Casimersen

CAMBRIDGE, Mass.--( BUSINESS WIRE )--Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today reported financial results for the third quarter 2024. “ I am pleased to report another strong quarter of performance, as we posted $429.8 million in net product revenue for the third quarter, a 39% increase over the same quarter of the prior year. Reflecting our detailed preparation and track record of commercial execution, the launch of ELEVIDYS is proceeding to plan. ELEVIDYS net product revenue was $181.0 million in the quarter, exceeding prior guidance. If one includes royalty revenue generated on Roche’s ex-US sales of ELEVIDYS, total ELEVIDYS performance was $190.5 million for the quarter. Likewise, net product revenue for our three PMOs -- EXONDYS 51, VYONDYS 53, and AMONDYS 45 – performed well, achieving approximately $248.8 million in the quarter and, as anticipated, reflecting a lack of near-term cannibalization from the launch of ELEVIDYS,” said Doug Ingram, president and chief executive officer, Sarepta Therapeutics. “ At the same time, we have made important decisions regarding portfolio prioritization and have made great progress on our pipeline in the quarter. As examples, by mid-2025 we will have submitted a Biologics License Application for one and will be in clinical trials for two others of our Limb-girdle muscular dystrophy programs. Assuming success, these three therapeutic candidates will deliver our next wave of approved therapies as our multi-program platform advances productively.” Third Quarter 2024 and Recent Developments: Sarepta has made the decision to discontinue the SRP-5051 (vesleteplirsen) development program. This decision was informed by information available to date, including the risk-benefit of the program, feedback from the FDA, and the evolving therapeutic landscape for Duchenne. Presented new data from its neuromuscular portfolio at 2024 World Muscle Society Congress (WMS 2024): Among the multiple presentations from Sarepta at WMS 2024 were new safety and efficacy results from several studies in the SRP-9001 clinical development program. These data included: Skeletal muscle MRI data from Study 9001-301 EMBARK where multiple muscles from a subset of patients (n=39) were evaluated using MRI/MRS and MRI T2 signal prior to treatment and at 52 weeks post treatment. Across all measures, patients treated with SRP-9001 showed improvement over the placebo group with less accumulation of fat and fibrosis. The finding correlates with the functional outcomes in Part 1 of EMBARK which showed stabilization or slowing of disease progression in patients treated with SRP-9001 compared to placebo. Cardiac MRI data from EMBARK where an assessment of a subgroup of patients (n=19), found no negative effects on cardiac safety compared to placebo at 52 weeks and no differences in cardiac measures in SRP-9001-treated patients compared to the placebo group at one year. Sarepta plans for future longitudinal cardiac MRI studies to evaluate the long-term protection of cardiac muscle. Five-year functional results from Study SRP-9001-101, the longest-term data to date for a gene therapy in Duchenne. These patients, with an average age of 10 years at the time of the assessment, were stable or showed a slowing of disease progression with an increase in divergence from natural history over time as shown by an external control analysis. Notably this evaluation was conducted at an age when many Duchenne patients are entering the steep decline phase of the disease. The five-year results showed: A 9.8 point (p=0.0127) increase in change from baseline in the North Star Ambulatory Assessment (NSAA) total score to five years. At year five the sustained increase in NSAA total score was statistically significant and clinically meaningful when compared to an external control cohort. An 8.8 second decrease (p=0.0198) in time to rise from floor, change from baseline to five years. The improvement was statistically significant and clinically meaningful when compared to an external control cohort. Patients maintained their 10-meter walk test time throughout the five years. No new safety signals. Results from EMBARK study of delandistrogene moxeparvovec published in Nature Medicine : In early October, efficacy and safety results from Part 1 of the EMBARK study of delandistrogene moxeparvovec-rokl for the treatment of Duchenne muscular dystrophy were published in Nature Medicine . These published results demonstrate a treatment benefit with delandistrogene moxeparvovec that is clinically meaningful and similar regardless of age and a favorable risk-benefit profile. EMBARK, also known as Study SRP-9001-301, is a global, randomized, double-blind, placebo-controlled, Phase 3 clinical study of delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy between the ages of 4 through 7 years. Conference Call The event will be webcast live under the investor relations section of Sarepta's website at https://investorrelations.sarepta.com/events-presentations and following the event a replay will be archived there for one year. Interested parties participating by phone will need to register using this online form . After registering for dial-in details, all phone participants will receive an auto-generated e-mail containing a link to the dial-in number along with a personal PIN number to use to access the event by phone. Q3 2024 Financial Highlights 1 For the Three Months Ended September 30, 2024 2023 QTD Change (in millions, except for per share amounts) $ % Total Revenues $ 467.2 $ 331.8 135.4 41 % Operating income (loss): GAAP $ 22.2 $ (20.8 ) 43.0 NM* Non-GAAP $ 74.9 $ 37.7 37.2 99 % Net income (loss): GAAP $ 33.6 $ (40.9 ) 74.5 NM* Non-GAAP $ 67.0 $ 31.5 35.5 113 % Diluted earnings (loss) per share: GAAP $ 0.34 $ (0.46 ) 0.80 NM* Non-GAAP $ 0.62 $ 0.31 0.31 99 % For the Nine Months Ended September 30, 2024 2023 YTD Change (in millions, except for per share amounts) $ % Total Revenues $ 1,243.6 $ 846.6 397.0 47 % Operating income (loss): GAAP $ 56.4 $ (292.4 ) 348.8 NM* Non-GAAP $ 216.5 $ (123.5 ) 340.0 NM* Net income (loss): GAAP $ 76.2 $ (581.6 ) 657.8 NM* Non-GAAP $ 191.9 $ (146.1 ) 338.0 NM* Diluted earnings (loss) per share: GAAP $ 0.78 $ (6.56 ) 7.34 NM* Non-GAAP $ 1.78 $ (1.65 ) 3.43 NM* *NM: not meaningful [1] For an explanation of our use of non-GAAP financial measures, please refer to the “Use of Non-GAAP Financial Measures” section later in this press release and for a reconciliation of each non-GAAP financial measure to the most comparable GAAP measures, see the tables at the end of this press release. As of September 30, 2024 As of December 31, 2023 (in millions) Cash, cash equivalents, restricted cash and investments $ 1,395.8 $ 1,691.8 Revenues Total revenues increased by $135.4 million for the three months ended September 30, 2024, compared to the same period of 2023. The increase primarily reflects the initial product launch of ELEVIDYS in June 2023 and expanded label in June 2024, partially offset by a $22.5 million decrease in the amortization of the single, combined performance obligation under our collaboration agreement with F. Hoffman-La Roche Ltd. (“Roche”), which was fully amortized as of December 31, 2023. Total revenues increased by $397.0 million for the nine months ended September 30, 2024, compared to the same period of 2023. The increase primarily reflects the initial product launch of ELEVIDYS in June 2023 and expanded label in June 2024, as well as the $48.0 million of collaboration revenue recognized related to an option declined by Roche to acquire the ex-US rights to a certain external, early stage Duchenne-specific program, partially offset by a $66.8 million decrease in the amortization of the single, combined performance obligation under our collaboration agreement with Roche, which was fully amortized as of December 31, 2023. Additionally, included in total revenues for the three and nine months ended September 30, 2024, is $37.4 million and $45.8 million, respectively, of contract manufacturing and other revenues associated with commercial ELEVIDYS supply delivered to Roche and royalty revenue received from Roche, with no similar activity for the same periods of 2023. Cost of sales (excluding amortization of in-licensed rights) Cost of sales (excluding amortization of in-license rights) increased by $54.7 million and $80.6 million for the three and nine months ended September 30, 2024, respectively, compared with the same periods of 2023. The increases in both periods primarily reflect the initial product launch of ELEVIDYS in June 2023 and expanded label in June 2024. For the three and nine months ended September 30, 2024, we recognized $13.7 million and $15.4 million of cost of sales related to products sold to Roche under our collaboration agreement, with no similar activity for the same periods of 2023. Operating expenses and others Research and development expenses increased by $30.2 million for the three months ended September 30, 2024, compared with the same period of 2023. The increase in research and development expense primarily reflects $55.4 million of costs associated with the termination of the development, commercial manufacturing and supply agreement (the “Thermo Agreement”) related to Brammer Bio MA, LLC, an affiliate of Thermo Fisher Scientific, Inc. in August 2024, net of the reimbursable termination costs by Roche, partially offset by a decrease in clinical and manufacturing activity for our PPMO platform and Eteplirsen program. Research and development expenses decreased by $77.3 million for the nine months ended September 30, 2024, compared with the same period of 2023. The decrease in research and development expense primarily reflects capitalization of commercial batches of ELEVIDYS manufactured after its approval in June 2023, partially offset by $55.4 million of costs associated with the termination of the Thermo Agreement, net of the reimbursable termination costs by Roche. Non-GAAP research and development expenses increased by $35.9 million for the three months ended September 30, 2024, compared with the same period of 2023. Non-GAAP research and development expenses decreased by $65.0 million for the nine months ended September 30, 2024, compared with the same period of 2023. Selling, general and administrative expenses increased by $7.3 million and $43.8 million for the three and nine months ended September 30, 2024, compared with the same periods of 2023. The increase in selling, general and administrative expenses for both periods is primarily driven by professional services used to support the continued efforts to commercialize ELEVIDYS and ongoing litigation matters, the timing of charitable contributions, compensation due to changes in headcount, as well as the achievement of performance conditions related to certain Performance Stock Units. Non-GAAP selling, general and administrative expenses increased by $7.4 million and $40.3 million for the three and nine months ended September 30, 2024, respectively, compared with the same periods of 2023. For the three months ended September 30, 2024, other income (loss), net increased by $24.1 million, compared with the same period of 2023, which primarily reflects an impairment of a strategic investment during the three months ended September 30, 2023, with no similar activity in 2024. For the nine months ended September 30, 2024, other income (loss), net increased by $300.6 million compared with the same period of 2023, which primarily reflects a $387.3 million loss on debt extinguishment offset by a $102.0 million gain on the sale of a Priority Review Voucher (“PRV”) during the nine months ended September 30, 2023, with no similar activities in 2024. Income tax expense for the three months ended September 30, 2024 and 2023, was approximately $0.4 million and $7.8 million, respectively. Income tax expense for the nine months ended September 30, 2024 and 2023, was approximately $12.8 million and $21.2 million, respectively. Income tax expense for all periods presented primarily relates to state, federal and foreign income taxes for which available tax losses or credits were not available to offset. Use of Non-GAAP Measures In addition to the GAAP financial measures set forth in this press release, we have included the following non-GAAP measurements: Non-GAAP income (loss) is defined by us as GAAP net income (loss) excluding interest income, net, depreciation and amortization expense, stock-based compensation expense, the estimated income tax impact of each pre-tax non-GAAP adjustment and other items. Non-GAAP earnings (loss) per share is defined by us as non-GAAP net income (loss), as defined previously, divided by the weighted-average number of shares of common stock and dilutive common stock equivalents outstanding. The non-GAAP earnings per share is calculated using diluted shares whereas the non-GAAP net loss per share is calculated using basic shares as all other instruments are anti-dilutive. Non-GAAP operating income (loss) is defined by us as GAAP operating income (loss) excluding depreciation and amortization expense, stock-based compensation expense and other items. Non-GAAP research and development expenses are defined by us as GAAP research and development expenses excluding depreciation and amortization expense, stock-based compensation expense and other items. Non-GAAP selling, general and administrative expenses are defined by us as GAAP selling, general and administrative expenses excluding depreciation expense, stock-based compensation expense and other items. The following components are used to adjust our GAAP financial measures into the previously defined non-GAAP measurements: Interest, depreciation and amortization - Interest income, net amounts can vary substantially from period to period due to changes in cash and debt balances and interest rates driven by market conditions outside of our operations. Depreciation expense can vary substantially from period to period as the purchases of property and equipment may vary significantly from period to period and without any direct correlation to our operating performance. Amortization expense primarily associated with patent costs are amortized over a period of several years after acquisition or patent application or renewal. Stock-based compensation expenses - Stock-based compensation expenses represent non-cash charges related to equity awards we have granted. Although these are recurring charges to operations, we believe the measurement of these amounts can vary substantially from period to period and depend significantly on factors that are not a direct consequence of operating performance that is within our control. Therefore, we believe that excluding these charges facilitates comparisons of our operational performance in different periods. Other items - We evaluate other items of expense and income on an individual basis. We take into consideration quantitative and qualitative characteristics of each item, including (a) nature, (b) whether the items relate to our ongoing business operations, and (c) whether we expect the items to continue or occur on a regular basis. These other items include impairment of strategic investments, change in fair value of derivatives, gain from sale of the PRV and loss on debt extinguishment and may include other items that fit the above characteristics in the future. We exclude from our non-GAAP results: The impairment of any strategic investments as it is a non-cash item and is not considered to be a normal operating expense due to the variability of amount and lack of predictability as to the occurrence and/or timing of such impairments. The loss on debt extinguishment, which is considered to be an infrequent and non-cash event as it is associated with a distinct financing decision and is not indicative of the performance of our core operations, which accordingly, would make it difficult to compare our results to peer companies that also provide non-GAAP disclosures. The gain from sale of the PRV obtained as a result of the FDA accelerated approval of ELEVIDYS in June 2023 as it is a non-recurring event. The change in fair value of derivatives related to 1.) regulatory-related contingent payments meeting the definition of a derivative to Myonexus selling shareholders as well as to an academic institution under a separate license agreement and 2.) the derivative asset associated with capped call options for our $570.0 million aggregate principal amount of senior convertible notes due on November 15, 2024, as these are non-cash items and are not considered to be normal operating expenses due to the variability of amounts and lack of predictability as to occurrence and/or timing. Beginning in the fourth quarter of 2023, amortization of in-licensed rights (formerly included within depreciation and amortization expense) and income tax (benefit) expense are no longer excluded from the non-GAAP results. We now include the income tax effect of adjustments, which represents the estimated income tax impact of each pre-tax non-GAAP adjustment based on the applicable effective income tax rate. Non-GAAP financial results for the for the three and nine months ended September 30, 2023 have been updated to reflect this change for comparability. We use these non-GAAP measures as key performance measures for the purpose of evaluating operational performance and cash requirements internally. We also believe these non-GAAP measures increase comparability of period-to-period results and are useful to investors as they provide a similar basis for evaluating our performance as is applied by management. These non-GAAP measures are not intended to be considered in isolation or to replace the presentation of our financial results in accordance with GAAP. Use of the terms non-GAAP research and development expenses, non-GAAP selling, general and administrative expenses, non-GAAP other income and loss adjustments, non-GAAP operating income (loss), non-GAAP net income (loss), and non-GAAP diluted net earnings (loss) per share may differ from similar measures reported by other companies, which may limit comparability, and are not based on any comprehensive set of accounting rules or principles. All relevant non-GAAP measures are reconciled from their respective GAAP measures in the attached table “ Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures.” About EXONDYS 51 EXONDYS 51 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 51 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 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein. EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This indication is approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. EXONDYS 51 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental. Important Safety Information About EXONDYS 51 Hypersensitivity reactions, including bronchospasm, chest pain, cough, tachycardia, and urticaria have occurred in patients who were treated with EXONDYS 51. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the EXONDYS 51 therapy. Adverse reactions in DMD patients (N=8) treated with EXONDYS 51 30 mg or 50 mg/kg/week by intravenous (IV) infusion with an incidence of at least 25% more than placebo (N=4) (Study 1, 24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%), vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most common adverse reactions were balance disorder and vomiting. Because of the small numbers of patients, these represent crude frequencies that may not reflect the frequencies observed in practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is not recommended. The most common adverse reactions from observational clinical studies (N=163) seen in greater than 10% of patients were headache, cough, rash, and vomiting. Other adverse events may occur. To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For further information, please see the full Prescribing Information . About VYONDYS 53 VYONDYS 53 (golodirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 53 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 53 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein. VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. VYONDYS 53 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental. Important Safety Information for VYONDYS 53 CONTRAINDICATIONS: VYONDYS 53 is contraindicated in patients with a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53. Anaphylaxis has occurred in patients receiving VYONDYS 53. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Hypersensitivity reactions, including anaphylaxis, rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in VYONDYS 53-treated patients, some requiring treatment. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion, interrupting, or discontinuing the VYONDYS 53 therapy and monitor until the condition resolves. VYONDYS 53 is contraindicated in patients with a history of a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53. Kidney Toxicity: Kidney toxicity was observed in animals who received golodirsen. Although kidney toxicity was not observed in the clinical studies with VYONDYS 53, the clinical experience with VYONDYS 53 is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking VYONDYS 53. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein- to-creatinine ratio should be measured before starting VYONDYS 53. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting VYONDYS 53. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to- creatinine ratio every three months. Only urine expected to be free of excreted VYONDYS 53 should be used for monitoring of urine protein. Urine obtained on the day of VYONDYS 53 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any VYONDYS 53 that is excreted in the urine and thus lead to a false positive result for urine protein. If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation. ADVERSE REACTIONS: Adverse reactions observed in at least 20% of treated patients and greater than placebo were (VYONDYS 53, placebo): headache (41%, 10%), pyrexia (41%, 14%), fall (29%, 19%), abdominal pain (27%, 10%), nasopharyngitis (27%, 14%), cough (27%, 19%), vomiting (27%, 19%), and nausea (20%, 10%). Other adverse reactions that occurred at a frequency greater than 5% of VYONDYS 53-treated patients and at a greater frequency than placebo were: administration site pain, back pain, pain, diarrhea, dizziness, ligament sprain, contusion, influenza, oropharyngeal pain, rhinitis, skin abrasion, ear infection, seasonal allergy, tachycardia, catheter site related reaction, constipation, and fracture. Other adverse events may occur. To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For further information, please see the full Prescribing Information . About AMONDYS 45 AMONDYS 45 (casimersen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology 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. Exon skipping is intended to allow for production of an internally truncated dystrophin protein. AMONDYS 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. AMONDYS 45 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental. Important Safety Information for AMONDYS 45 CONTRAINDICATIONS : AMONDYS 45 is contraindicated in patients with a known serious hypersensitivity to casimersen or any of the inactive ingredients in AMONDYS 45. Instances of hypersensitivity including angioedema and anaphylaxis have occurred. WARNINGS AND PRECAUTIONS Hypersensitivity: Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45. If a hypersensitivity reaction occurs, institute appropriate medical treatment, and consider slowing the infusion, interrupting, or discontinuing the AMONDYS 45 infusion and monitor until the condition resolves. AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45. Kidney Toxicity : Kidney toxicity was observed in animals who received casimersen. Although kidney toxicity was not observed in the clinical studies with AMONDYS 45, kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking AMONDYS 45. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting AMONDYS 45. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio (UPCR) every three months. Only urine expected to be free of excreted AMONDYS 45 should be used for monitoring of urine protein. Urine obtained on the day of AMONDYS 45 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any AMONDYS 45 that is excreted in the urine and thus lead to a false positive result for urine protein. If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation. Adverse Reactions: Adverse reactions occurring in at least 20% of patients treated with AMONDYS 45 and at least 5% more frequently than in the placebo group were (AMONDYS 45, placebo): upper respiratory infections (65%, 55%), cough (33%, 26%), pyrexia (33%, 23%), headache (32%, 19%), arthralgia (21%, 10%), and oropharyngeal pain (21%, 7%). Other adverse reactions that occurred in at least 10% of patients treated with AMONDYS 45 and at least 5% more frequently than in the placebo group were: ear pain, nausea, ear infection, post-traumatic pain, and dizziness and light-headedness. Other adverse events may occur. To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For further information, please see the full Prescribing Information . About ELEVIDYS (delandistrogene moxeparvovec-rokl) ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack of dystrophin protein – through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle. ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age. For patients who are ambulatory and have a confirmed mutation in the DMD gene For patients who are non-ambulatory and have a confirmed mutation in the DMD gene. The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). IMPORTANT SAFETY INFORMATION CONTRAINDICATION: ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene. WARNINGS AND PRECAUTIONS: Infusion-related Reactions: Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following ELEVIDYS administration. Closely monitor patients during administration and for at least 3 hours after the end of infusion. If symptoms of infusion-related reactions occur, slow, or stop the infusion and give appropriate treatment. Once symptoms resolve, the infusion may be restarted at a lower rate. ELEVIDYS should be administered in a setting where treatment for infusion-related reactions is immediately available. Discontinue infusion for anaphylaxis. Acute Serious Liver Injury: Acute serious liver injury has been observed with ELEVIDYS, and administration may result in elevations of liver enzymes (such as GGT, GLDH, ALT, AST) or total bilirubin, typically seen within 8 weeks. Patients with preexisting liver impairment, chronic hepatic condition, or acute liver disease (e.g., acute hepatic viral infection) may be at higher risk of acute serious liver injury. Postpone ELEVIDYS administration in patients with acute liver disease until resolved or controlled. Prior to ELEVIDYS administration, perform liver enzyme test and monitor liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months following ELEVIDYS infusion. Continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT, and total bilirubin levels return to near baseline levels). Systemic corticosteroid treatment is recommended for patients before and after ELEVIDYS infusion. Adjust corticosteroid regimen when indicated. If acute serious liver injury is suspected, consultation with a specialist is recommended. Immune-mediated Myositis: In clinical trials, immune-mediated myositis has been observed approximately 1 month following ELEVIDYS infusion in patients with deletion mutations involving exon 8 and/or exon 9 in the DMD gene. Symptoms of severe muscle weakness, including dysphagia, dyspnea, and hypophonia, were observed. Limited data are available for ELEVIDYS treatment in patients with mutations in the DMD gene in exons 1 to 17 and/or exons 59 to 71. Patients with deletions in these regions may be at risk for a severe immune-mediated myositis reaction. Advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea, or hypophonia, as these may be symptoms of myositis. Consider additional immunomodulatory treatment (immunosuppressants [e.g., calcineurin-inhibitor] in addition to corticosteroids) based on patient’s clinical presentation and medical history if these symptoms occur. Myocarditis : Acute serious myocarditis and troponin-I elevations have been observed following ELEVIDYS infusion in clinical trials. If a patient experiences myocarditis, those with pre-existing left ventricle ejection fraction (LVEF) impairment may be at higher risk of adverse outcomes. Monitor troponin-I before ELEVIDYS infusion and weekly for the first month following infusion and continue monitoring if clinically indicated. More frequent monitoring may be warranted in the presence of cardiac symptoms, such as chest pain or shortness of breath. Advise patients to contact a physician immediately if they experience cardiac symptoms. Preexisting Immunity against AAVrh74: In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels. Following treatment with ELEVIDYS, all patients developed anti-AAVrh74 antibodies. Perform baseline testing for presence of anti-AAVrh74 total binding antibodies prior to ELEVIDYS administration. ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers greater than or equal to 1:400. Adverse Reactions: The most common adverse reactions (incidence ≥5%) reported in clinical studies were vomiting, nausea, liver injury, pyrexia, and thrombocytopenia. Report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Sarepta Therapeutics at 1-888-SAREPTA (1-888-727-3782). For further information, please see the full Prescribing Information . About Sarepta Therapeutics Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit www.sarepta.com or follow us on LinkedIn , X (formerly Twitter) , Instagram and Facebook . Forward-Looking Statements In order to provide Sarepta’s investors with an understanding of its current results and future prospects, this press release contains statements that are forward-looking. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “will,” “may,” “intends,” “prepares,” “looks,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements relating to our future operations, financial performance and projections, business plans, market opportunities, priorities and research and development programs and technologies; the potential benefits of our technologies and scientific approaches, including the potential benefits of SRP-9003; and expected milestones and plans, including our expectation that by mid-2025 we will have submitted a Biologics License Application for one, and will be in clinical trials for two others, of our Limb-girdle muscular dystrophy programs. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta’s control. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: success in preclinical and clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful, and the results of future research may not be consistent with past positive results or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; we may not be able to comply with all FDA post-approval commitments and requirements with respect to our products in a timely manner or at all; certain programs may never advance in the clinic or may be discontinued for a number of reasons, including regulators imposing a clinical hold and us suspending or terminating clinical research or trials; if the actual number of patients suffering from the diseases we aim to treat is smaller than estimated, our revenue and ability to achieve profitability may be adversely affected; we may not be able to execute on our business plans, including meeting our expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing our product candidates to market, for various reasons, some of which may be outside of our control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, and regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; and those risks identified under the heading “Risk Factors” in our most recent Annual Report on Form 10-K for the year ended December 31, 2023, and our most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review. Internet Posting of Information We routinely post information that may be important to investors in the 'Investors' section of our website at www.sarepta.com . We encourage investors and potential investors to consult our website regularly for important information about us. Sarepta Therapeutics, Inc. Condensed Consolidated Statements of Income (Loss) (unaudited, in thousands, except per share amounts) For the Three Months Ended September 30, For the Nine Months Ended September 30, 2024 2023 2024 2023 Revenues: Products, net $ 429,771 $ 309,322 $ 1,149,803 $ 779,805 Collaboration and other 37,401 22,495 93,764 66,750 Total revenues 467,172 331,817 1,243,567 846,555 Cost and expenses: Cost of sales (excluding amortization of in-licensed rights) 91,691 37,026 186,795 106,167 Research and development 224,483 194,301 604,569 681,870 Selling, general and administrative 128,200 120,893 393,999 350,171 Amortization of in-licensed rights 602 439 1,804 796 Total cost and expenses 444,976 352,659 1,187,167 1,139,004 Operating income (loss) 22,196 (20,842 ) 56,400 (292,449 ) Other income (loss), net: Other income (expense), net 11,810 (12,332 ) 32,631 17,309 Gain from sale of Priority Review Voucher — — — 102,000 Loss on debt extinguishment — — — (387,329 ) Total other income (loss), net 11,810 (12,332 ) 32,631 (268,020 ) Income (loss) before income tax expense 34,006 (33,174 ) 89,031 (560,469 ) Income tax expense 395 7,763 12,841 21,163 Net income (loss) $ 33,611 $ (40,937 ) $ 76,190 $ (581,632 ) Earnings (loss) per share: Basic $ 0.35 $ (0.46 ) $ 0.80 $ (6.56 ) Diluted $ 0.34 $ (0.46 ) $ 0.78 $ (6.56 ) Weighted average number of shares of common stock used in computing earnings (loss) per share: Basic 95,390 88,889 94,669 88,609 Diluted 100,448 88,889 99,572 88,609 Sarepta Therapeutics, Inc. Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures (unaudited, in thousands, except per share amounts) For the Three Months Ended September 30, For the Nine Months Ended September 30, 2024 2023 2024 2023 GAAP net income (loss) $ 33,611 $ (40,937 ) $ 76,190 $ (581,632 ) Interest income, net (13,415 ) (17,593 ) (43,156 ) (46,565 ) Depreciation and amortization expense* 9,204 10,489 25,465 32,229 Stock-based compensation expense 43,450 48,061 134,624 136,688 Change in fair value of derivatives (1,535 ) 2,000 8,565 1,200 Gain from sale of Priority Review Voucher — — — (102,000 ) Loss on debt extinguishment — — — 387,329 Impairment of strategic investments — 27,500 — 27,821 Income tax effect of adjustments** (4,300 ) 1,992 (9,772 ) (1,197 ) Non-GAAP net income (loss)** $ 67,015 $ 31,512 $ 191,916 $ (146,127 ) GAAP net earnings (loss) per share - diluted: $ 0.34 $ (0.46 ) $ 0.78 $ (6.56 ) Add: impact of GAAP to Non-GAAP adjustments $ 0.28 $ 0.77 $ 1.00 $ 4.91 Non-GAAP net earnings (loss) per share - diluted*** $ 0.62 $ 0.31 $ 1.78 $ (1.65 ) Weighted average number of shares of common stock used in computing diluted earnings (loss) per share:**** GAAP 100,448 88,889 99,572 88,609 Non-GAAP 108,548 101,722 107,672 88,609 *Beginning in the fourth quarter of 2023, depreciation and amortization excludes amortization of in-licensed rights. Non-GAAP financial results for the three and nine months ended September 30, 2023, have been updated to reflect this change for comparability. **Beginning in the fourth quarter of 2023, income tax (benefit) expense is no longer excluded from the non-GAAP results. We have replaced this metric with income tax effect of adjustments, which represents the estimated income tax impact of each pre-tax non-GAAP adjustment based on the applicable statutory income tax rate. Refer below for a reconciliation of effective tax rates. Non-GAAP financial results for the three and nine months ended September 30, 2023, have been updated to reflect this change for comparability. ***Non-GAAP earnings per share is calculated using diluted shares whereas non-GAAP net loss per share is calculated using basic shares as all other instruments are anti-dilutive. There was a $0.04 impact to the calculation of non-GAAP net earnings per share as a result of the inclusion of diluted shares for the three months ended September 30, 2023. ****The difference between the weighted average number of shares of common stock used in computing diluted GAAP and non-GAAP earnings per share for the three and nine months ended September 30, 2024, is a result of the exclusion of the potential share settlement of the 2027 Notes from the GAAP earnings per share as the inclusion of such shares was anti-dilutive. For the Three Months Ended September 30, For the Nine Months Ended September 30, 2024 2023 2024 2023 Total effective tax rate, GAAP 1.2 % (23.4 ) % 14.4 % (3.8 ) % Less: impact of GAAP to Non-GAAP adjustments 6.2 (16.7 ) (3.8 ) (24.4 ) Total effective tax rate, Non-GAAP 7.4 % (40.1 ) % 10.6 % (28.2 ) % Sarepta Therapeutics, Inc. Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures (unaudited, in thousands) For the Three Months Ended September 30, For the Nine Months Ended September 30, 2024 2023 2024 2023 GAAP research and development expenses $ 224,483 $ 194,301 $ 604,569 $ 681,870 Stock-based compensation expense (18,034 ) (22,325 ) (54,113 ) (60,315 ) Depreciation and amortization expense (6,664 ) (8,109 ) (18,692 ) (24,794 ) Non-GAAP research and development expenses $ 199,785 $ 163,867 $ 531,764 $ 596,761 For the Three Months Ended September 30, For the Nine Months Ended September 30, 2024 2023 2024 2023 GAAP selling, general and administrative expenses $ 128,200 $ 120,893 $ 393,999 $ 350,171 Stock-based compensation expense (25,416 ) (25,736 ) (80,511 ) (76,373 ) Depreciation expense (2,540 ) (2,380 ) (6,773 ) (7,435 ) Non-GAAP selling, general and administrative expenses $ 100,244 $ 92,777 $ 306,715 $ 266,363 For the Three Months Ended September 30, For the Nine Months Ended September 30, 2024 2023 2024 2023 GAAP operating income (loss) $ 22,196 $ (20,842 ) $ 56,400 $ (292,449 ) Stock-based compensation expense 43,450 48,061 134,624 136,688 Depreciation and amortization expense 9,204 10,489 25,465 32,229 Non-GAAP operating income (loss) $ 74,850 $ 37,708 $ 216,489 $ (123,532 ) Sarepta Therapeutics, Inc. Condensed Consolidated Balance Sheets (unaudited, in thousands, except share and per share data) As of September 30, 2024 As of December 31, 2023 Assets Current assets: Cash and cash equivalents $ 197,855 $ 428,430 Short-term investments 1,000,534 1,247,820 Accounts receivable, net 434,524 400,327 Inventory 565,924 322,859 Manufacturing-related deposits and prepaids 321,055 102,181 Other current assets 165,477 77,714 Total current assets 2,685,369 2,579,331 Property and equipment, net 305,788 227,154 Right of use assets 140,898 129,952 Non-current inventory 202,550 191,368 Non-current investments 181,770 — Other non-current assets 83,559 136,771 Total assets $ 3,599,934 $ 3,264,576 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 118,774 $ 164,918 Accrued expenses 344,830 314,997 Deferred revenue, current portion 127,001 50,416 Current portion of long-term debt 91,595 105,483 Other current liabilities 17,289 17,845 Total current liabilities 699,489 653,659 Long-term debt 1,135,965 1,132,515 Lease liabilities, net of current portion 170,009 140,965 Deferred revenue, net of current portion 325,000 437,000 Contingent consideration 47,400 38,100 Other non-current liabilities 1,000 3,000 Total liabilities 2,378,863 2,405,239 Stockholders’ equity: Preferred stock, $0.0001 par value, 3,333,333 shares authorized; none issued and outstanding — — Common stock, $0.0001 par value, 198,000,000 shares authorized; 95,493,005 and 93,731,831 issued and outstanding at September 30, 2024, and December 31, 2023, respectively 10 9 Additional paid-in capital 5,588,839 5,304,623 Accumulated other comprehensive income, net of tax 2,245 918 Accumulated deficit (4,370,023 ) (4,446,213 ) Total stockholders’ equity 1,221,071 859,337 Total liabilities and stockholders’ equity $ 3,599,934 $ 3,264,576 Source: Sarepta Therapeutics, Inc.

According to Global Info Research (GIR), the global antisense oligonucleotide (ASO) drug market reached approximately USD 2.8 billion in sales in 2023 and is projected to grow to around USD 10.6 billion by 2030, with a compound annual growth rate (CAGR) of 21.5%. Notably, the global oligonucleotide drug market grew from USD 10 million in 2016 to USD 3.25 billion in 2021, reflecting an impressive CAGR of 217.8%. As a cutting-edge therapeutic approach, ASOs precisely target the mRNA or pre-mRNA of disease-causing genes, modulating their expression to offer novel solutions for genetic and neurodegenerative diseases and other hard-to-treat conditions. With high specificity and a direct mechanism of action, ASOs not only correct abnormal gene expression but also inhibit harmful protein synthesis at the source, demonstrating significant potential for clinical applications. Advances in technology and ongoing clinical trials are driving ASO therapies towards maturity, heralding a new era of precision medicine focused on gene regulation. The transaction status of ASOs in Patsnap SynapseFactors driving ASO market growth include:·Increased Research and Development: A surge in R&D activities related to gene therapy and personalized medicine has fueled demand for ASO technology. With advancements in genomics, scientists are gaining a better understanding of gene expression regulation mechanisms and can utilize ASO technology to precisely target specific gene sequences. ·Rising Incidence of Genetic Disorders: The growing prevalence of genetic disorders has increased demand for effective treatments, and ASO technology offers promising options. For example, in the case of genetic conditions like Duchenne muscular dystrophy (DMD), ASOs can restore the production of functional proteins by altering mRNA splicing. ·Advances in Drug Delivery: Progress in ASO delivery methods, including peptide carriers and lipid nanoparticles, has simplified ASO therapy administration. These delivery technologies not only enhance ASO stability and bioavailability but also reduce side effects, improving therapeutic efficacy. ·Supportive Regulatory Environment: Regulatory agencies are increasingly supportive of innovative gene therapies, creating favorable conditions for ASO drug development. For instance, both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have established pathways to expedite the approval process for rare and orphan drugs. ·Strategic Collaborations: Collaborations between biotech firms, major pharmaceutical companies, and research institutions promote innovation and accelerate ASO therapy development. These partnerships facilitate resource sharing, expertise exchange, and technology advancements, speeding the transition of drugs from the lab to the market. How Does ASOs Work?ASOs play a vital role in gene expression regulation through several mechanisms: ·Gene Targeting: ASOs are designed to target specific genes or mRNA molecules. Each ASO molecule is complementary to a particular mRNA sequence, enabling it to bind and interact with the target mRNA. RNase H-Mediated mRNA Degradation: Once inside the cell, the ASO binds to the target mRNA. This binding recruits RNase H, which degrades the mRNA paired with the ASO, leading to mRNA breakdown. Complementary Base Pairing: The ASO’s guide strand binds to complementary mRNA through base pairing. This binding is highly specific and only occurs when there is a perfect or near-perfect match between the ASO and the target mRNA. ·mRNA Degradation: The ASO-mRNA binding triggers RNase H to cleave the mRNA at the interaction site. This cleavage prevents the mRNA from being translated into functional proteins. ·Gene Expression Silencing: As mRNA is degraded, the cell cannot produce the corresponding protein. This effectively silences the gene’s expression, reducing or entirely stopping the production of the protein encoded by the gene. ·Temporary Effect: ASO-mediated gene silencing is typically temporary. As the affected mRNA degrades and cellular machinery continues to function, gene expression can return to normal once the ASO is no longer present. RNase H Degradation Mechanism of ASOsIn addition, ASOs can modify pre-mRNA splicing through steric hindrance, thus regulating gene translation. These combined mechanisms make ASOs a powerful gene expression regulation tool suitable for treating various diseases, including but not limited to genetic disorders, cancer, infectious disease prevention, and neurological disease treatment. ASO Drug Segmentation TrendsDue to their high molecular weight and charged properties, ASOs have difficulty naturally crossing cell membranes in the body, thus requiring specialized delivery systems. Below are some main classifications of ASO delivery methods: Delivery of ASOs1.Naked Oligonucleotides: ·Direct Administration: Unmodified ASOs are directly administered via injection or other methods, typically at higher doses due to susceptibility to enzymatic degradation and challenges with cellular uptake. 2.Chemical Modifications: ·Modified Oligonucleotides: Chemical modifications enhance ASO stability, such as 2'-O-methylation, phosphorothioate (PS) modification, and locked nucleic acid (LNA) modifications, which improve stability, reduce degradation, and increase cellular uptake efficiency. 3.Ligand Conjugation: ·GalNAc Conjugation: Conjugating ASOs with GalNAc (N-acetylgalactosamine) ligands enhances selective delivery to liver cells, a method used in Alnylam Pharmaceuticals' products. ·Other Ligands: Various ligands are used to target delivery to specific cells or tissues. 4.Nanoparticles: ·Lipid Nanoparticles (LNPs): Encapsulating ASOs within LNPs protects them from degradation and aids cellular entry. LNPs can circulate through the bloodstream to target organs or tissues and enter cells via endocytosis. ·Polymer Nanoparticles: Using polymer matrices to encapsulate ASOs also enhances stability and internalization efficiency. 5.Exosomes: ·Exosome Delivery: Using naturally secreted vesicles (exosomes) as carriers delivers ASOs to target cells, reducing immune responses and enhancing specificity. 6.Viral Vectors: ·Adeno-Associated Virus (AAV): Though primarily used in gene therapy, AAV may also be utilized to deliver ASOs in certain cases. 7.Localized Delivery: ·Direct Injection: Directly injecting ASOs into the affected area, such as muscle or the central nervous system, is suitable for treating diseases localized to specific organs or tissues. ·Inhalation Therapy: For respiratory diseases, ASOs can be delivered to the lungs via inhalation. Each delivery method has unique advantages and limitations, and selecting the appropriate system depends on the therapeutic target, disease type, and ASO's chemical properties. With technological advancements, new delivery platforms and methods are emerging, aiming to improve the efficacy and safety of ASO therapies. ASO Applications by IndicationTop 10 ASOs indications in Patsnap Synapse1.Genetic Disorders: ·DMD: Drugs like Exondys 51 and Vyondys 53 from Sarepta Therapeutics, and Roche's Ryonspurt (Golodirsen), facilitate exon skipping to restore functional dystrophin protein synthesis. ·Spinal Muscular Atrophy (SMA): Spinraza (Nusinersen) from Biogen modifies SMN2 gene splicing to increase SMN protein levels. 2.Neurological Diseases: ·Familial Amyloid Polyneuropathy (FAP): Drugs like AstraZeneca’s Onpattro (Patisiran) and Takhzyro (Lanadelumab), the former using RNAi to reduce TTR protein levels, while the latter, a monoclonal antibody, prevents hereditary angioedema attacks. ·Amyotrophic Lateral Sclerosis (ALS): Tofersen from Biogen targets mutant SOD1 protein reduction for treating SOD1 gene mutation-associated ALS. 3.Metabolic Disorders: ·Transthyretin Amyloidosis (ATTR): Tegsedi (Inotersen) by Akcea Therapeutics and Ionis Pharmaceuticals, and Vyndaqel (Tafamidis) by Pfizer, reduce circulating TTR levels or stabilize the TTR tetramer to prevent amyloid fiber formation. ·Familial Hypercholesterolemia (FH): Waylivra (Volanesorsen) from Akcea Therapeutics and Ionis Pharmaceuticals lowers lipoprotein(a) levels for treating homozygous familial hypercholesterolemia (HoFH). 4.Viral Infections: ·Chronic Hepatitis B (CHB): Viread (Tenofovir Disoproxil Fumarate) and Hepcludex (Bulevirtide) from Gilead Sciences, with the former suppressing viral replication and the latter as the first approved ASO for chronic hepatitis B treatment. ·Cytomegalovirus Infection (CMV): Vitravene (Fomivirsen) from Isis Pharmaceuticals, treats CMV retinitis in immunocompromised individuals. 5.Cancer: ·Hematologic Malignancies: Revlimid (Lenalidomide) from Celgene and Erwinaze (Erwinia L-asparaginase) from Jazz Pharmaceuticals, with the former treating multiple myeloma and the latter acute lymphoblastic leukemia (ALL). 6.Cardiovascular Diseases: ·Heart Failure (HF): Cardior Pharmaceuticals is developing RNA-based therapies to restore myocardial function by inhibiting non-coding RNAs (ncRNAs). 7.Other Rare Diseases: ·Homozygous Familial Hypercholesterolemia (HoFH): Waylivra (Volanesorsen) from Akcea Therapeutics and Ionis Pharmaceuticals lowers lipoprotein(a) levels to treat HoFH. Regional Analysis of ASO DevelopmentASOs are experiencing robust growth globally, with North America and Europe leading the way due to their advanced technologies and regulatory frameworks. Meanwhile, the Asian market, especially China, is rapidly emerging as a significant driver of global ASO drug development, fueled by its vast demand potential and increasing innovation capacity. Global Distribution of ASO Research and Development RegionsIn recent years, the ASO industry has been undergoing a global transformation with notable growth momentum, particularly in the North American market. For a time, market control was firmly held by the two major players, Sarepta and Ionis. However, 2023 marked a turning point. A wave of new oligonucleotide drugs gained approval, reshaping the competitive landscape. In May 2023, Tofersen, an ASOs co-developed by Biogen and Ionis, received regulatory approval. This was followed by the December approval of Eplontersen, an ASO therapy introduced by AstraZeneca in collaboration with Ionis. Concurrently, Novo Nordisk's RNAi therapy Nedosiran was successfully launched in September, and Astellas's nucleic acid aptamer drug Izervay for geographic atrophy received approval in August. This shift in approvals has gradually disrupted the Sarepta-Ionis market duopoly. Key Players in the ASO Development MarketCompetitive Landscape of ASOs in Patsnap Synapse1.Ionis Pharmaceuticals Ionis Pharmaceuticals is a pioneer in the field of ASO therapies and remains at the forefront of ASO development. Since its founding in 1989, Ionis has led the ASO sector with a core platform that includes ligand-conjugated antisense technology (LICA), allowing targeted delivery of drugs to specific cells and tissues by conjugating ligands with specific cell surface receptors. As of 2023, Ionis has developed seven ASO products, collaborating with various pharmaceutical companies for late-stage drug development. 2.Sarepta Therapeutics A leader in the DMD space, Sarepta Therapeutics actively participates in ASO discovery and development, focusing on muscle-related diseases. The company has achieved FDA approval for four DMD drugs, including Eteplirsen, Golodirsen, Casimersen, and Elevidys. The first three are ASOs, while Elevidys is a gene therapy. Sarepta’s core platform utilizes phosphorodiamidate morpholino oligomer (PMO) technology to enable exon skipping, allowing pre-mRNA to bypass mutated exons during translation to restore functional dystrophin protein, alleviating symptoms of DMD. 3.Biogen Biogen focuses on developing ASO therapies for neurological disorders. In collaboration with Ionis, Biogen developed Nusinersen (marketed as SPINRAZA), the world’s first ASO drug for treating spinal muscular atrophy (SMA). Since its launch in 2016, Nusinersen’s sales have approached $10 billion, demonstrating ASO’s vast market potential. Biogen and Ionis’s joint development of Qalsody (tofersen), approved by the FDA in April 2023, treats amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations, marking the fourth new drug approved for ALS globally. Recent Innovations in ASO DevelopmentThe ASO field has seen significant advancements recently, such as the approval of Tofersen by Biogen and Ionis for specific types of ALS and Eplontersen by AstraZeneca and Ionis for treating transthyretin amyloidosis (ATTR). These developments not only expand therapeutic options but also offer new hope for patients with rare and severe diseases. Moreover, companies like Ausper Biopharma and SicaGene are advancing their own ASO pipelines, further enriching the field and highlighting ASO technology's potential in precision medicine. ConclusionASOs have shown tremendous potential as an emerging treatment modality within precision medicine. By targeting disease-causing mRNA, ASOs can effectively inhibit harmful protein synthesis or correct faulty splicing, providing novel therapeutic avenues for genetic disorders, neurodegenerative diseases, and certain cancer types. In recent years, successful market entries of drugs like Tofersen and Eplontersen have not only demonstrated ASO therapies' efficacy and safety in clinical applications but also signal the arrival of more innovative drugs that will benefit a broader patient population. These advancements signify the maturation of ASO technology in biomedical research, injecting fresh momentum into the healthcare industry and ushering in a new era of gene-regulation-centered therapies. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Reference 1. O'Leary, K., Guiding the development of individualized ASO therapies. Nat Med, 2023.2. Schuele, R., et al., Advancing ASO therapies from development to implementation. Nat Med, 2024. 30(10): p. 2725-2726.3. Crooke, S.T., et al., Antisense technology: an overview and prospectus. Nat Rev Drug Discov, 2021. 20(6): p. 427-453.