Q1 2026 Sarepta Therapeutics Inc Earnings Call

May 6, 2026

Operator 2: Good afternoon, welcome to Sarepta's Q1 2026 Earnings Results Call. As a reminder, today's program is being recorded. I would now like to turn the call over to Tam Thornton, Sarepta's Director of Investor Relations. Please go ahead.

Operator: Good afternoon, welcome to Sarepta's Q1 2026 Earnings Results Call. As a reminder, today's program is being recorded. I would now like to turn the call over to Tam Thornton, Sarepta's Director of Investor Relations. Please go ahead.

Speaker #1: Please go ahead.

Speaker #2: Thank you, Antoine, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the first quarter of 2026.

Tamara Thornton: Thank you, Antoine, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for Q1 2026. The press release, along with our presentation slides and supplementary information, will be available on the investor section of our company website. We plan to file our Form 10-Q for the quarter today with the SEC. Joining me on the call today are Doug Ingram, our CEO, Dr. Louise Rodino-Klapac, President of Research and Development and Technical Operations, Dallan Murray, our Chief Commercial Officer, and Ryan Wong, our Chief Financial Officer. Additionally, joining us in the Q&A portion of the call are Ian Estepan, President and Chief Operations Officer, and Dr. James Richardson, our Chief Medical Officer. Before we begin the formal remarks, I would like to note that during this call, we will be making a number of forward-looking statements.

Tam Thornton: Thank you, Antoine, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for Q1 2026. The press release, along with our presentation slides and supplementary information, will be available on the investor section of our company website. We plan to file our Form 10-Q for the quarter today with the SEC.

Speaker #2: The press release, along with our presentation slides and supplementary information, will be available on the Investor section of our company website. We plan to file our Form 10Q for the quarter today, with the SEC.

Speaker #2: Joining me on the call today are Doug Ingram, our CEO; Dr. Louise Rodino Klapack, President of Research and Development and Technical Operations; Patrick Moss, our Chief Commercial Officer; and Ryan Wong, our Chief Financial Officer.

Tam Thornton: Joining me on the call today are Doug Ingram, our CEO, Dr. Louise Rodino-Klapac, President of Research and Development and Technical Operations, Dallan Murray, our Chief Commercial Officer, and Ryan Wong, our Chief Financial Officer. Additionally, joining us in the Q&A portion of the call are Ian Estepan, President and Chief Operations Officer, and Dr. James Richardson, our Chief Medical Officer.

Speaker #2: Additionally, joining us in the Q&A portion of the call are Ian Estepan, President and Chief Operations Officer, and Dr. James Richardson, our Chief Medical Officer.

Speaker #2: Before we begin the formal remarks, I would like to note that during this call, we will be making a number of forward-looking statements. Please refer to Slide 2 of our presentation to view the formal text of these Safe Harbor statements.

Tam Thornton: Before we begin the formal remarks, I would like to note that during this call, we will be making a number of forward-looking statements. Please refer to Slide 2 of our presentation to view the formal text of these safe harbor statements. These statements involve varying risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and such risks can adversely affect our business, our results of operations, and the trading price with Sarepta's common stock.

Tamara Thornton: Please refer to slide two of our presentation to view the formal text of these safe harbor statements. These statements involve varying risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and such risks can adversely affect our business, our results of operations, and the trading price with Sarepta's common stock. We strongly encourage all listeners to review the company's most recent SEC filings for a detailed description of these applicable risks. Sarepta explicitly states that it does not undertake any obligation to publicly update or revise its forward-looking statements or financial projections based on subsequent events. Furthermore, please note that we will discuss non-GAAP financial measures during today's webcast. Complete descriptions and reconciliations of our GAAP to non-GAAP financial measures are included in today's press release and the accompanying slide presentation available to investors on our website.

Speaker #2: These statements involve varying risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements in such risks can adversely affect our business, our results of operations, and the trading price of Sarepta's common stock.

Speaker #2: We strongly encourage all listeners to review the company's most recent SEC filings for a detailed description of these applicable risks. Sarepta explicitly states that it does not undertake any obligation to publicly update or revise its forward-looking statements or financial projections based on subsequent events.

Tam Thornton: We strongly encourage all listeners to review the company's most recent SEC filings for a detailed description of these applicable risks. Sarepta explicitly states that it does not undertake any obligation to publicly update or revise its forward-looking statements or financial projections based on subsequent events. Furthermore, please note that we will discuss non-GAAP financial measures during today's webcast.

Speaker #2: Furthermore, please note that we will discuss non-GAAP financial measures during today's webcast. Complete descriptions and reconciliations of our GAAP to non-GAAP financial measures are included in today's press release, in the accompanying slide presentation available to investors on our website.

Tam Thornton: Complete descriptions and reconciliations of our GAAP to non-GAAP financial measures are included in today's press release and the accompanying slide presentation available to investors on our website. With that, I will now turn the call over to our CEO, Doug Ingram. Doug?

Speaker #2: With that, I will now turn the call over to our CEO, Doug Ingram. Doug?

Tamara Thornton: With that, I will now turn the call over to our CEO, Doug Ingram. Doug?

Speaker #3: Thank you, Tam. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics' first quarter 2026 financial results conference call. We entered 2026 with a clear set of priorities: stabilize the business, restore confidence in growth, maintain financial strength, and continue advancing a pipeline with the potential to define Sarepta's next era.

Doug Ingram: Thank you, Tam Thornton. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics' Q1 2026 financial results conference call. We entered 2026 with a clear set of priorities: stabilize the business, restore confidence and growth, maintain financial strength, and continue advancing a pipeline with the potential to define Sarepta's next era. In the Q1, we made meaningful progress against each of these priorities. First, our marketed product performance has stabilized following the disruption and uncertainty of 2025. With expanded field reach, increased physician engagement, and a growing body of compelling evidence supporting the disease-modifying impact of ELEVIDYS, we believe that therapy is positioned to return to growth. Second, Sarepta remains in a strong financial position.

Doug Ingram: Thank you, Tam. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics' Q1 2026 financial results conference call. We entered 2026 with a clear set of priorities: stabilize the business, restore confidence and growth, maintain financial strength, and continue advancing a pipeline with the potential to define Sarepta's next era. In the Q1, we made meaningful progress against each of these priorities.

Speaker #3: In the first quarter, we made meaningful progress against each of these priorities. First, our marketed product performance has stabilized following the disruption and uncertainty of 2025, with expanded field reach, increased position engagement, and a growing body of compelling evidence supporting the disease-modifying impact of a levitis we believe that therapy is positioned to return to growth.

Doug Ingram: First, our marketed product performance has stabilized following the disruption and uncertainty of 2025. With expanded field reach, increased physician engagement, and a growing body of compelling evidence supporting the disease-modifying impact of ELEVIDYS, we believe that therapy is positioned to return to growth. Second, Sarepta remains in a strong financial position.

Speaker #3: Second, Sarepta remains in a strong financial position. We ended the quarter with approximately $748 million in cash and investments, delivered positive GAAP and non-GAAP earnings, generated positive cash flow excluding arrowhead-related payments, and remain on track for positive cash flow even under our base case assumptions.

Doug Ingram: We ended the quarter with approximately $748 million in cash and investments, delivered positive GAAP and non-GAAP earnings, generated positive cash flow, excluding Arrowhead-related payments, and remain on track for positive cash flow even under our base case assumptions. The financial strength matters. It allows us to fund our pipeline without relying on the equity markets. We are fully funding our programs in DM1, FSHD, Huntington's disease, the spinocerebellar ataxias, and our preclinical and research portfolio. Third, we are making progress in what we believe is a potentially best-in-class portfolio of siRNA therapies. As Dr. Louise Rodino-Klapac will discuss shortly, we are especially encouraged by the early data from SRP-1001 in FSHD and SRP-1003 in DM1, and we look forward to additional readouts in H2 of this year.

Speaker #3: The financial strength matters. It allows us to fund our pipeline without relying on the equity markets. We are fully funding our programs in DM1, FSHD, Huntington's disease, the Spinocerebellar ataxias, and our preclinical and research portfolio.

Doug Ingram: We are fully funding our programs in DM1, FSHD, Huntington's disease, the spinocerebellar ataxias, and our preclinical and research portfolio. Third, we are making progress in what we believe is a potentially best-in-class portfolio of siRNA therapies. As Dr. Louise Rodino-Klapac will discuss shortly, we are especially encouraged by the early data from SRP-1001 in FSHD and SRP-1003 in DM1, and we look forward to additional readouts in H2 of this year.

Speaker #3: And third, we are making progress in what we believe is a potentially best-in-class portfolio of siRNA therapies. As Dr. Louise Rodino Klapack will discuss shortly, we are especially encouraged by the early data from SRP1001 and FSHD and SRP1003 in DM1, and we look forward to additional readouts in the second half of this year.

Doug Ingram: Turning to Q1 performance, total net product revenue was $331 million. That included $229 million from our PMO therapies, EXONDYS, VYONDYS, AMONDYS, and $102 million from ELEVIDYS. Starting with the PMO franchise, we were pleased that the FDA agreed that we can submit our clinical data and real-world evidence for VYONDYS and AMONDYS. We have submitted sNDAs seeking to transition those therapies from accelerated approval to traditional approval. That is an important step for patients, physicians, and of course, the durability of this franchise. Turning to ELEVIDYS, Patrick will provide more detail on the commercial initiatives underway and the early signs of progress we are seeing. I want to underscore the central point. Our confidence in ELEVIDYS is grounded in evidence, not in mere aspiration.

Speaker #3: Turning to first quarter performance, total net product revenue was $331 million. That included $229 million from our PMO therapies, Exondys, Vyondys, Amondys, and $102 million from Elevidys.

Speaker #3: Starting with the PMO franchise, we were pleased that the FDA agreed that we can submit our clinical data and real-world evidence for Viondis and SMDAs seeking to transition those therapies from accelerated approval to traditional approval.

Speaker #3: That is an important step for patients. Physicians and, of course, the durability of this franchise. Turning to a levitis, Patrick will provide more detail on the commercial initiatives underway and the early signs of progress we are seeing.

Doug Ingram: That is an important step for patients, physicians, and of course, the durability of this franchise. Turning to ELEVIDYS, Patrick will provide more detail on the commercial initiatives underway and the early signs of progress we are seeing. I want to underscore the central point. Our confidence in ELEVIDYS is grounded in evidence, not in mere aspiration.

Speaker #3: But I want to underscore the central point: our confidence in a levitis is not is grounded in evidence, not in mere aspiration. To date, more than 1,300 patients have been treated with a levitis across clinical trials and commercially used around the world.

Doug Ingram: To date, more than 1,300 patients have been treated with ELEVIDYS across clinical trials and commercial use around the world. The totality of the evidence continues to strengthen. The data show that ELEVIDYS is protecting muscle and changing the trajectory of Duchenne. It is giving boys and young men an opportunity that, until now, this disease has never afforded them. We saw this in EMBARK, the only robust double-blinded placebo-controlled trial demonstrating the benefit of a gene therapy in Duchenne. We saw meaningful benefits at year 1. We saw those benefits grow at year 2. Yet again, at year 3, boys continued to diverge on every measure from the expected course of untreated disease. That matters because Duchenne does not wait. Muscle damage is progressive, irreversible, and cumulative. Every month of delay risks further loss. The evidence increasingly supports a simple but urgent message.

Speaker #3: The totality of the evidence continues to strengthen the data show that a levitis is protecting muscle and changing the trajectory of Duchenne. It is giving boys and young men an opportunity that, until now, this disease has never afforded them.

Speaker #3: We saw this in EMBARK—the only robust, double-blinded, placebo-controlled trial demonstrating the benefit of a gene therapy in Duchenne. We saw meaningful benefits at year one.

Doug Ingram: We saw meaningful benefits at year 1. We saw those benefits grow at year 2. Yet again, at year 3, boys continued to diverge on every measure from the expected course of untreated disease. That matters because Duchenne does not wait. Muscle damage is progressive, irreversible, and cumulative. Every month of delay risks further loss. The evidence increasingly supports a simple but urgent message.

Speaker #3: We saw those benefits grow at year two. And yet again, at year three, boys continue to diverge on every measure from the expected course.

Speaker #3: Of untreated disease. That matters because Duchenne does not wait. Muscle damage is progressive, irreversible, and cumulative. Every month of delay risks further loss. The evidence increasingly supports a simple but urgent message: physicians and families should evaluate Elevidys now before additional irreversible damage occurs.

Doug Ingram: Physicians and families should evaluate ELEVIDYS now before additional irreversible damage occurs. We have also seen supportive muscle MRI evidence showing that ELEVIDYS dystrophin helps protect muscle from damage, resulting in less muscle loss and less replacement by fat and fibrotic tissue. This is exactly the kind of biological evidence one would hope to see from a therapy intended to alter the course of Duchenne. We are confident that as physicians and families better understand the disease-modifying potential of ELEVIDYS and the urgency of intervening before further decline, more patients will move towards treatment. That said, we are still in the middle of our commercial and educational initiatives, and the path from consideration to infusion takes time. For that reason, we are reiterating our full-year guidance of $1.2 to 1.4 billion and would counsel prudence in raising estimates prematurely.

Speaker #3: We have also seen supportive muscle MRI evidence showing that a levitis dystrophin helps protect muscle from damage, resulting in less muscle loss and less replacement by fat and fibrotic tissue.

Speaker #3: This is exactly the kind of biological evidence one would hope to see from a therapy intended to alter the course of Duchenne. We are confident that as physicians and families better understand the disease-modifying potential of a levitis, and the urgency of intervening before further decline, more patients will move towards treatment.

Doug Ingram: We are confident that as physicians and families better understand the disease-modifying potential of ELEVIDYS and the urgency of intervening before further decline, more patients will move towards treatment. That said, we are still in the middle of our commercial and educational initiatives, and the path from consideration to infusion takes time. For that reason, we are reiterating our full-year guidance of $1.2 to 1.4 billion and would counsel prudence in raising estimates prematurely.

Speaker #3: That said, we are still in the middle of our commercial and educational initiatives, and the path from consideration to infusion takes time. For that reason, we are reiterating our full-year guidance of 1.2 to 1.4 billion dollars and would counsel prudence in raising estimates prematurely.

Speaker #3: Now, staying with a levitis, we are also advancing our endeavor cohort 8 study, which uses serolimus as a pretreatment. More than 25% of sites are already using serolimus on their own initiative.

Doug Ingram: Now staying with ELEVIDYS, we are also advancing our ENDEAVOR cohort A study, which uses sirolimus as a pretreatment. More than 25% of sites are already using sirolimus on their own initiative. In our interim analysis from the long-term real-world evidence study that we have ongoing, patients pretreated with sirolimus have shown no evidence of elevated liver enzyme to date. That gives us further confidence in cohort A and in the potential with the success of that study and the concurrence of the FDA to resume offering ELEVIDYS to non-ambulatory patients. Turning to the pipeline, our focus is execution. We are rapidly advancing our siRNA portfolio, including our DM1 and FSHD programs. The first data readout earlier this year showed encouraging signals that these may be differentiated, potentially best in class approaches for 2 very challenging diseases. We look forward to providing additional data later this year.

Speaker #3: In our interim analysis from the long-term real-world evidence study that we have ongoing, patients pretreated with serolimus have shown no evidence of elevated liver enzymes to date.

Speaker #3: That gives us further confidence in cohort 8 and in the potential, with the success of that study and the concurrence of the FDA, to resume offering a levitis to non-ambulatory patients.

Doug Ingram: That gives us further confidence in cohort A and in the potential with the success of that study and the concurrence of the FDA to resume offering ELEVIDYS to non-ambulatory patients. Turning to the pipeline, our focus is execution. We are rapidly advancing our siRNA portfolio, including our DM1 and FSHD programs. The first data readout earlier this year showed encouraging signals that these may be differentiated, potentially best in class approaches for 2 very challenging diseases. We look forward to providing additional data later this year.

Speaker #3: Turning to the pipeline, our focus is execution. We are rapidly advancing our siRNA portfolio including our DM1 and FSHD programs. The first data readout earlier this year showed encouraging signals that these may be differentiated, potentially best-in-class approaches for two very challenging diseases.

Speaker #3: We look forward to providing additional data later this year. We have initiated, and are on track to dose our first patients, in our Huntington's disease program, and we are progressing clinical trials in SCOT2 and idiopathic pulmonary fibrosis.

Doug Ingram: We have initiated and are on track to dose our first patients in our Huntington's disease program, we are progressing clinical trials in SCA2 and idiopathic pulmonary fibrosis. To summarize, the business has stabilized. ELEVIDYS is supported by an increasingly compelling body of evidence. Our financial position is strong, our high-value siRNA pipeline is advancing across multiple programs. We believe Sarepta is well-positioned in 2026 and beyond. With that, let me turn the call over to Louise, who will provide an update on our siRNA portfolio and broader development progress. Louise?

Speaker #3: So, to summarize, the business is stabilized. A levitis is supported by an increasingly compelling body of evidence. Our financial position is strong and our high-value siRNA pipeline is advancing across multiple programs.

Doug Ingram: Our financial position is strong, our high-value siRNA pipeline is advancing across multiple programs. We believe Sarepta is well-positioned in 2026 and beyond. With that, let me turn the call over to Louise, who will provide an update on our siRNA portfolio and broader development progress. Louise?

Speaker #3: We believe Sarepta is well-positioned in 2026 and beyond. And with that, let me turn the call over to Louise, who will provide an update on our siRNA portfolio and broader development progress.

Speaker #3: Louise?

Speaker #4: Thanks, Doug. And good afternoon, everyone. Our diverse and advancing rare disease portfolio has always been driven by a core fundamental truth: pursue the very best science and then follow where it leads.

Louise Rodino-Klapac: Thanks, Doug, good afternoon, everyone. Our diverse and advancing rare disease portfolio has always been driven by a core fundamental truth: pursue the very best science and then follow where it leads. In March of this year, we announced positive preliminary data from our lead programs to treat FSHD and DM1, which are based on the potential of our alpha-v beta-6 integrin-targeting ligand to produce best-in-class therapies in these unmet disease areas. Importantly, our integrin receptors are highly expressed in muscle in addition to other tissues. They're also actively trafficked between the cell surface and endosomal compartments through relatively well-understood pathways. Non-clinical data show that targeting these integrin receptors via small peptides leads to enhanced skeletal muscle uptake compared to using a much larger TFR1 antibody.

Speaker #4: In March of this year, we announced positive preliminary data from our lead programs to treat FSHD and DM1. Which are based on the potential of our alpha B, beta 6 integrin targeting ligand to produce best-in-class therapies in these unmet disease areas.

Louise Rodino-Klapac: Importantly, our integrin receptors are highly expressed in muscle in addition to other tissues. They're also actively trafficked between the cell surface and endosomal compartments through relatively well-understood pathways. Non-clinical data show that targeting these integrin receptors via small peptides leads to enhanced skeletal muscle uptake compared to using a much larger TFR1 antibody.

Speaker #4: Importantly, our integrin receptors are highly expressed in muscle in addition to other tissues. They are also actively trafficked between the cell surface and the endosomal compartments through relatively well-understood pathways.

Speaker #4: Non-clinical data show that targeting these integrin receptors via small peptides leads to enhanced skeletal muscle uptake compared to using a much larger TFR1 antibody.

Speaker #4: It's also important to note that based on data to date, our alpha B, beta 6 integrin targeting ligand provides superior muscle concentration compared to transferrin-based approaches without dose-limiting toxicity.

Louise Rodino-Klapac: It is also important to note that based on data to date, our alpha-v beta-6 integrin-targeting ligand provides superior muscle concentration compared to transferrin-based approaches without dose-limiting toxicity. I will now summarize the early data from our FSHD and DM1 programs. SRP-1001 is an siRNA-based treatment designed to reduce or knock down the production of DUX4 protein in skeletal muscle in patients living with FSHD1. Study 1001-101 is our combined Phase 1/2 single ascending dose and multiple ascending dose randomized placebo-controlled trial in participants with FSHD1 aged 16 through 70. As previously shared, we believe our preliminary data from the Phase 1/2 SAD study supports the potentially differentiated attributes of SRP-1001, including a dose-dependent increase in plasma exposure up to the highest dose cohort.

Speaker #4: I will now summarize the early data from our FSHD and DM1 programs. SRP1001 is an siRNA-based treatment designed to reduce or knock down the production of DUX4 protein in skeletal muscle in patients living with FSHD1.

Speaker #4: Study 1001-101 is our combined phase 1/2 single ascending dose and multiple ascending dose randomized placebo-controlled trial in participants with FSHD1 aged 16 through 70.

Louise Rodino-Klapac: Study 1001-101 is our combined Phase 1/2 single ascending dose and multiple ascending dose randomized placebo-controlled trial in participants with FSHD1 aged 16 through 70. As previously shared, we believe our preliminary data from the Phase 1/2 SAD study supports the potentially differentiated attributes of SRP-1001, including a dose-dependent increase in plasma exposure up to the highest dose cohort.

Speaker #4: As previously shared, we believe our preliminary data from the phase 1/2 SAD study supports the potentially differentiated attributes of SRP1001, including a dose-dependent increase in plasma exposure up to the highest dose cohort, also superior delivery to muscle enabled by a differentiated approach with the alpha B, beta 6 integrin including no saturation of drug uptake, significant suppression of DUX4-related genes, and a rapid and robust reduction in CK to support functional impact.

Louise Rodino-Klapac: Also, superior delivery to muscle enabled by a differentiated approach with the alpha-v beta-6 integrin, including no saturation of drug uptake, significant suppression of DUX4-related genes, and a rapid and robust reduction in CK to support functional impact. Finally, a favorable safety and tolerability profile with repeated dosing, including no indication of anemia, which physicians have indicated represent an important therapeutic advantage. We look forward to sharing results from the MAD portion of this study later in the year, which we expect will include at least 6 months of follow-up for our 6 and 12 mg/kg MAD cohorts, which is equivalent to 4 and 8 mg/kg siRNA dosing. This is with respect to safety, PK/PD data, including circulating biomarkers and DUX4-related regulated genes as well as early functional data.

Speaker #4: Finally, a favorable safety and tolerability profile with repeated dosing including no indication of anemia, which physicians have indicated represent an important therapeutic advantage. We look forward to sharing results from the MAD portion of this study later in the year.

Louise Rodino-Klapac: We look forward to sharing results from the MAD portion of this study later in the year, which we expect will include at least 6 months of follow-up for our 6 and 12 mg/kg MAD cohorts, which is equivalent to 4 and 8 mg/kg siRNA dosing. This is with respect to safety, PK/PD data, including circulating biomarkers and DUX4-related regulated genes as well as early functional data.

Speaker #4: Which we expect will include at least six months of follow-up for our sixth and 12-megapercig MAD cohorts, which is equivalent to four and eight megapercig siRNA dosing.

Speaker #4: This is with respect to safety, PKPD data, including circulating biomarkers, and DUX4-related regulated genes, as well as early functional data. We also plan to discuss our post-phase 2 with FDA to define an optimal registrational pathway.

Louise Rodino-Klapac: We also plan to discuss our post Phase 2 with FDA to define an optimal registrational pathway. Moving to DM1. SRP-1003 is an siRNA-based treatment for DM1 designed to target or knock down or silence the DMPK mRNA in target cells. Study SRP-1003-101 is a first-in-human Phase 1/2 SAD/MAD randomized placebo-controlled clinical trial being conducted in individuals with DM1 aged 18 to 65. The early data we generated for DM1 is important for 2 reasons. First, our preclinical models are predictive of what we would see in the clinic with respect to muscle concentration. Of note, an increase in plasma exposure has translated into enhanced dose-dependent delivery to the muscle, resulting in robust target engagement. Second, the demonstrated DMPK knockdown we observed was impressive and directionally strong.

Speaker #4: Now moving to DM1. SRP1003 is an siRNA-based treatment for DM1 designed to target or knock down or silence the DMPK mRNA in target cells.

Speaker #4: Study SRP1003-101 is a first-in-human phase 1/2 SAD/MAD randomized placebo-controlled clinical trial being conducted in individuals with DM1 aged 18 to 65. The early data we generated for DM1 is important for two reasons.

Louise Rodino-Klapac: The early data we generated for DM1 is important for 2 reasons. First, our preclinical models are predictive of what we would see in the clinic with respect to muscle concentration. Of note, an increase in plasma exposure has translated into enhanced dose-dependent delivery to the muscle, resulting in robust target engagement. Second, the demonstrated DMPK knockdown we observed was impressive and directionally strong.

Speaker #4: First, our preclinical models are predictive of what we would see in the clinic with respect to muscle concentration. Of note, an increase in plasma exposure has translated into enhanced dose-dependent delivery to the muscle, resulting in robust target engagement.

Speaker #4: Second, the demonstrated DMPK knockdown we observed was impressive and directionally strong. As you're aware, DM1 is driven by an expanded CUG trinucleotide repeat in DMPK transcripts, causing mutant DMPK mRNA to accumulate in the nucleus and disrupt RNA splicing.

Louise Rodino-Klapac: As you're aware, DM1 is driven by an expanded CUG trinucleotide repeat in DMPK transcripts, causing mutant DMPK mRNA to accumulate in the nucleus and disrupt RNA splicing. As a result, for any therapy to be therapeutically effective, it must effectively target and knock down or silence DMPK in the target cell. SRP-1003 is being developed to achieve exactly that. We look forward to sharing these results from the additional SAD and MAD cohorts in this study later in the year, which we expect will include multiple doses measuring mechanistic and functional endpoints with at least 6 months of follow-up for our 6 mg per kg cohort, which is equivalent to 4 mg per kg siRNA. Specifically, we expect to share safety, serum and muscle PK, DMPK knockdown, CASS2 splicing indices, and vHOT analyses.

Speaker #4: As a result, for any therapy to be therapeutically effective, it must effectively target and knock down or silence DMPK in the target cell. SRP1003 is being developed to achieve exactly that.

Speaker #4: We look forward to sharing these results from the additional SAD and MAD cohorts in this study later in the year. Which we expect will include multiple doses measuring mechanistic and functional endpoints with at least six months of follow-up for our six megapercig cohort, which is equivalent to four megapercig siRNA.

Louise Rodino-Klapac: We look forward to sharing these results from the additional SAD and MAD cohorts in this study later in the year, which we expect will include multiple doses measuring mechanistic and functional endpoints with at least 6 months of follow-up for our 6 mg per kg cohort, which is equivalent to 4 mg per kg siRNA. Specifically, we expect to share safety, serum and muscle PK, DMPK knockdown, CASS2 splicing indices, and vHOT analyses.

Speaker #4: Specifically, we expect to share safety, serum and muscle PK, DMPK knockdown, CASI22 splicing indices, and VHOT analyses. We will plan our IND submission for US studies shortly after completing our MAD studies.

Louise Rodino-Klapac: We will plan our IND submission for US study shortly after completing our MAD study. We believe these trials, if successful, will support and provide a clear path to support registration. In summary, enhanced muscle delivery, robust target engagement, and maximal knockdown are well-recognized as the gold standard for FSHD and DM1. We're excited by the potential of our therapies to reach this standard. In terms of our other siRNA pipeline program, we are on track for first patient in for Huntington. Our SCA2 trial is fully enrolled. We look forward to sharing data as it becomes available. Turning to ELEVIDYS. We are pleased to announce in March that screening and enrollment are underway in cohort 8 of ENDEAVOR for study SRP-9001-103.

Speaker #4: We believe these trials, if successful, will support and provide a clear path to support registration. In summary, enhanced muscle delivery, robust target engagement, and maximal knockdown are well-recognized as the gold standard for FSHD and DM1, and we're excited by the potential of our therapies to reach this standard.

Louise Rodino-Klapac: We're excited by the potential of our therapies to reach this standard. In terms of our other siRNA pipeline program, we are on track for first patient in for Huntington. Our SCA2 trial is fully enrolled. We look forward to sharing data as it becomes available. Turning to ELEVIDYS. We are pleased to announce in March that screening and enrollment are underway in cohort 8 of ENDEAVOR for study SRP-9001-103.

Speaker #4: In terms of our other siRNA pipeline programs, we are on track for first patient in for Huntington's and our SCAW2 trial is fully enrolled.

Speaker #4: We look forward to sharing data as it becomes available. Now turning to Aleptus. We are pleased to announce in March that screening and enrollment are underway, and cohort 8 of Endeavor, where study SRP9001-103.

Speaker #4: To remind you, the purpose of cohort 8 is to assess prophylactic seromatous treatment as part of an enhanced safety protocol during treatment with Aleptus in non-ambulant individuals with Duchenne.

Louise Rodino-Klapac: To remind you, the purpose of cohort 8 is to assess prophylactic sirolimus treatment as part of an enhanced safety protocol during treatment with ELEVIDYS in non-ambulant individuals with Duchenne. Data from cohort 8 will be used to determine whether administering sirolimus prior to and after ELEVIDYS infusion can help reduce acute liver injury, a known risk associated with AAV gene therapy. The cohort is enrolling approximately 25 participants in the United States who are non-ambulatory, and dosing is currently underway. As a reminder, the immunosuppression regimen will include 14 days of peri-infusion sirolimus dosing prior to ELEVIDYS administration and will continue for 12 weeks after ELEVIDYS administration. Primary endpoints include incidence of ALI and ELEVIDYS dystrophin expression at 12 weeks. The approach is based on preclinical data and shaped by real-world clinical experience, including guidance from independent specialists in Duchenne and liver health.

Speaker #4: Data from cohort 8 will be used to determine whether administering seromatous prior to and after Aleptus infusion can help reduce acute liver injury. Known risk associated with AAV gene therapy.

Speaker #4: The cohort is enrolling approximately 25 participants in the United States who are non-ambulatory, and dosing is currently underway. As a reminder, the immunosuppression regimen will include 14 days of peri-infusion seromatous dosing prior to Aleptus administration, and will continue for 12 weeks after Aleptus administration.

Louise Rodino-Klapac: As a reminder, the immunosuppression regimen will include 14 days of peri-infusion sirolimus dosing prior to ELEVIDYS administration and will continue for 12 weeks after ELEVIDYS administration. Primary endpoints include incidence of ALI and ELEVIDYS dystrophin expression at 12 weeks. The approach is based on preclinical data and shaped by real-world clinical experience, including guidance from independent specialists in Duchenne and liver health.

Speaker #4: Primary endpoints include incidents of ALI and Aleptus dystrophin expression at 12 weeks. The approach is based on preclinical data and shaped by real-world clinical experience, including guidance from independent specialists in Duchenne and liver health.

Louise Rodino-Klapac: As Doug mentioned, in addition to EMBARK 3-year functional data, we also reported at MDA caregiver-reported impressions from EMBARK through 2 years of follow-up, offering complementary perspectives on treatment impact beyond clinician-reported and performance-based outcomes. We are pleased that our body of evidence for ELEVIDYS continues to grow with an unprecedented number of patients dosed as well as the years of follow-up. We remain steadfast in our commitment to serve the Duchenne community by generating clinical and real-world data to support understanding of long-term outcomes. This also includes our phase 4 observational study, ENDURE. Now moving to AMONDYS 45 and VYONDYS 53. In March, we announced that we requested a meeting with FDA to discuss submitting supplemental new drug applications, or sNDAs, seeking conversion of the accelerated approval of AMONDYS 45 and VYONDYS 53 to traditional approvals.

Speaker #4: As Doug mentioned in addition to EMBARC three-year functional data, we also reported at MDA caregiver-reported impressions from EMBARC through two years of follow-up. Offering complementary perspectives on treatment impact beyond clinician-reported and performance-based outcomes.

Speaker #4: We are pleased that our body of evidence for Aleptus continues to grow, with an unprecedented number of patients dosed as well as years of follow-up.

Speaker #4: We remain steadfast in our commitment to serve the Duchenne community by generating clinical and real-world data to support understanding of long-term outcomes. This also includes our Phase 4 observational study, ENDUR.

Louise Rodino-Klapac: We remain steadfast in our commitment to serve the Duchenne community by generating clinical and real-world data to support understanding of long-term outcomes. This also includes our phase 4 observational study, ENDURE. Now moving to AMONDYS 45 and VYONDYS 53. In March, we announced that we requested a meeting with FDA to discuss submitting supplemental new drug applications, or sNDAs, seeking conversion of the accelerated approval of AMONDYS 45 and VYONDYS 53 to traditional approvals.

Speaker #4: Now moving to Amandus 45 and Viandus 53. In March, we announced that we requested a meeting with FDA to discuss submitting supplemental new drug applications or SNDAs, seeking conversion of the accelerated approval of Amandus 45 and Viandus 53 to traditional approvals.

Speaker #4: This request was supported by data from the ESSENCE Confirmatory Study, as well as substantial published real-world evidence supporting treatment in the favorable safety profiles of both therapies.

Louise Rodino-Klapac: This request was supported by data from the ESSENCE confirmatory study, substantial published real-world evidence supporting treatment, and the favorable safety profiles of both therapies. Sarepta received feedback from the agency confirming that we were clear to submit our data from ESSENCE and real-world evidence as part of the sNDAs. We are pleased to share that we successfully submitted our sNDAs at the end of April. In summary, we have numerous value-building milestones upcoming across our Duchenne and siRNA portfolio. Thank you, and I'll now turn the call over to Patrick for an update on our commercial performance. Patrick?

Speaker #4: Throughout the received feedback from the agency, confirming that we were cleared to submit our data from ESSENCE and real-world evidence as part of the SNDAs.

Speaker #4: We are pleased to share that we successfully submitted our SNDAs at the end of April. In summary, we have numerous value-building milestones upcoming across our Duchenne and siRNA portfolio.

Louise Rodino-Klapac: We are pleased to share that we successfully submitted our sNDAs at the end of April. In summary, we have numerous value-building milestones upcoming across our Duchenne and siRNA portfolio. Thank you, and I'll now turn the call over to Patrick for an update on our commercial performance. Patrick?

Speaker #4: Thank you, and I'll now turn the call over to Patrick for an update on our commercial performance. Patrick?

Speaker #1: Thank you, Louise, and good afternoon. Today, I'll summarize our performance in the first quarter for our on-market therapies provide an update on execution of our 2026 initiatives, and close with how that translates into performance for second quarter and the balance of the year.

Dallan Murray: Thank you, Louise, and good afternoon. Today, I will summarize our performance in Q1 for our on-market therapies, provide an update on execution of our 2026 initiatives, and close with how that translates into performance for Q2 and the balance of the year. For Q1, total product revenue was $331 million, including net product revenue of $102 million for ELEVIDYS and $229 million for the PMOs. For ELEVIDYS, Q1 results reflected measured demand, which we believe was influenced by the ongoing information gap within the ambulatory population. This reflects the dynamics we outlined last quarter as we advance efforts to rebalance the discussion around safety and efficacy to support informed decision-making for ELEVIDYS treatment. Importantly, Q1 demand fundamentals have not deteriorated.

Patrick Moss: Thank you, Louise, and good afternoon. Today, I will summarize our performance in Q1 for our on-market therapies, provide an update on execution of our 2026 initiatives, and close with how that translates into performance for Q2 and the balance of the year. For Q1, total product revenue was $331 million, including net product revenue of $102 million for ELEVIDYS and $229 million for the PMOs.

Speaker #1: For the first quarter, total product revenue was $331,000,000, including net product revenue of $102,000,000 for Aleptus and $229,000,000 for the PMOs. For Aleptus, first quarter results reflected measured demand.

Patrick Moss: For ELEVIDYS, Q1 results reflected measured demand, which we believe was influenced by the ongoing information gap within the ambulatory population. This reflects the dynamics we outlined last quarter as we advance efforts to rebalance the discussion around safety and efficacy to support informed decision-making for ELEVIDYS treatment. Importantly, Q1 demand fundamentals have not deteriorated.

Speaker #1: Which we believe was influenced by the ongoing information gap within the ambulatory population. This reflects the dynamics we outlined last quarter as we advance efforts to rebalance the discussion around safety and efficacy to support informed decision-making for Aleptus treatment.

Speaker #1: Importantly, Q1 demand fundamentals have not deteriorated. Instead, we are addressing the information gap we know exists and are building momentum around a robust label and new data following the events of 2025.

Dallan Murray: Instead, we are addressing the information gap we know exists and are building momentum around a robust label and new data following the events of 2025. The PMO franchise continued to demonstrate durability with demand remaining stable and in line with expectations for mature therapies that are foundational for slowing the decline of Duchenne. We experienced seasonal dynamics in Q1, which contributed to the quarter-over-quarter decrease versus Q4. Our focus for 2026 and beyond remains squarely on ensuring that patients and physicians have a balanced, data-driven understanding of ELEVIDYS' benefit risk profile. The treatment journey for ELEVIDYS has multiple touch points, including patient identification, referral, evaluation, and payer review, in addition to the time and information a family needs when deciding to pursue treatment.

Patrick Moss: Instead, we are addressing the information gap we know exists and are building momentum around a robust label and new data following the events of 2025. The PMO franchise continued to demonstrate durability with demand remaining stable and in line with expectations for mature therapies that are foundational for slowing the decline of Duchenne.

Speaker #1: The PMO franchise continued to demonstrate durability with demand remaining stable and in line with expectations for mature therapies that are foundational for slowing the decline of Duchenne.

Speaker #1: We experienced seasonal dynamics in Q1, which contributed to the quarter-over-quarter decrease versus Q4. Our focus for 2026 and beyond remains squarely on ensuring that patients and physicians have a balanced data-driven understanding of Aleptus's benefit-risk profile.

Patrick Moss: We experienced seasonal dynamics in Q1, which contributed to the quarter-over-quarter decrease versus Q4. Our focus for 2026 and beyond remains squarely on ensuring that patients and physicians have a balanced, data-driven understanding of ELEVIDYS' benefit risk profile. The treatment journey for ELEVIDYS has multiple touch points, including patient identification, referral, evaluation, and payer review, in addition to the time and information a family needs when deciding to pursue treatment.

Speaker #1: The treatment journey for Aleptus has multiple touch points including patient referral, evaluation, and payer review, in addition to the time and information of family needs when deciding to pursue treatment.

Speaker #1: While our commercial model supports all touch points within this treatment journey, as discussed last quarter, we are actively implementing a number of initiatives to augment our execution, including expanding the number of field resources to support referring physicians.

Dallan Murray: While our commercial model supports all the touch points within this treatment journey, as discussed last quarter, we are actively implementing a number of initiatives to augment our execution, including expanding the number of field resources to support referring physicians, extending our reach within sites of care. In addition, the company is deploying new educational resources and tools to support patients and families. We have increased our footprint fielding a contract sales force to focus on physicians who may be in a position to refer patients to a site of care for gene therapy or prescribe one of our exon-skipping therapies. This team recently completed training and deployment in the field is underway. We expect the team to be fully operational as we enter the H2 of this year.

Patrick Moss: While our commercial model supports all the touch points within this treatment journey, as discussed last quarter, we are actively implementing a number of initiatives to augment our execution, including expanding the number of field resources to support referring physicians, extending our reach within sites of care. In addition, the company is deploying new educational resources and tools to support patients and families.

Speaker #1: Extending our reach within sites of care, in addition, the company is deploying new educational resources and tools to support patients and families. We have increased our footprint fielding a contract sales force to focus on physicians who may be in a position to refer patients to a site of care for gene therapy or prescribe one of our exon-skipping therapies.

Patrick Moss: We have increased our footprint fielding a contract sales force to focus on physicians who may be in a position to refer patients to a site of care for gene therapy or prescribe one of our exon-skipping therapies. This team recently completed training and deployment in the field is underway. We expect the team to be fully operational as we enter the H2 of this year.

Speaker #1: This team recently completed training and deployment in the field is underway. We expect the team to be fully operational as we enter the second half of this year.

Speaker #1: Expanding our footprint with a contract sales force has enabled us to deepen our efforts at sites of care with our Sarepta sales team. Our sales team will devote time to more robust interactions with prescribers at sites of care and engage with the extended care team.

Dallan Murray: Expanding our footprint with a contract sales force has enabled us to deepen our efforts at sites of care with our Sarepta sales team. Our sales team will devote time to more robust interactions with prescribers at sites of care and engage with the extended care team. In addition to my team's initiatives, the company is developing more educational resources and tools to aid patients and families in their preparation for a conversation with their clinician. In an age where information online is abundant and can be difficult to navigate, having clear resources and tools available to caregivers and patients is Sarepta's response to supporting the unique and very personal journey of each patient. All these interactions with referring clinicians, prescribers, supportive care providers, families, and caregivers are grounded in clarity, repetition, and transparency as we recognize the decision to treat with ELEVIDYS requires time and trust.

Patrick Moss: Expanding our footprint with a contract sales force has enabled us to deepen our efforts at sites of care with our Sarepta sales team. Our sales team will devote time to more robust interactions with prescribers at sites of care and engage with the extended care team. In addition to my team's initiatives, the company is developing more educational resources and tools to aid patients and families in their preparation for a conversation with their clinician.

Speaker #1: In addition to my team's initiatives, the company is developing more educational resources and tools to aid patients and families in their preparation for a conversation with their clinician.

Patrick Moss: In an age where information online is abundant and can be difficult to navigate, having clear resources and tools available to caregivers and patients is Sarepta's response to supporting the unique and very personal journey of each patient. All these interactions with referring clinicians, prescribers, supportive care providers, families, and caregivers are grounded in clarity, repetition, and transparency as we recognize the decision to treat with ELEVIDYS requires time and trust.

Speaker #1: In an age where information online is abundant and can be difficult to navigate, having clear resources and tools available to caregivers and patients is Sarepta's response to supporting the unique and very personal journey of each patient.

Speaker #1: All these interactions with referring clinicians, prescribers, supportive care providers, families, and caregivers are grounded in clarity, repetition, and transparency as we recognize the decision to treat with Aleptus requires time and trust.

Speaker #1: To date, a growing body of empirical evidence supports that Aleptus is changing the trajectory at Duchenne. We integrated the long-term embark data including muscle MRI findings into our educational efforts and discussions with clinicians addressing what matters most: preservation of muscle over time.

Dallan Murray: To date, a growing body of empirical evidence supports that ELEVIDYS is changing the trajectory at Duchenne. We integrated the long-term EMBARK data, including muscle MRI findings, into our educational efforts and discussions with clinicians addressing what matters most: preservation of muscle over time. Our efforts are having an impact, and feedback from prescribers and the patient advocacy community affirms our approach. Safety must be considered within the totality of evidence, including the durable benefit of ELEVIDYS. HCPs and the ambulatory population were directly affected by misperceptions of ELEVIDYS, so education remains essential and is a focal point of our work. We remain confident that all these initiatives should address the needs of prescribers and patients. I do want to set expectations very clearly. The time from enrollment form to infusion is a 6-month process.

Patrick Moss: To date, a growing body of empirical evidence supports that ELEVIDYS is changing the trajectory at Duchenne. We integrated the long-term EMBARK data, including muscle MRI findings, into our educational efforts and discussions with clinicians addressing what matters most: preservation of muscle over time. Our efforts are having an impact, and feedback from prescribers and the patient advocacy community affirms our approach.

Speaker #1: Our efforts are having an impact, and feedback from prescribers and the patient advocacy community affirms our approach. Safety must be considered within the totality of evidence, including the durable benefit of Aleptus.

Patrick Moss: Safety must be considered within the totality of evidence, including the durable benefit of ELEVIDYS. HCPs and the ambulatory population were directly affected by misperceptions of ELEVIDYS, so education remains essential and is a focal point of our work. We remain confident that all these initiatives should address the needs of prescribers and patients. I do want to set expectations very clearly. The time from enrollment form to infusion is a 6-month process.

Speaker #1: HCPs and the ambulatory population were directly affected by misperceptions of Aleptus, so education remains essential and is a focal point of our work. We remain confident that all these initiatives should address the needs of prescribers and patients.

Speaker #1: But I do want to set expectations very clearly. The time from enrollment form to infusion is a six-month process. Given this, it will take time to see the potential impact of my team's action to be reflected in sales.

Dallan Murray: Given this, it will take time to see the potential impact of my team's action to be reflected in sales. Last quarter, I said we are seeing green shoots, early signals that give us confidence we are headed in the right direction, and the team is squarely focused on delivering the efficacy message to drive demand. Enrollment form activity is more geographically diverse. Sites have previously paused activity in 2025 are participating and submitting enrollment forms. Across the broader referral ecosystem, we are seeing more consistent HCP engagement, suggesting that awareness and understanding of the benefits of ELEVIDYS is resonating. We expect momentum to build progressively through 2026, with greater visibility into improvement most likely to emerge in the latter part of this year and into 2027.

Patrick Moss: Given this, it will take time to see the potential impact of my team's action to be reflected in sales. Last quarter, I said we are seeing green shoots, early signals that give us confidence we are headed in the right direction, and the team is squarely focused on delivering the efficacy message to drive demand. Enrollment form activity is more geographically diverse. Sites have previously paused activity in 2025 are participating and submitting enrollment forms.

Speaker #1: Last quarter, I said we are seeing green shoots—early signals that give us confidence we are headed in the right direction. And the team is squarely focused on delivering the efficacy message to drive demand.

Speaker #1: For example, enrollment form activity is more geographically diverse. Sites have previously paused activity in 2025. Our participating and submitting enrollment forms. Across the broader referral ecosystem, we are seeing more consistent HCP engagement, suggesting that awareness and understanding of the benefits of Aleptus is resonating.

Patrick Moss: Across the broader referral ecosystem, we are seeing more consistent HCP engagement, suggesting that awareness and understanding of the benefits of ELEVIDYS is resonating. We expect momentum to build progressively through 2026, with greater visibility into improvement most likely to emerge in the latter part of this year and into 2027.

Speaker #1: We expect momentum to build progressively through 2026. With greater visibility into improvement, most likely to emerge in the latter part of this year and into 2027.

Speaker #1: Our efforts are substantive in responding to the needs of prescribers and patients and will improve with reach and repetition. Reestablishing momentum will lead to steady growth over time and not a sharp inflection.

Dallan Murray: Our efforts are substantive in responding to the needs of prescribers and patients and will improve with reach and repetition. Reestablishing momentum will lead to steady growth over time and not a sharp inflection. We believe our guidance assumptions for 2026 appropriately reflect a measured trajectory, accounting both for timing dynamics and patient decision cycles. Given this reality, we are comfortable with the Q2 consensus. As Doug stated earlier, we reiterate the full year guidance of $1.2 to 1.4 billion and would counsel prudence in raising estimates prematurely. Our long-term conviction in ELEVIDYS remains strong. As the only FDA-approved gene therapy for Duchenne muscular dystrophy, we have treated more than 1,300 patients in both the clinical and commercial settings with ELEVIDYS.

Patrick Moss: Our efforts are substantive in responding to the needs of prescribers and patients and will improve with reach and repetition. Reestablishing momentum will lead to steady growth over time and not a sharp inflection. We believe our guidance assumptions for 2026 appropriately reflect a measured trajectory, accounting both for timing dynamics and patient decision cycles. Given this reality, we are comfortable with the Q2 consensus.

Speaker #1: We believe our guidance assumptions for 2026 appropriately reflect a measured trajectory accounting both for timing dynamics and patient decision cycles. Given this reality, we are comfortable with the Q2 consensus.

Speaker #1: And as Doug stated earlier, we reiterate the full-year guidance of $1.2 to $1.4 billion and would counsel prudence in raising estimates prematurely. Our long-term conviction in Aleptus remains strong.

Patrick Moss: As Doug stated earlier, we reiterate the full year guidance of $1.2 to 1.4 billion and would counsel prudence in raising estimates prematurely. Our long-term conviction in ELEVIDYS remains strong. As the only FDA-approved gene therapy for Duchenne muscular dystrophy, we have treated more than 1,300 patients in both the clinical and commercial settings with ELEVIDYS.

Speaker #1: As the only FDA-approved gene therapy for Duchenne muscular dystrophy, we have treated more than 1,300 patients in both the clinical and commercial settings with Aleptus.

Speaker #1: The current and growing body of data demonstrates the disease-modifying potential of Aleptus and as a result, we believe Aleptus has the opportunity to remain a cornerstone therapy in Duchenne for years to come.

Dallan Murray: The current and growing body of data demonstrates the disease-modifying potential of ELEVIDYS, as a result, we believe ELEVIDYS has the opportunity to remain a cornerstone therapy in Duchenne for years to come. Finally, a brief update on the PMO franchise. The PMO franchise remains durable in 2026, supported by long-standing physician experience, a well-understood safety profile, a continued commitment to preserving muscle function, and exceptionally high rates of adherence with our therapies. Physicians continue to view exon skipping as an important treatment, particularly for patients who are not candidates for gene therapy or for those who choose to defer treatment. The robust body of real-world evidence that demonstrates meaningful benefits in survival and cardiac function reflects more than a decade-long commitment of Sarepta's scientific investment and leadership dedicated to improving outcomes for those with Duchenne.

Patrick Moss: The current and growing body of data demonstrates the disease-modifying potential of ELEVIDYS, as a result, we believe ELEVIDYS has the opportunity to remain a cornerstone therapy in Duchenne for years to come. Finally, a brief update on the PMO franchise. The PMO franchise remains durable in 2026, supported by long-standing physician experience, a well-understood safety profile, a continued commitment to preserving muscle function, and exceptionally high rates of adherence with our therapies.

Speaker #1: And finally, a brief update on the PMO franchise. The PMO franchise remains durable in 2026, supported by long-standing physician experience. A well-understood safety profile, a continued commitment to preserving muscle function, and exceptionally high rates of adherence with our therapies.

Speaker #1: Physicians continue to view exon-skipping as an important treatment, particularly for patients who are not candidates for gene therapy or for those who choose to defer treatment.

Patrick Moss: Physicians continue to view exon skipping as an important treatment, particularly for patients who are not candidates for gene therapy or for those who choose to defer treatment. The robust body of real-world evidence that demonstrates meaningful benefits in survival and cardiac function reflects more than a decade-long commitment of Sarepta's scientific investment and leadership dedicated to improving outcomes for those with Duchenne.

Speaker #1: The robust body of real-world evidence that demonstrates meaningful benefits in survival and cardiac function reflects more than a decade-long commitment of Sarepta's scientific investment and leadership dedicated to improving outcomes for those with Duchenne.

Speaker #1: In closing, our commercial focus in 2026 is clear. Execute with discipline, educate with data-driven conversations, build momentum, and support the unique needs of each and every patient.

Dallan Murray: In closing, our commercial focus in 2026 is clear: execute with discipline, educate with data-driven conversations, build momentum, and support the unique needs of each and every patient. We are encouraged by the early rebuilding signals for ELEVIDYS, the stability of our PMO business, and the long-term opportunity to support those with Duchenne and change the trajectory of the disease. Thank you, and I'll turn the call over to Ryan. Ryan?

Patrick Moss: In closing, our commercial focus in 2026 is clear: execute with discipline, educate with data-driven conversations, build momentum, and support the unique needs of each and every patient. We are encouraged by the early rebuilding signals for ELEVIDYS, the stability of our PMO business, and the long-term opportunity to support those with Duchenne and change the trajectory of the disease. Thank you, and I'll turn the call over to Ryan. Ryan?

Speaker #1: We are encouraged by the early rebuilding signals for Aleptus: the stability of our PMO business and the long-term opportunity to support those with Duchenne and change the trajectory of the disease.

Speaker #1: Thank you, and I'll turn the call over to Ryan. Ryan?

Speaker #2: Thank you, Patrick, and good afternoon, everyone. On behalf of the Sarepta team, I'm pleased to report a strong quarter of financial execution to start the year.

Ryan Wong: Thank you, Patrick, and good afternoon, everyone. On behalf of the Sarepta team, I'm pleased to report a strong quarter of financial execution to start the year, where our base business was profitable and cash flow positive. In my brief remarks today, I'll share highlights from the quarter and some perspective on how we're thinking about the rest of 2026. Starting with the P&L, first quarter total revenues were $731 million, a decrease of 2% compared to Q1 of last year. The decrease in our net product revenues year over year was driven by lower ELEVIDYS sales and was partially offset by an increase in collaboration and other revenues. In Q1, we reported $400 million of collaboration and other revenues.

Speaker #2: We're our base business was profitable and cash flow positive. In my brief remarks today, I'll share highlights from the quarter and some perspective on how we're thinking about the rest of 2026.

Speaker #2: Starting with the P&L, first quarter total revenues were $731 million, a decrease of 2% compared to Q1 of last year. The decrease in our net product revenues year over year was driven by lower Aleptus sales, and it was partially offset by an increase in collaboration and other revenues.

Ryan Wong: Starting with the P&L, first quarter total revenues were $731 million, a decrease of 2% compared to Q1 of last year. The decrease in our net product revenues year over year was driven by lower ELEVIDYS sales and was partially offset by an increase in collaboration and other revenues. In Q1, we reported $400 million of collaboration and other revenues.

Speaker #2: In Q1, we reported $400 million of collaboration and other revenues, and consistent with previous guidance, this included $325 million of non-cash collaboration revenue related to Roche declining a program option, as well as $40 million of milestone revenue from the first commercial sale of Aleptus in Japan.

Ryan Wong: Consistent with previous guidance, this included $325 million of non-cash collaboration revenue related to Roche declining a program option, as well as $40 million of milestone revenue from the first commercial sale of ELEVIDYS in Japan. Turning to gross margin, total cost of sales for the quarter was $109 million, a decrease of 21% compared to last year, driven primarily by lower sales volume. On a unit sales basis, gross margins were 82%. Moving now to OpEx. Combined R&D and SG&A expenses in Q1 were $263 million and $224 million on a GAAP and a non-GAAP basis, respectively. Both included the $50 million annual Arrowhead collaboration license fee recorded to R&D.

Speaker #2: Turning to gross margin, total cost of sales for the quarter was $109 million, a decrease of 21% compared to last year, driven primarily by lower sales volume.

Ryan Wong: On a unit sales basis, gross margins were 82%. Moving now to OpEx. Combined R&D and SG&A expenses in Q1 were $263 million and $224 million on a GAAP and a non-GAAP basis, respectively. Both included the $50 million annual Arrowhead collaboration license fee recorded to R&D.

Speaker #2: On a unit sales basis, gross margins were 82%. Moving now to OPEX. Combined R&D and etching expenses in the first quarter were $263 million, and $224 million, on a gap and a non-gap basis, respectively.

Speaker #2: Both included the $50 million annual Arrowhead collaboration license fee recorded to R&D. This was a significant decrease compared to the prior year quarter because of the cost restructuring initiatives enacted last summer and as the prior year quarter included the upfront transaction costs from the Arrowhead collaboration.

Ryan Wong: This was a significant decrease compared to the prior year quarter because of the cost restructuring initiatives enacted last summer and as the prior year quarter included the upfront transaction cost from the Arrowhead collaboration. Putting it all together, in Q1, we delivered a GAAP operating profit of $358 million and a non-GAAP operating profit of $398 million. These results are reflective of the strength of our underlying business and the non-cash collaboration revenue recognized during the period. Shifting to the balance sheet, we ended Q1 with $748 million of cash and investment, a sequential decrease of $206 million, driven by $250 million of payments to Arrowhead for the second DM1 milestone and the annual collaboration payment I just mentioned.

Speaker #2: Putting it all together in the first quarter, we delivered a gap operating profit of $358 million, and a non-gap operating profit of $398 million.

Speaker #2: These results are reflective of the strength of our underlying business and the non-cash collaboration revenue recognized during the period. Shifting to the balance sheet, we ended the first quarter with $748 million of cash and investments, a sequential decrease of $206 million.

Ryan Wong: These results are reflective of the strength of our underlying business and the non-cash collaboration revenue recognized during the period. Shifting to the balance sheet, we ended Q1 with $748 million of cash and investment, a sequential decrease of $206 million, driven by $250 million of payments to Arrowhead for the second DM1 milestone and the annual collaboration payment I just mentioned.

Speaker #2: Driven by $250 million of payments to Arrowhead—the second DM1 milestone and the annual collaboration payment I just mentioned. Also, as noted earlier, excluding these planned payments, our base business continued to generate positive cash flow.

Ryan Wong: Also, as noted earlier, excluding these planned payments, our base business continued to generate positive cash flow. Looking ahead to the remainder of the year, we are reaffirming our prior revenue and OpEx guidance, as well as our expectation of profitability and to be growing our cash balance from here. As you heard earlier on the call, we are very encouraged by the early data emerging from our FSHD and DM1 programs. If the data continue to translate clinically as they have so far, we believe they represent significant opportunities to benefit patients with unmet needs and create long-term value for investors. In closing, I will highlight that our current operating expense outlook and medium-term planning fully contemplate advancing both programs through late-stage development.

Speaker #2: Looking ahead to the remainder of the year, we are reaffirming our prior revenue and OPEX guidance, as well as our expectation of profitability and to be growing our cash balance from here.

Speaker #2: As you heard earlier on the call, we are very encouraged by the early data emerging from our FSHD and DM1 programs. And if the data continues to translate clinically as they have so far, we believe they represent significant opportunities to benefit patients with unmet needs and create long-term value for investors.

Ryan Wong: If the data continue to translate clinically as they have so far, we believe they represent significant opportunities to benefit patients with unmet needs and create long-term value for investors. In closing, I will highlight that our current operating expense outlook and medium-term planning fully contemplate advancing both programs through late-stage development.

Speaker #2: In closing, I will highlight that our current operating expense outlook and medium-term planning fully contemplate advancing both programs through a late stage of development.

Speaker #2: Leveraging the strength and durability of our commercial execution, we believe we are uniquely positioned to fund and execute these programs and our broader pipeline responsibly, without placing strain on the balance sheet.

Ryan Wong: Leveraging the strength and durability of our commercial execution, we believe we are uniquely positioned to fund and execute these programs and our broader pipeline responsibly without placing strain on the balance sheet. With that, I'll turn the call back to Doug. Doug?

Speaker #2: And with that, I'll turn the call back to Doug. Doug?

Speaker #3: Thanks, Ryan. Let's open the call for questions.

Doug Ingram: Thanks, Ryan. Let's open the call for questions.

Speaker #4: Thank you. At this time, we'll conduct the question-and-answer session. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced.

Operator 2: Thank you. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, we ask that you please limit yourself to one question each. Our first question comes from Anupam Rama from JPMorgan. Please go ahead.

Operator: Thank you. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. In the interest of time, we ask that you please limit yourself to one question each. Our first question comes from Anupam Rama from JPMorgan. Please go ahead.

Speaker #4: To withdraw your question, please press star 11 again. In the interest of time, we ask that you please limit yourself to one question each.

Speaker #4: Our first question comes from Anupam Rama from JPMorgan. Please go ahead.

[Analyst] (JPMorgan): Hey, guys. This is Joyce on for Anupam. Thanks so much for taking our question. With your sales force expansion and ongoing initiatives to help close some of these information gaps, I was just wondering if you could comment on feedback you've been receiving regarding your 3-year EMBARK data and which parts of this data specifically have been especially resonating with physicians. Thanks so much.

Speaker #5: Hey, guys. This is Joyce on for Anupam. Thanks so much for taking our question. With your Salesforce expansion and ongoing initiatives to help close some of these information gaps, I was just wondering if you could comment on feedback you've been receiving regarding your three-year EMBARK data, and which parts of this data specifically have been especially resonating with physicians.

Speaker #5: Thanks so much.

Doug Ingram: I'll turn this over to Dallan briefly. You can sort of comment on some of the advisory boards you've had and some of the direct interactions you've had with physicians on the 3-year data and other data.

Speaker #3: I'll turn this over to Patrick briefly. You can sort of comment on some of the advisory boards you've had and some of the direct interactions you've had with physicians on the three-year data and other data.

Speaker #2: Yeah. Thanks, Doug. And so we've been having multiple ad boards and discussions with physicians, both myself and Ian, and Doug, one-on-ones, but also the field team as they're out there engaging.

Dallan Murray: Yeah. Thanks, Doug. We've been having multiple ad boards and discussions with physicians, both myself and Ian and Doug one-on-one, but also the field team as they're out there engaging. What's moving the needle is the efficacy data, as well as the MRI data. Once the physicians see both, the divergence over time from natural history of patients that are treated with ELEVIDYS tied down with the MRI data, that's moving the needle and also reflects exactly what they were expecting from a therapy like ELEVIDYS, as well as what they're seeing in their clinic.

Patrick Moss: Yeah. Thanks, Doug. We've been having multiple ad boards and discussions with physicians, both myself and Ian and Doug one-on-one, but also the field team as they're out there engaging. What's moving the needle is the efficacy data, as well as the MRI data. Once the physicians see both, the divergence over time from natural history of patients that are treated with ELEVIDYS tied down with the MRI data, that's moving the needle and also reflects exactly what they were expecting from a therapy like ELEVIDYS, as well as what they're seeing in their clinic.

Speaker #2: And what's moving the needle is the efficacy data as well as the MRI data. And once the physicians see both the divergence over time from natural history of patients that are treated with Aleptus tied down with the MRI data, that's moving the needle.

Speaker #2: And also, it reflects exactly what they were expecting from a therapy like Aleptus, as well as what they're seeing in their clinic.

Speaker #3: Yeah. And I think all that's exactly right. You had more experience with it even than I have. But there's a couple of reasons that this is occurring.

Doug Ingram: Well, I think all that's exactly right, and you've had more experience with it even than I have. You know, there are a couple reasons that this is occurring. The first is the data itself is really impressive. If you look at the one-year EMBARK data on every secondary measure, every time measure, we were statistically significant on this placebo-controlled and blinded, well-controlled study. You look at two years on all measures, we are doing much better. ELEVIDYS is doing much better than untreated patients. That gap grows even more in year three, exactly what you'd expect from a disease-modifying therapy that's changing the trajectory of disease.

Speaker #3: The first is the data itself. It's really impressive. If you look at the one-year embark data, on every secondary measure, every time measure, we were statistically significant on this placebo-controlled and blinded well-controlled study.

Speaker #3: And then you look at two years—on all measures, we are doing much better. Aleptus is doing much better than untreated patients. And that gap grows even more.

Doug Ingram: ELEVIDYS is doing much better than untreated patients. That gap grows even more in year three, exactly what you'd expect from a disease-modifying therapy that's changing the trajectory of disease. From an urgency perspective, we have muscle MRI data, which is exactly what you'd expect to see, which is that if you get treated, you are going to save yourself from a lot of damage and the fat and fibrotic tissue that comes from that damage and the loss of muscle.

Speaker #3: In year three, exactly what you'd expect from a disease-modifying therapy that's changing the trajectory of disease. And then, from an urgency perspective, we have muscle MRI data, which is exactly what you'd expect to see, which is that if you get treated, you are going to save yourself from a lot of damage and the fat and fibrotic tissue that comes from that damage and the loss of muscle.

Doug Ingram: From an urgency perspective, we have muscle MRI data, which is exactly what you'd expect to see, which is that if you get treated, you are going to save yourself from a lot of damage and the fat and fibrotic tissue that comes from that damage and the loss of muscle. It's understandable that it's compelling when you talk to physicians about all of this data, and that's not even all the data that we have. We obviously have the five-year data from our original cohort as well. The other thing that's important to understand when you think about our initiatives is something that is both frustrating but in a big opportunity, which is when you do market research, what I've just told you now and what Patrick's mentioned to you now isn't well understood.

Speaker #3: And so it's understandable that it's compelling when you talk to physicians about all of this data. And that's not even all of the data that we have.

Doug Ingram: It's understandable that it's compelling when you talk to physicians about all of this data, and that's not even all the data that we have. We obviously have the five-year data from our original cohort as well. The other thing that's important to understand when you think about our initiatives is something that is both frustrating but in a big opportunity, which is when you do market research, what I've just told you now and what Patrick's mentioned to you now isn't well understood.

Speaker #3: We obviously have the five-year data from our original cohort as well. The other thing that's important to understand when you think about our initiatives is something that is both frustrating but in a big opportunity.

Speaker #3: Which is when you do market research, what I've just told you now and what Patrick's mentioned to you now, isn't well understood that in large measure because of a lot of the important things that happened last year, but that were distracted us last year, there was a lot of focus away from what this therapy was doing for patients.

Doug Ingram: That in large measure because of a lot of the important things that happened last year but that were distracting us last year, there was a lot of focus away from what this therapy was doing for patients. As we sit here right now, both in the patient community and significantly in the physician community, there is a massive information gap around those issues. When you sort of take that and kind of shake off the frustration that comes from that and realize that's actual opportunity, you think about the initiatives that Dallan's putting in place, gives us an enormous amount of confidence for the future. We've more than doubled the size of our sales force. We have a contract sales force. We have grand data now. We have much better promotional material founded on that great data.

Speaker #3: And as we sit here right now, both in the patient community and significantly in the physician community, there is a massive information gap around those issues.

Speaker #3: So when you sort of take that, you kind of shake off the frustration that comes from that and realize that's actual opportunity, and then you think about the initiatives that Patrick's putting in place, gives us an enormous amount of confidence for the future.

Doug Ingram: When you sort of take that and kind of shake off the frustration that comes from that and realize that's actual opportunity, you think about the initiatives that Dallan's putting in place, gives us an enormous amount of confidence for the future. We've more than doubled the size of our sales force. We have a contract sales force. We have grand data now. We have much better promotional material founded on that great data.

Speaker #3: We'd more than double the size of our Salesforce. We have a contract Salesforce. We have brand data now. We have much better promotional material, founded on that great data.

Speaker #3: We have great educational efforts in the patient community and the like. And we have the muscle MRI data that makes the point that you cannot wait, that you will never catch up, if you wait.

Doug Ingram: We have great educational efforts in the patient community and the, and the like, and we have the muscle MRI data that makes the point that you cannot wait, That you will never catch up if you wait. There's an enormous amount of opportunity here to benefit patients and to get ELEVIDYS moving. Now, with that said, I'm gonna say what I said in my script, and I do wanna be very careful. We are excited about where we are. We have these initiatives that are in play. This is a long cycle process and, you know, we're reiterating our guidance, $1.2 to 1.4 billion, and we'd ask you along with us to exercise some prudence in changing estimates until we get these initiatives going along the way.

Speaker #3: There's an enormous amount of opportunity here to benefit patients and to get Aleptus moving. Now, with that said, I'm going to say what I said in my script, and I do want to be very careful.

Doug Ingram: Now, with that said, I'm gonna say what I said in my script, and I do wanna be very careful. We are excited about where we are. We have these initiatives that are in play. This is a long cycle process and, you know, we're reiterating our guidance, $1.2 to 1.4 billion, and we'd ask you along with us to exercise some prudence in changing estimates until we get these initiatives going along the way. The good news is that we're in a great place, even in a base case situation, to fully fund without the need to go to the equity markets, what is a very, very exciting siRNA pipeline.

Speaker #3: We are excited about where we are. We have these initiatives that are in play. This is a long cycle process. And we're reiterating our guidance: 1.2 to 1.4 billion dollars.

Speaker #3: And we'd ask you, along with us, to exercise some prudence in changing estimates until we get these initiatives going along the way. And the good news is, base case situation to fully fund without the need to go to the equity markets.

Doug Ingram: The good news is that we're in a great place, even in a base case situation, to fully fund without the need to go to the equity markets, what is a very, very exciting siRNA pipeline.

Speaker #3: What is a very, very exciting SIRNA pipeline.

Speaker #4: Thank you. Our next question comes from Kostas Biliaris. From Oppenheimer, please go ahead.

Operator 2: Thank you. Our next question comes from Kostas Biliouris from Oppenheimer. Please go ahead.

Operator: Thank you. Our next question comes from Kostas Biliouris from Oppenheimer. Please go ahead.

Speaker #6: Thank you so much for taking the question. One question on this and Vyondis SNDA and sorry if I missed it. Can you clarify whether you have requested or received priority review there and when should we expect the decision from the FDA?

Kostas Biliouris: Thank you so much for taking the question. One question on AMONDYS and VYONDYS sNDA, and sorry if I missed it. Can you clarify whether you have requested or received priority review there? When should we expect a decision from the FDA? Thank you.

Speaker #6: Thank you.

Speaker #3: Yeah. This are SNDAs. We didn't ask for priority review. So it's the regular time cycle. So we would imagine that the PDUFA date will be sometime in February of next year.

Doug Ingram: Yeah, this is, these are sNDAs. We didn't ask for priority review, it's the regular time cycle. We would imagine that the PDUFA date will be sometime in February of next year.

Speaker #6: Thanks.

Kostas Biliouris: Thanks.

Speaker #4: Thank you. Our next question comes from Ellie Merrill from Barclays. Please go ahead.

Operator 2: Thank you. Our next question comes from Ellie Merrill from Barclays. Please go ahead.

Operator: Thank you. Our next question comes from Ellie Merrill from Barclays. Please go ahead.

Ellie Merrill: Hey, guys. Just two questions from me. You mentioned some Q1 seasonal dynamics. Can you just elaborate on what you saw there and how we should think about the appropriate run rate as we head into Q2 and beyond for both the PMO franchise and ELEVIDYS? A question on the Huntington's program. Can you walk us through what you see as potentially differentiating versus other silencing approaches in development and what we could expect from the proof of biology data next year? Thanks.

Speaker #5: Hey, guys. Just two questions from me. You mentioned some 1Q seasonal dynamics. Can you just elaborate on what you saw there and how we should think about the appropriate run rate as we head into 2Q and beyond for both the PMO franchise and Aleptus?

Speaker #5: And then a question on the Huntington's program. Can you walk us through what you see as potentially differentiating versus other silencing approaches in development, and what we could expect from the proof-of-biology data next year?

Speaker #5: Thanks.

Doug Ingram: Sure. I'll turn the first part of the call over to Patrick, after which Louise can touch on the Huntington's program.

Speaker #3: first part of the call over to Patrick after which Luis can touch on the Huntington's program.

Dallan Murray: What we do know and what we do see is quarter-to-quarter dynamics, they're noisy, right? It reflects just a small number of patients, either this quarter or the next quarter. When we look at it's not, you know, something that we can be extremely precise on. We do know things like illnesses, you know, patient family dynamics do impact those quarterly dynamics. That's something that, you know, we do look at and evaluate as we provide our guidance.

Speaker #2: Yeah. And what we do know and what we do see is quarter to quarter dynamics. They're noisy, right? And so it reflects just a small number of patients, either this quarter or the next quarter.

Patrick Moss: What we do know and what we do see is quarter-to-quarter dynamics, they're noisy, right? It reflects just a small number of patients, either this quarter or the next quarter. When we look at it's not, you know, something that we can be extremely precise on. We do know things like illnesses, you know, patient family dynamics do impact those quarterly dynamics. That's something that, you know, we do look at and evaluate as we provide our guidance.

Speaker #2: And so when we look at it, it's not something that we can be extremely precise on. But we do know things like illnesses, patient family dynamics do impact those quarterly, quarterly dynamics.

Speaker #2: And that's something that we do look at. And evaluate as we provide our guidance.

Speaker #3: Yeah. One thing I will say about that as well is remember, the reason for all of that is that this is a one-time therapy.

Doug Ingram: Yeah. One thing I will say about that as well is, remember, the reason for all of that is that this is a one-time therapy. You know, with a chronic therapy, you kind of get this installed base, and you're really just forecasting on the margin. With a one-time therapy, you're forecasting new to every quarter. With a therapy with like ELEVIDYS, which is a couple of million dollars net, a couple patients that have the flu in the last week of the quarter can impact. There's just a little more variability here. As much as we have a nice line of sight, there's more variability here than you might see in a chronic therapy.

Speaker #3: So with a chronic therapy, you kind of get this installed base, and you're really just forecasting on the margin with a one-time therapy. You're forecasting anew every quarter.

Speaker #3: And with a therapy like Aleptus, which is a couple of million dollars net, a couple of patients that have the flu in the last week of the quarter can impact.

Doug Ingram: With a therapy with like ELEVIDYS, which is a couple of million dollars net, a couple patients that have the flu in the last week of the quarter can impact. There's just a little more variability here. As much as we have a nice line of sight, there's more variability here than you might see in a chronic therapy.

Speaker #3: So there's just a little more variability here as much as we have a nice line of sight. There's more variability here than you might see in a chronic therapy.

Dallan Murray: On the PMO side, with there's lumpiness in the ex-US business as well as the beginning of the year, we do see insurance changes, and so that does impact the PMO side of the ledger.

Speaker #2: And then on the PMO side, there's lumpiness in the XUS business as well as the beginning of the year, we do see insurance changes.

Patrick Moss: On the PMO side, with there's lumpiness in the ex-US business as well as the beginning of the year, we do see insurance changes, and so that does impact the PMO side of the ledger.

Speaker #2: And so that does impact the PMO side of the ledger.

Doug Ingram: With that, we will turn the call to Louise.

Speaker #3: And with that, we will turn the call to Luis.

Doug Ingram: With that, we will turn the call to Louise.

Speaker #5: Thank you. As you mentioned, we're very excited about the Huntington's program. And we think that we are potentially differentiating for several reasons. So the first is really the use of the mechanism of action.

Louise Rodino-Klapac: Thank you. As you mentioned, we're very excited about the Huntington's program, and we think that we are potentially differentiating for several reasons. The first is really the use of the mechanism of action, and that's using the TFR ligand in combination with the subcutaneous injection. This really allows us, based on preclinical data, to get into the deep brain regions, which is essential for Huntington's disease, like the striatum. Based on the preclinical data in mouse models as well as non-human primates, we have particularly high knockdown in these deep regions, and that's really what set this program apart for us and got us excited. It's early days.

Speaker #5: And that's using the TFR ligand in combination with the subcutaneous injection. And this really allows us, based on preclinical data, to get into the deep brain regions, which is essential for Huntington's disease like the striatum.

Louise Rodino-Klapac: This really allows us, based on preclinical data, to get into the deep brain regions, which is essential for Huntington's disease, like the striatum. Based on the preclinical data in mouse models as well as non-human primates, we have particularly high knockdown in these deep regions, and that's really what set this program apart for us and got us excited. It's early days.

Speaker #5: And based on the preclinical data in mouse models as well as non-human primates, we have particularly high knockdown in these deep regions, and that's really what set this program apart for us and got us excited.

Speaker #5: So it's early days. We are on track for first patient in, but we will be looking for proof of biology in terms of safety.

Louise Rodino-Klapac: We are on track for first patient in. We will be looking for proof of biology, in terms of safety and then evidence of activity in terms of knockdown, in the first data that we see, and that'll be earlier next year. Very excited based on preclinical data and very much looking for differentiation based on the mechanism of action and the dosing itself, which is much less invasive than some other programs.

Speaker #5: And then evidence of activity in terms of knockdown in the first data that we see. And that'll be earlier next year. So very excited based on preclinical data and very much looking for differentiation based on the mechanism of action and the dosing itself.

Speaker #5: Which is much less invasive than some other programs.

Speaker #4: Thank you. Our next question comes from Andrew Tsai from Jefferies. Please go ahead.

Operator 2: Thank you. Our next question comes from Andrew Tsai from Jefferies. Please go ahead.

Operator: Thank you. Our next question comes from Andrew Tsai from Jefferies. Please go ahead.

Matthew Barcus: Hey, congrats on the quarter. This is Matthew Barcus on for Andrew Tsai. I just wanted to ask about what you guys are expecting in terms of the reduction of ALI incidence in the non-ambulatory cohort 8 from this data set expected later this year. I think you said you wanted to see a 50% reduction in ALI rates, where I think the clinical rate is around 40%. Is it different in the real world? Might ALI rates in cohort 8 actually mimic the real world setting?

Speaker #6: Hey, congrats on the quarter. This is Matt Barkus on for Andrew Tsai. I just wanted to ask about what you guys are expecting in terms of the reduction of ALI in the non-ambulatory cohort AIDS trauma data set expected later this year.

Speaker #6: And I think you said you wanted to see a 50% reduction in ALI rates. Where I think the clinical rate is around 40%. But is it different in the real world?

Speaker #6: And might ALI rates in cohort AIDS actually mimic the real-world setting?

Speaker #3: Yeah, so I'm going to turn this question over to Luis. But before I do, let me make a quick comment, which is that we do have some evidence before cohort AIDs that gives us some confidence around the success of cohort AIDs.

Doug Ingram: Yeah. I'm gonna turn this question over to Louise, but before I do, let me make a quick comment, which is that we do have some evidence for cohort 8 that gives us some confidence around the success of cohort 8. Dr. Soslow, as you may know, has pre-treated a number of patients and presented that data in the World Muscle Society earlier this year, and in that setting, the pretreatment with sirolimus completely abated any increase in liver enzymes. Also, we have the real-world evidence study, ENDEAVOR, I believe, and we've done an interim analysis there early days, and I wanna be very clear, the overlapping evidence 'cause some of sirolimus, some of Dr. Soslow's data is in there as well.

Speaker #3: Dr. Soslo, as you may know, has pre-treated a number of patients and presented that data. I believe at World Muscle earlier. This year. And in that setting, the pre-treatment with serolimus completely abated any increase in liver enzymes.

Doug Ingram: Also, we have the real-world evidence study, ENDEAVOR, I believe, and we've done an interim analysis there early days, and I wanna be very clear, the overlapping evidence 'cause some of sirolimus, some of Dr. Soslow's data is in there as well. In that setting as well, we've seen no increases in liver enzymes so far when a patient is pretreated with sirolimus. Obviously, we need to dose more patients.

Speaker #3: Also, we have the real-world evidence study endeavor, I believe. And we've done an interim analysis there early days. And I want to be very clear the overlapping evidence because some of Dr. Soslo's data is in there as well.

Speaker #3: But in that setting as well, we've seen no increases in liver enzymes so far when a patient is pre-treated with serolimus. Obviously, we need to dose more patients.

Doug Ingram: In that setting as well, we've seen no increases in liver enzymes so far when a patient is pretreated with sirolimus. Obviously, we need to dose more patients. Obviously, we need to get cohort A dosed and get the readout on there. As you can imagine, given that, given our preclinical data, and given the experience anecdotally from other physicians who've used sirolimus in other immunosuppression regimens, we feel a significant amount of conviction around the potential success of cohort A and the ability to get back to offering this therapy to nonambulatory patients who desperately need a therapeutic option, would have none but for this therapy. With that, I'll turn it over to Louise to talk about the clinical trial itself and what the standards are there pursuant to the stat plan.

Speaker #3: Obviously, we need to get cohort AIDS dosed and get the readout on there. But as you can imagine, given that and given our preclinical data and given the experience anecdotally from other physicians who've used serolimus in other immunosuppression regimens, we feel a significant amount of conviction around the potential success of cohort AIDS and the ability to get back to offering this therapy to non-ambulatory patients who desperately need a therapeutic option would have none but for this therapy.

Doug Ingram: Obviously, we need to get cohort A dosed and get the readout on there. As you can imagine, given that, given our preclinical data, and given the experience anecdotally from other physicians who've used sirolimus in other immunosuppression regimens, we feel a significant amount of conviction around the potential success of cohort A and the ability to get back to offering this therapy to nonambulatory patients who desperately need a therapeutic option, would have none but for this therapy. With that, I'll turn it over to Louise to talk about the clinical trial itself and what the standards are there pursuant to the stat plan.

Speaker #3: But with that, I'll turn it over to Luis to talk about the clinical trial itself and what the standards are there pursuant to the STAT plan.

Speaker #5: Sure. And you were correct. We were looking for a 50% reduction in the incidence of ALI the trial is an open-label trial. The rolling approximately 25 patients.

Louise Rodino-Klapac: Sure. You were correct. We were looking for a 50% reduction in the incidence of ALI. The trial is an open label trial that's enrolling approximately 25 patients. We do have the ability to look at the data and enhance the end if required. In regarding the ability to reach that 50%, I'm gonna ask Dr. Richardson to just comment on it in the clinical trial versus the real world.

Speaker #5: We do have the ability to look at the data and enhance the end if required. But regarding the ability to reach that 50%, I'm going to ask Dr. Richardson to just comment on it in the clinical trial versus the real world.

James Richardson: Yeah. Thank you, Louise and Hannah. Well, thank you, Louise. You're quite right that we have seen a different instance of ALI in the clinical trial setting versus the real-world setting. That's partly driven by the use of the research as the GLDH in the clinical trial setting. We'll be using that in cohort A. Our primary analysis will be to look at a reduction of 50% or more versus our historical clinical trial rates, which include GLDH. We'll also be able to look at it without GLDH to make sure that there is no specific signal to that biomarker. As Louise says, as an open label study, should we see anything that deviates from these original assumptions, we'll be able to adjust the sample size accordingly.

Matthew Barcus: Yeah. Thank you, Louise and Hannah.

Speaker #2: Yeah. Thank you, Luis. And yeah, thank you, Luis. And you're quite right that we have seen a different instance of ALI in the clinical trial setting versus the real-world setting.

James Richardson: Well, thank you, Louise. You're quite right that we have seen a different instance of ALI in the clinical trial setting versus the real-world setting. That's partly driven by the use of the research as the GLDH in the clinical trial setting. We'll be using that in cohort A. Our primary analysis will be to look at a reduction of 50% or more versus our historical clinical trial rates, which include GLDH.

Speaker #2: That's partly driven by the use of the research SAGLDH in the clinical trial setting. Will be using that in cohort AIDS and so on.

Speaker #2: Our primary analysis will be to look at a reduction of 50% or more versus our historical clinical trial rates, which include GLDH. We'll also be able to look at it without GLDH to make sure that there is no specific signal to that biomarker.

James Richardson: We'll also be able to look at it without GLDH to make sure that there is no specific signal to that biomarker. As Louise says, as an open label study, should we see anything that deviates from these original assumptions, we'll be able to adjust the sample size accordingly.

Speaker #2: And as Luis says, as an open-label study, should we see anything that deviates from these original assumptions, we'll be able to adjust the sample size accordingly.

Speaker #4: Thank you. Our next question comes from Brian Abrams from RBC Capital Markets. Please go ahead.

Operator 2: Thank you. Our next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.

Operator: Thank you. Our next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.

Speaker #7: Hi, guys. This is Kevin on for Brian. Thank you for taking our questions. Maybe following up on the serolimus study. Can you talk a bit about your new end-of-20 phase 4 enhanced study of patients receiving Alavitas and serolimus in the real world?

[Analyst] (RBC Capital Markets): Hi, guys. This is Kevin on for Brian. Thank you for taking our questions. Maybe following up on the sirolimus study. Can you talk a bit about your new N of 20 Phase 4 enhanced study of patients receiving ELEVIDYS and sirolimus in the real world? Just curious how that fits with your potential regulatory strategy for nonambulatory patients, whether maybe it was required by regulators, and just your considerations on, you know, potentially just simply upsizing the current study versus running this real-world study in parallel as well. Thank you.

Speaker #7: Just curious how that fits with your potential regulatory strategy for non-ambulatory patients, whether maybe it was required by regulators. And just your considerations on potentially just simply upsizing the current study versus running this real-world study in parallel as well.

Speaker #7: Thank you.

Speaker #3: Well, Luis, yeah, I'm going to turn it to James in a minute. But at a highest level, so this phase 4 study gives us the ability to look at the use of serolimus in ambulatory patients as well as well as looking at gene expression based on this.

Doug Ingram: Love to, Louise?

Louise Rodino-Klapac: Yeah. I'm gonna turn this to James in a minute, at a highest level, the Phase 4 study gives us the ability to look at the use of sirolimus in ambulatory patients as well, as well as looking at gene expression based on this. These two elements are important to looking at sirolimus in a population other than the nonambulatory population. James, maybe you can give a few more details about the study.

Speaker #3: So these two elements are important to looking at serolimus in a population other than the non-ambulatory population. But James, maybe you can give a few more details about the study.

Speaker #6: Yeah. Sure. Absolutely. I mean, this is a study looking at commercially dosed patients under the same serolimus regimen as we're using in cohort AIDS.

James Richardson: Yes. Sure. Absolutely. I mean, this is a study looking at commercially dosed patients under the same sirolimus regimen as we're using in cohort A. It's not part of a broader regulatory strategy, but simply just asking the hypothesis about the use of sirolimus and its mitigation of ALI in a broader Duchenne population. The data could be supportive to cohort A, but is not necessary for that nonambulatory strategy. We'll simply reaffirm the current sort of hypothesis that sirolimus is equally well tolerated across a broad range of Duchenne patients, and we would expect a similar efficacy in terms of reduction of ALI.

Speaker #6: It's not part of a broader regulatory strategy. But simply just asking the hypothesis about the use of serolimus and its mitigation of ALI in a broader Duchenne population the data could be supportive to cohort AIDS but is not necessary for that non-ambulatory strategy.

James Richardson: The data could be supportive to cohort A, but is not necessary for that nonambulatory strategy. We'll simply reaffirm the current sort of hypothesis that sirolimus is equally well tolerated across a broad range of Duchenne patients, and we would expect a similar efficacy in terms of reduction of ALI.

Speaker #6: But we'll simply reaffirm the current sort of hypothesis that serolimus is equally well tolerated across a broad range of Duchenne patients, and we would expect a similar efficacy in terms of reduction of ALI.

Speaker #7: Thank you.

[Analyst] (RBC Capital Markets): Thank you.

Speaker #4: Our next question comes from Mike Oops from Morgan Stanley. Please go ahead.

Operator 2: Our next question comes from Michael Ulz from Morgan Stanley. Please go ahead.

Operator: Our next question comes from Michael Ulz from Morgan Stanley. Please go ahead.

Speaker #8: Hi. It's Avi Novak on the line for Mike. Thank you for taking our questions. I guess just a quick one on guidance. I think on the prior call, you indicated that you're more comfortable with the low end of guidance.

Avi Novak: Hi. It's Avi Novak on the line for Mike. Thank you for taking our questions. I guess just a quick one on guidance. I think on the prior call you indicated that you're more comfortable with the low end of guidance, so that would be more likely. I guess, given the, you know, the positive, green shoots you've seen early this year, I guess, would you be more comfortable, you know, that maybe, you know, the middle or high end of guidance might be more likely? I guess, if not, what do you need to see to sort of get there? Thanks.

Av Novak: Hi. It's Avi Novak on the line for Mike. Thank you for taking our questions. I guess just a quick one on guidance. I think on the prior call you indicated that you're more comfortable with the low end of guidance, so that would be more likely.

Speaker #8: And that would be more likely. I guess given the positive green shoots you've seen early this year, I guess would you be more comfortable that that may be the middle or high end of guidance might be more likely?

Av Novak: I guess, given the, you know, the positive, green shoots you've seen early this year, I guess, would you be more comfortable, you know, that maybe, you know, the middle or high end of guidance might be more likely? I guess, if not, what do you need to see to sort of get there? Thanks.

Speaker #8: And I guess if not, what do you need to see to sort of get there? Thanks.

Speaker #3: Yeah. Thanks for your question. You're exactly right. We guided 1.2 to 1.4 and sort of advised folks that they should be thinking toward the lower end of the 1.2 to 1.4 until we see more the short answer is that we are making very good progress in our initiatives.

Doug Ingram: Yeah. Thanks for your question. You're exactly right. We guided 1.2 to 1.4 and sort of revised folks that they should be thinking toward the lower end of the 1.2 to 1.4 until we see more. The short answer is that we are making very good progress in our initiatives, but the initiatives are long cycle initiatives. A number of them have already gone underway. As an example, our sales force is doubled, and they're out in the field talking to physicians, and that's great. We've got great marketing material. We have additional marketing material coming out with our 3-year data as well, so that's going to be great. We've got educational efforts.

Speaker #3: But the initiatives are long-cycle initiatives. A number of them have already gotten underway. As an example, our Salesforce is doubled and they're out in the field talking to physicians.

Doug Ingram: As an example, our sales force is doubled, and they're out in the field talking to physicians, and that's great. We've got great marketing material. We have additional marketing material coming out with our 3-year data as well, so that's going to be great. We've got educational efforts.

Speaker #3: And that's great. We've got great marketing material. We have additional marketing material coming out with our three-year data as well. So that's going to be great.

Speaker #3: We've got an educational effort. We've got a contract Salesforce that'll be getting in the field very, very shortly. And it's been trained up. But with all of that said, as excited as we are and the conviction we have about these tools, we want to speak cautiously for the time being.

Doug Ingram: We got a contract sales force that'll be getting in the field very, very shortly and has been trained up. With all of that said, and as, you know, as we are and the conviction we have about these tools. We wanna speak cautiously for the time being and just be thoughtful. We're not changing our guidance, and we would caution others to be prudent in raising their internal estimates prematurely. Let's get underway and get these initiatives going. We do see some green shoots, and we certainly see when we, you know, qualitatively when this information is understood by physicians, and understood by patients, it has a meaningful impact.

Speaker #3: And just be thoughtful. And so we're not changing our guidance. And we would caution others to be prudent in raising their internal estimates prematurely.

Speaker #3: Let's get underway and get these initiatives going. And we do see some green shoots. And we certainly see when we qualitatively when this information is understood by physicians and understood by patients, it has a meaningful impact.

Doug Ingram: Let's get underway and get these initiatives going. We do see some green shoots, and we certainly see when we, you know, qualitatively when this information is understood by physicians, and understood by patients, it has a meaningful impact. It's going to take some time because these are all, you know, long cycle, essentially, resetting people and getting them to really understand this, the evidence set, both on safety and efficacy.

Speaker #3: But it's going to take some time because these are all long-cycle essentially resetting people and getting them to really understand the evidence set both on safety and efficacy.

Doug Ingram: It's going to take some time because these are all, you know, long cycle, essentially, resetting people and getting them to really understand this, the evidence set, both on safety and efficacy.

Speaker #8: All right. Great. Thank you for taking our question.

Avi Novak: All right. Great. Thank you for taking our question.

Av Novak: All right. Great. Thank you for taking our question.

Speaker #3: Thank you.

Doug Ingram: Thank you.

Speaker #4: Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

Operator 2: Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

Operator: Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

Speaker #9: Thanks for taking our question. This is Tommy on for Salveen. Maybe if we could get to send that you're available the details on patient numbers at dose levels for the siRNA data by year-end.

[Analyst] (Goldman Sachs): Thanks for taking our question. This is Tommy on for Salveen Richter. Maybe if we could get to send that you're available the details on patient numbers at dose levels for the siRNA data by year-end. Especially how will the functional measures for this data factor into how you're thinking about the registrational outlook and kind of competitive comparisons? Thank you.

Speaker #9: And especially how will the functional measures for this data factor into how you're thinking about the registrational outlook and kind of competitive comparisons? Thank you.

Speaker #3: Great. I'll turn this to Louise.

Doug Ingram: Great. I'll turn this to Louise.

Speaker #9: Sure. So just for both studies, so for FSHD, we will have data from our 6 and 12 mg/kg MAD cohorts. And so those are our highest-dose cohorts.

Louise Rodino-Klapac: Sure. Just for both studies. For FSHD, we will have data from our 6 and 12 mg per kg MAD cohorts. Those are our highest dose cohorts. It is equivalent to 4 and 8 mg per kg siRNA. With respect to DM1, we will have our follow-up from our 6 mg per kg MAD cohort, which is equivalent to 4 mg per kg siRNA. As I mentioned, we will be looking at safety, biomarkers, and early evidence of functional outcomes. James, perhaps you can comment on how we are thinking about the functional data as it is early in terms of the follow-up and the number, patient numbers.

Speaker #9: It's equivalent to 4 and 8 mg/kg siRNA. With respect to DM1, we will have our follow-up from our 6 mg/kg. MAD cohort, which is equivalent to 4 mg/kg siRNA.

Speaker #9: So as I mentioned, we'll be looking at safety, biomarkers, and early evidence of functional outcomes. And James perhaps you can comment on how we're thinking about the functional data.

Louise Rodino-Klapac: As I mentioned, we will be looking at safety, biomarkers, and early evidence of functional outcomes. James, perhaps you can comment on how we are thinking about the functional data as it is early in terms of the follow-up and the number, patient numbers.

Speaker #9: Is it early in terms of the in terms of follow-up and the number of patient numbers?

Speaker #6: Yeah. Thank you, Louise. I mean, I think primarily as you say, safety and the PD biomarkers will help us select the appropriate dose to carry forward into the phase 3 program.

James Richardson: Yeah. Thank you, Louise. I mean, I think primarily as you say, safety and the PD biomarkers will help us select the appropriate dose to carry forward into the Phase 3 program. Clearly we're gonna look at the functional data to understand what we think is supposed to be the most responsive outcome that help us select our and drive our design for our Phase 3. I would not, as Louise has said, expect any significant movement in the functional measures at six months in FSHD. In DM1, we would expect to see a signal in VHOT at this timeframe, but similarly for the other time function tests, it's very early in this disease state and in the size of cohorts to make any definitive conclusions.

Speaker #6: Clearly, we're going to look at the functional data to understand what we think is supposed to be the most responsive outcome that help us select our and drive our design for our phase 3.

Speaker #6: But I would not, as Louise said, expect any significant movement in the functional measures at six months in FSHD, in DM1. We would expect to see a signal in V hot at this time frame.

James Richardson: I would not, as Louise has said, expect any significant movement in the functional measures at six months in FSHD. In DM1, we would expect to see a signal in VHOT at this timeframe, but similarly for the other time function tests, it's very early in this disease state and in the size of cohorts to make any definitive conclusions.

Speaker #6: But similarly for the other times function tests, it's very early in this disease state and in this size of cohort to make any definitive conclusions.

Operator 2: Thank you. Our next question comes from Tazeen Ahmad from Bank of America. Please go ahead.

Operator: Thank you. Our next question comes from Tazeen Ahmad from Bank of America. Please go ahead.

Speaker #4: Thank you. Our next question comes from Taseen Ahmed from Bank of America. Please go ahead.

Tazeen Ahmad: Hi, guys. Thank you so much for taking my questions. A couple on FSHD and DM1, or rather one on those. How do you think about comparing the data that you've presented so far to products that have already shown data that might be, you know, further ahead in development? Specifically, how should we be thinking about what the right endpoints should be in order to look at? I know that there's a Novartis study that's being debated as to whether or not in DM1 the right endpoint is being used. I'd love to hear your thoughts on that. Secondly, as you talk to FDA about the shift to get the PMOs to permanent approval, can you talk about if there's been any change, any further change in who you talk to in the divisions that are relevant?

Speaker #10: Hi, guys. Thank you so much for taking my questions. A couple on FSHD and DM1, or rather one on those. How do you think about comparing the data that you've presented so far to products that have already shown data that might be further ahead in development?

Speaker #10: Specifically, how should we be thinking about what the right endpoints should be in order to look at? I know that there's a Novartis study that's being debated as to whether or not in DM1, the right endpoint is being used.

Tazeen Ahmad: I know that there's a Novartis study that's being debated as to whether or not in DM1 the right endpoint is being used. I'd love to hear your thoughts on that. Secondly, as you talk to FDA about the shift to get the PMOs to permanent approval, can you talk about if there's been any change, any further change in who you talk to in the divisions that are relevant? Just trying to get a sense of continuity of people that you might be engaging with. Thanks.

Speaker #10: So I'd love to hear your thoughts on that. And secondly, as you talk to FDA about the shift to get the PMOs to permanent approval, can you talk about if there's been any change, any further change in who you talk to in the divisions that are relevant?

Speaker #10: Just trying to get a sense of continuity of people that you might be engaging with. Thanks.

Tazeen Ahmad: Just trying to get a sense of continuity of people that you might be engaging with. Thanks.

Doug Ingram: Yeah. I would turn this over to Louise.

Speaker #3: Yeah. I would turn this over to Louise.

Speaker #9: Sure. Regarding the comparative data as we've as we mentioned in the disclosure call, in terms of what we're looking at and why we think that our program differentiates in terms of the amount of siRNA that we're getting into the muscle.

Louise Rodino-Klapac: Sure. Regarding the comparative data, as we've, as we mentioned in the disclosure call, in terms of what we're looking at and why we think that our program is differentiated in terms of the amount of siRNA that we're getting into the muscle, and that's using the alpha-v beta-6 targeting ligand. That truly, in terms of comparison, allows us the more you can get into the muscle, the more knockdown you can get, and that leads to better biomarkers and downstream functional markers. That's the way we're thinking about it with this early data is how can we get the highest level into the muscle so that we can have the most robust effect.

Speaker #9: And that's using the alpha V beta 6 targeting ligand. And so that truly in terms of comparison allows us the more you can get into the muscle, you're more knocked down.

Louise Rodino-Klapac: That truly, in terms of comparison, allows us the more you can get into the muscle, the more knockdown you can get, and that leads to better biomarkers and downstream functional markers. That's the way we're thinking about it with this early data is how can we get the highest level into the muscle so that we can have the most robust effect.

Speaker #9: You can get and that leads to better biomarkers and downstream functional markers. And so that's the way we're thinking about it with this early data is how can we get the highest level into the muscle so that we can have the most robust effect.

Speaker #9: We want to make sure that we are having a product that is giving us the best chance of efficacy and consequent function. So with regards to the functional outcomes, I'm going to turn that to Dr. Richardson in a second regarding DM1.

Louise Rodino-Klapac: We wanna make sure that we are having a product that is giving us the best chance of efficacy and consequent function. With regards to functional outcomes, I'm gonna turn that to Dr. Richardson in a second regarding DM1. On the PMOs, we're generally interacting with the same individuals in the agency that we have been for the PMO programs and for those sNDAs. James, perhaps you can comment on the DM1 function.

Speaker #9: On the PMOs, we're generally seeing the same, interacting with the same individuals in the agency that we have been for the PMO programs and for those SMDAs.

Speaker #9: But James, perhaps you can comment on the DM1 function.

Speaker #6: Yeah. I mean, I think we're seeing in the DM1 space what you commonly see as developers move into a disease space that we see an evolution in our understanding of the functional endpoints.

James Richardson: I mean, I think we're seeing in the DM1 space what you commonly see, as developers move into a disease space, that we see an evolution in our understanding of the functional endpoints, and we also see a greater investment in natural history data. We've seen recently with Nick Johnson's group publishing from the NM1 study, which is building on our understanding of the appropriate functional outcomes.

Speaker #6: And we also see a greater investment in natural history data and we've seen recently with the Nick Johnson's group publishing from the NDM1 study which is building on our understanding of the appropriate functional outcomes.

James Richardson: I think from our point of view as a sponsor, without commenting on other sponsors' program, we're at, you know, an advantage position of being able to take these natural history data internally, be able to speak to people like Nick Johnson and others and take their opinion on the primary endpoints, and then look at the functional data coming out of the cohorts we're seeing in Phase 1 and 2, put that together and reach our own decision on what we think is the most appropriate primary and secondary endpoints for our Phase 3 study, and obviously discuss that subsequently with the FDA.

Speaker #6: So I think from our points of view as a sponsor without calling another sponsor's program, we're an advantaged position of being able to take these natural history data internally, be able to speak to people like Nick Johnson and others and take their opinion on the primary endpoints.

Speaker #6: And then look at the functional data coming out of the cohorts we're seeing in phase 1 and 2, put that together and reach our own decision on what we think is the most appropriate primary and secondary endpoints for our phase 3 study and obviously discuss that subsequently with the FDA.

Speaker #4: Thank you. Our next question comes from Joe Swartz from Lee Rink Partners. Please go ahead.

Operator 2: Thank you. Our next question comes from Joe Schwartz from Leerink Partners. Please go ahead.

Operator: Thank you. Our next question comes from Joe Schwartz from Leerink Partners. Please go ahead.

Speaker #11: Thanks very much. I have a question on the siRNA programs, which will have data on later this year. First, is there any data preclinical or otherwise which suggests that deeper reductions in DUX4 expression would be expected to translate into greater clinical benefits for your approach in FSHD compared to competitor therapies with lower knockdown profiles?

Joseph Schwartz: Thanks very much. I have a question on the siRNA programs, which we'll have data on later this year. First, is there any data, preclinical or otherwise, which suggests that deeper reductions in DUX4 expression would be expected to translate into greater clinical benefits for your approach in FSHD compared to competitor therapies with lower knockdown profiles? In DM1, what specific magnitude of splicing correction would you wanna see in the upcoming MAD cohorts to prove that 1003's differentiated delivery can translate into a best-in-class clinical profile? Why wouldn't vHOT improve fairly quickly for your approach, since it has seemed to be fairly sensitive for other RNA approaches early on?

Speaker #11: And then in DM1, what specific magnitude of splicing correction would you want to see in the upcoming MAD cohorts to prove that 1,003 is differentiated delivery can translate into a best-in-class clinical profile?

Joseph Schwartz: In DM1, what specific magnitude of splicing correction would you wanna see in the upcoming MAD cohorts to prove that 1003's differentiated delivery can translate into a best-in-class clinical profile? Why wouldn't vHOT improve fairly quickly for your approach, since it has seemed to be fairly sensitive for other RNA approaches early on?

Speaker #11: And why wouldn't V hot improve fairly quickly for your approach since it has seemed to be fairly sensitive for other RNA approaches early on?

Doug Ingram: I'll turn this to Louise. I will note that I think James did suggest that vHOT may be an appropriate measure at in the MAD, but that the other longer-term functional endpoints require more time with the disease. With that, I'll just turn to Louise to answer both of those questions.

Speaker #3: I'll turn this to Louise. I will note that I think James did suggest that V hot may be an appropriate measure at in the MAD, but that the other longer-term functional endpoints require more time with the disease.

Speaker #3: Would that I'll just turn to Louise to answer both of those questions.

Speaker #9: Sure. On FSHD and the knockdown of DUX4, so if you recall, DUX4 is shouldn't be expressed at this time in late development. It's expressed early in development and then turned off.

Louise Rodino-Klapac: Sure. On FSHD and the knockdown of DUX4. If you'll recall, DUX4 shouldn't be expressed at this time in late development. It's expressed early in development, then turned off. It should not be expressed in adults. Any stochastic expression is toxic. Therefore, the greatest amount of knockdown gives you the greatest amount of benefit. If it's 100% knockdown would be fantastic. Obviously more knockdown is better, and that's what we're looking for. In terms of the target for DMPK knockdown, the answer is similar in terms of what we're looking for. We're looking for increases in muscle concentration leading to improvement in DMPK knockdown. We know that increased from preclinical data, correlation of DMPK knockdown correlates with functional improvement.

Speaker #9: It should not be expressed in adult. So any stochastic expression is toxic. And so therefore, the greatest amount of knockdown gives you the greatest amount of benefit.

Speaker #9: So if 100% knockdown would be fantastic. So obviously, more knockdown is better. And that's what we are what we're looking for. In terms of the target for DMPK knockdown, the answer is similar in terms of what we're looking for.

Louise Rodino-Klapac: Obviously more knockdown is better, and that's what we're looking for. In terms of the target for DMPK knockdown, the answer is similar in terms of what we're looking for. We're looking for increases in muscle concentration leading to improvement in DMPK knockdown. We know that increased from preclinical data, correlation of DMPK knockdown correlates with functional improvement.

Speaker #9: So we're looking for increases in muscle concentration leading to improvement in DMPK knockdown. We know that increased from preclinical data, correlation of DMPK knockdown correlates with functional improvement.

Speaker #9: And so that's what we are looking for. And based on the data to date, we've seen dose-dependent increase in muscle concentration. We'll be looking at the DMPK knockdown with our MAD data later in the year.

Louise Rodino-Klapac: That's what we are looking for. Based on the data to date, we've seen dose-dependent increase in muscle concentration. We'll be looking at the DMPK knockdown with our MAD data later in the year. Then, as Doug already mentioned on the VHOT, we certainly would expect earlier signals, as you said, for VHOT as an early sign of function. James, anything to add to that?

Speaker #9: And then as Doug already mentioned on the V hot, we're certainly would expect earlier signals as you said for V hot is an early sign of function.

Speaker #9: James, anything to add to that?

James Richardson: No, just completely agree. To distinguish between vHOT, as we said, which we do think we will see a signal with at this point, and other functional outcomes which will take longer.

Speaker #11: No, no. Just completely agree. Just to distinguish between V hot as we said, which we do think we will see a signal with at this point and other functional outcomes which will take longer.

Speaker #3: Thank you.

Joseph Schwartz: Thank you.

Speaker #4: Thank you. As a reminder, to ask a question, we ask that you please press star 11 on your telephone and wait for your name to be announced.

Operator 2: Thank you. As a reminder, to ask a question, we ask that you please press star 11 on your telephone and wait for your name to be announced. In the interest of time, we ask that you please limit yourself to one question. Our next question comes from Yigal Nochomovitz from Citigroup. Please go ahead.

Operator: Thank you. As a reminder, to ask a question, we ask that you please press star 11 on your telephone and wait for your name to be announced. In the interest of time, we ask that you please limit yourself to one question. Our next question comes from Yigal Nochomovitz from Citigroup. Please go ahead.

Speaker #4: In the interest of time, we ask that you please limit yourself to one question. Our next question comes from Yugal Noco Mavitz. From City Group, please go ahead.

Yigal Nochomovitz: Hi. Great. Thank you for taking the questions. I had a question on SRP-1001 and the dose response with respect to muscle concentration. When you doubled the dose, you got about a 6-fold super linear increase in the muscle concentration. I'm just curious if you could comment on that in terms of the mechanistic rationale and whether in the multiple ascending dose part of the study, you would also expect that kind of far exceeding linear dose proportionality at the higher doses. Thanks.

Speaker #12: Hi. Great. Thank you for taking the questions. I had a question on SRP 1001 and the dose response with respect to muscle concentration. When you doubled the dose, you got about a sixfold supralinear increase in muscle concentration.

Speaker #12: So I'm just curious if you could comment on that in terms of the mechanistic rationale and whether in the multiple sending dose part of the study, you would also expect that kind of far exceeding linear dose proportionality at the higher doses.

Speaker #12: Thanks.

Doug Ingram: Louise?

Speaker #3: Louise?

Speaker #9: Yeah. We certainly saw an increase there which wasn't linear. We would expect to see it start to plateau based on the preclinical data. We did see a jump from the lowest dose which wasn't unexpected based on preclinical data.

Louise Rodino-Klapac: Yeah, we certainly saw an increase there which wasn't linear. We would expect to see it start to plateau based on the preclinical data. We did see a jump from the lowest dose, which wasn't unexpected based on preclinical data, but we would see it plateau at the higher doses, but certainly continue to increase based on the preclinical data.

Speaker #9: But we would see it plateau at the higher doses, but certainly continue to increase based on the preclinical data.

Yigal Nochomovitz: Okay. Just one follow-up with regard to the study that you mentioned for sirolimus in the real world where you didn't see any evidence of liver enzyme elevations, could you just expand on that in the sense that where there were no grade 1 or any abnormalities in liver enzymes in that real-world study?

Speaker #12: Okay. And just one follow-up. With regard to the study that you mentioned for serolimus in the real world where you didn't see any evidence of liver enzyme elevations, could you just expand on that in the sense that where there were no grade 1 or any abnormalities in liver enzymes in that real-world study?

Doug Ingram: Sure. Louise?

Speaker #3: Sure. Louise?

Speaker #9: Yeah. So this is our real-world data where we can go back and survey the results from investigators and this is investigator called in terms of ALI.

Louise Rodino-Klapac: Yeah. So this is our real-world data where we can go back and survey the results from investigators, and this is in-investigator called in terms of ALI. We see that 25% are using it, and we're not seeing any evidence of ALI as determined by the investigator.

Speaker #9: So we see that 25% are using it and we're not seeing any evidence of ALI as determined by the investigator.

Yigal Nochomovitz: Okay. Thank you.

Speaker #12: Okay. Thank you.

Speaker #4: Thank you. Our next question comes from Ritu Barel. From TD Cowen, please go ahead.

Operator 2: Thank you. Our next question comes from Ritu Baral from TD Cowen. Please go ahead.

Operator: Thank you. Our next question comes from Ritu Baral from TD Cowen. Please go ahead.

Joshua Fleishman: Hi, team. This is Joshua Fleishman on for Ritu. Thanks for taking our question. I wanted to start by asking what is the current progress of cohort 8 recruitment, and are there any current timelines to enrollment completion? What FSHD functional data will be included in the H2 2026 data release? Lastly, what are Sarepta's plans for additional BD deals, thinking about both timelines to a deal and potential disease areas? Thank you.

Speaker #13: Hi, team. This is Joshua Fleischman on for Ritu. Thanks for taking our question. I wanted to start by asking what is the current progress of cohort 8 recruitment and are there any current timelines to enrollment completion?

Speaker #13: On the call, you guys also mentioned DM1 functional data, but what FSHD functional data will be included in the second half '26 data release?

Speaker #13: And then, lastly, what are Sarepta's plans for additional BD deals, thinking about both timelines to a deal and potential disease areas? Thank you.

Doug Ingram: On cohort 8, I'll just be quick on it and then turn the FSHD question to Louise. I'll touch on the BD. First on cohort 8, just so we're clear, we're right where we said we would be. We're dosing patients now, and our goal is to have the study complete and the data available by the end of the year. We're on track for that. With respect to business development, you know, the good news is that we're in a great place as an organization. We are not required to do business development for our future success. We have a very straightforward strategy right now. We've stabilized the business. We have 4 approved therapies. They are performing well, and we think they'll perform, as it relates to ELEVIDYS, even better with our new initiatives.

Speaker #3: So on cohort 8, I'll just be quick on it and then turn the FSHD question to Louise. I'll touch on the BD. First, on cohort 8, just so we're clear, we are right where we said we would be.

Speaker #3: We're dosing patients now and our goal is to have the study complete and the data available by the end of the year. And so that we're on track for that.

Speaker #3: With respect to business development, the good news is that we're in a great place as an organization. We are not required to do business development for our future success.

Doug Ingram: We are not required to do business development for our future success. We have a very straightforward strategy right now. We've stabilized the business. We have 4 approved therapies. They are performing well, and we think they'll perform, as it relates to ELEVIDYS, even better with our new initiatives.

Speaker #3: We have a very straightforward strategy right now. We've stabilized the business. We have four approved therapies. They are performing well and we think they'll perform as it relates to Levitis even better with our new initiatives.

Speaker #3: We are in a very strong financial position as an organization. We saw that we were profitable on a gap and non-gap basis, absent our arrowhead payments.

Doug Ingram: In a very strong financial position as an organization, we saw that we were profitable on a GAAP and non-GAAP basis. Absent our Arrowhead payments, we were cash flow positive. We'll be cash flow positive going forward, even in our base case assumption. That allows us to fully fund our siRNA pipeline, and we're really excited about this siRNA pipeline. You've seen the DM1 and FSHD data, early though it is, and we're excited to see that data later this year. We have Huntington's disease and IPF and multiple SCAs and six research programs, so we're in great shape there. With that said, we have a very active search and evaluation group that looks for transactions, and we'll continue that. We've got a very, very, proactive head of business development in Joe Zankas, and we're constantly looking for opportunities.

Speaker #3: We were cash flow positive. We'll be cash flow positive going forward even in our base case assumption that allows us to fully fund our SIRNA pipeline.

Speaker #3: And we're really excited about this SIRNA pipeline. You've seen the DM1 and FSHD data early though it is and we're excited to see that data later this year.

Doug Ingram: You've seen the DM1 and FSHD data, early though it is, and we're excited to see that data later this year. We have Huntington's disease and IPF and multiple SCAs and six research programs, so we're in great shape there. With that said, we have a very active search and evaluation group that looks for transactions, and we'll continue that.

Speaker #3: We have Huntington's disease and IPF and multiple scars and six research programs. So we're in great shape there. With that said, we have a very active search and evaluation for transactions and we'll continue that.

Speaker #3: And we've got a very, very proactive head of business development in Josankis. And we're constantly looking for opportunities. But we also have a very high bar for that.

Doug Ingram: We've got a very, very, proactive head of business development in Joe Zankas, and we're constantly looking for opportunities. You know, we also have a very high bar for that. That's where we are with that. With that, I will turn the FSHD question to Louise.

Doug Ingram: You know, we also have a very high bar for that. That's where we are with that. With that, I will turn the FSHD question to Louise.

Speaker #3: So that's where we are with that. And with that, I will turn the FSHD question to Louise.

Speaker #9: Sure. So the question was what functional outcomes are we looking for in FSHD? So James, do you want to comment?

Louise Rodino-Klapac: Sure. The question was, what functional outcomes are we looking for in FSHD? James, do you wanna comment?

Speaker #3: Yeah. Absolutely. I mean, I guess to reiterate the primary purpose of this study is to assess safety at PK and then the PD response and I think we particularly excited about also looking at circulating biomarkers at this point.

James Richardson: Yeah, absolutely. I mean, I guess to reiterate, the primary purpose of this study is to assess safety, PK, and then the PD response. I think we're particularly excited about also looking at circulating biomarkers at this point. We are obviously conducting functional assessments as part of the study, including reachable workspace, standard battery of timed function test, and strength testing that you would expect. This is a slowly progressive neuromuscular disease, and this is, you know, not a point in time where I would expect a very strong signal from a functional endpoint perspective. Clearly, if we do see something at this point, that would be a fantastic upside.

Speaker #3: We are obviously conducting functional assessments as part of the study including reachable workspace standard battery of times function test and strength testing that you would expect.

Speaker #3: This is a slowly progressive neuromuscular disease and this is not a point of time where I would expect a very strong signal from a functional endpoint perspective.

James Richardson: This is a slowly progressive neuromuscular disease, and this is, you know, not a point in time where I would expect a very strong signal from a functional endpoint perspective. Clearly, if we do see something at this point, that would be a fantastic upside. Anything what we do see in terms of responsiveness at the end, the various endpoints compared to one another will help us select the appropriate primary outcome for our phase 3 study.

Speaker #3: But clearly, if we do see something at this point, that would be a fantastic upside. And any signal we do see in terms of responsiveness of the various endpoints compared to one another will help us select the appropriate primary outcome for our phase 3 study.

James Richardson: Anything what we do see in terms of responsiveness at the end, the various endpoints compared to one another will help us select the appropriate primary outcome for our phase 3 study.

Speaker #13: And then out of reachable workspace time function tests and strength, which of those will be included in the second half 26 data release?

Joshua Fleishman: Out of reachable workspace, timed function tests, and strengths, which of those will be included in the H2 2026 data release?

Doug Ingram: James.

Speaker #3: James.

Louise Rodino-Klapac: James.

Speaker #9: James.

Speaker #3: Yeah. I mean, we will have data on all of these endpoints. I think that we'll be able to give a summary of the above.

James Richardson: Yeah. I mean, we will have data on all of these endpoints. I think that we'll be able to give a summary of the above. Again, as I said, I wouldn't be expecting a priority to see significant changes in any of them.

Speaker #3: But again, as I said, I wouldn't be expecting a priority to see significant changes in any of them.

Speaker #13: Thank you.

Joshua Fleishman: Thank you.

Speaker #4: Thank you. Our next question comes from David Huang. From Deutsche Bank, please go ahead.

Operator 2: Thank you. Our next question comes from David Huang from Deutsche Bank. Please go ahead.

Operator: Thank you. Our next question comes from David Huang from Deutsche Bank. Please go ahead.

Speaker #13: Hi there. Thanks for taking my questions. So, maybe one on Levitis. Do you have any sense of how many centers are currently offering Levitis, and maybe how does that compare to the number at the time of initial launch?

David Huang: Hi there. Thanks for taking my questions. Maybe one on ELEVIDYS. Do you have any sense of how many centers are currently offering ELEVIDYS, and maybe how does that compare to the number at the time of initial launch? Just quickly on cohort A, could you talk about the regulatory path after you have the data in hand? Would this be like submitting an sNDA, or just how should we think about the FDA interaction with cohort A data? Thank you.

Speaker #13: And then just quickly on cohort 8, could you talk about the regulatory path after you have the data in hand? With this be like submitting an SNDA or just how should we think about the FDA interaction with cohort data cohort 8 data?

Speaker #13: Thank you.

Speaker #3: I don't think we've have we given information on numbers of sites historically, Patrick?

Doug Ingram: I don't think Have we given information on numbers of sites historically, Patrick?

Speaker #13: I mean, we've talked about the number of sites that we've had just in the market. So we've got 75-plus sites that are available and offering up a Levitis.

Dallan Murray: I mean, we've talked about the number of sites that we've had just in the market. We've got, you know, 75 plus sites that are available and offering up ELEVIDYS, and that has not changed over time, so it's still consistent out there.

Patrick Moss: I mean, we've talked about the number of sites that we've had just in the market. We've got, you know, 75 plus sites that are available and offering up ELEVIDYS, and that has not changed over time, so it's still consistent out there.

Speaker #13: And that has not changed over time, so it's still consistent out there.

Doug Ingram: We have also seen, again, in the green shoots category, we have seen sites that with some of the dislocation of last year, it paused, that have picked up and commenced submitting start forms again. That's a positive green shoot as well. With that, I'll turn the second part of the question over to Louise.

Speaker #3: We have also seen again in the green shoots category we have seen sites that with some of the dislocation of last year it paused that have picked up and the commenced submitting STAR forms again.

Speaker #3: So that's a positive green shoot as well. And with that, I'll turn the second part of the question over to Louise.

Speaker #9: Sure. Once we have the cohort 8 data in hand, we'll meet with the agency and then we'll determine the path forward after that. So we've committed to share the data with them as soon as we have it and that's we will meet with them and discuss?

Louise Rodino-Klapac: Sure. Once we have the cohort A data in hand, we'll meet with the agency, and then we'll determine the path forward after that. Louise committed to share the data with them as soon as we have it, and that's we will meet with them and discuss.

Doug Ingram: You know, we have to have a meeting with the FDA to figure out the exact regulatory process one has to go through. In the event that the sirolimus data proves to be, change the risk-benefit of this therapy significantly in favor of the non-ambulatory patient, we would hope that the agency would work with us to get this therapy offered to non-ambulatory patients as fast as possible for the obvious reason. Duchenne generally is a disease that doesn't permit waiting. It's just not a therapy that can wait. Every day these kids are damaged, and no group of patients know that better than the non-ambulatory patients who have a desperate need for intervention to save what muscle that they have remaining after they've become non-ambulatory and have progressed the disease.

Speaker #3: Certainly, our hope—we have to have a meeting with the FDA to figure out the exact regulatory process one has to go through. But in the event that the role of this data proves to be—to change the risk-benefit of this therapy significantly in favor of the non-ambulatory patient, we would hope that the agency would work with us to get this therapy offered to non-ambulatory patients as fast as possible, for the obvious reason. Duchenne, generally, is a disease that doesn't permit waiting.

Doug Ingram: Duchenne generally is a disease that doesn't permit waiting. It's just not a therapy that can wait. Every day these kids are damaged, and no group of patients know that better than the non-ambulatory patients who have a desperate need for intervention to save what muscle that they have remaining after they've become non-ambulatory and have progressed the disease.

Speaker #3: It's just not a therapy that can wait every day. These kids are damaged, and no group of patients know that better than the non-ambulatory patients, who have a desperate need for intervention to save what muscle they have remaining after they've become non-ambulatory and have progressed through the disease.

Doug Ingram: With that said, we've got to meet with the agency, as Louise has said, but it is our very hope that the FDA will work creatively with us to get the indication back in the label so we can begin to have thoughtful conversations with physicians and families and offer this therapy to them.

Speaker #3: So with that said, we've got to meet with the agency as Louise has said, but it is our very hope that the FDA will work creatively with us to get the indication back in the label so we can begin to have thoughtful conversations with physicians and families and offer this therapy to them.

Speaker #4: Thank you. Our next question comes from Andy Chen. From Wolf Research, please go ahead.

Operator 2: Thank you. Our next question comes from Andy Chen from Wolfe Research. Please go ahead.

Operator: Thank you. Our next question comes from Andy Chen from Wolfe Research. Please go ahead.

Speaker #14: Hey, this is Brandon for Andy. Thanks for taking the question. So you noted that Levitis or the business has stabilized. Does a return to growth assume only access in the ambulatory setting or does that growth assume that you're able to resume treatment in non-AM patients?

[Analyst] (Wolfe Research): Hey, this is Brandon for Andy. Thanks for taking the question. You noted that ELEVIDYS or the business has stabilized. Does a return to growth assume only access in the ambulatory setting, or does that growth assume that you're able to resume treatment in non-ambo patients? Thank you.

Speaker #14: Thank you.

Speaker #3: Yeah. When we talk about return to growth, we're talking about in the ambulatory population right now. Obviously, with the success of Serolimus and Cohort 8, if it is successful—and we certainly have conviction that it will be—and getting that back in the label, then of course we'll have to re-forecast the post-step.

Doug Ingram: Yeah. When we talk about return to growth, we're talking about in the ambulatory population right now. Obviously, with the success of solinumab and cohort A, if it is successful, and we certainly have conviction that it will be, and getting that back in the label, then of course, we'll have to reforecast the post-AB. When we talk about our initiatives right now and the return to growth, we're talking about the ambulatory population because obviously non-ambulatory is not in our label. We would never promote to non-ambulatory as it is not in our label. We're talking about ambulatory.

Speaker #3: But when we talk about our initiatives right now and the return to growth, we're talking about the ambulatory population, because obviously non-ambulatory is not in our label.

Speaker #3: We would never promote to non-ambulatory as it is not in our label. So we're talking about ambulatory.

Speaker #4: Thank you. Our next question comes from Jaya Wang from Miziho. Please go ahead.

Operator 2: Thank you. Our next question comes from Jiayue Wang from Mizuho. Please go ahead.

Operator: Thank you. Our next question comes from Jiayue Wang from Mizuho. Please go ahead.

Jiayue Wang: Hello, this is Jiayue Wang on behalf of Vamil Divan. I guess I just want to ask about, you know, the 20% you mentioned the sites that are already using sirolimus. I guess, what's holding the remaining 75% from adopting this regimen, assuming it's really gonna help reduce the ALI risk? Do you think it's because you're concerned about any immunosuppressing side effects, or they're just not familiar with the regimen?

Jiayi Wang: Hello, this is Jiayue Wang on behalf of Vamil Divan. I guess I just want to ask about, you know, the 20% you mentioned the sites that are already using sirolimus. I guess, what's holding the remaining 75% from adopting this regimen, assuming it's really gonna help reduce the ALI risk? Do you think it's because you're concerned about any immunosuppressing side effects, or they're just not familiar with the regimen?

Speaker #15: Hello. This is Jaya Wang on behalf of Warrior. I guess I just want to ask about the 20% you mentioned the sites that are already using Serolimus.

Speaker #15: I guess what's holding the remaining 75% from adopting this regimen assuming it's good, it's going to help reduce the ALI risk? Do you think it's because you're concerned about any immunosuppressing side effects or they're just not familiar with the regimen?

Doug Ingram: Our best guess would be that education and information has to flow between physicians and thought leaders and the like. One of the things that we are not permitted to do is play a proactive role in that. We don't have solinumab as our label, we can't promote to it. You know, the simple approach, which would be to go and share data with physicians, is something that we are not permitted to do. The spontaneous use of solinumab in 25% of the physicians comes entirely from physician practice and from sharing of best practices among physicians.

Speaker #3: My best guess would be that the education and information has to flow between physicians and thought leaders and the like. One of the things that we are not permitted to do is play a proactive role in that.

Speaker #3: We don't have Serolimus on our label. We can't promote to it. So the simple approach, which would be to go and share data with physicians, is something that we are not permitted to do.

Speaker #3: So the spontaneous use of Serolimus in 25% of the physicians comes entirely from physician practice and from sharing a best practices among physicians. I would anticipate that it would grow, but we can't play a role in that growth.

Doug Ingram: I would anticipate that it would grow, but we can't play a role in that growth, and so that will mute that growth until we get the cohort A data out, we get the ability to get this in the label for non-ambulatory patients in particular.

Speaker #3: And so that will mute that growth until we get the cohort 8 data out and we get the ability to get this in the label for non-ambulatory patients in particular.

Speaker #4: Thank you. Our next question comes from William Pinkering. From Bernstein, please go ahead.

Operator 2: Thank you. Our next question comes from William Pickering from Bernstein. Please go ahead.

Operator: Thank you. Our next question comes from William Pickering from Bernstein. Please go ahead.

Speaker #16: Hi. Thank you for taking my question. For DM1 and FSHD, are you seeing any difference in half-life across the two drugs and any implications that might have on dosing interval in a phase 3 trial?

William Pickering: Hi, thank you for taking my question. For DM1 and FSHD, are you seeing any difference in half-life across the two drugs and any implications that might have on dosing interval in a phase 3 trial? We read in the protocol documents that the FSHD half-life is expected to be twice as long as DM1, 5 weeks versus 2 and a half weeks. Hence the question. Thank you.

Speaker #16: We read in the protocol documents that the FSHD half-life is expected to be twice as long as DM1—five weeks versus two and a half weeks—since the question.

Speaker #16: Thank you.

Doug Ingram: Louise?

Speaker #3: Louise?

Louise Rodino-Klapac: Sure. We're seeing similarities, because we're using the same peptide across the programs. With respect to the timing interval, we are looking at 10 weeks versus 12 weeks in terms of the dosing interval. James, perhaps you'd like to comment on how we're analyzing that in the protocol.

Speaker #9: Sure. We're seeing similarities because we're using the same peptide across the programs. With respect to the timing interval, we are looking at 10 weeks versus 12 weeks in terms of the dosing interval.

Speaker #9: James, perhaps you'd like to comment on how we're analyzing that in the protocol.

Speaker #3: Yeah, no. Just to reiterate what you've said, really, Louise, that we're not expecting a differential half-life between the two products, given that they are chemically very similar.

James Richardson: Yeah, no, just to reiterate what you said, really, Louise, that we're not expecting differential half-life between the two products, given that they are chemically very similar, same ligand and just different siRNA cargo. And the clinical data that we've seen is largely supportive of our preclinical data, but that we do think that we can probably drive a little bit better efficacy even than we've seen already by reducing dosing interval to 10 weeks. We will see those results as part of the cohort 5, DM1, and the subsequent FSHD cohort 7.

Speaker #3: Same ligand and just different siRNA cargo and the clinical data that we've seen is largely supportive of our preclinical data. But then we do think that we can probably drive a little bit better efficacy even though we've seen already by reducing dosing interval to 10 weeks.

Speaker #3: We will see those results. It's part of the cohort 5 DM1 and the subsequent FSHD cohort 7.

Speaker #4: Thank you. Our next question goes to Mitchell Kapoor from HC Wainwright. Please go ahead.

Operator 2: Thank you. Our next question goes to Mitchell Kapoor from H.C. Wainwright. Please go ahead.

Operator: Thank you. Our next question goes to Mitchell Kapoor from H.C. Wainwright. Please go ahead.

[Analyst] (H.C. Wainwright): Hi. Thanks for taking our question. It is Jade on for Mitchell. Just on ELEVIDYS, could you comment on the recent FDA Adverse Event Reporting System-listed fatality due to cardiac and breathing issues, which was reported three weeks ago? If so, how much time elapsed between the patient receiving ELEVIDYS and this incident? How old was the patient? What was their ambulatory status, and do you have any information on the specifics of their DMD mutation?

Speaker #17: Hi. Thanks for taking our question. It's Jade on for Mitchell. So just on Levitis, could you comment on the recent FDA adverse event reporting system listed fatality due to cardiac and breathing issues, which was reported three weeks ago?

Speaker #17: And if so, how much time has elapsed between the patient receiving Levitis and this incident? How old is the patient? What was their ambulatory status?

Speaker #17: And do you have any information on the specifics of their DMD mutation?

Doug Ingram: Louise.

Speaker #3: Louise.

Louise Rodino-Klapac: Yep. That was a commercially treated patient treated with ELEVIDYS, nearly 14 months post-treatment. Based on the available information, we analyzed it, and it was deemed to be unrelated to ELEVIDYS treatment.

Speaker #9: Yeah. So that was a commercially treated patient treated with Levitis nearly 14 months post-treatment. And so based on the available information, we analyzed it and it was deemed to be unrelated to Levitis treatment.

Speaker #4: Thank you. Our next question comes from Brian Scorney from Baird. Please go ahead.

Operator 2: Thank you. Our next question comes from Brian Skorney from Baird. Please go ahead.

Operator: Thank you. Our next question comes from Brian Skorney from Baird. Please go ahead.

[Analyst] (Baird): Hi, this is Luke on for Brian. Thanks for taking the question. Just wanted to get an update on your efforts at addressing AAV immunity, maybe to treat lower titer patients or eventual retreatment. Thanks.

Speaker #18: Hi. This is Luke on for Brian. Thanks for taking the question. Just wanted to get an update on your efforts at addressing AAV immunity.

Speaker #18: Maybe to treat lower titer patients or eventual retreatment. Thanks.

Doug Ingram: Louise.

Speaker #3: Louise.

Speaker #9: Sure. So we've this data will be presented. So we have preliminary data from our apheresis study and some preliminary data from the study with Hansa as well.

Louise Rodino-Klapac: Sure. This data will be presented, so we have preliminary data from our apheresis study and some preliminary data from the study with Hans as well, indicating there is some ability to reduce titers in patients that are antibody positive. This is something that we've paused those studies for now, but something that we will certainly look to in the future and that we do see the potential to lower antibodies and have an effect, but it would need more clinical study.

Speaker #9: Indicating there is some ability to reduce titers in patients that have antibody-positive so this is something that we've positive studies for now, but something that we will certainly look to in the future and that we do see the potential to lower antibodies and have an effect, but it would need more clinical study.

Speaker #4: Thank you. This does conclude the question and answer session. I will now turn it back over to Doug Ingram for a closing remarks.

Operator 2: Thank you. This does conclude the question and answer session. I will now turn it back over to Doug Ingram for closing remarks.

Operator: Thank you. This does conclude the question and answer session. I will now turn it back over to Doug Ingram for closing remarks.

Speaker #3: Yeah. Thank you for that, and thank you all for joining us this evening and for your very thoughtful questions. We are, as I said before, tracking through 2026 with an enormous amount of opportunity in front of us.

Doug Ingram: Yeah, thank you for that. Thank you all for joining us this evening and for your very thoughtful questions. You know, we are, as I said before, tracking through 2026 with an enormous amount of opportunity in front of us, and we have a very straightforward strategy to capitalize on that opportunity. We have four, in my view, tremendous therapies, and our goal is to maximize the opportunity with those four approved therapies, first and foremost for the Duchenne patients who benefit from them, but also for our investors. The second, of course, is our very strong financial position. You will have seen that we were profitable on a GAAP and a non-GAAP basis. We have over $750 million in cash and investments. We were cash flow positive, if you exclude the Arrowhead payment.

Speaker #3: And we have a very straightforward strategy to capitalize on that opportunity. We have four, in my view, tremendous therapies, and our goal is to maximize the opportunity with those four approved therapies.

Doug Ingram: We have four, in my view, tremendous therapies, and our goal is to maximize the opportunity with those four approved therapies, first and foremost for the Duchenne patients who benefit from them, but also for our investors. The second, of course, is our very strong financial position. You will have seen that we were profitable on a GAAP and a non-GAAP basis. We have over $750 million in cash and investments. We were cash flow positive, if you exclude the Arrowhead payment.

Speaker #3: First and foremost, for the Duchenne patients who benefit from them, but also for our investors. The second, of course, is our very strong financial position.

Speaker #3: You will have seen that we were profitable on a gap and a non-gap basis. We have over $750 million in cash and investments we were cash flow positive.

Speaker #3: If you exclude the arrowhead payment, we'll be cash flow positive on a go-forward basis even in our basest case with respect to our approved therapies.

Doug Ingram: We'll be cash flow positive on a go-forward basis, even in our basest case with respect to our approved therapies. All of that allows us to fund this very exciting siRNA pipeline and to do it very independently. We've got a lot there, DM1, FSHD, Huntington's disease, IPF, SCA2, SCA1, SCA3, the research programs. We're really excited about them. We've seen some great data on DM1 and FSHD to lead the way, and we're very excited at the second half of this year to share with you more robust data still on both of those programs, which we think could potentially be best in class. The fourth pillar of our strategy is our employees. We have a really dedicated group of very seasoned expert folks who, say what you will, have shown nothing but exceptional execution over these many years.

Speaker #3: And all of that allows us to fund this very exciting siRNA pipeline and to do it very independently. We've got a lot there. DM1, FSHD, Huntington's disease, IPF, SHA-2, SHA-1, SHA-3, the research programs.

Speaker #3: We're really excited about them. We've seen some great data on DM1 and FSHD to lead the way and we're very excited that the second half of this year to share with you a more robust data still on both of those programs which we think could potentially be best in class.

Doug Ingram: We've seen some great data on DM1 and FSHD to lead the way, and we're very excited at the second half of this year to share with you more robust data still on both of those programs, which we think could potentially be best in class. The fourth pillar of our strategy is our employees. We have a really dedicated group of very seasoned expert folks who, say what you will, have shown nothing but exceptional execution over these many years.

Speaker #3: And the fourth pillar of our strategy is our employees. We have a really dedicated group of very seasoned expert folks who say what you will, have shown nothing but exceptional execution over these many years.

Speaker #3: And I think taking those four pillars into account, we have one of the most exciting opportunities in front of us that we've had as an organization in our long history.

Doug Ingram: I think taking those four pillars into account, we have one of the most exciting opportunities in front of us than we've had as an organization in our long history. I look forward over the course of this year to sharing more information on our execution and some of our milestones. With that, have a lovely evening, everybody.

Speaker #3: And I look forward, over the course of this year, to sharing more information on our execution and some of our milestones. And with that, have a lovely evening, everybody.

Operator 2: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Operator: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.