Q1 2023 Sarepta Therapeutics Inc Earnings Call

Speaker 1: Good afternoon and welcome to the start of the therapeutics first quarter, twenty, twenty three earnings call at this time. All participants are in a listening 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 one one on your telephone.

Speaker 1: You will then hear an automated message advising your hand is raised to withdraw your question. Please press star one one 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. Thank you. Shannon and thank you all for joining today's call.

Speaker 2: Earlier this afternoon, we released our financial results for the first quarter of 2023. The press release is available on our website at SREpta.com and our 10Q is filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Esteban, Dallin Murray, and Dr. Louise Rodino-Claypack. After our formal remarks, we'll open the call for Q&A.

Speaker 2: 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 surreptice control. Actual results could materially differ from these forward-looking statements, and any such risks could predispose those who have also arrived at the U.S. moment of

Speaker 2: can materials inadvertently affect the business, the results of operations, and trading prices for disruptive common stock.

Speaker 2: For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on form type 2 files with the SEC, as well as the company's other SEC filings.

Speaker 2: The company does not undertake any obligations publicly updated for looking statements, including any financial projections provided today based on subsequent events or circumstances.

Speaker 2: And now I'll turn the call over to our President and CEO , Doug Ingram, to provide an overview of our recent progress. Doug.

Speaker 3: Thank you, Mary. Good afternoon and thank you for joining Soretta Therapeutics first quarter 2023 financial results conference call.

Speaker 3: Perhaps you will see this is a break from the past, but I intend to keep my remarks this evening brief. As you know, in a mere ten days from now, we will be attending and presenting at the FDA advisory panel for S. R. P. nine zero zero one. Our gene therapy intended for the treatment of Duchenne muscular dystrophy.

Speaker 3: We believe that the primary areas of discussion at the advisory committee will be these. Whether the totality of evidence supports the conclusion that SRP9001-disrophin protein at the levels expressed by this therapy is reasonably likely to predict clinical medicine. The totality of the evidence will include natural history.

Speaker 3: the preclinical data, biomarker results, and the functional results from our clinical trials.

Speaker 3: The panel will also address the risk benefit analysis associated with the administration of SRP 9001 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.

Speaker 3: or study 301, the proposed post-marketing confirmatory trials support the accelerated approval of SRP 9001 in the event that accelerated approval is granted.

Speaker 3: The team is well prepared and excited to share with the advisory committee the wealth of compelling evidence supporting the conclusion that SRV 9001 distrofit protein and the amounts expressed by that therapy is reasonably likely to predict clinical death.

Speaker 3: So to set expectations for this call, we intend to discuss first quarter performance and Dr. Luis Rodino Clayback 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 the

Speaker 3: at $253.5 million. Next 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.

Speaker 3: It is this very patient-oriented execution that we intend to apply to SRP 9001 if approved.

Speaker 3: We continue to progress our important post-marketing commitments for our three approved PMO 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 Bionis and Amondis.

Speaker 3: We were fully enrolled last year and that trial is proceeding. With respect to mission, which is our dose ranging post-marketing commitment for exodis, part two of that study is substantially enrolled and progressive. As relates to SRP 9001 in addition to preparing for the May 12th.

Speaker 3: 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.

Speaker 3: That includes three GMP inspections.

Speaker 3: and two GCP inspections.

Speaker 3: With our partner, Kablet, we are producing material to successfully launch 9001 upon approval, and we are finalizing our launch readiness work.

Speaker 3: And we are finalizing our plans to commence the studies necessary to expand the 9001 label to the broadest population supported by the science.

Speaker 3: 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 RA-74.

Speaker 3: Beyond that, we've been advancing our broader pipeline and Dr. Rideenal Clayton will provide an update on our pipeline momentarily.

Speaker 3: Now, the coming weeks and months are monumentally important to the patients that we serve.

Speaker 3: As I have said many times by now, we stand at a bellwether moment.

Speaker 3: with the greatest evidence-based hope yet in history to bring a better life to families today living with.

Speaker 3: And unfortunately today died from.

Speaker 3: today dying from Duchenne muscular dystrophy.

Speaker 3: And we are also well aware that this VLA stands and they build weather tests for gene therapy itself and for the ability to effectively lean in and use the tools available to us to translate ground-breaking genetic science to medicine.

Speaker 3: that can extend and improve patients' lives now, not merely at some theoretical point.

Speaker 3: was now, not merely at some theoretical point in the future.

Speaker 3: We feel an enormous obligation to the patients that we serve and our every decision in action is taken and done with that obligation front-up line. And with that, let me turn the call over to our Head of R&D and Chief Scientific Officer, Dr. Luis Rino playback.

Speaker 3: enormous obligation to the patients that we serve and our every decision in action is taken and done with that obligation front of line. And with that, let me turn the call over to our head of R&D and Chief Scientific Officer, Dr. Luis Rodino Plentak. The recent.

Speaker 4: Thanks, Doug, and good afternoon. As we look forward to the week and months ahead.

Speaker 4: We remain resolute in our conviction and our values to follow the science and present the objective evidence of support. At SRP 900, their lost abilities change the trajectories of the shed muscular dystrophy.

Speaker 4: Our goal with SRV900W 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 dystrophy to the muscle.

Speaker 4: Zeraptos generated the most compelling pre-clinical, biomarker, and clinical functional results to date, more than any other gene therapy in development for T-Shet.

Speaker 4: We have been able to demonstrate based on the strong, scientific, other pinning of our constructs that early SRP 9001 data provided breakthrough for our positive clinical experience with the therapy.

Speaker 4: 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 MHCK7 as our promoter.

Speaker 4: 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 a clinical benefit at the target dose in patients' positions.

Speaker 4: I will explain in a bit more detail. Individuals who shed don't have a functioning distroven associated smoking complex for doxy.

Speaker 4: Understanding this, when we inserted a functional sterile infrosy, we saw up-regulation of the ducts being in animal models.

Speaker 4: More specifically, we saw an almost one-for-one of regulation of the DAPC.

Speaker 4: When there was expression of the SR-39001 destruction.

Speaker 4: confirming the protective properties of the protein. Further, we saw significant reduction in increase in kinase for CKID.

Speaker 4: BK is an enzyme associated with muscle damage. The reduction of BK provided further proof that SRP900 long is reasonably likely to predict clinical benefits.

Speaker 4: Since 2018 and across multiple studies, it does the largest number of dishemp patients.

Speaker 4: more than any other gene therapy and development for the disease. And the clinical results have surpassed our exercise patients.

Speaker 4: In summary, SRP9001 demonstrated robust expression of destruction, far above what literature would suggest is necessary to be protected on the

Speaker 4: All of it is properly localized to the bustle membrane or stark dilemma, or to act as a shock absorber.

Speaker 4: We developed a cell-based telepsi that shows that SRP900 wanted active, functional, and protective at the muscle memory.

Speaker 4: And as an animal model, with robust expression of SRP9001, it's thus significant reduction of decay.

Speaker 4: Finally, expression of SRP9001 in patients leads to upregulation of the DAPC.

Speaker 4: In addition to all of this compelling evidence, you're able to show functional benefits versus what natural history will predict on NSAA for the North Star and military assessment. This is our primary functional endpoint.

Speaker 4: We observe benefit across one, two, and four year trial points.

Speaker 4: Based on the totality of the data, we believe that SRV-90001 follows by a disease modified by aging. At the levels of dystrophinic stress are reasonably likely to predict clinical benefit and patients with your share.

Speaker 4: Now moving to loan girl hospital district, your LGMD.

Speaker 4: We remain committed to advancing our LGMD portfolio in the process of a variety of sub-times. I look forward to providing updates on these important programs in the month ahead.

Speaker 4: Currently, we're making excellent progress on Journey, our LGMD natural history study, and in Voyaging, our phase one study evaluating SRT9003 for the treatment of limb girdle muscular dystrophy type 2E in ambulance adult patients and non-ambulance patients.

Speaker 4: using clinical process SRT9003 material.

Speaker 4: Combined with positive expression functional data shared from our initial study, at SRT 90030101, we will leave the data for voyaging to give us insights into a broader patient population.

Speaker 4: study using commercially representative process materials later in the year.

Speaker 4: Finally, we are attracted to commencement of systemic pilot studies for SRP.

Speaker 4: 6-0-0, 6-0-0 support, dual vector, R-8-74-88 and gene therapy to treat LG and GCC, characterized by the absence of the protein to swirl it.

Speaker 4: Turning down to the progress we made with our RNA platform.

Speaker 4: We're pleased to complete enrollment in the first quarter of 2023 for a moment in study for SRP 5051. And we remain on track to announce the date of study in the back half of 2023.

Speaker 4: In regards to our post-marketing studies for the piano, the mentioned last quarter, we completed enrollment in the ESF's trials for post-marketing requirements for Gola Durson that has been.

Speaker 4: Thank you. I continue to make good progress with our mission study to contract the fully enrolled this year.

Speaker 4: In closing, we're looking forward to the advisory committee on Friday, May 12th, as it will provide us the opportunity to share the clients and the data and support.

Speaker 4: of Rp9-001. I'd like to say this opportunity to thank our surrounding team for diligently working these past months.

Speaker 3: And that will turn the call over to down for an update on our commercial activities. Down? Thank you, Louise, and good afternoon. In the first quarter of 2023, the team executed on our core RNA business to deliver another strong performance across all three of our RNA-based KMO days. As Doug mentioned, we delivered 231.5 million dollars in nap product revenue.

Speaker 3: We want to be of historic leasting an impact that you must do to be expected in church changes at the beginning of each year.

Speaker 3: Due to the extraordinary efforts of the team in navigating those access headwinds, we saw higher than expected revenue in the US in the first quarter. Each of our teams is prepared for each challenge, and I'm very proud of their steadfast commitment and sense of urgency with which they serve to shed community.

Speaker 3: They know that every minute matters for each one of those patients be served.

Speaker 3: Total XUS net product revenue in the first quarter was roughly 31 million dollars. 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 the last quarter.

Speaker 3: ?, it's upgraded to 925 million event products celebrity?? for animal authorities.

Speaker 3: This guidance reflects all of the factors that we navigate and monitor in supporting patients for our needs. It is increasing global revenue-based through a continued disease fluctuations in that not exported in order.

Speaker 3: Importantly as well in the US market, we have now hit mature phase with all three products and as such we expect more modest growth in new patient starts in the coming order which we will continue on business.

Speaker 3: Turning now into individual net product revenues for the first quarter of 2023.

Speaker 3: For our three approved eras. Izy here on advanced eras, as well as outline the area where this field will be submitted. It is very complex.

Speaker 3: Ex on this 51 totally 132.6Million dollars. Representing more than 13% of Q1 of 2022.

Speaker 3: For bi-onus 53 sales worth 33 million dollars, growing roughly 18% over the first border of 20 times two.

Speaker 3: And for a Monde 45 sales told $65.9 million representing more than 50% growth versus Q1 of 2022.

Speaker 3: In addition to the strong performance in our core business, the team has been simultaneously preparing and laying the groundwork for the SRP Dynoservic 101 launch.

Speaker 3: The full team has embraced being rigorously trained as we speak, and I can say with confidence that they are ready to execute if that's our few dinosaurs or the ones with great.

Speaker 3: This module will represent a historic moment not only for Sarepta, but for the Duchenne community and for genetic medicine.

Speaker 3: The level of the 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 launching to Shen Market.

Speaker 3: Over the past several months, our field teams and strength leadership have been meeting for the engaged with roughly 75 sites of care on street heat here in operational site readiness matters.

Speaker 3: These important interactions will ensure that the sites are ready to go efficiently, safely, provide SRP 9001 to keep their view. Detachants as soon as possible.

Speaker 3: We've also been working closely with sites to provide education and training, as well as ensuring that they have the necessary equipment and resources to deliver their applications.

Speaker 3: In addition to site readiness, we know from our experience with PEO therapies that access and reimbursement are crucial to successfully delivery SRP NL-001 patients.

Speaker 3: We're committed to ensuring that our gene therapy produced channels accessible to all patients who meet us. And we recognize that uniquely engaging with Pagers is a critical part of achieving that role.

Speaker 3: We found that the payers are asking important questions pertaining to the SRP9301 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 meeting with both commercial and Medicaid payers.

Speaker 3: If approved, Niger-Zero 1.4th potentially transformative therapy to patients who have been waiting for far too long.

Speaker 3: The team has done a tremendous job preparing for what will be the largest team therapy launch to date if SRP 9001 is approved.

Speaker 3: 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 group today.

Speaker 3: But I've 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 S. Pembroke on our financials. Ian.

Speaker 5: Thanks, Dalin, and hello all. This afternoon's financial results press release provided details for the first quarter of 2023 on a non-Gap basis as well as a gap basis.

Speaker 5: Please refer to the press release available on THREPS's website for a full reconciliation of gap to non- GAAP financial results. For the three months ended March 31, 2023, the company recorded total revenues of $253.5 million, which consists of net product revenues and collaboration revenues.

Speaker 5: Compared to revenues of $210.8 million for the same period of 2022, the increase of $42.7 million. Net product revenue for the first quarter of 2023 from our PMO Exxon skipping franchise was $231.5 million.

Speaker 5: compared to $188.8 million for the same period of 2022. The increase in net product revenue primarily reflects increasing demand of our products.

Speaker 5: In each of the quarters ended March 31, 2023 and 2022, we recognized $22 million of collaboration revenue, which relates to our collaboration arrangement with Roche. The reimbursable co-development cost under the Roche agreement totaled $20.3 million for the first quarter of 2023 compared to $17.7 million.

Speaker 5: for the same period of 2022.

Speaker 5: On a GAT basis, we reported a net loss of $516.8 million, or $5.86, and $105 million, or $1.20 cents per basic and vibuted share for the first quarter of 2023 and 2022 respectively.

Speaker 5: This changes primarily due to the law 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.

Speaker 5: We reported a non-gap net loss of $85.5 million or $97.97 per basic and diluted share in the first quarter of 2023 compared to a non-gap net loss of $48.6 million or $56.00 per basic and diluted share in the first quarter of 2022. In the first quarter of 2023, we recorded approximately $35 million.

Speaker 5: in the same period of 2022, partially offset by decrease in the royalty payments during the three months ended March 31, 2023 due to changes in the Biomaran royalty terms. On a GAAP basis, we recorded $245.7 million.

Speaker 5: 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.

Speaker 5: On a non-gap 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, and increased the $47.5 million. Now turning to SGNA on a gap basis, we recorded approximately 110.7 million.

Speaker 5: a launch of SRP-9-0-0-1.

Speaker 5: account through the investment mix of our investment portfolio as well as the reduction of interest expense incurred as a result of the repayment of our December 2019 term loan during 2022.

Speaker 5: In the first quarter, we exchange a portion of our 2024 notes with an aggregate principal value of $313.5 million dollars, and issued approximately $4.5 million shares of our common stock. The account is for the exchange and 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 $300. The exchange date is for the exchange and the debt extinguishment, recognizing the difference of the fair value of the shares of common stock transferred on the exchange date.

Speaker 5: We remain well capitalized to execute on our goals for the year and support our transition to profitability assuming an approval of SRP9001. And with that, I'll turn the call back over for Doug to start the Q&A. Doug?

Speaker 3: Thank you, Ed. Now, before we begin the QA, let me reiterate. Ed, in lineup and in respect of the impending FK Advisory Committee, we will not be entertaining questions on the regulatory process or the upcoming Advisory Committee meeting for SRP 9-0-0-1 tonight.

Speaker 3: 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.

Speaker 1: Thank you. As a reminder to ask a question, please press star 11 or your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. We ask that you please limit yourself to one question each. Please symbol when we compile the Q&A roster. Our first question comes from the line of Colin Burstow with UBS. Your line is now open.

Speaker 6: an unexpected production ramp at the Maryland site. And then to sort of within this, in terms of patient logistics, can you talk about your expectations for the initial timelines from a physician prescribing 9.001 to a patient receiving a therapy, giving the needs for antibody testing, and other potential laboring requirements? Thank you.

Speaker 3: 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 watch and supply the community assuming that we are able to get an approval.

Speaker 3: Of course, our goal right now is to get an approval at the day, which is day 29. We have seen the comments made by catalyst. So we're very clear that. Those comments and the issues that they were discussing do not play any. A role in or have any effect on our plans or our production.

Speaker 3: of land to this land and 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 Ninjas or one of this gene therapy has its...

Speaker 3: 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 free infusion, antibody test that's sufficiently close to the infusion that is valid, and then, of course, you're not.

Speaker 3: Typically, you have to work through access to reimbursement and codes in the life. So from a planning perspective, while we'll be launching this graphically, one should anticipate really seeing a quarter or two before we really start seeing a significant ramp.

Speaker 1: Thank you. Our next question comes from the line of Gina Wang with Barclays. Your line is now open.

Speaker 1: Thank you. I also wanted to ask one commercial questions. What is your estimate patient numbers for initial indication in the US and also regarding the manufacturing capacity? Any major expansion you need to do in order to supply patient for the initial indication in the US? Yes.

Speaker 3: All right, let me ask you 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 give you the broadest of strokes. There's somewhere in this.

Speaker 3: 12,000, 10 to 15,000 patients in the United States. Our goal, again, assuming that we are approved that will produce a date, the goal is to serve all ambulatory patients. The ambulance patients are about 50%, so it's roughly 50% ambulance, 50% non-ambulant.

Speaker 3: We've covered the ambulance population and then there will be, of course, patients that would be excluded because they have preexisting neutralizing antibodies based on our most recent data. And that's about 13.5 percent of patients would be currently excluded on the basis of having preexisting antibodies to binding antibodies to RNA.

Speaker 3: 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 the non-angulate.

Speaker 3: They have sufficient safety and expression data from that study to seek an update to our label early next year to get non-antio-patients in the label so we can begin to dose them. And we're starting as well, two additional studies for two alternative approaches.

Speaker 3: As well, you know, oftentimes we 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's the second worst day of their lives was finding out that their kids are one of these rare kids, about 13% of kids who have test positives for preexisting, neutralizing the antibodies. So we need to move fast to try to solve that issue for them.

Speaker 3: you know, oftentimes we 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's the second worst day of their lives was finding out that their kids are one of these rare kids, about 13% of kids who have test positives for preexisting to get your life to anybody. So we need to move fast to try to solve that issue for them. Thank you for those questions, Tizzi.

Speaker 7: Thank you. Our next question comes from the line of Brian Abrams with RBC Capital Markets here. Line is now open. 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 9.00100 accelerated approval or would prefer to wait for a full approval and should we expect sort of a similar mix as with the exonskippers with regards to the proportion of patients initially receiving access? Thanks.

Speaker 3: I'll let me say the broadest of strokes and down on you can fall if I'm missing anything. First of all, the conversations have gone very well. We've been in dialogue with...

Speaker 3: Payers regarding the potential for SR-9001 for many years now. I can, you know, going back as far as mid-2018, down in myself and others were meeting with payers that are actively in person and team and then meeting with payers significantly.

Speaker 3: 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.

Speaker 3: With that said, I'm going to be very clear, of course, as is the case with rare disease therapies right now, acid reimbursement is a complicated, challenging thing. The good news for all of us is that 9001 is going to be launched by Sirepta. And, you know, we're going to be very clear.

Speaker 3: at the risk of sounding a bit immodest. In my view, there is no team better than this to rep the 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.

Speaker 3: 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 is...

Speaker 3: From our perspective, the approach that one should be taking with respect to 9 years or 1 can in the data that we have in front of us.

Speaker 3: 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 at, you know, we're, we're, prior to lost, they're asking great questions about the timing and the patient population.

Speaker 3: 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 way from day one.

Speaker 1: We're experienced in battle hard and team. Thank you. Our next question comes from the line of Judah Farma with Credit Suisse. Your line is open.

Speaker 3: For those who are amenable to this therapy, which at launch, we are successful. And our VLA would be handling patients excluding a very narrow range of mutations who are from R874 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...

Speaker 3: Those patients that have been on the PMO and remained on the PMO post-docs, and we have good data that supports that. On the value-based agreements in the like, I'm not at a place right now when 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. I will tell you that we have done a lot of work.

Speaker 3: to frame the value proposition and the pharmacoeconomic borrow for one-time therapies like SRT9001 and are approached to the payer community pricing, value-based agreements in the LIG will be inside the frame of that value framework itself.

Speaker 3: And the one thing I will tell you qualitatively at least, and the right time to talk quantitatively, is that the value that this therapy will bring to do shed patience.

Speaker 1: Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open. 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 relationship in order to address the supply that's required over at least the first year or second or for two years of launch year?

Speaker 3: Sure, so we're building inventory as we speak to be ready for launch. So that's obviously an ongoing activity with catalysts. It's a high priority for us and fortunately also a high priority for catalysts. So we're in great shape there. And that's great for launch and we're in great shape there.

Speaker 3: If you look down the road, longer term, of course we also have our relationship with ThermoFisher. We have an entire standalone site with ThermoFisher. 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 that complexity associated with that.

Speaker 3: 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.

Speaker 3: of the running and qualified as well. The good news is that watch our site with Catalyn and our sweet with Catalyn is sufficient to fall asleep in the therapy and serve the community.

Speaker 1: Thank you. Our next question comes from the line of Gil Blum with Needham & Company. The line is now open.

Speaker 3: the clearing of antibody studies, what about planning a study in younger patients? I'm assuming that as with all gene therapy, younger is usually better. Thank you. Yeah, well, let me comment on that last piece first. It is extremely important that we get to younger patients as well. I'm going 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 nine years or one that can restore functional district entitentations won't be beneficial. There is no child that's beyond value. That's important to remember. So if you're 19 years old and you've been in a wheelchair...

Speaker 1: 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 inspection of the

Speaker 5: of our normal manufacturing process. If he looks 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 like nothing to be concerned and should be expected continue to go far.

Speaker 3: And then as relates to the second question, all of the inspections are completed and any of the observations have been entirely satisfied. So we're in great shape from an inspection perspective.

Speaker 3: And then, as relates to the second question, all of the inspections are completed and any of the observations have been entirely satisfied. So we're in great shape from an inspection perspective. Thank you.

Speaker 1: Our next question comes from the line of Danielle Brill with Raymond James. Your line is now open. Hi, guys. Thanks so much. I actually have a couple of questions on EMBARQ. 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?

Speaker 1: and how our missing data imputed. Thank you. No, I'm sorry, I can't get to the last part, but the first part of the conversation. So the study was completely enrolled last fall, so we can expect the one-year endpoint.

Speaker 4: to close out this fall with the study report early next year. These are the primary endpoints for the NSA is that one year, but we measure it at intervals prior to that. Certainly.

Speaker 3: I want the data to step back and that's the results. Thank you. Our next question comes from the line of Mike Ols with Morgan Stanley . Your line is now open. Hey guys, thanks for taking the question. Just another one on the 9-001 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. So let me say two things. First, we don't anticipate at launch a significant impact on our current PMO revenue perspective.

Speaker 3: In the long run, one might, 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.

Speaker 8: A lot of studies you've talked about, you have to build the label out, you'll set the internal and believe your pipeline is described as 40 compound feet.

Speaker 8: So that's some like a lot of our ideas and I'd like to hear your thoughts around that, which is probably many extremely well spent. But maybe if that also includes your thoughts around pricing, a men's general one? Well, I'm going to say two things that much for this to Ian who can comment about capital employment.

Speaker 8: approved and our plans come to fruition would have us being profitable next year. As relates to the pricing for 9001, the pricing of 9001 will occur in the context of the pharmacoreconomic models we use to ensure that the value is appropriate for that therapy and that as I said before.

Speaker 8: that the value brought to the patients and their lives from this therapy is much greater than the cost of the healthcare system.

Speaker 5: But beyond that, you want to comment on the travel deployment plan? 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.

Speaker 5: But obviously, as you know, investing in our R&Ds and our lead to continued growth, and we're going to be focused on moving programs forward that has high probability of success based on the data which we generate. We also think the market conditions right now lend itself to...

Speaker 5: 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, and we're not going to stray from that.

Speaker 1: Thank you. Our next question comes from the line of Kristen Kuska with Cancer Fitzgerald. You'll let it open. 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 pre-treatments for those with pre-existing antibodies to aid?

Speaker 8: approaches that we're taking right now. One is of course with our partner, Hansa, and in Liffodase to cleave and therefore remove antibodies that we stand the way of the child getting 9-0-0-1 and the other is using a breech to clear antibodies.

Speaker 4: Is there anything else that you missed? Hi, you guys. We have strong preclinical data with both approaches and as Doug mentioned, we're planning to start two clinical studies on both approaches. So this has been important to us to make sure that we can serve the entire community.

Speaker 1: Thank you. Our next question comes from Hartas Singh with the Oppenheimer Company. You'll let us know. Great. Thanks for the question. I just got a quick question on the where you study in LGMD. Thank you.

Speaker 9: 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 two and phase three give you? Into the other LGMDs. I mean, could you move faster? You know, could regulators be amenable to...

Speaker 9: looking at them holistically versus very separately. And then how easy will it be to scale the manufacturing of all the other agencies? Thank you for the question. Yeah, I want to say broadly, one is seeing public presentations from Dr. Peter Marx.

Speaker 8: 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 casket, which we are in connection with the LGMDs, that you should be learning from each of them.

Speaker 8: being able to greatly shorten the timeline. I think that 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 are 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.

Speaker 8: enormously from 9001. Remember, most of our limb girdles, the majority at least, use the same promoter as 9001, and they all use the same capsid R874. So there is this virtuous cycle where we ought to be able to start moving faster and faster over time.

Speaker 8: It's going to take some time to do that. I would say we 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, manufacturing.

Speaker 8: Much of the asset work. Some of the asset work can be very translatable, but a lot of the asset work is bespoke from program to program. And so that does take some time, and it will take some time to respect

Speaker 3: Our next question comes from the line of Devjit Chhatapatiyeh with Guggenheim. Your line is now open. 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.

Speaker 8: One of the issues that we just need to discuss at the advisory committee is that, and Mark, which is our proposed confirmatory trial, obviously needs to complete and complete on time. So one of the obviously reasonable questions one would pose is, you know, are you confident that.

Speaker 8: If we give you an approval now on an accelerated basis, that EMBARK 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 EMBARK. As you know, EMBARK actually was fully enrolled as of last year, September of last year.

Speaker 8: 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.

Speaker 8: to other accelerated approval therapies, we are in a particularly advantageous, brilliant position with respect to the completion of our confirmatory trial. Thank you.

Speaker 3: Our next question comes from the line of Joseph Schwartz with the S.V. Security. Sheerline is the open. 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. Yeah, I understand.

Speaker 8: 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...

Speaker 8: opinion. We're going to do a brilliant job, sorry I'm putting a lot of pressure on you Louise, 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.

Speaker 8: 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.

Speaker 1: Thank you. Our next question comes from the line of Z-Shoe with Baron Bird. Your line is open.

Speaker 5: Good afternoon. Thanks for taking my questions. Maybe going back to the manufacturing ramp, some expectations on how many patients do you plan to treat for.

Speaker 3: And so we're preparing ourselves to have a robust launch. Thank you. Our next question comes from the line of Gavin Clark-Gartner with Evercore ISI. Your line is now open. 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? 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 NSAA. Today it's called NSAD, but not mistaken. It's been adapted for Lingerdol. But we'll obviously also be looking at expression and safety with respect to nine years here at the end.

Functional endpoint would likely be a form of NSAA. Today's called NSAB if I'm not mistaken. It's been adapted for Lynn girdle But we'll obviously also be looking at expression and safety with respect to you. Thank you Thank you

Our next question comes from the line of RITU Barol with TD Cowan. You want to know open. Hi guys, it's Sandra Dawn for RITU today. Can you confirm the timing of MBOC 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 901 is approved this month? Our forecast to assume approval this month.

So, I'm sorry what the 1st question was. Then there's been no change in the embark readout. The 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 get in this year early next year. Thank you. Our next question comes from the line of Brian with Baird open.

Hey, good afternoon. Thanks for taking my question. I guess I'm going to jump in off on some of the questions around the ability to successfully conclude. Embariff that you mentioned, can you just talk to us about StudyCon. And is there any risk that a accelerated approval could put on StudyCon. or Dokka Risk?

I think you said before that most of the 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 were going to be able to successfully maintain study conduct on and off once you have commercially available and line-juried 01 under AA? Dr. pict Nicolas

There's no risk.

There's no risk. Zero risk.

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 those even as we speak. Any kid that has yet to be dose will be those in the next few months, the maximum. So, the market going very well will read out.

crossover are being dosed even as we speak. Any kid that has yet to be dosed will be dosed in the next few months at maximum. So the March is going very well. We'll read out on time.

dosed even as we speak. Any kid that has yet to be dosed will be dosed in the next few months at maximum. So the remarks are going very well. We'll read out on time. Regardless.

on whether we receive accelerated approval. There's no reasonable risk to that study.

whether we received accelerated approval. There's no reasonable risk to that study. Thank you.

Our next question comes from the line of Anna Palm-Roma with JP Morgan. Your line is now open. Hey guys, thanks so much for taking a question. On SRP9003, could we see any portions of the voyaging data this year maybe starting ahead of the commercial material Phase 3? I think the PR only committed to like enrollment completion, but not data itself potentially.

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, indirect with you. I look forward to, obviously we're all looking 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 of this team to present the data well and to frame it brilliantly, as I said before. And then I look forward to coming back together thereafter and discussing where we are.