Q4 2019 Earnings Call

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Unknown Executive: BF-WATCH TV 2021

Unknown Executive: Ladies and gentlemen, thank you for standing by, and welcome to the Sarepta Therapeutics' fourth quarter 2019 earnings call. At this time, all participants are in listen-only mode.

Unknown Executive: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star one on your telephone. As a reminder, today's program may be recorded. I would now like to introduce your host for today's program, Ian Estepan, Senior Vice President, Chief of Staff, and Corporate Affairs. Please go ahead, sir.

The speakers presentation, there will be a question and answer session to ask a question during the session you'll need to press star one on your telephone.

A reminder, today's program may be recorded I would now like to introduce your host for today's program you know the pen senior Vice President and Chief of staff and Corporate Affairs. Please go ahead Sir.

Ian M. Estepan: Thank you so much, Jonathan, and thank you all for joining today's call. Earlier today, we released our financial results for the fourth quarter and the full year 2019. The press release is available on our website at www.sarepta.com, and our 10-K was filed with the FEC earlier this afternoon. Joining us on the call today are Doug Ingram, Sandy Mahatmang, Bo Cumbo, Dr. Gilmore O'Neill, and Dr. Louise Rodino-Kleipax.

[music] fourth quarter and all year.

The press releases are available on our website.

That's right.

And our 10-K.

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Well, the Gilmore O'neil and Dr.

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Ian M. Estepan: After our formal remarks, we'll open up the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risk and uncertainty, any of which are beyond Sarepta's control. Actual results can materially differ from these forward-looking statements, and any and all such risk can materially and adversely affect the business, the results of operations, and trading prices for Sarepta's common stock. For a detailed description of applicable risk and uncertainty, we encourage you to review the company's most recent annual report on Form 10-K, filed with the Securities and Exchange Commission, 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.

I'd like to know that during this call will be making a number.

Please take a moment to review our spot.

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These statements involve risk and uncertainty any of which are beyond threats control.

[music] materially differ.

Statement in any industry materially and adversely affected.

The results of operation and trading price.

For a detailed description of applicable risks and uncertainty.

Urge you to review the company's most annual report on form 10-K.

Securities and exchange information.

The company.

[music] undertakes no obligation.

These forward looking statement.

Any financial projections provided a big.

Unknown Executive: And with that, I'd like to turn the call over to Doug Ingram on Corpus.

Yeah.

I'd like to turn the call overprint stuck in ground work or something.

Douglas S. Ingram: Thank you Ian. Good afternoon, and thank you all for joining Sarepta Therapeutics' fourth quarter 2019 conference. In 2018, we defined our vision to become one of the world's leaders in precision genetic medicine to treat rare diseases, founded both on our precise and efficient RNA platform and on the build of a gene therapy engine capable of rapidly advancing multiple constructs through development into the patient community. In 2019, we executed, further matured, and brought that vision into greater focus, and in 2020 through 2020, we will, if successful, realize much of that vision. We have an enormous number of milestones in 2020, but before we discuss them, let us review the progress that we have made in 2019. I will begin with our R&A platform. As we announced at the J.D. Morgan conference in January, our fourth quarter 2019 revenue stands at $100 million.

Thank you again good afternoon. Thank you all for joining Sarepta Therapeutics fourth quarter 2019 conference calls.

In 2018, we defined our vision to become one of the world leaders in precision genetic medicine to treat rare disease foundries both.

Our precisely that they should already platform and on the build the gene therapy engine capable of rapidly advancing multiple constructs.

Redevelopment into the patient community in 2019, we executed further matured and brought that vision into greater focus.

2020 through 2020, well if successful realize much of that vision.

We have enormous number of milestones in 2020, but before we discuss them. Let US review the progress that we have made in 29 team I need to begin with our R&D platform.

As we announced at the JP Morgan Conference in January our fourth quarter 2019 revenue.

$100 million.

Douglas S. Ingram: In our third full year since launch, our 2019 revenue was $381 million, a 26% increase over the prior year. I will remind you that we have never taken a price increase since launch, so our growth comes from continuing to serve the Duchenne community. Our 2020 guidance for Exondus is $420 million to $430 million. As we are just launching Vyondist, we will wait until later this year before providing revenue guidance. But you can expect a launch curve similar to that of expectation.

Our third full year since launch our 2019 revenue was $381 million, a 26% increase over prior year I will remind you that we have never taken a price increase since launch so our growth comes from continuing to serve the Duchenne community.

Our 2020 guidance for axon this is $420 million to $430 million.

We're just logic BYOD. This we will wait until later this year before providing revenue guidance.

But you can expect to launch curve similar to not have axogen.

Douglas S. Ingram: In the fourth quarter, we obtained FDA approval for our second RNA therapy, Byondus 53. The approval of Biondis was a win for objective, evidence-based decision-making, it was a win for hard-working professionals at the FDA Neurology Division who were responsible for this review, and, most importantly, it was a win for Exxon 53 amenable patients. With the regulatory pathway reconfirmed, we submitted our rolling NDA for Kazimierzyn, having announced positive results earlier in 2009. Assuming Casimiracin is approved, we will have three therapies capable of treating approximately 30% of the Duchenne community in the United States. We will have doubled the number of patients who may benefit from our PMO technology versus exondus alone. And we will be among an exceedingly small number of biotechnology companies who have internally discovered, developed, and brought to the patient community three or more medicines.

In the fourth quarter, we obtained FDA approval for our second R&D therapy high on this 53.

The approval that by August was a win for objective evidence based decision making.

As a win for hard working professionals at the FDA Urology Division that was responsible for this review and most importantly, it was a win for exon 53 amenable patients.

With the regulatory pathway reconfirmed, we submitted our rolling NDA for CASM Pearson, having announced positive results earlier in 2019.

Human cancer Nursing is approved we will have three therapies capable of treating approximately 30% the duchenne community in the United States. We will have doubled the number of patients who may benefit from our PMO technology versus axon. This alone.

We will be a money money, an exceedingly small number of biotechnology companies, who have internally discovered and developed and brought to the patient community three or more medicines.

Douglas S. Ingram: In 2019, we commenced our multi ascending dose study for our next generation PMO technology. The Pesticide Conjugated PMO or PPMO. Now, let's move on to our gene therapy engine. We've made great progress in 2019 as well. Starting with SRP 9001, our gene therapy for the treatment of Duchenne muscular dystrophy, using our microdistrophin construct, we have completed all dosing in what became a 41 patient placebo-controlled trial, Study 102. Patients are now crossing over at the end of their 48-week period.

2019, we commenced our multi ascending dose study for our next generation PMO technology, the peptide conjugated PMO or ppm out for short.

Now, let's move onto our gene therapy engine. There we've made great progress in 2019 as well.

Starting with SRP nine 001, our gene therapy for the treatment of Duchenne muscular dystrophy, using our micro dystrophin construct we have completed all dosing and what became a 41 patient placebo code placebo controlled trial.

Study one or two.

Patients are now crossing over at the end up there 48 week period by now between our first proof of concept study our main study for one out to you.

Douglas S. Ingram: By now, between our first proof-of-concept study, our main study for 102, and our crossover, we have dosed more than 30 Duchenne boys with active gene therapy. The study continues uninterrupted, and the last patient's last visit should occur in December of this year. We have designed our next placebo-controlled trial using our commercial process material, and we've received initial feedback from the agency. This trial, which we call Study 301, is designed as a global, placebo-controlled, multi-center trial. We have made significant progress in manufacturing. With our partners Thermo Fisher and Catalent, we have built significant capacity with a dedicated facility completed in Lexington, Massachusetts, and even greater capacity than that built at Catalent. Our hybrid manufacturing approach is taking shape with ADPD expertise at our Columbus site and a dedicated ADPD facility in Burlington, Massachusetts.

Crossover we have those more than 30, Duchenne boys with active gene therapy. The study continues on interrupted and the last patient last visit should occur in December of this year.

We have designed or next placebo controlled trial using our commercial process material and we've taken initial feedback from the agency. This trial, which we call study three a one is designed as a global placebo controlled multicenter trial.

We have made significant progress on manufacturing.

With our partners Thermo Fisher and catalysts, we have built significant capacity with a dedicated to Brazil facility completed a Lexington, Massachusetts, and even greater capacity the not built that's catalent.

Or hybrid manufacturing approach is taking shape with AG PD expertise and our Columbus side in a dedicated 80 PD site in Burlington, Massachusetts.

Douglas S. Ingram: This intellectual hub has been responsible for some of our most meaningful advances in 2009. Consider that we have now achieved, at scale, commercially viable yield, for SRP 9001. We announced at J.P. Morgan that we had commenced engineering runs.

This intellectual hub has been responsible for some of our most meaningful advances in 2019.

Consider that we've now achieved at scale commercially viable yields.

CSR P. 900 work.

We announced the JP Morgan that we had commenced engineering runs by now I can tell you that we have commenced our GMP runs for SRP nine 001, and we're making great progress on assay development as well.

Douglas S. Ingram: By now, I can tell you that we have commenced our GMP runs for SRP 9001, and we're making great progress on assay development as well. We've made great progress on our limb-girdle pipeline in 2019. To remind you, LGMD, or limb-girdle muscular dystrophy, is an umbrella name for a collection of serious, often fatal neuromuscular diseases.

We made great progress our limb girdle pipeline in 2019 to remind you LG M.D. or limb girdle muscular dystrophy.

He is an umbrella name for a collection of serious often fatal neuro fatal neuromuscular diseases. None of these diseases have available therapies. So the opportunity to bring better life for these patients is compelling.

Douglas S. Ingram: None of these diseases have available therapies, so the opportunity to bring a better life for these patients is compelling. In the first quarter of 2019, we exercised our option and acquired Myonexus, gaining access to its five LGMD programs, and then we later entered into a license agreement with NCH to gain access to Dr. Zarif Saheng's LGMD candidate for LGMD2A. These six programs together have the potential to provide treatment for over 70% of patients with LGMD. In the first quarter of 2019, we presented expression and safety data from our first three-patient proof-of-concept cohort for LGMB2E, and it was impressive. Expression was 50% on IHC and 37% of normal on Western blots.

In the first quarter of 2019, we exercised our option and acquired mile Nexus gaining access to its five LG have de programs and then we layered entered into a license option with nch to gain access to doctors to reach the hey.

LG M.D. candidate for El GMT two way.

Six programs together have the potential of providing treatments for over 70% of patients with LG empty.

Hey, the first quarter of 2019, we presented expression and safety data from our first three patients proof of concept cohort for LG MDG, We said it was impressive.

Expression was 50% or I see and 30% 37% of normal on Western Blot, we came back in the fourth quarter and we updated with nine month functional data.

Douglas S. Ingram: We came back in the fourth quarter, and we updated with nine months of functional data indicating that every child was improving on every function. We commenced one additional higher dose three patient cohort in 2019 at a four times higher dose with the goal of making a dose selection for 2020 this year. Moving on to the rest of our gene therapy engine, 2019, was equally consequential. With our partner lysogene, we commenced the gene therapy trial for MPS3A, or Sanfilippo syndrome type A, a devastating neurological lysosomal storage disorder. We built out our gene therapy center of excellence.

Indicating that every child was improving on every functional endpoint.

So we commenced one additional higher dose three patient cohort of 2019 at a four times higher does with the goal of making a dose selection in 2020 this year.

Moving on to the rest of our gene therapy edge in 2019 was equally consequential with our partner Lysa genes. We commenced a gene therapy trial for MPS, three a or San Felipe as syndrome type a devastating neurological lysosomal storage disease.

We built out our gene therapy Center of excellence in Columbus, Ohio, Our center of Excellence is already building new constructs.

Douglas S. Ingram: In Columbus, Ohio, our Center of Excellence is already building new constructs and Advancing the Science of Gene Therapy. We entered into 14 transactions in 2019, and we in-licensed or purchased 18 new constructs, bringing the total number of research and development programs to 42 across our two platforms. And we have employed a clever incubation strategy that allows us to build an enormously large pipeline while still permitting us to remain razor focused on our near-term objectives and models. And, of course, we entered into a transformational alliance with Roche in the fourth quarter of 2019, where Roche will take SRP 9001 to patients outside the United States. This alliance, by far the largest ex-U.S. single candidate licensed in biopharmaceutical history, validates our approach, our progress, and the value of our program. But it also serves our mission.

And advancing the science of gene therapy.

We entered into 14 transactions in 2019, and we in licensed purchased 18, new constructs, bringing the total number of research and development programs to 42 across our two platforms and we have employed a clever incubation strategy that allows us to build and then.

Normally large pipeline, while still permitting us to remain razor focused on or near term objectives and milestones.

And of course, we entered into a transformational alliance with Roche in the fourth quarter of 2019, where Roche will take SRP nine 0012 patients outside the United States.

This alliance by far the largest X U.S. single candidate license at biopharmaceutical history validates our approach our progress and the value of our program.

But it also serves our mission if SRP nine 001 proves successful Roche with its very impressive actually U.S. resources and international expertise will bring our therapy too far more patients far faster than we could have ever done on era.

Douglas S. Ingram: If SRP 9001 proves successful, Roche, with its very impressive ex-U.S. resources and international expertise, will bring our therapy to far more patients far faster than we could have ever done on our own. And it places us in an enviable position with the resources to drive our vision and to execute our plan. With the close of our alliance this quarter, we have well over $2 billion of cash on our balance sheet today. Add to that the fact that we have just entered into an agreement to sell our Biondis Priority Review Voucher for $111,000,000, and add again to that our revenue this year for Oksandas and Vyandas, and it should become clear that we are well positioned with the resources, the assets, and the talent to drive our ambitious strategy to fruition. Looking forward, you will see that 2020 is dense with miles. So starting with our gene therapy portfolio for 2020 with respect to SRP901A, SRP902A,

And it places us in an enviable position with the resources to drive our vision and to execute our plants.

With the close of our alliance this quarter.

Yeah, well over $2 billion of cash on our balance sheet today.

Adds to that the fact that we have just entered into an agreement to sell our buy on this priority review Boucher for $111 million.

Out again to that our revenue this year for XR This and buy on this and it should become clear that we are well positioned with the resources the assets and the talent to drive our ambitious strategy to fruition.

Looking forward you will see that 2020 is dealt with milestones.

Starting with our gene therapy portfolio Folio for 2020 with respect to SRP nine 001.

Douglas S. Ingram: We will continue to execute Study 102 with our 48-week last patient, last visit in December of this year. We will unblind, evaluate, and release those results, which should occur in the first quarter of 2021. We are preparing to commence our Commercial Supply Trial, Study 301. Broadly, we have three work streams for Study 301. We must complete site initiation and training.

We'll continue to execute study one or two with our 48 week last patient last visit in December of this year.

We will unblinded evaluate and released those results, which should occur in the first quarter of 2021.

We are permit preparing to commence our commercial supply trial study three a one broadly we have three work streams for study Rio one we must complete site initiation and training we must complete our assay work, our engineering work and our GMP runs.

Douglas S. Ingram: We must complete our assay work, our engineering work, and our GMP runs. And if all goes well, we should have GMP material released this July.

All goes well, we should have GMP material released.

This July.

Douglas S. Ingram: We need to work with the division to obtain their approval on the commencement of Study 301. So, of course, there's a lot to do here, but the team is making exceptional progress. With respect to our LGMD pipeline, we have dosed all three patients now in our high-dose cohort for LGMD2E. We will have expression and safety results available in the second quarter, and we anticipate announcing that data at an appropriate medical meeting in the second quarter. We will make a formal dose selection decision in the third step.

We need to work with the division to obtain their concurrence on the commencement of study three our work. So of course, there's a lot to do here, but the team is making exceptional progress today.

With respect to our LG MD about pipe why we have dose all three patients now in our high dose cohort for LG and the two week, we will have expression and safety results available in the second quarter, and we anticipate announcing that data at an appropriate medical meeting in the second quarter.

I will make a formal does selection decision in the third quarter.

Douglas S. Ingram: We will complete the assay and process development work for LGMD2E with the goal of having GMP material available in time to commence a trial in early 2021. We will also begin the ADPD work for other of our LGMD constructs as well. We will continue our dialogue with the FDA and come to a view on the development and regulatory pathway for LGMD2E and then the remainder of the LGMD pipeline. Our goal is to have all of that completed by year end so we can commence a trial with commercial process material early next year. We have also dosed 17 patients on our MPS 3A gene therapy program and intend to complete all the dosing by the middle of the year. Our collaborator on CMT, otherwise known as Charcot-Marie-Tooth, Dr. Cerise Sahank at Nationwide Children's Hospital had intended to commence her proof of concept study for CMT last year but did not have NCH released material enabling her to do that. That material should be available this year, and Dr. Sahank intends to commence that study.

We will complete the assay in process development work for LG and the two we with the goal of having GMP material available in time to commence a trial in early 2021. We will also begin the 80 PD work for other of our LG M.D. constructs as well we will continue our dialogue with the.

Okay and come to a view on the development and regulatory pathway for LG and these two we and the remainder of the LG and the pipeline. Our goal is to have all that completed by year end. So we could commence a trial with commercial process material early next year.

We have also dose 17 patients on our NPS Threeeight gene therapy program and intend to complete all the dosing by middle of the year.

Our collaborator I'd CMT, otherwise known as Shopko Murray to doctors lease the Hank nationwide children's hospital.

Had intended to commence or proof of concept study for CMT last year, but did not have nch released material, enabling her to do that that material shouldn't be available. This year adopters the Hank intends to commence that study in 2020.

Douglas S. Ingram: In addition to our Gene Therapy Center of Excellence in Columbus, Ohio, we are also building a separate Gene Editing Innovation Center under the guidance of Dr. Charlie Gerspach of Duke University in Durham, North Carolina, and should have that largely complete this year. We also have significant milestones for our RNA platform. We should complete our rolling submission for Kazimiercin in the second quarter. We plan to release the results from our PROMOVI study at the MDA Scientific Conference in March. These results from patients that met the enrollment criteria for 201-202, that's the study which formed the basis for the Teflixin approval, are consistent with the 201-202 data. And we will have dosing and safety insight on our next generation RNA platform, the PPMO, this year as well.

In addition to our gene therapy Center of excellence in Columbus, Ohio Here also building a separate gene editing innovation center under the guidance a doctor Charlie Gerspach of Duke University in Durham, North Carolina, and should have that largely complete this year.

We have also significant milestones for our already platform this year.

We should complete a rolling submission for CASM yourself in the second quarter 2020.

We plan to resolve to released the results from our PROMOVI study.

The MD Eightys scientific conference in March these results from patients that met the enrollment criteria or to a one two or two that's the study which formed the basis for the attempt was an approval are consistent with the two or want to our 2000.

And we will have dosing and safety inside our next generation already a platform. The PPL, though this year as well the PBM I was successfully could be a significant advancement in our already technology and platform.

Douglas S. Ingram: If the PPMO is successful, it could be a significant advancement in our RNA technology. In summary, we have an enormous amount of work to do this year, but that work will be profoundly consequential. Sarepta, And of course, more importantly, for the patients that we serve. To those who may say our plans are ambitious, I would agree. But they are not driven by hubris. They are informed instead by an abiding conviction founded on objective evidence. That the science of genetic medicine has come of age, that a revolution in health care is upon us now, and that Sarepta is playing a leading role in translating that science to practical therapies that improve countless lives otherwise stolen by serious, rare genetic disorders. It's in that spirit that...

In summary, we have an enormous amount of work to do this year that work will be profoundly consequential.

For Sarepta.

Of course, more importantly for the patients that he served.

To those who may say, our plans are ambitious I would agree but they are not driven by you were by numerous they are formed instead of buying the biting conviction.

I would it on objective evidence that the science of genetic medicine has come of age that a revolution of health care is upon us now and that Sarepta is playing a leading role in translating that science to practical therapies that have proved countless wise otherwise stolen by serious rare genetic disease and it is there.

Douglas S. Ingram: and rare disease patients in the U.S. and around the world in recognizing Rare Disease Day this Saturday, February 29. As we continue to bring awareness about rare diseases and the work that remains to bring therapies to patients fighting those diseases every day.

That spirit that I would invite you to join Sarepta and rare disease patients in the U.S. and around the world and recognizing rare disease day. This Saturday February 29.

As we continue to bring awareness about rare diseases.

The work that remains to bring therapies to patients fighting those diseases.

Every day.

Sandy: And with that, I will turn the call over to Sandy to provide an update on the financials. Sandy? Thank you, Terry.

And without I will turn the call over to Sandy to provide an update on the financials Sandy.

Sandy: Thank you, sir. Good afternoon, everyone.

Thanks, Doug.

Good afternoon, everyone.

Sandy: Over the course of 2019, we advanced the business in several significant ways. We beat gravity guidance for Exandus 51, launched another of our RNA medicines, Viandus 53, significantly bolstered our financial position, and struck several new licensing deals, bringing our total number of development programs up to 42. We also struck a partnership with Roche that closed earlier this month and that brought in $1.15 billion into the company. This collaboration brings significant capital to fully fund our pipeline, including cost-sharing payments, and it provides us access to Roche's significant expertise and greatly expands the global opportunity for our lead gene therapy program, SRP 9001. Now moving to the financials, this afternoon's press release provided details for the fourth quarter of 2019 on a non-GAAP basis as well as on a GAAP basis.

Over the course of 29 GT advanced the business in several significant ways.

We need revenue guidance for EXONDYS 51.

Launched another of our R&D medicines I am just 53.

Significantly bolstered our financial position and struck several new licensing deals, bringing our total number of development programs up to 42.

We also start apartment issue.

Roche that closed earlier this month and that brought him $1.15 billion into the company.

This collaboration brings significant capital to fully fund our pipeline, including our sharing payments and provides us access through roshe significant expertise agreed to expand the global opportunity for our lead gene therapy program SRP nine 001.

Now moving to the financials. This afternoon's press release provided details for the fourth quarter for any 19.

Basis, as well as a gabby.

Sandy: The press release is available on Sarepta's website. Please refer to it for a full reconciliation of GAAP to non-GAAP. Net product revenue for the fourth quarter of 2019 was $100.1 million, compared to $84.4 million for the same period of 2018. The increase primarily reflects higher demand for Exonus 51. On a GAAP basis, the company reported a net loss of $235.7 million and $140.9 million, or $3.16 and $2.05 per basic and diluted shares, for the fourth quarter of 2019 and 2018, respectively. We reported a non-Gap Med loss of $116.9 million, or $1.57 per basic and diluted share, in the fourth quarter of 2019, compared to a non-gap net loss of 58.7, or 85 cents per basic and diluted share, in the fourth quarter of 2018.

The press releases available circles web sites. These are funded for full reconciliation of GAAP non-GAAP.

Net product revenue for the fourth quarter of 29 was 100.1 billion compared to 84.4 million from same 2080.

The increase primarily reflects higher demand demand for EXONDYS 51.

Our GAAP basis, the company reported a net loss of 235.3 million.

140.9 billion.

On $3, a 16 stands at $2, a five cents per basic and diluted shares for the fourth quarter funny 19 and aging respectively.

We reported a non-GAAP net loss of 116.9 billion or $1.57, our basic and diluted share in fourth quarter 29 gene.

Non-GAAP net loss of 58.7 or 85 cents per basic and diluted shares.

In the form part of 2018.

In last quarter 2019 recorded approximately 15.6 million in cost of sales.

Sandy: In the last quarter of 2019, we recorded approximately $15.6 million in cost of sales, compared to $13.1 million in the same period of last year. The increase was driven by royalties due to Biomarine Pharmaceuticals and the University of Western Australia, as well as higher production costs as a result of increasing demand for Exondus 51. On a gap basis, we recorded $223.1 million and $146.2 million in R&D expenses for the fourth quarter of 2019 and 2018, respectively, which is a year-over-year increase of 76.9 million. This increase is primarily related to $40 million of increasing expenses in clinical and manufacturing. $10.8 million increase in compensation and other personnel expenses, as well as a 10.4 million increase in milestone payments. On a non-gap basis, R&D expenses were $135.4 million for the fourth quarter of 2019, compared to 77 million for the same period in 2018, an increase of 58.4 million.

He point 1 billion in same during the fossil fuel.

The increase was driven by raunchy student Biomarin pharmaceuticals.

In Western Australia, as not as high production costs as a result of increasing demand for EXONDYS 51.

On a GAAP is recorded 222.1 billion.

$46.2 million in R&D expenses for the fourth quarters of 2019 and 28, respectively.

Which is a year over year increases 76.9 million.

This increase is primarily related to $40 million, increasing expenses and clinical and manufacturing.

A 10.8 million dollar increase in compensation and other personnel expenses.

As opposed to 10.4 billion degrees in milestone payments.

Our non-GAAP basis, R&D expenses were 135.4 million fourth quarter funny 90.

Okay semi somebody from same here in 2018.

He is a 15.4 million.

Sandy: The year-over-year growth in non-GAAP R&D expenses was driven primarily due to a computing ramp-up for a micro-distributed program, the RSS program, and the initiation of certain post-marketing studies for Examiners 51. Turning to SG&A, on a gap basis, we recorded $81.4 million and $64.2 million of expenses in the four quarters of 2019 and 2018, respectively. A year-over-year increase of $17.2 million. On a non-GAAP basis, SG&E expenses were $65.8 million for the fourth quarter of last year, compared to $52.9 million for the same period of 2018, an increase of $12.9 million. The year-over-year increase was driven by significant organizational growth and expansion supporting our commercial launch, as well as 4D therapies in various stages of development across several therapeutic modalities. On a gap basis, we recorded $4.8 million in other expenses for the fourth quarter of 2019, compared to $2.3 million in expenses for the same period of 2018. The unfavorable change is primarily driven by an increase in interest expense, which is recognized for a new term loan that was received by the company in December of 2019.

The year over year growth and non-GAAP R&D expenses was driven primarily due to continuing ramp up in for Mike registration program, Our essence program and initiation of certain post marketing studies for EXONDYS 51.

Turning to as Jamie.

GAAP basis, we recorded $81.4 million.

4.2 million of expenses.

Orders of 20 1920, respectively.

A year over year increased 17.2 million.

Among obesity is union expenses were 65.8 million for fourth quarter of last year.

But a 52.9 meters with same period of 20 gene and increased 12.9 million.

The year over year increase was driven by significant organizational growth.

Spansion supporting our commercial launch.

As most 40 therapies in various stages of development across several therapeutic modalities.

On a GAAP basis, we recorded 4.8 million and other expenses.

In order to 29 gene.

$2.3 million expenses.

2018.

The unfavorable change is primarily from like increasing interest expense, which is recognized for a new term loan that was received by the company in December of 2019.

We had approximately $1.1 billion in cash cash equivalents investments.

Sandy: We had approximately $1.1 billion in cash, cash influence, and investments as of the end of last year. In addition, with the closing of our alliance with Roche this quarter, we have well over $2 billion in cash on our balance sheet today. With that, I would like to turn the call over to Bo for a commercial update. Thank you, Sandy. Good afternoon, everyone.

And as last year.

In addition, with the close of our alliance with was this quarter run over 2 billion pounds in cash Carbavance yesterday.

I would like to turn the call them to both for commercial art.

Yes.

Thank you Sandy good afternoon, everyone.

Bo: Toward our 2019 objectives around execution and our commitment to deliver on our stated goals, I am pleased to report the following on behalf of the organization. We exceeded revenue consensus expectations for both the fourth quarter and the full year of 2019, totaling $100.1 million and $380.8 million, respectively. As Doug mentioned, our 2020 guidance for Exodus 51 is $420 million to $430 million.

Toward our 2019 objectives around execution and our commitment to deliver on her stated goals.

Im pleased to report calling on behalf of the organization.

We see the red meat consensus expectations for both the fourth quarter and the full year 2019, totaling 100.1 million and 380.8 million respectively.

As Doug mentioned.

Our 2020 guidance for EXONDYS 51 is 420 million 430 million.

Bo: In terms of continuing to serve the community, we know that there are additional patients who may benefit from Exodus 51, and we will continue to overcome access and reimbursement challenges to get patients on therapy. Gola Dursun, or Bionis 53, received accelerated approval by the FDA on December 12, 2019. Bionics 53 treats Duchenne Muscular Dystrophy patients who are amenable to skipping Exxon 53. Acting with urgency and the knowledge that patients were waiting, we launched Bionics 53 within 24 hours of FDA approval, just as we did with Exondus 51. We submitted all of our compendium, contracting, and reporting requirements and buyondus53.com, a critically important resource for families to buy. While we are leveraging our deep knowledge and expertise for the Exondus 51 launch, it is important to understand that there will be standard procedures and required reimbursement policies associated with launching a new drug with a unique NDC or National Drug Code. Our team is prepared to work through these requirements as we have in the past, and we anticipate a measured and steady launch trajectory.

In terms of continuing to serve the Judy we know that there are additional patients who may benefit from EXONDYS 51, and we will continue to overcome access and reimbursement challenges you get patients on therapy.

Go look person or my office would be three receive accelerated approval by the FDA on December.

29 team.

I understood three treat you ship muster just treat patients are amenable to skipping exon 53.

Acting with urgency in the knowledge that patients were waiting we launched by almost 53 within 24 hours of that FDA approval.

As we did what things on this if you want.

We submitted all Mark India contracting every 40 to 40 requirements and by almost 53 dot com a critically important resourceful families.

Right.

While we are leveraging our deep knowledge and expertise and honest 51 launch. It is important to understand that there will be Stan standard procedures and required reimbursement policies associated with launching a new drug with a unique NDC our national drug code.

Our team is prepared to work through these requirements as we have in the past.

And we anticipate a measure and steady launch trajectory for by almost 53 resembling the launch curve for me is honest would be one.

Bo: Exodus 53, resembling the launch curve for Exodus 51. The only difference is that we were preparing and planning for the amenable Exxon 53 space to be competitive, in support of our goal to increase access for Biomass 53. We are pursuing a multi-problem strategy. Although commercial and state Medicaid plans now have a much better understanding of Duchenne, we are continuing to educate people about disease progression and the benefits of treatment. Our goal is to work towards coverage that is all-inclusive, regardless of ambulation status, age, or gender. However, we do expect commercial payers to have medical policies in place faster than Medicaid.

The only difference is that we're preparing and planning for the amenable to exon 53 space.

Yes.

In support of our goal to increase access for Biovance 53.

We are pursuing multi pronged strategy.

Although commercial and state Medicaid plans now having much better understanding duchenne, we're continuing to educate about disease progression and the benefits of treatment.

Our goal is to work towards coverage to be all inclusive regardless of emulation as age for gender we.

We do expect commercial payers have medical policies in place faster than Medicaid.

Bo: We also understand from our previous launch that the mix of commercial to Medicaid patients will adjust over time, and we believe it will eventually move towards a 50-50 mix or higher for Medicaid. Furthermore, we are continuing to engage with state Medicaid plans regarding the CMS Guidance Letter on the obligation of state Medicaid programs to make accelerated approval treatments available to patients. As you know, this is critically important information based on the percent of patients covered under Medicaid plans. While the launch over the Christmas holiday did delay some physicians and patients seeking treatment during that period of time, We have been receiving STAR forms from top-tier centers across the U.S. and are working with health care providers to ensure they are educated around amenability to skipping Exxon-53, and this population is different from Exxon 51 with some exceptions

We also understand that from our previous launched at the mix of commercial to Medicaid patients will adjust overtime.

We believe it will eventually move towards a 50 50 mix or higher Medicaid.

Further we are continuing to engage with state Medicaid plans regarding the CMS guidance later on the obligation of state Medicaid to make accelerated approval treatments available to patients.

As you know that is critically important partnership based on the percent of patients covered under Medicaid plans.

While the launch over Christmas holiday is delayed some physician and patient seeking treatment during that period of time.

We have been receiving start forms from top to centers across the U.S. and are working with health care providers to ensure they were educated around them and ability for skipping exon 53.

As this population is different from exon 51 with some exceptions.

Bo: Epidemiology suggests that Biondis 53 can serve approximately 8% of the Duchenne community, but we will have to take into consideration that there are a number of patients already enrolled in or being recruited for clinical trials, or who have a deletion that would be amenable to Exxon 51 and therefore could already be on Exxonus 51. With that said, we continue to have conversations with health care providers about the number of patients within their clinics and with payers about the number of patients eligible for treatment under their plans.

Epidemiology suggest that that by almost 53 cancer approximately 8% of the Duchenne community.

But we will have to take into consideration that there are a number of patients already enrolled him or being recruited for clinical trials or have the deletion that would be amenable to exon 51, and therefore could already be on EXONDYS 51.

With that said, we continue to have conversations with health care providers about the number of patients within their clinics and with payers about the number of patients eligible for treatment under their plan.

Bo: We are working with both healthcare providers and payers to get all amenable patients on Biontis 53 as soon as possible. Our mission to be the global leader in precision genetic medicine started with Exondys 51 and has continued with the approval and launch of Iondys 53. We are now preparing for the potential launch of Kazimersik for patients amenable to skipping Exxon 45. Behind these important medicines is an industry-leading pipeline of programs, 42 in all. Driven by new modalities designed to treat complex rare diseases, including MPS3A and Limb-Girdle-Muster, Sarepta is working with Urgency and is focused on understanding the epidemiology and global prevalence of these diseases. We are continuing to refine our analysis and uncover additional insights while collaborating with top neuromuscular specialists.

We are working with both health care providers and payers to get all amenable patients by almost 53 as soon as possible.

Our mission to be the global to be the global leader in precision genetic medicine started with EXONDYS 51, and has continued with the approval and launch a buy on this may be three.

We are now preparing for the potential launch on CASM or is it for patients amenable to skipping exon 45.

Behind these important medicines is industry, leading pipeline programs 42 at all.

Driven by new modalities designed to treat complex rare diseases, including MPS Iiib again, when girl must or just.

Sarepta is working with urgency and is focused on understanding the epidemiology and global prevalence of these diseases.

We are continuing to refine our analysis and uncover additional insights while collaborating with top neuromuscular specialist.

Bo: Each day we are learning more about these diseases, and with each piece of evidence that we gather, we are able to apply these insights to our disease awareness and patient identification efforts that are already underway. 2019 was a year of great accomplishments, not only for the commercial organization but for the company overall. Looking to the future, patient care will continue to be our driving force as we translate scientific innovation into medicines designed to improve the lives of patients around the world.

Each day, we are learning more about these diseases and with each piece of evidence that we gather we're able to apply these insights to our disease awareness in Asia I Didnt do application efforts that are already underway.

2019 was a great.

As a year of great accomplishments not only for the commercial organization, but the company overall looking to the future patient fear will continue to be are driving force as we translate scientific information that the medicines designed to improve their lives of patients around the world.

And with that I'll turn the call back over to Doug.

Douglas S. Ingram: Thank you, Bo, and thank you for Bo Sandy. With that, let's open the call to questions.

Thank you Bowen. Thank you before boasts ended with that let's open the call for questions.

Unknown Executive: Certainly, once again, ladies and gentlemen, if you have a question at this time, please press star, then one on your touchtone telephone. If your question has been answered, and you'd like to remove yourself from the queue, please press the pound key. We'd like to ask that you please limit yourself to one question. You may get back in the queue as time allows. Our first question comes from the line of Ritu Baral from Cowan.

Certainly once again, ladies and gentlemen, you have a question at this time. Please press Star then one and you touched on telephone. If your question has been answered and you'd like to move yourself from the Q. Please press the pound key we'd like to ask that you. Please limit yourself to one question you may get back into queue. As time allows our first question comes on the line of reduced Farrell from.

Ritu Baral: Your question, please. Good afternoon. Thanks for taking the question so early and accommodating the Rare Disease Week agenda here in DC, guys. Appreciate it. Doug, can you let us know when the last patient for gene therapy was dosed? Basically, what is the shortest follow-up period, both for microdystrophin as well as for limb girdle?

Cowen Your question please.

Good afternoon. Thanks, Laura Thanks for taking the questions. So early in the accommodating.

The agenda here and keep the guys appreciate it.

Okay.

Can you want to know when the last patient.

Or gene therapy.

So basically what is what is the shortest follow up period.

Both for.

But just given as well as limb girdle can you talk about.

Douglas S. Ingram: Well, I can just tell you very broadly that, as a...

The safety profile, especially especially liberal, especially platelets.

Douglas S. Ingram: For the 41 patient study, 102, the last patient, the last visit will be in December, so if you work backwards, you'll see that the last patient was right at, I think it actually might have been the very first week in the 2020s, so that was the first 41 patients dosed. We have now dosed six patients with limb girdle, both the previous dose and now the higher dose in limb girdle, and of course, a lot of that's blinded, so we'll all see together both the safety and the full safety and efficacy, but broadly speaking, I will say again, consistent with our preclinical models, we have never seen anything that looks like complementary. You know, reductions in platelet counts below the normal line.

In that time period for both program. Thanks.

Well I can say very broadly that.

Sure backward engineer and weren't going to have that for the 41 patient study one or two the last patient last bit it'll be a december so be worked at work backwards, you'll see that the last station was right at that I think it actually my been a very first weekend.

2020, so that was the first 41 patients dosed, we're continuing on an ongoing basis to those patients on crossover as well with does a significant number as I've mentioned to you now but in study one to two between the proof of concept what a one between the main.

In 41 patient study and between the crossovers Weve dosed over 30 patients with active therapy, we have now dosed six patients with limb girdle that.

Douglas S. Ingram: Things continue as they were. Study 102 continues completely uninterrupted. We're making great progress there. The exciting thing about 102 is that we'll have our last patient in December, and we'll have a readout in the first quarter of 2021. And I will remind you that this is a readout not merely on expression and on safety but also on function using NSF.

The previous dose and now the higher Denison limb girdle and of course, a lot of that's blinded so that that we'll see together both the safety in the full safety and efficacy, but broadly speaking I will say again consistent with our preclinical models, we have never seen anything that looks like complement or you know reductions in platelet counts below.

The normal level, so that sort of things continue as they were study.

Say, one or two continues completely uninterrupted, making great progress there the exciting thing about one or two as they will that last station in December and we'll have a readout in the first quarter of 2021, and I will remind you that is a read out not merely on expression on safety, but also on function using as.

Thank you for your question.

Tazeen Ahmad: Thank you very much. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your question, please. Hi. Good afternoon, guys.

Our next question comes the line does mean Ahmed from Bank of America. Your question. Please.

Hi, Good afternoon, guys. Thanks for taking my question I, just wanted to ask about P. PMO.

Tazeen Ahmad: Thanks for taking my question. I just want to ask about PPMO. You've talked about data for this year. Specifically, Doug, what kind of data do you think that we'd be able to see, and can you just narrow the timeline for us on what part of the year that would be? And then, related to that, assuming that this data looks better ultimately than PMO and that you also do have gene therapy approved, how do you think about the package that you're offering overall for PMD patients? Why would they need to be, let's say, on PPMO?

It's about data for this year, specifically, Doug what kind of data do you think that we'd be able to see and can you just narrow the timeline for us on what part of the or that would be and then I guess related to that assuming that.

The state it looks better ultimately them PMO.

But you also do you have gene therapy approved how do you how do you think about the package than your offering overall DMD patients why would they need to be let's say on PPI and gene therapy potentially thanks.

Douglas S. Ingram: Thanks for that. I'm really glad you're asking about PPMO because we're very excited. We're excited about our RNA technology generally. We're very excited about what PPMO may mean. Of course, we don't have the results yet. I'm going to turn this over briefly to Dr. O'Neill to talk about some of the data that we'll get. But let me give you a couple broad strokes.

Thanks for that I'm really glad you're asking about ppm out because we're very excited we're excited about our already technology generally we're very excited about what what PPL not made course, we don't have the results yet I'm going to turn this over briefly to Dr. a meal to talk about some of the data that will get me. The couple of broad stroke, So where do you know we're targeting the middle of the year.

Douglas S. Ingram: We're targeting the middle of the year for some data. We're continuing to dose escalate, and things look great.

First about all we're continuing to dose escalate.

Gil Blum: We might even dose escalate beyond the middle of the year, but we'll have safety and efficacy exposure and dosing information by the middle of the year. I'll let Dr. O'Neill sort of give you some more detail on that. On the broader question about what this might mean for patients if we have both gene therapy and either our current RNA or a next generation version of RNA PPMO in the future, that's work that we're doing right now. I know that there are a lot of investors that have kind of assumed for planning purposes that there would be great cannibalization of the RNA franchise when gene therapy comes. If it turns out in the end that the gene therapy that we're working on is so profoundly impactful that it alone is meaningful and that it cannibalizes it, then so be it.

Things look great, we might even dose escalate beyond the middle of the year, but we'll have safety.

And.

Safety exposure in dosing information by the middle of the year and I'll, let dr. aneel sort of give you some more detail on that on the broader question about what what the what this might be for patients. If we have those gene therapy at either our current R&D or a next generation version of our R&D PMO in the future that's work that we're doing.

Right now I know that there are a lot of investors that have kind of assumed for planning purposes that there would be.

Great cannibalization or BRD franchise with gene therapy comps and if it turns out in the Yang that the gene therapy that that we're working on it so profoundly impactful that it alone.

It is meaningful and that it cannibalizes. It then so be it will be thrilled with that answer for patients, but I think there's a lot of hypotheses ensign theses and some literature actually that would support the conclusion that there may be a comment at the value of gene therapy and are in anyway, and I think would the PBM out it really was up.

Gil Blum: We'll be thrilled with that answer for patients, so we're doing a bunch of work on that right now. We'll come back likely early next year and provide additional insight and views on what the combination of our RNA technology and gene therapy might mean. And there are two things to look at. There's science, obviously, the science of that. And, of course, there's the access and reimbursement-related issues that Bo and his team are working on. And with that, I will turn it over to Dr. O'Neill to talk a bit about the information.

Profoundly significant advancement over our current technology might make that even more meaningful. So we're doing a bunch of work on that right now we'll come back likely early next year and provide additional insight in views on what the combination of our R&D technology gene therapy might mean, and there's two things to look at their science, obviously the science.

That in that and of course, there's the access and reimbursement related issues that by what his team are working on and with that ill turn it over to Dr and be able to talk a bit about the information that will receive around the middle of this year and thanks very much Doug and I says he thanks for your question.

Gil Blum: Thanks very much Doug and hi Tazeen, thanks for your question. What we actually will be looking at is a combined data set in the second quarter from both Healthy Volunteers, which is a single ascending dose study, and a serial court multi-ascending dose study in Duchenne patients in which we will have comprehensive safety data, we will have systemic exposure, that is blood exposure, we will actually have muscle exposure using muscle biopsy, and we will actually also be looking at some pharmacodynamic data with the particular folks at Exxon Skipping because these will be short follow-ups at this point.

What we actually took out a combined datasets.

India and the second quarter from both at healthy volunteers, which is a single ascending dose study and a series of course multi ascending dose study in duchenne patients in which we will have a comprehensive safety data you ought to have systemic exposure, but exposure, we will actually have muscle exposure using.

Muscle biopsy I'd be what I should also be looking at some from the kind of data the particular folks exon skipping because these would be short follow ups at this point.

Right.

Thank you.

Unknown Executive: Thank you. Our next question comes from the line of Joel Bainey from Citi. Your question, please. Hi, this is Sean Egan calling in for Joel.

Next question comes on line of Jobing from Citi. Your question. Please.

Hi, This is Sean Egan, calling it for Joel Thanks for the update today and profit for taking my questions.

Unknown Executive: Thanks for the update today and also for taking my questions. On DMD gene therapy, I know that you guys have previously said that you plan to have adequate supply to address the market. But in a scenario where supply is limited, are there conditions in the agreement with Roche that dictate how product will be allocated between the U.S. and the rest of the world? Thank you.

DMD gene therapy, I know that you guys have previously said to you plan to have adequate supply to address the market.

But in a scenario where supply is limited or their conditions in the agreement with Roche that dictate how product will be allocated between the U.S. and rest of world. Thank you.

The short answers will will you know again, we are trying to be to our goal and our goal is to ensure at the moment.

Douglas S. Ingram: The short answer is, again, we are tracking to our goal, and our goal is to ensure at the moment of launch and availability to the community in each of the various regions that we, and then in the U.S., and then Roche with us, outside the U.S. will go, that we'll have adequate supply for patients. Obviously, we've got much work to do with Roche on that, particularly as we think about how broad this could be outside And we'll just plan for that. You know, the real work on, the most significant work, at least for us now, is on the AFI development and process development and getting GMP runs and getting buy-in from the agency and commencing this trial. We've already built a significant amount of capacity. We've got a stand-alone site in Lexington, Massachusetts.

Launch and the availability to the community in each of the various regions that we and then in the U.S. and then Roche with us outside the U.S. will go that we'll have adequate supply.

For patients obviously, we've got much work to do with Roche on that particularly as we think about how broad this could be outside the U.S. when you have.

A partner with the resources the Roche and we'll just plan for that you know the real world.

The most significant work at least for US now is on the assay development and process development. It getting GMP runs in getting volume from the agency commencing this is trial weve built already a significant amount of capacity, we've got as Standalone site Lexington, Massachusetts, We got significantly more already.

Douglas S. Ingram: We've got significantly more already over at Paragon Cattlemen's. And as we do the work and we progress, if we need more capacity still, we can certainly do that. We have a relationship with Paragon alone that would provide us with the ability to take additional sweeps. Additional capacity as we proceed. So we're planning for success. Quite confident in our relationship with Roche, we'll both be playing.

Over at Paragon Catalent.

And as we do the work and we progress if we need more capacity still.

We can certainly do that we've got a relationship with Paragon loved that would provide us with the ability to take additional suites and add additional capacity as we proceed. So we're planning for success and I'm quite confident in our relationship with Roche will both be plenty for success.

Thank you. Our next question comes from the line that Chris right from the Maureen Your question. Please.

Douglas S. Ingram: Thank you. Our next question comes from the line about Christopher Mirai from Nomura.

Christopher Marai: Your question, please. Thanks for taking the time to answer my question. One on MPS 3A, your progress there. I was wondering if you could comment a little bit on the age of the patients that are being enrolled, and then perhaps a little bit on the type of endpoints you're going to be looking at, and then your confidence in being able to see a difference between, I believe, it is the natural history that you're looking at. And that's it. Thank you.

Hey, Thanks for taking the question one on NPS three behavior progress. There I was wondering given that the legal if you could comment a little bit on the need to the patients that are being enrolled and then perhaps a little bit on tight, but I would point, they're going to be looking at.

And your confidence in being able to be a difference between believes that the natural history.

And I'll turn that's it thank you.

Gil Blum: Chris, thanks for your question. So I think there were two elements you wanted to know about outcomes based on the age of the patients. The study, and you can see it on clinicaltrials.gov, actually requires patients to have at least an age of six months. But the key ceiling for age is really created by a requirement that they have a development quotient of 50% or greater. So that naturally restricts the upper age group there. With regard to the outcome measure, I've kind of hinted at it, which is the development quotient. It is the primary outcome measure. And essentially, that is a way of capturing the cognitive behavioral development of the children in this trial. And that quotient is, not surprisingly, a ratio determined by the outcome measured by one of two measures. The Bailey scale, which is a development measure for infants and toddlers for the Kauffman Assessment Battery. Each one is used depending on the age of the patient.

Hi, great, Dr and they'll be right.

Thanks for your question. So I think there were two elements you wants to know about outcomes of the age of the patients.

The study.

You can see is on trust sub Gov actually requires patience a habit. These major six month of the key.

Ceiling for ages really created by requirement.

They haven't developed quotient of 50% or greater so that naturally restricts the upper age.

Group.

There with regards the outcome measure that kind of hinted assets, which is the development quotient is the primary outcome measure and essentially that is a way of capturing the cognitive behavioral development of the children in this trial.

Potion to essentially is not surprised me a ratio.

Determined by the outcome measures in one of two measures the had the Bailey.

As scale.

Which is a development measure for instance, and tubers or the commitment assessment battery.

Each one is used depending on the age of the patient.

Gil Blum: And then to your point, yes, we are looking at the outcome versus a natural history, which is, again, described in some process. Thanks for your question. Thank you. Our next question comes from the line of Brian Abrahams from RBC Capital Markets. Hi, this is Erdogan for Brian. Thank you very much for taking our question. I was just interested to get your thoughts on Pfizer's Phase 3 study design and timing and see, I guess, where you think you have a lead on DMD at this point. And then, after your initial feedback from the FDA on Study 3, have there been any changes to your plan to approach the agency with the 12-month functional data from Study 2 and the 3-month expression data from Study 3? Presumably in early 2021 to determine the potential for that to make up a sufficient and following data set.

Then to your point, yes, we are looking at the.

Outcome.

Versus a natural history.

Rich.

Again describes infants process.

Thanks for your question.

Thank you. Our next question comes from the line of Brian Abrahams from RBC capital markets. Your question. Please.

Hi, I heard on for Brian. Thank you very much for taking your question.

I was interested to get your thoughts on Pfizer's phase three study design and timing and see I guess, where you think how much of the lead you think you have at this point yes.

DMD and then after your initial feedback from the FDA on study three there been any changes to your plan to approach the agency.

With the 12 month functional data from study to with the three month expression data from study three.

Presumably in early 2021.

To determine the potential for that's making up sufficient falling data says.

Unknown Executive: So, a couple thoughts. First, on that latter thought, there's nothing in our discussions with the agency that's impacted our broad perspective on the approach, both to 301 and our current study, 102. Obviously, we've taken the views of the agency and the considerations into account and made modifications, but they've been modest to date. Going back to the Pfizer posting on clinicaltrials.gov, I'm going to turn this over briefly to Dr. O'Neill, who can provide insight into that.

Yeah. So a couple of thoughts first on the latter thought there was nothing our discussions with the agency that's it.

Impacted our our abroad.

Perspective on the approach spoke to three Oh wind in our current study one or two obviously, we've taken views of the entity the consideration and made modifications, but then they've been modest today.

Going back to the Pfizer posting on clinical trials I go hungry to turn this over the briefly to Dr. really can provide insight into that broadly speaking I will say of course that.

Douglas S. Ingram: Broadly speaking, I will say, of course, that anybody working in this area of the Shellmuster District should deserve kudos. This is, of course, an important area, and all of us worked to drive this in this direction positively. You can imagine our views on our own construct and its value, particularly given the results that we've seen so far, both in safety and expression. We've had enormous expression, as you can see in the first four patients dosed with our current dosing. And from a functional perspective, I think you've seen all four of those boys at nine months showed significant improvement and improvement over natural history at every single functional endpoint. So we're very excited about where we are and where we're driving, and certainly, we see ourselves as the leader of Duchenne muscular dystrophy and the leader of gene therapy for Duchenne muscular dystrophy. But kudos to anyone working in this area. But with that said, I would turn this over to Dr. O'Neill to give you his view on the submission. Thank you.

Anybody working in this area.

So much who dystrophies you deserve to does this is a this is of course that are important area and all of US worked in driving in this direction as a positive.

I can imagine our views on our own construct and its value, particularly given the results that we've seen so far both.

Safety.

And in expression, we've had enormous expression as you've seen in the first for patients dosed with our our current dosing.

And from a bunch of perspective, I think you've seen all four of those boys.

Nine minds.

Showed significant improvement in improvement over.

Natural history.

Every single functional endpoints. So we're very excited about where we aren't where we're driving and certainly we see ourselves as the leader of the shaft muscular dystrophy and in the leader of gene therapy for Duchenne muscular dystrophy, but kudos to anyone working in this area, but with that said I would turn semiconductor Neal to give your view on the submission. Thank you Doug.

Gil Blum: Thank you, Doug, and thanks, Bertolt. As a group of people who are passionately committed to Duchenne Boys and helping them take on this disease, we're obviously always very happy to see the increasing investment and increasing attention of the scientific community and, frankly, the commercially sponsored community in treating Duchenne. And why does that matter?

You know as as a group of people who are passionate commitment to add Duchenne boys in helping them and take on this disease, obviously always very happy to see the increasing investment increasing attention of.

The scientific community and frankly, the commercial sponsored community in treating Duchenne I think what's important to say is that.

We are.

Gil Blum: Because it targets that expression to secretion of cardiac muscle, which are the two critical organs or tissues adversely impacted by Duchenne. Second, as Doug has said, we have seen high degrees of expression of microdystrophin in muscle in treated Duchenne Boys in our proof of concept study. And third, we have not seen cognitive activation.

On track.

Our activities for the budgets and the caused site and setup.

We have very excited.

Investigators variances excavators and patients and are you don't have very happy about the progress and the commitment that we are receiving.

I think it's also important to see them as our program has involved we're seeing some emerging and differentiation factors some of which are the name for one obviously is our promoter.

Gil Blum: And four, and very importantly, with regard to our program, we have fully enrolled a 41-patient, double-blind, randomized, placebo-controlled study, and we are on track to actually get a readout of its evaluation of the clinical benefit of microcystrophin expression in Duchenne boys in the first quarter of next year. Thanks very much. Thank you. Our next question comes from the line of Alephia Young from Cantor Fitzgerald. Your question, please. Hey guys, thanks for taking my question. I guess I just wanted to ask a little bit about the upcoming limb girdle readout. And I mean, obviously, you got a pretty good, quite good response at the low dose of about 50% expression. I mean, is that do you think sufficient? Or if you if you're able to see more, would you potentially go into the higher dose? Just kind of help us think about where the

In which we have a specific promoter.

Which is both highly efficient and very precise in targeting expression of microscopes.

And why does that matter because the target that expression to speech that cardiac muscle, which are two critical organs or tissues adversely impacted by Duchenne and second.

That said we have seen.

Hi degrees expression of Microdisplay open in muscle increases Duchenne boys in our proof of concept study.

Three we have not seen contracted nation.

And for and very importantly.

We've got to a program.

We have fully enrolled at 41 patient double blind randomized placebo controlled study.

And we are on track to actually.

A readout up it's a valuation of the clinical benefit of microscope expression in Duchenne boys in the first quarter next year, thanks very much.

Thank you. Our next question comes from a line of Alethia Young from Cantor Fitzgerald. Your question. Please.

Douglas S. Ingram: Yeah, it's a great question. So again, just to remind everyone, we dosed three patients in our first dose. Last year, we saw a couple of things. One, the therapy was well tolerated, with some elevated liver enzymes. And I think I guess everyone by now realizes that they are going to see elevated liver enzymes. The good news is, both our

Hey, guys. Thanks for taking my question I guess I just wanted to ask a little bit about upcoming Lindero read out I mean, obviously you got a pretty good quite good response in the low does that about 50% expression. I mean is that do you think suspension or if you if you're able to theme or would you potentially go on to the I guess I'm just kind of help us think about what are the plans part with that.

Yes. Good question. So again just to remind everyone. We had that we we dose.

Three patients in our first dose last year, we saw a couple of things one the therapy was well tolerated with.

With something up elevated liver enzymes and I think I guess, everyone by now sees them. They these are going to see elevated liver enzymes. The good news is both into our Mike Michigan program ended as Lynn Girl program elevated liver enzymes have responded well to steroids in are manageable would come back down to baseline and that's where expression perspective, and then from a expression.

Douglas S. Ingram: Microdischarge Programming in the Limb-Kernel Program, elevated liver enzymes have responded well to steroids and are manageable. And then from an expression perspective, in our first dose cohort, as I mentioned in my prepared remarks, we saw, on immunohistochemistry, about 51% protein-positive fibers, very good intensity, which is an important thing to consider whenever anyone looks at protein-positive fibers. You should always be asking about intensity as well. I think the intensity here was, if my memory is correct, something like 47%. Someone please tell me if I'm wrong.

Respective in our first dose cohort I mentioned in my prepared remarks, we saw on.

I mean is the chemistry about 51% protein positive fibers very good.

Intensity, which is an important thing to consider whatever anyone look said.

Protein positive fiber she should always be asking about intensity as well I think the intensity here was memory is correct something like 47% someone tell me if I'm correct now what is telling me I'm incorrect and then we saw in western blot about 37% of normal.

Douglas S. Ingram: And then, on top of that, as you know, we had nine-month functional data from these three children. And the good news is that every child on every functional measure was improving. So what are we doing now?

And then on top of that as you know we had nine month functional data from these three children and the good news is every child. When every functional measure was improving so what are we going out we were doing one goes higher for ex that dose. So we can make a dose decision between those two and we are I think in a theory.

Douglas S. Ingram: We're doing one dose higher, 4X that dose, so we can make a dose decision between those two. And we are, I think, in a very good position right now because, from our perspective, from what we've seen, both in animal models and the like, the dose, the expression that we're getting right now, and the signals that we're getting right now are sufficient to imagine that we have a very transformative therapy for limb girdle type 2E. And so we want to explore one dose higher. If we, you know, and then we're going to make a dose decision. It's going to obviously be a risk-benefit analysis, and we're going to look at the benefits, and we're going to see if we see significantly increased expression with the same safety profile.

Good position right now because from our perspective from what we've seen both in animal models and and the like the dose the expression that we're getting right now and the signals that we're getting right now are sufficient to envision that we have a very transformative transformative therapy for limb girdle type two we and so we.

Explore one does higher if we you know there and then we're going to make those decision it's going obviously be a risk benefit analysis and we're going to look at the benefits of we're going to see if we see significantly increased expression with the same safety profile Blitz imagine how does one scenario then certainly we go higher dose if we see about the same.

Douglas S. Ingram: What's imagine that as one scenario, then certainly we go to a higher dose. If we see about the same expression between the two, then there would be no value to it. Of course, we're going to have to look at tolerability and safety as well. So the good news is I think either decision, both decisions, you know, decisions will be made based on objective evidence. We'll see that evidence in the second quarter. We'll make an official decision in the third quarter, but I think there's no answer that will be a bad one for us. It'll just be objective. And more important than us, I think it'll be a good decision in either event for patients that are living with and degenerating from Web Girdle.

Expression between the two then there would be no value to it in of course, we're going after.

Right to look at Tolerability and safety as well so the good news is I think either decision. Both the said you know the decisions will be made based on the objective evidence, we'll see that evidence in the second quarter, we'll make an official decision in the third quarter, but I think there's no answer that will be about one for us. It will just be objective lead driven.

And more important than us that I think there'll be a good decision in there that either event for patients that are living with.

And the generating from when girdle tied to it.

Okay.

Matthew Harrison: Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your question, please. Hi, this is Max.

Thank you. Our next question comes on line of Matthew Harrison from Morgan Stanley. Your question. Please.

Hi, This is Mac score on from Matthew Harrison.

Unknown Executive: Unknown Executive, Huidong Wang, Hartaj Singh, Gavin Clark, Ian Estefan, Francesca Nolan

Regarding the limb girdle to eat program could you provide an update on discussion discussions with regulators has your view changed at all on a potential accelerated approval pathway. Thank you very much.

Unknown Executive: An update on discussions with regulators, has your...

Douglas S. Ingram: Has your view changed at all on a potential Accelerated Approval Pathway? So we've just started that process. I think we may have mentioned at the JPMorgan conference that we've

So we just started that process I think we may have mentioned that the JP Morgan conference that we just opened up the dialogue with the agency. We're envisioning that this is going to be a process is going to take the dialogue in education fairness.

Douglas S. Ingram: [inaudible] study and this focus on Lynn Gerbel is so compelling because there are no therapies. And because there are no therapies for it, it is not characterized as well as, for instance, Duchenne muscular dystrophy. So education is part of this process. So we've got an ongoing dialogue with the FDA, where we will share information, and we will discuss. We will come to the right development regulatory approach. And we have some time to do that, because at the same time, we've got to do the assay development and the process development. And then we have to

To the division one of the one of the things that makes this.

Study and the is focused on than girls. So compelling is that there are no therapies for it and because there are other therapies for it is not characterized as well as for instance, duchenne muscular dystrophy. So education is part of this process. So we've got to ongoing dialogue with the with the FDA, where well we'll share.

Our information will dialogue will come to the right development regulatory approach and we have some time to do that because with the same time, we've got to be the assay development and the process development and then you've got to build GMI p. material. Our goal is to actually have GMP material released by the end of this year. So we wanted to complete that discussion before the end of this year have all regulatory.

Douglas S. Ingram: GMP material. Our goal is to actually have GMP material released by the end of this year. So we wanted to complete that discussion before the end of this year, have a regulatory and development pathway developed by the end of this year, and start a trial by early next year. Our view remains the same, which is that for an ultra-rare disease like lymph nodal 2E where this is a gene therapy, and the gene therapy here intends to insert a gene that codes for the structural native unaltered protein, a structural protein in a monogenic disease distinguished by the fact that it is a missing protein that is causing degeneration and death in these children, that we should be able, in dialogue with the agency, to So it's a long-winded way of saying we have more dialogue with the agency to have, and we'll have a good answer on that by the end of the year.

On the pathway developed by the end of this year has started a trial by early next year. Our view remains the same which is that for an ultra rare disease like limb girdle to me, where this is a gene therapy and the gene therapy view it tends to.

To answer a gene that codes for the actual native on altered protein a structural protein in a monogenic disease distinguished by the fact that is a missing protein is causing the generation at that these children that we should be able in dialogue with the agency to come with the agency to inefficient path.

The way to bring these therapies to these patients as fast as possible and.

Reasonably considered in light at the constraints to come from dealing with a rare.

Very ultra rare and heterogeneous disease. So the so long winded way of saying we have more dialogue with the agency to happen, we'll have a good answer on that by the end of this year.

Thank you. Our next question comes the line Gena Wang from Barclays. Your question. Please.

Gena Wang: Thank you. Our next question comes from the line of Gena Wang from Barclays. Your question, please. Judah Virginia Wang, congratulations on the update of the project, and thank you. [inaudible] I'm sorry, I apologize. We cannot hear you. Apologies for that.

Yeah.

Yes.

Yes.

Hi, Paul.

One question I'm, sorry, I apologize I, we cannot hear you apologies for the [noise].

Unknown Executive: Ah, can you hear me okay?

Can you can you hear me okay.

Indeed, who can't.

Unknown Executive: Thank you for listening. Be safe out there. Be well.

Hello.

Yeah. We continue now thank you okay great.

Unknown Executive: and David Kenyon.

Unknown Executive: Yeah, we can hear you now. Thank you. Okay, great.

I guess my question on not modeling purpose modeling I guess, how should we think about the impact of the Roche or you're still on opex over the next few years.

Gena Wang: I guess my question about our modeling is, how should we think about the impact of the ROHS or USTL on OPACs over the next few years? For example, I think your RND19 was roughly 560. How much of that is attributed to DMD gene therapy? How should we think about modeling cost savings based on cost-sharing payments?

For example, I think your R&D 19 was roughly 560, how much of that is attributed to Tim do gene therapy and.

How should we think about modeling cost savings based on cost sharing payments.

Sandy: I'm going to turn this over to Sandy, but just to remind everyone on the call so that people can keep track, the relationship that we've entered into with Roche has a number of components. We had an upfront payment that was between a fee and a premium-based equity purchase just shy of about $1.2 billion. We have additional milestone payments along the way, about $1.7 billion if I'm not mistaken. We have significant mid-team royalties associated with revenue, ex-U.S., net sales ex-U.S. upon rolling that out ex-U.S., and then we have cost sharing. And so the cost sharing is that from the execution of the agreement, actually not the closing of the agreement, but from the execution of that agreement, Roche is responsible for half of all of the global expenses for our development program for our micro-distributed program, SRP 9001. And then to the extent along the way there are any additional ex-U.S. required studies, Roche would be 100% responsible. So with that, Sandy, do you want to comment on its impact on the burn rate?

Yes, so just to remind I'm going to turn this ever to sandy, but just to remind everyone on the call. So that people drop that we at the relationship that we've entered into with Roche has a number of compounds. We had an upfront payment that was.

Between a fee and a premium based equity purchase just shy of about $1.2 billion. We have additional milestone payments along the way about $1.7 billion, if I'm not mistaken we have.

Significant mid teen royalties associated with revenue ex U.S. that sales ex us.

Upon rolling that out ex U.S. and then we have cost here and so the cost sharing is that from the execution of the agreement actually not the closing of the agreement, but from the execution of that agreement.

She was responsible for half of all of the global.

Expenses for our development program for our Microdisplay program SRP, Nigeria Zero, one and then to the extent along the way there was any additional ex U.S. required studies roast would be roughly 100% responsible for that so with that said you want to comment on it its impact on the burn rate over the next year.

Sandy: Thanks for the question. In terms of the burn rate, to go back to your question, The Roast Deal should bring us cost-sharing payments, and that will help with the burn rate, about $75, maybe even $100 million this year and in the next few years. But aside from that, the Rose Dude is primarily about bulking up our finances. It gives us a significantly longer cash flow because it's almost $1.2 billion. It brings in, in addition to the PRB, also adds another $110 billion to our balance sheet. But I don't think they should be significant.

Yes, so thanks for the question.

In terms of the burn rate would your question.

The rules do you should bring us caution payments and that will help with the burn rate about 75, maybe $100 million this year and the next few years.

But aside from that the rules do this primarily about bulking up our finances gives us a significant longer Kashmir, because almost $1.2 billion. It brings and in addition, the PRB also adds another $110 million tomorrow.

Our balance sheet, but I don't think this should be significant.

Sandy: Enhancement to the modeling that work that you'd be doing, in terms of modeling the cat. And just to talk about the cash spend, if you remember last year, we had almost $300 billion in business development, primarily due to the $170 million we spent on my... In addition, we're also glad that we'll be investing heavily in gene therapy, both in 2019 and 2020. For 2019, I think they indicated about $600 to $650 million.

Enhancement to the modeling that werent that you'd be doing.

In terms of modeling of the cash spend just to talk about the cash spend if you remember last year.

Almost $300 million of business development deals, primarily due to $170 million, we spent on my Nexus.

In addition, we would also guided that we'll be investing heavily in gene therapy will be 29 Jean.

As 120, 20, I think that indicated about 600 $650 million will spend and that's really where the bulk of our spend is between business development and gene therapy manufacturing. In addition in anticipation of.

Sandy: And that's really where the bulk of our spend is, between business development and gene therapy. In addition, in anticipation of a, [inaudible] This is another area that, from an R&D... point of view, is directing us. Aside from that, I don't think our core spend should increase dramatically over what you saw in... And just going back to your question, I don't think the worst trials...

Buying this approval and that's also bumping up our inventory for a potential customers in Google. This is another area that from an R&D manufacturing perspective, the via directing some of our span.

Aside from that I don't think of course and should increase dramatically over what you saw.

Fourth quarter.

Just going back to your question I want to be most transaction significant impacts out what's your modeling aside from the castle.

Sandy: Thank you. Our next question comes from the line of Debjit Chattopadhyay from HC Wainwright: Hey, good afternoon.

Thank you. Our next question comes from the line up dip chip from H.C. Wainwright. Your question. Please.

Debjit D. Chattopadhyay: So first clarification on the PPMA program: I believe the update will be a 12-week biopsy. So if that's the case, how would you set expectations in terms of de novo dystrophin expression? And number two, for the limb girdle program, would you automatically expect a dose-dependent increase in a better cycle of glycan? Given that, historically, when we look at the XLMTM program from our dentists, a 3x increase in dose did not necessarily translate into more protein but provided a much better morphology and higher genomes per cell. So that should give more durability. So just kind of thoughts around what the expectation should be for both the dystrophin in PPMO and the protein expression for limb girdle muscular dystrophy. Thank you.

Hey, good afternoon, Sue first clarification on.

The payment program I believe the update will be 12 speak biopsy. So if that's the case how would you set expectations in terms of deal, but dystrophin expression and number two for the limb go to program would you automatically expect.

Just had been an increase in a better stack look I kind of like in given that.

When we look at the actual MTM program from a dentist a truly ex increasing those did not necessarily translate into more protein, but provided a much better morphology and higher genome supercell. So that should get more durability. So just kind of parts around what the expectation should be for a bought the dystrophin MPP.

And the especially important expression for them go to muscular dystrophy. Thank you.

Douglas S. Ingram: Okay, I'm going to give the second question to Louise, but before I do, let me touch briefly on the PPMO results. So you're exactly right, it's 12-week biopsies, and so the expectations for dystrophin shouldn't exist because we aren't even going to look for dystrophin at this early stage. As you may recall, for dystrophin expression in our PMO, it was a 48-week process before we really started looking to achieve expression. So this is early for dystrophin production. We will see exon skipping, so that will be a strong correlate to the kinds of dystrophin that you would see over time as it builds over time. And that's fine, because the actual value of this update, this really significant kind of go-no-go on PPMO, is frankly dose and safety. So to remind everyone of what the PPMO is about. So our RNA technology has the PMO, the base PMO, has two things about it that have been very laudable. It's precise, and it's safe.

Okay, I'm, Oh, I'm going to give the second question to Luisa before I do want to touch briefly on that the PBM. Our results. So you're exactly right was 12 week biopsies and so the expectations on dystrophin shouldn't exist, because where we aren't even going to look at for dystrophin at this early stage as you may recall.

For dystrophin expression for our PMO. It was it was 40 week expression before we really started looking to TCV expressed and so this is early for dystrophin production, we will see exon skipping so that will be as a strong correlate to the kinds of dystrophin that he would see over time as it builds over time, but that's and that's fine.

Because the actual value of there's nothing there is real significant kind of go no go on ppm out is frankly dose and safety so to remind.

Every one of what the PBM I was about so they are already technology has the PMO. The basically a minus two things about that had been very laudable its precise and it's safe to create exon skipping. It has taken creates dystrophin and it's very safe and safe it even at high density.

Douglas S. Ingram: It causes exon skipping, and it creates dystrophin, and it's very safe and saves it even at high doses. It has a limitation associated with it, and that limitation is that it is a neutrally charged molecule that gets into cells passively, and that's a limitation. Our goal with the PPMO is to reduce or remove that limitation by using a positively charged peptide that interacts with negatively charged proteoglycans and drags the PMO into the cell in greater abundance. Animal models tell us that it works brilliantly, at least in animal models, knowing that and that we get, if we can get to the right doses, we get very high increases in exon skipping, and therefore in dystrophin production. There are literally, at the right dose, you could get as much as an order of magnitude increase.

It has the limitation associated with it and that limitation is that is that neutrally charged molecule that it gets into cells passively and that's a limitation our goal to be PMO is to reduce this remove that limitation by using a positively towards peptide that would it interacts with negatively chart prudent glycans and drags the pm.

Though into the sell in greater blended animal models tell us that it works brilliantly at least in animal models going that.

We get if we get to the right doses, we get very high increases and exon skipping and therefore in dystrophin production. There are literally at the right doshi, who get as much as an order of magnitude.

Increase so real opportunity to be a significant improvement. The one significant question for US is that can we get to those doses can one actually get up to the kinds of doses that we would we would believe over time would develop dystrophin significantly greater than the PML and that's what we will have insight into by the middle that machine.

Douglas S. Ingram: So this has the real opportunity to be a significant improvement. The one significant question for us is, can we get to those doses? Can one actually get up to the kinds of doses that we would believe over time would develop dystrophin significantly greater than the PMO? And that's what we will have insight into by the middle of this year, safety insight, some exposure insight, exon skipping insight, and we'll have a view on our ability to get to those doses, and then we can imagine what dystrophin would look like if we looked at it. And with that, I will turn it over to Louise to answer some of the questions about the limb verbal.

As we will have safety inside.

There's some exposure inside exon skipping insight and we'll have a view on our ability to get to those those doses and then we can we can envision what dystrophin would look like if we looked at it yourself and with that I will turn over to lease to answer some of the questions about the Lindbergh.

All right. The question was around what we expect to see higher expression at this higher death given.

Louise R. Rodino: I think the question was around whether we would expect to see higher expression at this higher dose given the preclinical data. So based on our nonclinical data, you're right to say that we typically don't see changes in expression unless you're at a threefold or a half log higher dose. So in this case, we're at a fourfold higher dose in our high dose cohort, and based on our nonclinical data, we would expect to see higher levels of expression. Getting back to Doug's point, we see very good levels of expression, 50 percent, in our low dose, and this is already a transformative dose. We would, based on nonclinical data, expect to see higher levels than that, but this will be a decision based on both safety and efficacy in the end, and we'll look at the data collectively. I think to your point about higher doses, since our high dose in the limb girdle is equivalent to microdystrophin, we're quite happy with where we'd be at. If you were pushing the dose even higher, you might end up seeing saturation, and you might not see increased levels of expression.

The preclinical data so based on our Nonclinical data, you're right to say that we typically don't see changes and expression.

Unless you're out a threefold or half blog.

So in this case, we're at a fourfold higher dose in our high dose cohort.

On our Nonclinical data, we would expect to see higher level of expression.

Getting back to that point, we we see very good levels expression, 50% and our loved Allison. This is already a transformative does.

We would be some nonclinical data expect to see above that but this will be a decision based on safety and efficacy and then well look at the data collectively I think to your point about higher doses since our our high dose and limb girdle is equivalent to micro distress and we're quite happy with.

It would be out if you were pushing that does have been hires where you might end up seeing saturation that you might not see increased level of expression. So in the dosing levels that were on based on Nonclinical data.

Louise R. Rodino: So at the dosing levels that we're on, based on nonclinical data, we feel like we're in a very good range to see increased expression. Thank you. Our next question comes from the line of Anupam Rama from J.P. Morgan. Your question, please. Hey guys, thanks so much for taking the question. Just a quick one from me. I guess following on some of the limb girdle questions, it sounds like we're going to have a pretty good look in 2Q of, So what's that incremental work that needs to be done between the 2Q update and when we get dose selection?

Feel like we're in a very good ranged Sydney increased expression.

The Q our next question comes online.

From a from JP Morgan your question. Please.

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

Just a quick one for me I guess following on some of the limb girdle questions. It sounds like we're going to have a pretty good look into Q Oh.

Kind of expression and then safety and other factors so what's the incremental work that needs to be done between.

Unknown Executive: That's a great question.

The Twoq you update and then when we get.

Douglas S. Ingram: A lot of time. So we're going to look at that data, and we'll have it presented at a medical meeting in the second quarter. We just want to make sure that we're thoughtful, that we make sure we've looped in the DSMB in the process, and the like. Honestly, there's not a ton of work to do from reviewing the data and releasing the data to the actual dose selection, but we just want to make sure, for technical reasons, that we don't overpromise and that we can make a formal dose selection in the third quarter. So not an enormous amount of work.

Sort of dose selection. Thanks, so much.

That's a great question.

Not a time so we're going to look at that data. We'll have we'll have it presented in at a medical meeting in the second quarter. We just want to make sure that we're thoughtful that we make sure we moved in the DSMB B.

In the process and the like so if we're honest.

Honestly, there's not a kind of work to do from reviewing the dad and releasing the data to the actual does selection, but we just want to make sure for for technical reasons that where we've done over promise and that we can make a formal this election in the third quarter. So not have enormous amount of work.

Thank you. Our next question comes in the line of Salveen Richter from Goldman Sachs. Your question. Please thanks for taking the question. This Thrace on first I'll be in so just given the current timelines with stay one or two in one of three and expectations for.

Salveen Jaswal Richter: Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Your question, please. Thanks for taking the question. This is Rahsaan for Salveen.

Unknown Executive: So just given, you know, the current timelines with studies 102 and 103 and expectations for, you know, 102 that last patient in December of 2020, do you guys think you're still in a position to conduct that three-month comparatability by, you know, I guess, by year-end or even early 1Q20? If not, when should we expect that to occur? And then I just have a follow-up on the MPS-3 study.

One or two that last patient in December 2020.

Do you guys think you're still in a position to conduct a three month compared ability.

And I guess, you know by year end or even early one Q 20, if not when when should we expect that to occur and then I just have a follow up on the MPS three study.

Douglas S. Ingram: Yeah, so on that, the short answer is yes, we're still progressing well. In fact, you know, this is study 301, to remind everyone, which is a significant international multi-center trial. So we also believe there's going to be significant demand for that trial, and we'll be recruiting, I think, briskly when that study starts. So we feel right now we have a lot to do. So it is always, it's always risky predicting the future, but we feel good that we'll be in a position to look at both functional data out of 102 and, at the same time, look at with respect to a subset of 301, an appropriate subset of 301 expression safety and CMC-related work in early 2021. So we think

Yes, so on that the short answer is yes, we're still progressing well.

Right.

This is that the study three one to remind everyone is a significant international multicenter trial. So we are also believe there's going to be significant demand for that trial that will will be recruiting I think.

Briskly when that studying starts so we feel the right now there's a lot to do so it's always it's always risky predicting the future, but we feel good that will be in a position to look at both functional data out of one or two and at the same time look at with respect to a subset of three a one appropriate subset of three or one.

Expression safety and CMC related work.

In early 2021, so we think we're on track.

Unknown Executive: And if I might intervene just for a second, Doug, I just want to make sure it's quite clear that the last patient in to 102, well, has already occurred. We're talking about the last patient in question, I would actually imply that it was the last patient in, essentially, the last patient's last visit for the one year of functional data. Just to be sure that I was clear.

As we make intravenous or second Doug I want to make sure. It's quite here the last patient into one of them to law has already occurred.

Junkie last patient answer that.

Question on flagships items last patient in essentially the last patient last business, yes, indeed for the one year functional data just so be sure that it was clear on that yes. So one of the two was the bulk of one of one or two was it was all dosed in.

Douglas S. Ingram: Yeah, so what one or two was the bulk of what one or two was all dosed in In 2019, as you know, it was a 40-patient study. It's now a 41-patient study. One patient was dosed in early 2020, and that will result in the last patient having his last visit in December. We'll be able to compile that information unblinded and have those results in the first quarter of 2021. And at that same time, if everything goes to plan, we should also have expression, CMC, and safety data from a subset of study 301, which is the commercial material trial.

In 2019 as you know it was a 40 patient studies now 41 patient study one patient was dosed in early 2020 that will result in the last patient last visit in December we'll be able to compile that that information on blinded and have that those results.

In the first quarter 2021, and at that same time, if we if everything goes to plan will also we should also have expression.

CMC and safety data from from a subset of study three one.

Which is the commercial material trial.

Unknown Executive: Our next question comes from Vincent Chen from Bernstein. Your question, please. Great, thank you very much for taking the question. On the manufacturing process for your DMT gene therapy, what are the major analytical assays that are remaining to be developed or finalized? And one specific question: what is the potency assay that you use? And have regulators indicated that it's satisfactory, or is that still being sorted out?

Thank you.

Next question comes on the line from fits in Chen from Bernstein. Your question. Please.

Great. Thank you very much for taking the question on the manufacturing process for your DMT gene therapy, what are the major analytical acetate their remaining to be developed for finalized and one specific question. What is the potency assay that you use and have regular indicate that says factory or is that still being sorted out.

We still want to touch on that that question.

Louise R. Rodino: Louise, do you want to touch on that question?

It's worth it.

Louise R. Rodino: All of the release assays have been developed. They're just in the final stages of validation. Currently, we're using an in vivo potency assay, with an in vitro potency assay in development.

Oh really sets have been developed at best and final stages.

Validation. So currently our were using a in vivo patents yesterday with a in vitro see assay in development.

Whitney Item: Thank you. Our next question comes from a line from Whitney Item from Guggenheim. Hey guys, just a quick question from me, and sorry if I missed it, but for the NPS 3A program, I think you said 17 patients treated. Can you remind us what the time point for the primary end point is and if there are any interims or any potential to get kind of an interim read on that, given you have treated a significant number of patients there? Thanks.

Yes.

Yes.

Thank you. Our next question comes on line of Whitney Ijem from Guggenheim. Your question. Please.

Hey, guys. Just a quick question for me and sorry, if I missed it but for the Dampier three a program I think he said 17 patients treated can you remind us what the timeframe for the primary endpoint is an up there any interest or any potential to get kind of an income read on that giving you have treated a significant never a patient there. Thanks.

Gil Blum: Yeah, so the current protocol is a 20 patient study. Our goal is to have all the patients dosed before the middle of this year. We're obviously well on the way to that, 17 of 20 have already dosed. It's against a matched natural history cohort. It's a two-year study with a one-year interim, so there is the chance of an interim look at the data in the middle of 2021.

Yes. It is the current protocol has led to 20 patient study. Our goal is to have all the patients dose before the middle of this year, obviously well on the way towards that 17 of 20 already does its.

Against the matched natural history cohort, it's a two year study with a one year interim so there is the chance of an interim look at the at the data in the middle of 2021.

Joseph Patrick Schwartz: Thank you. Our next question comes from the line of Joseph Schwartz from SVB Lyric. Good afternoon. Thanks for taking our questions. This is Dagon dialing in for Joe.

Thank you. Our next question comes from Windup, Joseph Schwartz from SBB Leerink. Your question. Please.

Good afternoon. Thanks for taking your question. This is our take on dialing in for Joe I'm, just a question and a follow up if I may regarding your PMO filing strategy. So what you're rolling NDA submission to initiate a for CASM Mersenne I. Following your Golar Dursun experience I was wondering if there's any additional requirements.

Unknown Executive: Just a question and a follow-up, if I may, regarding your PMO filing strategy. So, with your rolling NDA submission initiated for Kazimerson, following your GoloDursen experience, I was wondering if there are any additional requirements to submit that NDA or any particular commitments on your part, either prior to or after the potential approval. And sorry if I missed this, but can you clarify the guidance for the Mission 51 confirmatory trial for Ediplersen? I understand Essence is due to complete by 2024, but I wanted to get the number for Mission 51, please.

To submit that and D.A. or any particular commitments on your part either prior on or after the potential approval and sorry, if I missed this but can you clarify the guidance for the mission 51 confirmatory trial for Eteplirsen.

Just Dennis instance, due to complete by 2024, but I wanted to get the number for admission 51. Please.

Douglas S. Ingram: So going through the PMO strategy, the short answer is no. We had a very positive, very thorough review from the neurology division, at the end of which the neurology division firmly recommended approval of that therapy. And of course, while there was a delay, it got that approval for us. And so we're going to follow the same pathway for Kazimiercin. We're in the midst of a rolling NDA. We should have that rolling NDA completed in the second quarter. Then we'll have our PDUFA date.

So going to the PMO strategy. The short answer is now we had a very positive very thorough review from Neurology division at the end of which the neurology Division formally.

A recommended the approval of that therapy and of course, while there was a delay it was it.

Got that approval for us and so we're going to follow the same pathway for cashmere, saying, we're in the midst of enrolling India. We should have that rolling out the completed in the second quarter that we'll have our PDUFA date will be.

Douglas S. Ingram: With respect to Teplersen, I apologize; I missed the exact question. The short answer with respect to Teplersen, just to remind everyone, is that we have a confirmatory study with respect to Teplersen. It really is two studies. It required first a healthy human volunteer study. I would remind everyone that this is a bit of an unusual confirmatory trial. If you imagine a normal confirmatory trial using a placebo control, you would have the current dose approved versus a placebo control. This is different. This is our current dose versus an escalating higher dose of Teplersen to really ask the question if even higher doses of Teplersen would confer additional benefits over the benefits already achieved with the current dose of Teplersen. That required, because those doses were not yet approved, that required, as a predicate, a healthy human volunteer study to be conducted to ensure that it was safe, and that was completed and read out, and it was safe, and we've commenced study 402 remission, and we're on our way with it. But was there a very specific question? I mean, the short answer is that we're on our way. It'll be Obviously, it'll take some time to complete that study.

Providing updates along the way.

With respect to top worsen, where because there was I apologize I missed the exact question sort of answer with established and just to remind everyone is that we have a confirmatory study with respect to temper citigroup. It really is two studies. It required first helping human volunteer study I would remind everyone that this is a bit of an unusual confirmatory trial.

Well you imagine the normal confirmatory trial using a.

Well see both control you would have the current dose approved versus the placebo control. This is different this is our current dose.

Versus an escalating higher dose of a kept worsened.

He asked the question is even higher doses of a tough worsen would confer additional benefit over the benefits already achieved the current dose of a tupperware, saying that required because that those doses were not yet a proof that required as a predicated a.

A healthy involved volunteer study to be conducted to ensure that it was safe and that was completed and read out and it was safe and we've commenced study for a two were mission and where we're on our way with it but it was very very specific question I missed the short answer is well underway they'll be obviously it'll take some time to complete that study.

Thank you. Our next question comes on line of Tim to go from William Blair. Your question. Please.

Tim Lugo: Thank you. Our next question comes from Tim Lugo from William Blair. Your question, please. Hey, this is Lachlan on for Tim. Thanks for taking the question. I was wondering if you could provide an update on the number of patients that have enrolled in the second site for the microdistribution studies at UCLA and whether you've sort of seen or heard any differences in the experience there compared to dosing in the prior patients at Nationwide, especially as it pertains to safety.

Hi, This is lock on attempt thanks for taking my question.

I was wondering if you could provide an update on the number of patients that have enrolled in the second thoughts that micro district study that you see a law and whether you sort of state or any differences in the experience that competitive dosing.

In the prior prior patients a nationwide, especially as it pertains to safety.

Unknown Executive: Tolerability

Tolerability.

Douglas S. Ingram: Sure, answering your first question first, the bulk of the patients obviously were enrolled and dosed at Nationwide Children's Hospital under Dr. Jerry Mandel. He had the bulk of the patients before we had increased the end of the trial from 24 to 40 and what became 41. So the bulk of the patients who were at Nationwide. And answering your second question, the answer is no.

Sure. The first the after your first question first the bulk of the patients obviously were were enrolled and dosed at nationwide children's hospital under Dr., Jerry Mendell as he had the bulk of the patient before we have increased the end of the trial from 24 to 40 and what became 41.

So the bulk of the basins, where nationwide and answering your second question the answers now.

We have heard of no significant differences in experience between the two cents.

And just add to that of course lines. This is a blinded study. So of line has been maintained and so.

Douglas S. Ingram: You may I just add that, of course, the blind. This is a blinded study, so the blind has been maintained.

Let me jump by the experience experiences type level.

Lisa Baker: We can't comment on safety or efficacy experiences, so that data remains lying to us. Thank you. Our next question comes from the line of Lisa Baker from JMP Securities. Your question, please. Hi, thanks for taking the question. Doug, you seem a little hesitant about the Commercial Supply Study 301. Can you maybe comment? Are you tracking? Is everything going as planned thus far? And just to clarify, are you expecting the GMP product to be available in July, or is that when the study will actually start enrolling? Just to clarify that. Thanks.

Comment on safety or see experience update remain blinded.

I was sorry, I was doing rendered.

We recognize your exit.

[laughter].

Thank you. Our next question comes in the line at least the big from JMP Securities. Your question. Please.

Hi, Thanks, taking my question.

A little hesitant on.

On the commercial by study three one can you maybe.

Are you tracking as everything going as planned but are you.

And just to clarify are you expecting GMP product to be available in July or is that when study will actually start.

Start enrolling.

Douglas S. Ingram: The short answer is the team is doing brilliantly. I can give nothing but kudos to our technical operations team and our clinical operations team for progressing towards the commencement of Study 301. We've done great work in process development, clinical development, and site readiness, so we're tracking right now, and we will have GMT material released in July. The precise date that we will commence the trial is predicated on three things.

Hi, though.

Yeah.

The short answer is the team's doing brilliantly I can give nothing for kudos to our.

To go operations team and our clinical operations team and progressing towards the commenced study three one we've done a great work from a process development and clinical development at site rate. So we're tracking right now and we will have GMP material released in July.

The precise date that we was commenced the trial is predicated on free things. It's proved it is certainly predicate on having that material available that is an enormously significant part of this and that's why we were so excited to have to be achieving commercially viable yields by the end of 2019 and with the fact that we were able to start engineering run.

Douglas S. Ingram: It is certainly predicated on having that material available. That is an enormous amount of material. A significant part of the, That's why we were so excited to be achieving commercially viable yields by the end of 2019. And the fact that we were able to start engineering runs was exciting for all of us. The idea that we were able to start GMP runs was exciting for us as well.

This was exciting for all of US the idea that we will start GMP runs was exciting for us as well of course, we built an enormous amount of capacity to be ready for that.

Douglas S. Ingram: And of course, we've built an enormous amount of capacity to be ready for that. Then the two other things that we have to do along the way are we have to have site readiness. That means we have to get all the sites initiated and trained and the like. I think we're well on the way to getting all of that done. And the team's very focused on that. And the third thing that we're going to have to do as a prerequisite is to gather the data and engage with the agency and ensure that we're on the same page with the agency to commence the study. We have much to do, but we have made an enormous amount of progress if one stands back for a bit and considers where we were at the beginning of this journey just a year and a half or so ago, and we're tracking well to the commencement of study 301, and we're tracking well to the completion of study 102.

The two other things that we have to do across the way our.

We have to we have site readiness that means we have initiated a train to alike.

I think we're well on the way to getting all of that down to the teams very focused on that as the third thing that we're going to have to do is a predicate is to gather the data and engage with the agency and ensure that we're on the same page with the agency to commence the study three one so.

Much to do but we have made an enormous amount of progress if one stems back for a bit and considers where we were at the beginning of this journey, just a year and a half or so ago yeah.

Tracking well to the commencement of three or wind and we're tracking well to the completion of study one or two.

Douglas S. Ingram: Thank you. Our next question is a follow-up on the line from Christopher Mariah from Nomura Institute.

Thank you. Our next question is a follow ups and the line up because from right from the more.

Vincent Chen: Your question, please? Hi, yeah, thanks for taking the follow up. I was wondering if you can comment perhaps on the phase three trial and its design for the gene therapy product 9001. I guess Pfizer reported their Trail Design or recently announced their trial design on clinical trial.gov. It appears they are dosing patients with their gene therapy as well as a steady dose of steroids throughout the period of the trial, so it seems to be on top of steroids. And I was wondering if you could comment on your plans for any regulatory discussions in that regard. Because, as I recall, you're not dosing on top of regular steroid doses.

Your question please.

Hi, Thanks for taking the follow up I was wondering if you can comment perhaps on.

The phase three trial.

It's designed to report.

Therapy product nine there one I guess thought Pfizer reported there.

Hi, the trial design, or recently announced Carlyn and clinical trial the blackout.

It appears war on.

Tens in patients with their gene therapy, as well as Doug Stapleton said steroids.

Note.

The period of the trial. So it seems to be on top of steroids. I was wondering if you could comment on your plans or any regulatory discussions on in that regard I recall you are not dosing on top of regular stairway doses. Thanks.

Douglas S. Ingram: Thanks.

So with that.

Douglas S. Ingram: Boys with Duchenne Muscular Dystrophy are a standard of care on steroids. So we would maintain in all of our studies children on regular steroids throughout the study. We also have a protocol to modestly increase steroids in advance of the treatment as a prophylaxis, which is typical so we've you know the study 301 tracks toward the commencement and we've talked about the design before it hasn't changed in a significant way it is a currently envisioned to be a one-to-one placebo control trial in the main study 301 it's currently envisioned to be four to seven years old it'll be a multi-center trial as well obviously blinded we will separate studies as well along the way and we're moving as fast as possible for them as well one of those is a study we call 303 which is for study focused on non-ambulatory patients we think it's extraordinarily important to focus as well on the non-ambulatory patients even though I think there's a strong argument that in the United States one can achieve an approval across a broader age group when the mechanism of action would presume that that all age groups would benefit even if you studied a smaller age group but both for access and reimbursement purposes in the United States as well as for approvals ex-us it's important that we study a broad age population and we'll do that through study 303 as well as through 301.

Boys with Duchenne muscular dystrophy are as standard of care on steroids. So we would maintain and all of our studies children on a regular steroids throughout the study. We also on the protocol to modestly increase there would you need to answer the treatment as approved prophylactic.

Which is typical.

We still him the study three one tracks.

Toward the commencement in that we've talked about the design before hasn't changed in a significant way.

It is a currently in addition to be a one to one placebo controlled trial and the main study three one it's currently vision to before to seven years old it'll be a multi center.

Trial as well, obviously blinded we will have separate studies as well along the way and we're moving as fast as possible for them as well one of those is a study we call three or three which is we're study focused on non ambulatory patients. We think it's extraordinarily important to focus as well on the non ambulatory patients, even though I think there's a strong.

Argument that in the United States, one can achieve.

And approval across a broader age group when the mechanism of action.

I would presume that that all age groups would benefit even if you study the smaller age group by both for access and reimbursement purposes in the United States as well as for approvals ex U.S.. It's important that we study abroad age.

Population and we'll do that through studies, we have three as well as through three or one.

Douglas S. Ingram: Thank you. This does conclude the question and answer session for today's program. I'd like to hand the program back to Doug Ingram for any further remarks.

Q.

This does conclude be question answer session of today's program I'd like to hand, the program back to Doug Ingrid commit any further remarks.

Douglas S. Ingram: Thank you all for joining us this evening and for your questions. We appreciate them all. As I think everyone can see, we've made a lot of progress over the last few years toward our broader vision of becoming one of the most significant leaders in genetic medicine focused both on RNA and the build of this, what we believe to be a profound gene therapy engine upon which we are working. So thank you very much for that. I look forward to the opportunity over the course of 2020 to keep everyone updated as we progress. Thank you.

Thank you all for joining us this evening for your questions. You appreciate them all as I think everyone can see.

We've made a lot of progress over the last few years toward our broader vision of becoming one of the most significant leaders in genetic medicine focus both on ordinary and to build of this what we believed to be profound gene therapy engine upon which we are working 2020, well be an enormous.

The important year for us we've got a lot to do here and if were successful in doing it and if science.

Cooperates with us.

Then we will make an enormous leap towards achieving our vision of bringing a better life to countless patients who are living with the generating from far too often dying from.

Unknown Executive: Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.

Rare genetic disease. So thank you very much better look forward to the opportunity over the course of 2020 to keep everyone updated as we progress.

Thank you.

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

[music].