Q4 2021 Sarepta Therapeutics Inc Earnings Call

Good afternoon, ladies and gentlemen, and welcome to the <unk> Therapeutics fourth quarter and full year 2021 earnings call. At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time, if anyone should require assistance during the conference. Please press <unk>.

Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics fourth quarter and full year 2021 earnings call.

At this time, all participants are in a listen only mode.

Later, we will conduct a question and answer session and instructions will follow at that time.

And then zero on your Touchtone telephone.

If anyone should require assistance during the conference, please press star then zero on your touchtone telephone. As a reminder, today's program is being recorded.

As a reminder, today's program is being recorded at this time I'll turn the call over to Mary Jenkins Senior manager of Investor Relations. Please go ahead.

At this time, I'll turn the call over to Mary Jenkins,

Thank you ma'am and thank you all for joining today today's call earlier today, we released our financial results for the fourth quarter and full year 2021. The press release is available on our website at <unk> Dot Com and our 10-K with filed with the Securities and Exchange Commission earlier this afternoon.

Senior Manager, Investor Relations.

Joining us on the call today are Doug Ingram in at the time, Alan Murray and Dr. Louise Rodino, Quebec. After our formal remarks, we'll open the call for Q&A I would 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 throughout this 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 the operations and trading prices for <unk> common stock for a detailed description of applicable risks and uncertainties. We encourage you to review the company's most recent annual annual report on Form 10-K 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.

Please go ahead.

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

Thank you Mary good afternoon, everyone and thank you all for joining the <unk> therapeutics fourth quarter and full year 2021 Investor Conference call.

Thank you, Mel, and thank you all for joining today's call.

Earlier today, we released our financial results for the fourth quarter and full year 2021. The press release is available on our website at Sarepta.com and our 10K was filed with the Securities and Exchange Commission earlier this afternoon.

Among the thousands of public and private biotech companies currently existing in the United States and around the world throughout the Citron of select in small group.

<unk> integrated commercial stage biotech enterprise.

With a proven track record of translating brilliant science into approved therapies, and then supporting the patient community and physicians in gaining and maintaining access to those.

<unk> therapy, this operational focus and commitment to patients was on full display throughout 2021.

We have greater than 40 programs in our pipeline of potentially life enhancing therapies focused on rare genetic diseases across multiple platforms, including RNA gene therapy and gene editing.

Joining us on the call today are Doug Ingram, Ian Estepan, Fallon Murray, and Dr. Louise Rodino-Koipak.

But more than that in 2021, we entered a pivotal registrational trials for our lead programs in both our RNA and gene therapy platforms.

Encouraging data from our <unk>.

Mentum part a study we commenced the part B of the study our pivotal trial for SRP 50, 51, our next generation RNA based PMO.

The treatment of Duchenne patients with exon 51 amenable mutations.

Additionally, we commenced dosing embark the pivotal registrational trial for SRP 9001, our micro dystrophin gene therapy to treat Duchenne muscular dystrophy embarked which includes sites both in and outside the United States.

He is currently the only truly global trial dosing a gene therapy.

For the treatment of Duchenne.

And we translate our development activity two approved therapies.

With the approval and launch of a modest 45 in February of 2021, we now have three approved therapies, serving the Duchenne community.

The fourth quarter of 2021, we enjoyed our 'twenty one.

Great quarter of strong quarter over quarter revenue growth fourth quarter total revenues, which consist primarily of our net product revenue plus our collaboration revenue reached 201 5 million and <unk>.

Net product revenue for our three RNA based therapies reached $178 7 million.

A 46% increase over the same quarter the prior year.

For the full year of 2021.

Total revenue reached $701 9 million.

Net product revenue was 612.

$4 million, a 34% increase.

Over the prior year since 2017 first full year launch for exon 51, this year up to his recognized sustained growth with a compounded annual product revenue growth rate.

Of over 40%.

And our growth continues we entered 2022 and a position of financial strength with our total revenue guidance at over $880 million and our net product revenue guidance of over $800 million.

A 30% growth over the prior year. Additionally, we enter 2022 with $2 1 billion.

And cash on our balance sheet and the financial discipline to make the most.

Okay.

And our pipeline continues to perform in the first quarter of this year, we announced statistically significant functional results.

And continued confirmation of our differentiated safety profile.

For SRP nine tier one for part two of study one or two.

With the objected conviction that comes from consistent results and what is the largest body of clinical evidence in duchenne to date we.

We continue to enroll and dose patients in need.

Embark and the momentum studies, while also advancing our deep multi platform pipeline.

Now our strategy has taken us far over the last five years, but it is all only the beginning as we look to the future and through our strategic plan.

If our late stage clinical programs are successful.

We should achieve profitability.

By the end of 2024.

By 2025.

Yearly revenue.

$4 billion.

And if our pipeline is successful.

By the end of the decade.

<unk> product revenue could approach $10 billion generated from our internal programs alone.

We have the strongest team in <unk> history, and I believe at least.

One of the most astute and strategically minded teams.

And all of genetic medicine in biotech and we stand ready to continue executing translating our programs into life enhancing therapies for the patients that we serve.

Also benefiting the investors that have placed their trust in us.

After our formal remarks, we'll open the call for Q&A.

And with that let me turn the call over to our head of R&D and our Chief Scientific Officer, Dr. Louise Rodino quite back who will give us an update on our research and development activities waste.

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.

Thanks, Doug.

The results of the operations and trading prices per Sarepta's 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.

My decision to join or up to four years ago was driven by the strong foundation of the R&D organization.

This unmatched dedication to sign them for patients.

By the time, the R&D group is growing in breadth and depth to become a truly integrated.

<unk> focused on propelling <unk> scientific endeavors and vast pipeline for it.

Today, the R&D organization totaled nearly 300 employees.

And then on a mission to translate the very best Science.

Mary Beth treatments for patients in the shortest time possible.

I am proud to lead such a strong and committed team of cycle.

Together with R&D is achieve great things and this is an especially exciting time for implementation.

We are fostering and leveraging our internal research capabilities capitalizing on our current strength.

To ensure we are positioned for sustained growth into the future.

Sure.

As a fully integrated organization.

We have expertise in the manufacturing of our RNA and gene therapy asset all of our research grade materials to be one tunnel and we have developed and validated the analytics to characterize and really material.

I am, particularly proud of our competency in this area is just the capability unique.

We are creating efficiencies and streamline development of our pipeline candidates.

<unk> manufacturing process.

We've also established internal DLP capability genetic therapies.

One for <unk> and Columbus, Ohio.

As far as the maximum flexibility agility and speed of preclinical studies.

Additionally, in the past two years alone we've created an internal innovation engine driven by your subject matter expertise that has resulted in the advancement of over 50 therapeutic candidate construct the kras gene therapy gene editing and RNA.

And Congress collaboration with our business development and Alliance management function, we are continuing to invest selectively and best in class disease, modifying our pencil supplementing our internal R&D toolbox.

With these approaches our goal is to further enhance our delivery platform that we can reach more patients with our therapy faster.

We are also investing in next generation technology to ensure that we are developing best in class therapy not only for today.

Sure.

We are completely foster home R&D culture of scientific inquiry creativity, and a sustained focus on innovation.

As an example in 2021, we successfully advanced our partnership with Janet.

Encouraging initial in vivo results.

One of the most significant challenges when developing a non viral delivery mechanism is establishing good muscle tropism. The results from this collaboration demonstrating the potential of that polymer quantifiable to deliver therapeutic cargo the muscle tissue. Following systemic administration to allow for targeted non viral a systemic delivery of genetics.

Our partnership with genetic reflects our strategy to leverage a variety of therapeutic modalities to treat rare neuromuscular diseases as.

As a result, we have a large pipeline of programs at various stages underdevelopment internally and externally.

Of which is evaluated the probability of success and unmet need.

Same set of criteria.

Our translation of functions within R&D, including quantitative pharmacology genomics preclinical safety and translational biology.

And the continuum from discovery through clinical development.

These internal capabilities, which are supplemented by external resources ensure tailored monitoring first trial participants from both the safety and efficacy and patient experience perspective.

Our innovative scientific mindset is not only research for research.

Our development organization from prices development.

Regulatory affairs, and Pharmacovigilance takes pride in creative approach rooted in specialized experience with one another.

And.

Yes.

Prime examples being our success to the P&L as well as the initiation of a phase III global trial for SRP 9001, our lead gene therapy program for Duchenne, which include sites and do that.

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.

Now turning to updates on our late stage clinical programs.

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

In January of this year, we announced topline data from a therapy and 001 102 study 102, part two which further amplifies their confidence and if there is potential to alter the trajectory of the business with an emphasis on prudent function quality of life and preventing premature and early death.

Driving this transformative effect as the underlying strength of our contracts combined with our deep understanding of addition, neuromuscular disease and our science to.

Doug?

To remind you that he wanted to was a double blind randomized.

This placebo controlled trial evaluating SRP 9001, micro dystrophin to 41 participant position between the ages of 47.

Thank you, Mary.

So do you want us to FRP.

SRP 901 clinical process material.

Two primary endpoint micro dystrophin expression at 12 weeks and changing anything total score or at 48 weeks compared to placebo.

Data from part one study 102 shared in January of 2021.

We evaluated the 48 week results of 20 patients on therapy against 21 patients were randomized to placebo.

And part two the study remains blinded the participants and investigators.

Good afternoon, everyone, and thank you all for joining Sarepta Therapeutics' fourth quarter and full year 2021 investor conference call.

All participants in the placebo group cross sell with the active treatment.

Among the thousands of public and private biotech companies currently existing in the United States and around the world, Sarepta sits in a select and small group, of fully integrated commercial stage biotech enterprises with a proven track record of translating brilliant science into approved therapies and then supporting the patient community and physicians in gaining and maintaining access to those approved therapies. This operational focus and commitment to patients was on full display throughout 2021.

We have greater than 40 programs in our pipeline of potentially life-enhancing therapies focused on rare genetic diseases across multiple platforms, including RNA, gene therapy, and gene editing.

Zero, one and all participants were followed by another 48 week safety and efficacy were evaluated.

But more than that, in 2021, we entered pivotal registrational trials for our lead programs in both our RNA and gene therapy platforms.

And parts to the goal of the primary analysis.

Look at the 'twenty, one patient placebo crossover cohort.

First is the propensity score weighted external control.

The external control included inclusion and exclusion criteria and rigorously mass baseline characteristics for H NSA, a lifetime and 10 meter walk run.

In this regard we showed that the external controls on nearly perfectly matched against the crossover patient baseline.

As a reminder, this proposal.

Used car method was prospectively defined and shared with the FDA prior to database lock and unwinding of the part two data.

It is important to understand that in the absence of a placebo arm propensity score method scientifically rigorous and widely used to match controls across multiple factors relevant to continental.

It provides as close an approximation of possible of what would be expected to occur in a randomized trial setting with a well balanced placebo control group.

Encouraging data from our Momentum Part A study, we commenced Part B of the study, a pivotal trial for SRP5051, our next generation RNA-based PPMO for the treatment of Duchenne patients with Exon 51 amenable mutations.

The data.

Additionally, we commence dosing MBARC, the pivotal registrational trial for SRB9001, our microdistrophin gene therapy to treat Duchenne muscular dystrophy. MBARC, which includes sites both in and outside the United States, is currently the only truly, global trial dosing a gene therapy for the treatment of Duchenne.

Now here's marijuana treated participants in the placebo crossover Gordon statistically significant two points higher on the mean MSA at 48 weeks compared to the propensity score weighted external control.

Achieving impressive P value of 0.0009.

Mean, NSA scores from new part two participants improved one three points from baseline for the SRP 9001 treated group.

T NSA scores and the external control group with an end of 103 patients declined <unk> seven points from baseline.

It's important to note that these children, where on average seven to four years of age at the time of baseline MSA and over eight years old at the west functional test.

And we translate our development activity to approved therapy.

As a scientist with a passion for change lots of patients I'm thrilled with these yourself.

With the approval and launch of Amandus 45 in February of 2021, we now have three approved, therapies serving the Duchenne community.

They demonstrated consistency with our previous studies study 101, 31, or two part one and study one month free.

Just over 80 patients across the two trials alone.

In the fourth quarter of 2021, we enjoyed our 21st straight quarter of strong quarter-over-quarter, revenue growth. Fourth quarter total revenues, which consist primarily of our net product revenue plus, our collaboration revenue, reached $201.5 million. And net product revenue for our three RNA-based therapies reached $178.7 million, a 46% increase, over the same quarter of the prior year. For the full year 2021, total revenue reached $701.9 million. And net product revenue was $612.4 million, a 34% increase over the prior year.

Based on these results we would expect the treatment benefit to continue to increase over time due to the progressive nature of Duchenne.

Since 2017, first full-year launch for Exondus 51, SREPTA has recognized sustained growth, with a compounded annual product revenue growth rate of over 40%.

Across these studies, we've seen sustained functional equivalents compared to natural history with the longest now a year for a follow up.

The safety for study 102 part two is entirely consistent with the safety results in part one of the study the most common adverse events have been bombing there were no treatment related serious adverse events and no.

Discontinuation due to adverse events.

It continues to generate data from studies 101, one to one O three including two year data from part one maybe one or two in one year data from study one of three.

We plan to perform an integrated analysis of the one year data from studies 101, one or two in one O three for all patients to receive the target dose.

Our plan is to share the totality of these data with regulators and 1% all of these results at a medical meeting thereafter.

In parallel we are actively involved in park, a 120 patient global double blind placebo controlled phase III trial largest study of its kind in duchenne.

Embark is a multicenter clinical trial evaluating commercially representing 39 001 material and patients with Duchenne between the ages of four to seven.

Now continuing with a gene therapy franchise SRP 9003 is our lead <unk> program.

A full length beta circle Gladson CDMA. This is the same AAV <unk> 74 caps at an MHC K seventh familiar is the SRP 9001 program.

Is generating promising expression and functional data from the ongoing SRP 9001 on one.

This study treat LG MTGE with SRP 9003 clinical process material.

We look forward to sharing the impressive body of data we've generated to date at the upcoming MDA clinical and scientific conference.

When we are ready to test commercially representing the SRP nine three material in a clinical trial, we will discuss with <unk>. The design of a registrational study for <unk> in parallel we are enrolling patients in Germany, a global multicenter and longitudinal natural history study of <unk> and <unk>.

C patients.

As a reminder, we've received written feedback from both the FDA and EMA regarding our plans for SRP 9003, confirming the possibility of using posting expressions endpoint for accelerated approval in the U S and for conditional approval in Europe .

Turning now to our RNA based platform in the fourth quarter of 2021, we initiated part D. A momentum a multi arm global ascending dose study of SRP 5051 achieved monthly assessing dystrophin protein levels and skeletal muscle tissue following FRP $50 51 treatment.

SRP 5051 is our next generation PMO treat patients physician, who are amenable to exon 51 skipping.

Studies enrolling between 20 and 40 patients between the ages of 7% to 21 amenable to exon 51, skipping who are naive to FRP 50 51 <unk>.

Additionally, those previously studied 50 51 201 part a study to see 51, one or two who meet the entry criteria are eligible to participate.

Ambulatory and non ambulatory patients are also eligible for participation.

In May of 2021, we announced results from part a of the momentum study showing that after 12 weeks 30 mix per kg FRP $50 51 dose monthly resulted in 18 times the exon skipping eight times of dystrophin production of the type of person.

Weekly for four weeks.

Moving forward, we anticipate part B a momentum to serve as a pivotal study for SRP 5051, and we plan to seek accelerated approval. If the trial is successful.

He is enrolling on pace and as we've guided we anticipate it to be fully enrolled in the second half of 2022.

And our growth continues.

In conclusion I'd like to thank my colleague daily basis dedicate themselves to the advancement of our programs for the betterment of patients around the globe.

Thanks, as well to our partners and science clinical trial investigators and the patient community for their commitment as we work together to propel the science forward.

I will now turn the call over to Allan for an update on our commercial activities down.

We entered 2022 in a position of financial strength, with our total revenue guidance, at over $880 million and our net product revenue guidance of over $800 million, a 30% growth over the prior year. Additionally, we entered 2022 with $2.1 billion in cash on our balance sheet and the financial, discipline to make the most.

Thank you Luis and good afternoon, everyone.

2021 represented an incredible year of execution, whereby our team delivered net product revenue growth of more than 30% and $150 million.

Over that of 2020. This strong growth was driven over the course of the year by exceeding expectations in all three of our approved RNA based PMO therapies.

In 2021 compared to the prior year, we delivered nearly 8% growth of exon 51, and more than 160% growth of <unk> 53 in the face of a competitive market.

Additionally, we recognized.

$68 $5 billion in revenue from a modest 45 after launching within just 24 hours of approval in the first quarter of 2021.

This success was generated by mission driven collaboration across all of our field teams.

Deep commercialization experience gained over nearly six years since the approval of <unk> 51.

Flawless execution in the field is supported by cross functional partners throughout the rest of world intensely dedicated to serving Duchenne community.

And our pipeline continues to perform.

I'll begin by highlighting some of our 2021 achievements.

In the first quarter of this year, we announced statistically significant functional results, and continued confirmation of our differentiated safety profile for SRP 9001 from Part 2 of, Study 102.

The team got off to a strong start setting the stage for the entire year by successfully navigating the reauthorization process starting in January of 'twenty, one and maintaining more than a 90% success rate and re authorizations throughout the year.

With the objective conviction that comes from consistent results in what is the largest, body of clinical evidence in Duchenne to date, we continue to enroll in dose patients in the EMBARQ and the Momentum studies while also advancing our deep multi-platform pipeline.

Now our strategy has taken us far over the last five years, but it is all only the beginning. As we look to the future and to our strategic plan, if our late-stage clinical programs, are successful, we should achieve profitability by the end of 2024.

This robust start coupled with continued high adherence rates served as the foundation for four more quarters of revenue growth for exon 51 in 2021.

And by 2025, our yearly revenue is $4 billion.

<unk> 53, we ended 2021 in a strong position.

And if our pipeline is successful, by the end of this decade, our yearly product revenue, could approach $10 billion.

And market share maintaining our leadership role in the Duchenne space and growing at a robust triple digit rate over 2020.

Further the team continued to demonstrate the operational launch exports with the launch of our third RNA based PMO a modest 45.

As we mentioned in the past the penetration rate of start forms of the exon 45 market was similar to that seen in 2016, and the exon 51 market, where we launched exon 51.

The key difference being a much faster conversion rates exceeding the Exxon, just 51 launch and our own expectations, allowing us to surpass the revenue of 553 with a modest 45 within one calendar year.

I'll take a moment to focus on a modest 45, because its performance relative to bonds 53 requires further explanation.

Literature suggests exon 45, and exon 53 have similar prevalence however, with experience, it's becoming clearer that the a modest 45 population is larger and the buyout of <unk> 53 population. Therefore, a modest 45 appears to be a greater opportunity than we originally thought.

So we anticipate a strengthening growth trajectory of a modest 45 in the coming quarters.

That said, we're very pleased with the performance and continued growth of <unk> 53.

We have the strongest team in Sarepta's history, and I believe at least, one of the most astute, and strategically minded teams in all of genetic medicine and biotech, and we stand ready to continue executing, translating our programs into life-enhancing therapies for the patients that we serve, and also benefiting the investors that have placed their trust in us.

Despite the entrance of a new cover in the U S. Exon 53 market the revenue trajectory of the file on just 53, so minimal impact throughout 2021.

As the exon 53 market reaches full penetration, we expect the growth rate to contribute modestly in coming quarters.

As mentioned in prior quarters, the vast majority of exon 53 treated patients continue to choose to raptor.

It is 53.

Overall, our deep experience with Duchenne has enabled us to serve more patients expedite access to drug and offer best in class support services through selective.

Across all three of our approved therapies, serving nearly 30% of individuals living with Duchenne in the United States.

And with that, let me turn the call over to our Head of R&D and our Chief Scientific Officer,

Dr. Louise Rodino-Kleipac, who will give us an update on our research and development activities.

Turning now to our performance in the fourth quarter of 2021.

Executed in Peru, the RNA based PMO business by a robust 46% over the fourth quarter of 2020.

Louise?

Total net product revenue for the fourth quarter was $178 $7 million.

Bringing the total net product revenue for the year to $612 4 million, reaching the upper end of our 2021 guidance of $605 million to $615 million. As a reminder, the final net product revenue guidance reflects two increases over the course of 2021 and representing.

Thanks, Doug.

My decision to join Sarepta four years ago was driven by the strong foundation of the R&D, organization and Sarepta's unmatched dedication to science and to patients.

Over performance of greater than $70 million over our original guidance.

<unk> outperformance of 2021 was mostly driven by a modest 45, and we believe our 2022 net product revenue guidance of greater than $800 million.

Accurately captures the performance of all three of our approved therapies.

I'll now outline individual net product revenues for the fourth quarter of 2021 for our three approved RNA based PMO therapies.

Beginning with <unk>, 51, which totaled roughly $119 million, representing approximately 11% growth over the fourth quarter of 2020.

553 revenue totaled nearly $25 million, representing roughly 66% growth versus the fourth quarter of 2020.

And a modest 45 revenue totaled nearly $35 million representing greater.

30% sequential growth over the third quarter of 2021.

I'm proud of what we accomplished in 2021, and most importantly, I'm grateful for our team's enduring commitment and unwavering efforts to serve nearly 30% of the Duchenne community, who are amenable to one of our three approved.

RNA based therapies.

Since that time, the R&D group has grown in breadth and depth to become a truly integrated, team focused on propelling Sarepta's scientific endeavors and vast pipeline forward.

Today, the R&D organization totals nearly 300 employees, grounded in a mission to translate, the very best science into the very best treatments for patients in the shortest time possible.

As a fully integrated biotechnology company, we look forward to working in close collaboration with our R&D colleagues as they discover and develop therapies for.

I am proud to lead such a strong and committed team of scientists.

Together, we as R&D have achieved great things, and this is an especially exciting time for our, organization. We are fostering and leveraging our internal research capabilities, capitalizing on our, current strengths, while also ensuring we are positioned to sustain growth into the future.

An even larger proportion of the duchenne population as well as advance our deep portfolio of therapies and gene therapy.

Hey.

Gene editing.

As a fully integrated organization, we have expertise in the manufacturing of our RNA, and gene therapy assets. All of our research-grade materials produced internally, and we have developed and validated, the analytics to characterize and release this material.

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

I am particularly proud of our competency in this area, as it's a capability unique to, Sarepta.

Thanks, Alan good afternoon, everyone.

This afternoon's financial results press release provided details for the fourth quarter and full year 2021 on a non-GAAP basis as well as the GAAP basis. Please refer to the press release available on <unk> website for a full reconciliation of GAAP to non-GAAP financial results.

We are creating efficiencies and streamlining development of our pipeline candidates using, a consistent manufacturing process.

We've also established internal GLP capabilities at our Genetic Therapy Center of Excellence, or GCCoE, in Columbus, Ohio. This affords us maximal flexibility, agility, and speed for preclinical studies.

Additionally, in the past few years alone, we've created an internal innovation engine, driven by our subject matter expertise that has resulted in the advancement of over 50 therapeutic candidate constructs across gene therapy, gene editing, and RNA.

In collaboration with our business development and alliance management functions, we are, continuing to invest selectively in best-in-class disease-modifying approaches, supplementing our internal R&D toolbox. With these approaches, our goal is to further enhance our delivery platform so that we can, reach more patients with our therapies faster.

We are also investing in next-generation technologies to ensure that we are developing best-in-class, therapies not only for today, but for the future, and that we are continually fostering an R&D culture of scientific inquiry, creativity, and sustained focus on innovation.

As an example, in 2021, we successfully advanced our partnership with GenEdit, following encouraging, initial in vivo results. One of the most significant challenges when developing a non-viral delivery mechanism is establishing good muscle tropism. The results from this collaboration demonstrated the potential of genetic polymer nanoparticles to deliver therapeutic cargo to muscle tissue, following systemic administration to allow for targeted, non-viral systemic delivery of genetic medicine.

Our partnership with GenEdit reflects our strategies to leverage a variety of therapeutic modalities to treat rare neuromuscular diseases. As a result, we have a large pipeline of programs at various stages under development, both internally and externally, each of which is evaluated for probability of success and unmet need using the same set of criteria.

Our translational functions within R&D, including quantitative pharmacology, genomics, preclinical safety, and translational biology, span the continuum from discovery through clinical development.

These internal capabilities, which are supplemented by external resources, ensure tailored monitoring for our trial participants, from both a safety, advocacy, and patient experience perspective.

And now to the data.

Beginning in the fourth quarter of 2021 due to recent SEC comment letter issued to a couple of biotech companies upfront and milestone payments associated with the company's license and collaboration agreement settlement and license charges and collaboration revenue along with related transaction costs incurred.

Our innovative scientific mindset is not only reserved for research.

SRP 9001 treated participants in the placebo crossover group scored a statistically significant 2 points higher on the mean MSAA at 48 weeks compared to the propensity score weighted external controls, achieving an impressive p-value of 0.0009. Mean MSAA scores from these Part 2 participants improved 1.3 points from baseline for the SRP 9001 treated group.

Our development organization, comprised of development sciences, regulatory affairs, and pharmacovigilance, takes pride in a creative approach rooted in specialized experience in both genetic medicine and neuromuscular disease.

The MSAA scores in the external control group with an N of 103 patients declined 0.7 points from baseline.

Primary examples being our success with our PMOs, as well as the initiation of our Phase III global trial for SRP9001, our lead gene therapy program for Duchenne, which includes sites in the U.S.

It's important to note that these children were on average 7.24 years of age at the time of baseline MSAA and over 8 years old at the last functional test.

Now, turning to updates on our late-stage clinical programs. In January of this year, we announced top-line data from SRP9001-102, or Study 102 Part 2, which further amplifies our confidence in the therapy's potential to alter the trajectory of the disease with an emphasis on improving function, quality of life, and preventing premature and early death.

As a scientist with a passion to change the lives of patients, I'm thrilled with these results.

Driving this transformative effect is the underlying strength of our construct, combined with our deep understanding of Duchenne neuromuscular disease and our science.

To remind you, Study 102 is a double-blind, one-to-one randomized placebo-controlled trial, evaluating SRP9001 microdystrophin in 41 participants with Duchenne between the ages of 4 to 7.

Study 102 uses SRP9001 clinical process material and has two primary endpoints, microdystrophin expression at 12 weeks and change in NSA total score at 48 weeks compared to placebo.

Data from Part 1 of Study 102 were shared in January of 2021. We evaluated the 48-week results of 20 patients on therapy against 21 patients who were randomized to placebo.

In Part 2, the study remained blind to the participants and investigators.

All participants in the placebo group crossed over to active treatment, SRP9001, and all participants were followed for another 48 weeks while safety and efficacy were evaluated.

In Part 2, the goal of the primary analysis was to look at the 21-patient placebo crossover cohort, versus the propensity score-weighted external control. The external control included inclusion and exclusion criteria, and rigorously matched baseline characteristics for age, NSAA, rise time, and 10-meter walk-run. In this regard, we show that the external controls are nearly perfectly matched against the crossover patient baselines.

As a reminder, the propensity score method was prospectively defined and shared with the FDA prior to database lock and unblinding of the Part 2 data. It's important to understand that in the absence of a placebo arm, the propensity score method is scientifically rigorous and widely used to match controls across multiple factors relevant to prognosis. It provides as close an approximation as possible of what would be expected to occur in a randomized trial setting with a well-balanced placebo control group.

Are no longer excluded for non-GAAP expenses and income.

They demonstrated consistency with our previous studies, Study 101, Study 102 Part 1, and Study 103, having just over 80 patients across these two trials alone.

Although collaboration revenue slightly confounds, our core business operations to conform with these updates.

Based on these results, we would expect the treatment benefit to continue to increase over time due to the progressive nature of Duchenne.

Across these studies, we have seen sustained functional improvements compared to natural history, with the longest now Year 4 follow-up.

The safety for Study 102 Part 2 is entirely consistent with the safety results in Part 1 of the study.

The most common adverse event has been vomiting. There were no treatment-related serious adverse events and no discontinuations due to an adverse event.

We continue to generate data from Studies 101, 102, and 103, including two-year data from Part 1 of Study 102 and one-year data from Study 103.

non-GAAP financial results for the fourth quarter and full year 2020 has been updated to reflect this change for comparable purposes.

For the three months ended December 31, 2021, the company recorded total revenues of $201 5 million, which consist primarily of net product revenue and collaboration revenues compared to total revenues of $145 1 million for the same period of 2020, an increase of $56.

$4 million.

Total net product revenue for the fourth quarter of 2021 from our PMO exon skipping franchise was $178 7 million compared to $122 6 million for the same period of 2020.

The fourth quarter of 2021 individual net product sales were $119 $1 million for exon 50, $134 $7 million for a modest 45 and $24 9 million for <unk> 53.

The increase in net product revenue, primarily reflects higher demand for our products and the launch of a <unk> 45.

And I would like to remind you that Doug mentioned earlier, our 2022 product revenue guidance for our RNA franchise is greater than $800 million.

We plan to perform an integrated analysis of the one-year data from Studies 101, 102, and 103 for all patients who received the target dose. Our plan is to share the totality of these data with regulators and then present all of these results at a medical meeting thereafter.

In the quarter ended December 31, 2021, and 2020, we recognized $22 $7 million and $22 5 million respectively.

In parallel, we are actively enrolling EMBARQ, a 120-patient, global, double-blind, placebo-controlled Phase 3 trial, the largest study of its kind in Duchenne. EMBARQ is a multi-center clinical trial evaluating commercially represented SRP9001 materials in patients with Duchenne between the ages of 4 to 7.

Now, continuing with our gene therapy franchise, SRP9003 is our lead LGMD program in which a full-length beta-cycloglycan cDNA uses the same AAV Rh74 capsid and the MHTK7 promoter as the SRP9001 program. It is generating promising expression and functional data in the ongoing SRP9003-101 study to treat LGMD2E with SRP9003 clinical process material.

We look forward to sharing the impressive body of data we've generated to date at the upcoming MDA Clinical and Scientific Conference.

When we are ready to test commercially representative SRP 9003 material in a clinical trial, we will discuss with OTAP the design of a registrational study for SRP 9003.

In parallel, we are enrolling patients in Journey, our global, multi-center, longitudinal natural history study of LGMD2E, 2D, and 2C patients.

As a reminder, we've received written feedback from both the FDA and EMA regarding our plans for SRP 9003, confirming the possibility of using protein expression as an endpoint for cellular approval in the U.S. and for conditional approval in the U.S.

Turning now to our RNA-based platform, in the fourth quarter of 2021, we initiated Part B of Momentum, a multi-arm, global, ascending-dose study of SRP 5051 infused monthly, assessing dystrophin protein levels in skeletal muscle tissue following SRP 5051 treatment. SRP 5051 is our next-generation PCMO to treat patients with Duchenne who are amenable to exon 51 skipping. The study is enrolling between 20 and 40 patients between the ages of 7 to 21 amenable to exon 51 skipping who are naive to SRP 5051.

Additionally, those previously dosed in Study 5051-201 Part A or Study 5051-102 who meet the entry criteria are eligible to participate. Both ambulatory and nonambulatory patients are also eligible for participation. In May of 2021, we announced results from Part A of the Momentum study, showing that after 12 weeks, 30 mg per kg of SRP 5051 dosed monthly resulted in 18 times the exon skipping and 8 times the dystrophin production of the teplersin, dosed weekly for 24 weeks.

Moving forward, we anticipate Part B of Momentum to serve as a pivotal study for SRP 5051, and we plan to seek accelerated approval if the trial is successful. Part B is enrolling on pace, and as we've guided, we anticipate it to be fully enrolled in the second half of 2022.

<unk> of collaboration and other revenue, which primarily relates to our collaboration arrangement with Roche reimburse co development costs under the Roche agreement totaled $18 6 million for the fourth quarter of 2021 compared to $34 2 million for the same period of 2020.

In conclusion, I'd like to thank my selected colleagues who on a daily basis dedicate themselves to the advancement of our programs for the betterment of patients around the globe.

Thanks as well to our partners in science, clinical trial investigators, and the patient community for their commitment as we work together to propel the science forward.

I will now turn the call over to Dallin for an update on our commercial activities.

On a GAAP basis, we reported a net loss of $122 million and $189 $3 million or $1 42, and $2 40 per basic and diluted share for the fourth quarter of 2021 and 2020, respectively.

We reported a non-GAAP net loss of $66 million or.

<unk> 70, <unk> 77 per basic and diluted share in the fourth quarter of 2021 compared to a non-GAAP net loss of $133 2 million or $1 69 per basic and diluted share in the fourth quarter of 2020.

In the fourth quarter of 2021, we recorded approximately $31 $7 million and cost of sales compared to $22 4 million in the same period of 2020. The increase in cost of sales was primarily due to increasing demand for our products.

On a GAAP basis, we recorded a $197 $3 million and $207 $2 million and R&D expenses for the fourth quarter of 2021, and 2020, respectively. A year over year decrease of $9 $9 million. This decrease is primarily due to decreases in milestone payments made in the fourth.

Quarter 2021 related to our license and collaboration agreement compared to similar activity during the fourth quarter of 2020 as well as a decrease in clinical trial expenses due to the timing of expenses incurred.

On a non-GAAP basis, R&D expenses were $175 5 million for the fourth quarter of 2021 compared to $191 4 million for the same period of 2020, a decrease of $15 $9 million.

Now turning to SG&A on a GAAP basis, we recorded approximately $78 1 million and $86 million for taxes for the fourth quarter of 2021, and 2020, respectively, a decrease of $7 $9 million.

Year over year decrease was driven primarily by a decrease in professional services expenses.

On a non-GAAP basis, the SG&A expenses were $60 1 million for the fourth quarter of 2021 compared to $65 $2 million for the same period of 2020, a decrease of $5 $1 million.

On a GAAP basis, we recorded $16 $1 million and other expenses net for the fourth quarter of 2021 compared to $17 $8 million and other expenses net for the same period of 2020. The decrease primarily reflects the reduction of interest expense incurred on our convertible debt related to the adoption of ASU 2020.

We had approximately $2 $1 billion in cash cash equivalents and investments as of December 31, 2021 based on our current assumptions. We believe our balance sheet provides us runway beyond the readout of study 301 and into 2024 and with that I'll turn the call back over to Doug to start the Q&A Doug.

Dallin?

Thank you, Luis, and good afternoon, everyone.

2021 represented an incredible year of execution, whereby our team delivered net product revenue growth of more than 30% and $150 million over that of 2020. This strong growth was driven over the course of the year by exceeding expectations in all three of our approved RNA-based PMO therapies. In 2021, compared to the prior year, we delivered nearly 8% growth of Exondys 51 and more than 160% growth of Vyondys 53 in the face of a competitive market. Additionally, we recognized $68.5 million in revenue from Amandus 45 after launching within just 24 hours of approval in the first quarter of 2021.

This success was generated by mission-driven collaboration across all of our field teams and their deep commercialization experience gained over nearly six years since the approval of Exondus 51. The flawless execution in the field is supported by cross-functional partners throughout Sarepta who are all intensely dedicated to serving the Duchenne community.

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

I'll begin by highlighting some of our 2021 achievements. The team got off to a strong start setting the stage for the entire year by successfully navigating the reauthorizations process starting in January of 21 and maintaining more than a 90% success rate in reauthorizations throughout the year. This robust start coupled with continued high adherence rates served as the foundation for four more quarters of revenue growth for Exondus 51 in 2021.

For Vyondus 53, we ended 2021 in a strong position in market share, maintaining our leadership role in the Duchenne space and growing at a robust triple-digit rate over 2020. Further, the team continued to demonstrate their operational launch excellence with the launch of our third RNA-based PMO, Amandus 45.

As we mentioned in the past, the penetration rate of start forms in the Exon 45 market was similar to that seen in 2016 in the Exon 51 market when we launched Exondus 51. The key difference being a much faster conversion rate exceeding the Exondus 51 launch and our own expectations, allowing us to surpass the revenue of Vyondus 53 with Amandus 45 within one calendar year.

I'll take a moment to focus on Amandus 45 because its performance relative to Vyondus 53 requires further explanation.

Sure thing. Thank you, ladies and gentlemen, if you have a question at this time. Please press the star and then the number one key on your Touchtone telephone again there'll be star then the number one key on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the husky and as a reminder, please leave it there.

Yourself to one question.

The literature suggests Exon 45 and Exon 53 have similar prevalence.

Your first question comes from the line of Douglas <unk>.

<unk> of Guggenheim. Your line is now open you may ask your question.

However, with experience, it's becoming clear that the Amandus 45 population is larger than the Vyondus 53 population.

Hey, good afternoon, and thank you for taking my question.

The prepared remarks indicated consolidated analysis about patients who've received the correct dose.

The engagement with the regulators.

This includes all 33 patients in study 103.

Will you supplement with a biopsy data from the Inbox study.

And what would be the timing of the engagement and how closely is the Roche aligns with the strategy.

Well first of all everything we do is in.

Therefore, Amandus 45 appears to be a greater opportunity than we originally thought.

Concert whether in consultation with our partner Roche I should say that to begin with I'll make a few comments and then Luis you can provide additional commentary. So obviously a couple of things to know so there we have a we have a number of different analytics.

So we anticipate a strengthening growth trajectory of Amandus 45 in the coming quarters.

That said, we're very pleased with the performance and continued growth of Vyondus 53. Despite the entrance of a newcomer in the U.S. Exon 53 market, the revenue trajectory of Vyondus 53 saw minimal impact throughout 2021.

As the Exon 53 market reaches full penetration, we expect the growth rate to continue modestly in coming quarters.

As mentioned in prior quarters, the vast majority of Exon 53 treated patients continue to choose Sorepta or Clionidus 53.

Overall, our deep experience with Duchenne has enabled us to serve more patients, expedite access to drugs, and offer best-in-class support services through SoreptaSys across all three of our approved therapies, serving nearly 30% of individuals living with Duchenne in the United States.

Turning now to our performance in the fourth quarter of 2021, the team executed and grew the RNA-based PMO business by a robust 46% over the fourth quarter of 2020. Total net product revenue for the fourth quarter was $178.7 million, bringing the total net product revenue for the year to $612.4 million, reaching the upper end of our 2021 guidance of $605 to $615 million.

As a reminder, the final net product revenue guidance reflects two increases over the course of 2021 and represents an overperformance of greater than $70 million over our original guidance.

This outperformance of 2021 was mostly driven by AMANDUS-45, and we believe our 2022 net product revenue guidance of greater than $800 million accurately captures the performance of all three of our approved therapies.

I'll now outline individual net product revenues for the fourth quarter of 2021 for our three approved RNA-based PMO therapies, beginning with Exondys-51, which totaled roughly $119 million, representing approximately 11% growth over the fourth quarter of 2020.

Thanks, Dallin.

As a fully integrated biotechnology company, we look forward to working in close collaboration with our R&D colleagues as they discover and develop therapies for an even larger proportion of the Duchenne population, as well as advance our deep portfolio of therapies in gene therapy, RNA, and gene editing.

Good afternoon, everyone.

And now I'll turn the call over to Ian Estepan for an update on our financials.

This afternoon's financial results press release provided details for the fourth quarter and full year 2021 on a non-GAAP basis as well as a GAAP basis. Please refer to the press release available on SREPTA's website for a full reconciliation of GAAP to non-GAAP financial results.

Ian.

Beginning in the fourth quarter of 2021, due to recent SEC comment letters issued to a couple of biotech companies, upfront and milestone payments associated with the company's license and collaboration agreements, settlement and license charges, and collaboration revenue, along with related transaction costs incurred, are no longer excluded from non-GAAP expenses and income.

Although collaboration revenue slightly confounds our core business operations, to conform with these updates, non-GAAP financial results for the fourth quarter and full year 2020 have been updated to reflect this change for comparable purposes.

And data we want to share that information first with the agency and have some discussions and then we will share that appropriate medical meeting down. The road that includes additional information about the part two of one or two the data from 103 of its integrated analysis that you've made reference to the integrated analysis will be an integrated analysis looking back.

For the three months ended December 31, 2021, the company recorded total revenues of $201.5 million, which consists primarily of net product revenues and collaboration revenues, compared to total revenues of $145.1 million for the same period of 2020, an increase of $56.4 million.

And with that, I'll turn the call back over to Doug to start the Q&A.

For the fourth quarter of 2021, individual net product sales were $119.1 million for Exondus 51, $34.7 million for Amandus 45, and $24.9 million for Vyondus 53.

Doug?

The increase in net product revenue primarily reflects higher demand for our products and the launch of Among Us 45.

And I'd like to remind you, as Doug mentioned earlier, our 2022 product revenue guidance for our R&A franchise is greater than $800 million. When the quarter ended December 31st, 2021 and 2020, we recognized $22.7 million and $22.5 million, respectively, of collaboration and other revenues, which primarily relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $18.6 million for the fourth quarter of 2021, compared to $34.2 million for the same period of 2020.

On a gap basis, we reported a net loss of $122 million and $189.3 million, or $1.42 and $2.40 per basic and diluted share, for the fourth quarter of 2021 and 2020, respectively.

Thank you very much, Ian.

We reported a non-gap net loss of $66 million, or $0.77 per basic and diluted share, in the fourth quarter of 2021, compared to a non-gap net loss of $133.2 million, or $1.69 per basic and diluted share, in the fourth quarter of 2020. In the fourth quarter of 2021, we recorded approximately $31.7 million in cost of sales, compared to $22.4 million in the same period of 2020. The increase in cost of sales is primarily due to increasing demand for our products.

On a gap basis, we recorded $197.3 million and $207.2 million in R&D expenses for the fourth quarter of 2021 and 2020, respectively, a year-over-year decrease of $9.9 million. This decrease is primarily due to decreases in milestone payments made in the fourth quarter of 2021, related to our license and collaboration agreements, compared to similar activity during the fourth quarter of 2020, as well as a decrease in clinical trial expenses due to the timing of expenses incurred.

On a gap basis, we recorded $16.1 million in other expenses, net for the fourth quarter of 2021, compared to $17.8 million in other expenses, net for the same period of 2020. The decrease primarily reflects a reduction of interest expense incurred on our convertible debt related to the adoption of AFU 2020-06.

We had approximately $2.1 billion in cash, cash equivalents, and investments as of December 31, 2021. Based on our current assumptions, we believe our balance sheet provides us runway beyond the readout of Study 301 and into 2024.

That safety and function for those children, who were dosed at the target dose across the various studies that we have and I will remind you that we have a wealth of.

Insightful data all very consistent but just if you just take embark and put it to one side right now which is we're continuing to dose should move.

We already have across all of these studies over 80 children that have been dosed with SRP 9001. So thats. The current plan, we'll package that together, we'll have we'll get we'll provide that to the agency one of the things that you should know is that our regulatory professionals have.

Suggest extraordinary to us that we share that information and have that dialogue with the agency before we discuss it externally said, we'll do just that and then we will of course find an appropriate medical meeting on the timing of those discussions.

As I said before I'm not going to provide a lot of detail around that right now and provide the blow by blow other than to say we're gathering the information now.

Have that submitted to the agency in the not too distant future. We'll have those discussions and then when we get to a place where we have some clarity on those discussions we will provide an update certainly to the investment community and of course as I said following the submission to the agency that information by the medical meeting.

To discuss some of that data about which we're pretty excited the one thing I do want to say because we are talking a lot about discussions with the agency. This year I want to remind everybody that while we are certainly going to have discussions with the FDA about the state of our information and creative.

Creative ways in which we might get therapies to children even sooner.

In our pivotal trial, our base case assumption and the assumption that you should make is that the embarq is our.

Pathway to an approval for SRP nine barrels or one and it's a pretty exciting pathway to remind you we will around the middle of this year, we will have fully dosed SRP. Nine here was you wanted to embark that means we will have a readout.

Around the middle of next year 2023, and we will very shortly thereafter submit our BLA in our base case scenario given all of the information that we have to date, including the consistency of the information we have to date, both expression partially been safety.

We are very very confident and convicted and embark and that's why we're moving as fast as we can to get it.

<unk> fully there, but with that said.

If there is additional detail I have omitted.

I think you covered it really well I think the only thing I would add is that there was one question around the integrated analysis for study 103. So there. We went includes the patients that are four to seven that were consistent with studies.

One I went out to if you recall, we also thats older non ambulatory patients, which we'll certainly look at that data, but it won't be included in that way.

But when you're integrating your analysis.

Now let's open the lines for questions and answers.

Yes.

Thank you next question comes from the line of Brian Abrahams RBC capital markets. Your line is now open you may ask your question.

Guys. Thanks, so much for taking my question Congrats on all the progress I guess just following up to that first question recognizing that embark is the base case.

I'm wondering as you've gathered the data whether there's been any evolution in your level of confidence in the feasibility of a faster path for approval.

The change in FTE leadership in some of the pledges around the accelerated approval path might impact your views there and then where you might stand with respect to come.

Commercial supply.

In terms of supply in the market. If you were to get an accelerated approval versus after the embarq readout. Thanks.

Well I'm going to be a little careful on the first question because it could reveal a lot about data that we don't yet have I'll just broadly say that we have an enormous amount of conviction around our program and our data both safety function and expression.

I think the leadership changes at the FDA.

Certainly we'll have to the best of our belief about negative implication on any any strategy that we might have or any faster pathway and actually might.

Handset I think Dr.

Dr. <unk> is.

It's a very good choice for that head of the FDA and has shown a historically a commitment to the use of what is tremendously valuable pathway to translate science to therapy to stabilize which is the accelerated approval.

Pathway just to remind you that.

That is a tablet at save a lot of lives over the years, both cancer and HIV and as well as in Neurodegenerative diseases.

10 patients so were were.

Excited about about that.

Luis if I missed anything there.

Okay.

One final there was one final thing I think you asked about commercial.

Material again, just to remind you I wanted to be careful because if I had my enthusiasm I may keep sounding like and pivoting off of our base case, our base case assumption is that embark will be the basis for our approval and we're moving like mad to get that fully dose and that will in a very short order have a readout, which will be in the middle of next.

Each year, but in the event that we had a faster pathway to an approval. We will have all of the commercial material that will need to serve the community at that point, we will be ready in the event that we had them faster.

Apologies.

Cut you off.

Got it.

Thank you.

Okay. Thank you we have the next question comes from the line of Andrew <unk> of Jpmorgan. Your line is now open you may ask your question.

Sure thing.

Thank you.

Ladies and gentlemen, if you have a question at this time, please press the star and then the number one key on your touchtone telephone.

Again, that will be star, then the number one key on your touchtone telephone.

Hey, guys. Thanks, so much for taking the question.

If your question has been answered or you wish to remove yourself from the queue, please press the hash key.

And as a reminder, please leave it yourself to one question.

Doug maybe more of a housekeeping question.

This question came up at the conference and in subsequent discussions, but where are you in terms of your contract and your future with Zurich day. Thanks, So much.

Your first question comes from the line of Dejit Chattopadhyay of Guggenheim.

So by way of background for those who may not know I joined <unk> in late June of 2017, and I joined pursuant to a.

Your line is now open.

Five year agreement with that said, let me be clear I have.

You may ask your question.

Hey, good afternoon.

One of the strongest.

I think first and certainly throughout the history, but more than that I think in all of biotech I'd say that referenced in not only my direct reports, but the broader team that is to replicate as extraordinary professionals and I'll ask a lot of them and asking them to be dedicated and passionate and committed.

Thank you for taking my question.

The prepared remarks indicated consolidated analysis of all patients who received the correct dose and then engagement with regulators. So would this include all 33 patients in Study 103?

Will you supplement with biopsy data from the MBARC study?

What would be the timing of the engagement and how closely is Roche aligned with the strategy?

First of all, everything we do is in concert with and in consultation with our partner Roche, I should say that to begin with.

I'll make a few comments and then Luis, you can provide additional commentary.

So our patients into the future a threat and I can't ask more of them then I ask of myself. So the avoidance of doubt as my every intention.

So obviously a couple things to know.

So we have a number of different analytics and data.

We want to share that information first with the agency and have some discussions, and then we will share that in an appropriate medical meeting down the road that includes additional information out of Part 2 of 102, the data from 103, and this integrated analysis that you've made reference to.

The integrated analysis will be an integrated analysis looking both at safety and function for those children, who were dosed at the target dose across the various studies that we have.

Two.

So to wrap up beyond my five year agreement and to continue to drive with my colleagues towards a better life for these patients and frankly quite directly where would I go that would be as exciting and challenging with as much opportunity to do good and do well at the same time as the reps that we've got an enormous pipeline we've got.

And I will remind you that we have a wealth of insightful data, all very consistent.

But if you just take MBARC and put it to one side right now, which is we're continuing to dose, and move with what we already have across all of these studies, over 80 children that have been dosed with SRP 9001.

So that's the current plan.

We'll package that together.

We'll provide that to the agency.

Multi platforms, we're in pivotal trials in our two late stage platforms. We've had extraordinary growth, we're sitting with $2 $1 billion on the balance sheet. So that we can continue to execute if you look into the future.

Just look where we could go right. If all is well we will be profitable by the end of 2024 of our late stage programs are successful and I have to say I for one am very very confident in where we're headed we will approach $4 billion in the next few years by 2025, and if you look out into the future by.

One of the things that you should know is that our regulatory professionals have suggested strongly to us that we share that information, and have that dialogue with the agency before we discuss it externally.

So we'll do just that, and then we will, of course, find an appropriate medical meeting.

The end of this decade, if our pipeline performance, we could be approaching $10 billion. So I'm extremely excited about the future of the company.

Thrilled to be working with the people that I work with.

Few things that are as.

As rewarding while at the same time challenging I was working at this company in serving these patients. So I have every intention.

Continuing to lead this company with my colleagues. So thank you for that question.

Thank you we have the next question comes from the line of Susan If Bank of America. Your line is now open you may ask your question.

Hi, guys. Good afternoon, Thanks for taking my question.

Doug I was hoping to get a little bit more granular on.

Your $10 billion in peak sales by the end of the decade.

Where are the components that go into that.

And how would how would we think about DMD gene therapy is approved the contribution of that versus the contribution of either PMO or P. PMO. Thank you.

So I can go to a ton of detail because we haven't provided a lot of granularity, but to give you a broad strokes on his first no. This lot of times when people create strategic plans. They have essentially yet on identified development programs or the like that might make up their future revenue projections and goals that is not.

Everything that I'm talking about comments from the internal programs that we have today, even as we continue to look for new opportunities as an organization first and foremost.

The success of our plans.

Rely on the success of 9001 of which we are very excited.

If we're successful there as I've said together with our other programs will get you to approaching $4 billion by 2025, and then we have the limb girdles and some other programs coming on behind it.

Our current assumptions and I don't and I think it's a conservative assumption and we're challenging ourselves there is that with the success of 9001 of gene therapy that it would have a significant cannibalizing effect on our existing.

RNA therapy, even though there are already therapy would remain viable and a lot of places and there will be different different places, where it where cannibalization wouldn't occur. So we're assuming.

A significant amount of.

Of cannibalization and we would still get to something around $10 billion by the end of this decade, which still get even with significant cannibalization to about $4 billion by 2025 and again, we're doing a lot of work right now.

To test the thesis that there is a significant amount of cannibalization in the event of that.

<unk> is there a one success because there may be a very real opportunity, we're accommodative benefit of RNA and gene therapy together. So that those are kind of the broad strokes of that.

Our strategic plan for us.

Thank you. Your next question comes from the line of Gena Wang with Barclays. Your line is now open you may ask your question.

Thank you I have one question regarding the MD presentations in two weeks I know you have a sweet presentation, just wondering specifically regarding Dr. German Dallas presentation on this study 102.

I'm wondering when we see two year data from the drug arm with propensity score waiting analysis with external control and also regarding the 50 50 lumpy PMO part a data will we see longer follow up data from that data.

Yes, I'll, let <unk>.

Luis answer some of the detail, but let me let me answer the broad strokes of the first part of it.

So as I've said before we have a significant amount of additional analytics.

Done and being completed after which we're going to collect them altogether and share them with our regulatory agency and then we're going to find a medical need it and have that discussion thereafter, we have been strongly encouraged by our our regulatory professionals to avoid.

Presenting any additional data until we have those discussions with the FDA for host of technical reasons, and we certainly want to have the most successful reading that.

Can win their division when.

When we can have it and the second issue for US is that that have been presented.

The main.

Primary information and material information at JP Morgan, we want to make sure that we put this all together in one medical meeting and we don't look like where we're trying to essentially promote individual pieces of data across.

The year. So the short answer is that Dr. <unk> presentation will be essentially the data that you've seen before.

The additional commentary as you can well imagine in direct inside and then we're going to be in the <unk>.

Short order gather all of our information additional information Edo part two additional interesting analytics around it the two year data of 103 that go with the first cohort of 103 about 20 patients an integrated analysis, we're going to provide that all to the agency in the form of a well thought through briefing book and then we will find the medical need.

And we'll disclose all of that information and have a discussion about where we are.

Sometime this year.

It is reasonably possible to do that.

Yes.

Yes, so just to add on 50, 51%.

There won't be new data from part a little bit.

We previously presented this is obviously a live audience and this would be nice to be able to present that.

And interact with people at MDA around this data as you know we are now enrolling part b of the study, but part a will be.

Similar to what we presented previously.

Thank you. The next question comes from the line of Lithia Yao from Cantor. Your line is now open you may ask your question.

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

I just actually wanted to talk about.

Yes, the base case of drug being approved roughly a year or so.

So.

But if it is not just can you talk a little bit about how you're thinking about kind of like launching into this group of people with gene therapy. Obviously, we know the cadence of your kind of.

Currently as they stand, but I guess, how should we think about kind of the early sets of patients that might be interested in its treatment.

And just how to think about the overall population into onto you guys have been thinking about it.

Okay.

Yes, I mean, a lot of it is going to be subject to discussions with the division, obviously first and foremost whether there is even a.

Faster pathway and that's a very much an open issue as I've said many times.

I really would my primary investment thesis I would say it's personally my investment thesis as everyone knows <unk> been a significant investor in throughout the personally over the years.

Additional stock last.

Last year I bought on the assumption that embark is going to be wildly successful et cetera, et cetera, a very personal level.

But we need to have additional discussions with the agency. First question is is there a pathway that would be even faster than embark second.

Question is what is the size of the patient population inside of that that is going to be subject to discussions with the division is at a subset of patients or is it more than a subset of patients. Those are all discussions that have not occurred yet, but we need to have the one thing I can say to you.

Is that we will be well prepared to launch the therapy under any of those various scenarios.

Neither a subset or a larger one or of course, we will obviously be prepared for our base case assumption. So it will be we'll be prepared in a number of regards.

Commercially.

Dallas and his team are well aware of.

Various possibilities and we'll be prepared to make the most of this therapy and to get it to patients as soon as possible it will be.

Aware, we'll be.

Prepared from a from a supply chain perspective from a manufacturing perspective and from an inventory perspective any event. So it's difficult to say exactly what that launch would look like first because it's only theoretical right now at segment because it would require additional discussions even if we were successful.

Thank you next question comes from the line of Colin Bristow of UBS. Your line is now open you may ask your question.

Hi, This is Tim on for Colin Thank you for taking our questions and congrats on progress. So we have a follow up question on the ongoing or anticipated competitions with FDA.

Could we know when do you expect to be in a position to provide an update on the potential filing for.

Oh, one and also when we think of your estimate of the potential.

Unlike the typical achieving 4 billion by 2025, how should we think coffee you're asking based on what the potential 19 times will not not all one thank you.

Yes, So let me answer the second question first when we talk about our strategic plan and we talk about the revenue potential out of our platform.

We're assuming our base case scenario were assuming that embark which is our pivotal trial well controlled well powered 120 patients.

Placebo controlled blinded study is the pathway to getting this therapy approved versus the United States and then around the world and it is on that basis that all of our plans from our strategic plan perspective have been built.

On the timing of those discussions, as I said before, I'm not going to provide a lot of detail around that right now, and provide the blow-by-blow other than to say we're gathering the information now.

And then the second one to the first question.

We're not going to provide detail on.

Sort of a blow by blow as discussions we obviously still have gathered information create a briefing book submit that have a meeting that meeting maybe one or a few the one thing I will say is we will do it we'll do it as expeditiously as is reasonably possible ensuring that we have the data to have a very successful one.

We'll have that submitted to the agency in the not-too-distant future.

For discussion with the agency and when we are at a point in those discussions where we have sufficient.

We'll have those discussions.

Alrighty that we can provide additional color, we'll do that at that time so I.

That would be generally confident that will occur over the course of this year, but I can't give you more detail on the exact timing of that.

And then when we get to a place where we have some clarity on those discussions, we will provide an update certainly to the investment community.

Thank you we have the next question comes from the line of Matthew Harrison of Morgan Stanley . Your line is now open you may ask your question.

And, of course, as I said, following the submission to the agency of that information, we'll find a medical meeting to discuss some of that data about which we are pretty excited.

Thanks, Good afternoon.

I guess I was just hoping to just clarify one point about.

The set of information that youre going to provide to the FDA and I.

I guess my question is have you asked them specifically on the kind of information you're going to provide to them. In this package or is this sort of solely been designed by you and your regulatory folks thanks very much.

Yes.

It's been designed by US I mean, let's be clear.

<unk> book and the information that we share obviously constructed by US we have provided to them historically some of the statistical analysis plans that we're using so they have they.

They should have in advance a good understanding of the kinds of information that we'll be discussing but it is essentially on us to ensure that we have a robust package that can inform our our discussions with that said I will also.

Enormous kudos to both our development scientists and regulatory professionals, who have a very keen understanding of what might be required to ensure not that will ultimately be successful in finding a pathway faster than embark I don't want to suggest that but again I will say over and over again.

The one thing I do want to say, because we're talking a lot about discussions with the agency this year, I want to remind everybody that while we are certainly going to have discussions with the FDA about the state of our information and creative ways in which we might get therapies to children even sooner than our pivotal trial, our base case assumption and the assumption that you should make is that EMBARQ is our pathway to an approval for SRP 9001.

That I think everybody ought to assume that embark is a pathway and it's an exciting and very coming.

Coming up very quick pathway, but that but that we will have a very good well informed robust discussion based on what I believe to be very scientifically rigorous analytics.

And it's a pretty exciting pathway to remind you.

Thank you we have the next question comes from the line of Ritu <unk> of Cowen. Your line is now open you may ask your question.

We will, around the middle of this year, we will have fully dosed SRP 9001 in EMBARQ.

Good afternoon, everyone. Thanks for taking the question. So 2020 for breakeven implies obviously some revenue from <unk>.

And assuming you are filing on the Embarq data that kind of gives you no time for any potential reimbursement delays, which has been.

Super challenging for gene therapies can you talk about maybe lessons learned from other people's mistakes.

And what's your groundwork youre laying now in advance to get reimbursement out of the gate.

24 breakeven 2025 4 billion revenues.

Yes, I mean, I would say broadly speaking.

Down in teams spend an enormous amount of time.

<unk> the ground work.

For laying the groundwork to ensure that we can launch this as appropriately as possible serving this community no one.

Is it going to be empty modest than me, but I say this on behalf of my commercial and medical Affairs colleagues no. One is as prepared to launch and support of Duchenne muscular dystrophy therapy as to wrap. This is a this is a hole in the team that knows what it's doing and while we are still in a very.

<unk> nascent field of gene therapy.

We do have the benefit of looking over our shoulder at what others have done.

<unk>, what they've done that's been good and mirroring and to the extent that our colleagues in other companies have haven't had the benefit of seeing others that have stumbled to be able to benefit from from that learn and certainly I think novartis has done a really good job with it. So there's learnings there and I think where we've had some.

Time to get ourselves ready and to prepare for that with Alan do you have any other additional thoughts.

No.

Everything that micro microscope on this.

Yes, no absolutely everything.

Doug said and I think our forecast assumptions are based on our experience launching three PMO. So so so that those assumptions incorporate.

Everything we've learned in the Duchenne market in the last several years.

Yes, I mean, one mistake, we could make is to assume that launching a gene therapy is identical to launching one of our RNA therapy, but the good news is valid or if you don't do that.

Thought.

A lot about the ways in which the gene therapy capacity issues centers for excellence and the like and all of the pre work associated with having discussions with Payors long in advance would need to happen and that's happened a bunch I mean, we've had a significant number of interactions with payers.

More much more to come but I will also say I mean look at our look at our track record if one wonders whether we know how to translate.

Therapeutic approvals and meaningful.

Therapies for patients getting them access and keeping them maintained on access and getting great revenue growth demand. This is a brilliant example of that you know a lot of time with company gets an approval and then they launch a couple of months later three months later four months later.

These folks literally launched essentially within it with either 24 or 48 hours and we had our first start form within I think 24 hours.

Our first infusion with him on this.

Within days literally within days, we translated that to being patient impact amazingly fast and I think we have the opportunity to do the same. So I think we have lofty goals, but I think our strategic.

Our plan is realistic.

Thank you we have the next question comes from the line of Brian's Corny of Baird. Your line is now open you may ask your question.

Hey, good afternoon.

That means we'll have a readout around the middle of next year, 2023, and we will very shortly thereafter submit our DLA in our base case scenario.

Afternoon, everyone, maybe departing from a 90 or is there a one for me I was just wondering on the limb girdle programs. I think you said that the rate limiting step here has been CMC. So just wanted to see if we get an update on where you are in terms of building out a cgmp production here and when could we possibly see initiation of a pivotal program.

And given all of the information that we have to date, including the consistency of the information we have to date, both expression, function, and safety, we are very, very confident and convicted in EMBARQ, and that's why we're moving as fast as we can to get EMBARQ fully dosed.

But with that said, at least if there's additional detail that I have omitted.

I think you covered it really well.

I think the only thing I would add is that there was one question around for the integrated analysis for study 103.

So there we would include the patients that are four to seven that were consistent with studies 101 and 102.

If you recall, we also just older non-ambulatory patients, which will certainly look at that data, but it won't be included in the one year integrated analysis.

Thank you.

Thanks.

Yeah, So you're exactly right.

Next question comes from the line of Brian Abrahams of RVC Capital Markets.

The rate limiting step for the commencement of a pivotal trial I mean, it is we still have to have further discussions with the agency to confirm that.

Your line is now open.

<unk> on the development program itself, but the predicate to all of that is the CMC and in relation to the CMC, it's really more than anything else assay work, you've got additional assays that still need to get bell.

They will get built.

It takes time it reminds me a lot of the sort.

Where we were with 9001 of 2019, you'll recall in 2019 I was telling people.

We're building our manufacturing process, but.

But we don't have for them. This is not the case with 90 903, but if we just adopt building assets for the most part but could.

With 90 days or one youll recall I was telling the external world.

Yields aren't yet where we need them to be from a manufacturing process perspective, but we're going to get there.

It's the same answer we do gas as we have additional assay work to do it's an engineering.

And in <unk> process, we don't have any significant inventive steps here, we know exactly how we need to get there. It just takes some time so once we have that CMC.

Completely of the assays can believe that we can have a discussion with the agency and start what we would hope to be the pivotal trial for this.

For two weeks beyond two we I can tell you a couple of additional things, we're working really hard on the other historical Glycomed I'm trying to get them in a place where they could be as close to two we as possible. That's a big effort for US right now and we will also start a pilot program.

For <unk>, which is this growing apathy.

If I'm not mistaken Louise this year, we will start on a pilot program, which could be really really interesting. We're doing a pilot program because there's obviously a little bit different than the other programs, including the circle glide, Kansas a dual vector approach. So it has that get their gold.

That different technical aspects to it and we want to do a pilot program and see it its effect before we move into a.

Pivotal trial, but we've got a lot going on one of the reasons, we raised additional resources last year.

Number one to ensure that we're well funded but also to ensure that we're moving those along.

As well as with the success of 50 50 could be one ensuring that we're moving the.

The other <unk>, along as well and we are.

Thank you next question, we have the line of acre.

Oppenheimer. Your line is now open you may ask your question.

You may ask your question.

Hello. This is Dirk I'll take already dialing in for hard cash think thank you for taking our question I want from us.

I'm going to be a little careful on the first question because it could reveal, you know, a lot about data that we don't yet have.

I'll just broadly say that we have an enormous amount of conviction around our program and our data.

Both safety function and the expression.

I think the leadership changes at the FDA, you know, certainly will have no, to the best of our belief, have no negative implication on any strategy that we might have or any faster pathway and actually might enhance it.

On the limb girdle muscular <unk> muscular dystrophy program also.

I think Dr. Kittles, you know, is a great example of that.

And just to remind you, you know, that that is a pathway that saved a lot of lives over the years, both in cancer and in HIV and as well as in neurodegenerative diseases and Duchenne patients.

So we're we're excited about about that.

Luis, have I missed anything there?

So some key opinion leaders, we have spoken with have emphasized.

No.

The natural history for <unk> is fully defined and that Theres, a strong unmet need with a lack of trials as well as difficulty of conducting trials.

Correct.

Our question is if you could elaborate on those points and ourselves.

On your conviction that interrupted the entire <unk> portfolio. Thank you.

Sure Luis do you want to take this one.

Sure.

I'll emphasize that we are currently doing a natural history study in limb girdle journey and Thats for the cycles like <unk> see tough inform that we do have natural history data in Q2. For example, we have previously shared data where we showed the comparison of our one on one patient for comparison to natural history.

We're certainly for some indications like to turn the opposite.

Actually a wealth of natural history data, where there is.

In absence of data and we're making sure that we are doing studies in its well informed.

It's certainly a newer field than dish in terms of natural history that we are making sure that we're making the best decisions for patients and gathering natural history data, where we need to and being creative in terms of our approach to making every patient.

In our trials and maximizing the amount of information we get from that.

Thank you for that question.

Thank you. The next question comes from the line of Jim <unk> with Needham and company. Your line is now open you may ask your question.

One final, there was one final thing I think you asked about commercial material.

Good afternoon, and thanks for taking our question.

Again, just to remind you, I want to be careful because of my enthusiasm, I may keep sounding like I'm pivoting off of our base case.

Maybe focusing a little on the PPA. Most here. So you guys have never taking a price increase on your PMO franchise.

But considering the potential for an improved clinical benefit was 50 51.

Would there be discussions around this is this is it something you are considering thank you.

Well, we haven't gotten to a point, where we thought about the exact pricing for the <unk>. It certainly if it is successful could be a significant and profound benefit to patients even over our current PMO is.

A number of regards of course.

To remind everybody what we've seen so far.

Born out in our pivotal trial, which is momentum.

Part D. Just to remind you we saw 6% dystrophin, we saw 18 times more exon skipping about eight times more dystrophin minutes, Sean as we saw it in half the time at 20% of the doors, so that the product profile could be significantly different now with that said.

We haven't made those decisions and we will look at that carefully I can give you our current general philosophy, which doesn't speak exactly to what our pricing will be for <unk>, but it should give everyone a sphere.

We are the company.

We're a company that believes in pricing our therapies appropriately to ensure that.

Programs like this can be successful more patients in and wells.

For additional innovation, but once launched we don't believe in trying to meet our goals for instance by unmatched.

Unnecessarily or inappropriate raising price and that's why to your very good point.

We've launched axon is what will this year be six years ago, and we have never taken a single price for Exxon.

And then we got him on the set of my honest approved there was at least in the argument that could be made for pricing at a premium to Exxon maybe in part because they are smaller patient population and we didn't do that we priced them all at parity. So generally speaking.

Our goal is to price our therapy as appropriate at inception, and did not use to use our performance and our.

The patient community and serving the community as the basis for our success.

Not using things like unnecessary or.

Gratuitous price increases.

As a way of satisfying our obligations and so far it's worked.

By the way.

I'll go back and I guess.

Given enormous.

Credit to our commercial and medical Affairs group and everyone that supported them because we've had 21 quarters.

Consistent sequential strong quarter over quarter growth, we've grown 40% CAGR over the last.

Five years, we will do over $800 million in product net product revenue this year.

And so I think the philosophy that we have has worked well for us now, but the exact price where the <unk> will be something that will mobile side will get closer, but one should assume it'll be we'll take we're not going to take advantage of.

The benefits of the <unk>.

We will make sure that we price it appropriately to serve the community.

Testify future innovation.

Thank you next question comes from the line of Joseph Slides SBB Securities. Your line is now open you may ask your question.

Alright, thanks, very much could you provide us with any phase III enrollment statistics for 9001, such as the proportion of sites that have been activated or patients that have been enrolled and dosed. So far and maybe also describe the impact that your new inclusion and exclusion criteria has had.

Ted on enrollment.

What percentage of patients.

Due to C screening out on this criteria.

Our base case assumption is that Embark will be the basis for our approval and we're moving, you know, like mad to get that fully dosed.

Yes, so I'll give you the broad strokes, we can give any of that we can that I've missed.

And broadest of strokes, we're not giving details on numbers of sites activated get our patients dose other than to say we are dosing patients I think someone asked me recently.

And that will, in a very short order, have a readout, which will be in the middle of next year.

But in the event that we had a faster pathway to an approval, we will have all of the commercial material that we'll need to serve the community at that point. We will be ready in the event that we had a faster approval.

Dosing patients in the U S. Yet that has been I think for a lot of people a significant challenge in the short answer is yes designations in the U S. We are on track to complete the dosing of our study.

Apologies, Luis.

I think I might have cut you off.

In the middle of 2022 which is our goal. So that's great. We've got more sites to initiate and we're working working.

Thank you.

Well to do that.

The United States and even some additional sites in the United States. So we got more work to do but the team is executing well.

And we are on track to hit our goals on the inclusion exclusion criteria as Luis can give some of the data on what you think.

The.

Percentage of patients that might be excluded from that might be but broadly speaking, there's such an extraordinary need and demand for this therapy.

Families and the investigators are well aware of this that I don't believe that is going to be an impediment to the robust enrollment numbers.

Study Luis.

Yeah, that's correct, we have not seen a significant.

Fluence of state revise inclusion exclusion criteria for 301 importance on our earlier studies.

The demand is high and recruitment is on track.

Thank you. He has the next question comes from the line of Judah Frommer of Credit Suisse. Your line is now open you May ask your question Hi, Thanks for taking my question and just to follow up on the last one just kind of given the continued clinical holds placed on AAV gene therapies any impact positive or negative you can sense and enrolling.

Okay, thank you.

We have the next question comes from the line of Ana Panorama of JP Morgan.

On the sites.

Is it and see maybe from investigators or patients obviously.

Kind of a kind of different AAV here, and then tied to that somewhat within the long term guidance can you make any comments on comp.

Competition for your gene therapy.

Yes.

So I will say a couple on the last one let me say that.

Our long term strategic plan.

Base case assumes robust competition, whether or not that's accurate or not is something we'll all find out over time, but we're trying to be thoughtful and conservative in our strategic plan approach, though we actually assumed.

Our plan and our revenue assumptions.

<unk> robust competition for our therapies, even including our gene therapy.

So that's built in.

On the first part of the question.

Don't believe the Luis you can correct me that there has been any significant impact from the issues that have occurred with.

With our colleagues.

Their companies, both Pfizer and solid with respect to Aes <unk> and the like in the most recent very difficult.

Situation that occurred with Pfizer.

That investigators are fairly well informed the SRP 9001 is substantially different than those others. It has performed differently than most others from a safety perspective, and I think patients are generally.

Pretty sophisticated in this space and generally are aware of that but Luis you might have more color on this.

I agree with everything you said the physicians.

Our ear as long as the patients for 301. They ask good questions I think one thing that we're seeing is that the.

The pis are becoming increasingly sophisticated and ask the right questions, which is good to see is we're tracking along in development as well as IR. These they're asking the right questions and I think we're in a good space in terms of education of the community.

That's a great question to ask convenient forms talent.

All positive from my perspective.

Your line is now open.

Thank you. The next question comes from the line of Sylvan Richter of Goldman Sachs. Your line is now open you may ask your question.

You may ask your question.

Hi, Thanks for taking the question. This is Tommy on for solving our question is on the Genentech collaboration team is non viral delivery has had some setbacks in the past what is giving you confidence that their platform could be successful. Thank you.

Hey, guys.

Luis you might wanted to take this one.

Yeah. Thank you for that question I think as I mentioned with non viral delivery one of the challenges is beginning to muscle in the first place is the non file.

Very mechanisms have been very efficient in client places they deliver as you would expect and so one of the hurdles to get over that sort of consistently and deliver it to muscle and so on we delivered.

<unk> expression in muscle here, we're thrilled with that.

The progress on that now we have a ways to go it's early but we're this is the first time, we really saw.

Measurable expression somewhere we're excited about where that kick up again its early research but.

Got it.

Thank you I have one finally.

So it's a very good question. One thing you should know is that we're taking a number of different approaches simultaneously because to your point it's.

It's very this is a very challenging concept.

<unk>.

Yes.

AAV has been successful there are lots of interesting opportunities if one could either enhance AAV something were working on or find an alternative to AAV, but its challenging. So this gen. Ed. It's exciting there are other approaches we're taking as well and the hope that we can advance the science of genetic medicine.

Okay. Thank you the next question.

Sorry go on.

No no go ahead.

Thanks so much for taking the question.

Sorry about that thank you. So on for the next question we have from the line of <unk> <unk>. Your line is now open you may ask your question.

Doug, maybe more of a housekeeping question.

Hi, Thanks very much for taking my question. So my question is a follow up one on ppm platform and was a better clinical profile how possible would you think.

Platform can potentially expand the patient population convincing those patients who are not committed to receiving exon skipping therapies to get on treatment and given that you said the exon exon 51, and maybe even by almost 53 sales are nearing plateauing. So.

I know that you are very confident in the gene therapy program.

You do decide to work on additional candidates how fast do you think you can move to the next one into the clinic.

We're moving from a preclinical perspective, we're moving as fast as we can obviously everything takes more time than one would like when youre dealing with it.

Often ferocious neuro degenerative diseases like Duchenne muscular dystrophy, but we're moving fast.

As far as the potential opportunity for the PPA I think it's enormous enormous in many ways first remember with our first three therapies, we treat about 29% of the Duchenne muscular dystrophy Duchenne community.

We can both with our PMO or P. Bmo's treat easily 50% of the patients because theoretically up to over 80%.

Challenges when you get to the really rare exxon's, but we can treat a significant number of patients and we can make a bet on the PMO platform that gets us to a significantly greater percentage of patients than just 29% beyond just that.

There.

Our ex U S.

On a named patient basis, a managed access program very much a responsive program.

And while patients do benefit from our therapies outside of the United States.

Vast majority of all of our sales will happen inside of the United States with our <unk> and that relationship.

I figure out ways to start with some of the history with the PMO as the way they were approved.

And alike, I think with the.

The PMO and certainly with a therapy that if successful could make.

10% or so over the course of the year.

Truncated, but functional district, English literature would say would be a profound.

Change in trajectory of disease, potentially I think the ex U S opportunity.

It's far more viable and that would really expand the potential for this therapy to treat patients around the world and then therefore as a result of that benefit.

Really greatly enhance the long term revenue associated with TJ Maxx, So theres a lot of one of the exciting opportunities in the <unk> and we're moving as fast as we can with respect to that.

Okay.

Thank you we have the next question comes from the line of <unk> of Baird. Your line is now open you may ask your question.

Great. Thanks, very much good afternoon.

I wanted to ask about your your 2025 revenue aspiration of $4 billion. I think you just look at the consensus right now to point to $2 3 billion. What do you think the screening missing here.

Inc.

Delta can be accounted for.

I'm not 100% sure where they are deriving.

There are number I can tell you, where we're deriving our number where.

And understanding of the prevalent population that is.

That's much better than certainly the literature.

And it's a very thoughtful bottoms up approach to building our revenue guidance.

You might be assuming a complete cannibalization of the RNA franchise with the launch behind you or is there a one that would be I don't think it inaccurate assumption so.

Can't say with precision I suspect frankly that we've just done.

Significantly more modeling than one would expect from from folks. This is all we do is.

These genetic medicines.

Yeah.

It's also partially being driven by probability of success.

Okay.

Thank you the last question.

They may just be discounting or if that's a good good question good point.

Sorry that yet so we have the last question comes from the line of does it catch up I'd ask Dugan hanging Ma'am. Your line is now open you may ask your question.

Hey, Thanks for letting me back in again.

So any progress with EMA.

With respect to SRP 5051 on the threshold of.

Dystrophin expression for potential MMA submission also are you expecting top line by the end of this year.

Alicia I'll take those questions.

Yes.

So it's certainly something that with 50 50 Rand terms at the levels that we expect that we will have discussions with regulators.

Oh yeah.

In the United States and with EMA.

This study will be.

Enrolled this year.

We will look towards.

Just tariff in expression at 20 weeks thereafter, and well provide guidance simply as we track towards that.

Yeah.

We'll say that.

Having been <unk>.

Personally involved in and involved in the discussions with CAH M. P. In EMA and I do think we would have a different I suspect anyway, I should say it will all be subject to discussion I think we would have a different dialogue with the division with the EMA and then ultimately <unk>.

P.

With the therapy that was making 6% to 10% district.

I think the probability of success would be much higher for them.

An approval or conditional approval.

Thank you I am showing no further question at this time I would now like to turn the conference back to President and CEO , Doug Ingram Sir.

This question came up at the conference and in subsequent discussions.

Thank you very very much so I'll be brief yesterday was global rare disease day. It is a time when we reflect on those around the world who are living with a rare disease very often a rare genetic disease.

But where are you in terms of your contract and your future with Sarepta?

The external world.

And are often seen chaotic and uncertain.

Particularly these days and that can be particularly distracting, but reflecting on rare disease days and in our mission to bring a better life to our patients and their families that live with Baird degenerative disease. It reminds us that we don't have the luxury of getting distracted. Unfortunately, we don't have to be distracted.

We have the team we have the science, we have the programs where the revenue we have.

Balance sheet.

We have talent to stay focused and to execute our plans with.

With the benefit of our patients and thus to the reward those of our investors who place their trust in our resources with US we will.

Thanks so much.

So just by way of background for those of you who don't know, I joined Sarepta in late, June of 2017 and I joined pursuant to a five-year agreement.

To execute in 2022, and I look forward to additional updates with you across this year.

With that said, let me be clear.

I have one of the strongest teams, I think, first and certainly in Sarepta history, but, more than that, I think in all of biotech. I say that referencing not only my direct reports, but the broader team that is Sarepta, extraordinary professionals, and I ask a lot of them. I'm asking them to be dedicated and passionate and committed to our patients and to the future, of Sarepta, and I can't ask more of them than I ask of myself.

So the avoidance of doubt is my every intention to stay at Sarepta beyond my five-year agreement, and to continue to drive with my colleagues towards a better life for these patients.

And frankly, quite directly, where would I go that would be as exciting and challenging, with as much opportunity to do good and to do well at the same time as Sarepta?

We've got an enormous pipeline.

We've got multi-platforms.

We're in pivotal trials in our two late-stage platforms.

With that have a good evening and thank you for joining us today.

We've had extraordinary growth. We're sitting with $2.1 billion on the balance sheet so that we can continue to execute.

If you look into the future, just look where we could go, right?

If all is well, we'll be profitable by the end of 2024.

If our late-stage programs are successful, and I have to say, I for one am very, very, confident in where we're headed, we will approach $4 billion in the next few years by 2025. And if you look out into the future, by the end of this decade, if our pipeline performs, we could be approaching $10 billion. So I'm extremely excited about the future of the company.

So thank you for that question.

Thank you ladies and gentlemen that concludes today's conference call. Thank you all for participating you may now disconnect.

I'm thrilled to be working with the people that I work with.

Thank you.

There are a few things that are as rewarding, while at the same time challenging, as working, at this company and serving these patients.

We have the next question.

So I have every intention of continuing to lead this company with my colleagues.

It comes from the line of the Zin Ahmed of Bank of America.

Your line is now open.

You may ask your question.

Hi, guys.

Good afternoon.

Thanks for taking my question.

[music].

[music].

Doug, I was hoping to get a little bit more granular on, you know, your $10 billion in, peak sales by the end of the decade.

What are the components that go into that?

And how would we think about if C&D gene therapy is approved, the contribution of that versus, the contribution of either PMO or PPMO?

Thank you.

Doug, I can't go into a ton of detail because we haven't provided a lot of granularity, but I'll give you the broad strokes on this.

First, know this. A lot of times when people create strategic plans, they have essentially yet unidentified, development programs or the like that might make up their future revenue projections and goals.

That is not us.

Everything that I'm talking about comes from the internal programs that we have today, even as we continue to look for new opportunities as an organization.

First and foremost, the success of our plans rely on the success of 9001, of which we are, very excited.

And if we're successful there, as I've said, together with our other programs, we'll get, to, you know, approaching $4 billion by 2025.

And then we have the Lindberghs and some other programs coming on behind it.

Our current assumptions, and I think it's a conservative assumption and we're challenging, ourselves there, is that with the success of 9001 gene therapy, that it would have a significant cannibalizing effect on our existing RNA therapy, even though our RNA therapy would remain viable in a lot of places and there will be different places where cannibalization wouldn't occur.

So we're assuming a significant amount of cannibalization and we would still get to, something around $10 billion by the end of this decade. We'd still get, even with significant cannibalization, to about $4 billion by 2025.

And again, we're doing a lot of work right now, to test the thesis that there is a significant amount of cannibalization in the event of 9001 success because there may be a very real opportunity for a combinative benefit of RNA, and gene therapy together.

We have been strongly encouraged by our regulatory professionals to avoid presenting any additional data until we have those discussions with the FDA for a host of technical reasons.

So that those are kind of the broad strokes of the strategic plan for us.

And we certainly want to have the most successful meeting that we can within the vision when we can have it.

Thank you.

The second issue for us is that having presented the main primary information and material information at JPMorgan, we want to make sure that we put this all together in one medical meeting and we don't look like we're trying to essentially promote individual pieces of data across the year.

Next question comes from the line of Gena Wang of Barclays.

So the short answer is that Dr. Mendel's presentation will be essentially the data that you've seen before.

Your line is now open.

You may ask your question.

He has additional, commentary, as you can well imagine, and direct insight.

Thank you.

I have one question regarding the MD presentations in two weeks.

I know you have three presentations.

Just wondering specifically, you know, regarding Dr. Gerald Mandel's presentation on the study 102, wondering will we see two-year data from the drug arm with propensity score weighting analysis with external control?

And also regarding the 50-51 PPMO Part A data, will we see longer follow-up data, from that data outset?

And then we're going to, in short order, gather all of our information, additional information out of Part 2, additional interesting analytics around it, the two-year data, 103, the first cohort of 103, about 20 patients, and integrated analysis.

Yeah, I'll let Louise answer some of the detail, but let me answer the broad strokes in the first part of it.

We're going to provide that all to the agency in the form of a well thought through briefing book and then we'll find a medical meeting and we'll disclose all of that information and have a discussion about where we are sometime this year, as soon as it's reasonably possible to do that.

So as I've said before, we have a significant amount of additional analytics done and being completed after which we're going to collect them all together and share them with our regulatory agency.

Louise?

And then we're going to find a medical need and have that discussion thereafter.

Yeah, so just to add on 50-51, this is, there won't be new data from Part A.

It'll be what we've previously presented where this is obviously a live audience and this, would be nice to be able to present this and interact with people at MDA around this data.

As you know, we're now enrolling Part B of the study, but Part A readout will be, similar to what we've presented previously.

I just actually wanted to talk about, I know, you know, obviously, you have the base case of the drug being approved, you know, roughly in a year or so, but if it's not, can you talk a little bit about how you're thinking about kind of, like, launching into this group of people with gene therapy?

Thank you.

The next question comes from the line of Alicia Young

from Canter.

Your line is now open.

You may ask your question.

Obviously, we know the cadence of your kind of launches currently, as they stand, but I guess, you know, how should we think about, you know, kind of early sets of patients that might be interested in this treatment, and, and, and just how to think about the overall population in general?

Hey guys, thanks for taking my question, and congrats on all the progress.

I'm sure you guys have been thinking about it.

Yeah, I mean, a lot of it's going to be subject to discussions with the division, obviously, first and foremost, you know, whether there is even a, faster pathway, and that's a very much an open issue.

As I've said, you know, many times, I really would.

My, my primary investment thesis, and I will say it's personally my investment thesis, as everyone knows,

I've been a significant investor in Sarepta personally over the years.

I bought additional stock.

Last year, I bought on the assumption that Embarq's going to be wildly successful, etc., etc., at a very personal level.

But we need to have additional discussions with the agency.

First question is, is there a pathway that would be even faster than Embarq?

Second, question is, what is the size of the patient population inside of that?

The one thing I can say is that we will be well prepared to launch the therapy under any of those various scenarios, either a subset or a larger one, or of course, we'll be obviously be prepared for our base case assumption. So we'll be, we'll be prepared in a number of regards.

That is going to be subject to discussions with the division.

We'll be prepared commercially.

Is it a subset of patients?

Is it more than a subset of patients?

Those are all discussions that have not occurred yet, but we need to have them.

Dallin and his team are, you know, well aware of the various possibilities and will be prepared to make the most of this therapy and to get it to patients as soon as possible.

And we'll be, aware, we'll be prepared from a supply chain perspective, from a manufacturing perspective, and from an inventory perspective in the event.

So it's difficult to say exactly what that launch would look like.

First, because it's only theoretical right now.

And second, because it would require additional discussions, even if we were successful.

Thank you.

Hi, this is Ting on for Colleen.

Next question comes from the line of Colleen Bristow of UBS.

Thank you for taking our question and congrats on progress.

Your line is now open.

So we have a follow up question on the ongoing or anticipated conversations with FDA.

You may ask your question.

Can we know when do you expect to be in a position to provide an update on their potential filing for 901?

And also, when we think of your estimates of the potential, like your long term goal of achieving 4 billion by 2025, how should we think of your estimates of the potential launching time for 901?

Thank you.

When we talk about our strategic plan and we talk about the revenue potential out of our platform, we're assuming our base case scenario. We're assuming that EMBARQ, which is our pivotal trial, well controlled, well powered, 120 patient, placebo controlled, blinded study, is the pathway to getting this therapy approved first in the United States and then around the world. And it is on that basis that all of our plans from our strategic plan perspective have been built.

Yeah, so let me answer the second question first.

And in effect, going to the first question, you know, we're not going to provide detail on the sort of the blow by blows and discussions.

We obviously still have to gather information, create a briefing book, submit that, have a meeting. That meeting may be one or a few.

The one thing I will say is, you know, we'll do it as expeditiously as reasonably possible, ensuring that we have the data to have a very successful and thoughtful discussion with the agency.

And when we are at a point in those discussions where we have sufficient clarity that we can provide additional color, we'll do that at that time.

So I would be generally confident it will occur over the course of this year, but I can't give you more detail on the exact time.

Your line is now open.

Thank you.

You may ask your question.

We have the next question.

Thanks.

It comes from the line of Matthew Harrison of Morgan Stanley.

Good afternoon.

I guess I was just hoping to just clarify one point about the set of information that you're going to provide to the FDA.

I guess my question is, have you asked them specifically on the kind of information you're going to provide to them in this package, or has this solely been designed by you and your regulatory folks?

Thanks very much.

They should have in advance a good understanding of the kind of information that we'll be discussing, but it is essentially on us to ensure that we have a robust package that can inform our discussions.

With that said, I will also give enormous kudos to both our development folks and scientists and regulatory professionals who have a very keen understanding of what might be required to ensure – not that we'll ultimately be successful in finding a pathway faster than EMBARQ.

Good afternoon, everyone.

I don't want to suggest that.

Thanks for taking the question.

Again, I will say over and over again that I think everybody ought to assume that EMBARQ is our pathway, and it's an exciting and coming up very quick pathway, but that we will have a very good, well-informed, robust discussion based on what I believe to be very scientifically rigorous analytics.

So, Deb, 2024 breakeven implies obviously some revenue from 9001, and assuming you're filing on the EMBARQ data, that kind of gives you no time for any potential reimbursement delays, which has been super challenging for gene therapies.

Thank you.

Can you talk about maybe lessons learned from other people's mistakes and what sort of groundwork you're laying now in advance to get reimbursement out of the gates to meet 2024 breakeven, 2025, 4 billion revenues?

We have the next question.

Yeah, I mean, I would say broadly speaking, Dallin and team spend an enormous amount of time laying the groundwork for, you know, laying the groundwork to ensure that we can launch this as appropriately as possible, serving this community.

It comes from the line of Ritu Baram of Cowen.

No one, this is going to be immodest of me, but I say this on behalf of my commercial medical affairs colleagues, no one is as prepared to launch and support a Duchenne muster dystrophy therapy as Sarepta. This is a honed team that knows what it's doing.

Your line is now open.

You may ask your question.

And, you know, while we are still in a very nascent field of gene therapy, you know, we do have the benefit of looking over our shoulder at what others have done, seeing what they've done that's been good and mirroring it.

And to the extent that our colleagues and other companies have, haven't had the benefit of seeing others and have stumbled to be able to benefit from that and to learn.

And certainly I think, you know, Martis has done a really good job.

There's learnings in it there.

And I think we've had some time to get ourselves ready and to prepare for that.

But Dallin, do you have any other additional thoughts?

Douglas Biren Amin, Uy Ear, Salveen Richter, Gil Blum, Gena Wang, Anupam Rama, Kristen Kluska, Ian Estepan, Douglas Biren Amin, Tim Lugo, Ritu Baral, Brian Estepan, Dallan Murray, Gena Wang, Hartaj Singh, Andreas Argyrides, Francesca Nolan, Sarepta Therapeutics Inc, Douglas Biren Amin, Uy Ear, Salveen Richter, Gil Blum, Gena Wang, Hartaj Singh, Andreas Argyrides, Francesca Nolan, Sarepta Therapeutics Inc, Hey, good afternoon, everyone.

Departing from 9001 for a minute, I was just wondering on the limb-girdle programs.

I think you said that the rate-limiting step here has been CMC.

So, I just wanted to see if we could get an update on where you are in terms of building out a CGMP production here, and when could we possibly see initiation of a pivotal program?

Thanks.

Yeah, so you're exactly right.

The rate-limiting step or the commencement of a pivotal trial, I mean, we still have to have further discussions with the agency to confirm and agree on the development program itself. But the predicate to all of that is the CMC.

And in relation to the CMC, it's really more than anything else assay work.

We've got additional assays that still need to get built.

They will get built. It just takes time.

It reminds me a lot of sort of where we were with 9001 in 2019.

You'll recall in 2019, I was telling people, you know, we're building our manufacturing process.

But we don't have the – for them, this is not the case with 9003.

But 9003 is just about building assays for the most part.

But with 9001, you'll recall I was telling the external world, you know, the yields aren't yet where we need them to be from a manufacturing process perspective. But we're going to get there.

It's the same answer with these assays.

We have additional assay work to do.

It's an engineering and empirical process.

We don't have any significant inventive steps here.

We know exactly how we need to get there. It just takes some time.

So once we have that CMC complete and we have the assays complete, then we can have a discussion with the agency and start what we would hope to be the pivotal trial for this, for TUI.

Beyond TUI, I can tell you a couple of additional things.

We're working really hard on the other sarcoglycans, and trying to get them in a place where they could be as close to TUI as possible. That's a big effort for us right now.

And we'll also start a pilot program for TUI-B, which is this spironopathy, if I'm not mistaken, this year, we'll start our pilot program, which could be really, really interesting.

We're doing a pilot program, because the spironopathy is a little bit different than the other programs, including the sarcoglycans.

It's a dual-vector approach, so it has that different technical aspect to it, and we wanna do a pilot program and see its effect before we move into a pivotal trial.

But we've got a lot going on.

One of the reasons we raised additional resources last year, was, number one, to ensure that we were well-funded, but also to ensure that we were moving the blimp girdles along, as well as, with the success of 5051, ensuring that we're moving the other PPMOs along as well.

And we are.

Thank you.

Next question, we have the line of Eka Didowry of Oppenheimer.

Your line is now open.

Hello, this is Eka Didowry dialing in for Hartage Bank.

You may ask your question.

Thank you for taking our question.

One from us on the limb girdle muscular dystrophy program, also, so some key opinion leaders we have spoken with have emphasized that the natural history for LGMD is fully defined, and that there's a strong unmet need with the lack of trials, as well as difficulty of conducting trials in this ultra-rare disease.

Our question is, if you could elaborate on this point, and also, on your conviction, it has interrupted the entire LGMD portfolio.

Thank you.

You know, I'll emphasize that we are currently doing, a natural history study in limb girdle called Journey, and that's for the sarcoglycans 2E, 2D, and 2C, to help inform that.

Sure, Louise, do you wanna take this one?

Sure.

We do have natural history data in 2E, for example. We've previously shared data, where we've shown the comparison of our one-on-one patients in comparison to natural history.

We're certainly, for some indications, like the thrombinopathy, there is actually a wealth of natural history data.

So, where there is an absence of data, we're making sure that we are doing studies, and it's well-informed.

It's certainly a newer field than Duchenne, in terms of natural history, but we are making sure that we're making the best decisions for patients and gathering natural history data where we need to, and then being creative in terms of our approach to making every patient count in our trials and maximizing the amount of information we get from that.

Thank you for that question.

We've grown 40% CAGR over the last five years. We'll do over $800 million in net product revenue this year.

Thank you.

And so I think the philosophy that we have has worked well for us.

We have the next question

Now, what the exact price for the PPMO will be is something that we'll decide when we get closer, but one shouldn't assume it'll be.

comes from the line of Jill Blom of Needham & Company.

We're not going to take advantage of the benefits of the PPMO.

Your line is now open.

We'll make sure that we price it appropriately to serve the community and justify future innovation.

In broadest of strokes, we're not giving details on numbers of sites activated yet our patients, dose, other than to say we're dosing patients. I think someone's asked me recently if we were dosing patients in the U.S. yet.

[music].

You may ask your question.

Thank you.

That has been, I think, for a lot of people, a significant challenge, and the short answer is yes, we're dosing patients in the U.S. We are on track to complete the dosing of our study in the middle of 2022, which is our goal, so that's great.

Good afternoon, and thanks for taking our question.

Next question comes in the line of Joseph Schwartz of SVB Securities.

We've got more sites to initiate.

So, maybe focusing a little on the PPMOs here.

Your line is now open.

So, you guys have never taken a price increase, on your PMO franchise, but considering the potential for an improved clinical benefit with 50-51, would there be discussions around this?

You may ask a question.

We're working well to do that outside the United States and even some additional sites in the United States, so we've got more work to do, but the team is executing well, and we're on track to hit our goals.

Is this even something you're considering?

Hi.

Thank you.

Thanks very much.

Well we haven't gotten to a point where we've thought about the exact pricing for the PPMOs and certainly if it is successful, could be a significant and profound benefit to patients even over our current PMOs in a number of regards of course.

Could you provide us with any Phase III enrollment statistics for 9001, such as the proportion of sites that have been activated or patients that have been enrolled in DOS so far?

Generally speaking, our goal is to price our therapies appropriate at inception and to use our performance and our commitment to the patient community and serving the community as the basis for our success and not using things like unnecessary or gratuitous price increases as a way of satisfying our obligations.

And maybe also describe the impact that your new inclusion and exclusion criteria has had on enrollment.

On the inclusion-exclusion criteria, Louise can give some of the data on what she thinks the percentage of patients that might be, excluded from that might be, but broadly speaking, there's such an extraordinary need and demand for this therapy, both from families, and investigators are well aware of this, that I don't believe that is going to be an impediment to the robust enrollment of this study.

And so far it's worked.

What percentage of patients do you see screening out on this criteria?

Louise?

By the way, I'll go back and I want to give an enormous credit to our commercial and medical affairs group and everyone that's supported them because we've had 21 quarters of consistent, sequential, strong quarter-over-quarter growth.

Yes, that's correct.

We've not seen a significant, influence of the revised inclusion-exclusion criteria for 301, which was informed on our earlier studies.

The demand is high, and the recruitment is on track.

Thanks for taking the question, and just to follow up on the last one, just kind of given the, you know, continued clinical holds placed on AAV gene therapies, any impact, positive or negative, you can sense at enrollment sites, any hesitancy, maybe from investigators or patients, obviously, you know, kind of different AAV here, and then tied to that somewhat, within the long-term guidance, can you make any comments, on competition for your gene therapy?

Thank you.

So, I will say a couple.

We have the next question.

It comes in the line of Judah Frommer of Credit Suisse.

Your line is now open.

On the last one, let me say that the long-term strategic plan, base case, assumes robust competition. Whether or not that's accurate or not is something we'll all find out over time, but, we're trying to be thoughtful and conservative in our strategic plan approach, so we actually assume in our plan and our revenue assumptions robust competition for our therapies, even including our gene therapy.

You may ask your question.

So, that's built in.

Hi.

On the first part of the question, I don't believe, but Luis, you can correct me, that there has been any significant impact from the issues that have occurred with our colleagues at other companies, both Pfizer and Solid, with respect to AEs,

SAEs, and the like, and the most recent very difficult situation that occurred with Pfizer.

I think that investigators are fairly well-informed that SRP 9001 is substantially, different than those others and has performed different than those others from a safety perspective, and I think patients are generally pretty sophisticated in this space and generally are aware of that, but Luis, you might have more color on that.

I agree with everything you said.

The physicians are eager, as well as the patients for 301.

They ask good questions.

I think one thing that we're seeing is that the PIs are becoming increasingly sophisticated and ask the right questions, which is good to see as we're tracking along development, as well as IRBs, they're asking the right questions.

This is Tommy on for Salveen.

So I think we're in a good space in terms of education of the community of knowing the right questions to ask and being informed.

Our question is on the genetic collaboration.

So it's all positive from a TAMARC perspective.

Seeing as non-viral delivery has had some setbacks in the past, what is giving you confidence that their platform could be successful?

Thank you.

Thank you.

The next question comes from the line of Salveen Richer of Goldman Sachs.

Yeah.

There are lots of interesting opportunities if one could either enhance AAV, something we're working on, or find an alternative to AAV, but it's challenging.

Your line is now open.

Louise, you might want to take this one.

So genetics is exciting.

You may ask your question.

Yeah.

There are other approaches we're taking as well in the hope that we can advance the science of genetic medicine.

Hi.

Thank you for that question.

Thank you.

Thanks for taking the question.

I think, as I mentioned, with non-viral delivery, one of the challenges is getting to muscle in the first place.

We have the next question.

So I know that you're very confident in the gene therapy program, but if you do decide to work on additional candidates, how fast do you think you can move the next one into the clinic?

So the non-viral delivery mechanisms have been very efficient at going to places like the liver, as you would expect.

Sorry, go on.

Well, we're moving from a preclinical perspective.

And so one of the hurdles to get over this was to efficiently deliver to muscle.

No, go ahead.

And so when we delivered with genetic systemically and saw expression in muscle, we were thrilled with the progress on that.

Sorry.

Now, we have a ways to go.

Sorry about that.

We're moving as fast as we can. Obviously, everything takes more time than one would like when you're dealing with often ferocious neurodegenerative diseases like Duchenne muscular dystrophy, but we're moving fast.

It's early, but this is the first time we really saw measurable expression in muscle.

Thank you.

And so we're excited about where that could go.

So for the next question, we have from the line of use of BTIG.

Again, it's early.

Your line is now open.

It's research, but we're excited.

You may ask your question.

As far as the potential opportunity for the PPMO, I think it's enormous. Enormous in many ways.

Thank you.

Hi.

I have one final thing.

Thanks very much for taking the question.

It's a very good question.

So my question is a follow-up one on PPMO platform.

One thing you should know is that we're taking a number of different approaches simultaneously.

And with a better clinical profile, how possible do you think the platform can potentially expand the patient population, convincing those patients who are not committed to receiving exon skipping therapies to get on treatment?

First, remember, with our first three therapies, we treat about 29% of the Duchenne muscular dystrophy, the Duchenne community.

To your point, this is a very challenging concept.

And given that you said that exon is 51 and maybe even vion is 53, the sales are nearing plateauing.

We can, both with our PMOs or PPMOs, treat easily 50% of the patients and theoretically up to over 80%.

AAV has been successful.

That relates in significant ways to some of the history with the PMOs, the way they were approved, and the like.

I think with a PPMO and certainly with a therapy that, if it's successful, could make 10% or so over the course of a year of a truncated but functional dystrophy, which the literature would say would be a profound change in trajectory of disease, potentially.

I think the XQS opportunity becomes far more viable, and that would really expand the potential for this therapy to treat patients around the world. And then, therefore, as a result of that benefit, I think would really greatly enhance the long-term revenue associated with the PPMOs.

So there's a lot of exciting opportunities in the PPMOs, and we're moving as fast as we can.

Thank you.

We have the next question comes from the line of Zhi Chang Xu of Berenberg.

Your line is now open.

You may ask your question.

Great.

Thanks very much.

Good afternoon.

I want to ask about your 2025 revenue aspiration of $12 billion.

I think just look at the consensus right now is $2.2, $2.3 billion.

What do you think is missing here and what do you think that Delta can be accounted for?

Thank you.

Your line is now open.

I'm not 100% sure where they're deriving their number.

You may ask your question.

I can tell you we're deriving our number with an understanding of the prevalent population that is much better than certainly the literature.

Hey, thanks for letting me back in again.

It's a very thoughtful bottoms-up approach to building our revenue guidance.

So any progress with EMA with respect to SRP 5051 and the threshold of distribution expression for potential MMA submission?

They might be assuming complete cannibalization of the RNA franchise with the launch of 9001.

Also, are you expecting to apply by the end of this year?

There's certainly something that with 5051 in terms of the levels that we expect that we will revisit, and have discussions with regulators in the United States and then with EMA.

That would be, I think, an inaccurate assumption.

Luis, do you want to take this question?

This study will be enrolled this year, and so we'll look towards distribution expression at 28 weeks thereafter.

So I can't say with precision.

So we'll provide guidance as we track towards that.

I suspect, frankly, that we've just done significantly more modeling than one would expect from folks.

I will say that having been personally involved in and involved in the discussions with CHMP and EMA, and I do think we would have a different – I suspect anyway, I should say.

This is all we do is these genetic medicines.

It will all be subject to discussion.

I would now like to turn the conference back to President and CEO Doug Ingram, sir.

It's also partially being driven by probability of success.

I think we would have a different dialogue with the division, with EMA, and then ultimately CHMP with a therapy that was making 6% to 10% disreparate.

Thank you very much.

Thank you.

I think the probability of success would be much higher for an approval or conditional approval.

So, I'll be brief.

The last question comes from the – They may just be discounting.

Thank you.

That's a good question.

I am showing no further questions at this time.

You know, yesterday was Global Rare Disease Day. It is a time when we reflect on those around the world who are living with a rare disease, very often a rare genetic disease.

Good point.

Sorry about that.

So we have the last question comes from the line of Dejit Chattopadhyay of Guggenheim.

The external world can often seem chaotic and uncertain, you know, particularly these days, and that can be particularly distracting.

But reflecting on Rare Disease Days and on our mission to bring a better life to our patients and their families that live with rare degenerative disease, it reminds us that we don't have the luxury of getting distracted, and fortunately, we don't have to be distracted.

We will continue to execute in 2022, and I look forward to additional updates with you across this year.

With that, have a good evening, and thank you for joining us today.

Thank you, ladies and gentlemen.

That concludes today's conference call.

Thank you all for participating.

You may now disconnect.

,

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