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spk09: Good afternoon, and welcome to the Startup to Therapeutics first quarter 2023 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Mary Jenkins, Associate Director, Investor Relations. Please go ahead.
spk20: Thank you, Shannon, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the first quarter of 2023. The press release is available on our website at Sarepta.com, and our 10-key was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estefan, Dallin Murray, and Dr. Louise Rodino-Playback. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond SRAPTA's control. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations, and trading prices for SRAPTA's common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 1022, filed with the SEC, as well as the company's other SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. And now I'll turn the call over to our President and CEO, Doug Ingram, to provide an overview of our recent progress. Doug.
spk02: Thank you, Mary. Good afternoon, and thank you for joining Sarepta Therapeutics' first quarter 2023 financial results conference call. Perhaps you will see this as a break from the past, but I intend to keep my remarks this evening brief. As you know, in a mere 10 days from now, we will be attending and presenting at the FDA Advisory Panel for SRP 9001, our gene therapy intended for the treatment of Duchenne muscular dystrophy. We believe that the primary areas of discussion at the advisory committee will be these, whether the totality of evidence supports the conclusion But SRP9001 dystrophin protein at the levels expressed by this therapy is reasonably likely to predict clinical benefit. The totality of the evidence will include natural history, the preclinical data, biomarker results, and the functional results from our clinical trials. The panel will also address the risk-benefit analysis associated with the administration of SRP9001 for the treatment of ambulatory patients with BMD, in the context of accelerated approval. And finally, an assessment of the ability to bring to conclusion, embark, or study 301, the proposed post-marketing confirmatory trial to support the accelerated approval of SRP 9001 in the event that accelerated approval is granted. The team is well-prepared and excited to share with the advisory committee the wealth of compelling evidence supporting the conclusion that SRP9001-distributed protein and the amounts expressed by that therapy is reasonably likely to predict clinical death. So to set expectations for this call, we intend to discuss first-quarter performance, and Dr. Luis Rodino-Klapek will provide a pipeline update. But to respect the process and in light of how soon the meeting will take place. We will not discuss or entertain questions on regulatory matters pertaining to SRP 9001 or the upcoming advisory committee meeting until it's concluded on May 12th. Moving now to the quarter, I am very pleased to announce another strong quarter of performance. First quarter total revenue came in at $253.5 million. Net product revenue came in at $231.5 million. That's a 23% increase over the same quarter of the prior year and exceeding analyst consensus. It is this very patient-oriented execution that we intend to apply to SRP 9001 if approved. We continue to progress our important post-marketing commitments for our three approved TMO therapies. We have already completed 11 of our post-marketing commitments. With respect to Essence, which is our two-year blinded placebo-controlled study for Vionis and Imondas, we were fully enrolled last year, and that trial is proceeding. With respect to Mission, which is our dose-ranging post-marketing commitment for Exondas, part two of that study is substantially enrolled and progressing. As relates to SRP 9001, in addition to preparing for the May 12 advisory committee and prosecuting the BLA with the May 29 PDUFA date in mind, we are ensuring that we will be prepared to successfully launch 9001 and serve the community if and when approved. By now, we have successfully concluded all FDA inspections. That includes three GMP inspections and two GCP inspections. With our partner, Catalan, we are producing material to successfully launch 9001 upon approval, and we are finalizing our launch readiness work. And we are finalizing our plans to commence the studies necessary to expand the 9001 label to the broadest population supported by the science, including our commencement of our non-ambulatory study in vision, or study 303, and our multiple studies to explore the removal of neutralizing antibodies to RH74. Beyond that, we've been advancing our broader pipeline, and Dr. Rodino-Clayfat will provide an update on our pipeline momentarily. Now, the coming weeks and months are monumentally important to the patients that we serve. As I have said many times by now, we stand at a bellwether moment. with the greatest evidence-based hope yet in history to bring a better life to families today living with and unfortunately today dying from Duchenne muscular dystrophy. And we are also well aware that this BLA stands as a bellwether test for gene therapy itself and for the ability to effectively lean in and use the tools available to us to translate groundbreaking genetic science to medicine that can extend and improve patients' lives now, not merely at some theoretical point in the future. We feel an enormous obligation to the patients that we serve, and our every decision and action is taken and done with that obligation front of mind. And with that, let me turn the call over to our head of R&D and chief scientific officer, Dr. Luis Rodino-Kleipach. Luis.
spk11: Thanks Doug and good afternoon. As we look forward to the weeks and months ahead, we remain resolute in our conviction and our values to follow the science and present the objective evidence that supports SRP 9001's ability to change the trajectory of Duchenne Muscular Dystrophy. Our goal with SRP 9001 is to alter the course of this fatal disease by treating the underlying cause of Duchenne with a one-time gene therapy that delivers functional dystrophis to the muscle. Sirepta has generated the most compelling preclinical, biomarker, and clinical functional results to date, more than any other gene therapy in development for Duchenne. We've been able to demonstrate, based on the strong scientific underpinning of our constructs, that early SRP9001 data provided read-through for a positive clinical experience with the therapy. After years of research, we identified an optimal gene cassette able to retain the most critical, protective, and functional elements and fit inside the AAV, thereby enabling its delivery. This gene cassette was packaged into our AAV of choice, RH74, and we chose MHTK7 as our promoter. The early data showed robust expression across skeletal, diaphragm, and cardiac muscles. And as a result of that expression, as well as the dystrophin protein demonstrating functional benefits, we saw clinical benefit at the target dose in patients with Duchenne. I will explain in a bit more detail. Individuals with Duchenne don't have a functioning dystrophin-associated protein complex, or DAPC. Understanding this, when we inserted a functional dystrophin protein, we saw upregulation of the DAPC in animal models. More specifically, we saw an almost one-for-one upregulation of the DAPC when there was expression of the SRP9001 dystrophin, confirming the protective properties of the protein. Further, we saw significant reduction in crazy kinase, or CK. CK is an enzyme associated with muscle damage. The reduction of CK provided further proof that SRP9001 was reasonably likely to predict clinical benefits. Since 2018, and across multiple studies, it does the largest number of descent patients. more than any other gene therapy in development for this disease, and the clinical results have surpassed our expectations. In summary, SRP9001 demonstrated robust expression of dystrophin, far above what literature would suggest is necessary to be protective of the muscle. All of it is properly localized at the muscle membrane, or sarcolemma, where it acts as a shock absorber. We developed a cell-based potency assay that showed that SRP9001 is active, functional, and protective at the muscle membrane. And as an animal model, with robust expression of SRP9001, we saw significant reduction in CK. Finally, expression of SRP9001 in patients leads to upregulation of the DAPC. In addition to all of this compelling evidence, we were able to show functional benefits versus what natural history would predict on MSAA for the North Star Ambulatory Assessment. This is our primary functional endpoint. We observed benefit across one, two, and four-year time points. Based on the fatality of the data, we believe that SRP9001 qualifies as a disease-modifying agent as the levels of dystrophin expressed are reasonably likely to predict clinical benefit in patients with DHS. Now moving to lung or lumbar dysphilia, or LGMD. We remain committed to advancing our LGMD portfolio across a variety of subtypes. I look forward to providing updates on these important programs in the months ahead. Currently, we are making excellent progress on Journey, our LGMD natural history study, and in Boyazine, our phase one study evaluating SRT9003 for the treatment of limb girdle muscular dystrophy type 2E in ambulant adult patients and non-ambulant patients. using clinical process SRP 9003 material. Combined with positive expression and functional data shared from our initial study, SRP 9003-101, we believe the data from Voyaging will give us insights into a broader patient population. Our next milestones for Voyaging include completing enrollment in the second half of the year and beginning our Phase III study using commercially representative process materials later in the year. Finally, we are on track to commence a systemic pilot study for SRP6004 dual-vector RH74-mediated gene therapy to treat LGMG2B, characterized by the absence of the protein Dysferilin. Turning now to the progress we've made with our RNA platform. We were pleased to complete enrollment in the first quarter of 2023 for a momentum study for SRP5051. and we remain on track to announce data from the study in the back half of 2023. In regards to our post-marketing studies for the PMOs, as mentioned last quarter, we completed enrollment in the ESSIS trial for post-marketing requirements for Gola Durson and Casper and continue to make good progress with our mission study, which is on track to be fully enrolled this year. In closing, we are looking forward to the Advisory Committee meeting on Friday, May 12th as it will provide us the opportunity to share the science and the data in support of RP9001. I'd like to take this opportunity to thank our disruptive team who have been diligently working these past months. I'll now turn the call over to Dallin for an update on our commercial activities. Dallin?
spk02: Thank you, Louise, and good afternoon. In the first quarter of 2023, the team executed on our core RNA business and delivered another strong performance across all three of our RNA-based PMO therapies. As Doug mentioned, we delivered $231.5 million in net product revenue in the first quarter, representing well over 20% growth over the first quarter of 2022. Notably, Q1 of 2023 exceeded our expectations and represented the most successful first quarter in the history of our market therapies. In Q1, we have historically seen an impact in the U.S. due to the expected Due to the extraordinary efforts of the team in navigating those access headwinds, we saw higher than expected revenue in the U.S. in the first quarter. Each year our team is prepared for these challenges and I'm very proud of their steadfast commitment and sense of urgency with which they serve the Duchenne community. They know that every minute matters for each one of the patients we serve. Total ex-U.S. net product revenue in the first quarter was roughly $31 million. This represented a decrease over the prior quarter, which was expected and fully reflected in our annual guidance forecast. As discussed on last quarter's call, we expect to see continued fluctuations in XUS ordering patterns quarter to quarter. Overall, the fundamentals of the business coming out of Q1 are completely in line with what we expected at this point in the year. and we reiterate our full-year guidance of greater than $925 million in net product revenue for our TMO therapies. This guidance reflects all of the factors that we navigate and monitor in supporting patients globally. With its increasing global revenue base, we will continue to see fluctuations in net product revenue from quarter to quarter. Importantly as well, in the U.S. market, we have now hit a mature phase with all three products, and as such, We expect more modest growth and new patient starts in the coming quarters for the chemo business. Turning now to individual net product revenues for the first quarter of 2023 for our three approved RNA-based chemo therapies. Exondys 51 totaled $132.6 million, representing more than 13% growth over Q1 of 2022. For Biondys 53, sales were $33 million, growing roughly 18% over the first quarter of 2022. And for Mondas 45, sales totaled $65.9 million, representing more than 50% growth versus Q1 of 2022.
spk05: In addition to the strong performance in our core business, the team has been simultaneously preparing and laying the groundwork for the SRP 9001 launch.
spk02: The full team is in place, being rigorously trained as we speak, and I can say with confidence that they are ready to execute if SRP 9001 is approved. This launch will represent a historic moment not only for Sarepta, but for the Duchenne community and for genetic medicine. The level of enthusiasm and confidence of the team is at an all-time high, and they are eager for this opportunity to demonstrate what we are capable of and what would be our fourth launch into the cashier market. Over the past several months, our field teams and disruptive leadership have meaningfully engaged with roughly 75 sites of care on strategic and operational site readiness matters. These important interactions will ensure that the sites are ready to efficiently, safely provide SRP 9001 gene therapy to patients as soon as possible. We've also been working closely with sites provide education and training, as well as ensuring that they have the necessary equipment and resources to deliver the therapy to patients. In addition to site readiness, we know from our experience with PMO therapies that access and reimbursement are crucial to successfully delivering SRP 9001 to patients. We're committed to ensuring that our gene therapy for Duchenne is accessible to all patients who need it, and we recognize that meaningfully engaging with payers is a critical part of achieving that goal. We found that the payers are asking important questions pertaining to the SRP 9001 clinical data, potential patient population size, launch timing, and infusion sites. We are encouraged by the positive response we have received thus far and are pleased at the progress we have made in engaging with both commercial and Medicaid payers. If approved, 9001 will bring forth the potentially for far too long. The team has done a tremendous job preparing for what will be the largest gene therapy launch to date if SRP9001 is approved. I'd like to take this opportunity to personally thank the whole organization who are not only executing to support 30% of patients on our PMO therapies today, but who have also risen to the occasion so that we can be ready as a team for this paradigm-shifting moment. And now I'll turn the call over to Ian Espen for an update on our financials.
spk21: Ian. Thanks, Dallin, and hello all. This afternoon's financial results press release provided details for the first quarter of 2023 on a non-GAAP basis as well as a GAAP basis. Please refer to the press release available on Threbs' website for a full reconciliation of GAAP to non-GAAP financial results. For the three months ended March 31st, 2023, The company recorded total revenues of $253.5 million, which consists of net product revenues and collaboration revenues, compared to revenues of $210.8 million for the same period of 2022, an increase of $42.7 million. Net product revenue for the first quarter of 2023 from our PMO Exxon Skipping franchise was $231.5 million, compared to $188.8 million for the same period of 2022. The increase in net product revenue primarily reflects increasing demands of our products. In each of the quarters ended March 31st, 2023 and 2022, we recognized $22 million of collaboration revenue, which relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $20.3 million for the first quarter of 2023 compared to $17.7 million for the same period of 2022. On a gap basis, we reported a net loss of $516.8 million or $5.86 and $105 million or $1.20 per basic and diluted share for the first quarter of 2023 and 2022 respectively. This change is primarily due to the loss on debt extinguishment of $387.3 million A non-cash expense incurred in the three months ended March 31, 2023, with no similar activity for the same period of 2022. We reported a non-GAAP net loss of $85.5 million, or 97 cents per basic and diluted share, in the first quarter of 2023 compared to a non-GAAP net loss of $48.6 million, or 56 cents for basic and diluted share in the first quarter of 2022. In the first quarter of 2023, we recorded approximately $35 million in cost of sales compared to $31.4 million in the same period of 2022. The increase in cost of sales is primarily due to an increasing demand for our products, as well as write-off of certain batches of our products not meeting the quality specifications for the three months ended March 31st, 2023, with no similar activity in the same period of 2022, partially offset by a decrease in the royalty payments during the three months ended March 31st, 2023, due to changes in the Biomarin royalty terms. On a GAAP basis, we recorded $245.7 million and $194.3 million in R&D expenses for the first quarter of 2023 and 2022 respectively, a year-over-year increase of $51.4 million. The increase is primarily due to an increase in our manufacturing expenses. On a non-GAAP basis, R&D expenses were $220.7 million for the first quarter of 2023, compared to $173.2 million for the same period of 2022, an increase of $47.5 million. Now, turning to SG&A, on a GAAP basis, we recorded approximately $110.7 million and $71.8 million for expenses for the first quarters of 2023 and 2022, respectively, an increase of $38.9 million. The increase was driven primarily by an increase in professional service expenses to prepare for a potential launch of SRP 9001. On a non-GAAP basis, the SG&A expenses were $83.3 million for the first quarter of 2023, compared to $53.2 million for the same period of 2022, an increase of $30.1 million. We expect that our R&D and SG&A expense will increase next quarter as we continue to prepare for a potential launch of FRP 9001. On a GAAP basis, we recorded $12.7 million in other income, net for the first quarter of 2023, compared to $17.3 million in other expense net for the same period of 2022. The change is primarily due to an increase in interest income and a creation of an investment discount through the investment mix of our investment portfolio, as well as a reduction of interest expense incurred as a result of the repayment of our December 2019 term loan during 2022. In the first quarter, we exchanged a portion of our 2024 notes with an aggregate principal value of $313.5 million and issued approximately 4.5 million shares of our common stock. We accounted for the exchange of the debt extinguishment, recognizing the difference of the fair value of the shares of common stock transferred on the exchange date and the net carrying amount of the extinguished debt as a loss of $387.3 million, inclusive of the 69.5 6.9 million of third-party debt conversion costs. Just again, to reiterate, this is a non-cash expense. We had approximately $1.9 billion in cash, cash equivalents and investments and long-term restricted cash as of March 31st, 2023. We remain well-capitalized to execute on our goals for the year and support our transition to profitability, assuming approval of SRP 9001. And with that, I'll turn the call back over for Doug to start the Q&A. Doug?
spk02: Thank you, Ann. Now, before we begin the Q&A, let me reiterate that in light of and in respect of the impending FDA Advisory Committee, we will not be entertaining questions on the regulatory process for the upcoming Advisory Committee meeting for SRP 9001 tonight. I do look forward to discussing those matters with you once the May 12 Advisory Committee meeting has concluded. And with that, Shannon, let's open the line for questions.
spk09: Thank you. As a reminder, to ask a question, please 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. We ask that you please limit yourself to one question each. Please stand by while we compile the Q&A roster. Our first question comes from the line of Colin Bristow with UBS. Your line is now open.
spk18: Hey, good afternoon, and a huge congrats for being on the cusp of this approval. So on your supply at launch, can you talk about the capacity and ability to meet demand? I'm just asking in light of the fact of, or in light of some of the comments from your partner around a slower than expected production ramp at the Maryland site. And then just sort of within this, in terms of patient logistics, can you talk about your expectations for the initial timelines from a physician prescribing 9001 to a patient receiving a therapy given the need for antibody testing and other potential neighboring requirements. Thank you.
spk02: Yeah, thank you very much for that, Colin. So on the first part of the question, as we've said, our goal, and we will meet that goal, is to be able to fully launch and supply the community, assuming that we are able to get an approval. Of course, our goal right now is to get an approval at the PDUFA date, which is May 29. We have seen the comments made by Catalan, so we're very clear that those comments and the issues that they were discussing do not play any role in or have any effect on our plans or our production plans in this land, so we should be in good shape there. With respect to the launch, our goal is to launch this therapy as rapidly as possible, and I think we have proven ourselves over the last few years very capable of doing exactly that. With that said, The 9001, this gene therapy, has its own particular complications. You've got to, for instance, in addition to not simply having a start form for that, you've got to do a number of other things, including getting a pre-infusion antibody test that's sufficiently close to the infusion. And then, of course, typically you have to work through access and reimbursement and codes and the like. So from a planning perspective, while we'll be launching this rapidly, one should anticipate really seeing a quarter or two before we really start seeing a significant ramp.
spk09: Thank you. Our next question comes from the line of Gina Wang with Barclays. Your line is now open. Thank you. I also wanted to ask one commercial question.
spk08: What is your estimate patient numbers for initial indication in the U.S.? And also regarding the manufacturing capacity, any major expansion you need to do in order to supply patient for the initial indication in the U.S.? ?
spk02: Let me answer the second part first. The answer is no. There are no major capital expenditures or additional expansion that is required to launch this therapy and serve the community at launch. On the addressable patient population, I can give you the broadest of strokes. They're somewhere in the 12,000, 10,000 to 15,000 patients in the United States. Our goal, again, assuming that we are approved at a PDUFA date, the goal is to serve all ambulatory patients. The ambulant patients are about 50%, so it's roughly 50% ambulant, 50% non-ambulant. We'd be covering the ambulant population. And then there will be, of course, patients that would be excluded because they have pre-existing neutralizing antibodies. Based on our most recent data, that's about 13 and a half percent of patients would be currently excluded on the basis of having pre-existing antibodies to binding antibodies to RH74. And then there is a subset of patients who would have some of these earlier mutations in a range. in a region that may have a risk of an innate immune response, that'll be less than 5% of patients. So that remainder is the addressable patient population at launch. Now, with that said, I'm going to go ahead and give you our plans for the future as well because, you know, very soon we're going to be starting a number of studies in an effort to fully build out the addressable patient population to the extent that science allows us to. We're pretty confident about that so that the biggest opportunity obviously is to get to the non-ambulant patients. That is extraordinarily important to us and to them. Non-ambulant patients don't have the luxury of time, so we've got to move as fast as possible. We are starting our study 303 for the non-ambulant population very soon. The goal is to have sufficient safety and expression data from that study to seek an update to our label early next year. to get non-ambulant patients in the label so we can begin to dose them. And we're starting as well two additional studies for two alternative approaches to clear pre-existing neutralizing antibodies. And if we're capable of doing that, then that would also bring back into frame for the ability to dose patients that are currently excluded because they have um they have something that reacts and is a pre-existing neutralizing antibody that's an extraordinarily important issue as well you know oftentimes you'll when you talk to patients and their families parents will say that the worst day of their lives was getting the news that their child had to shed muscular dystrophy and that the second worst day of their lives was finding out that their kids are one of these you know, rare kids, about 13% of kids who have test positive for pre-existing neutralizing antibodies. So we need to move fast to try to solve that issue for them. Thank you for those questions, Judy.
spk09: Thank you. Our next question comes from the line of Brian Abrams with RBC Capital Markets. Your line is now open.
spk17: Hi, good afternoon. Thanks for taking my question. Can you expand on what you've been hearing in your preliminary conversations with payers? Is your sense that they would be open to paying for 9001 under accelerated approval or would prefer to wait for full approval? And should we expect sort of a similar mix as with the ExxonSkippers with regards to the proportion of patients initially receiving access? Thanks.
spk02: I'll just take the broadest of strokes, and, Dallin, you can follow up if I'm missing anything. First of all, the conversations have gone very well. We've been in dialogue with Payers regarding the potential for SRP 9001 for many years now, and I can, you know, I think going back as far as mid-2018, Dallin, myself, and others were meeting with payers that our access and reimbursement team have been meeting with payers significantly. The amount of evidence that we have that supports the conclusion that 9001 is a beneficial therapy for kids and it's going to do a lot of good, is very very robust so these discussions have gone very well with that said let me be very clear of course you know as is the case with rare disease therapies right now Aspen reimbursement is a complicated challenging thing the good news for all of us is that 9001 is going to be launched by Sarepta and you know at the risk of sounding a bit immodest in my view there is no team better than this Sarepta team to serve these patients, work intelligently with payers, and gain access for this therapy for these kids as rapidly as possible. And I am quite confident that's going to occur, and quite confident payers are going to do the right thing. And certainly, I believe that they're going to do the right thing in the context of accelerated approval, which
spk03: one given the data that we have in front of us.
spk02: Yeah, and I think Doug's really covered it. There are, as we said in the opening remarks, really constructive, great dialogue going on with the payers. And right now, we're prior to launch. They're asking great questions about the timing and the patient population. And I think more specifically, Colin, to your question, regardless of when the policies are put in place, the payers are going to look at each patient on a case-by-case basis. And so the team, as Doug said, is ready to manage that right from day one. We're an experienced and battle-hardened team.
spk09: Thank you. Our next question comes from the line of Judah Farmer with Credit Suisse. Your line is now open.
spk23: Hi, thanks for taking the question. Another one sort of from the payer angle. Any idea if there could be kind of a difference in RAMP for patients that are, you know, I guess naive to RNA therapies versus those that are on the PMOs gaining access? And then any indications around potential value-based payments given, like you said, this is going to be the biggest gene therapy launch ever. So, from a cost perspective, could there be any, I guess, interesting dynamics to the time of payments? Thank you.
spk02: Yeah, as it relates to the first question, I don't think there's going to be a difference in RAP. I think this is a, you know, for those who are amenable to this therapy, which at launch we are successful in our BLA, would be ambulant patients excluding a very narrow range of mutations who are RH74 negative. I think this therapy is going to be extraordinarily important and I think that there's going to be an equal ramp whether you're naive or not naive to the PMOs. And in fact, we have dosed patients that have been on the PMO and remained on the PMO post-dose, so we have good data that supports that. On value-based agreements and the like, I'm not at a place right now where we're going to discuss those issues yet. I will tell you that we have done an enormous amount of work, about which I am extremely impressed and proud, to frame the value proposition and the pharmacoeconomic model for one-time therapies like SRP 9001. And our approach to the payer community, pricing, value-based agreements, and the like, will be inside the frame of that value framework itself. And the one thing I will tell you, qualitatively at least, and then we'll at the right time talk quantitatively, is that the value that this therapy will bring to Duchenne patients is going to be significantly greater than the cost of this therapy to the healthcare system, which is what we all should want.
spk09: Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.
spk15: Good afternoon. Thanks for taking my question. With regard to manufacturing, can you just provide us with some details of where you stand on inventory as you look to this launch and then the breadth of your manufacturing relationships in order to address the supply that's required over at least the first year or second or first two years of launch here?
spk02: Sure. So we're building inventory as we speak to be ready for a launch. So that's obviously an ongoing activity with Catalyst. It's a high priority for us and fortunately also a high priority for Catalyst. So we're in great shape there. And that's great for launch and we're in great shape there. If you look down the road, longer term, of course, we also have our relationship with Thermo Fisher. We have an entire standalone site with Thermo Fisher. One of the decisions we made in connection with our PLA submission was not to try to get two sites approved at the same time. The complexity associated with that would have created a significant risk of delay, and I think as we've said a million times, delay is not something that patients with Duchenne can have. So what we will do post-launch is work with the division to get the Thermo Fisher site up and running and qualified as well. The good news is at launch, our site with Catalan and our suites with Catalan is sufficient to launch the therapy and serve the community.
spk09: Thank you. Our next question comes from the line of Gil Blum with Needham & Company. Your line is now open.
spk04: Good afternoon, everyone, and thanks for taking our question. Doug, in your earlier comments, you mentioned that the company is planning to start some of the other studies, including non-ambulatory patients and the clearing of antibody studies. What about planning a study in younger patients? I'm assuming that, you know, as with all gene therapy, younger is usually better. Thank you.
spk02: Yeah, well, let me comment on that last piece first. It is extremely important that we get to younger patients as well. I want to be very clear. But I want to be also clear that from our perspective, there is no place across this journey of Duchenne where the intervention of a therapy like 9001 that can restore functional dystrophin to patients won't be beneficial. There's no trial that's beyond value. That's important to remember. So if you're 19 years old and you've been in a wheelchair for five years, you are as valuable to us as a very young child. So that's why we're very focused on the non-ambulance side, but we are focused on the very young as well. We've already dosed kids that are down to three years old. Luis, you might want to comment on other plans we have that dose much younger children as well.
spk11: Yes, we've got three-year-olds in our 103 study, and then we're also planning an additional study along with Roche to just even younger than the three-year-olds, and that will begin in the short term.
spk09: Thank you. Our next question comes from the line of Kazeen Ahmad with Bank of America. Your line is now open.
spk14: Hi, good afternoon. Thanks for taking my questions. I guess, Ian, I just wanted to clarify a comment that you made regarding write-offs of certain batches of the company's products that weren't meeting quality specs. Which products were they? Can you share, and have you resolved that issue? And then also maybe just to follow up on comments that Doug made regarding inspections being completed, can you also confirm whether or not FDA has any comments on the inspection, and if they have, have they been resolved? Thanks.
spk21: Sure, I'll take the first one first. That was regarding the PMO. This is just part of our normal manufacturing process. If you look back over several quarters, that's happened. So, you know, this is just something that's part of the normal manufacturing process. And, you know, there's some batches that don't meet specs and we have to write it off. But nothing to be concerned and to be expected to continue to go forth.
spk02: And then as relates to the second question, all of the inspections are completed and any of the observations have been entirely satisfied.
spk03: So we're in great shape from an inspection perspective.
spk09: Thank you. Our next question comes from the line of Danielle Brill with Raymond James. Your line is now open.
spk10: Hi, guys. Thanks so much. I actually have a couple of questions on Embark. I'm curious. what percent of patients have completed that trial, just trying to gauge how back-end loaded enrollment was. And then also, how frequently do you measure NSA and how are missing data imputed? Thank you.
spk03: The last part, the first part on the completion.
spk11: study was completely enrolled last fall, so we can expect the one-year endpoint to close out this fall with the study report early next year. In terms of the NSA, these are the primary endpoints. The NSA is at one year, but we measure it at intervals prior to that, certainly part of the one-year endpoint.
spk03: We'll update on the staff plan when we
spk09: Thank you. Our next question comes from the line of Mike Oles with Morgan Stanley. Your line is now open.
spk19: Hey, guys. Thanks for taking the question. Just another one on the 9001 launch. Do you have a sense of how many patients might want to switch from some of your PMO therapies, and how do you plan to manage that? Thanks.
spk02: So let me say two things. First, we don't anticipate at launch a significant impact on our current PMO revenue, just from a revenue perspective. In the long run, one should assume some significant cannibalization. It won't happen early on. To the extent that a patient wants to switch from PMO to have access to the gene therapy, we will embrace that. and be excited for them.
spk09: Thank you. Our next question comes from the line of Nina with Citi. Your line is now open.
spk13: Hey, guys. Thanks for taking my question. I just wanted to go back to some of the questions on the payer conversation so far. Can you just Tell us a little bit about whether any of your conversations so far have suggested that payers may wait to actually issue coverage determinations until they see the Embark data, and if so, how they may think about, you know, kind of restrictions and the coverage policy post-Embark. Thanks.
spk02: We intend to launch this therapy and work with payers to get access to this therapy immediately. I would remind folks that we have... Three approved therapies today, Xondas, Vionis, and Imondas, all of them were approved via the accelerated approval pathway. And the team has done, in my opinion, an absolutely brilliant job of working with payers to ensure rapid access for patients who are amenable to those three therapies. We'll take that same execution focus. We will apply it to 9001. And we anticipate that payers are going to respond well, given the robustness of our data, and that kids are going to have access immediately.
spk09: Thank you. Our next question comes from the line of Tim Lugo with William Blair. Your line is now open.
spk07: Yeah, thanks for taking the question, and best of luck, obviously. Can you talk about how you view capital deployments in a post-approval world. You know, you obviously have a lot of studies we've talked about. You have to build the label out, you also have to build the girdle, and I believe your pipeline is described as 40 compounds deep. So that sounds like a lot of R&D, and I'd love to hear your thoughts around that, which is, you know, probably money extremely well spent. But maybe if that also influences your thoughts around pricing of 901.
spk02: Well, I'm going to say two things. I want to turn this to Ian, who can comment about capital deployment in a more general sense. First, we are going to significantly focus on research and development and the like, of course, and we will continue to do that deep into the future. That notwithstanding, our current plans, assuming that we're approved, and our plans come to fruition, would have us being profitable next year. As it relates to the pricing for 9001, the pricing of 9001 will occur in the context of the pharmacoeconomic models we use to ensure that the value is appropriate for that therapy and that, as I've said before, that the value brought to the patients and their lives from this therapy is much greater than the cost of the healthcare system. But beyond that, Ian, do you want to comment on the capital deployment plans?
spk21: Yeah, no, I think you're exactly right. We're obviously going to continue to invest in R&D, but we're also going to be focused on profitability and follow metrics that will guide that and ensure returns for shareholders. But obviously, as you know, investing in R&D is going to lead to continued growth, and we're going to be focused on moving programs forward that have high probability of success based on the data which we generate. We also think the market conditions right now lend itself to being in a position to partner or acquire technologies that we think are scientific breakthroughs as we continue to build out our pipeline. So we're going to be very consistent with the approach that we've used previously. So obviously, put us in a position where we're one of the leading emerging biotech companies, then we're not going to stray from that.
spk09: Thank you. Our next question comes from the line of Kristen Koska with Cantor Fitzgerald. Your line is now open.
spk01: Hi, good afternoon, and best wishes to your team this month. Can you talk about the latest as it relates to looking at some of the ways you're looking to address pretreatments for those with preexisting antibodies to AAV? I saw that you're presenting with HANSA some preclinical data at ASGCT. The agenda was literally just released about an hour ago, so can you talk about some of those efforts, please?
spk02: Yeah, so there are two approaches, and there's more to say beyond this, but we've Broadly, there are two approaches that we're taking right now. One is, of course, with our partner HANSA and then Lifidase to cleave and therefore remove antibodies that would stand in the way of a child getting 9001. And the other is using aparesis to clear antibodies. Is there anything else?
spk11: We have strong preclinical data with both approaches. And as Doug mentioned, we're planning to start that we can serve the entire community.
spk09: Thank you. Our next question comes from Harthash Singh with Oppenheimer and Company. Your line is now open.
spk06: Great. Thank you. Thanks for the question. I just got a quick question on the voyaging study in LGMD. You know, assuming you get that phase three started with commercially representative material by the end of the year, How much insight will the Phase II and the Phase III give you into the other LGMDs? I mean, could you move faster? You know, could regulators be amenable to looking at them holistically versus, you know, very separately? And then how easy will it be to scale the manufacturing for all the other LGMDs? Thank you for the question.
spk02: Yeah, let me say broadly, you know, once seen public presentations from Dr. Peter Marks, you'll know that his ultimate goal, his long-term goal, is to get to a place where you can build therapy upon therapy, and particularly if you're using the same tacit, which we are in connection with the LGMDs, that you should be learning from each of them. being able to greatly shorten the timelines. And I think a form of that will occur with our limb girdles. But we are in the early days of limb girdles, so it won't be fully formed like that as we're moving through. We do get significant value and learning from each of these programs that we apply to. The next one, the limb girdles are benefiting enormously from 9001. most of our limb girdles, the majority at least, use the same promoter as 9001, and they all use the same caps at R874. So there is this virtuous cycle where we ought to be able to start moving faster and faster over time. It's going to take some time to do that. I would say, finally, I'd say on manufacturing, we definitely benefit from prior knowledge as we move forward, but each of these programs is its own program and requires some bespoke elements, including, for instance, much of the assay work. Some of the assay work can be very translatable, but a lot of this assay work is bespoke from program to program, and so that does take some time, and it will take some time with respect to some of these referrals.
spk09: Thank you. Our next question comes from the line of Debjit Chattopadhyay with Guggenheim. Your line is now open.
spk12: Hey, good afternoon, and thanks for taking my question. I just wanted to clarify one of the comments you made in your prepared remarks. You brought up Embark in the context of the adcom. Could you clarify and frame that question again?
spk02: Oh, I think, oh, yes. One of the issues that we just need to discuss at the advisory committee is that EMBARQ, which is our proposed confirmatory trial, obviously needs to complete and complete on time. And so one of the obviously reasonable questions one would pose is, you know, are you confident that if we give you an approval now on an accelerated basis that EMBARQ will in fact complete, that there won't be something about the approval of this therapy that would somehow influence the ability to successfully complete EMBARQ. As you know, Embark actually was fully enrolled as of last year, September of last year. So I think relative to other accelerated approval therapies, we are in a particularly advantageous, brilliant position with respect to the completion of our confirmatory trial.
spk09: Thank you. Our next question comes from the line of Joseph Schwartz with the SDV Securities. Your line is now open.
spk25: Hi, everyone. Thanks very much. Since we're so close to the panel, I was wondering if you have seen the FDA's briefing documents at this point and if you can give us your gestalt about their tone so that we can be more prepared for what to expect.
spk02: Yeah, as I said, We are 10 days away and counting from the advisory committee meeting. I want to be very clear about this. What we're all doing together right now is extraordinarily serious. It's important to us and it's important to our investors, but it is vastly more serious and important to the patients living with Duchenne muscular dystrophy. This is literally a potential life or death issue for them. So in regard to that, we are going to be mission-driven. And what that means to us is we're going to stay very focused on prosecuting our BLA, preparing for our adcom. We're not going to discuss the adcom or the briefing books or the regulatory process right now. We're going to get ready for, and in my humble opinion, we're going to do a brilliant job. Sorry, I'm putting a lot of pressure on you, Luis. We're going to do a brilliant job of presenting what I believe to be the wealth of evidence that supports that, the conclusion that 9001 and the amounts made by this therapy is reasonably likely to predict clinical benefits. So, and why did that, and with all respect and apologies for not answering your question, I'm not going to answer your questions on the regulatory process through the advisory committee until after May 12th. And then we're going to all come together and I'm going to be thrilled to talk about all of these issues with you.
spk09: Thank you. Our next question comes from the line of Zishu with Barenburg. Your line is now open.
spk22: Good afternoon. Thanks for taking my questions. Maybe going back to the manufacturing ramp, so I've seen some expectations on how many patients do you plan to treat for 9001? And secondly, on 9003, a link growth program, And obviously commented the phase three will start in the second half of the year. Is there any possibility for accelerated approval pathway for this program as well? Thanks very much.
spk02: So answering the second question first, ultimately we will propose a form of accelerated approval for 9003. This is an ultra, ultra rare disease. 9-0-0-3 makes the negative protein, the absence of which is the sole and exclusive cause of the demise and ultimately the death of patients that suffer I admit in the phase three that we're starting, we are going to propose an accelerated approval pathway. As to the first question, I'm not going to provide numbers on numbers of patients other than to say our goal is to treat every patient that's amenable to this therapy as quickly as reasonably possible. And so we're preparing ourselves to have a robust launch.
spk09: Thank you. Our next question comes from the line of Gavin Clark-Gartner with Evercore ISI. Your line is now open.
spk26: Hey, thanks for fitting me in. Just to follow up on the LGMD2E question, what's your base case assumption for the Phase III primary endpoint and trial design? When will you align with the FDA on this?
spk02: So, the short answer is we're going to start that study before the end of this year. We will align with the agency on that along the way. We've got work to do there. Obviously, we've been prioritizing 9001 right now. The functional endpoint would likely be a form of NSA, which I think is called NSA-D, if I'm not mistaken. It's been adapted for Lynn Kirtle. But we'll obviously also be looking at expression and safety with respect to 9003. Thank you.
spk09: Our next question comes from the line of Ritu Baral with TD Cowan. Your line is now open.
spk16: Hi, guys. This is Vandana for Ritu today. Can you confirm the timing of MBARC top line data? Have there been any changes to that? And then any updates to your long-term revenue guidance of $4 billion in 2025? How will you be revising this if 9001 is approved this month?
spk02: Our forecasts assume approval this month. So I'm sorry, what the first question was?
spk04: Embark readout.
spk02: Yeah, there's been no change in the Embark readout. Embark was fully enrolled as of September of last year. It's going swimmingly. It's obviously blinded, so it's being executed swimmingly, and we anticipate top line really at the end of this year or early next year.
spk09: Thank you. Our next question comes from the line of Brian Scorney with Baird. Your line is now open.
spk24: Hey, good afternoon. Thanks for taking my question. I guess kind of jumping off on some of the questions around the ability to successfully conclude and embark that you mentioned, can you just talk to us about study conduct and is there any risk that an accelerated approval could put study conduct at risk? You know, I think you said before that most U.S. patients have actually had their last visit. So can you just kind of review what you would say to someone questioning whether or not you're going to be able to successfully maintain study conduct on and off once you have commercially available manager 01 under AA? There's no risk. Zero risk.
spk02: A study was enrolled, fully enrolled, September of last year. All of the kids in part one of the study have received their doses. The kids on crossover are being dosed even as we speak. Any kid that has yet to be dosed will be dosed in the next few months, the maximum. So the march is going very well. We'll read out on time. Regardless,
spk09: Thank you. Our next question comes from the line of Anupam Rama with J.P. Morgan. Your line is now open.
spk05: Hey, guys. Thanks so much for taking the question. On SRP 9003, could we see any portions of the voyaging data this year maybe starting ahead of the commercial material phase three? I think that we are only committed to, like, enrollment completion but not data itself potentially. But just wondering if we could see some.
spk02: I'm sorry for jumping in there. It's not clear whether we'd have data this year, so we'll update you later in the year on that.
spk09: Thank you. I would now like to hand the conference back over to Doug Ingram for closing remarks.
spk02: Well, thank you all very much for joining us this evening, and thank you for your questions. And thank you for accommodating my request that we not talk about the regulatory process or the advisory committee. As much as you want to ask questions about that and as much as I want to answer questions about that, if I'm going to be honest and direct with you, I look forward to, obviously we all look forward to May 12th. That advisory committee meeting is an unbelievably important moment for patients living with Duchenne. I'm extraordinarily confident in the ability And then I look forward to coming back together thereafter and discussing where we are and the paths forward. So thank you all. Have a lovely evening.
spk09: This concludes today's conference call. Thank you for participating. You may now disconnect.
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