: Composition of Matter
+Added: February 2, 2029
+Added: United States
Methods of Use
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2016-1937, 2016-2086 (consolidated)) voluntarily dismissed July 27, 2017.)
+Added: Reissue application of U.S.
+Added: 9,243,245 pending.
Reissue of U.S.
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2017-1078) voluntarily dismissed July 27, 2017.)
−Removed: Reissue application of U.S.
−Removed: 9,243,245 pending.
Patent Number
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June 28, 2025
−Removed: EP 2 203 173 B1 2
−Removed: Methods of Use
−Removed: October 27, 2028
Previously involved in EPO Opposition and appeal procedure.
EPO decision of Appeal Board dated December 12, 2019 maintained the patent in amended form.
−Removed: Involved in EPO Opposition proceedings initiated on September 22, 2016.
−Removed: EPO ordered revocation of our (BioMarin/AZL) patent on April 4, 2018.
−Removed: Appeal filed June 8, 2018 is pending.
The various types of regulatory exclusivity for which our products have been granted and our product candidates are anticipated to be eligible to receive are generally discussed below, under ‘Government Regulation’ – ‘Data and Market Exclusivities’ and ‘Orphan Drug Designation and Exclusivity’.
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November 12, 2030
+Added: United States
+Added: Methods of Use
+Added: November 12, 2030
Reissue application of U.S.
13 unchanged sentences
Stated expiration dates do not account for any patent term extension, supplemental protection certificate or pediatric extensions that may be available.
+Added: The various types of regulatory exclusivity for which our products have been granted and our product candidates are anticipated to be eligible to receive are generally discussed below, under ‘Government Regulation’ – ‘Data and Market Exclusivities’ and ‘Orphan Drug Designation and Exclusivity’.
+Added: In connection with its FDA approval on February 25, 2021, the FDA granted AMONDYS 45 (casimersen) NCE exclusivity until February 25, 2026, and Orphan Drug Exclusivity until February 25, 2028.
In addition to the foregoing composition of matter and method of use patents that protect eteplirsen, casimersen and golodirsen, we either solely own or exclusively license from UWA, BioMarin or AZL patents and patent applications in the U.S.
8 unchanged sentences
We are the owner of multiple federal trademark registrations in the U.S.
−Removed: including, but not limited to, Sarepta, Sarepta Therapeutics, the double-helix logo, EXONDYS, and EXONDYS 51.
+Added: including, but not limited to, Sarepta, Sarepta Therapeutics, the double-helix logo, EXONDYS, EXONDYS 51, the EXONDYS 51 Logo, VYONDYS, VYONDYS 53, and the VYONDYS 53 Logo.
In addition, we have multiple pending trademark applications in the U.S.
−Removed: and in major foreign markets, including, but not limited to, VYONDYS and VYONDYS 53.
+Added: and in major foreign markets, including, but not limited to, AMONDYS, AMONDYS 45, and the AMONDYS 45 Logo.
Trademark protection varies in accordance with local law, and continues in some countries as long as the trademark is used and in other countries as long as the trademark is registered.
107 unchanged sentences
We have initiated key activities in support of the potential launch of our products in the EU, such as building out commercial infrastructure and scaling-up manufacturing.
−Removed: As of the date of this Annual Report, EXONDYS 51 and VYONDYS 53 have only been approved for sale and marketing in the U.S.
+Added: As of the date of this Annual Report, EXONDYS 51, VYONDYS 53 and AMONDYS 45 have only been approved for sale and marketing in the U.S.
by the FDA, and EXONDYS 51 has been approved in addition for sale and marketing in Israel by the Israeli Ministry of Health.
1 unchanged sentence
Irrespective of whether it concerns an FDA approved or investigational drug, the commencement of clinical trials and the subsequent marketing of a drug product in foreign countries are subject to preliminary approvals from the corresponding regulatory authorities of such countries.
−Removed: For example, the conduct of clinical trials in the EU is currently still governed by the Clinical Trials Directive 2001/20/EC and Directive 2005/28/EC laying down the principles and guidelines on GCP.
−Removed: Both Directives provide a system for the approval of clinical trials, which has been implemented through national legislation in the member states in the EU.
−Removed: Under this system, a sponsor must obtain approval from the competent national authority of an EU member state in which the clinical trial is to be conducted, or in multiple member states if the clinical trial is to be conducted in a number of countries.
+Added: For example, the conduct of clinical trials in the EU is currently still governed by the Clinical Trials Directive 2001/20/EC and Directive 2005/28/EC laying down the requirements for the conduct of clinical trials in the EU and the principles and guidelines on GCP.
+Added: Both Directives provide a system for the approval of clinical trials, which has been implemented through national legislation in the member states of the EU (“EU Member States”).
+Added: Under this system, a sponsor must obtain approval from the competent national authority of an EU Member State in which the clinical trial is to be conducted, or in multiple EU Member States if the clinical trial is to be conducted in a number of countries.
Furthermore, the sponsor may only start a clinical trial at a specific study site after the competent ethics committee has issued a favorable opinion.
−Removed: The Clinical Trials Application (“CTA”) must include the supporting information prescribed by Directive 2001/20/EC and Directive 2005/28/EC, corresponding national laws of the member states, and as further detailed in the applicable guidance documents.
+Added: The Clinical Trials Application (“CTA”) must include the supporting information prescribed by Directive 2001/20/EC and Directive 2005/28/EC, corresponding national laws of the EU Member States, and as further detailed in the applicable guidance documents.
In April 2014, the EU adopted a new Clinical Trials Regulation (EU) No 536/2014 to replace the current Clinical Trials Directive 2001/20/EC.
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It will also apply to clinical trials that were authorized under the previous legislation if they are still ongoing three years after the Regulation has come into operation.
−Removed: No legislation needs to be adopted to implement the new Regulation into national law.
+Added: No legislation needs to be adopted to implement the new Regulation into national EU Member State law.
The new Regulation provides an overhaul of the system, in order to harmonize the assessment of the submission and assessment of clinical trials conducted in EU Member States and to ensure greater consistency with the highest standards of patient safety in the EU.
1 unchanged sentence
Under the new coordinated procedure, the sponsor of a clinical trial is required to submit a single application to a reporting EU Member State.
−Removed: The reporting Member State will consult and coordinate with all other Member States in which the clinical trial is planned to be conducted.
−Removed: If the application is rejected, it can be amended and resubmitted through a central EU Portal.
−Removed: If an approval is issued, the sponsor can start the clinical trial in all Member States concerned.
−Removed: However, a Member State can in certain cases declare an “opt-out” from the approval.
−Removed: In such a case, the clinical trial cannot be conducted in such Member State(s).
+Added: The reporting EU Member State will consult and coordinate with all other EU Member States in which the clinical trial is planned to be conducted.
+Added: If the application is rejected, it can be amended and resubmitted through CTIS, the central EU portal.
+Added: If an approval is issued, the sponsor can start the clinical trial in all EU Member States concerned.
+Added: However, a EU Member State can in certain cases declare an “opt-out” from the approval.
+Added: In such a case, the clinical trial cannot be conducted in such EU Member State(s).
The Clinical Trials Regulation also aims to streamline and simplify the rules on safety reporting for clinical trials.
1 unchanged sentence
Applicants are required to demonstrate the quality, safety and efficacy of the medicinal product in the application for marketing authorization, which implies the requirement to conduct human clinical trials to generate the necessary clinical data.
−Removed: Furthermore, all applications for marketing authorization for new medicines have to include the results of studies as described in an agreed pediatric investigation plan (“PIP”).
+Added: Furthermore, all applications for marketing authorization for new medicines have to include the results of studies as described in an agreed pediatric investigation plan (“PIP”) aimed at ensuring that the necessary data are obtained through studies in children, unless the medicine is exempt because of a deferral or waiver.
Regulation (EC) No 726/2004 of the European Parliament and of the Council lays down the rules applicable to the centralized procedure for the authorization of medicinal products.
−Removed: The centralized procedure allows pharmaceutical companies to submit s a single application to EMA, which is followed by a single evaluation and which results in a single approval to market the medicinal product throughout the European Economic Area (the “EEA”), on the basis of a single market authorization.
+Added: The centralized procedure allows pharmaceutical companies to submit a single application to the EMA, which is followed by a single evaluation and which results in a single approval to market the medicinal product throughout the European Economic Area (the “EEA”), on the basis of a single market authorization.
Approval via the centralized procedure is a two-step process whereby the CHMP first evaluates the MAA and issues an opinion on whether the medicinal product may be authorized or not (step 1).
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The centralized procedure is mandatory for medicinal products derived from biotechnological and other high-tech processes, orphan medicinal products, advanced therapy medicinal products and products indicated for the treatment of HIV/AIDS, cancer, diabetes, auto-immune and other immune dysfunctions, viral diseases and neurodegenerative diseases.
−Removed: For medicinal products that do not fall under any of the aforementioned categories, a submission via the centralized procedure is possible, provided that it concerns a new active substance or product that can demonstrate a significant therapeutic, scientific or technical innovation and for which approval would be in the interest of public health.
+Added: For medicinal products that do not fall under any of the aforementioned categories, a submission via the centralized procedure is possible, provided that it concerns (i) a new active substance or (ii) product that can demonstrate a significant therapeutic, scientific or technical innovation and for which approval would be in the interest of public health.
Given the foregoing, our portfolio of innovative orphan products for neurodegenerative diseases is subject to the mandatory centralized procedure.
−Removed: Innovative medicinal products which have been authorized in accordance with the centralized procedure, benefit from an eight-year period of data protection and a ten-year period of marketing protection.
+Added: Innovative medicinal products which have been authorized in accordance with the centralized procedure, benefit from an eight-year period of data protection/exclusivity and a ten-year period of marketing protection/exclusivity.
During the data exclusivity period, applicants for approval of generics of these innovative products cannot reference or rely upon data contained in the marketing authorization dossier submitted for the innovative medicinal product.
Furthermore, the marketing protection entails that even if the generic product is approved, it cannot be placed on the market until the full ten-year period of market protection has elapsed from the initial authorization of the reference medicinal product.
−Removed: The marketing protection period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder for the innovative product obtains an authorization for new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies or as the result of significant pre-clinical or clinical trials.
−Removed: Pharmaceutical companies can apply for the designation as an orphan medicine.
−Removed: In the EU, applications for orphan designation are evaluated by the EMA.
−Removed: In order to qualify as an orphan medicine, the medicinal product must be intended to diagnose, prevent or treat condition that is life-threatening or chronically debilitating, with a prevalence of no more than 5 in 10,000 people in the EU or for which it is unlikely that its sale would generate sufficient returns to justify the investment needed for its development.
−Removed: In addition, the sponsor is required to demonstrate that no satisfactory method of diagnosis, prevention or treatment of the condition can be authorized in the EU or, if such method exists, the medicinal product is of significant benefit to those affected by the condition as compared to approved methods.
−Removed: The benefits of being granted orphan designation are significant, including up to ten years of market exclusivity.
−Removed: During this ten-year period, the EMA may not accept a new marketing application for a similar medicinal product for the same therapeutic indication as the approved orphan medicinal product.
−Removed: Pursuant to Regulation (EC) 1901/2006 on medicinal products for pediatric use, the ten-year orphan market exclusivity can be extended to a maximum period of twelve years on the satisfactory completion of all the key elements of the agreed PIP.
−Removed: We have been granted orphan drug designation for eteplirsen in the EU.
+Added: The marketing protection period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder for the innovative product obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
Similar to the U.S., marketing authorization holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA and/or the national competent authorities of the EU Member States.
This oversight applies both before and after the granting of manufacturing and marketing authorizations.
−Removed: It includes compliance with EU GMP and GDP rules in relation to such activities as distribution, importing and exporting of medicinal products, rules governing conduct of pharmacovigilance and requirements governing advertising, promotion and sale of medicinal products.
+Added: It includes compliance with EU GMP and GDP rules in relation to such activities as distribution, importing and exporting of medicinal products, rules governing conduct of pharmacovigilance (including good pharmacovigilance practices (“GVP”)) and requirements governing advertising, promotion and sale of medicinal products.
Failure to comply with the EU Member State laws implementing the EU Community Code on medicinal products, and EU rules governing the promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices, with the EU Member State laws that apply to the promotion of medicinal products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements can result in enforcement action by the relevant EU Member State authorities.
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Market exclusivity prohibits any marketing of the same drug for the same indication.
−Removed: In the U.S., the FDA will generally grant an NCE that is the subject of an NDA with five years of regulatory data exclusivity, during which time a competitor generally may not submit an application to the FDA based on a sponsor’s clinical data.
+Added: In the U.S., the FDA will generally grant a n NCE that is the subject of a n NDA with five years of regulatory data exclusivity, during which time a competitor generally may not submit an application to the FDA based on a sponsor’s clinical data.
A competitor, however, may file an Abbreviated New Drug Application (“ANDA”) seeking approval of a generic drug four years from the date of approval of the innovative product if it is accompanied by a so-called Paragraph IV certification .
12 unchanged sentences
Safety and efficacy of a compound must be established through adequate and well-controlled studies.
−Removed: If a product which has an orphan drug designation subsequently receives FDA approval for the indication for which it has such designation, the product is generally entitled to an orphan drug exclusivity period of seven years, which means the FDA may not grant approval to any other application to market the same chemical entity for the same indication for a period of seven years, except in limited circumstances, such as where an alternative product demonstrates clinical superiority to the product with orphan exclusivity.
+Added: If a chemical or biological product which has an orphan drug designation subsequently receives FDA approval for the indication for which it has such designation, the product is generally entitled to an orphan drug exclusivity period of seven years, which means the FDA may not grant approval to any other application to market the same chemical or biological product for the same indication for a period of seven years, except in limited circumstances, such as where an alternative product demonstrates clinical superiority to the product with orphan exclusivity.
In addition, holders of exclusivity for orphan drugs are expected to assure the availability of sufficient quantities of their orphan drugs to meet the needs of patients.
1 unchanged sentence
Competitors may receive approval of different drugs or biologics for the indications for which a prior approved orphan drug has exclusivity.
−Removed: In Europe, the EMA may grant orphan status to product candidates thereby providing such product candidates with up to ten years of marketing exclusivity, meaning that another application for marketing authorization of a later, similar medicinal product for the same therapeutic indication will generally not be approved in Europe during that time period.
+Added: Pharmaceutical companies can apply for the designation as an orphan medicine.
+Added: In the EU, applications for orphan designation are evaluated by the EMA in accordance with Regulation (EC) No 141/2000.
+Added: In order to qualify as an orphan medicine, the medicinal product must be intended to diagnose, prevent or treat a condition that is life-threatening or chronically debilitating, with a prevalence of no more than 5 in 10,000 people in the EU or for which it is unlikely that its sale would generate sufficient returns to justify the investment needed for its development.
+Added: In addition, the sponsor is required to demonstrate that no satisfactory method of diagnosis, prevention or treatment of the condition has been be authorized in the EU or, if such method exists, the medicinal product is of significant benefit to those affected by the condition as compared to approved methods.
+Added: The benefits of being granted orphan designation are significant, including up to ten years of market exclusivity.
+Added: During this ten-year period, the EMA may not accept a new marketing application for a similar medicinal product for the same therapeutic indication as the approved orphan medicinal product.
+Added: Pursuant to Regulation (EC) 1901/2006 on medicinal products for pediatric use, the ten-year orphan market exclusivity can be extended to a maximum period of twelve years upon the satisfactory completion of all the key elements of the agreed PIP.
+Added: We have been granted orphan drug designation for eteplirsen in the EU.
Expanded / Early Access
6 unchanged sentences
There is no obligation for a pharmaceutical manufacturer to make its drug products available to such eligible patients as a result of the Right to Try Act.
−Removed: We have initiated an EAP for eteplirsen in select countries in Europe, North America, South America and Asia where it currently has not been approved.
−Removed: We are also in the process of initiating an EAP for golodirsen outside of the U.S.
+Added: We established a global EAP for eteplirsen and golodirsen in some countries where eteplirsen and golodirsen currently have not been approved.
The EAP provides a mechanism through which physicians can prescribe our products, within their professional responsibility, to patients who meet pre-specified medical and other criteria and can secure funding.
−Removed: We have commenced shipments through the EAP and continue to expand the EAP to include more countries.
−Removed: In addition, we contracted with third party distributors and service providers to distribute our products in certain areas outside the U.S., such as Brazil and certain countries in the Middle East, on a named patient basis.
Other Regulatory Requirements
17 unchanged sentences
In addition, under the federal Civil Monetary Penalty Law, the Department of Health and Human Services Office of Inspector General has the authority to exclude from participation in federal health care programs or to impose civil penalties against any person who, among other things, knowingly presents, or causes to be presented, certain false or otherwise improper claims.
+Added: A federal healthcare fraud statute prohibits the knowing and willful execution, or attempt to execute, a scheme to defraud a health care benefit program, including private health plans, or obtain, through false or fraudulent pretenses, money or property owned by, or under the custody or control of, such a health care benefit program.
The majority of states also have anti-kickback, false claims, and similar fraud and abuse laws and although the specific provisions of these laws vary, their scope is generally broad, and there may not be regulations, guidance or court decisions that apply the laws to particular industry practices.
11 unchanged sentences
The legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an increasing focus on privacy and data protection issues with the potential to affect our business.
−Removed: Within the U.S.
−Removed: , our operations may be affected by the Health Insurance Portability and Accountability Act of 1996 as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations ( collectively, “ HIPAA ”) , which impose obligations on certain “covered entities” (healthcare providers, health plans and healthcare clearinghouses) and certain of their “business associate” contractors with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
−Removed: Although we believe that we currently are neither a “covered entity” nor a “business associate” under the legislation, a business associate relationship may be imputed from facts and circumstances even in the absence of an actual business associate agreement.
−Removed: In addition, HIPAA may affect our interactions with customers who are covered entities or their business associates because HIPAA affects the ability of these entities to disclose patient health information to us.
−Removed: Various states also have laws that regulate the privacy and security of personal information and so may affect our business operations.
−Removed: For example, we are subject to the California Consumer Privacy Act (“CCPA”), that became effective on January 1, 2020.
−Removed: The CCPA gives California consumers (defined to include all California residents) certain rights, including the right to ask companies to disclose information regarding the collection, use and disclosure of their personal information.
−Removed: The CCPA also imposes several obligations on companies to provide notice to California consumers regarding a company’s data processing activities.
−Removed: Additionally, the CCPA gives California consumers the right to ask companies to delete a consumer’s personal information and it places limitations on a company’s ability to sell personal information, including providing consumers a right to opt out of sales of their personal information.
−Removed: The compliance obligations imposed by the General Data Protection Regulation (the “GDPR”) and the CCPA have required us to enhance our operations.
−Removed: The CCPA contains significant penalties for companies that violate its requirements and provides California residents a private right of action, including the ability to seek statutory damages, in the event of a data breach involving their data.
−Removed: Outside the U.S., other laws regulating the privacy and security of personal information may apply.
−Removed: For example, the processing of personal data in the EEA, is subject to the GDPR, which took effect in May 2018.
−Removed: The GDPR increases obligations with respect to clinical trials conducted in the EEA, such as in relation to the provision of fair processing notices, exercising data subject rights and reporting certain data breaches to regulators and affected individuals, as well as how we document our relationships with third parties that process GDPR-covered personal data on our behalf.
−Removed: The GDPR also increases the scrutiny applied to transfers of personal data from the EEA (including from clinical trial sites in the EEA) to countries that are considered by the European Commission to lack an adequate level of data protection, such as the U.S.
−Removed: Fines for non-compliance with the GDPR have the potential to be significant—the greater of EUR 20.0 million or 4% of our global annual revenue in the previous financial year.
−Removed: The GDPR imposes a private right of action on data subjects and their representatives for breaches of certain data protection requirements.
+Added: Our ongoing efforts to comply with evolving laws and regulations may be costly and require ongoing modifications to our policies, procedures and systems.
+Added: Failure to comply with laws regarding data protection would expose us to risk of enforcement actions and penalties under such laws.
+Added: Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our business, financial condition, results of operations or prospects.
+Added: Within the U.S., there are numerous federal and state laws and regulations related to the privacy and security of personal information.
+Added: For example, at the federal level, the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended, and its implementing regulations establish privacy and security standards that limit the use and disclosure of individually identifiable health information, or protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of protected health information.
+Added: While we have determined that we are neither a “covered entity” nor a “business associate” directly subject to HIPAA, many of the U.S.
+Added: health care providers with which we interact are subject to HIPAA, and we may have assumed obligations related to protecting the privacy of personal information.
+Added: States are increasingly regulating the privacy and security of personal information.
+Added: For example, the California Consumer Privacy Act, or CCPA, which took effect on January 1, 2020, gives California consumers (defined to include all California residents) certain rights, including the right to ask covered companies to disclose the types of personal information collected, the categories of sources from which such information was collected, the business purpose for collecting or selling the consumer’s personal information, the categories of third parties with whom a covered company shares personal information, and specific pieces of information collected by a covered company.
+Added: The CCPA imposes several obligations on covered companies to provide notice to California consumers regarding their data processing activities.
+Added: The CCPA also gives California consumers the right to ask covered companies to delete a consumer’s personal information and it places limitations on a covered company’s ability to sell personal information, including providing consumers a right to opt out of sales of their personal information.
+Added: In addition, we may be subject to privacy and security laws in the various jurisdictions in which we operate, obtain or store personally identifiable information.
+Added: The legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an increasing focus on privacy and data protection issues with the potential to affect our business.
+Added: For example, the processing of personal data in the European Economic Area (“EEA”), is subject to the General Data Protection Regulation (the “GDPR”), which took effect in May 2018.
+Added: The GDPR increases obligations with respect to clinical trials conducted in the EEA, such as in relation to the provision of fair processing notices, responding to data subjects who exercise their rights and reporting certain data breaches to regulators and affected individuals.
+Added: The GDPR also requires us to enter certain contractual arrangements with third parties that process GDPR-covered personal data on our behalf.
+Added: The GDPR also increases the scrutiny applied to transfers of personal data from the EEA (including from clinical trial sites in the EEA) to countries that are considered by the European Commission to lack an adequate level of data protection, such as the United States.
+Added: The July 2020 invalidation by the Court of Justice of the European Union of the EU-U.S.
+Added: Privacy Shield framework, one of the mechanisms used to legitimize the transfer of personal data from the EEA to the U.S., has led to increased scrutiny on data transfers from the EEA to the U.S.
+Added: generally and may increase our costs of compliance with data privacy legislation.
+Added: If our or our partners’ or service providers’ privacy or data security measures fail to comply with the GDPR requirements, we may be subject to litigation, regulatory investigations, enforcement notices requiring us to change the way we use personal data and/or fines of up to 20 million Euros or up to 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, as well as claims by affected individuals, negative publicity, reputational harm and a potential loss of business and goodwill
Pharmaceutical Pricing and Reimbursement
11 unchanged sentences
Under the Medicaid Drug Rebate Program, participating manufacturers are required to pay a rebate for each unit of product reimbursed under the state Medicaid programs.
−Removed: The amount of the rebate for each product is set by law and may be subject to an additional discount if certain pricing increases more than inflation.
+Added: The amount of the rebate for each product is set by law and depends in part on the prices at which our products are sold to certain other purchasers and may be subject to an additional discount if certain pricing increases more than inflation.
State Medicaid programs and Medicaid managed care plans can seek additional “supplemental” rebates from manufacturers in connection with favorable positioning on formularies.
−Removed: Medicare is a federal program that is administered by the federal government that covers individuals age 65 and over as well as those with certain disabilities.
+Added: Medicare is a federal program that is administered by the federal government that covers individuals age 65 and over, disabled individuals and individuals with certain conditions.
Our products are eligible for reimbursement under Medicare Part B.
−Removed: Medicare Part B generally covers drugs that must be administered by physicians.
+Added: Medicare Part B generally covers drugs that are usually administered by physicians or other clinicians.
Medicare Part B pays for such drugs under a payment methodology based on the average sales price (“ASP”) of the drugs.
Reimbursement levels and reimbursement methodologies have come under scrutiny and may be subject to change.
+Added: See “ Government Regulation – Healthcare and Other Reform.
” The Centers for Medicare & Medicaid Services (“CMS”) are also increasingly bundling drug reimbursement into procedure costs, which can severely decrease the reimbursement rates for some manufacturers’ drugs.
17 unchanged sentences
The court reasoned that the “individual mandate” was not severable from the rest of the Healthcare Reform Act and found the entire Healthcare Reform Act was an unconstitutional exercise of Congressional authority.
−Removed: In December 2019, a federal appeals court agreed that the individual mandate provision was unconstitutional, but remanded the case back to the district court to assess more carefully whether any provisions of the Healthcare Reform Act were severable and could survive.
−Removed: Pending action by the district court and resolution of any appeals, which could take some time, the Healthcare Reform Act is still operational in all respects.
−Removed: There have been other reform initiatives under the Trump Administration.
−Removed: For example, in May 2018, President Trump and the Secretary of the Department of Health and Human Services released a “blueprint” to lower prescription drug prices and out-of-pocket costs.
−Removed: Certain proposals in the blueprint, and related drug pricing measures proposed since the blueprint, could cause significant operational and reimbursement changes for the pharmaceutical industry.
−Removed: As another example, in October 2018, the CMS solicited public comments on potential changes to payment for certain Medicare Part B drugs, including reducing the Medicare payment amount for selected Medicare Part B drugs to more closely align with international drug prices.
−Removed: As another example, legislation passed in 2019 revised how certain prices reported by manufacturers under the Medicaid Drug Rebate Program are calculated, a revision that the Congressional Budget Office has estimated will save the Medicaid program approximately $3.0 billion in the next ten years.
+Added: The case Texas v.
+Added: Azar, which challenges the constitutionality of the Healthcare Reform Act, including provisions that are unrelated to healthcare reform but were enacted as part of the Healthcare Reform Act, was argued before the Supreme Court in November 2020.
+Added: Pending resolution of the litigation, all of the Healthcare Reform Act but the individual mandate to buy health insurance remains in effect.
+Added: Beyond the Healthcare Reform Act, there have been ongoing health care reform efforts, including a number of recent actions.
+Added: In 2020 and early 2021, the U.S.
+Added: Department of Health and Human Services has issued various rules that affect pricing or payment for drug products.
+Added: For example, effective January 2022, revisions to the federal anti-kickback statute would remove protection for traditional Medicare Part D discounts offered by pharmaceutical manufacturers to PBMs and health plans.
+Added: Additional healthcare reform efforts have sought to address certain issues related to the COVID-19 pandemic, including an expansion of telehealth coverage under Medicare and accelerated or advanced Medicare payments to healthcare providers.
+Added: Some of these changes have been and may continue to be subject to legal challenge.
+Added: For example, courts have temporarily enjoined a new “most favored nation” payment model for select drugs covered under Medicare Part B that was to take effect on January 1, 2021 and would limit payment based on international drug price.
+Added: The nature and scope of health care reform in the wake of the transition from the Trump administration to the Biden administration remains uncertain, although President Biden supported reforms to lower drug prices during his campaign for the presidency.
+Added: Adoption of new healthcare reform legislation at the federal or state level could affect demand for, or pricing of, our products or product candidates if approved for sale.
+Added: We cannot predict, however, the ultimate content, timing or effect of any healthcare reform legislation or action, or its impact on us, and healthcare reform could increase compliance costs and may adversely affect our future business and financial results.
There have also been efforts by government officials or legislators to implement measures to regulate prices or payment for pharmaceutical products, including legislation on drug importation.
4 unchanged sentences
General legislative cost control measures may also affect reimbursement for our products.
−Removed: The Budget Control Act, as amended, resulted in the imposition of 2% reductions in Medicare (but not Medicaid) payments to providers in 2013 and will remain in effect through 2029 unless additional Congressional action is taken.
+Added: The Budget Control Act of 2011, as amended, resulted in the imposition of 2% reductions in Medicare (but not Medicaid) payments to providers in 2013 and remains in effect through 2030 (except May 1, 2020 to March 31, 2021) unless additional Congressional action is taken.
Any significant spending reductions affecting Medicare, Medicaid or other publicly funded or subsidized health programs that may be implemented and/or any significant taxes or fees that may be imposed on us could have an adverse impact on our results of operations.
1 unchanged sentence
We currently have no products approved for marketing outside the U.S., other than a marketing authorization for EXONDYS 51 in Israel.
−Removed: We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products.
+Added: We may need to conduct long-term pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products.
In the EU and certain other territories, price controls and Health Technology Assessments for new, highly priced medicines are expected.
11 unchanged sentences
our ability to complete clinical development and obtain regulatory approvals for our product candidates;
−Removed: the efficacy, safety and reliability of our product candidates;
+Added: the efficacy, safety and reliability of our products and product candidates;
+Added: the dosing, strength, convenience and other product profile attributes of our products and product candidates;
the timing and scope of regulatory approvals;
1 unchanged sentence
protection of our proprietary rights and the level of generic competition;
−Removed: the ability to have freedom to operate to commercialize our product candidates;
+Added: the ability to have freedom to operate to commercialize our products and product candidates;
the speed at which we develop product candidates;
−Removed: our ability to supply commercial quantities of a product to the market;
+Added: our ability to supply commercial quantities of a product meeting FDA specifications to the market;
obtaining reimbursement for product use in approved indications;
1 unchanged sentence
the availability of substantial capital resources to fund development and commercialization activities, including the availability of funding from the U.S.
−Removed: DMD Program Competition .
−Removed: Currently, other than EXONDYS 51 and VYONDYS 53, no disease-modifying product has been approved for the treatment of DMD in the U.S.
−Removed: Other companies, however, have product candidates or other interests in development for the treatment of DMD.
−Removed: Wave Life Sciences (“Wave”) until recently was developing an exon 51 skipping product candidate for DMD, suvodirsen (WVE-210201).
−Removed: Wave also reported its intent to develop an exon 53 skipping product candidate, WVE-N531.
−Removed: On December 16, 2019, Wave announced the discontinuation of suvodirsen development for DMD (exon 51 amenable patients) and the suspension of further development of WVE-N531 for DMD (exon 53 amenable patients).
+Added: EXONDYS 51, VYONDYS 53 and AMONDYS 45 were the first three disease modifying therapeutics approved by FDA for the treatment of DMD for patients with a confirmed mutation that is amenable to exon 51 skipping, exon 53 skipping or exon 45 skipping, respectively.
+Added: However, in the field of DMD alone, these products and those in our pipeline face a variety of competitors who either have FDA approval or are being clinically developed for the treatment of DMD.
+Added: In addition, there are many companies who have announced plans to transition pre-clinical candidates to clinical development for the treatment of DMD.
+Added: While we are uniquely positioned to be pursuing disease-modifying therapies for DMD based on our RNA, gene therapy and gene editing platforms, our competitors may also pursue therapies based on any or all of the platforms or modalities that are competitive with ours.
+Added: The following paragraphs summarize some of these competitors of interest that have disease-modifying therapeutics commercially available or in clinical development.
Nippon Shinyaku Co.
−Removed: (“Nippon”) has reported clinical data for its exon 53 skipping candidate, viltolarsen (NS-065/NCNP-01), from a Phase 1/2 study in Japan and a Phase 2 study in the U.S.
−Removed: Viltolarsen has been reported to have received an orphan drug designation in the U.S., was granted fast track designation by FDA and received a “SAKIGAKE designation” in Japan from the Japanese Ministry of Health, Labor, and Welfare (“MHLW”).
−Removed: Nippon reported in February 2019 that it had initiated a rolling NDA submission with the FDA.
−Removed: Nippon announced on February 7, 2020 that the FDA has filed its NDA for viltolarsen setting a target action date of the third calendar quarter of 2020.
−Removed: Nippon announced on September 26, 2019 that it submitted its NDA for viltolarsen in Japan to the MHLW.
−Removed: Daiichi Sankyo (“Daiichi”) has reported a phase 1/2 clinical trial being underway in Japan for its exon 45 skipping candidate, DS-5141b.
−Removed: In April 2018, Daiichi announced top-line results of the Phase 1/2 clinical trial in Japan of DS-5141 and that Daiichi will continue to develop DS-5141b.
−Removed: Daiichi continues to sponsor an ongoing Phase 1/2 clinical trial of DS-5141b that is active and not recruiting.
−Removed: Solid Biosciences, LLC (“Solid”) has reported that its micro-dystrophin gene transfer product candidate for DMD, SGT-001 began a Phase 2 clinical study in December 2017.
+Added: (“Nippon”) has an exon 53 skipping candidate, VILTEPSO (viltolarsen) (codenamed:
+Added: NS-065/NCNP-01), that is a morpholino based oligonucleotide.
+Added: On March 25, 2020, Nippon announced that the Japanese Ministry of Health, Labor, and Welfare (“MHLW”) has approved Viltepso Intravenous Infusion 250 mg (viltolarsen) for the treatment of patients with DMD who are amendable to exon 53 skipping therapy making it the first regulatory approval for viltolarsen in the world and the first non-steroidal treatment for DMD approved in Japan.
+Added: Nippon further announced on August 13, 2020 that the FDA approved VILTEPSO (viltolarsen) injection for patients with DMD who are amenable to exon 53 skipping therapy.
+Added: Nippon has announced plans to pursue global registration for viltolarsen.
+Added: Wave Life Sciences (“Wave”) is developing oligonucleotides for the treatment of DMD.
+Added: It was developing an exon 51 skipping product candidate for DMD, suvodirsen (WVE-210201) until on December 16, 2019, Wave announced the discontinuation of suvodirsen development for DMD (exon 51 amenable patients).
+Added: Wave more recently reported its intent to develop an exon 53 skipping product candidate, WVE-N531, with plans to submit a CTA in 2021.
+Added: Daiichi Sankyo (“Daiichi”) has reported a phase 1/2 clinical trial conducted in Japan for its exon 45 skipping oligonucleotide candidate, DS-5141b.
+Added: In April 2018, Daiichi announced top-line results of the Phase 1/2 clinical trial of DS-5141 and that Daiichi will continue to develop DS-5141b.
+Added: Daiichi is sponsoring a Phase 2 clinical trial of DS-5141b.
+Added: Solid Biosciences, LLC (“Solid”) has reported that its micro-dystrophin gene transfer product candidate for DMD, SGT-001 began a Phase 2 clinical study (“IGNITE DMD”) in December 2017.
SGT-001 was granted fast track designation by the FDA in October 2018, orphan drug designation in August 2016, and rare pediatric disease designation in 2017.
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Solid announced on January 9, 2020 that in response to the FDA placing the SGT-001 IGNITE DMD trial on clinical hold, previously announced in November 2019, it is conducting its analyses of SGT-001 to determine how to address the clinical hold and resume dosing.
−Removed: (“Pfizer”), following its acquisition of Bamboo Therapeutics, Inc., has initiated a Phase 1 clinical trial in January 2018 to test the safety and tolerability of its AAV-9 / micro-dystrophin gene transfer product candidate for DMD, PF-06939926/BMB-D001.
+Added: Solid recently announced that it has been cleared to resume dosing in its IGNITE DMD clinical trial.
+Added: (“Pfizer”), following its acquisition of Bamboo Therapeutics, Inc., initiated a Phase 1 clinical trial in January 2018 to test the safety and tolerability of its AAV-9 / mini-dystrophin gene transfer product candidate for DMD, PF-06939926/BMB-D001.
The related orphan designation was granted in Europe in August 2016, and in the U.S.
Rare pediatric disease designation was granted by the FDA in April 2018.
−Removed: In June 2019, Pfizer presented initial Phase 1b clinical data on PF-06939926, and on January 28, 2020, it announced that it expects proof-of-concept readouts for PF-06939926 in the first half of 2020.
−Removed: Other companies continue to pursue approval of products for the treatment of DMD and their products may or may not prove to be safer and/or more efficacious than the products and product candidates in our DMD pipeline.
−Removed: Regarding any of these competitors, it is unknown if further clinical development of these or other exon-skipping compounds is planned.
−Removed: Additionally, companies such as Santhera, PTC Therapeutics, Catabasis, Fibrogen, ReveraGen, Capricor, BioPhytis, Mallinckrodt, Astellas Pharma, and Tivorsan have product candidates with mechanisms of action distinct from ours in different stages of development or approval in DMD which we believe could be seen as complementary to exon skipping and not a direct replacement of our products or product candidates at this time.
−Removed: In addition, several companies and institutions have recently entered into collaborations or other agreements for the development of product candidates, including mRNA, gene (CRISPR, AAV, etc.) or small molecule therapies that are potential competitors for therapies being developed in the muscular dystrophy, neuromuscular, CNS and rare disease space, including but not limited to Audentes (now Astella), 4D Molecular Therapeutics, Biogen Inc., Ionis, Synthena AG, Alexion Pharmaceuticals, Inc., Sanofi, Takeda, Roche, Novartis, Eli Lilly, Alnylam Pharmaceuticals, Inc., Moderna Therapeutics, Inc., Akashi, Oxford University, Exonics Therapeutics (acquired by Vertex Pharmaceuticals), CRISPR Therapeutics and Editas Medicine.
+Added: In June 2019, Pfizer presented initial Phase 1b clinical data on PF-06939926.
+Added: In January 2021, Pfizer announced the first dose of its Phase 3 CIFFREO study that will evaluate the efficacy and safety of PF-06939926 in boys with DMD.
+Added: There are several companies in addition to those mentioned above that are pursuing disease modifying programs for DMD that are at the pre-clinical stage.
+Added: These companies are pursuing oligonucleotides, gene transfer therapy or gene editing.
+Added: Some of these pre-clinical approaches have been announced by BioMarin, Ultragenyx, Dyne Therapeutics, Avidity, Regenxbio, Astellas and Exonics (Vertex).
+Added: Other companies continue to pursue development and approval of products for the treatment of DMD and their products may or may not prove to be safer and/or more efficacious than the products and product candidates in our DMD pipeline.
+Added: Regarding any of these competitors, it is unknown if clinical development of these or other compounds is planned or would be continued.
+Added: Additionally, companies such as Santhera, PTC Therapeutics, Fibrogen, ReveraGen, Capricor Therapeutics, BioPhytis, Mallinckrodt, and Antisense Therapeutics have product candidates with mechanisms of action distinct from ours in different stages of development or approval in DMD which we believe could be seen as complementary to exon skipping and not a direct replacement of our products or product candidates at this time.
+Added: In addition, several companies and institutions have recently entered into collaborations or other agreements for the development of product candidates, including mRNA, gene (CRISPR, AAV, etc.) or small molecule therapies that are potential competitors to therapies being developed by us in the muscular dystrophy, neuromuscular, CNS and rare disease space, including but not limited to Audentes (now Astella), Arrowhead Pharmaceuticals, 4D Molecular Therapeutics, Biogen Inc., Ionis, Synthena AG, Alexion Pharmaceuticals, Inc., Sanofi, Takeda, Roche, Novartis, Eli Lilly, Alnylam Pharmaceuticals, Inc., Moderna Therapeutics, Inc., Akashi, Oxford University, Exonics Therapeutics (acquired by Vertex Pharmaceuticals), CRISPR Therapeutics and Editas Medicine.
Platform Technology Competition .
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Competitors with respect to our RNA-targeted technologies include, but are not limited to, Alnylam, Tekmira Pharmaceuticals Corp., Deciphera Pharmaceuticals, Ionis, BioMarin, Sanofi, Synthena AG, Roche Innovation Center Copenhagen (formerly Santaris Pharma A/S) , Shire plc (now Takeda), Nippon, Daiichi Sankyo, Moderna Therapeutics, Avidity, Dyne Therapeutics, Stoke Therapeutics and Wave.
−Removed: As of December 31, 2019, we had 743 employees, 387 of whom hold advanced degrees.
−Removed: Of these employees, 397 are engaged directly in research and development activities and 346 are in selling, general and administration including 71 in the sales force.
−Removed: None of our employees are covered by collective bargaining agreements and we consider relations with our employees to be good.
+Added: Human Capital Resources
+Added: Our urgent mission – to engineer precision genetic medicine for rare diseases that devastate lives and cut futures short – is dependent on our ability to attract, develop and retain the industry’s best and brightest talent across all dimensions of diversity.
+Added: This understanding informs our approach to managing our human capital resources.
+Added: General Information.
+Added: As of December 31, 2020, we had 866 employees globally, 461 of whom hold advanced degrees.
+Added: Of these employees, 494 are engaged directly in research and development activities and 372 are in selling and general and administration.
+Added: None of our employees in the United States are covered by collective bargaining agreements and we consider relations with our employees to be good.
+Added: Equity, diversity, and inclusion .
+Added: We strive to promote diversity, inclusion and equal opportunity across the organization.
+Added: In the area of gender diversity, representation of women has increased over the past several years:
+Added: in 2017 and 2018, women made up 51% of our workforce, and in 2019, this percentage increased to 54%.
+Added: As of December 31, 2020, women made up 55% of our workforce.
+Added: The number of women in leadership positions has also consistently increased.
+Added: In 2017, women represented 35% of the leadership positions at the Director level and above.
+Added: This percentage increased to 36% in 2018, 44% in 2019 and 47% as of December 31, 2020.
+Added: As of December 31, 2020, women held 28.6% of the seats of our Board of Directors, including the Chair of the Board.
+Added: Racial and ethnic diversity has also increased in the past few years, from 23% of our workforce being racially/ethnically diverse in 2017 and 2018, to 26% in 2019 and 29% as of December 31, 2020.
+Added: As of December 31, 2020, 44% of our Executive Committee, which represents the most senior leadership positions in the Company, is diverse based on gender and ethnicity.
+Added: Compensation, Benefits and Ongoing Professional Development.
+Added: We are committed to rewarding, supporting, and developing the employees who make it possible to deliver on our strategy.
+Added: To that end, we offer a comprehensive total rewards package that includes market-competitive pay, broad-based equity grants and bonuses, healthcare benefits, pension and retirement savings plans, paid time off and family leave, caregiving support, fitness subsidies, tuition reimbursement and an Employee Assistance Program.
+Added: We offer robust onsite learning opportunities for employees at every stage in their career, and in 2020 we launched ELEVATE – our leadership development program, the participants of which reflect ethnic, racial and gender diversity.
+Added: In recognition of the new challenges the COVID-19 pandemic brought, we took various steps to support our employees, including by transitioning to remote work and by offering flexible schedule, childcare assistance and sessions focused on resilience and happiness in uncertain times.
+Added: At the same time, we protected our facility-dependent employees, including those needed to maintain manufacturing and clinical research, by instituting strict protocols designed to ensure they remain healthy.
General Corporate Information
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Our common stock is quoted on the Nasdaq Global Select Market under the symbol “SRPT”.
−Removed: While we achieve revenue from EXONDYS 51 and VYONDYS 53 in the U.S.
−Removed: and through distribution of eteplirsen on a named patient basis or through our EAP outside the U.S., we are likely to continue to incur operating losses in the near term associated with our ongoing operations, research and development activities and potential business development activities.
+Added: While we achieve revenue from our products in the U.S.
+Added: and through distribution of eteplirsen, golodirsen and casimersen through our EAP outside the U.S., we are likely to continue to incur operating losses in the near term associated with our ongoing operations, research and development activities and potential business development activities.
For more information about our revenues and operating losses, see Item 7, Management’s Discussion and Analysis of Financial Condition and Results of Operations .
−Removed: As of December 31, 2019 , we had approximately $ 1,134.4 million of cash, cash equivalents and investments, consisting of $ 835.1 million of cash and cash equivalents, $ 289.7 mil lion of short-term investments and $ 9.6 million of long-t erm restricted cash investment s .
+Added: As of December 31, 2020, we had approximately $1,947.8 million of cash, cash equivalents and investments, consisting of $1,502.6 million of cash and cash equivalents, $435.9 million of short-term investments and $9.3 million of long-term restricted cash investments.
We believe that our balance of cash, cash equivalents and investments is sufficient to fund our current operational plan for at least the next twelve months.
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.