Sarepta Therapeutics Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 2, 2023

There are 17 speakers on the call.

Operator

As a reminder, today's program is being recorded. At this time, I'll turn the call over to Francesca Nolan, Executive Director, Investor Relations and Corporate Communications. Please go ahead.

Speaker 1

Thank you, Jonathan, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the Q2 2023. The press release is available on our website at sirepta.com and our 10 Q was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estapan, Dalen Murray and Doctor. Louise Rodino Klapac.

Speaker 1

After our formal remarks, we'll open the call for Q and 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 Sarepta's control. Actual results could materially differ from these forward looking statements and any such risks can materially and adversely affect the business, the results of operations and trading prices for Sarepta's common stock.

Speaker 1

For For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10 Q 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, Officer, including any financial projections provided today based on subsequent events or circumstances. And now, I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress.

Speaker 2

Ted? Thank you, Fran. Good afternoon and thank you for joining our Q2 2023 financial Gold's conference call. The Q2 of this year was perhaps the most consequential period in the long consequential history of Sarepta. For families living with Duchenne, it was far more than that still.

Speaker 2

Buddy Cassidy, living with Duchenne and an Alevitus Advisory Committee member, shared the collective view of the Duchenne community on the June approval in words far more eloquent than I could possibly muster. As Buddy said, and I quote, there is more to do. But now let us pause and bask in the glow of our achievement. Let us bask in gratitude. Let us pause in celebration.

Speaker 2

Let us watch as dawn rises and brings in the day. In May of this year, the FDA held an advisory committee meeting on our gene therapy SRP-nine thousand and one now called Alevitus. With a majority vote, the advisory committee recommended the approval of alevitus for the treatment of ambulatory patients with Duchenne muscular dystrophy. On June 22, the FDA granted an accelerated approval for Alevitus to treat Duchenne muscular dystrophy, currently labeled for 45 year old patients. At the time of the approval, FDA leadership informed Sarepta and the patient community That if our confirmatory trial, IMbark, meets its objectives, the FDA will, in the words of Doctor.

Speaker 2

Peter Marks, Move with maximum speed following submission of the data to the agency, minimizing any impediments to review results rapidly and broadening the label by removing any age restrictions. So we have our path. Our confirmatory trial is well designed and powered to show a statistically significant benefit in the studied population. For the avoidance of doubt, we have powered this study to show a benefit in the studied population and Chief Executive Officer of the company's 4 years to 7 years old. And with that, we will have confirmed the mechanism of action in Duchenne patients applicable to all age ranges.

Speaker 2

We will have the top line for Embark in the Q4 of this year. We will announce top line results as we submit them to the division, followed shortly by a label supplement. If successful, we should be able to expand our label in the first half of 2024 to include the majority of Duchenne patients. Additionally, we have already commenced our non ambulatory trial in vision or Study 303. And we intend to commence 2 trials with alternative approaches to cleaving or clearing pre existing antibodies.

Speaker 2

Our goal is to expand our label for olebitis to cover as much as 95% of the Duchenne patients. In a moment, our Chief Customer Officer, Dalen Murray will provide details on the early days of the ELEVADIS launch. ELEVADIS is our 4th approved Duchenne therapy and we have been very successful with all of our prior launches. Consistent with our track record, the Alevitus launch is going well. A significant number of sites are now initiated and ready to infuse.

Speaker 2

Payer discussions and negotiations have been more positive than our prior successful therapies and there is a significant amount of enthusiasm from physicians and families as we have a substantial number of start forms and more coming weekly. In fact, I am pleased to announce That the first reimbursed Alevitus infusion occurred earlier today. That is faster than we projected and speaks to the team's ability to execute. Now as positive as this is, please bear in mind that the significant ramp in infusions will begin later this year. This is primarily due to payer logistics and to the release protocol for Alevitus, which requires that both we and the FDA release each allot.

Speaker 2

Shortly, our Head of Research and Development and Chief Scientific Officer, Doctor. Luis Rodino Klapac, will provide an overview of our development activities, including progress with our next generation PPMO SRP-five thousand and fifty one and on the gene therapy side with our LGMD portfolio. To remind you, in addition to alevitus, we have a deep pipeline and are advancing And we continue to advance our next generation viral capsid, Myo AAV, which in early animal models Looks to be as much as 10 fold more tropic than current AAVs. From a manufacturing perspective, our technical operations Professionals more than 400 in all are focused with our partner Catalent on producing and releasing launch to support our launch. Looking to the midterm, we will also continue to work to establish comparability at our Thermo Fisher plant for Alevitus.

Speaker 2

And then looking to the future, we are advancing our approach to manufacturing to support our entire pipeline. In fact, we have made great progress and Next Generation Suspension Technology, which we will use across our gene therapy portfolio, including the LGMD programs and even potentially for Alevitus. In fact, we have largely completed our suspension based process development for Alevitus And we have made 3 runs at 2 50 liters with a 4th run to occur later this year with the goal of scaling to 1,000 liters in the near term. We have seen yields that are multiples greater than the current standard. As the leader in gene therapy for rare diseases, we will continue to focus on improving the science and the delivery of our therapies.

Speaker 2

Moving finally to quarterly performance, we have had another strong quarter with our 3 approved PMOs, XONDYS, Amandis and Viandis. I am pleased to announce that 2nd quarter total revenue came in at 261 $200,000 in net product revenue from our PMOs came in at $239,000,000 exceeding internal estimates and analyst consensus. In the Q2, we saw no negative impact on the approved PMOs from any warehousing related to the Alevitus approval and do not anticipate substantial impact over the course of the year. We remain comfortable with our full year guidance of $925,000,000 for total PMO netproductrevenue with the current bias to modestly exceeding that guidance. It is too early in the launch to provide and accurate guidance for Alevitus, but we will continue to evaluate that.

Speaker 2

At Sarepta, we have a distinct culture. It is easy to say one is patient focused, but our words are backed by action. We put the welfare of our patients Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer,

Speaker 3

our Chief Executive Officer, our Chief

Speaker 2

Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our

Speaker 3

Chief Executive Officer, our Chief Executive

Speaker 2

Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our Chief Executive Officer, our

Speaker 4

Chief Executive Officer, our Chief Executive Officer,

Speaker 2

our Chief Executive Officer, our Chief Executive Officer, and the courage to represent the patients who depend upon us. Our fight may not always be easy, but it is paying off. We have 4 approved therapies and a wealth of potentially life enhancing programs in our pipeline. We will achieve $925,000,000 on the first three of our 4 approved therapies this year and far more next year when our newest approval is considered. We have a near term high probability of success plan to broaden the label of the first and only gene therapy for Duchenne.

Speaker 2

And if our plans are successful, we could be profitable in the next few quarters. We have done a lot already, but with our plans, our pipeline and our commitment To dogged execution, we have only just begun. And with that, I will turn the call over to Doctor. Rodino Klapac, who will provide an update on our research and development progress. Luis?

Speaker 5

Thanks, Doug. The accomplishments within R and D over the last quarter are many and highlighted by the approval of OLEVITUS on June 22, 2023. The approval of OLEVITUS via the accelerated approval pathway represents a win for the Duchenne community and an important step towards the broad approval for individuals living with Duchenne regardless of age or ambulatory status. As we look forward to the weeks months ahead, We remain firmly committed to our values to follow the science and present objective evidence that supports OLEVITUS' ability to change the trajectory of Duchenne muscular dystrophy. Since 2018 and across multiple studies, we've dosed the largest number of Duchenne patients More than any other gene therapy in development for this disease, to remind you, we've shown consistent results across 3 clinical studies with respect to both biomarker expression and functional results.

Speaker 5

In clinical trials, Alevitus demonstrated positive results at multiple time points, Including 1, 2 and 4 years after treatment, in addition to a consistent safety profile. The BLA for elovidus included efficacy and safety data from studies 101, 102,103 or Endeavour as well as an integrated analysis across these three clinical studies comparing functional results to propensity score matched external control. Importantly, the functional data reinforce the consistency of NSAA improvement across these 3 independent trials and show mean improvements across key secondary functional endpoints such as time to rise and 10 meter walkrun. The data from studies 101, 102 and 103 Cohort 1, which is ages 4 to 7, have now been either published or accepted for publication in peer reviewed journals. When compared to appropriate control populations, Elevatus has consistently shown a treatment effect as measured by change in MSAA score at 1 year.

Speaker 5

We have applied the learnings from studies 101,102 and 3 in the design, the execution and statistical analysis plan for our Phase 3 EMBARQ study. To remind you, Embark is a double blind randomized placebo controlled trial of ELEVITUS in Duchenne patients ages 4 to 7. We completed enrollment in the fall of 2022. The trial will be considered successful if the entire treated population Shows a statistically significant positive difference in NSAA scores at 1 year compared to placebo. Our conviction around IMbark is founded in data And was designed based on our experience with studies 101,102 and 103 along with our propensity weighted external controls and natural history data sources.

Speaker 5

We took extensive measures to ensure success, which include the following. The EMBARK study design improves on Study 102 with measures to increase homogeneity, including a floor and a ceiling on baseline NFAA and a requirement for Ryerson floors to be less than 5 seconds at Screening. We also ensured a balanced distribution between treatment arms by including a stratification factor for baseline NSAA score. We also increased the target sample size to 120 to increase power and enrolled 125 patients. All of these measures results in a study powered well over 90%.

Speaker 5

As discussed at the advisory committee in May, With an assumed standard deviation of 3.5 points in 120 patients, Embark was powered greater than 90% to see a 2.2. Difference on NFAA. Thus, we've always been confident in the powering of the study. We've also done extensive analysis and modeling that provides additional confidence in the success of Embark. First, When the integrated summary of efficacy population included in the BLA, which was an N of 52, is narrowed to those who meet 301 entry criteria For an N of 33, the standard deviation goes down, confirming increased homogeneity.

Speaker 5

We also performed Simulation models of 4 scenarios drawn from existing program data that have all yielded greater than 90% power. Given the entire protocol, we're able to detect an even lower treatment effect. For example, with an assumed standard deviation of 3.5 points, Our analysis will predict statistical significance at observed treatment effects in the overall intent to treat population With regards to additional lebodis studies, we've commenced dosing on EVISION, our placebo controlled Phase 3 study in non ambulant and older Ambulance patients with Duchenne. We are also on track to commence an apheresis study as well as an amylifidase study in AAVrh74 antibody positive Duchenne patients this year. This is all with the goal of serving the entire Duchenne population.

Speaker 5

Now moving to Limb Girdle Muscular Dystrophy or LGMD. We remain committed to advancing our LGMD portfolio across a variety of subtypes and look forward to providing updates on these important programs in the months ahead. We're pleased to report that we have fully enrolled JOURNEY for LGMD Natural History Study. 126 patients with sarcoglycanopathy have been enrolled and will be followed for 36 months. We've also made excellent progress in rolling VOYAGINE, our Phase 1 study evaluating SRP-nine thousand and three Using clinical process SRP-nine thousand and three material.

Speaker 5

Combined with positive expression and functional data shared from our initial study, SRP-nine thousand and three-one hundred and one. We believe the data from Voyaging will give us insights into a broader patient population. Our next milestones for VOYAGENE include completing enrollment in Q3 of this year and initiating our Phase 3 study using commercially representative process material later in the year. Finally, we've commenced dosing of a systemic pilot study, Navigene, for our SRP-six thousand and four dual vector rh74 mediated gene therapy to treat LGMD2b, Characterized by the absence of the protein Dysferlin. The innovative dual vector strategy allows us to deliver the full length Dysferlin gene, The sole cause of LGMD2b.

Speaker 5

We also continue to make progress in manufacturing for all LGMD candidates in our pipeline and look forward to initiating clinical studies as rapidly as possible. Turning now to the progress we've made with our RNA platform. We were pleased to complete enrollment in the Q1 of 2023 for a MOMENTUM study for SRP-five thousand and fifty one, and we remain on track to announce data from the study in the back half of twenty twenty three. In regard to our post marketing studies for the PMOs, As mentioned last quarter, we completed enrollment in the ESSENCE trial, our post marketing requirement for golodirsen and casimersen and continues to make good progress with our mission study, which is on track to be fully enrolled this year. The accomplishments of 2023 and the opportunities before us speak to the promise of science to fundamentally impact and change the lives of patients around the world.

Speaker 5

On the research side, we continue to make excellent progress on the Myo AAV platform along with an exciting pipeline of genetic medicine candidates. My deepest gratitude to our R and D colleagues across RNA, gene therapy and gene editing for their extraordinary work to get us where we are today. Finally, to the patient community, we understand the urgency and we're working tirelessly to bring forth transformative genetic medicines as rapidly as science will We are doing everything we can to expedite the EMBARK study readout so that we can expand the Alevitus label. We expect the data will be available in the next 3 to 4 months. I will now turn the call over to Dalen for an update on our commercial activities.

Speaker 5

Dalen?

Speaker 4

Thank you, Luis, and good afternoon. We were thrilled to receive approval for Alevitus on June 22nd, And we owe a tremendous debt of gratitude to the patients who participated in the trials, the KOLs and our R and D colleagues for getting us to this point. As Doug and Louise have said, we are deeply committed to broadening the label at the earliest time point that is feasible. During this time, the team is diligently working day and night to expedite access to this potentially transformative therapy for all eligible 4 to 5 year old Duchenne patients. Their dedication is focused on ensuring swift and seamless access for those who can benefit from Alevitus.

Speaker 4

In these early stages, much of our focus is on supporting those sites who have boys turning 6 years old. At the same time, we are also rapidly preparing the sites to treat all of the patients who are eligible today and laying the groundwork to be ready for a broader patient population when the time comes. The team's remarkable progress and Unwavering sense of urgency in executing our now 4 Duchenne launches are truly commendable and reflect our commitment to providing timely access to potentially transformative therapies for patients. The commercial and medical teams began educating the centers within 24 hours of approval, as we've done in our previous three launches. Right from day 1, our case managers were fully prepared to assist patients in navigating the intricate aspects of the gene therapy treatment journey.

Speaker 4

Doug has previously highlighted the unique components of a gene therapy launch, which we must get right in order to serve the community. The three areas of focus are site readiness, payer engagement and building the capabilities for antibody testing. In terms of gene therapy site readiness, as of today, we have over 50 sites trained, activated and ready to receive product. We have achieved this ahead of our own aggressive timelines. On the payer front, Since approval, the team has engaged both commercial and Medicaid payers, representing approximately 250,000,000 lives.

Speaker 4

Continued progress has been made in educating and informing them on the clinical data to support policy formation to our approved FDA label. As an example, UnitedHealthcare, one of the largest commercial insurers in the United States, published their coverage policy for levetis yesterday, Aligning the therapy to its FDA approved label. And finally to touch on antibody testing. Over 700 kits were in the hands of our key sites within a day or 2 of approval. Testing is currently underway And the process is working smoothly.

Speaker 4

We've seen very strong demand for Alebitis and are encouraged by the discussions with KOLs, Payers and the broader community. We began receiving enrollment forms within hours of approval, and we continue to see them come in on a daily basis. Since June 22, the team has had over 500 interactions with both treating and referring sites. In these early discussions, our focus has been 1st and foremost on patient safety, eligibility, procurement, Dosing and Preparation and Reimbursement. Launching the first gene therapy for Duchenne patients requires a multifaceted approach with a high level of communication, not only with HCPs and sites, but also patients, families and payers to ensure patients and Chief Executive Officer

Speaker 3

of the company have timely access to this

Speaker 4

groundbreaking therapy. As a result of our preparation and diligent efforts, we are now at the point where patients can begin receiving Alevitus with confidence. As I previously highlighted, our engagement with payers has been constructive. The team is optimistic in making progress towards our goal of ensuring timely access. Of note, we are seeing states to reach out to their local KOLs and experts to inform policies.

Speaker 4

We expect to have payer policies in place within 3 to 6 months depending on the plan. In the interim, we are working with payers on a case by case basis to obtain access for patients. To that end, we have received multiple authorizations. And as Doug mentioned, we were thrilled to announce that the first patient was dosed today. Over the course of the next week and a half, we have a handful of additional infusions across the country scheduled with patients representing a combination of Commercial and Medicaid Insurance Coverage.

Speaker 4

We are gratified by the tremendous work being done across of the country to support patients. In particular, there has been a concerted effort since approval to rally around those patients who are approaching Their 6th birthday. The incredible efforts to support those patients from all involved has been truly humbling. While we are encouraged by our progress and accomplishments to date, it's important to reiterate that we are not providing revenue guidance in the early stages of this one of a kind launch. As Doug made clear on the approval call, we expect this to take Some time in the early stages before dosing can begin in earnest to generate the launch ramp we are confident will come.

Speaker 4

I want to take a moment prior to reflecting on our PMO business to thank everyone within Sarepta and our key partners who have worked So hard to make this launch a reality and allowed us to be ready to serve these patients right from day 1. Now regarding our PMO business, it's critical to highlight the fact that we have not lost a step supporting our PMO patient community While we've risen to the challenge of the first Duchenne gene therapy launch. As Doug mentioned, we delivered $239,000,000 in net product revenue in the second Quarter, representing 13.1 percent growth over the Q2 of 2022. EXONDYS 51 totaled $134,700,000 representing 6.6% growth over Q2 of 'twenty two. For VyONDYS 53, sales were $32,600,000 growing roughly 8.2% over the Q2 of 2022.

Speaker 4

And for Amondis 45, sales totaled $71,700,000 representing more than 31% growth versus Q2 of 20 22. Total ex U. S. Net product revenue in the Q2 was roughly $35,000,000 This represented an increase over the prior quarter, which was expected and fully reflected in our annual guidance and forecast. As discussed on last quarter's call, we expect to see even more quarter to quarter fluctuations in the overall net product revenue as the ex U.

Speaker 4

S. Becomes a bigger percentage of the overall PMO mix. Importantly, these quarter to quarter fluctuations along with the shifting mix of the PMO revenue base have all been anticipated and fully reflected in our annual guidance. Overall, the fundamentals of the PMO business coming out of Q2 are completely in line with what we expected at this point in the year, and we reiterate our full year guidance of $925,000,000

Speaker 3

in net

Speaker 4

product revenue for our PML therapies. In closing, our teams are fully engaged and executing today to support patients with all 4 of our approved therapies. I'm particularly pleased to see the continued success of our PMO business in the Q2. In fact, looking back on the execution of all 3 of our PMO launches should provide a high level of confidence in the future of Sarepta and our potential to transform of Duchenne's space with Alebitis and pave the way for precision genetic medicines for other rare patient populations such as limb girdle muscular dystrophy. And with that, I'll turn the call over to Ian S.

Speaker 4

DePend for an update on our financials. Ian?

Speaker 6

Thanks, Dalen. Good afternoon, everyone. This afternoon's financial results press release provided details for the Q2 of 2023 on a non GAAP basis as well as a GAAP basis. Please refer to the press release available on Sarepta's website for a full reconciliation of GAAP to non GAAP financial results. For the 3 months ended June 30, For 2023, the company recorded total revenues of $261,200,000 which consists of net product revenues and collaboration revenues Compared to revenues of $233,500,000 for the same period of 2022, an increase of $27,700,000 Net product revenue for the Q2 of 2023 from our PMO ex non skincare franchise was $239,000,000 Compared to $211,200,000 for the same period of 2022.

Speaker 6

The increase in net product revenue primarily reflects increasing demand for our PMO products. In each of the quarters ended June 30, 2023, 2022, we recognized $22,300,000 of collaboration revenues, which relates to our collaboration arrangement with Roche. The reimbursable co development costs under the Roche agreement totaled $28,200,000 for the Q2 of 2023 compared to $26,400,000 for the same period of 2022. On a GAAP basis, we reported a net loss of $23,900,000 or $0.27 per basic and diluted share and $231,500,000 or $2.65 per basic and diluted share for the Q2 of 2023 and 2022 respectively. We reported a non GAAP net loss of $75,200,000 or $0.85 per basic and diluted share in the Q2 of 2023 compared to a non GAAP net loss of $103,000,000 or $1.18 per basic and diluted share in the Q2 of 2022.

Speaker 6

In the Q2 of 2023, we recorded approximately $34,100,000 in cost of sales compared to $37,800,000 in the same period of 2022. The decrease in cost of sales primarily reflects a decrease in our royalty payments during the 3 months ended June 30, 2023, due to changes in the BioMarin royalty terms and a decrease in write offs of certain batches of our products not meeting our All of these specifications for the 3 months ended June 30, 2023, as compared to the same period of 2022, partially offset by an increase in demand for our PMO products. On a GAAP basis, we recorded $241,900,000 and $252,300,000 in R and D expenses for the Q2 of 2023 2022, respectively, A year over year decrease of $10,400,000 The decrease is primarily due to a decrease in manufacturing expenses, for $212,200,000 for the Q2 of 2023 compared to $230,400,000 for the same period of 2022, A decrease of $18,200,000 Now turning to SG and A on a GAAP basis, we recorded approximately $118,600,000 $154,300,000 of expenses for the 2nd quarters of 2023 2022, respectively, a decrease of $35,700,000 The decrease was driven primarily by a decrease in stock based compensation expense. On a non GAAP basis, SG and A expenses were $90,300,000 for the Q2 of 2023 compared to $3,700,000 for the same period of 2022, an increase of $26,600,000 On a GAAP basis, we recorded $16,900,000 in other income net for the Q2 of 2023 Compared to $17,000,000 in other expense net for the same period of 2022, the change is primarily due to an increase in interest income and accretion of investment Account 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 during 2022.

Speaker 6

In the Q2, we entered into an agreement to sell the rare pediatric disease cardiomy review voucher received from the FDA in connection with the approval of oledivitis for a consideration of $102,000,000 with no commission costs. The net proceeds were recorded as a gain from the sale of the PRB as the Levitus did not have a carrying value at the time of the sale. And finally, we had approximately $1,900,000,000 in cash, cash Equivalent Investments and Long Term Restricted Cash as of June 30, 2023. So in closing, I'd just like to reiterate how exciting What time it is for Sarepta and the patients we serve, seeing the first patient dose today brought true joy to all of our hearts. And then from a financial perspective, we're looking forward to being one of the rare biotech companies to actually make the transition to profitability.

Speaker 6

In fact, we anticipate becoming non GAAP EPS positive in the upcoming quarters. So this has truly been quite an accomplishment on all branch for us and we're particularly proud of what we've been able to do. And with that, I'll turn the call over back to Doug to start the Q and A.

Speaker 2

Thank you very much, Ian, and here to those last comments. Jonathan, let's open the call for questions.

Operator

Certainly. Ladies and gentlemen, we ask that you please limit yourselves to one question each. You may get back in the queue as time allows. One moment for our first question. Our first question comes from the line of Colin Risto from UBS.

Operator

Your question please.

Speaker 7

Hey, good afternoon and congrats on another milestone with The first patient dosed. I guess a sort of 2 part question around the comments you made around Embark, Hitting with as low as the 1.3. Delta, I'm curious what is the powering the 1.3 delta is at? And as I've been in discussion with FDA whether this would be considered clinically meaningful and then just as a sort of follow-up from that, I think the most common question we're getting is that If Embark misses the primary in the overall population, but shows a directional benefit in 4 to 5 year olds, given there's no multiplicity The strategy has FDA given any indication on whether this would be sufficient to maintain the approval status? Thank you.

Speaker 2

So I'm going to turn the question over to Luis on the powering issue. But real quickly just On the latter question, so we haven't had discussions with the agency directly about clinically meaningfulness of a particular number. But I want to remind you that the effect one sees at 52 weeks Isn't the effect, it's a signal of the long term effect. Using an artful metaphor, If we took off in from Los Angeles and we were one degree off trying to get to Tokyo, by the time we hit Catalina Island, we wouldn't be that far off. But If we continue with that one degree, we'd be 500, 600 miles away from Tokyo.

Speaker 2

That's what we're dealing with here. This is a disease that Is degenerative over time. If we can see a statistically significant benefit in a mere 52 weeks, We have clearly changed the trajectory of this disease in a very positive way. So with that said, let me turn The technical question on the powering calculations over to Doctor. Rodino Klapac.

Speaker 5

Thanks, Doug. So based on the modeling that we did, this isn't a traditional power calculation. So this was a simulation model in order to determine The lowest effect size that we could see in order to hit stat sig. So we put the following assumptions into our model, 125 patients, which is the number of patients we enrolled, no dropouts because we've not seen any dropouts in Embark. We assumed a standard deviation of 3.5 across the entire 4 to 7 year old population.

Speaker 5

And then we varied the effect size in order to see how low we could Go in order to still hit statistical significance. And that's how we arrive at the equal to or greater than 1.3 as This isn't to be assumed effect size. This is as low as the modeling will show us to still see statistical significance.

Speaker 2

And then one final thing. Colin, you had asked about the way the agency would look at the data. Again, we are powered for success in Embark and our goal is to see statistically significant meaningful I benefited from the therapy in 52 weeks. At the end of the day, the agency's standard is to look at the totality of evidence across the primary and the secondary. So, sort of statistical significance, we'd look at the presumably look at the totality of evidence to justify the mechanism of action and

Operator

And our next question comes from the line of Brian Abrahams from RBC Capital Markets. Your question please.

Speaker 8

Hey guys, good afternoon and thanks for taking my question. So in the back half of this year, we're going to see data from several late stage DMD gene therapies. I I guess, I'm curious based on what you're seeing on the ground so far, if you have a sense as to what physicians and patients are going to be looking for as they potentially to choose a gene therapy to take, assuming there's multiple therapies available. And What are your views on the potential approval pads based on interim functional analysis? Is that something that you guys ever explored with the contemplated or explored with the FDA?

Speaker 8

Thanks.

Speaker 2

We are not we have there's one therapy that's approved for Duchenne muscular dystrophy, that's a gene therapy. And to be honest, we think very little about other organizations right now. We have A path in front of us, we have to serve the patients that are available to benefit from our therapy today And we need to broaden that label and that's what we're focused on right now. And of the things that we worry about right now, those are All of the top priorities and worrying about other organizations and their plans is Tertiary or less than tertiary to

Operator

us. Thank you.

Speaker 2

Is to prioritize Children ensure they can get access if at all possible before they age out of the label. And you saw that, poignantly today with a boy who You've accessed today one day before her 6th birthday. But, Dalen, do you have any other thoughts on that?

Speaker 4

Yes. Gina, thank In the short term, we've been focused on those boys that are turning 6 in the next while. As Doug said in the earnings call, we there's an incident population in Duchenne of 400 patients born each year. Now not all of those patients are diagnosed by the age of their 6th birthday. There's actually a pretty good percentage that don't get diagnosed by their 6th birthday, but there is a good number of patients Sitting in the sites that are turning 6 and a big focus in terms of our execution.

Speaker 4

As Doug also said and as we've said before, We are guiding around patient numbers. We're going to focus on net revenue as we've done with the other launches.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Salveen Richter from Goldman Sachs. Your question please.

Speaker 9

Good afternoon. Thanks for taking my question and congrats as well on treating the first patient here. With regard to the 3.5 standard deviation assumption, recognize that that's what you saw, I believe, in Study 103. I guess, is there anything else that you're using to support that assumption? And in the context of heterogeneity and even with stratification, What would be how you're thinking about the impact here if it's higher?

Speaker 9

Thank you.

Speaker 2

Well, actually, One would actually presume potentially the opposite. So the 3.5 standard deviation was the original powering for Embark. That considered the historical trials, but didn't take into consideration the various Tightening of the protocol that occurred with respect to Study 301 or Embark to reduce heterogeneity and make Create more homogeneity. You'll recall we have a very strong ceiling and floor in that trial. You'll recall That we have stratified not only on the basis of NSAA baselines, but also on age, the 4 to 5 and 6 to 7 Your old range will recall that we have restricted all of the patients to rise time under 5 seconds.

Speaker 2

All of that should theoretically at least reduce heterogeneity, create more homogeneity across the population and reduced standard deviation. But the 3.5 points that Luis mentioned was considered before those and didn't take those into consideration. And indeed, when the leadership team did their modeling, they didn't change the standard deviation. So they didn't and Executive Officer. Actually, I'm going to ask for their modeling purposes.

Speaker 2

So we feel very good about where we are right now. And then remind you, we the study was powered off of 120 patients with a presumption of some dropouts. We sit here today, the study was over enrolled. It's now 125 patients and we've had absolutely 0 dropouts And frankly, don't anticipate any dropouts before the last patient last visit, which will occur in mid September. So we feel very good about where we are right now.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Joe Blum from Needham and Company. Your question please.

Speaker 3

Good afternoon, everyone and thanks for taking our question. Maybe a bit of a rephrasing on an earlier question here. Is there a situation in which you think the data from Embark will be Broken out based on age, given potential different feedback from the agency. Thank you.

Speaker 2

No, no, we don't. The study has been powered To see a treatment effect in the studied population, which is 4 to 7, it's very well powered to see that. And we've had conversations with the FDA and FDA leadership, which has confirmed that if we are successful In our trial, they will move rapidly once we've submitted data to them to review that data and to remove the age limitations.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Weier from Mizuho. Your question please.

Speaker 10

Hey guys. Congrats on the dosing the first patients. So my question is just referring to what Doug said in the prepared remarks. You said you're going to expand the label in the first half to The majority of patients, can you kind of elaborate by what you mean by that? Will the older patients and the non ambulatory Patients, will those be included or will that come much later, where I think your goal is to reach 95% of the patients?

Speaker 10

Thanks.

Speaker 2

Yes. Thank you very much for your question. So let's go. There's sort of 2 steps to this. So as we stand here today, we have a label for 45 year old patients.

Speaker 2

When Embark is successful and we have a lot of conviction around Embark and the success of Embark, We will immediately submit that data to the agency before we've even submitted a BLA supplement with the goal of them beginning the review as soon as they receive that data. Assuming that IMbark is successful, we would assume that all age limitations will be removed from the label And that gets us to the majority of patients, both ambulatory, non ambulatory and all age ranges. As we've said, we've had conversations with the agency about removing all of the age ranges. There would be no logical basis to assume that Ambulation status would be a reason to limit access. It's not as if this Progene is aware that a patient is in a wheelchair or not.

Speaker 2

So we feel very confident about that. There is one additional thing we'll do, which is we'll take a cut from our current Non ambulatory study to have additional safety data that supplements the safety data we already have on the older and non ambulatory patients as well. So that's our goal. 1st, early next of regulatory patients as well. So that's our goal first, early next year to have a broad label that covers all patients.

Speaker 2

There are 2 There will still remain 2 limitations in the ability to receive that therapy. One of them is this 5% or so of Mutations that are that cover exon 8 and or 9 that are Contraindicated for those mutations. That will remain for some time. We're going to continue to do work on that and hopefully narrow that, but for the time being that will be in the label. And then the second one is pre existing antibodies.

Speaker 2

About 13.9% based on our seroprevalence study represent patients that have some environmental Exposure to something that looks like an antibody for rh74, those patients cannot currently be Dosed, but as Doctor. Rudin Klapac mentioned in her prepared remarks, we're starting 2 different alternative approaches to clear those antibodies, 1 in the lifidase to cleave them and apheresis is the second alternative to clear antibodies. And if 1 or both of those are successful, That in the near term, we could start presumably empowering physicians to safely and effectively dose even patients that have pre existing That would get us to more than just the majority of patients to potentially as much as 95% of patients. So that's our goal.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Mike Ulz from Morgan Stanley. Your question please.

Speaker 11

Hey guys, thanks for taking the question. Maybe just another one on the Levitus launch. In your prepared remarks, you mentioned greater than 50 sites are trained and activated currently. Just curious if you can give us The total number of sites expected, just trying to get a sense of whether that represents a majority currently or where you're at in that process? Thanks.

Speaker 2

50 sites is a tremendous number of sites. We are I am completely Thrilled with the team's ability. 50 so about 80% of all Duchenne patients are covered by about 50 Centers of Care in the United States. So 50 sites is an enormous number of sites To infuse levidus, our goal is to get to as many as 70 sites over time, and we're Significantly ahead of schedule in our goal to do that. So we're in really great shape from a site perspective and And Dalen and his team deserve an enormous amount of kudos for where we've gotten right now.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Danielle Brill from Raymond James. Your question please.

Speaker 9

Hi, guys. Good afternoon. Thanks for the question. I have a quick follow-up to Salveen's question on the standard deviation. I guess, I'm curious, are you able to see blinded SD data or any other blinded data from Embark that allows you to stress test your powering assumptions?

Speaker 9

Just kind of hoping you can elaborate further on your confidence in the assumptions. Thanks.

Speaker 2

We do not have access to so looking at the blinded data wouldn't be very insightful and we don't have access to the unblinded data. So We feel very comfortable with is that our initial study was powered With the standard deviation that we were seeing in studies that did not have the homogenizing restrictions that Embark has in it. And yet when we did the simulations, when Louise and her team and our stats group did the simulations to test The powering assumptions and the like, they did not actually take into account the homogenizing aspects of the Change in protocol, things like, as I've mentioned before, stratifying on age and making sure that all kids had a rise Time under 5 seconds and having strong floors and ceilings and the like. So we feel very good about the powering of the study and we feel good As we sit here today on the standard deviation, but we haven't had access to unblinded data to test those assumptions.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Ritu Baral from TD Cowen. Your question please.

Speaker 12

Good afternoon, guys. Thanks for taking the question. Just back to the centers for a second. Doug, can you say if the handful of patients that you were referencing In the next couple of weeks, will they be at 5 different centers and

Speaker 1

Of the

Speaker 12

50, and then can you talk a little bit about, are there centers that you expect to move faster than others, maybe given their History with Zolgensma and how comfortable they are. And then if I can squeak another one in, do you know how many Antibody tests have been run and can you release that?

Speaker 2

So I don't know the last I can answer for you. I can answer the first two. All of them are so all of the handful are different sites. So they're broadly across different sites. And then if any sites are faster.

Speaker 2

The good news on these sites, first of all, the amount of passion from the physicians He is really wonderful and everyone's trying to move as fast as possible to get kids Infused and benefit these kids, particularly kids that might otherwise age out. We have really benefited and the team has really benefited from the fact Most of these sites, the majority of these sites have had experience with Zolgensma and know how to infuse gene therapies. So They were well prepared before we went in and got the process of initiating them and getting them site ready. So I would say broadly speaking, there's a lot of enthusiasm to move as fast as reasonably possible to get patients benefiting from olebitis.

Operator

Thank you. One moment for opening

Speaker 3

up the call. Yes.

Speaker 4

And in terms of the antibody testing, It's going smoothly and functioning well, and we are disclosing the numbers right now, But it is working well and going smoothly. And we're happy with the demand.

Operator

Thank you. Our next question comes from the line of Anupam Rama from JPMorgan. Your question please.

Speaker 4

Hey, guys. Thanks so much for taking the question. Just a clarification point, sorry if I missed this. What are the gating factors Starting that FRP-nine thousand and three pivotal study later this year. Thanks so much.

Speaker 2

I'll turn this over to Luis about getting any of it wrong, but I think it's all just CMC and manufacturing, if I'm not mistaken. But Luis, you tell me If I'm missing a nuance.

Speaker 5

No, that's accurate. Still the making sure the release essays are in place and we're set. But we As we mentioned, we fully enrolled Journee and have a great deal of patients lined up and most of them having Natural History Data as well.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Joseph Schwartz from Leerink Partners. Your question please.

Speaker 13

Hi, all. This is Will on for Joe today. Thanks for taking our questions and I'll add my congrats on the progress this quarter. So one for us, Wondering what the opportunity is for SRP-five thousand and fifty one relative to the PMOs that you currently market. Is this a potential franchise And are there any reasons why a patient is not currently on a PMO, but would be a candidate for PPMO?

Speaker 13

Thank you.

Speaker 2

So not on it. So I think broadly speaking, if it was successful, So we'll see the data later this year and then we'll if we're successful with the data later this year and the risk benefit justifies it, we're going to seek an NDA for 5,051 next year. The goal then would be there's a couple of things. The first goal is that it would be A more convenient and potentially much more powerful version of our PMOs. So for patients already on the therapy, It would be a great transition to this therapy for them and benefit them.

Speaker 2

You could envision in the United States that We might have even we've had a great success record with Access. We might have even greater success with Access If we were making 3%, 4%, 5%, which would be multiple folds more dystrophin than of the PMOs. And then it does always offer the theoretical opportunity to move outside of the United States, which Something we're very excited to do, which is bringing our RNA technology more broadly around the world to benefit patients. So there's a lot of potential Opportunity with the PPMOs, if successful. So we're looking forward to looking at the Part B of momentum later this year and then making some decisions across the portfolio and aggressively bringing things forward if we see success with 5,051.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Kristin Klaszka from Cantor Fitzgerald. Your question please.

Speaker 14

Hi, everyone. Congrats on today's milestone. Given that you're taking all these steps now across sites, Payers and antibody testing, is it your expectation that if you end up getting a broader label in the first half of next year That the 3 to 4 month timeline you've communicated to us in terms of patients getting on therapy could be shortened? Thank you.

Speaker 2

Yes. The answer is generally speaking, yes. This really is an initiation issue with The launch of the therapy policies have to be in place. In some places, codes have to be in place and the like. And then of course, we have this current release process.

Speaker 2

So we ought to be in a position to move faster over time. But as I said before, We've had a lot of very fantastic early success, but we should assume that the real ramp begins later this year.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Tim LeGoe from William Blair. Your question please.

Speaker 3

Hi, Tim. This is John on for Thanks so much for taking our question. So I was just wondering beyond the effort that the team is making to get access to patients approaching 6 years of age, Just wondering if you could talk a little about any higher demand you're seeing from the patients approaching that age cutoff and if you're seeing more patient starts from those patients?

Speaker 2

I'll turn this over to, Dalen.

Speaker 4

Yes. Thanks for the question. We're seeing demand broadly in both the 45 Year Old Age Group. In terms of access early on, it is skewing heavily to those patients that are that have the birthdays, Just more so maybe because of the urgency and the dialogue that's happening between KOLs, payers and the teams right now. So early on, yes, we are seeing it skewed towards 6 year the people with birthdays turning 6, But we expect that to normalize very quickly as we start to work towards all of the patients

Speaker 2

that are eligible in that 4 to 5 Age Group. So we're seeing demand in start forms across the ages. We'll likely get access skewing to the older Kids in that age range for the obvious reason that we want to get them dosed before there's an issue with the label. Yes.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Brian Skorney from Baird. Your question please.

Speaker 15

Hey, this is Luke on for Brian. Thanks for taking our question. Regarding the pace of progress getting the ENVISION trial up and running, have you seen any signals that the availability of commercial product Might be a headwind to enrollment in the ambulatory population?

Speaker 2

The answer to that is going to be no. So we were very thoughtful about the protocol for Envision. In fact, we've significantly limited the number of patients that are going to come out of the States to ensure that we don't have an issue with the progress of that therapy as we broaden the label. Now that does mean that the enrollment for Envision will move slower than for instance, Embark, which rapidly enrolled as everyone may recall. But ultimately, we're not seeing an impact from this approval on that basis and part of it's because we're going to get to enroll the Majority of subjects outside of the United States.

Operator

Thank you. One moment for our final question for today. And our final question for today comes from the line of Divjit Chattopadhyay from Guggenheim. Your question please.

Speaker 16

Hey, good afternoon and thanks for taking me getting my question in. What is the current gross margin for Elipatus? And where do you think it will migrate, either on peak capacity or if you could successfully migrate to the 1,000 liter scale.

Speaker 2

Sure. I'll turn this over to Ian.

Speaker 6

Sure. So we've said that we would expect the margins to be like high quality Targeted Agent. So kind of in that 80% range, similar to what we're seeing with our PMOs. Now obviously, It's going to be higher when the earlier patients are being dosed and then as heavier patients and we And the label trend down, but basically into kind of that 80% range. And then obviously, to your good point, we could see A big change.

Speaker 6

We're not in a position to quantify that from where we are from a manufacturing perspective on our suspension process. But obviously, it has To Doug's point, a big impact on our yield, and so we could see Matt driving that number higher, but obviously we're not willing to commit to that just yet.

Operator

Thank you. This does conclude the question and answer session of today's program. I'd like to hand the program back to management for any further remarks.

Speaker 2

Thank you, Jonathan, and thank you everyone for joining us this evening and for your questions. I appreciate it. We've obviously made, from my perspective, great progress So far this year, both with the approval of Alevitus and then serving patients, both with Alevitus and with our existing PMOs, I will remind us The team has done a brilliant job of continuing to serve the community with our PMOs and we feel very confident about our current guidance on the PMOs. We have a lot to do for the rest of the year, both serving these patients, continuing to serve the patients with the PMOs, getting the in park readout about which we have an enormous amount of conviction and then we will share that with you At essentially the same time that we share it with our colleagues at the FDA and our goal of course is to broaden this label as soon as reasonably possible and bring Alebitis to the vast majority of patients living with Duchenne and their families. With that, I look forward to updating everyone over the course of the quarter, and I would ask everyone to have a lovely evening.

Operator

Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.

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Earnings Conference Call
Sarepta Therapeutics Q2 2023
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