Q4 2022 Sarepta Therapeutics Inc Earnings Call

Operator: Good afternoon, and welcome to Surreth Therapa Therapeutics' fourth quarter and full year 2022 earnings call. At this time, all participants are on a listen-only conference call.

Speaker 2: Good afternoon and welcome to the Sorepta Therapeutics fourth quarter and full year 2022 earnings call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question at that time, please press star 11 on your telephone.

Operator: After the next episode. After the speaker's presentations, there will be a question-and-answer session.

Operator: If you want to ask a question at that time, please press star 1-on on your telephone. As a reminder says, the conference caller is being recorded. At this time, I'm trying to call over to Mary Jenkins, Associate Director of Best Relations.

Operator: to relations. Please go ahead.

Speaker 2: As a reminder, today's conference call is being recorded.

Mary Jenkins: Thank you, Valerie, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the fourth quarter and full year 2020.

Speaker 2: At this time, I will turn the call over to Mary Jenkins, Associate Director of investor relations. Please go ahead.

Speaker 3: Thank you, Valerie, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the fourth quarter and full year 2022. The press release is available on our website at Sarepta.com, and our 10-K was filed with Securities and Exchange permission this afternoon.

Mary Jenkins: The press release is available on our website at surrepta.com, and our 10k was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estepon, Dallan Murray, and Dr. Louise Rodino Claypack. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call,

Speaker 3: Joining us on the call today are Doug Ingram, Ian Estipan, Fallon Murray, and Dr. Louise Rodino-Claypack. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will 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.

Mary Jenkins: We will 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 Surreptus' control. Actual results could materially differ from these forward-looking statements.

Speaker 3: These forward-looking statements involve risks and uncertainties, many of which are beyond surreptice control. Multiple results could materially differ from these forward-looking statements.

Mary Jenkins: And any such risks can materially and adversely affect the business, the results of operations, and trading prices for Surreptus Common Stock.

Speaker 3: And any such risks can materially and adversely affect the business, the results of operations and trading prices for surreptit common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual report on Form 10-K filed with the SEC as well as the company's other SEC filings.

Mary Jenkins: For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual report on Form 10K 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. I'll now turn the call over to President and CEO, Doug Ingram, who will provide an overview of our recent progress.

Speaker 3: 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. I'll now turn the call over to President and CEO Doug Ingram, who will provide an overview of our recent progress. Doug? Mr. wearableBUZZ.

Douglas S. Ingram: Thank you, Mary. Good afternoon, everybody, and thank you for joining Surreth Therapeutics for our fourth quarter and full year 2022 financial results conference call.

Speaker 4: Thank you, Mary. Good afternoon, everybody, and thank you for joining Soretta Therapeutics for our fourth quarter and full year 2022 financial results conference call.

Douglas S. Ingram: 2023 may be the most

Douglas S. Ingram: eventful year in Sarepta's event-filled history. Our Biologics License Application, or BLA, for our gene therapy, SRP-001, for Duchenne Muscular District Dyser, will be a significant bellwether moment. First, for the Duchenne families who are waiting without the luxury of patients for a therapy that might arrest the brutal decline associated with this disease, and next for the promise of gene therapy as a class to deliver meaningful improvements in the lives of patients with rare degenerative diseases, not at some distant vanishing point in the future, but in time to do good now.

Speaker 4: 2023 may be the most eventful year in Sarepta's event-filled history. Our Biologics License Application, or BLA, for our gene therapy SRP9001 for Duchenne muscular dystrophy will be a significant bellwether moment.

Speaker 4: First, for the Duchenne families who are waiting without the luxury of patience, for a therapy that might arrest the brutal decline associated with this disease.

Speaker 4: And next for the promise of gene therapy as a class, to deliver meaningful improvements in the lives of patients with rare degenerative diseases.

Douglas S. Ingram: Given the keen interest in the 901 BLA submission, I'm going to comment on the BLA review before I move to quarterly and yearly performance. As you will recall, in the fall of last year, we submitted our BLA for SRP 9001 to treat ambulant Duchenne patients. And in the fourth quarter, the FDA accepted the DLA for filing, granted 901 priority review, and set May 29, 23, as our action date. We have been diligently prosecuting the BLA.

Speaker 4: Not at some distant vanishing point in the future, but in time to do good now.

Speaker 4: Given the keen interest in the 9001-BLA submission, I'm going to comment on the BLA review before I move to quarterly and yearly performance. As you will recall, in the fall of last year, we submitted our BLA for SRP-9001 to treat ambulance-dishend patients, and in the fourth quarter, the FDA accepted the BLA for filing.

Speaker 4: granted 9001 priority review and set May 29, 2023 as our action date. We have been diligently prosecuting the BLA. We have by now completed a very productive mid-cycle review with the Division. At the mid-cycle, we have completed a very productive mid-cycle review.

Douglas S. Ingram: We have by now completed a very productive mid-cycle review with the division. At the mid-cycle, the division requested additional CMC information, and we have by now provided answers to all of those questions. The division formally informed us, as well, at the mid-cycle meeting, that they see no.

Speaker 4: the Division requested additional CMC information and we have by now provided answers to all of those questions.

Douglas S. Ingram: They see no significant safety issues that have been identified.

Speaker 4: The Division formally informed us as well at the mid-cycle meeting that they see no significant safety issues that have been identified.

Douglas S. Ingram: And the division has determined that there is no need for an advisory committee meeting for SRP 9001 BLI. As you may have read, FDA has announced that the Office of Tissues and Advanced Therapies, or OTAT, is being reorganized into a new super office entitled the Office of Therapeutic Products, or OTP, is being established. The goal is to improve alignment, increase resources and capacity, and enhance expertise. A couple of thoughts. First, Serepta is delighted by the establishment of OTP. We believe it will enhance reviews and serve Dr. Peter Mark's publicly stated vision to lean in and accelerate the transformative potential of cell and gene therapy.

Speaker 4: And the Division has determined that there is no need for an Advisory Committee meeting for SRP 9001-BLA.

Speaker 4: As you may have read, FDA has announced that the Office of Tissues and Advanced Therapies, or OTAT, is being reorganized, and a new super office entitled the Office of Therapeutic Products, or OTP, is being established.

Speaker 4: The goal is to improve alignment, increase resources and capacity, and enhance expertise.

Speaker 4: A couple of thoughts. First, Sarepta is delighted by the establishment of OTP. We believe it will enhance reviews and serve Dr. Peter Marks publicly stated vision to lean in and accelerate the transformative potential of cell and gene therapy.

Douglas S. Ingram: Second, the FDA is

Douglas S. Ingram: that the reorganization and establishment of OTP will not impact on any time, and we can confirm that we have not experienced any delay or disruption of any kind as a result of this reorganization.

Speaker 4: Second, FDA has stated that the reorganization and establishment of OTP will not impact any time once.

Speaker 4: and we can confirm that we have not experienced any delay or disruption of any kind as a result of this reorganization. Indeed, we see the establishment of OTP as unequivocally positive and a potentially great benefit to patients. So going forward, we're going to focus on the following.

Douglas S. Ingram: Indeed, we see the establishment of OTP as unequivocally positive.

Douglas S. Ingram: and potentially a great benefit to patients. Going forward, we're going to focus on the following. First, answering any remaining questions the FDA may have on the file. Second, preparing for and managing pre-approval inspections. The FDA has already scheduled three pre-approval manufacturing inspections, and along with our manufacturing partner Catalan, we are preparing to make those inspections a success. Third, building inventory for launch, and fourth, of course, completing our launch readiness.

Speaker 4: First, answering any remaining questions the FDA may have on the file. Second, preparing for and managing pre-approval inspections. The FDA has already scheduled three pre-approval manufacturing inspections and along with our manufacturing partner, Catalin. We are preparing to make those...

Speaker 4: inspections a success. Third building inventory for launch and fourth of course completing our launch readiness.

Douglas S. Ingram: Now I've provided an update on the mid cycle today as there has been a significant amount of interest.

Speaker 4: Now, I've provided an update on the mid-cycle today as there has been a significant amount of interest in whether the division would see the need for an advisory committee.

Douglas S. Ingram: and whether the division would see the need for an advisory committee. However, from here on, we will be focusing on prosecuting the BLA and will provide an update on or after the 9-0-01 action. Moving now to performance. As you ponder how Serepta may execute the launch of 901, if given that opportunity, I would ask you to consider the team's consistent performance, quarter over quarter and year over year, serving the Duchenne community with our three approved therapies, Exondis, V, and Amman.

Speaker 4: However, from here we will be focusing on prosecuting the BLA and will provide an update on or after the 9001 action date.

Speaker 4: Moving now to performance, as one ponders how Sorepta may execute the launch of 9-0-0-1, if given that opportunity, I would ask you to consider the team's consistent performance, quarter over quarter and year over year, serving the Duchenne community with our three approved therapies, Exondas, Biondas and Amondas.

Speaker 4: From an in-market perspective, 2022 was yet another year where our cross-functional team, including commercial, medical affairs, patient services, access and reimbursement, and manufacturing and supply chain, to name a few, executed together and delivered for our patients.

Speaker 4: Fourth quarter total revenue stood at $258.4 million, while net product revenue came in at $235.9 million. That is a 32% increase over the same quarter of the prior year.

Douglas S. Ingram: From an in-market perspective, 2022 was yet another year where our cross-functional team, including commercial, medical affairs, patient services, access and reimbursement, and manufacturing and supply chain, to name a few, executed together and delivered for us. Fourth quarter total revenue stood at $258.4 million, while net product revenue came in at $235.9 million. That is a 32% increase over the same quarter of the prior year. Full year total revenue came in at $933 million, and net product revenue for the year came in at $8.

Speaker 4: Full year total revenue came in at $933 million. And net product revenue for the year came in at $843.8 million, representing a 38% year-over-year increase. For the last five years, we have grown at a consistent 40% compounded annual growth rate.

Speaker 4: All of which performance comes from serving the Deshem community and none of which comes from price increases.

Speaker 4: Now, as we announced at the J.P. Morgan conference in January , for 2023, our net product revenue guidance for our three currently approved PMO therapies, excluding the impact of a 9001 hope, is $925 million or greater.

Douglas S. Ingram: $8 million, representing a 38% year-over-year increase. For the last five years, we have grown at a consistent 40% compounded annual growth, all of which comes from serving the Duchenne community, and none of which comes from Price. Now, as we announced at the J. In January, for 2023, our net product revenue guidance for our three currently approved PMO therapies, excluding the impact of a 9-001 approval, is $925 million or greater. Moving back to SRP 901 for a moment, we are commencing studies this year to ensure that we have the broadest label for SRP 9001 as is possible consistent with the science.

Speaker 4: Moving back to SRP 9001 for a moment, we are commencing studies this year to ensure that we have the broadest label for SRP 9001 as is possible consistent with the science.

Speaker 4: We have already commenced our study to limit mutation related exclusions. Further, in the coming months, we will be starting a study in the non-angulate population called InVision.

Speaker 4: or study 303. And we will commence two separate studies with alternative approaches to removing preexisting antibodies to make SRP-9001 available to RH74-NAB-positive patients as well.

Speaker 4: Additionally, we are making significant progress with our Limb-Girdle pipeline, as Dr. Luis Rodino-Kwabak will discuss in a moment as she provides updates across our research and development activities.

Speaker 4: on the RNA platform.

Speaker 4: We will complete enrollment of the Momentum study this quarter. Momentum, as you know, is our study for our first next-generation peptide conjugated PMO, also known as a PPMO, and that's SRP5051 designed to treat Duchenne patients who are exon 51 amenable. Momentum will read out later this year and, if successful, will be available for the next quarter.

Douglas S. Ingram: We have already commenced our

Douglas S. Ingram: to limit mutation-related exclusion, further In the coming months, we will be starting a study in the non-amblant population called Envision, or study 303. And we will commence two separate studies with alternative approaches to removing pre-existing antibodies to make SRP 901 available to R874 NAB positive patients as well.

Speaker 4: we will discuss a filing for SRP 5051 with the neurology division this year. I am proud of the progress that we have made these last six years.

Speaker 4: SRP 5051 with the neurology division this year. I am proud of the progress that we have made these last six years and yet it pales.

Speaker 4: in comparison to the good that we can do in the coming years together. We have the potential to improve the lives of countless patients and to greatly reward those who have been committed to and invested in this mission. Indeed, the opportunity in front of us is breathtaking.

Douglas S. Ingram: Additionally, we are making significant progress with our limb girdle pipeline, as Dr. Luis Rodino Clayback will discuss in a moment as she provides updates across our research and development activities. On the R&A platform, we will complete enrollment in the Momentum study this quarter. Momentum, as you know, is our study for our first next-generation, Hepthide conjugated PMO, also known as a PPMO, and that's SRP 5051, designed to treat Duchenne patients who are Exxon 51 amenem.

Speaker 4: To realize that opportunity, we will need laser-focused and tenacious execution.

Speaker 4: But as Sarepta has proven time and again, this is a team that knows how to execute. And with that, let me turn the call over to our head of R&D and Chief Scientific Officer, Dr. Luis Redino-Clapek. Luis. Luis, tell me, can you hear me OK? S leadership?

Speaker 4: as Sarepta has proven time and again, this is a team that knows how to execute. And with that, let me turn the call over to our head of R&D and Chief Scientific Officer, Dr. Luis Redino-Clapek. Luis. Thanks, Bug.

Speaker 3: The accomplishments of 2022 and the opportunities before us in 2023 and beyond speak to the promise of science to fundamentally impact and change the lives of patients around the world. My deepest gratitude to our R&D colleagues across RNA, gene therapy, and gene editing for their extraordinary work to get us where we are today.

Douglas S. Ingram: Momentum will read out later this year, and if successful, we will discuss a filing for SRP 5051 with the Neurology Division this year. I am proud of the progress that we have made these last six years, and yet it pales in comparison. So the good that we can do in the coming years together. We have the potential to improve the lives of countless patients and to greatly reward those who have been committed to and invested in this mission.

Speaker 3: And where we are today represents an important moment in genetic medicine and an important moment for Sirepta. Firstly, we were thrilled to learn last November that the FDA accepted our BLA for review via the accelerated approval pathway for our lead gene therapy candidate SRP9001.

Speaker 3: This decision was based on our ability to show robust expression of the SRP9001 dystrophin protein, a shortened functional version of dystrophin serving as a surrogate endpoint reasonably likely to predict clinical benefit in patients with Duchenne muscular dystrophy.

Douglas S. Ingram: Indeed, the opportunity in front of us is breath-free. To realize that opportunity, we will need laser-and tenacious execution. But, as Serepta has proven time and again, this is a team that knows how to execute. And with that, let me turn the call over to our head of R&D and chief scientific officer, Dr. Luis Rino Claypeg.

Speaker 3: Duchenne results from a mutation in the gene that codes for dystrophin. Dystrophin acts as a shock absorber in our muscles, attaching to the muscle membrane and distributing force as we move, thereby protecting our muscles from damage. Individuals with Duchenne lack dystrophin, and as a result, their muscles become progressively worse.

Dr. Louise Rodino-Klapac: The accomplishments of 2022 and the opportunities before us in 2023 and beyond speak to the promise of science to fundamentally impact and change the lives of patients around the world. My deepest gratitude to our R&D colleagues across RNA, gene therapy, and gene editing for their extraordinary work to get us where we are today. And where we are today represents an important moment in genetic medicine.

Speaker 3: Our goal was SRP9001. It's to change the course of the fatal disease by treating the underlying cause of dishing with a one-time gene therapy that delivers functional disturbance to the muscles.

Speaker 3: Based on well-established precedent, the FDA has approved four therapies to date using shortened functional dystrophin as a surrogate endpoint.

Speaker 3: Further, Syrupda has generated the most compelling pre-clinical, biomarker, and clinical functional results to date. What is particularly interesting about SRP-9001, but not completely surprising, based on the strong scientific underpinning of our construct, is that the early SRP-9001 data provided a breakthrough to our positive clinical experience.

Dr. Louise Rodino-Klapac: Firstly, we were thrilled to learn last November that the FDA accepted our BLA for review via the accelerated approval pathway for our lead gene therapy candidate SRP 9001. This decision was based on our ability to show robust expression of the SRP-001 dystrophin protein, a shortened functional version of dystrophin.

Dr. Louise Rodino-Klapac: dystrophin, serving as a surrogate endpoint reasonably likely to predict clinical benefit in patients with Duchenne muscular dystrophy. Deschen results from a mutation in the gene that codes for dystrosin. Dystrofen acts as a shock absorber in our muscle, attaching to the muscle membrane and distributing force as we move, thereby protecting our muscles from damage.

Speaker 3: and fit easily into A to B, thereby enabling delivery.

Speaker 3: This gene cassette was packaged into our AAV of choice, RH74, and we chose MHDK7 as our promoter.

Speaker 3: We were pleased with the early data, which showed robust expression across skeletal, diaphragm, and cardiac muscle. And as a result of that expression, as well as the dystrophin protein demonstrating functional benefits, we saw significant restoration of function at the clinical target dose. To understand the significance of the...

Dr. Louise Rodino-Klapac: Individuals with Duchenne lack dystrophin, and as a result, their muscles become progressively worse. Our goal with SRP 9001 is to change the course of the fatal disease by treating the underlying cause of Duchenne with a one-time gene therapy that delivers

Speaker 3: results and their importance in the context of a viable therapy for Duchenne. It's critical to understand the Distrofen Associated Protein Complex or DAPC. DAPC is a collection of proteins to which the stroke and attaches, and it's absence these proteins disassemble. Individuals with Duchenne don't have a functioning Distrofen Associated Protein Complex.

Dr. Louise Rodino-Klapac: that delivers functional dystrophin to the muscle. Based on well-established precedent, the FDA has approved four therapies to date using shortened functional dystrophin as a surrogate endpoint.

Dr. Louise Rodino-Klapac: Furthermore, Surrepta has generated the most compelling preclinical biomarker and clinical functional results to date.

Dr. Louise Rodino-Klapac: What is particularly interesting about SRP 901 but not completely surprising based on the strong scientific underpinning of our construct.

Speaker 3: 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.

Dr. Louise Rodino-Klapac: is that the early SRP 901 data provided read-to our positive clinical experience with the therapy.

Dr. Louise Rodino-Klapac: Over the course of 10 plus years, I, along with Dr. Jerry Mendel, built, researched, and tested numerous constructs to determine what areas of the protein were functional and protective. We eventually identified an optimal gene cassette that would be able to retain protective and functional elements and fit easily into AAV.

Speaker 3: Further, we saw a significant reduction increase in kinase, or CK, levels. CK is an enzyme associated with muscle damage. The reduction in CK provided further proof that SRP9001 was reasonably likely to predict clinical benefit.

Speaker 3: The strength of this early work gave us the confidence and conviction to advance SRP9001 into the clinic. Since 2018 and across multiple studies, we've dosed over 140 patients, more than any other gene therapy being developed for Duchenne, and the clinical results have surpassed our expectations. to the

Dr. Louise Rodino-Klapac: enabling its delivery. This gene cassette was packaged into our AAV of choice, and we chose MHCK7 as our promoter. We were pleased with the early data, which showed robust expression across

Dr. Louise Rodino-Klapac: diaphragm, and cardiac muscle. And as a result of that expression, as well as the dystrophin protein demonstrating functional benefits, we saw significant restoration of function at the clinical target dose. To understand the significance of the results and their importance in the context of a viable therapy for Duchen, it's critical to understand the dystrophen-associated protein complex, or Dapsi. Dap C is a collection of proteins to which Dysrofen attaches. In its absence, these proteins disassemble.

Speaker 3: SRP 9001 demonstrated robust expression of dystrophin far above what literature would suggest is necessary to be protective of muscle.

Speaker 3: All of it is properly localized at the muscle membrane or sarcolemma where it acts as a shock absorber.

Speaker 3: We also developed a cell-based potency assay that shows that SRP9001 is active, functional, and protective at the muscle membrane.

Speaker 3: And as in the animal models 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 also able to show functional benefits versus what natural history would predict. NSAA, or the North Star Ambulosory Assessment, is our primary functional endpoint.

Dr. Louise Rodino-Klapac: Individuals with Duchen, Dishin don't have a functioning Dysrophin-associated protein complex. 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 regulation of the DAPC when there was expression of the SRPIN, 001 dystrophin, confirming the protective properties of the proceeds.

Speaker 3: we were able to show benefit across one, two, and four-year time points. In summary, based on the fatality of the data, we were able to provide objective evidence that SRP9001 qualifies as a disease-modifying agent and that the levels of dystrophin expressed based on vast clinical evidence and experience are reasonably likely to predict clinical benefit in patients with Duchenne.

Dr. Louise Rodino-Klapac: Further, we saw a significant reduction in creating

Dr. Louise Rodino-Klapac: and kinates or cK levels. CK is an enzyme associated with muscle damage. The reduction in CK provided further proof that SRP 9001 was reasonably likely to predict clinical benefits. The strength of this early work gave us the confidence and conviction to advance

Speaker 3: As Doug mentioned in his opening comments, since the agency is not planning on holding an advisory committee for SRP 9001, the team is focused on responding to any remaining requests.

Speaker 3: As a reminder, and because we are at active review with the FDA, we do not anticipate publicly sharing additional data cuts from the SRP9001 studies leading up to the 2023 regulatory milestones and the EMBARQ data readout, which is on track for the fourth quarter of this year. Join now with our gene therapy platform and our list of

Dr. Louise Rodino-Klapac: to advance SRP 901 into the claim.

Dr. Louise Rodino-Klapac: Since 2018, and across multiple studies, we've dosed over 140 patients, more than any other gene therapy being developed for Duchenne, and the clinical results have surpassed our expectations. SRP 9001 demonstrated robust expression of dystrophin, far above what literature would suggest is necessary to be protective of muscle. All of it is properly localized at the muscle membrane or sarculoma, where it acts as a shock absorber. We also developed a cell-based potency assay that shows that SRP 901 is active, functional, and protective at the muscle membrane.

Speaker 3: for the treatment of limb girdle muscular dystrophy type 2E in ambulant adult patients and non-ambulant patients using clinical process SRP9003 material.

Speaker 3: Combined with positive expression and functional data shared from our initial study, SRP9003-101, we believe the data from Voyaging will give us insights into the broader patient population as we finalize plans for a global Phase III study using commercially representative process material that we intend to begin later this year.

Dr. Louise Rodino-Klapac: and as in the animal models, robust expression of SRP 901, we saw

Dr. Louise Rodino-Klapac: a significant reduction in CK. Finally, expression of SRP-001

Dr. Louise Rodino-Klapac: leads to upregulation of the DAPSE. In addition to all of this compelling evidence, we were also able to show functional benefit versus what natural history would predict. NSAA, or the North Star Ambulatory Assessment, is our primary functional endpoint. We were able to show benefits across one, two, and four-year time periods. In summary, based on the fatality of the data, we were able to provide objective evidence that SRP-0-1 qualifies as a disease-modifying agent and that the levels of dystrosin expressed, based on vast clinical evidence and experience, are reasonably likely to predict

Speaker 3: In addition, we plan to commence a systemic pilot study for our SRP6004 dual-vector RH74-mediated gene therapy to treat LGMD2B characterized by the absence of the protein disverlin.

Speaker 3: We believe our gene therapy platform is well suited to generate medicines for the LIMGIRTLE muscular dystrophies. Our work in this area continues on pace and represents a key priority for surreptive.

Speaker 3: We believe our gene therapy platform is well suited to generate medicines for the limb-girdle muscular dystrophies. Our work in this area continues on pace and represents a key priority for Sirepta. Turning now to our RNA platform.

Dr. Louise Rodino-Klapac: and patients with Dushan. As Doug mentioned in his opening comments, since the agency is not planning on holding

Speaker 3: Momentum study for our next generation PPMO SRP 5051 is ongoing and we remain on track to announce data to the BACASA 2023. Further, we were pleased to complete enrollment in the essence trial or post-marketing requirements for Golders and CAST merchants. And lastly, we are making good progress with our mission study and it continues on pace. In closing, I want to take a moment to recognize Rare Disease Day and the over 300 million individuals around the world living with a rare disease.

Dr. Louise Rodino-Klapac: advisory committee for SRP 901. The team is focused on responding to any remaining requests. As a reminder, and because we are in an active review with the FDA, we do not anticipate publicly sharing additional data cuts from the SRP 9-01 studies leading up to the 2023 regulatory milestones and the embark data read-up, which is on track for the fourth quarter of this year.

Dr. Louise Rodino-Klapac: and our limb girdle muscular dystrophy program. We were pleased to announce earlier this month that the first patient was dosed in study.

Dr. Louise Rodino-Klapac: and study SRP 903102.

Dr. Louise Rodino-Klapac: Voyaging is a phase one study evaluating SRP 9003 for the treatment of limb girdle muscular dystrophy type 2E in ambulant adults.

Speaker 5: Thank you, Luis, and good afternoon.

Speaker 4: In 2022, the team delivered yet another year of strong double-digit growth across all three of our RNA-based PMO therapies.

Dr. Louise Rodino-Klapac: and non-ambulant patients using clinical process SRP 903 material. Combined with positive expression and functional data shared from our initial study, SRP 903 101, we believe the data from Voyageen will give us insights into the broader patient population as we finalize plans for a global phase three study using commercially representative process material that we intend to begin later this year. In addition, we plan to commence a systemic pilot study for our SRP 604-604 dual vector, RH74-mediated gene therapy to treat LGMD2B, characterized by the absence of the protein dysferlin. We believe our gene therapy platform is well suited to generate medicines for limb girdle muscular dystrophies. Our work in this area continues at pace and represents a key priority for surreptus.

Speaker 5: As Doug noted, our full year net product revenue was $843.8 million, which beat the upper end of our upwardly revised 2022 guidance of $825 to $840 million. This represented more than $230 million in growth over 2021 and a growth rate that approached 40% year over year.

Speaker 5: I'll take a moment to highlight some of our full year 2022 achievements for our PMO franchise. The team started the year in a strong position by successfully navigating the beginning of the year insurance changes and reauthorizations.

Speaker 5: This led to a reauthorization rate in the low to mid 90s throughout 2022. This robust start coupled with continued high adherence rates and strong ex-US revenues served as the foundation for full year, net product revenue growth of approximately 13% generated with Exondas 51, and net product revenue of roughly $511 million. For Biondas 53, we ended 2022 in a strong leadership position in market show.

Dr. Louise Rodino-Klapac: Turning now to our RNA platform. Momentum study for our next generation PPMO, SRP 5051, is ongoing, and we remain

Dr. Louise Rodino-Klapac: and we remain on track to announce data toward the back half of 2023. Furthermore, we were pleased to complete enrollment in the Essence trial or the post-marketing requirement for Goloderson and Kazmerson. And lastly, we are making good progress with our mission study, and it continues at pace. In closing, I want to take a moment to recognize rare disease day and the over 300 million individuals around the world living with a rare disease. This is my life's work, and I, along with my colleagues at Surrupta, will not rest until we do our part in advancing the science and developing treatments for waiting patients.

Speaker 5: $14.8 million.

Speaker 5: As we've noted in previous calls, our ex-US growth continued to accelerate and represented roughly 11% of our overall net product revenues in 2022. Ex-US net product revenue was $96.3 million for the full year of 2022. Our performance in 2022 is the result.

Speaker 5: of a highly committed and effective team focused on serving the nearly 30% of patients on medical to our therapies with the level of urgency that Duchenne requires. Turning now to our performance in the fourth quarter of 2022, we ended the year on a high note with net product revenues of $235.9 million. Once again, the team executed and grew the RNA-based chemo business by more than...

Speaker 5: 30% over the fourth quarter of 2021 and 13% over the prior quarter. I'll now outline individual net product revenues for the fourth quarter of 2022 for our three approved RNA-based PMO therapies. For Exhonda 51, net product revenue of 146 million.

Dr. Louise Rodino-Klapac: I would also like to say thank you to the patients and their families who so generously give of their time.

Dr. Louise Rodino-Klapac: who so generously give of their time and commitment to our trials. We could not undertake this important work without you. I will now turn the call over to Dallon for an update on our commercial activities. Thank you, Louise, and good afternoon.

Dallan Murray: In 2022, the team delivered yet another year of strong double-digit growth across all three of our RNA-based PMO therapy products. As Doug noted, our full year net product revenue was $8. $8 million, which beat the upper end of our upward-revised 2022 guidance of $825 to $840 million. This represented more than $230 million in growth over 2021 and a growth rate that approached 40% year over year. I'll take a moment to highlight some of our full year 2022 achievements for our PMO franchise.

Speaker 5: 2021.

Speaker 5: And finally, among this 45, net product revenue was $61.4 million in Q4 of 2022, representing nearly 80% growth versus the fourth quarter of 2021. At the business evolve and grew throughout 2022, we've seen more variability in our quarter over quarter revenue numbers.

Speaker 5: due to very strong XUS sales of $36.9 million.

Dallan Murray: The team started the year in a strong position by successfully navigating the beginning of the year insurance changes and reauthorization. This led to a reauthorization rate in the low to mid-nineties throughout 2022. This robust start, coupled with continued high adherence rates and strong XUS revenues, served as the foundation for full year net product revenue growth of approximately 13% generated with

Speaker 5: This strength allowed us to far exceed expectations for the quarter, however, we do not expect the same dynamic to persist into the first quarter of 2023. We want to provide you this level of visibility to help you model our revenues for the year. Our forecast anticipates this dynamic.

Speaker 5: and it is reflected in our 2023 PMO net product revenue guidance of greater than $925 million, which we issued in January . Despite the quarterly fluctuations, overall we expect a strong year and are confident in our guidance. Again, I'm proud of what we accomplished in 2022.

Dallan Murray: with Exhontas 51 and met with exonerated

Speaker 5: And most importantly, I'm grateful for our team's enduring commitment to the DeChin community and the patients we serve. This commitment to operational excellence will serve us and the patient community well as we apply the lessons learned to the upcoming launch of SRP 9001.

Dallan Murray: and net product revenue of roughly $511 million. For By Onda, we ended 2022 in a strong leadership position in market share. By Honda, 53 exceeded $100 million in revenues, ending the year with $117.4 million in total net product revenue and over 30% growth compared to 2021.

Speaker 5: In parallel with the team's execution of our existing business in 2022, the Custom Organization build for SRP-9001 is on track and nearly complete.

Speaker 5: Importantly, engagement with key gene therapy sites and US payers is well underway. If SRP9001 is approved, the team is once again prepared to demonstrate their capabilities and hard-fought expertise in our fourth launch into the Duchenne space.

Dallan Murray: And last but not least, the team's continued execution on Amandis 45 produced exceptional results.

Dallan Murray: growth in 2022 of over 200% with total net product revenue of $214 million. As we've noted in previous calls,

Speaker 5: with the first gene therapy to serve the patient community. And now I'll turn the call over to Ian Estapan for an update on our financials. Ian. Thanks, Dalon. Good afternoon, all. This afternoon's financial results press release provided details for the fourth quarter and full year of 2022 on a non-GAAP basis, as well as the GAAP.

Dallan Murray: growth continues to accelerate and represented roughly 11% of our overall net product revenues in 2022. XUS's net product revenue was $96.

Dallan Murray: For the full year of 2022. Our performance in 2022 is the result of a highly committed and effective team focused on serving the nearly 30% of patients amenable to our therapies with the level of urgency that Duchenne requires. Turning now to a performance in the fourth quarter of 2022, we ended the year on a high note with net product revenues of $235. Once again, the team executed and grew the RNA-based PMO business by more than 30% over the fourth quarter of 2021 and 13% over the prior quarter.

Speaker 6: and collaboration revenues, compared to revenues of $201.5 million for the same period of 2021, an increase of $56.9 million.

Speaker 6: Net product revenue for the fourth quarter of 2022 from our PMO Exxon skipping franchise was $235.9 million compared to $178.7 million for the same period of 2021.

Dallan Murray: I'll now outline individual net product revenues for the fourth quarter of 2022, for our three approved RNA-PML therapy. For Exhawn to 51, net product revenue of $146 million represented roughly 22% growth over Q4 of 21. My honest 53, fourth quarter 22, that product revenue total $28, representing roughly 15% growth versus the fourth quarter of 2021. And finally, Amondas 45's net product revenue was $61. $61.4 million in Q4 of 2022, representing nearly 80% growth versus the fourth quarter of 2021.

Speaker 6: The increase in net product revenue primarily reflects increasing demand for our products. So, the quarter has ended December 31, 2022 and 2021. We recognize $22.5 million and $22.7 million of collaboration and other revenues respectively, which primarily relates to our collaboration arrangement with Roche.

Speaker 6: The reimbursable co-development costs under the Roche Agreement totaled $51.7 million for the fourth quarter of 2022 compared to $29.7 million for the same period of 2021. On a GAAP basis, we reported a net loss of $109.2 million, or $1.24, and $122 million, or $1.42, per basic and diluted share for the fourth quarter.

Dallan Murray: As the business evolved and grew throughout 2022, we've seen more variability in our quarter over quarter revenue numbers due mainly to X US ordering patterns. We have observed lumpy quarter to quarter fluctuations and seasonality with our XUS orders. We expect this trend to continue going forward. For example, sales in the fourth quarter of 2022 were robust due to very strong XUS sales of $36. This strength allowed us to far exceed expectations for the quarter.

Speaker 6: of 2022 and 2021 respectively. We reported a non-GAAP net loss of $46.5 million or $0.53 per basic and diluted share in the fourth quarter of 2022 compared to a non-GAAP net loss of $66 million or $0.77 per basic and diluted share in the fourth quarter of 2021. In the fourth quarter of 2022, we recorded approximately a $30.8 million dollar loss.

Dallan Murray: However, we do not expect the same dynamic to persist into the first quarter of 2023. We want to provide you with this level of visibility to help you model our revenues for the year. Our forecast anticipates this dynamic, and it is reflected in our 2023 PMO net product revenue guidance of greater than $925 million, which we issued in January. Despite the quarterly fluctuations, overall, we expect a strong year and are confident in our guidance.

Speaker 6: during the three months and the December 31st, 2022, due to changes in our biomarkin royalty terms.

Speaker 6: On a GAAP basis, we recorded $213.8 million and $197.3 million in R&D expenses for the fourth quarter of 2022 and 2021 respectively, a year-over-year increase of $16.5 million. That increase is primarily due to increases in up-front and milestone expenses.

Dallan Murray: Again, I'm proud of what we accomplished in 2022, and most importantly, I'm grateful for our team's enduring commitment to the Dishan community and the patients we serve. This commitment to operational excellence will serve us in the patient community well as we apply the lessons learned to the upcoming launch of SRP 9001, in parallel with

Speaker 6: On a non-GAAP basis, R&D expenses were $186.8 million for the fourth quarter of 2022 compared to $175.5 million for the same period of 2021, an increase of $11.3 million.

Speaker 6: Now turning to SGMA on a GAAP basis, we recorded approximately $120.5 million and $78.1 million of expenses for the fourth quarter of 2022 and 2021 respectively, an increase of $42.4 million.

Dallan Murray: execution of our existing business in 2022, the customer organization billed for SRP 9001 is on track and nearly complete. Importantly, engagement with key gene therapy sites and U. US payers is well underway. If SRP 9001 is approved, the team is once again prepared to demonstrate their capabilities and hard-fought expertise in our fourth launch into the Buchenne space, with the first gene therapy to serve the patient community. And now I'll turn the call over to E&F for an update on our financials, Ian.

Speaker 6: The increase was driven primarily by an increase in stock-based compensation expense primarily due to additional expense recognized to the CEO grant modification agreement executed in 2022.

Speaker 6: On a non-GAAP basis, the SJMA expenses were $86.6 million for the fourth quarter of 2022 compared to $60.1 million for the same period of 2021, an increase of $26.5 million.

Ian Estefan: Thanks, Alan. Good afternoon, all.

Ian Estefan: This afternoon's financial results press release provided details for the fourth quarter and full year of 2022 on a non-gap basis as well as on a gap basis. Please refer to the press release available on the instructors' website for full reconciliation of gaps to non-gap financial results. For the three months ended December 31, 2022, the company recorded total revenues of $258.4 million, which consists primarily of net product revenues and collaboration revenues, compared to revenues of $201.5 million for the same period of 2021, an increase of $56.9 million. Net product revenue for the fourth quarter of 2022 from our PMO Exxpings franchise was $235.9 million, compared to $178.7 million for the same period of 20 The increase in net product revenue primarily reflects increasing demand for our product.

Speaker 6: On a gap basis, we recorded $5.5 million in other income net for the fourth quarter of 2022, compared to $16.1 million in other expenses net for the same period of 2021. The changes primarily due to an increase in interest income due to 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.

Speaker 6: We add approximately $2 billion in cash cash equivalents and long-term and restricted cash as December 31st. And we've made tremendous progress over the course of 2022. And this upcoming year has the potential to dwarf all that we have previously accomplished. I'm particularly pleased that we're well capitalized to execute on all of our plans that we've outlined.

Ian Estefan: For the quarters ended December 31, 22, and 2021, we recognized $22.5 million and $22.7 million of collaboration and other revenues, respectively, which primarily relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $51. For the fourth quarter of 2022, compared to $29.7 million for the same period of 2021, on a gap basis, we reported a net loss of $109.2 million, or $1.24 and $122 million per basic and diluted share for the fourth quarter of 2022 and 2021, respectively.

Speaker 2: today on the call. And with that I'll turn the call back over to Doug for Q&A. Doug. Thank you very much again. Valerie, let's open up the lines for questions and answers. Thank you. Again ladies and gentlemen, if you'd like to ask a question please press star one on your telephone. Again to ask a question please press star one one.

Speaker 2: We do ask that you please limit yourself to one question. Thank you. One moment, please. Our first question comes from the line of Anupam Rama of JP Morgan. Your line is open. Hey, guys. Thanks so much for taking the question, and congrats on all the progress. I noticed in the press release, and, Doug, in your comments, as well, that the FDA noted no major safety concerns in the filing for 9001. Was there any commentary on the mid-cycle review on the external control arm and that analysis?

Ian Estefan: We reported a non-gap net loss of $46.5 million, or 53 cents per basic and diluted share, in the fourth quarter of 2022 compared to a non-gap net loss of $66 million, or $77. cents per basic and diluted share in the fourth quarter of 2021. In the fourth quarter of 2022, we recorded approximately $30.8 million in cost of sales compared to $31.7 million in the same period of 2021. The decrease in cost of sales is primarily due to write-off of certain batches of our products, not meaning the quality specifications for the three months ended December 31, 2021, 2021, with no similar activity in the same period of 2022 and a decrease in our royalty payments during the three months ended December 31, 2022 due to changes in our biomarin royalty.

Speaker 4: explicitly and inviting informed us that they saw no, they see no significant safety issues with the file and with nine years or one. You know, that would, that should come as a little surprise, I suppose, to those who know our profile, but it was to say the least gratifying and encouraging that the FDA saw it the way we saw it.

Speaker 4: I'm not going to get into a lot of detail on the review beyond what I've already said. I will say on the clinical side of things, we're in an active review, as you know, there are lots of questions and analyses that we've done and questions. We've answered, I can at least say, at the mid-cycle review, the division did not identify any significant issues. I'm not going to get into a lot of detail on the review.

Ian Estefan: On a gap basis, we recorded $213 million and $197.3 million in R&D expenses for the fourth quarter of 2022 and 2021, respectively, a year-over-year increase of $16.5 million. The increase is primarily due to increases in upfront and milestone expenses. On a non-gap basis, R&D expenses were $186.8 million for the fourth quarter of 2022 compared to $175.5 million for the same period of 2021, an increase of $11.3 million. And that's running to SG&A On a gap basis, we recorded approximately $120.5 million and $78.1 million of expenses for the fourth quarters of 2022 and 2021, respectively, an increase of $42.4 million. The increase was driven primarily by an increase in stock-based compensation expense, primarily due to additional expense recognized under the CEO grant modification agreement executed in 2022. On a non-gap basis, SG&A expenses were $86.

Speaker 2: Thank you. One moment, please. Our next question comes from the line of Brian Abrams of RBC. Brian Abrams of RBC, your line is open. Hey, good afternoon. Thanks for taking my question and congrats on all the progress.

Speaker 5: Is there anything more you can say, at least more broadly, on the nature of the CMC dialogue and preparation for the manufacturing inspections? And I guess I'm curious, your level of manufacturing confidence and overall comfort that there would be sufficient time post these inspections to rectify any minor issues that might come up.

Speaker 4: and still have sufficient time to build supply. And then just maybe quickly, I'm wondering also if the FDA provided any specific reasons as to why no ADCOM would be required. I know sometimes they give specifics on that. Thanks. Yeah, thank you very much for that, Brian . First, on CMC, I think as everyone knows and certainly we've talked about before with respect to BLAs, and I think in particular with gene therapy, the CMC part of the submission in the Q&As.

Speaker 4: is some of the most significant ones. As I mentioned before, as relates to all of the questions that the agencies had, we're current and have answered all of their questions. So we feel like we're in very good shape there. We feel like we're very good shape with those questions. As relates to the timing of the pre-approval inspections themselves, yes, we're very, very confident in the timing. So we, you know, I'm not going to go into detail on the schedules, but we're confident about the schedules and the timing.

Ian Estefan: For the fourth quarter of 2022, compared to $60.1 million for the same period of 2021, an increase of $26.5 million. On a gap basis, we recorded $5.5 million in other income net for the fourth quarter of 2022 compared to $16.1 million in other expense net for the same period of 2021. The change is primarily due to an increase in interest income due to 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 for the three months ended December 31, 2022.

Speaker 4: and the ability to adapt ourselves. We don't, as we've said here today, have any reason to believe that there would be a delay in our producer date for this or any other reason right now, at least as of now. And then as relates to the decision that there wasn't a need for an advisory committee, there really isn't any additional color other than, we had the mid-cycle.

Speaker 4: They confirmed they saw no safety issues, significant safety issues with the program. They didn't identify any significant clinical issues or major deficiencies and then determine that they didn't need an ad car. That's where we are right now.

Speaker 4: confirmed they saw no safety issues, significant safety issues with the program. They didn't identify any significant clinical issues or major deficiencies and then determined that they didn't need an ad-com. That's where we are right now. Thank you. One moment, please.

Ian Estefan: We expect that both SG&A and R&D expenses will be higher in 2023 as we build inventory and prepare for the launch of SRP 9001. The increases in expenses will, however, be partially offset by the growth in our revenue. We had approximately $2 billion in cash and cash equivalents as of December 31st. And we've made tremendous progress over the course of 2022, and this upcoming year has the potential to dwarf all that we have previously accomplished. I'm particularly pleased that we're well capitalized to execute on all of our plans that we've outlined today on the call. And with that, I'll turn the call back over to Doug for Q&A.

Speaker 2: Our next question comes from the line of Colin Bristow of UBS. Your line is open. Hey, good afternoon, and congrats on all the progress. Another one on the outcome or lack thereof. Previously, you stated that one of the focal points of the outcome you're anticipating would be the surrogacy of truncated dystrophin. Did FDA comment on its comfort around this, or is this something that's part of an ongoing dialogue? It's just part of the outcome.

Douglas S. Ingram: Thank you very much, Ian. Valerie, let's open up the lines for questions and answers.

Speaker 4: functional distrofen is reasonably likely to predict the clinical benefit. As relates to the ad comments, you know, we see this, we obviously see the decision to have an ad comment as a positive. We had a very productive mid-cycle review. We're not going to speculate on, you know, what this means from the probability of success. But what we would say is that...

Operator: Thank you. Again, ladies and Joan, if you would like to ask a question, please press Star 1-1 on your telephone. Again, to ask the question, please press Star-1-1. We do ask that you please limit yourself to one question. Thank you. One moment, please. Our first question comes from the line of Anapum Rama of JPM Morgan. Your line is open.

Speaker 4: Given that we know that there are no significant safety issues, that there isn't going to be an ad-com, we can then spend our time really focusing on answering any remaining questions, preparing for and executing our pre-approval inspections and doing that successfully, making sure that we're launch ready and building inventory for launch. We haven't given exact patient numbers.

Anupam Rama: as well as that the FDA noted no major safety concerns in the filing for 90,

Anupam Rama: Was there any commentary on the mid-cycle review of the external control arm and that analysis? If I remember correctly, that was a pre-specified analysis.

Speaker 4: as it relates to manufacturing. But what we've said and we stand by it is that our goal is to launch this therapy and serve this community without back orders with all patients getting the therapy as soon as they are able to get it from an access and reimbursement perspective. And we wanna be in a position to do that, we will be. Thank you. Our next question comes from Matthew Harrison of Morgan Stanley and line is open.

Anupam Rama: pre-specified analysis by the FDA, and then quickly on manufacturing. Doug, in your opening comments, did you say that the site inspections had been scheduled?

Douglas S. Ingram: Yeah, thank you very much for your question, John and Pomps. So first, as you noted about safety, at the mid-cycle review, the division explicitly, in writing, informed us that they saw no, they saw no significant safety issues with the file and with 9-0-0-01. You know, that should come as a little surprise, I suppose, to those who know our profile, but it was, to say the least, gratifying and encouraging that the FDA saw it the way we saw it.

Speaker 6: Great, thanks very much. Appreciate the question. I guess, I guess to just follow ups for me. I know we've we've touched on many of the major issues here, but first, just on on manufacturing, can you just talk to the extent you can in a bit more detail? Are these multiple facilities or just lines in the same facility that are being inspected? You know, how comprehensive is this inspection?

Douglas S. Ingram: As really, I'm not going to get into a lot of detail on the review beyond what I've already said. But I will say on the clinical side of things, you know, we're in an active review. As you know, there are lots of questions and analyses that, um, that, you know, that we've done and questions we've answered. But, I can at least say at the mid-cycle review, the division did not identify any significant issues or material deficiencies with the clinical data set at all. So that's where we are as of the mid-cycle. And then finally, as relates to the site inspections, yes, all of the manufacturing inspections have been scheduled.

Speaker 6: versus maybe what you were expecting or thought you might see. And then just secondly, on the inventory and the supply that you are building now, is there any chance or any reason that the supply you started to build now could not be used?

Speaker 4: And could you just talk about, you know, supply you have now versus supply you're continuing to build? Thanks. Yeah, so 1st of all on the inspections, there are 3 separate facilities. They are exactly as we anticipated. In fact, that I would say none of the. Questions that have been posed and none of the.

Speaker 4: inspection notices that we've received have been in all a surprise. We've been very well prepared for them so we're in good shape there. From an inventory and supply perspective we're on track and no, I don't think there's any significant risk that inventory that we build won't be able to be used commercially so we're tracking there. We have a lot of work to do as an organization. Site readiness is a significant issue. Building inventory is a significant issue.

Operator: Thank you. One moment, please. Our next question comes from the line of Brian Abrams of R.

Operator: of RBC, Brian Abrams from RBC, your line is open.

Brian Corey Abrahams: Hey, good afternoon. Thanks for taking my question and congrats on all the progress. Is there anything more you can say, at least more broadly, on the nature of the CMC dialogue and preparation for the manufacturing inspections? And I guess I'm curious about your level of manufacturing confidence and overall comfort that there would be sufficient time after these inspections to rectify any minor issues that might come up and still have sufficient time. time to build supply. And then, just maybe quickly, I'm wondering also if the FDA provided any specific reasons as to why no advertising would be required. I know sometimes they give specific instructions.

Speaker 7: of Tadeen Ahmad of Bank of America. Your line is open.

Speaker 8: Hi, good afternoon. Thanks for taking my question. Can you give us, Doug, a sense of how the doctors' offices or facilities that the patients would have to go to might have to make any adjustments?

Speaker 8: Is the infrastructure already there for high demand for the physicians to be able to meet the potential volume demand that we would expect upon an approval? I don't know what your checks are telling you, but love to hear some color on that. Yeah, I think the first thing I'll say is that we start in a very good place, probably in a very privileged place because

Brian Corey Abrahams: They give specific examples from that. Yeah, thank you very much for that, Brian.

Douglas S. Ingram: Yeah, thank you very much for that, Brian. First on CMC, I think, as everyone knows, and certainly we've talked about before, with respect to BLAs, and I think, in particular with gene therapy, the CMC part of the submission in the Q&As is some of the most significant ones. As I mentioned before, as relates to all of the questions that the agencies had, we're current and have answered all of their questions. So we feel like we're in very good shape there.

Speaker 4: because of SMA and because of Zolgensma. So a significant percentage of the experts and the neuromuscular experts that would be treating patients with Duchenne muscular dystrophy with 9001 have previous experience with Zolgensma. So we're starting with at a good place. Now, certainly I'm gonna turn this over to Dallin to provide any additional color that I missed, but I would say there's certainly a lot of work still that we need to do to make sure.

Douglas S. Ingram: We feel like we're in very good shape with those questions. As relates to the timing of the pre-approval inspections themselves, yes, we're very, very close to the timing. So we, you know, I'm not going to go into detail on the schedules, but we're confident about the schedules and the timing and the ability to adapt ourselves. We don't, as we sit here today, have any reason that there would be a delay in our Padovade for this or any other reason right now, at least as of now.

Speaker 4: that very specific to 9001, the sites are up ready to go, properly educated and ready to make this therapy a success. Our goal at launch is to have about 50 of those sites up and running that would serve just about 80% of the Duchenne community. And then over time to be up as high as about 70 sites over the course of the next couple of quarters beyond that.

Douglas S. Ingram: And then as relates to the decision that there wasn't a need for an advisory committee, there really isn't any additional color other than we had the mid-cycle. They confirmed they saw no safety issues or significant safety issues with the program. They didn't identify any significant clinical issues or major deficiencies. And then they determined that they didn't need an adequate

Speaker 5: engaging with the sites. Every site is different, but they are, you know, it's, these are centers of excellence that are already treating these patients, these Duchenne muscular dystrophy patients. So they'll be ready to go and we'll be ready to go. Thank you. Our next question comes from the line of Robert Fink of Guggenheim. Your line is open.

Douglas S. Ingram: Thank you. One moment, please. Our next question comes from the line of Colin Bristow of UBS. Your line is open.

Operator: Hey, good afternoon, and congratulations on all the progress. Another one on the adcom or lack thereof. Previously, you had stated that one of the focal points of the outcome you're anticipating would be the surrogacy of truncated dystrophin. Did FDA comment on its comfort around this, or is this something that's part of an ongoing dialogue and just part of the review process? And then maybe just on the manufacturing supply side, if you are approved for the Perdufer, you just talk about the number of patients you expect to be able to supply at launch and how this will build over time. Thanks a lot. Sure.

get infused on day one, there's a process here, the access and reimbursement process and having to get tested for neutralizing antibodies and the policies have to get finalized. But the team is already doing an enormous amount of work with not only sites but payers right now so that we're in a position to begin to serve the community day one post approval assuming that we're fortunate and get approved. Yeah yeah we'll be ready

Colin Nigel Bristow: Sure, first I would say, you know, that entire discussion, that's sort of the fundamental issue in the review, the use of shortened functional dystrophine, is whether we can be likely to predict the clinical benefit. As relates to the ad comments, you know, we see this, we obviously see the decision to not hold an ad comment as a positive. We had a very productive mid-cycle review.

Douglas S. Ingram: We're not going to speculate on, you know, what this means from the probability of success. But what we would say is that given that we know that there are no significant safety issues, that there isn't going to be an outcome, we can then spend our time really focusing on answering any remaining questions, preparing for and executing our pre-approval inspections and doing that successfully, making sure that we're launch ready and building inventory for launch. We haven't given out exact patient numbers. as it relates to manufacturing.

you've seen in terms of our launches for our PMO exon skipping franchise and obviously to dub and balance the point. It takes time to get patients on therapy and through the access and reimbursement system and obviously there's state Medicaid and getting through the drug utilization review board process. So it is going to take a couple of quarters.

for patients to work through and you've seen that before, but then once we really work through those reimbursement steps, I think you're gonna see very, very strong uptake. Thank you. This question comes from the line of,

Douglas S. Ingram: But what we've said, and we stand by it, is that our goal is to launch this therapy and serve this community without back orders, with all patients getting the therapy as soon as they are able to get it from an access and reimbursement perspective. And we want to be in a position to do that. We will.

Gina Wang of Barclays, your line is open. Again, Gina Wang of Barclays, your line is open. Thank you. I have two quick questions. Doug, you mentioned that there are still remaining questions from the FDA. What are the natures of these remaining questions? And do you expect lay cycle review will be mainly focusing on these questions and no new questions remaining? And the second question is regarding the three sites. Do any of these three sites have any questions?

Operator: Thank you. Our next question comes from Matthew Harrison and Morgan Stanley, and the line is open.

Matthew Harrison: Great, thank you very much; I appreciate the question. I guess two just follow-ups for me. I know we've touched on many of the major issues here, but first, just on manufacturing, can you just talk to the extent you can in a bit more detail? Are these multiple facilities or just lines in the same facility that are being inspected? You know, how comprehensive is this inspection versus maybe what you were expecting or thought you might see.

Matthew Harrison: And then just secondly, on the inventory in the supply that you are building now, is there any chance or any reason that the supply you've started to build now could not be used? Could you just talk about, you know, the supply you have now versus the supply you're continuing to build? Thanks.

have established commercial experience with Isallus manufacturing? Well, there's not a lot, you know, there's not a ton of history. I'll answer the last question first. I remind you that, you know, what we're doing, if not a first, is nearly a first. So, you're not going to find a lot of organizations around the world are going to have an enormous amount of experience with commercial Isallus unless they happen to be Novartis. What I will say is, so when we're in an active review, one of the things I tried to make the point of in my script is that we provided detail about the mid-cycle review, you know, frankly, because there was this...

Douglas S. Ingram: Yeah, first of all, in the inspections, there are three separate facilities. They are exactly as we anticipated. In fact, I would say none of the questions that have been posed and none of the inspection notices that we've received have been at all a surprise. We've been very well prepared for them, so we're in good shape there. From an inventory and supply perspective, we're on track, and no, we don't think there's any significant risk that the inventory that we build will be

significant interest in whether we were having an advisory committee or not. We're now in the active review itself. It's an ongoing dialogue and questions and answers. In respect of that discussion and dialogue with the agency, I'm not going to go into a ton of detail along the way. There will be a late cycle review and then. An gallery will then To research to help god bless ages

Douglas S. Ingram: able to be used commercially, so we're tracking there. You know, a lot of work to do as an organization. Site readiness is a significant issue. Building inventory is a significant issue. Completing this review and satisfying any remaining questions, comments, or analyses from the FDA is extremely important to us, and we need to focus on that as well. But the team is very, very focused on all of this, and we're working hard to ensure that we have a successful BLA review.

We'll see where we are. The inspections will be completed. And then if all goes well, of course, we'll have an answer certainly by May 29, and we hope it's a positive one. We certainly think the patients deserve it. Thank you.

Just back to the ad comp for a second. When FDA put in their minutes that they were going to have an ad comp and now they're saying they don't, it sounds like they had a question around the biomarker that at least they figured out that they can answer on their own at this point. Does that revolve around any additional data sets or analyses around the ongoing follow up from 102 or 103 that they've requested that you've since submitted or is it really just sort of questions as you've discussed? And then just a quick one on CMC. The plants, the Harmon plant and the two others, have you done any other questions?

Operator: Our next question comes from the line of Tazine Ahmad of Bank of America. The line is open.

Tazeen Ahmad: Hi, good afternoon. Thanks for taking my question.

Tazeen Ahmad: Can you give us, Doug, of how the doctors

Tazeen Ahmad: Doctors, or facilities that the patients would have to go to might have to make any necessary adjustments to the infrastructure already there for high demand for the physicians to be able to meet the potential volume demand that we would expect upon approval. I don't know what your checks are telling you, but I'd love to hear some color on that. Yeah, I think the first thing I'll say is that we start in a very good place, probably in a very privileged place, because of SMA and because of Zolgenzma.

Tazeen Ahmad: So a significant percentage of the experts and the neuromuscular experts that would be treating patients with Dushemusker, district with 9-0-0-1, have previous experience with Zolgentina. So we're starting with a good place. Now, certainly, I'm going to turn this.

Douglas S. Ingram: over to Dallon to provide any additional color that I missed. But I would say there's certainly a lot of work still that we need to do to make sure that, very specifically for 9-001, the sites are up, ready to go, you know, properly educated, and ready to make this therapy a success. Our goal at launch is to have about 50 of those sites up and running. That would serve just about 80% of the Duchenne community. And then, over time, to be up as high as about 70 sites over the course of the next couple of quarters beyond that. But Dallon, what have I missed there?

we didn't need an ad-com. What did occur is that we said in connection with the BLA submission that we should all assume there's going to be an ad-com. And given an opportunity to do this the second time, I would do that exactly the same way as second time. Why? Because we needed to be ready for an advisory committee meeting. There's an enormous amount of work.

that goes into preparing for an advisory committee meeting. And we wanted to make sure that we had a mindset that had us in a good position, so that to the extent that the FDA, the division determined that it was wise or necessary to take external scientific advice, that we'd be well prepared to participate in that ad com. It was at the mid-cycle review, both in the written agenda and at the mid-cycle, that the agency had, for the first time, told us that they don't need an ad com for this file. So that's where we are with respect to that.

to preparing for an advisory committee meeting and we wanted to make sure that we had a mindset that had us in a good position so that's the extent that the FDA, the division determined that it was wise or necessary to take external scientific advice that we would be well prepared to participate in that ad hoc. It was at the mid cycle review, both in the agenda and at the mid cycle that the agency had for the first time told us that they don't need an ad hoc for this file. So that's where we are with respect to that. Thank you. One moment please.

Douglas S. Ingram: No, you covered it, Doug. I think these sites are

Dallan Murray: And I think these sites are really at the forefront of precision genetic medicine, and they have a lot on their plates, but they're absolutely heroic, and we're working already with them on whatever we can do from an educational standpoint prior to approval that is compliant and appropriate. So the team is out there today engaging with their sites. Every site is different, but they are, you know, these are centers of excellence that are already treating these patients, these Buchenne muscular dystrophy patients. So they'll be ready to go, and we'll be ready.

Next question comes in a line of Joe Schwartz of SB Ringlight. Elana's open. Hi, this is Beth on Fragile. Thanks for taking our question. We are wondering how much pressure you believe that exhalated approval on the basis of district and expression provides for 9-001. Specifically, we are also wondering if you've been able to quantify the benefit of higher expression of a less complete microdistriction compared to the lower expression of a more complete shortened district and produced by axon skippers and...

Dallan Murray: Thank you. Our next question comes from the line of Robert Fink of Guggenheim. Your line is up, Hey team. This is Rod.

Operator: I'll turn this over to Dallas. The short answer is that we're going to be ready to go on day one. Doesn't mean kids are going to get infused on day one. There's a, you know, there's a process here, the access and reimbursement process, and kids have to get tested for neutralizing antibodies, and the policies have to get finalized. But the team's already doing an enormous amount of work with not only sites but payers right now so that we're in a position to begin to serve the community day one post-approval.

if this is something that FDA has been considering throughout the review? Okay, let me, yeah, let me answer this question. Let me start with the second part of it, then work to the first part of it because there's, there's a fundamental misunderstanding, understanding, it's understandable that you have the misunderstanding, but there's a misunderstanding of the underlying science when one assumes that the 901 district which is shortened is sort of vastly shortened and then the district that's made by a Sondis or Vyondis or Amandis or in the, in the case of, of one of our competitors Bill Tepso.

Operator: Assuming that we're fortunate and get approved, yeah, yeah, we'll be ready in terms of day one, and we're already engaging with payers. I think we're going to do everything we can to accelerate access for eligible patients on day one and learn the lessons from past launches.

is very lightly edited. I think there are those who might imagine that the resulting dystrophin is one exon smaller. That isn't the case. There the exon skipping occurs to place, to restore the reading frame and allow the messenger RNA to make dystrophin. That reading frame is restored by the removal of that exon and then it will naturally include also the removal of that parts of the gene that are associated with the mutation. And so for instance, the resulting dystrophin that you can make can be 40% shorter, smaller, and yet very functional versus wild type dystrophin. And that's the same case in natural history with better light dystrophin.

Douglas S. Ingram: Yeah, one thing just to add to that. I think one thing just to add to that is that you guys have, you know, good precedent for what you've seen in terms of our launches for our PMO, the Exxon Skipping franchise, and obviously, Doves and Downs. It takes time to get patients on therapy and through the access and reimbursement system, and obviously, there's state Medicaid and getting through the drug utilization review board process, right?

Becker Distrofen can be 50% or more shortened from full length distrofen, but so long as the reading frame is intact and it can make distrofen and it retains the right hinges and repeats and the right anchoring places, then it's functional. And that's the end of the talk.

Douglas S. Ingram: So it is going to take, you know, a couple of quarters for patients to work through, and you've seen that before, but then once we really work through those reimbursement steps, I think you're going to see very, very strong uptake.

Operator: Thank you. Our next question comes from the line of Gina Wang.

Operator: Wang of Barclays, your line is open. Gina winging up our Claiolaola is

Gena Wang: Thank you. I have two quick questions. Doug, you mentioned that there are still remaining questions from the FDA. What are the natures of these remaining questions? And do you expect the lay cycle review will be mainly focusing on these questions, with no new questions remaining? And the second question is regarding the three sites. Do any of these three sites have established commercial experience with Icelas manufacturer?

or exandus and biondus and amandus and doltepso is very relevant here.

Those therapies, while it's a different mechanism to get there because it's the use of exon skipping and a chronic therapy, it is the same underlying concept where what you're doing is providing to the patient a shortened but functional distrofen which will protect them. The biggest difference, in addition to the mechanism of action being different, here we're using a gene to...

Gena Wang: Well, there's not a lot, you know; there's not a ton of history. I'll answer the last question first. I remind you that, you know, what we're doing is, if not a first, is nearly a first. So you're not going to find a lot of organizations around the world.

Douglas S. Ingram: They're going to have an enormous amount of experience with commercialize Ellis unless they happen to be no artists. What I will say is, so, I mean, we're in an active review. One of the things I tried to make the point of in my script is that we've provided detail about the mid-cycle review, frankly, because there was this significant interest in whether we were having an advisory committee or not. We're now in the active review itself.

things and then kind of going on here. But so we say, number one, do I think there's a significant amount of precedent? I absolutely do. And I think there's an enormous amount of precedent for the idea that shortened functional dystrophin is the right kind of biomarker, reasonably likely to predict clinical benefit. It's the right kind of upstream biomarker that we should all be looking for. And then second of all, there is not a significant...

Douglas S. Ingram: It's an ongoing dialogue of questions and answers. And, you know, in respect of that discussion and dialogue with the agency, I'm not going to go into a ton of detail along the way. There will be a late cycle review. Then we'll see where we are. The inspections will be completed soon. And then, if all goes well, of course, we'll have an answer, certainly, by May 29, and we hope it's a yes. You certainly think the patient

difference in what's happening with 9001 and what happens with the PMOs other than the amount of distrofen we're making. And then one final thing I'll say as long as I'm on my soapbox on this topic. One must remember that in nature Becker distrofen is the result of mutations.

So the fact that these kids can make the adults indicate the becker, I think the average age, average mortality rate, the becker's well into the 60s on average. The fact they can make the district is a happy accident. They still have a reading frame and they can make the district. 901 is different. Dr. Radeena Klaipak, along with her partner, Dr. Jury Mendel, worked for well over a decade. To put this bill a construct that would be shortened, deliverable, but functional.

Douglas S. Ingram: Pardon me, the line for Ritu Barrow of Cowan is open.

Operator: Hi guys, thanks for taking the question. Deb, just back to the adcom for a second. You know, when FDA put in their minutes that they were going to have an adcom, and now they're saying they don't. It sounds like they don't want one.

Ritu Baral: Like they had a question around the biomarker that at least they figured out that they could answer on their own at this point. Does that revolve around any additional data sets or analyses around the ongoing or follow-up from 102 or 103 that they've requested that you've submitted, or is it just sort of questions as to what you do.

Ritu Baral: as you've discussed. And then just a quick one on CMC, the plants, the Harmon plant, and the two others. Have you completed mock inspections at all of them? Are you inspection ready?

And, you know, in the end, they were able to not only do that, do it safely and do it in a way that creates a robust amount of expression and, you know, our position is a protection. So there's my long-winded answer to your very simple question. Thank you. Our next question comes from the line of Judah Frama of Credit Sweet, Shilana's open. Yeah, hi guys. Thanks for taking the question. Just curious. If embark came up in any way in the mid-cycle communication, and if so, in what context, and kind of same question for conversations, you know, pre-commercialization conversations with payers is embarking after the topic of conversation.

Ritu Baral: I'll answer the last question first. We are undoubtedly inspection ready. We are, you know, we're an organization that doesn't want to be surprised. So we are very much inspection ready, and we've done all of the work to put ourselves in a good position. And that gets to the first, so it gets to the first, answer the first question as well.

Douglas S. Ingram: So let me make sure I dispel perhaps a misunderstanding. There wasn't a point in which the agency said to us in writing that we were going to have an adcom and then later determined that we didn't need an adcom. What did occur is that we said in connection with the BLA submission that we should all assume there's going to be an ad. And given an opportunity to do this a second time, I would do that exactly the same way as the second time.

As it relates to the mid-cycle, there was no explicit discussion of the embark at the mid-cycle. On pre-commercial discussions, certainly we discussed the entire program and it includes the confirmatory trial embark. So yes.

As it relates to the mid-cycle, there was no explicit discussion of the embark at the mid-cycle. On pre-commercial discussions, certainly we discussed the entire program and it includes the confirmatory trial embark. So yes. If there's anything I missed there, let me know.

Douglas S. Ingram: Why? Because we needed to be ready for an advisory committee meeting. There's an enormous amount of work that goes into preparing for an advisory committee meeting, and we wanted to make sure that we had a mindset that

Nope, that's exactly right. Thank you. Our next question comes from Gil Bloom of Needham. Your line is open. Our next question comes from Gil Bloom of Needham. Your line is open. Thank you. I missed that last portion. One quick technical. Isn't May 29th a holiday, just having to expect on the filings?

Douglas S. Ingram: had us in a good position so that, to the extent of the FDA, the division,

Douglas S. Ingram: determined that it was wise or necessary to take external scientific advice that we'd be well prepared to participate in that adcom. It was at the mid-cycle review, both

The other question I have is do you think the payer pathway is going to follow closely kind of you know the road map set by little Gen Zama thanks. So on the first of yes, it is the holiday. But officially May 29 is our the Padeu today so we would assume we could here on May 29. This is Memorial Day or we'll hear the the business day before then which would be May 26. I'm not mistaken or we would hear the day after May 29. But we're using May 29 because that is indeed the actual current Padeu today. So and I think the question on the the the payer approach I think the payer approach. So Gen Zama is probably you know one.

Douglas S. Ingram: and the written agenda and at the mid-cycle that the agent

Douglas S. Ingram: that the agency has, for the first time, told us that they don't need an adcom for this file. So that's where we are with respect to that.

Operator: Thank you. One moment, please. Our next question comes on the line from Joe Schwartz of SB Ringwright. Your line is open.

Operator: Hi, this is Bethan.

Bethan: for Joe. Thanks for taking our question. We are wondering how

Bethan: precedent you believe that Exondis's accelerated approval on the basis of distrophine expression provides for 9-001. Specifically, we're also wondering if you've been able to quantify the benefit of higher expression of a less complete microdistrophin compared to the lower expression of a more complete shortened distrophin produced by Exxon Skippers and if this is something the FDA has been considering throughout.

construct. I think we have an enormous amount of descend specific experience with the payer community. Obviously we've now been supporting three therapies. The earliest approval happened over six years ago. So I think we're in very good shape to have, you know, productive dialogue with payers about access and reimbursement for 9-0-0-1, assuming that we're able to get approved. Thank you. One moment please. Our next question comes from the line of Daniel Borrell, a Raymond James, your line is open.

Douglas S. Ingram: Okay, let me, yeah, let me answer this question. Let me start with the second part of it, then work my way to the first part of it, because there's a fundamental misunderstanding, understand, understand, that you have the mis-examination. But there's a misunderstanding of the underlying science when one assumes that the 9001 distrophin, which is shortened, is sort of vastly shortened, and then the distrofen that's made by Exondis or Viandis, or in the term, in the case of one of our competitors, Bill Tefso, is very lightly edited.

Hi guys, thanks for the question. I have a question on the microdiscence follow-up data. I believe we saw 60-litre data from Part 1 of Study 102. Do you have additional expression data at that time point or any expression data at later time points? And then random question, do you see any legal risks for 901 from Regenix-style ISP claim? Thank you. On the second question I'll answer and say now we don't.

Douglas S. Ingram: I think there are those who might imagine that the resulting district in is one exx smaller. That isn't the case. Exxon skipping occurs in place to restore the reading frame and allow the messenger RNA to make dystrophin. That reading frame is restored by the removal of that Exxon, and then it will naturally include also the removal of the parts of the gene that are associated with the mutation. And so, for instance, the resulting distrophin that you can make can be, you know, 40% shorter and smaller.

On the first question, I'll turn it over to Luis if you have, if you understand what I didn't fully understand the question. Apologies. It was just about additional time points. There's no additional biopsy time points in the study that we have. Thank you. One moment, please.

Our next question comes from the line of Hari Tash Singh of Oppenheimer. Your line is open. Great. Thank you. And congratulations on a very big step forward. Looking forward to many more. Just a question, actually, on SRT 9003. I know you've got the Roydean trial starting, the phase one. You're doing additional work. Doug, you're also doing a lot of work around characterizing the material, the clinical material, commercial, et cetera.

Douglas S. Ingram: and yet very functional versus wild-type dystrophin. And that's the same case in natural history with Becker-like distrophin. Becker-distrophin can be 50% or more shortened from full-length distrophin. But so long as the reading frame is intact, and it can make distrafin, and it retains the right hinges and repeats and the right anchoring places, it's functional.

Douglas S. Ingram: And that's the same thing with the nine. 0901 distrofen. This is a reasonable proclamation of any other Becker-like distrofen, just like Xandis and Amandis and Viandis and Vyondis and Vyatso and So make. And so, from at least our perspective, the precedent for Exondis and Biondis and Beltepso is very relevant. Those therapies, while there's a different mechanism to get there because of the use of exon skipping and a chronic therapy, it is the same underlying concept where what you're doing is providing to the patient a shortened but functional dystrophine, which will protect them. The biggest difference is the biggest difference.

If you could just talk to that, but also just talk to us a little bit about what the phase three design could look like. I believe you've indicated that could start later this year. Thanks for the question.

just talk about that, but also just talk to us a little bit about the phase three design could look like. I believe you've indicated that could start later this year. Thanks for the question. Yeah. Luis, do you want to take that?

Yeah, thanks for that question. Certainly, we're looking at this closely. This is an ultra-rare indication, and so we're looking at all the data we have to date in both the ambulatory population and now the new population that we're studying, which is the older ambulatory and non-ambulatory. And so that's the totality of the patient population could be captured in that phase 3 design. So we don't have it finalized yet, but all of the results from these two trials will be taken into consideration when we have the ultimate study design for that phase 3 study.

Douglas S. Ingram: In addition to the mechanism of action being different, here we're using a gene cassette to make the distrofen. The biggest difference between these two is the amount of dystrophin we are making as well as over, you know, multiples of an order of magnitude more dystrophin with our gene cassette than we can make with the PMOs today, given the delivery limitations there. And so a couple of things, and then, you know, I'm kind of going on here, but so we say, number one, do I think there's a significant amount of precedent?

Thank you. Our next question comes from Yun Zong of BTIG. Your line is open. Thank you for taking the question. So my question is actually also on the LING-GO-DO program. And I was wondering, what is the purpose of the Phase 1 study and what kind of information are you trying to get? And given the small prevalence of the indication, what's your thinking on the patient allocation enrolling patient into the current study? I don't believe you have disclosed the size of the study versus maybe saving patients for future pivotal study. Yeah, I'll touch on it briefly and then I'll… Luis can answer it and correct me when I get this wrong. I mean, the reason that we're doing…

Douglas S. Ingram: I absolutely do, and I think there's an enormous amount of precedent for the idea that short and functional distrophin is the right kind of biomarkerone is the right kind of biome, and they are reasonably likely to predict clinical benefit. It's the right kind of upstream biomarker that we should all be looking for. And second of all, there is not a significant difference in what's happening with 9-0-01 and what happens with the PMOs other than the amount of distrofen we're making.

There are two reasons why we've done this clinical experience study. The first is that it gives us an opportunity to explore the safety and expression of the therapy in a broader patient population than we would typically do for our pivotal trial itself. So we will glean. But first off, students and faculty can take turns everything into account. What we do have in place is a video clip Good evening.

Douglas S. Ingram: And then one final thing I'll say as long as I'm on my soapbox on this topic: one must remember that, in nature, Becker dystrophin is the result of mutates. So the fact that these kids can make dystrophin, kids are adults, in the case of Becker, I think the average age, average mortality rate for Becker's as well into the 60s on average. The fact that they can make dystrophin is a happy accident. They still have a reading frame, and they can make dystrophin.

important information. And the second reason that we did it is that we had clinical material available to us. So for the pivotal trial, we need to have commercially appropriate material, and that has to be material that would be appropriate. So the launch of this therapy, we have very appropriate clinical material right now, and it seemed appropriate to...

Douglas S. Ingram: 9-0-0-1's different. Dr. Radino Clayback, along with her partner, Dr. Jerry Mandel, worked for well over a decade to purpose-build a construct that would be shortened, deliverable, but functional, and, you know, in the end, they were able to not only do that, do it safely, and do it in a way that creates a robust amount of expression. And, you know, our position is So there's my long-winded answer to you.

to make good of it to get additional insight and also to frankly to provide a benefit at the same time. Luis? I think you characterize it well to emphasize that this is a different patient population than we've previously studied in older patients where we can look at safety and efficacy and non-ambulatory and older ambulance, which is an important component of the prevalent population. Thank you. Our next question comes from a lot of Kristen Klaskov-Kentley. A lot is open. Hi, this is Rick Owen from Kristen. Thanks for taking our question. In the press release, I mentioned that the cattle in agreement structures how cattle and could support multiple gene therapy candidates in the LGMD pipeline. So could you maybe go into a little detail here on what this might mean?

Operator: Thank you. Our next question comes from the line of Judah Frama of Credit Suisse. Your line is open.

Judah C. Frommer: Yeah, hi, thanks for taking the question. Just curious.

Judah C. Frommer: if Embark came up in any way in the mid-cycle communication, and if so,

Judah C. Frommer: in what context and kind of same question for conversations, you know, pre-commercial?

Judah C. Frommer: and pre-commercialization conversations with payers is coming up as a topic of conversation now.

Douglas S. Ingram: As regards the relation to the priest, mid-sacel, there was no explicit discussion of embarkation at the mid-cycle. In pre-commercial discussions, you know, certainly we discussed the entire program, and it included the confirmatory trial in Bark. So yes.

Douglas S. Ingram: If there's anything I missed there, let me know. Nope, that's exactly right. Thank you.

Operator: Our next question comes from the line of Gil Bloom of Needham. Your line is open. Our next question comes in the line of Niels, from Gil Bloom. Your line is open.

Gil Blum: portion. One quick technical question, isn't May 29th a holiday? Is that the fact on the filing? And the other question I have is, do you think

Gil Blum: The other question I have is, do you think the payer pathway is going to follow closely, kind of, you know, the roadmap set by Zolenzema? So on the first one, yes, it is the holiday. Officially, May 29 is our Purdue date. So we would assume we could hear on May 29th, this is Memorial Day, or we'll hear the business day before then, which would be May 26, if I'm not mistaken, or we would hear the day after May. But we're using May 29 because that is indeed the current Padua Day.

is to have commercial representative material from the beginning and that's gonna be our goal. The potential of doing that with CataLink is a significant one. Thank you. Our next question comes from Gavin Clark Gardner of Avacor, your line is open.

Yeah, hey, thanks for taking the question. I'll phase three, you excluded ex-ounds 1-17, but as you noted, you've been dosing patients inside that range. Have you had any discussion on getting some of those ex-ounds included in the initial label? And is there any chance that something in here could represent a major amendment? Thanks. I won't be a major amendment because our BLA went in with the assumption that we would have a narrower exclusion. We already had good scientific rationale for why the label...

Douglas S. Ingram: Um, and I think the question on the payer approach. I think the payer approach, so Gensma, is probably, you know, one construct. I think, you know, we have an enormous amount of Duchenne-specific experience with the payer community. Obviously, we've now been supporting three therapies. The earliest approval happened over six years ago, so I think we're in very good shape to have, you know, productive dialogue with payers about access and reimbursement for 9-0-0-01, assuming that we're able to get approved.

The labeled exclusions needed should be narrower that we were being overly exclusive in those mutations. And then to support that thesis, we started this and we're nearly done enrolling a study to explore those mutations that's going quite well right now. But our initial BLA went in with the request that we have a narrower exclusion in our proposed.

Operator: Our next question comes from the line of Danielle Brill. Raymond James, your line is open.

Danielle Brill: Hi, thanks for the questions. I have a question on

Danielle Brill: the microdistrictment follow-up data. I believe we saw 60-lead data from part one of

label in connection with our initial BLA submission made that same assumption. Thank you. One moment, please. Our next question comes from the line of Salveen Richter. Your line is open. Hi, this is Tomie on for Salveen. Thanks so much for taking our questions and congrats on the progress. Just wondering how you're thinking about uptake in between that period after the accelerated approval but before EMBARK reads out any physician or payer commentary that some might wait to prescribe to see EMBARK. And can you just remind us how long it takes for patients to get tested for eligibility? Thanks so much. So we don't, with our current thinking based on all of our discussions, both with thought leaders and with certainly, you know, the

Danielle Brill: Study 102 study 102 does not have additional expression data at that time point or any expression data at a later time point. And then random questions.

Danielle Brill: Random question: do you see any legal risk for 901 from Regenic bio IP claims? Thank you.

Douglas S. Ingram: On the second question, I'll answer and say no, we don't. On the first question, I'll turn it over to Luis, if you have, if you understand what. I didn't fully understand the question, Paul. It was just about additional time points. There are no additional biopsy time points in the one study that we haven't done.

Operator: Our next question comes from the line of Hard Touch Singh of Oppenheimer. Your line is open.

Hartaj Singh: All great, thank you, and congratulations on a very big step forward; looking forward to many more. Just a question actually on SRP 9003.

Hartaj Singh: I know you've got the Roy Gene trial starting, phase one, you're doing additional work. Doug, Louise, you're also doing a lot of work around, you know, characterizing the material, the clinical material, commercial, et cetera. If you could just talk about that, but also just talk to us about what the phase three design could look like. You've indicated that it could start later this year. Thanks for Luis. Do you want to take that?

Dr. Louise Rodino-Klapac: Yeah, thanks for that question. Certainly, we're looking at this closely. This is an ultra-indication, and so we're

Dr. Louise Rodino-Klapac: Looking at all the data we have to date in both the ambulatory population and now this new population that we're studying, which is

treating physicians either. Certainly those who have seen what 9001 could do I don't think would want to wait.

As far as the process, you know, Dow and you want to touch on the process itself. Yeah, yeah, yeah, and just to underscore what you said about the urgency dug. That's what we're seeing out there as well. And I think in terms of what the team has for the process, the data is. And you want to say something about offering a particular ???

Dr. Louise Rodino-Klapac: is the older ambulatory and non-ambulatory patients so that the totality of the patient population could be

Dr. Louise Rodino-Klapac: patient population could be captured in that phase three design. So we don't have it finalized yet, but all of the results from these two trials will be taken into consideration when we have the ultimate study design for that phase three study. Thank you.

you know, to have a fully enrolled confirmatory trial at the time of approval is just such an incredible position to be in. And so that's going to inform all of our dialogue going forward on this.

Operator: for taking a question. So my question is actually also on the Lim GER program, and I was wondering, what is the purpose of the phase one study and what kind of information you are trying to get, and given the, you know, small prevalence of the indication, what you're thinking on patient allocation, and enrolling patients into the current study. I don't believe you have disclosed the size of the study versus

Thank you. I'm showing no further questions at this time. Let's turn the call back over to Doug Engram for any closing remarks. Well, thank you very much, everyone, for joining us this evening and for your very good questions. It is a poignancy. I think as Dr. Rodino-Kleibach noted, that today is indeed Rare Disease Day. We are completely committed to using great science and moving as fast as possible to bring a better life to.

Operator: versus maybe saving patients for a future pivotal study.

Operator: Yeah, I'll give you a brief name now, and Luis can answer it and correct me when I get this wrong. I mean, the reason that we're doing this, there are two reasons why we've done this clinical experience study. The first is that it gives us an opportunity to explore the safety and expression of the therapy in a broader patient population than we would typically do for our pivotal trial itself. Thus, we will glean important information.

Operator: And the second reason that we did it is that we had clinical material available. So for the pivotal trial, we need to have commercially appropriate material, and that has to be material that would be appropriate. So the launch of the therapy; we have very appropriate clinical material right now, and it seemed appropriate to make good use of it, to get additional insight and also, frankly, to provide a benefit at the same time. Luis? I think you characterize it well; just emphasize it.

Have a great day.

Douglas S. Ingram: That this is a different patient population than we've previously studied.

Dr. Louise Rodino-Klapac: and older patients where we can look at safety and efficacy and non-ambulatory and older ambulatory, which is an important component.

Dr. Louise Rodino-Klapac: and older ambulatory, which is an important component of the prevalent population.

Operator: Our next question comes from Alana Kristen Klasker of Canthi. Alon, please, is open.

Operator: Hi, this is Rick on behalf of Kristen. Thanks for taking our question. In the press release, it mentioned that the Catalan agreement lays out how Catalan could support multiple gene therapy candidates in the LGMD pipeline. So could you maybe go into a little detail here on what this might mean in terms of whether this could deal with clinical grade material or potentially commercial grade material for later stage trials and LGMD. Yeah.

Douglas S. Ingram: Yeah, our relationship with Catalan, and our goal is to, they would potentially have the opportunity to ban your factual content for us for Lim Gertil. Really, our goal going forward is to try to have commercial representative material from the first inpatient clinical trial. You know, historically, as we evolved from nationwide Children's Hospital, as you know, the first study with 9-001 started with clinical material. Likewise, 9-003 started with clinical material provided by nationwide. But the fastest pathway forward is to have commercial representative material from the beginning, and that's going to be our goal. And the potential to do that with Catalanches.

I.

Operator: Thank you. Our next question comes from Gavin Clark Gardner of Evercore. Your line is open.

Operator: Yeah, hey, thanks for taking the question.

Operator: excluded exons 1 through 17, but as you noted, you've been dosing patients inside that range. Have you had any discussion on getting some of those?

Operator: getting some of those exons included in the initial label, and is there any chance that something in here could represent a major amendment? Thanks.

Douglas S. Ingram: It won't be a major amendment because our BLA went in with the assumption that we would have a narrower exclusion. We already had good scientific rationale for why the labeled exclusions need to be narrower because we were being overly exclusive in those mutations. And then to support that thesis, we've started this, and we're nearly done enrolling a study to explore a study of those mutations. It's going quite well right now. But our initial BLA went in with the request that we have a narrow or exclusion in our proposed label in connection with our initial BLA submission made that same same assumption.

Operator: Thank you. One moment, please. Our next question comes from the line of Salving Richter.

Operator: Hi, this is Tommy on behalf of Selveen. Thanks so much for taking your questions and congrats on the progress. Just wondering how you're thinking about uptake in between that period after the accelerated approval that before Embark reads out, any physician or payer commentary that some might wait to prescribe to see Embark, and can you just remind us how long it takes for patients to get tested for eligibility? Thanks so much.

Douglas S. Ingram: So we don't, look, our current thinking based on all of our discussions, both with thought leaders and with, certainly, you know, with patient groups and families, that people wouldn't wait. Waiting is not a viable option for people with this degenerative disease. I would note that by the end of this call, somewhere around the world, a kid with Duchenne will have died, and another kid will be going on a vent, and another kid will be going into a wheelchair, never to get back out of a wheelchair.

I have you.

Douglas S. Ingram: So the luxury of patience isn't there for these families. So we don't intend to, you know, we don't imagine that people would wait for, you know, other readouts down the road and put their kids at risk. At least that's not our current assumption, nor do we think it's the assumption of the, the, um, the, um, the, uh, the, you know, treating for the, you know, physicians either. Certainly those who have seen what 9-001 can do, I don't think they would want to win.

Dallan Murray: As far as the process is concerned, Dalland, do you want to touch on the process itself? Yeah, and just to underscore what you said about the urgency, Doug, that's what we're seeing out there as well. And I think in terms of what the team has for the process, the data is, you know, to have a fully enrolled confirmatory trial at the time of approval is just such an incredible position to be in. And so that's going to inform all of our dialogue going forward.

Operator: I'm showing no further questions at this time. Let's turn the call back over to Doug Ingram for any closing remarks.

Douglas S. Ingram: Well, thank you very much, everyone, for joining us this evening and for your very good questions. It is a poignancy.

Douglas S. Ingram: I think, as Dr. Radino Clayback noted, that today is indeed rare disease day. We are completely committed to using great science and moving as fast as possible to bringing a better life to Duchenne patients and beyond Duchenne patients to other rare disease patients. And I look forward to updating people along the way, although I will note yet again that as relates to the BLA for 9001, the next substantive update you'll get is on our round on May 29th, which is our action date. So thank you all very much and have a lovely day. Ladies and gentlemen, this does conclude today's conference. Thank you all for your participation.

Operator: Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day, and and and and uh and uh and uh... and You and and You and and I uh... You uh... and You uh uh You and and and and and You and and You and and You.

Operator: Shortly, to raise and lower your hand during Q&A, you can dial Star 1-

Operator: Good afternoon, and welcome to the Surreth Therapeutics fourth quarter and full year 2022 earnings call. At this time, all participants are

Operator: on a listen-only mode. After the speaker's presentation, there'll be a question and answers session.

Operator: and answer session. To ask a question at that time, please press star 1-on on your telephone.

Operator: As a reminder says, the conference caller is being recorded. At this time, I was trying to call Mary Jenkins,

Operator: and Mary Jenkins, Associate Director, Bestor Relations. Please go ahead.

Operator: Thank you, Valerie, and thank you all for joining today's call.

Operator: we released our financial results for the fourth quarter and full year 2022. The press release is available on our website at Direcda.com, and our 10K was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, and Dr. Louise Rodino Claypec.

Operator: After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will 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 Suraptist 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 Surreptus common stock. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent annual report on Form 10k filed with the SEC, as well as the company's other SEC filings.

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

Operator: Thank you, Mary. Good afternoon, everybody, and thank you for joining Surreth Therapetics for our fourth quarter and full year 2022 financial results conference call. 2023 may be the most eventful year in Serepta's event-filled history. Our Biologics License Application, or BLA, for our gene therapy, SRP-001, for Duchenne Muscular District Dyser, will be a significant bellwether moment. First, for the Duchenne families who are waiting without the luxury of patients for a therapy that might arrest the brutal decline associated with this disease, and next for the promise of gene therapy as a class, to deliver meaningful improvements in the lives of patients with rare degenerative diseases not at some distant vanishing point in the future but in time to do good now.

Operator: Given the keen interest in the 901 BLA submission, I'm going to comment on the BLA review before I move to quarterly and yearly performance. As you will recall, in the fall of last year, we submitted our BLA for SRP 9001 to treat ambulant Duchenne patients. And in the fourth quarter, the FDA accepted the DLA for filing, granted 901 priority review, and set May 29, 23, as our action date. We have been diligently prosecuting the BLA.

Operator: We have by now completed a very productive mid-cycle review with the division. At the mid-cycle, the division requested additional CMC information, and we have by now provided answers to all of those questions. The division formally informed us, as well, at the mid-cycle meeting, that they see

Operator: that they see no significant safety issues that have been identified.

Operator: And the division has determined that there is no need for an advisory committee meeting for SRP 9001 BLF. As you may have read, FDA has announced that the Office of Tissues and Advanced Therapies, or OTAT, is being reorganized into a new super office entitled the Office of Therapeutic Products, or OTP, is being established. The goal is to improve alignment, increase resources and capacity, and enhance expertise. A couple of thoughts. First, Serepta is delighted by the establishment of OTP. We believe it will enhance reviews and serve Dr. Peter Mark's publicly stated vision to lean in and accelerate the transformative potential of cell and gene therapy.

Operator: Second, FDA has stated that the reorganization and

Operator: The establishment of OTP will not impact any time, and we can confirm that we have not experienced any delay or disruption of any kind as a result of this reorganization.

Operator: organization. Indeed, we see the establishment of OTP as unequivocally positive.

Operator: positive and potentially a great benefit to patients. Going forward, we're going to focus on the following. First, answering any remaining questions the FDA may have on the file. Second, preparing for and managing pre-approval inspections. The FDA has already scheduled three pre-approval manufacturing inspections, and along with our manufacturing partner, Catalan, we are preparing to make those inspections a success. Third, building inventory for launch, and fourth, of course, completing our launch readiness.

Operator: Now I've provided an update on the mid-cycle today as there has been a significant amount of interest.

Operator: and whether the division would see the need for an advisory committee. However, from here on, we will be focusing on prosecuting the BLA and will provide an update on or after the 9-0-01 action. Moving now to performance. As you ponder how Sirepta may execute the launch of 901, if given that opportunity, I would ask you to consider the team's consistent performance, quarter over quarter and year over year, serving the Duchenne community with our three approved therapies, Exondis, V, and Amman.

Operator: From an in-market perspective, 2022 was yet another year where our cross-functional team, including commercial, medical affairs, patient services, access and reimbursement, and manufacturing and supply chain, to name a few, executed together and delivered for us. Fourth quarter total revenue stood at $258.4 million, while net product revenue came in at $235.9 million. That was a 32% increase over the same quarter of the prior year; full year total revenue came in at $933 million, and net product revenue for the year came in at $8.8 million, representing a 38% year-over-year increase.

Good afternoon, and welcome to the Sorepta Therapeutics fourth quarter and full year 2022 earnings call. At this time, all participants are on a listen-only mode. After the speakers' presentations, there will be a question-and-answer session. To ask a question at that time, please press star-11 on your telephone. As a reminder, today's conference call is being recorded. At this time, I will turn the call over to Mary Jenkins, Associate Director of Investor Relations. Please go ahead. Thank you, Valerie, and thank you all for joining today's call. We'll be right back.

Earlier this afternoon, we released our financial results for the fourth quarter and full year 2022. The press release is available on our website at directed.com and our 10K with filed with the Security and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estipan, Alan Murray, and Dr. Louise Rodino Claypac. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we've been 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 threatless control. Actual results could materially differ from these forward-looking statements. And any such risks...

Operator: For the last five years, we have grown at a consistent 40% compounded annual growth, all of which performance comes from serving the Deschen community, and none of which comes from Price. Now, as we announced at the J.

Operator: For 2023, our net product revenue guidance for our three currently approved PMO therapies, excluding the impact of a 9-001 approval, is $925 million or greater. Moving back to SRP 901 for a moment, we are commencing studies this year to ensure that we have the broadest label for SRP 9001 as is possible consistent with the sign. We have already commenced our study to limit mutation-related exclusion; further, in the coming months, we will be starting a study in the non-amblant population called Envision, or study 303.

Operator: And we will commence two separate studies with alternative approaches to removing pre-existing antibodies to make SRP 901 available to R874 NAB positive patients as well. Additionally, we are making significant progress with our limb girdle pipeline, as Dr. Luis Rodino Clayback will discuss in a moment as she provides updates across our research and development activities. On the R&A platform, we will complete enrollment of

2023 may be the most eventful year in <unk> history.

<unk> license application or BLA for our gene therapy, SRP 9001 for Duchenne muscular dystrophy will be a significant bellwether moment first for the Duchenne families who are waiting without the luxury of patients.

Operator: momentum study this quarter. Momentum, as you know, is our study for our first next generation.

Operator: for our first next-generation, peptide conjugated PMO, also known as a PMO, and that's SRP 5051, designed to treat Duchenne patients who are Exxon 51 amenable. Momentum will read out later this year, and if successful, we will discuss a filing for SRP 5051 with the Neurology Division this year. I am proud of the progress that we have made these last six years, and yet it pales in comparison to the good that we can do in the coming years together.

Therapy that might arrest the brutal decline associated with this disease.

And next with the promise of gene therapy, as a class to deliver meaningful improvements in the lives of patients with rare degenerative diseases not at some distant vanishing point in the future, but in time to do good now.

Given the keen interest in the 9001 BLA submission.

Comment on the BLA review before I moved to quarterly and yearly performance.

As you will recall in the fall of last year, we submitted our BLA for SRP 9001 to treat Angela Duchenne patients and in the fourth quarter. The FDA accepted the BLA for filings granted <unk> priority review and set May 29, 2023, as our action date.

Operator: We have the potential to improve the lives of countless patients and to greatly reward those who have been committed to and invested in this mission. Indeed, the opportunity in front of us is breathless. To realize that opportunity, we will need laser-and tenacious execution. But as Serepta has proven time and again, this is a team that knows how to execute. And with that, let me turn the call over to our head of R&D and chief scientific officer, Dr. Luis R. Klepeg.

We have been diligently prosecuting the BLA, we have by now completed a very productive mid cycle review with the division.

At the mid cycle the division requested additional CMC information and we have by now provided answers all of those questions.

The division formally informed us as well at the mid cycle meeting that they see no significant safety issues that have been identified.

Operator: The accomplishments of 2022 and the opportunities before us in 2023 and beyond speak to the promise of science to fundamentally impact and change.

And the division has determined that there is no need for an advisory Committee meeting for SRP 9001 BLA.

Operator: lives of patients around the world. My deepest gratitude to our R&D colleagues across RNA, gene therapy, and gene editing for their extraordinary work to get us where we are today. And where we are today represents an important moment in genetics

As you May have read FDA has announced that the office of tissues and advanced therapies or <unk> is being reorganized in our new Super office entitled The office of therapeutic products or Otp is being established the goal is to improve alignment increased resources and capacity and enhanced expertise.

Operator: medicine and an important moment for Surre. Firstly, we were thrilled to learn last November that the FDA accepted our BLA for review via the accelerated approval pathway for our lead gene therapy.

Yes.

A couple of thoughts first <unk> is delighted by the establishment of Otp, We believe it will enhance reviews and serve Dr. Peter marks publicly stated vision to lean in and accelerate the transformative potential of cell and gene therapy second FDA has stated that the reorganization and establishment.

Operator: it at SRP 9001. This decision was based on our ability to show robust expression of the SRP 901 destroyer

Operator: dystrosin protein, a shortened functional version of dystrophin, serving as a surrogate endpoint reasonably likely to predict clinical benefit in patients with Duchenne muscular dystrophy. Deschen results from a mutation in the gene that codes for dystrosin. Dystrophon acts as a shock absorber in our muscle, attaching to the muscle membrane and distributing force as we move, thereby protecting our muscles from damage.

Of Otp will not impact any timelines and we can confirm that we have not experienced any delay or disruption of any kind as a result of this reorganization. Indeed, we see the establishment of Otp is unequivocally positive and potentially great benefit.

Two patients so going forward, we're going to focus on the following.

First answering any remaining questions. The FDA may have on the file.

Second preparing for and managing pre approval inspections. The FDA has already scheduled three pre approval manufacturing inspections and along with our manufacturing partner <unk>, we are preparing to make doses.

Operator: Individuals with Duchenne lack dystrophin, and as a result, their muscles become progressively worse. Our goal with SRP 9001 is to change the course of the fatal disease by treating the underlying cause of Duchenne with a one-time gene therapy that's

Sections of success.

Third building inventory for launch and fourth of course, completing our launch readiness.

Operator: that delivers functional dystrosin to the muscle. Based on well-established precedent, the FDA has approved four therapies to date using shortened functional dystrophin as a surrogate endpoint.

Now I'll provide an update on the mid cycle per day is there has been a significant amount of interest in whether the division would see the need for an advisory Committee. However.

Operator: Furthermore, Surrepta has generated the most compelling preclinical biomarker and clinical functional results to date.

Im here, we will be focusing on prosecuting the BLA and we will provide an update on or after the 900 <unk> action date.

Operator: What is particularly interesting about SRP 9001, but not completely surprising based on the strong scientific underpinning of our construct, is that the early SRPs

Moving now to performance as one ponders house the Rep. They may execute the launch of 9001, if given that opportunity I would ask you to consider the team's consistent performance quarter over quarter and year over year, serving the Duchenne community with our three approved therapies Exxon this.

Operator: 9001 data provided read-to our positive clinical experience with the therapy. Over the course of 10 plus years, I, along with Dr. Jerry Mendel, built, researched, and tested numerous constructs to determine what areas of the protein were functional and protective. We eventually identified an optimal gene cassette that will be able to retain protective and functional elements and fit easily into AAV, thereby enabling its delivery. This gene cassette was packaged into our AAZ of choice, and we chose MHCK7 as our promoter. We were pleased with the early data, which showed robust expression across skeletal, diaphragm, and cardiac muscles, and as a result of that expression, as well as the dystrophin protein.

By on this end demand is.

From an end market perspective, 2022 was yet another year, where our cross functional team, including commercial medical affairs patient services access and reimbursement and manufacturing and supply chain to name a few executed together and delivered for our patients fourth quarter total revenue stood at two.

$258 4 million, while net product revenue came in at $235 9 million that is a 32% increase over the same quarter of the prior year.

Operator: The dystrophin protein demonstrating functional benefits, we saw significant restoration of function at the clinical target dose.

Operator: To understand the significance of the results and their importance in the context of a viable therapy for Duchen, it's critical to

Full year total revenue came in at $933 million and net product revenue for the year came in at $843.

Operator: It's critical to understand the dystrophin-associated protein complex, or DAPC.

$8 million, representing a 38% year over year increase.

Operator: Dep C is a collection of proteins to which distrofen attaches.

Over the last five years, we have grown at a consistent 40% compounded annual growth rate all of which performance comes from serving the Duchenne community and none of which comes from price increases now.

Operator: In its absence, these proteins disassemble. Therefore, individuals with Dishin don't have a functioning dystrophin-associated protein complex. 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 SRPN of the SROFIN, confirming the protective properties of the protein

Now as we announced at the Jpmorgan Conference in January for 2023, our net product revenue guidance for our three currently approved PMO therapies, excluding the impact of a 9001 approval is $925 million or greater.

Moving back to SRP 9001 for a moment, we are commencing studies this year.

Operator: Further, we saw a significant reduction in kinates or cK levels. CK is an enzyme associated with muscle damage. The reduction in CK.

To ensure that we have the broadest label for SRP 9001 as is possible consistent with the science. We have already commenced our study to limit mutation related exclusions further in the coming months, we will be starting a study in the non ambulant population called envision or study <unk> III.

Operator: provided further proof that SRP 9001 was reasonably likely to predict clinical benefits. The strength of this early work gave us the confidence and conviction to advance SRP 901 into the clinic. Since 2018, and across multiple studies, we've dosed over 140 patients, more than any other gene therapy being developed.

And we will commence in two separate studies with alternative approaches to removing preexisting antibodies to make SRP 9001 available to <unk> 74, Nab positive patients as well.

Operator: is being developed for Duchenne, and the clinical results have surpassed our expectations. SRP 9001 demonstrated robust expression of dystrophin, far above what literature would suggest is necessary to be protective of muscle.

Additionally, we are making significant progress with our limb girdle pipeline as Dr. Louise Rodino, Kuwait back will discuss in a moment as she provides updates across our research and development activities.

Operator: All of it is properly localized to the muscle membrane or

Operator: Starka, where it acts as a shock absorber. We also developed a cell-based potency assay that shows that SRP 901 is active.

On the RNA platform, we will complete enrollment of the momentum study this quarter.

Mentum as you know is our study for our first next generation peptide conjugated PMO also known as a PMO.

Operator: active, functional, protective, and protective at the muscle membrane.

Operator: And as in the animal models, with robust expression of SRP 901, we saw a significant reduction in CK. Finally, expression of SRP 901 in patients leads to upregulation of the DAPC.

SRP $50 51 designed to treat duchenne patients who are exon 51.

Animal.

Momentum will read out later this year and if successful we will discuss a filing for SRP $50 51, with the neurology Division this year.

Operator: In addition to all of this compelling evidence, we were also able to show functional benefit versus what natural history would predict. NSAA, or the North Star Ambulatory Assessment, is our primary functional endpoint. We were able to show benefit across one, two, and four-year time periods. In summary, based on the fatality of the data, we were able to provide objective.

I am proud of the progress that we have made.

These last six years.

Yet it pales in comparison.

So the good that we can do in the coming years.

Together.

We have the potential to improve the lives of countless patients and to greatly reward those who have been committed to and invested in this mission. Indeed, the opportunity in front of us is breathtaking.

Operator: evidence.

Operator: SRP 9001 qualifies as a disease

To realize that opportunity, we will need laser focused and tenacious execution.

Operator: is a disease-

Operator: and that the levels of dystrosophers, based on vast clinical evidence and experience

But as <unk> proven time and again this is a team that knows how to execute.

Operator: are reasonably likely to predict clinical benefit in patients with Duchenne. As Doug mentioned in his opening comments, since the agency is not planning on holding an advice session,

And with that let me turn the call over to our head of R&D and Chief Scientific Officer, Dr. Louise Rodino playback Luis.

Thanks, Doug.

The accomplishments of 2022 and the opportunities before us in 2023 and beyond speak to the promise science to fundamentally impact and change the lives of patients around the world.

Operator: They are planning on holding an advisory committee for SRP 901. The team is focused on responding to any remaining requests. As a reminder, and because we are in an active review with the FDA, we do not anticipate publicly sharing additional data cuts from the SRP 9701 studies leading up to the 2023 regulatory milestones and the embark data read-up, which is on track for the fourth quarter of this year.

Deepest gratitude to our R&D colleagues across RNA gene therapy, and gene editing for their extraordinary work to get us where we are today.

And where we are today represents an important moment in genetic medicine, and an important moment for <unk>.

Firstly, we were thrilled to learn last November that the FDA accepted our BLA for review via the accelerated approval pathway for <unk>.

Operator: Continuing now with our gene therapy platform and our limb girdle muscular dystrophy program, we were pleased to announce earlier this month the first patient was dosed in study SRP 903, also known as Voyage. Voyaging is a phase one study evaluating SRP 9003 for the treatment of limb girdle muscular dystrophy type 2E in ambulant adult patients and non-regeant.

Lead gene therapy candidate SRP 9001.

This decision was based on our ability to show a robust expression of the SRP 900 on dystrophin protein a shortened functional version of dystrophin.

As a surrogate endpoint reasonably likely to predict clinical.

Clinical benefit in patients with Duchenne muscular dystrophy.

These strong results from a mutation in the gene that codes for the throw at them.

Operator: on ambulance patients using clinical process SRP 903 material, combined with positive expression and functional data shared from

Joe Fund acquisition muscle attaching to the muscle membrane and distributing for us ethylene those thereby protecting our muscle from damage.

Operator: initial study, SRP 903 101. We believe the data from Voyagee will give us insights into the broader patient population as we finalize plans for a global phase three study using commercially representative process material that we intend to begin later this year. In addition, we plan to commence a systemic pilot study for our SRP 604-604 dual vector, RH74-mediated gene therapy to treat LGMD2B, characterized by the absence of the protein dysferlind. We believe our gene therapy platform is well suited to generate medicines for limb girdle muscular dystrophies.

Individuals with Duchenne block this dosing and as a result their muscles become progressively worse.

Our goal with SRP 9001 is to change the course of the fatal disease by treating the underlying cause of duchenne with a onetime gene therapy that delivers functional dystrophin to the muscle.

Based on well established precedent.

FDA has approved for therapies to date using shortened functional dystrophin as a surrogate endpoint.

Further throughout that has generated the most compelling preclinical biomarker and clinical functional results to date.

What is particularly interesting about SRP 9001, but not completely surprising based on the strong scientific underpinning of our construct is that the early SRP 9001 data provided read through to our positive clinical experience with the therapy.

Operator: Our work in this area continues at pace and represents a key priority for surreptus. Now, turning now to our RNA platform. The momentum study for our next generation PPMO, SRP 5051, is ongoing, and we remain on track to announce data toward the back half of 2023. Additionally, we were pleased to complete enrollment in the essence trial, or post-marketing requirement, for Goloderson and Kazmerson. And lastly, we are making good progress with our mission study, and it continues at pace.

Over the course of 10 plus years I, along with Dr. Jerry Mendell built researched and tested numerous contracts to determine what areas of the protein with functional and protective. We eventually identified an optimal gene cassette that we'll be able to retain protective and functional elements and fit easily into ABB, thereby enabling its delivery.

This gene cassette with packaged into our AAV of choice are 74, and we chose MHC K seven is a promoter.

Operator: In closing, I want to take a moment to recognize rare disease day and the over 300 million individuals around the world living with a rare disease. This is my life's work, and I, along with my colleagues at Surrupta, will not rest until we do our part in advancing the science and developing treatments for waiting patients. I would also like to say thank you to the patients and their families who so generously give of their time and commitment to our trials. We could not undertake this important work without you.

We are pleased with the early data, which had robust expression across skeletal diaphragm and cardiac muscle and as a result of that expression as well as the dystrophin protein demonstrating functional benefits, we saw significant restoration of function the clinical target dose.

I understand the significance of the results and they are important in the context of a viable therapy for Duchenne, it's critical to understand the dystrophin associated protein complex or DAP seat.

Operator: I will now turn the call over to Dallon for an update on our commercial activities. Thank you, Louise, and good afternoon. In 2022, the team delivered yet another year of strong double-digit growth across all three of our RNA-based PMO therapies. As Doug noted, our full-year net product revenue was $8.

GAAP sees that collection of proteins to which just drove an attach it and its absence these proteins disassemble.

Individuals with Duchenne don't have a functioning dystrophin associated protein complex understanding when we had started a functional dystrophin protein we saw upregulation of the vaccine and animal model.

More specifically, we saw an almost one for one.

Operator: The upper end of our upward-revised 22-22 guidance of $825 to $840 million. This represented more than $230 million in growth over 2021 and a growth rate that approached 40% year over year.

Regulation of the Dfc.

Expression of the SRP 9001 disruption confirming the protective properties of the protein.

Further we saw significant reduction increase in kinase or CK levels.

<unk> is an enzyme associated with muscle damage the reduction of CK provide us further to SRP nine here with everyone was reasonably likely to predict clinical benefit.

Operator: I'll take a moment to highlight some of our full year 2022 achievements for our PMO franchise. The team started the year in a strong position by successfully navigating the beginning of the year insurance changes and reauthorization. This led to a reauthorization rate in the low to mid-90s throughout 2022. This robust start, coupled with continued high adherence rates and strong XUS revenues, served as the foundation for full year net product revenue growth of approximately 13% generated with Exondis 51 and net revenue growth

The strength of this early work gave us the confidence and conviction to advanced SRP 9001 into the clinic.

2018 and across multiple studies, we've dosed over 140 patients more than any other gene therapy being developed for Duchenne and.

And the clinical results that surpassed our expectations.

SRP nine <unk> demonstrated robust expression of disruption.

What literature would suggest with necessary can be protective of muscle.

All of it is properly localized at the muscle membrane sarcolemma, where it acts as a shock absorber.

We also developed our cell based potency assay that shows the SRP 9000 airlines active functional and protective at the muscle membrane.

Operator: and net product revenue of roughly $511 million. For Viandus 53, we ended 2022 in a strong leadership position in market share.

And as in the animal models with robust expression of SRP 9001, we saw a significant reduction in CK finally expression of SRP 9001 in patients at least the upregulation of the DAP seat.

Operator: Byondis 53 exceeded $100 million in revenues, ending the year with $117 million in total net product revenue and over 30% growth compared to 2021. And last but not least, the team continued execution on the model of 45 produced exceptional growth in 2022 of over 200% with total net product revenue of $214.8 million. As we've noted in previous calls, our XUS growth continues to accelerate, and it represented roughly 11% of our overall net product revenues in 2022. XUS net product revenue was $96. $96.

In addition to all of this compelling evidence. We are also able to show functional benefit versus what natural history would predict.

NSA, a or the Northstar ambulatory assessment is our primary functional endpoint.

We were able to show benefit across one two and four year timeline.

In summary, based on the totality of the data we are able to provide objective evidence.

9001 qualifies as a disease modifying agent.

And at the levels of distress and expressed based on vast clinical evidence and experience are reasonably likely to predict clinical benefit in patients with duchenne.

As Doug mentioned in his opening comments with the agency is not planning on holding an advisory committee for SRP 9001. The team is focused on responding to any remaining requests.

Operator: For the full year of 2022. Our performance in 2022 is the result of a highly committed and effective team focused on serving the nearly 30% of patients amenable to our therapies with the level of urgency that Duchenne requires. Turning now to a performance in the fourth quarter of 2022, we ended the year on a high note with net product revenues of $235. Once again, the team executed and grew the RNA-based PMO business by more than 30% over the fourth quarter of 2021 and 13% over the prior quarter.

As a reminder, and because we are an active review with the FDA, we do not anticipate publicly sharing additional data from the SRP nine turns airlines studies, leading up to the 2023 regulatory milestone and the Embarq data readout, which is on track for the fourth quarter of this year.

Continuing now with our gene therapy platform and our limb girdle muscular dystrophy programs were.

We are pleased to announce earlier this month. The first patient was dosed in steady SRP 90031, or two also known as Voyager.

Voyaging is a phase one study evaluating SRP 9003 for the treatment of lung girdle muscular dystrophy type <unk> E in ambulant adult patients not patients.

Operator: I'll now outline individual net product revenues for the fourth quarter of 2022, for our three approved RNA-PMO therapy. For Exander 51, net product revenue of $146 million represented roughly 22% growth over Q4 of 21. For My honest 53, fourth quarter 22, that product revenue totaled $28, representing roughly 15% growth versus the fourth quarter of 2021. And finally, Amondas 45, net product revenue was $61.

Patients using clinical process SRP nine there is there are three material combined.

Combined with positive expression and functional data from our initial study SRP 903, 101, we believe the data from voyaging will give us insights into the broader patient population as we finalized plans for our global Phase III study using commercially representative process material.

We intend to begin later this year.

In addition, we plan to commence a systemic pilot study for SRP six there for 600 for those alright, 74 mediated gene therapy to treat LG Andy to be characterized by the absence of the protein just Berlin.

Operator: $61.4 million in Q4 of 2022, representing nearly 80% growth versus the fourth quarter of 2021. As the business evolved and grew throughout 2022, we've seen more variability in our quarterly revenue numbers, due mainly to X US ordering patterns. We have observed lumpy quarter-to-quarter fluctuations and seasonality with our XUS orders, and we expect this trend to continue going forward. For example, sales in the fourth quarter of 2022 were robust due to very strong XUS sales of $36. This strength allowed us to far exceed expectations for the quarter. However, we do not expect the same dynamics to persist into the first quarter of 2023.

We believe our gene therapy platform is well suited to generate medicines for the limb girdle muscular dystrophy.

Our work in this area continues on pace and represents a key priority for <unk>.

Turning now to our RNA platform.

Well, that's a study for our next generation PMO therapy, 50, 51 is ongoing and we remain on track to announce data towards the back half of 2023.

We were pleased to complete enrollment in the essence trial, our post marketing requirement for Cologuard and Cathy Marsden and lastly, we're making good progress with our mission study and it continues on pace.

In closing I wanted to take a moment to recognize rare disease day any over 300 million individuals around the world living with a rare disease.

This is my life work and I, along with my colleague Best dropdown will not rest until we do our part in advancing the science and developing new therapies for waiting patients.

Operator: We want to provide you with this level of visibility to help you model our revenues for the year. Our forecast anticipates this dynamic, and it is reflected in our 2023 PMO net product revenue guidance of greater than $925 million, which we issued in January. Despite the quarterly fluctuations, overall, we expect a strong year and are confident in our direction. Again, I'm proud of what we accomplished in 2022, and most importantly, I'm grateful for our team's enduring commitment to the Dishan community and the patients we serve.

I would also like to say, thank you to the patients and their families who so generously give them their time and commitment to our trials.

Could not undertake this important work without you.

I will now turn the.

The call over to Allen for an update on our commercial activities talent.

Thank you Luis and good afternoon.

In 2022, the team delivered yet another year of strong double digit growth across all three of our RNA based piece.

M O therapies.

As Doug noted our full year net product revenue was $843 8 million.

The upper end of our upwardly revised 2022 guidance of $825 million to $840 million. This.

Operator: This commitment to operational excellence will serve us in the patient community well as we apply the lessons learned to the upcoming launch of SRP 9001. In parallel with the team's execution of our existing business in 2022, the customer organization billed for SRP 9001 is on track and nearly complete. Importantly, engagement with key gene therapy sites and U.S. payers is well underway. If SRP 9001 is approved, the team is once again prepared to demonstrate their capabilities and hard-thought expertise in our fourth launch into the Dushan space, with the first gene therapy to serve the patient community. Now, I'll turn the call over to Ian Fapan for an update on our financials.

This represented more than $230 million in growth over 2021, and a growth rate that approached 40% year over year.

I'll take a moment to highlight some of our full year 2022 achievements for our PMO franchise.

The team started the year in a strong position by successfully navigating the beginning of the year insurance changes and re authorizations. This led to a reauthorization rate in the low to mid Ninety's throughout 2022. This robust start coupled with continued high adherence rates and strong ex U S revenues served.

As the foundation for full year net product revenue growth of approximately 13% generated with exon 51 and <unk>.

Net product revenue of roughly $511 million.

For <unk> 153, we ended 2022 and a strong leadership position in market share by almost 53 exceeded $100 million in revenues.

Ending the year with $117 4 million and total net product revenue and over 30% growth compared to 2021.

Operator: Thanks, Alan. Good afternoon, all.

And last but not least the team's continued execution on a modest 45 produced exceptional growth in 2022 of over 200% with total net product revenue of $214 8 million.

Operator: This afternoon's financial results press release provided details for the fourth quarter and full year of 2022 on a non-gap basis as well as on a gap basis. Please refer to the press release available on Struptor's website for a full reconciliation of GAAP to non-GAAP financial results. For the three months ended December 31, 2022, the company recorded total revenues of $258.4 million, which consists primarily of net product revenues and collaboration revenues, compared to revenues of $201.5 million for the same period of 2021, an increase of $56.9 million. Net product revenue for the fourth quarter of 2022 from our PMO Exxpings franchise was $235.9 million, compared to $178.7 million for the same period of 20 The increase in net product revenue primarily reflects increasing demand for our product.

As we've noted in previous calls our ex U S growth continues to accelerate and represented roughly 11% of our overall net product revenues in 2022.

Ex U S. Net product revenue was $96 $3 million for the full year of 2022.

Our performance in 2022 is the result of our highly committed and effective team focused on serving the nearly 30% of patients on medical towards therapies with the level of urgency that duchenne requires.

Turning now to our performance in the fourth quarter of 2022.

We ended the year on a high note with net product revenues of $235 $9 million.

Once again, the team executed and glue the RNA based PMO business by more than 30% over the fourth quarter of 2021 and.

13% over the prior quarter.

I'll now outline individual net product revenues for the fourth quarter of 2022.

There are three approved RNA based PMO therapies.

For example, 51 net product revenue of $146 million represented roughly 22% growth over Q4 of 'twenty one.

Operator: For the quarters ended December 31, 22, and 2021, we recognize $22. $22.7 million of collaboration and other revenues, respectively, which primarily relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $51.

My honest 53 fourth quarter 2000 to 2022 that product revenue totaled $28 5 billion.

Representing roughly 15% growth versus the fourth quarter of 2021.

And finally, a modest 45 net product revenue was $61 4 million in Q4 of 2022 reps.

Representing nearly 80% growth versus the fourth quarter of 2021.

That's the business evolved and grew throughout 2022, we've seen more variability in our quarter over quarter revenue numbers due mainly to ex U S. Ordering patterns, we have observed lumpy quarter to quarter fluctuations and seasonality with our ex U S orders, we expect this trend to continue.

Operator: For the fourth quarter of 2022, compared to $29.7 million for the same period of 2021, on a gap basis, we reported a net loss of $109.2 million, or $1.24, and $122 million, or $1.42 per basic and diluted share for the fourth quarter of 2022 and 2021, respectively. We reported a non-gap net loss of $46.5 million, or 53 cents per basic and diluted share, in the fourth quarter of 2022 compared to a non-gap net loss of $66 million, or $77.

Q going forward.

For example sales in the fourth quarter of 2022, the robust due to very strong ex U S sales of $36 $9 million.

This strength allowed us to far exceed expectations for the quarter. However, we do not expect the same dynamic to persist into the first quarter of 2023.

We want to provide you this level of visibility to help you model our revenues for the year.

Our forecast anticipates this dynamic and it is reflected in our 2023 PMO net product revenue guidance of greater than $925 million, which we issued in January .

Despite the quarterly fluctuations overall, we expect a strong year and are confident in our guidance.

Again, I'm proud of what we accomplished in 2022, and most importantly, I'm grateful for our team's enduring commitment to the Duchenne community and the patients we serve.

Operator: cents per basic and diluted share in the fourth quarter of 2021. In the fourth quarter of 2022, we recorded approximately $30.8 million in cost of sales compared to $31.7 million in the same period of 2021. The decrease in cost of sales is primarily due to write-off of certain batches of our products, not meaning the quality specifications for the three months ended December 31, 2021, 2021, with no similar activity in the same period of 2022 and a decrease in our royalty payments during the three months ended December 31, 2022 due to changes in our Biomeran royalty. On a gap basis, we recorded $213.

This commitment to operational excellence will serve us and the patient community well as we apply the lessons learned to the upcoming launch of SRP nine days of one.

In parallel with the team's execution of our existing business in 2022, the customer organization build for SRP nine <unk> is on track and nearly complete.

Importantly engagement with key gene therapy sites in U S payers is well underway.

If SRP nine days otherwise approved the team has once again prepared to demonstrate their capabilities and hard fought expertise in our fourth launch into the Duchenne space.

With the first gene therapy to serve the patient community.

And now I'll turn the call over to E&S dependent for an update on our financials.

Thanks, Alan and good afternoon, all this afternoons financial.

<unk> press release provided details for the fourth quarter and full year of 2022 on a non-GAAP basis as well as the GAAP basis. Please refer to the press release available on <unk> website.

Operator: And $197.3 million in R&D expenses for the fourth quarter of 2022 and 2021, respectively, a year-over-year increase of $16.5 million. The increase is primarily due to increases in upfront and milestone expenses. On a non-gap basis, R&D expenses were $186.8 million for the fourth quarter of 2022 compared to $175.5 million for the same period of 2021, an increase of $11.3 million. And then turning to SG&A on a gap basis, we recorded approximately $120.5 million and $78.1 million of expenses for the fourth quarters of 2022 and 2021, respectively, an increase of $42.4 million.

Full reconciliation of GAAP to non-GAAP financial results.

For the three months ended December 31, 2022, the company recorded total revenue of $258 4 million, which consist primarily of net product revenue and collaboration revenues compared to revenues of $201 5 million for the same period of 2021, an increase of $56 $9 million.

Net product revenue for the fourth quarter of 2022 from our PMO exon skipping franchise with $235 9 million.

Compared to a $178 $7 million for the same period of 2021.

The increase in net product revenue, primarily reflects increasing demand for our products.

For the quarters ended December 31, 2022, and 2021, we recognized $22 $5 million and $22 $7 million of collaboration and other revenues, respectively, which primarily relates to our collaboration arrangement with Roche, we reimbursed about co development costs under the Roche agreement totaled $51.

Operator: The increase was driven primarily by an increase in stock-based compensation expense, primarily due to additional expense recognized under the CEO grant modification agreement executed in 2022. On a non-gap basis, SG&A expenses were $86.6 million for the fourth quarter of 2022 compared to $60.1 million for the same period of 2021, an increase of $26.5 million. On a gap basis, we recorded $5.5 million in other income net for the fourth quarter of 2022 compared to $16.1 million in other expense net for the same period of 2021.

$7 million for the fourth quarter of 2022 compared to $29 7 million for the same period of 2021.

On a GAAP basis, we reported a net loss of $109 2 million or $1 24.

And $122 million or $1 42.

Basic and diluted share for the fourth quarter of 2022 and 2021, respectively.

Reported a non-GAAP net loss of $46 5 million or <unk> 53 cents per basic and diluted share in the fourth quarter of 2022 compared to a non-GAAP net loss of $66 million or 77.

Basic and diluted share in the fourth quarter of 2021.

In the fourth quarter of 2022, we recorded approximately $38 million and cost of sales compared to $31 $7 million in the same period of 2021.

Operator: The change is primarily due to an increase in interest income due to 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 for the three months ended December 31st, 2022. We expect that both SG&A and R&D expenses will be higher in 2023 as we build inventory and prepare for the launch of SRP 9001. The increases in expenses will, however, be partially offset by the growth in our revenue.

Decrease in cost of sales was primarily due to write off of certain batches of our product not meeting the quality specifications for the three months ended December 31, 2021 with no similar activity in the same period of 2022 and a decrease in our royalty payments. During the three months ended December 31, 2022 due to changes in our.

Biomarin royalty check.

On a GAAP basis, we recorded $213 $8 million and $197 3 million.

Operator: We had approximately $2 billion in cash and cash equivalents and long-term restricted cash as of December 31st. And we've made tremendous progress over the course of 2022, and this upcoming year has the potential to dwarf all that we have previously accomplished. I'm particularly pleased that we're well capitalized to execute on all of our plans that we've outlined today on the call. And with that, I'll turn the call back over to Doug for Q&A.

R&D expenses for the fourth quarter of 2022, and 2021, respectively, a year over year increase of $16 $5 million.

Increase was primarily due to increases in upfront and milestone expenses.

On a non-GAAP basis, R&D expenses were $186 8 million for the fourth quarter of 2022 compared to $175 $5 million for the same period of 2021.

An increase of $11 $3 million.

Now turning to SG&A on a GAAP basis, we recorded approximately $125 million and $78 1 million of.

Operator: Thank you very much, and Valerie. Valerie, let's open up the lines for questions and answers.

<unk> expenses for the fourth quarter of 2022, and 2021, respectively, an increase of $42 4 million.

Operator: Thank you. Again, ladies and gentlemen, if you would like to ask a question, please press star 1-1 on your telephone. Again, to ask the question, please, press star-1-1. We do ask that you please limit yourself to one question. Thank you. One moment, please. Our first question comes from the line of Anapum Rama of JPM Morgan. Your line is open.

The increase was driven primarily by an increase in stock based compensation expense, primarily due to the additional expense recognized for the CEO Grant modification agreement executed in 2022.

On a non-GAAP basis, the SG&A expenses were $86 6 million for the fourth.

Quarter of 2022 compared to $60 1 million for the same period of 2021, an increase of $26 $5 million.

Operator: and Doug in your comments as well that the FDA noted no major safety concerns in the filing for 9001. Were there any comments on the mid-cycle review of the external control arm and that analysis? If I remember correctly, that

On a GAAP basis, we recorded $5 $5 million and other income net for the fourth quarter of 2022 compared to $16 1 million.

Operator: correctly that that was a prespecest by the FDA and then quickly on manufacturing, Doug, in your opening comments, did you say that the site inspections had been scheduled? Thanks so much. Yeah, thank you very much.

Other expense net for the same period of 2021. The change is primarily due to an increase in interest income due to 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 for the three months ended December 31 2022.

Operator: Yeah, thank you very much for your question, John and Pomps. So first, as you noted about safety, at the mid-cycle review, the division explicitly, in writing, informed us that they saw no, they saw no significant safety issues with the file and with 9-001. You know, that should come as a little surprise, I suppose, to those who know our profile, but it was, to say the least, gratifying and encouraging that the FDA saw it the way we saw it.

We expect that both SG&A and R&D expenses will be higher in 2023, as we build inventory and prepare for the launch of SRP nine here or there one.

The increases in expenses will however, be partially offset by the growth in our revenue.

We had approximately $2 billion in cash cash equivalents.

And in long term restricted cash at December 31, and.

And we've made tremendous progress over the course of 2022 in this upcoming year has the potential to dwarf all what we have previously accomplish I'm, particularly pleased that we are well capitalized to execute on all of our plans that we've outlined today on the call and with that I'll turn the call back over to Doug for Q&A.

Operator: As really, I'm not going to get into a lot of detail on the review beyond what I've already said. But I will say on the clinical side of things, you know, we're in an active review. As you know, there are lots of questions and analyses that, um, that we've done and questions we've answered. But, I can at least say at the mid-cycle review, the division did not identify any significant issues or material deficiencies with the clinical data set at all. So that's where we are as of the mid-cycle. And then finally, as relates to the site inspections, yes, all of the manufacturing inspections have been scheduled.

Thank you very much Ian Valerie, let's open up the lines for questions and answers.

Thank you again, ladies and gentlemen, I'd like to ask a question. Please press star one one of your telephone again to ask a question. Please press star one one we do ask that you. Please limit yourself to one question. Thank you.

One moment please.

Our first question comes from the line of Anupong Rama of Jpmorgan. Your line is open.

Hey, guys. Thanks, so much for taking my question and congrats on all the progress.

I noticed in the press release and Doug in your comments as well that the FDA noted no major safety concerns and the filing for <unk>.

Operator: Thank you. One moment, please. Our next question comes from the line of Brian Abrams of RBC, Brian Abrams of RBC, Brian Abrams of RBC.

Was there any commentary on the mid cycle review on the external control arm and that analysis, if I remember correctly, but that was a pre specified analysis by the FDA and then quickly on manufacturing.

Operator: of RBC, Brian Abrams from RBC, your line is open.

Operator: my question and congratulations on all the progress. Is there anything more you can say, at least more broadly, on the nature of the CMC dialogue and preparation for the manufacturing inspections? And I guess I'm curious about your level of manufacturing, confidence, and overall comfort that there'd be sufficient time after these inspections to rectify any minor issues that might come up and still have sufficient time to build supply. And then, just maybe quickly, I'm wondering also if the FDA provided any specific reasons as to why no adcom would be required.

Doug in your opening comments did you say that the site inspections have been scheduled thanks.

Thanks, so much.

Yes. Thank you very much for your question John So first as you noted on safety.

At the mid cycle review the <unk>.

Division explicitly in writing.

<unk> informed us that they saw no they see no significant safety issues with the filing with <unk> one.

That would that should come as little surprise I suppose to those who know our profile, but it was to say the least gratifying.

And encouraging that the FDA saw the way we saw it as really I am not going to give you a lot of detail on the.

Operator: I know sometimes they give specific comments. Yeah, thank you very much for that, Brian. First on CMC, I think as everyone knows, and certainly we've talked about before, with respect to BLAs, and I think, in particular with gene therapy, the CMC part of the submission and the Q&As are some of the most significant ones. As I mentioned before, as relates to all of the questions that the agencies had, we're current and have answered all of their questions.

Review beyond what I've already said.

We'll stay on the clinical side of things we are in an active review.

As you know there are lots of questions and analyses.

That we've done and questions. We've answered I can at least say at the mid cycle review.

The division did not identify any significant issues or material deficiencies with the clinical data set at all so thats, where we are as of the mid cycle and then finally as it relates to the site inspections, yes, all of the manufacturing inspections have been scheduled.

Operator: We feel like we're in very good shape there. We feel like we're in very good shape with those questions. As relates to the timing of the pre-approval inspections themselves, yes, we're very, very confident about the timing. So we, you know, I'm not going to go into detail on the schedules, but we're confident about the schedules and the timing and the ability to adapt ourselves. We don't, as we sit here today, have any reason that there would be a delay in our Padovade for this or any other reason right now, at least as of now.

Thanks for much for taking our questions.

Thank you one moment please.

Our next question comes from the line of.

Brian Abrahams of RBC, Brian Abrams of RBC. Your line is open.

Hey, good afternoon. Thanks for taking my question and congrats on all the progress.

Is there anything more you can say at least more broadly on the nature of the CMC dialogue in preparation for the manufacturing inspections, and I guess I'm curious your level of manufacturing confidence and overall comfort that there'd be sufficient time post these inspections to rectify any minor issues that might come up.

Operator: And then as relates to the decision that there wasn't a need for an advisory committee, there really isn't any additional color other than we had the mid-cycle. They confirmed they saw no safety issues or significant safety issues with the program. They didn't identify any significant clinical issues or major deficiencies. And then they determined that they didn't need an active committee. That's where we are.

Up.

And still have sufficient time to build supply and then just maybe quickly wondering if also if the FDA provided any specific reasons as to why no AD com would be required I know, sometimes they give specifics on that thanks.

Operator: Thank you. One moment, please. Our next question comes from the line of Colin Bristow of UBS. Your line is open.

Yes. Thank you very much for that Brian first of all CMC there.

Operator: Hey, good afternoon, and congratulations on all the progress. Another one on the outcome or lack thereof. Previously, you had stated that one of the focal points of the outcome you're anticipating would be the surrogacy of truncated dystrophin. Did FDA comment on its comfort around this, or is this something that's part of an ongoing dialogue, or just part of the review process? And then maybe just on the manufacturing supply side, if you are approved for the Purdue FA, you just talk about the number of patients you expect to be able to supply at launch and how this will build over time. Thanks a lot. Sure.

As everyone knows and certainly we've talked about before with respect to BLA and I think in particular with gene therapy. The CMC part of the submission in the Q&A as is.

Some of the most significant ones as I mentioned before.

As it relates to all of the questions that the agency has had with.

Recurrent and have answered all of their questions. So we feel like we're in very good shape there.

So like we're very good shape with those questions as it relates to the timing of the.

<unk>.

Preapproval inspections themselves, yes, we're very very confident.

And the timing so we are not going to go into detail on the schedules, but we're confident about the schedule and the timing and the ability to adapt ourselves.

Operator: Sure, first I would say, you know, that entire discussion, that's sort of the fundamental issue in the review, is whether the use of shortened functional dystrophin is reasonably likely to predict clinical benefit. As relates to the ad comments, you know, we see this, and we obviously see the decision to download an ad comment as a positive. We had a very productive mid-cycle review.

Don't as we sit here today have any reason to believe that there would be a delay in our produce a date for this or any other reason right now at least as of now and then as it relates to the.

The decision that there wasn't a need for an advisory committee and there really isn't any additional color other than we had the mid cycle.

Confirm they saw no safety issues significant safety issues with the program, we didnt identify.

Any.

Significant clinical issues or major deficiencies in that determined that they didn't need an ad com.

Operator: We're not going to speculate on, you know, what this means from the probability of success. But what we would say is that given that we know that there are no significant safety issues, that there isn't going to be an outcome, we can then spend our time really focusing on answering any remaining questions, preparing for and executing our pre-approval inspections and doing that successfully, making sure that we're launch ready and building inventory for launch. We haven't given out exact patient numbers. as it relates to manufacturing.

Where we are right now.

Okay.

Thank you one moment please.

Our next question comes from the line of Colin Bristow of UBS. Your line is open.

Hey, good afternoon, and congrats on all the progress another one on the account on the outcome or lack thereof.

Previously you had stated that you're one of the focal points of the outcome, you're anticipating would be the surrogacy a truncated dystrophin.

Did FDA comment on it.

Around this or is this something thats part of an ongoing dialogue.

Operator: But what we've said, and we stand by it, is that our goal is to launch this therapy and serve this community without back orders, with all patients getting the therapy as soon as they are able to get it from an access and reimbursement perspective. And we want to be in a position to do that. We will.

Part of the review process.

And then maybe just on the on the manufacturing supply side, if you are going to produce.

You just talk about the number of patients you expect to be able to supply at launch and how this will build over time. Thanks. So much.

Sure first I would say.

Operator: Our next question comes from Matthew Harrison and Morgan Stanley, and the line is open.

That entire discussion that has to go to the.

The fundamental issue and the review is that.

Operator: Great, thank you very much; I appreciate the question. I guess two just follow-ups for me. I know we've touched on many of the major issues here, but first, just on manufacturing, can you just talk to the extent you can in a bit more detail? Are these multiple facilities or just lines in the same facility that are being inspected? You know, how comprehensive is this inspection versus maybe what you were expecting or thought you might see.

Use of shortened functional dystrophin.

Reasonably likely to predict clinical benefit as it relates to the <unk> comments, we see this we obviously see the decision.

They had come in as a positive we had a very productive mid cycle review.

Not going to speculate on what this means from the probability of success, but what we would say is that.

Given that we know that there are no significant safety issues that there isn't going to be an AD com. We can then spend our time really focusing on answering any remaining questions preparing for and executing our.

Operator: And then just secondly, on the inventory in the supply that you are building now, is there any chance or any reason that the supply you've started to build now could not be used? Could you just talk about, you know, the supply you have now versus the supply you're continuing to build?

Preapproval inspections and doing that successfully making sure that we're launch ready and building inventory for launch.

We haven't given exact patient numbers as it relates to manufacturing, but what we've said and we stand by it is that our goal is to launch this therapy and serve this community without.

Operator: Yeah, first of all, in the inspections, there are three separate facilities. They are exactly as we anticipated. In fact, I would say none of the questions that have been posed and none of the inspection notices that we've received have been at all a surprise. We've been very well prepared for them, so we're in good shape there. From an inventory and supply perspective, we're on track, and no, we don't think there's any significant risk that the inventory that we build will be

Without back orders with all patients getting the therapy as soon as they are able to get it from an access and reimbursement perspective, and we wanted to be in a position to do that we will be.

Thank you.

Our next question comes from Matthew Harrison of Morgan Stanley . Your line is open.

Yeah.

Okay.

Great. Thanks, very much appreciate that.

Question, I guess I guess to just follow ups from me I know we've touched on many of the major issues here, but first just on.

Operator: able to be used commercially, so we're tracking there. You know, a lot of work to do as an organization. Site readiness is a significant issue. Building inventory is a significant issue. Completing this review and satisfying any remaining questions, comments, or analyses from the FDA is, you know, extremely important to us, and we need to focus on that as well. But the team is very, very focused on all of this, and we're working hard to ensure that we have a successful BLA review.

On manufacturing can you just talk to the extent you can in a bit more detail.

Are these multiple facilities are just lines in the same facility that are being inspected how comprehensive as this.

Inspection versus maybe what you what you were expecting or thought you might see and then just secondly on the on the inventory and the supply that you are building now is there is there any chance or any reason that the supply you have started to build now could not be used.

Operator: Our next question comes from the line of Tazine Ahmad of Bank of America. The line is open.

And could you just talk about supply you have now versus and why you are continuing to build thanks.

Operator: Hi, good afternoon. Thanks for taking my question. Can you give us, Doug, a sense of how the doctor's offices or facilities that the patients would have to go to might have to make any adjustments? The infrastructure is already there for high demand for the physicians to be able to meet the potential volume demand that we would expect upon approval. I don't know what your checks are telling you, but I'd love to hear some color on that. Yeah, I mean, the first thing I'll say is that we start in a very good place, probably in a very privileged place, because of SMA and because of Zola.

Yes, so first of all on the especially as there are three separate facilities. They are exactly as we anticipated in fact, I would say none of the questions that have been posed and none of the inspection.

Inspection notices that we've received have been at all or a surprise, we've been very well prepared for them. So we're in good shape there.

From an inventory and supply perspective, where we are on track and we don't think theres any significant risk that inventory that we build will be able to.

Be used commercially so where we're tracking there are a lot of work to do as an organization site readiness is a significant issue building as that inventory is a significant issue completing this review and satisfying any remaining questions or.

Operator: So a significant percentage of the experts and the neuromuscular experts that would be treating patients with Dushemuskidistency with 9-1 have previous experience with Zolgentina. So we're starting with a good place. Now, certainly, I'm going to turn this over to Dallin to provide any additional color that I miss, but I would say there's certainly a lot of work still that we need to do to make sure that, very specifically for 9001, the sites are up, ready to go, you know, properly educated, and ready to make this therapy a success.

Comments or analysis, the FDA is extremely important to us and we need to focus on that as well, but the team is very very focused on all of this and we're we're working overtime to ensure that we have a successful BLA review.

Thank you.

Our next question comes from the line of <unk> Ahmad of Bank of America. Your line is open.

Hi, good afternoon, Thanks for taking my question.

Can you give us a sense of how the doctors.

Doctors offices or facilities that the patients would have to go to might have to make any adjustments in the infrastructure already there for high demand for the physician to be able to meet.

Operator: Our goal at launch is to have about 50 of those sites up and running. That would serve just about 80% of the Duchenne community, and then over time, to be up as high as about 70 sites over the course of the next couple of quarters beyond that. But Dallin, what have I missed here?

The potential volumes and now that we would expect the PON and a profile I don't know what your checks are telling you, but love to hear some color on that.

Yes, I mean, I think the first the first thing I'll say is that we started a very good place probably in a very privileged place because because of SMA and because of xeljanz. So a significant percentage of.

Operator: No, you covered it, Doug, and I think these sites are really at the forefront of precision genetic medicine, and they have a lot on their sites, but they're absolutely heroic, and they are, you know, we're working already with them on whatever we can do from an educational standpoint prior to approval that is compliant and appropriate. So the team is out there today engaging with their sites. Every site is different, but they are, you know, these are centers of excellence that are already treating these patients, these Duchenne muscular dystrophy patients. So they'll be ready to go, and we'll be

The experts and the neuromuscular experts that would be treating patients with duchenne muscular dystrophy with 9001 have previous experience result, gentlemen, so we're starting with at a good place now certainly I'm going to turn this over to Darren to provide any additional color that I Miss but I would say there is certainly a lot of <unk>.

We're still that we need to do to make sure that very specific to <unk> zero one the sites are ready to go.

Properly educated and ready to to.

Two two.

Take this therapy a success our goal at launch is to have about 50 of those sites.

Operator: Our next question comes from the line of Robert Fink of Guggenheim, Yelina Zop. Hey team, this is Robert on for

<unk> been running that would serve just about 80% of the Duchenne community and then over time to be up as high as about 70 sites.

Operator: I'll turn this over to Dowell as well. The short answer is that we're going to be ready to go on day one. Doesn't mean kids are going to get infused on day one. There's a process here, the access and reimbursement process, and kids have to get tested for neutralizing antibodies, and the policies have to get finalized. But the team's already doing an enormous amount of work with not only sites but payers right now so that we're in a position to begin to serve the community day one post-approval.

Over the course of the next couple of quarters beyond that the Dell and whatever I missed there.

No I think we covered it Doug and I think these sites are really at the forefront of precision genetic medicine and and they have a lot on their plate, but they are absolutely her well look and they are working already with them with whatever we can do from an educational standpoint prior to approval that is compliant.

Appropriate so the team is out there today engaging with the sites every site is different.

But they are.

It's these are centers of excellence that are already treating these patients with duchenne muscular dystrophy patients so they'll be ready to go and we'll be ready to go.

Operator: Assuming that we're fortunate and get approved, yeah, yeah, we'll be ready for day one, and we're already engaging with payers, and so, I think we're going to do everything we can to accelerate access for eligible patients on day one and learn the lessons from past launches.

Thank you.

Our next question comes from the line of Robert Fink of Guggenheim. Your line is open.

Hey, Tim This is Robert on for <unk>, how quickly can serve to get reimbursement agreements in place following the approval and the <unk>.

Operator: Yeah, one thing just to add to that. I think one thing just to add to that is that you guys have, you know, good precedent for what you've seen in terms of our launches for our PMO, exon skipping franchise, and obviously, doves and down. It takes time to get patients on therapy and through the access and reimbursement system, and obviously, there's state Medicaid and getting through the drug utilization review board process, right?

He has to launch thank you.

Uh huh.

I'll turn this over to Gal as well the short answer is that we're going to be ready to go on day. One it doesn't mean kids are going to get infused on day one.

There's a process here, the access and reimbursement process and having to get tested for neutralizing antibodies and the policies I forget finalized, but the team is already doing an enormous amount of work.

With.

Not only sites the payers right now so that we're in a position to begin to serve the community day, one post approval, assuming that we're fortunate and get approved.

Operator: So it is going to take, you know, a couple of quarters for patients to work through, and you've seen that before, but then once we really work through those reimbursement steps, I think you're going to see very, very strong uptake.

Yeah, Yeah, it will be ready.

In terms of day, one that we're already engaging with payers.

So.

I think we're going to do everything we can to accelerate about chess for eligible patients on day one.

Operator: Thank you. Our next question comes from the line of Gina Wang of Barclays.

And learned the lessons from past launches.

Operator: Your line is open. Again, Gina is winging it up with our Claiselaida.

Yes, one thing just to add to that and I think one thing just to add to that is that you guys had.

Operator: Thank you. I have two quick questions. Doug, you mentioned that there are still remaining questions from the FDA. What are the natures of these remaining questions? And do you expect the lay cycle review will be mainly focusing on these questions, with no new questions remaining? And the second question is regarding the three sites. Do any of these three sites have established commercial experience with Icelas manufacturer?

Good precedent on what you've seen in terms of our launches for our PMO exon skipping franchise, and obviously 2000 down to the point it takes time to get patients on therapy and through the access and reimbursement system and obviously, there's state Medicaid and getting through the drug utilization review board process right. So it is going to take.

A couple of quarters.

For patients to work through and you have seen that before.

Operator: Well, there's not a lot, you know; there's not a ton of history. I'll answer the last question first. I remind you that, you know, what we're doing is, if not a first, is nearly a first. So you're not going to find a lot of organizations around the world.

But then once we really work through.

Those reimbursement.

Steps I think youre going to see very very strong uptake.

Thank you. Our next question comes from the line of Gena Wang of Barclays. Your line is open again.

Operator: They're going to have an enormous amount of experience with commercialize Ellis unless they happen to be no artist. What I will say is, so, I mean, we're in an active review. One of the things I tried to make the point of in my script is that we've provided detail about the mid-cycle review, frankly, because there was this significant interest in whether we were having an advisory committee or not. We're now in the active review itself.

Gena Wang of Barclays. Your line is open.

Thank you.

Two quick questions.

Doug you mentioned that there is still remaining questions from the FDA what are the nature of these remaining questions and do you expect late cycle review will be mainly focusing on these questions.

Two questions remaining.

Second question is regarding the three sites.

Any of these three sites have established commercial experience with Astellas manufacturing.

Operator: It's an ongoing dialogue of questions and answers. And, you know, in respect of that discussion and dialogue with the agency item, I'm not going to go into a ton of detail along the way. There will be a late cycle review, and then we'll see where we are. The inspections will be completed, and then, if all goes well, of course, we'll have an answer certainly by May 29, and we hope it's a yes. You certainly think the patient

Well, there's not a lot there's not a ton of history I'll answer. The last question first I would remind you that.

What we're doing is not our first is nearly a third so youre not going to find a lot of.

Organizations around the world, we're going to have an enormous amount of experience with commercial lifestyle us unless they happen to be novartis.

What I will say is so when we're in an active review one of the things I tried to make the point again.

Operator: Pardon me, the line of Ritu Barra of Calvin, the line of

My script is that we provided.

Operator: Hi guys, thanks for taking the question. Deb, just back to the adcom for a second, you know, when FDA put in their minutes that they were going to have an adcom, and now they're saying they don't. It sounds like they had a question around the biomarker that at least they figured out that they could answer on their own at this point.

Detail about the mid cycle review frankly, because there was this significant.

Interest in whether we were having an advisory committee or not we're now in the active review itself, it's an ongoing dialogue and questions and answers.

And.

Respect of that.

Discussion and dialogue with the agency I am not going to go into a ton of detail.

Operator: That revolves around any additional data sets or analyses around the ongoing or follow-up from 102 or 103 that they've requested that you've submitted or that were just sort of questions as you discussed. And then just a quick one on CMC, the plants, the Harmon plant and the two others, have you done completed?

Along the way there will be a late cycle review and then.

We will see where we are the inspections will be completed and then if all goes well of course, you will have an answer certainly by May 29, and we hope it's a positive one.

We certainly think the patients deserve it.

Okay.

Yeah.

Okay.

Pardon me a lot of with Humira of Cowen Your line is open.

Hi, guys. Thanks for taking the question.

Doug just back to the outcome for a second.

When the FDA put in their business that they were going to have an AD com and now they are saying they go it sounds like they had a question around the biomarker that at least they figured out that they can enter on their own at this point does that revolve around any additional datasets or analyses around the ongoing follow up from.

Operator: I completed mock inspections at all of them. Are you inspection ready?

Operator: I'll answer the last question first. We are undoubtedly inspection ready. We are, you know, we're an organization that doesn't want to be surprised. So we are very much inspection ready, and we've done all of the work to put ourselves in a good position. And that gets to the first, which sort of gets to the first, answer the first question as well.

One or two or three that they've requested that you'd say.

Good.

Or is it really just sort of questions SBU as you've discussed.

Then just a quick one on P&C.

Operator: So let me make sure I dispel that misunderstanding. There wasn't a point in which the agency said to us in writing that we were going to have an adcom and then later determined that we didn't need an adcom. What did happen is that we said in connection with the BLA submission that we should all assume there's going to be an ad, and given an opportunity to do this a second time, I would do that exactly the same way as I did the second time.

The plants the Hanmi plant two others have you done and completed mock inspections that all of them are new inspection ready.

I'll answer the last question first we are undoubtedly inspection ready.

Where we are.

We're an organization that doesn't want to get.

Surprise.

Very much inspection ready and we've done all the work to put ourselves in a good position and that gets to the first.

The first.

The first question as well so let me make sure I have this dispel.

Operator: Why? Because we needed to be ready for an advisory committee meeting. There's an enormous amount of work that goes into preparing for an advisory committee meeting, and we wanted to make sure that we had a mind.

Perhaps a misunderstanding there wasn't a point in which the agency said to us in writing that youre going to have an AD com and then later determined that we didn't need an AD com. What date occurs that we said in connection with the BLA submission that we should all assume theres going to be an ad com.

Operator: That put us in a good position so that to the extent that the FDA, the division, the division,

And given an opportunity to do this the second time I will do that exactly the same way a second time, why because we needed to be ready for an advisory Committee meeting there was an enormous amount of work that goes into preparing for an advisory Committee meeting and we wanted to make sure that we had a mindset that had us in a good position so that to the extent that the FDA.

Operator: determined that it was wise or necessary to take external scientific advice that we'd be well prepared to participate in that adcom. It was at the mid-cycle review.

Operator: Both in the written agenda and at the mid-cycle, the age

The division determined that it was wise are necessary to take external the external scientific advice that we'd be well prepared to.

Operator: cycle that the agency had, has for the first time told us that they don't need an adcom for this file. So that's where we are with respect to that.

Participated in that AD com. It was at the mid cycle review both in a written agenda in at the mid cycle that the agency had has for the first time and told us that they don't need an AD com for this fall so thats, where we are with respect to that.

Operator: Thank you. One moment, please. Our next question comes on the line from Joe Schwartz of SB Ringwright. Your line is open.

Operator: Hi, this is Beth on behalf of Joe. Thanks for taking our questions.

Thank you one moment please.

Our next question comes from the line of Joe Schwartz of <unk>. Your line is open.

Operator: We are wondering how much precedent you believe that the exon, accelerated

Hi, This is back on for Joe. Thanks for taking our question. We are wondering how much precedent you believe that Exxon. This is accelerated approval on the basis of dystrophin expression provides 4901.

Operator: Dishaphyphine expression provides for 9-01. Specifically, we're also wondering if you've been able to quantify the benefit of higher expression of a less complete microdistrophin compared to the lower expression of a more complete shortened distrophin produced by Exxon Skippers and if this is something the FDA's been considering throughout the review. Okay, let me, yeah, let me answer this question.

Specifically, we were also wondering if you've been able to quantify the benefit of higher expression of a left to micro dystrophin compare to the lower expression of a more complete shorten dystrophin produced by exon skippers and if this is something that FDA has been considering throughout the review.

Okay. Let me Yeah. Let me answer this question, let me start with the second part of it been worked through the first part of it because there is.

Operator: Let me start with the second part of it, then work my way to the first part of it, because there's a fundamental misunderstanding. Understand, understand why you have the mistake. But there's a misunderstanding of the underlying science when one assumes that the 9001 distrophin, which is shortened, is sort of vastly shortened, and then the distrophin that's made by Exondis or Viandis, or in the term, in the case of one of our competitors, Bill Tefso, is very lightly edited.

There is a.

Fundamental misunderstanding.

I understand you have the misunderstanding, but there is a misunderstanding of the underlying science when one assumes that the 9001 dystrophin, which is shortened.

Is it sort of vastly shortened and then the dystrophin that's made by Exxon The survey on the storm on this or in the in the case of <unk>.

One of our competitors they'll test so is very likely I think there are those who might imagine that the resulting dystrophin is one exxon smaller that isn't the case.

Operator: I think there are those who might imagine that the resulting distrofen is one axon smaller. That isn't the case; Exxon skipping occurs in place to restore the reading frame and allow the messenger RNA to make dystrophin. That reading frame is restored by the removal of that Exxon, and then it will naturally include also the removal of the parts of the gene that are associated with the mutation.

The exon skipping occurs.

Place to restore the reading frame and allow the messenger RNA to make dystrophin that reading frame is restored by the removal of that Exxon and then it will naturally include also the removal of that.

That parts of the the gene that are.

Operator: And so, for instance, the resulting dystrophin that you can make can be, you know, 40% shorter, smaller, and yet very functional compared to wild-type dystrophin. And that's the same case in natural history with Becker-like distrophin. Becker-distrophin can be 50% or more shortened from full-length distrophin. But so long as the reading frame is intact and it can make distrophen, and it retains the right hinges and repeats, and the right anchoring places, it's functional.

With the mutation and so for instance, the resulting dystrophin that you can make it.

Can be 40% shorter smaller and yet very functional versus wild type dystrophin and Thats. The same case in natural history with Becker like dystrophin Bechard Becker dystrophin can be 50% or more shortly from from.

From full length dystrophin, but so long as the reading frame is intact and it can make dystrophin in it retains the right hinges and repeats.

And the REIT injury Places then its functional and Thats. The same thing with the 9001 district and this is a reasonable approximation of another any other becker liked dystrophin, just like a scientist and a modest <unk> zomig and so that so from at least our perspective the precedent for us.

Operator: And that's the same thing with the nine. 0901 distrosin. This is a reasonable proxanation of any other Becker-like distrofen, just like Xandis and Amondis and Viandis and Vyondis and Vyondis and Veltepst so make. And so, from at least our perspective, the precedent for Exondis and Biondis and Amondis and Bill Tepso is very relevant. Those therapies, while there's a different mechanism to get there because of the use of exon skipping and a chronic therapy, it is the same underlying concept where what you're doing is providing to the patient a shortened but functional dystrophin, which will protect them.

Scientists and biologists and a modest in El Paso is very relevant here those therapies. While there is it's a different mechanism to get there because it's their use of exon skipping in a chronic therapy.

It is the same underlying concept, where what you're doing is providing to the patient a shortened but functional dystrophin, which will protect them, but the biggest difference. In addition to the mechanism of action being different here, we're using a gene cassette to make the district dystrophin.

Operator: The biggest difference, in addition to the mechanism of action being different,

Operator: mechanism of action being different. Here we're using a gene cassette to make the distrofen. The biggest difference between these two is the amount of distrophine we are making. We are making, you know, multiples of an order of magnitude more distrophin with our gene cassette than we can make with the PMOs today, given the delivery limitations there. And so a couple of things, and then, you know, I'm kind of going on here, but so we say, number one, do I think there's a significant amount of precedent?

The biggest difference between these two is the amount of dystrophin, we're making we are making as well.

Multiples multiples of an order of magnitude more dystrophin with our gene cassette then we can make with the PMO is today given the delivery limitations, there and so a couple of events.

Kind of going on here, but so when you say number one do I think theres a significant amount of precedent I, absolutely do and I think there is an enormous amount of precedent for the idea that shortened functional dystrophin.

Operator: I absolutely do, and I think there's an enormous amount of precedent for the idea that short and functional distrophin is the right kind of biomarkerone is the right kind of biome, and they are reasonably likely to predict clinical benefit. It's the right kind of upstream biomarker that we should all be looking for. And second of all, there is not a significant difference in what's happening with 9-0-01 and what happens with the PMOs other than the amount of distrophine we're making.

If the right kind of biomarker reasonably likely to predict clinical benefit its the right kind of upstream biomarker that we should all be looking for.

And then second of all.

There is not as significant.

Difference in the what's happening with them.

9301, and what's happened with the PMO is other than the amount of dystrophin, we're making and then one final thing I'll say as long as I'm on my Soapbox on this topic.

Operator: And then one final thing I'll say as long as I'm on my soapbox on this topic: one must remember that, in nature, Becker dystrophin is the result of mutates. So the fact that these kids can make dystrophin and kids are adults, in the case of Becker, I think the average age, average mortality rate for Becker's as well into the 60s on average. The fact that they can make dystrophine is a happy accident.

One must remember that.

In nature Becker Dystrophin is the result of mutations. So the fact that these kids can make dystrophin kids or adults in the case of Becker I think the average age.

Average mortality rate becker's as well into the <unk> on average the fact, they can make dystrophin is a happy accident they still have.

Operator: They still have a reading frame, and they can make dystrophin. 9-0-0-1 is also different. Dr. Rodino Clayback, along with her partner, Dr. Jerry Mandel, worked for well over a decade to purpose-build a construct that would be shortened but functional, and, in the end, they were able to not only do that, but do it safely, and do it in a way that creates a robust amount of expression. And, you know, our position is protection. So there's my long-winded answer to your very simple question.

Our reading frame and they can make dystrophin, neither a zero one's different Dr. Rodino <unk>, along with her partners Dr. Jerry Mendell works for well over a decade to purpose build.

A construct that would be shortened deliverable, but functional and.

And they were able to not only do that do it safely and do it in a way that creates a robust amount of expression.

Our position as a protection.

There is my long winded answer to your very simple question.

Operator: Thank you. Our next question comes from the line of Judah Frama of Credit Suisse. Your line is open.

Thank you. Our next question comes from the line of Judah Frommer of Credit Suisse. Your line is open.

Operator: Yeah, hi, thanks for taking the question. Just curious if Embark came up in any way in the conversation.

Yeah, Hi, guys. Thanks for taking the question just curious if embark came up in any way and in the mid cycle communication and if so in.

Operator: if Embark came up in any way in the mid-cycle communication, and if so, in what context. And kind of the same question for conversations, you know, pre-commercialization conversations with payers: is Embark coming up as a topic of conversation, then?

<unk> context, and kind of same question for conversations pre commercialization conversations with payers is this embarq coming up as a topic of conversation.

Yeah.

Operator: As regards the relation to the mid-s, the mid-sacl, there was no explicit discussion in

As it relates to the the bid cycle. There was no explicit discussion of the market that mid cycle.

Operator: explicit discussion of the market at the mid-cycle. In pre-commercial discussions, you know, certainly, we discussed the entire program, and it includes the confirmatory trial embark. So yes, if there's anything I missed there, let me know. Nope, that's exactly right. Thank you.

On pre commercial discussions certainly we discussed the entire.

Program and it includes the confirmatory trial embark sorry.

Yes.

And if there is anything I missed there let me know.

No.

Exactly right.

Operator: Our next question comes from the line of Gil Bloom of Needham. Your line is open. Our next question comes in the line of Niels, from Gil Bloom. Your line is open. Thank you. I missed that last portion.

Thank you.

Our next question comes from the line of Gil Blum with Needham Your line is open.

Okay.

Our next question comes from a lot of Neil.

Gil Blum from Needham Your line is open.

Thank you I missed that last portion.

Operator: portion. One quick technical question, isn't May 29th a holiday? Is this a fine line?

Quick technical.

Isn't it may 29th of holiday.

We expect on the filings.

Operator: The other question I have is, do you think the payer pathway is going to follow closely, kind of, you know, the roadmap set by Zolgenzama? So on the first one, yes, it is the holiday. Officially, May 29 is our Purdue date. So we would assume we could hear on May 29th, this is Memorial Day, or we'll hear the business day before then, which would be May 26, if I'm not mistaken, or we would hear the day after May 209, which would be May 29. But we're using May 29 because that is indeed the current Padua Day.

Yes.

The other question I have is do you think the payer pathway is going to follow closely.

The roadmap set by Xeljanz Omar thanks.

So on the first one yes it is the holiday.

Officially may 29 is our producer date, so we would assume where we assume we could here on May 29, which is memorial day or where we're here.

The business day, before then which would be May 26, if I'm not mistaken or we would hear the day after may 29.

But we're using a 29 because that is indeed, the actual current producer date.

Operator: Um, and I think the question on the payer approach. I think the payer approach, so Gensma is probably, you know, one construct. I think, you know, we have an enormous amount of Duchenne-specific experience with the payer community. Obviously, we've now been supporting three therapies, and the earliest approval happened over six years ago, so I think we're in very good shape to have, you know, productive dialogue with payers about access and reimbursement for 9-0-0-01, assuming that we're able to get approved.

So and I think the question on the payer approach I think the payer approach agenda is probably one.

Construct I think we have an enormous amount of duchenne specific experience with the payer community. Obviously, we've now been supporting three therapies.

The <unk>.

Earlier approval happened over six years ago. So I think we're in very good shape to to them.

Reductive dialogue with payers about <unk>.

Access and reimbursement for <unk>, assuming that we were able to get approved.

Thank you.

Operator: Our next question comes from the line of Danielle Brill. Your line is open.

One moment please.

Our next question comes from the line of Danielle Brill of Raymond James Your line is open.

Operator: Hi, thanks for the questions. I have a question on the

Hi, guys. Thanks for the question.

I have a question on the micro dystrophin follow up data I believe we saw 60. These data from part one study went out.

Operator: the microdistrictment follow-up data. I believe we saw 60-leadda from part one of study 102. Do we have, um,

Operator: additional expression data at that time point or any expression data later at that time point.

Additional exploration data at that time point or any expression data at later time points and then random question do you see any legal risk for <unk>.

Operator: And then a random question: do you see any legal risk for 901?

Operator: One from Regenic's claim. Thank you.

Janice.

P claim thank you.

On the.

Operator: On the second question, I'll answer and say no, we don't. On the first question, I'll turn it over to Luis, if you have, if you understand what. I didn't fully understand the question, Paul. It was just about additional time points. There are no additional biopsy time points in the one study that we haven't done.

Second question.

I'll answer and say now.

No.

On the first question and I'll turn it over to Luis if you do have to understand what.

Totally understand the question apologies.

It was just about additional timeline there is no additional biopsy time clients in a democratic.

Operator: That we haven't. I thought we hadn't.

Yeah.

Thank you.

Operator: Our next question comes from the line of Hard Touch Singh of Oppenheimer. Your line is open.

One moment please.

Our next question comes from the line of <unk> <unk> of Oppenheimer. Your line is open.

Operator: Great, thank you. And congratulations on a very big step forward; looking forward to many more. Actually, just a question on SRP 9003.

Alright, great. Thank you.

Congratulations on a very big step forward.

Looking forward to many more just a question actually on an Sop <unk> three.

Operator: I know you've got the Roy Gene trial starting, phase one. You're doing additional work. Doug, Louise, you're also doing a lot of work around, you know, characterizing the material, the clinical material, commercial, et cetera. If you could just talk about that, but also just talk to us about what the phase three design could look like. You've indicated that it could start later this year. Luis, do you want to take it?

No you've got the Voyager trial, starting the phase one youre doing additional work.

Doug you also being a lot of work around.

Characterizing the material the clinical material commercial et cetera, if you could just talk to that but also just talk.

Talk to us a little bit about the phase III design could look like I believe you've indicated that could start later this year.

Thanks for the question.

Luis do you want to take that.

Yes, thanks for that question.

Operator: Yeah, thanks for that question. Certainly, we're looking at this closely. This is an ultra-re indication, and so we're looking at all the data we have to date in both the ambulatory population and now this new population that we're studying, which is the older ambulatory and non-ambulatory population so that the totality of the patient population could be captured in that phase three disease.

Certainly.

We're looking at this closely that doesn't alter air.

Indication and so we're looking at all the data we have to date in both the ambulatory population and now the new population that we're studying which is D. All of the ambulatory and non ambulatory.

And so that the totality of the patient population could be captured in that and I think redesign we don't havent finalized yet, but all of the results from these two trials will be taken into consideration on me.

Operator: in that phase three design. So we don't have it finalized yet, but all of the results from these two trials will be taken into consideration when we have the ultimate study design for that phase three study. Thank you.

The ultimate study design for that.

Phase III study.

Thank you. Our next question comes from <unk> Zhang.

Operator: for taking a question. So my question is actually also on the Limberra program, and

<unk> Your line is open Sir.

For taking my question. So my question is actually also on the limb girdle program and I was wondering what is the purpose of the phase one study and what kind of information or trying to get and given the small prevalence of the indication what's your thinking on the patient allocation enrolled patients into the currency.

Operator: I was wondering what the purpose of the phase one study and what kind of information you are trying to get and, given the, you know, small prevalence of the indication, what you're thinking about patient allocation, and enrolling patients into the current study. I don't believe you have disclosed the size of the study versus maybe 60.

I don't believe you have disclosed the size of the study versus maybe say be patient for future pivotal study.

Operator: close the size of the study versus maybe saving patients for future pivotal studies. Yeah, I'll give you a brief name now; Louise can answer it and correct me when I get this wrong.

Yes, I'll touch on it briefly now Luis can answer it and correct me, where I get this wrong I mean, the reason that we're doing there.

Operator: I mean, there are two reasons why we've done this clinical experience study. The first is that it gives us an opportunity to explore the safety and expression of the therapy in a broader patient population than we would typically do for our pivotal trial itself. So we will glean important information. And the second reason that we did it is that we had clinical material available.

There are two reasons why we've done this clinical experience study.

The first is that it gives us an opportunity to explore the safety and expression of the therapy in a broader patient population than we would.

Typically do for our for.

Our pivotal trial itself, so we will lean in.

<unk> information and the second reason that we did it is that we have clinical material available to us so for the pivotal trial, we need to have commercially.

Operator: So for the pivotal trial, we need to have commercially appropriate material, and that has to be material that would be appropriate for the launch of the therapy. We have very appropriate clinical material right now, and it seemed appropriate to make good use of it, to get additional insight and also, frankly, to provide a benefit at the same time. Luis? I think you characterize it well, emphasizing that this is a different patient population than we've previously studied in older patients where we can look at safety and efficacy and non-ambulatory and older ambulatory, which is an important component of this prevalent population.

Appropriate material and that has to be material that would be appropriate for the launch of the therapy, we have very appropriate clinical material right now and it seemed appropriate to.

To make good to get additional insight and also frankly to provide a benefit at the same time Luis.

I think you characterized it well just emphasizing that this isn't that different patient population than we've previously studied and older.

Patients, where we can look at safety and efficacy in non ambulatory and older ample I'm, sorry, which is an important component.

Frontline population.

Operator: Our next question comes from Alana, Kristen Klasker, on cancer. Your line is open.

Thank you.

Our next question comes from the line of Christian <unk> of Cantor. Your line is open.

Operator: Hi, this is Rick on behalf of Kristen. Thanks for taking our question. In the press release, it mentioned that the Catalan agreement lays out how Catalan could support multiple gene therapy candidates in the LGMD pipeline. So could you maybe go into a little detail here on what this might mean in terms of whether this could deal with clinical grade material or potentially commercial grade material for later stage trials in LGMD?

Hi, This is Rick on for Chris and Thanks for taking our question.

The press release mentioned that Catlin agreement structures, how Cadillac could support multiple gene therapy candidates in the <unk> pipeline. So could you maybe go into a little detail here on what this might mean in terms of whether this could deal with clinical grade material or potentially commercial grade material for later stage trials and <unk>. Thanks.

Operator: Yeah, our relationship with Catalan, and our goal is to, they would potentially have the opportunity to ban your factual for us for limb girdle. Really, our goal going forward is to try to have commercial representative material from the first inpatient clinical trial. You know, historically, as we evolved from nationwide Children's Hospital, as you know, the first study with 9-001 started with clinical material. Likewise, 9-003 started with clinical material provided by nationwide. But the fastest pathway forward is to have commercial representative material from the beginning, and that's going to be our goal. And the potential of doing that with cattle

Yes, our relationship with Cadillac and our goal is to.

They would potentially have the opportunity to manufacturer for limb girdle really our goal going forward is to try to have commercial representative material from the first.

Inpatient clinical trial, you know historically as we.

Evolved from nationwide Children's hospital as you know the first study with 9001.

Starting with clinical material. There Likewise 903 started with clinical material provided by nationwide, but the fastest pathway forward is.

To have commercial representative material from the beginning and that's going to be our goal and the.

The potential of doing that with Cadillac is a significant one.

Operator: Thank you. The next question comes from Gavin Clark Gardner of Evercore.

Thank you.

Our next question comes from Gavin Clark Gardner of Evercore. Your line is open.

Operator: Yeah, thanks for taking the question. In phase three, you excluded Exxon's 1 through 17, but as you noted, you've been dosing patients inside that range. Have you had any discussion about getting some of those?

Yeah, Hey, thanks for taking the question phase III excluded exon 117, but as you noted you've been dosing patients inside that range have you had any discussion.

On getting some of those exxon's included in the initial label and is there any chance that something in here could represent.

Operator: are included in the initial label, and is there any chance that something here could represent a major amendment?

Operator: major amendment

Operator: It won't be a major amendment because our BLA went in with the assumption that we would have a narrower exclusion. We already had a good scientific rationale for why the label, the labeled exclusions need. It should be narrower, and we were being overly exclusive in those mutations. And then to support that thesis, we've started this, and we're nearly done enrolling a study to explore those mutations. It's going quite well right now, but our initial BLA went in with the request that we have a narrow or exclusion in our proposed label in connection with our initial BLA submission made that same assumption.

Andrew Amendment. Thanks.

It won't be a major amendment, because our BLA went in with the assumption that we would have a narrow narrower exclusion we.

<unk> already had good scientific rationale for why the label.

Label exclusions needed should be narrower that we were being overly exclusive and those mutations and then to support that thesis.

We started this and we're nearly done enrolling a study to explore those mutations it's going quite well right now, but our initial BLA went in with the.

Requests that we have.

And there were exclusion in our proposed.

Label in connection with our initial BLA submission made that same same assumption.

Operator: Thank you. One moment, please. Our next question comes from the line of Salvin Richter.

Thank you one moment please.

Our next question comes from the line of solving Richter.

Operator: Hi, this is Tommy on behalf of Selveen. Thanks so much for taking your questions and congrats on the progress. Just wondering how you're thinking about uptake in between that period after the accelerated approval that before Embark reads out, any physician or payer commentary that some might wait to prescribe to see Embark, and can you just remind us how long it takes for patients to get tested for eligibility?

Your line is open.

Hi, This is Tommy on for Celgene. Thanks, so much for taking our questions and congrats on the progress just wondering how you're thinking about uptake in between that period. After the accelerated approval that performed Barclays out any physician or a payer commentary that some might wait to prescribe to embark and that can you just remind us how long it takes.

Patients to get tested for eligibility. Thanks, so much.

Operator: eligibility. Thanks so much.

So we dealt with our current.

Operator: So we don't, with our current thinking based on all of our discussions, both with thought leaders and with, certainly, you know, with patient groups and families, that people wouldn't wouldn't wait you know waiting is not a viable option for people with this degenerative disease i would note that by the end of this call somewhere around the world a kid with duchesne will have died and another kid will be going on a vent and another kid will will go into a wheelchair never to get back out of a wheelchair so the luxury of patients isn't there for these families so um so we we don't intend to, you know, we don't imagine that people would wait for, you know, other readouts down the road and put their kids at risk. At least that's not our current assumption, nor do we think it's the assumption and the, um, the, um, the, you know, treating physicians either. Um, certainly those who have seen what 9-001 can do, I don't think would want to win.

We're thinking based on all of our discussions both with thought leaders and with.

With patient groups and families that people would.

Wei waiting is not a viable option for people with this degenerative disease.

I'd note that by the end of this call somewhere around.

Round the world the Kid with Duchenne will dive in another kid will be going on in that another kid well.

We'll go into a wheelchair never to get back out of a wheelchair so the luxury of patience isn't there for these families. So.

So we don't intend to we don't imagine that people would would wait for other readouts down the road put their kids at risk at least that's not our current assumption nor do we think that's the assumption.

The.

Sure.

Sure.

Treating physicians either.

Certainly those who have seen what nine joser one can do I don't think we'd want to win.

As far as the process down when you want to touch on the process itself.

Operator: As far as the process is concerned, Dalland, do you want to touch on the process itself? Yeah, and just to underscore what you said about the urgency, Doug, that's what we're seeing out there as well. And I think in terms of what the team has for the process, the data is, you know, to have a fully enrolled confirmatory trial at the time of approval is just such an incredible position to be in. And so that's going to inform all of our dialogue going forward on this.

Yeah, Yeah, Yeah, and just to underscore what you said about the urgency Doug.

That's what we're seeing out there as well and I think in terms of what the team has for the process. The data is.

As you know.

To have a fully enrolled confirmatory trial at the time of approval is just such an incredible position to be in so.

So that's going to inform all of our dialogue.

Going forward on this.

Operator: I'm showing no further questions at this time. Let's turn the call back over to Doug Ingram.

Thank you.

Im showing no further questions at this time I'd like to turn the call back over to Doug Ingram for any closing remarks.

Operator: over to Doug Ingram for any closing remarks.

Operator: Well, thank you very much, everyone, for joining us this evening.

Well. Thank you very much everyone for joining us this evening.

Operator: evening, and so you're very good questions. It is a poignancy.

For your very good questions.

Operator: I think, as Dr. Radino Clayback noted, that today is indeed rare disease day. We are completely committed to using great science and moving as fast as possible to bringing a better life to Dushen patients and beyond Dushen patients to other rare disease patients. And I look forward to updating people along the way, although I will note yet again that as relates to the BLA, the next substantive update you'll get is around May 29th, which is our action date. So thank you all very much and have a lovely evening.

It is a point in <unk> I think is.

Dr. Rodino playback noted that today is.

Deed rare disease day, we are completely committed to using great science and moving as fast as possible to bring a better life to duchenne patients and beyond duchenne patients to other rare disease patients and I look forward to updating people along the way, although I will note yet again, but as it relates to the BLA for nine years.

Zero one the next substantive update you'll get is on or around May 29, which is our action date. So thank you all very much and have a lovely evening.

Operator: Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all for participating you may now disconnect have a great day.