Q3 2019 Earnings Call

Hi, all participants' lines are in listen only mode.

Operator: These lines are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star then 1 on your telephone. As a reminder, today's call is being recorded. And now, I'd like to introduce your host for today's program. Ian Estepan, Senior Vice President, Chief of Staff, and Corporate Affairs. Please go ahead. Thank you, Michelle, and thank you all for joining today's call. Earlier today, we released our financial results for the third quarter of 2020. The press release is available on our website at www.sarepta.com, and our 10-Q was filed with the FEC earlier this year. Joining us on the call today are Doug Ingram, Sandy Mahame, Bo Cumbo, Dr. Gilmore O'Neill, and Dr. Rodino Claypack.

After the speakers presentation, there will be a question answer session.

Ask a question during this session you would need to press Star then one on your telephone.

As a reminder, today's call is being recorded.

And now I'd like to introduce your host for today's program.

And that's the <unk> senior Vice President Chief of staff in Corporate Affairs. Please go ahead.

Thank you Michelle Thank you all for joining today's call earlier today.

So results third quarter 29.

The press releases are available on our website www dot com and our 10-Q.

Okay, well combo, Dr. Gilmore, Aneel and Dr. Regina.

Operator: After our formal remarks, we'll open up the call for questions. I'd like to note that during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risk and uncertainty, any of which is beyond Sarepta's control. Actual results can materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations, and the trading prices throughout this conference. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on forms in queue 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 or circumstances.

For questions.

I'd like to know that during this call will be making a number of forward looking statement, we take a moment to review our slide on the webcast which contain forward looking.

These forward looking statements involve risks and uncertainty which are beyond <unk>.

Actual results could materially different from these forward looking statement.

Any such risks and materially and adversely affected.

Operation trading prices are up.

Description.

Certainly we encourage you to review the most recent quarterly report on Form 10-Q .

Exchange Commission as well.

The company does not undertake any obligation to publicly update.

Any financial projections provided today based on subsequent events or circumstances.

Ian M. Estepan: And with that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress. Thank you, Ian. Good afternoon and evening, and thank you all for joining us at Sarepta Therapeutics' third quarter 2019 conference. Our ambitious strategy involving one of the deepest multi-platform genetic medicine pipelines in biotech has required focused execution over the course of 2019. To remind you, we have more than 25 active programs across our RNA and gene therapy platforms, and we're either actively in or in late stage planning for some nine human clinical trials to advance our plan. I am pleased to say that over the course of 2019, and in the third quarter specifically, we have made very significant strides in advancing our programs and our strategic vision, and I am excited to discuss those advancements.

With that let me turn the call over to our CEO .

We'll provide an overview on our recent progress.

Thank you.

Good afternoon, and evolving and thank you all for joining us.

First Sarepta Therapeutics third quarter 2019 conference call.

Our ambitious strategy is holding one of the deepest multi platform genetic medicine pipelines in biotech that's required focused execution over the course of 2019.

To remind you we have more than 25 active programs across our ordinary and gene therapy platforms.

Where either actively in importantly exchange planning for some nine human clinical trials.

To advance our plants.

I'm pleased to say that over the course of 2019.

Third quarter, specifically, we have made very significant strides in advancing our program and our strategic vision and I'm excited to discuss does advancements. However, we're doing so we must also knowledge what we all know.

Ian M. Estepan: However, before doing so, I must also acknowledge what we all know, that we had a setback in the third quarter, and rather than burying it among or after a discussion of our successes, I will begin by commenting on our CRL disappointment. [inaudible] Having worked diligently on our submission for BIONIS 53, the generic name for which is Gola Dursun, for well over a year, and based on all Instead, as you know, we were surprised to have received a complete response letter, also known as a CRL, signed by the Office of Drug Evaluation 1. Our disappointment extends beyond Sarepta to the 8% of Exxon 53 amenable DMV patients in the United States, you degenerate every day while they await access to this therapy.

We have shot back in the third quarter and rather than bearing on or after a discussion of our successes I will begin by commenting on our CRL disappointment.

Well over a year in based on all of our interactions with the division of neurology products.

We were very confident that we would obtain approval on our PDUFA date.

Which was August 19th.

Instead as you know we were surprised you have received a complete response letter.

Also known as the CRL signed by the opposite drug evaluation one.

Our disappointment extends beyond sarepta to the 8% of exon 53 medical DMD patients.

I did states you the generate every day.

Well the away access to this therapy.

Ian M. Estepan: When I joined Sarepta, I made some commitments externally and in the division of neurology. We intended to build a positive relationship with the Division of Neurology, one founded on transparency and on solid evidence-based science, and consistent with that commitment. We will work with the agency to address the reasons for the CRL and determine a pathway for a potential approval if one is possible. I have heard from those who would prefer that I speak more often and more publicly on this issue, or that I would attempt to engage the patient community or others, to assist, for instance, in applying external pressure to bring this therapy along faster. I have no intention of doing either of those things.

When I joined Sarepta I made some commitments externally ended a division of neurology.

We have tended to build the positive relationship with a division of neurology one founded on transparency.

So we haven't space science.

Consistent with that commitment.

He will work with the agency to address the reasons for this year route.

And determine a pathway for a potential approval.

One is possible.

I heard you know she would prefer that I speak more often and more publicly on this issue.

And the war that I would attempt to engage the patient community or others.

To assist for instance in applying external pressure to bring this therapy along faster.

I have no intention of doing either of those things.

Douglas S. Ingram: If we can win the day with this therapy and with this issue, we will have done so on the science and on the regulations and in collaborative evidence-based discussions with our reviewers at the FDA. Now I've also heard some speculation about the implications of the CRL, so let me take a moment to address these as well. First of all, this CRL does have implications for our submission for our next PMO, Kazimir. As they are closely related, we will await...

If we get when today with the stare be and with this issue.

We will have done so on the science.

On the regulations.

With that evidence based discussions with our reviewers yes, yes.

Now I've also heard the speculation about the implications of the CRM. So let me take a moment to address these as well.

First of all I honesty already does have implications for our submission.

Nice PMO CASM ex.

They are closely related we will await.

Douglas S. Ingram: Clarity on the Biondis matter before we submit for Kazim Nursin in the United States. But let me disabuse anyone who might have concerns about our other programs. The CRL does not have any read-through to our microdystrophin gene therapy program.

Clarity on the buy on this matter before we submit for CASM nurses in the United States.

But let me disabuse anyone who might have concerns for other programs.

Well does not have any read through to our micro dystrophin gene therapy program.

Douglas S. Ingram: The CRL involved two safety signals in connection with an application for an accelerated approval. However, our microdiscipline program is overseen by a different part of the FDA, CBER, and we are not seeking accelerated approval there. There is simply no overlap in either substance or person.

The CRL involved to safety signals in connection with an application for an accelerated approval.

Our micro distribute program is overseen by a different parts of the FDA.

Fever, and we are not seeking accelerated approval there there is simply no overlap.

Neither substance or personnel.

Douglas S. Ingram: [inaudible] To those who may believe that the CRL suggests some sort of bias... On behalf of the Division of Neurology towards Sarepta, I would unequivocally and emphatically disagree. Let me reiterate that I remain convinced that we were treated very fairly and professionally by the Division of Neurology. Also, I am very proud of the Sarepta team and how they comported themselves during this review.

Second.

To those who we believe that the CRL suggested some sort of bias.

On behalf on behalf of the divisions of neurology towards Sarepta.

I would unequivocally anatomically disagree.

Let me reiterate that I remain convinced that we were treated very fairly and professionally.

Division of neurology.

So I'm very proud at the strip the team and how they reported themselves. During this review from my perspective, we have gone a long way in the last two in out years.

Douglas S. Ingram: From my perspective, we have gone a long way in the last two and a half years in forging a positive evidence-based working relationship with the division. We will work diligently to address the myondus CRL. But with that, I do not intend to provide a prediction on outcome or on timing or to provide interim views during the process.

In forging a positive evidence base working relationship with the division.

We will work diligently to address the buy on this CRM.

But with that I do not intend to provide a prediction on outcome.

We're on timing where to provide interviews during the process. However, I will provide an update to the patient physician and investment communities.

Douglas S. Ingram: However, I will provide an update to the patient, physician, and investment communities once we have definitive clarity on the outcome of those. Now moving to our positive achievements in the quarter, we have made some enormous amounts of progress in this third quarter. Exondus continues to perform well with third-quarter sales above consensus at $99 million, that is a 26% increase over the same quarter last year.

Once we have to faded clarity on the outcome of those discussions.

Now moving to more positive achievements in the quarter. We have made some enormous amount of progress in this third quarter.

Sean just continues to perform well with third quarter sales above consensus at $99 billion that has a 26% increase over same quarter last year.

Douglas S. Ingram: Commenting for a moment on our confirmatory trial for Exandus, to remind you this trial comprises three arms, one with extravagance at 100 units per cake, and another at 200 mg per cake versus our current dose at 30 mg per cake. The trial design, which was an FDA requirement, will answer whether higher doses of exondus provide even more benefit than the currently approved dose. Now since the comparator arms involve higher doses than the currently approved dose, we were required to begin our confirmatory trial with a healthy human volunteer study. We have completed this trial, and based on the results, we have initiated the main confirmatory trial. We will begin dosing this quarter.

How many for a moment honor confirmatory trial for Ics honest to remind you. This trial to break comprises three arms.

One would think scientists at 100 makes for keurig.

And then other at 200 makes for Keurig versus our current dose at 30 makes for kit.

The trial design, which was a hefty a requirement will answer whether higher doses of axon. This provides even more benefit.

Then the currently approved UBS.

Since the confirming the comparator arm involve higher doses then the currently approved dose we were required to begin our confirmatory trial with a healthy human volunteer study.

We have completed this trial and based on the results. We have initiated the main confirmatory trial, we will be getting dosing this quarter.

Douglas S. Ingram: Staying on our RNA franchise, we have moved to our multi-ascending dose trial for our next generation RNA platform, the PPMO, and we are dosing trial participants now. We will have safety and dosing insight in 2020. If our PBMO shows encouraging results, in addition to SRP 5051, that's the construct that we're currently in a multi-ascending dose trial regarding, we have five additional constructs that have already been built, which in total have the potential to treat as much as 43% of the BMD community.

Staying on our ornate franchise, we have moved to our multi ascending dose trial for our next generation already <unk> platform the PBM.

And we are dosing trial participants participants now.

We will have safety and dosing insight in 2020.

Our PBM those shows encouraging results. In addition to SRP 50, 51, such that concert that we're currently in a multi ascending dose regarding we have five additional constructs that have already been built which in total have the potential to treat.

As much as 43%.

DMD community.

Douglas S. Ingram: We are also conducting research now on new therapeutic targets that could be served by our PPMO platform. Moving next to our gene therapy platform, as you know, we are expending enormous resources and energy to build out our vision of an enduring gene therapy end. Between our research and clinical stage programs, we have more than 14 therapeutic candidates advancing through research and development. We have made great progress thus far this year and quarter, led by our most advanced program, SRP 9001 for DMD, which, at least to my knowledge, is the highest potential late-stage gene therapy program currently in biology. As you should be aware, our double-blind, placebo-controlled, SRP9001 microdistrophin trial, the trial that we call Study 2, was fully dosed by mid-year, but we took advantage of the availability of additional study material and previously announced that we had increased the study N from 24 patients to 40 patients, significantly increasing the study power and confidence in this study. In addition to our initial site with Dr. Jerry Mendel at Nationwide Children's Hospital, we have added a second site at UCLA with Dr. Perry Shea.

We're also conducting research now new therapeutic targets that could be served by our PMO platform.

Moving next door gene therapy platform as you know we are spending enormous resource and energy to build out our vision of an enduring gene therapy edge.

Between our research and clinical stage programs, we have more than 14 therapeutic candidates advancing through research and development.

We have made great progress thus far this year end quarter led by our most advanced program SRP nine 001 for DMD, which at least to my knowledge is the highest potential late stage gene therapy program currently in biotech.

You should be aware or double blind placebo controlled SRP nine 001 micro dystrophin trial the trial that we call study too.

Was fully dose by mid year, but we took advantage of the availability of additional study material and previously announced there'll be an increase the study yen from 24 patients to 40 patients significantly increasing the study power and confidence in this study.

In addition to our initial site with Dr., Jerry Mendell that nationwide children's hospital, we have added a second sight that you see away with Dr. Perry shape, I'm very proud to be associated with that clinician and investigator. Both sides are actively dosing patients that we remain on target to complete our dosing.

Douglas S. Ingram: I'm very proud to be associated with that clinician and investigator. Both sites are actively dosing patients, and we remain on target to complete our dosing by year end. Microdystrophin manufacturing is progressing well.

Right.

Mike or disturbing manufacturing is progressing well from a capacity perspective Brammer has now completed the build out of our single use micro distributed manufacturing facility.

Douglas S. Ingram: From a capacity perspective, Brammer has now completed the build-out of our single-use microdystrophin manufacturing facility in Lexington, Massachusetts. We also have dedicated suites with Paragon in Maryland with actually substantially greater capacity than our dedicated Lexington facility, which means we have robustly secured capacity well in advance of launch. Our analytical development work proceeds well, and we continue to make progress on process development and yield optimization. Given our recent capacity... Analytical development and process development progress, we remain on track to commence our next trial, Study 301, with commercial development supply by mid-2020. Study 2 is being conducted with clinical material from Nationwide Children's Hospital. Study 301 will be a multi-center, multi-country, placebo-controlled trial using commercial process material from our hybrid manufacturing model with Brammer and Paragon. The main study will include DMV patients ages 4 to 7, but we are also planning a separate study for older and non-ambulatory patients as well.

Turning to Massachusetts.

We also have dedicated suites with Paragon in Maryland.

We've actually substantially greater capacity that our dedicated Lexington facility.

Which means we have robust we secured capacity well in advance of launch.

Our analytical development work precedes well and we continue to make progress on process development and yield optimization.

Given our recent capacity.

Analytical development and process development progress we remain on track to commence our next trial study real one with commercial development supply.

I made 2020.

No study to is being conducted with clinical material from nationwide children's hospital.

Study 301 will be a multicenter multi country placebo controlled trial using commercial process material from our hybrid manufacturing model.

With brammer imperative.

The main study will include DMD patients ages four to seven.

But we're also planning a separate study.

For older non ambulatory passion patients as well.

Douglas S. Ingram: Commenting on a few of our other gene therapy programs, following exceptional expression and biomarker results in our first three-patient cohort dosed with our construct for Lim-Girdle 2E, in October, we announced positive nine-month functional results in that same cohort. Consistent with robust expression of the native beta-sarco-glycan protein that is the cause of the disease, all patients improved on every functional endpoint by the nine-month time point. Consistent with the protocol, we will treat an additional three-patient cohort with a higher dose, and then, in early 2020, we will decide on the dose for what we hope to be the pivotal trial. These results will help inform dosing, not only of our 2E program but also of other limb-verbal programs.

Comedy on a few of our other gene therapy program programs follow the exceptional expression in biomarker results in our first three patient cohort dosed with our constructs for limb girdle too he.

In October we announced positive nine month functional results in that same covert.

Consistent with robust expression of the native beta Starkel blanking on protein that is the causes the disease all patients improved on every functional endpoint by the nine month time point.

Consistent with the protocol, we will treat an additional three patient cohort with a higher dose and then in early 2020 people decide on the dose for where we hope to be the pivotal trial.

These results will help inform dosage not only of our TV program, but also on the other liberal programs in our pipeline.

Douglas S. Ingram: Inara Bhatt, We will also meet with the FDA in the near term to discuss the development pathway for our lingernal programs, and informed by this and further work on manufacturing, we will provide an update on the clinical pathway and the timing for our limb girdle portfolio in 2020. Next, led by our partner, Lysogene, the ADVANCE gene therapy study for MPS3A, also known as Sanfilippo syndrome type A, is proceeding well, with 13 patients having been dosed to date. MPS 3A is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and the spinal cord, causing severe cognitive decline, motor disease, behavioral decline, and, unfortunately, death.

We will also meet with the FDA in the near term to discuss the development pathway for limb girdle programs.

And informed by this and further work our manufacturing we will provide an update on the clinical pathway and the timing for our limb girdle portfolio.

2020.

Next led by our partner Lysa gene the 80 Vance gene therapy study for M. P. S. Three a also known as San Felipe Dos syndrome tie back.

Is proceeding well with 13 patients.

Having been dose to date.

MPS three a is a rare autosomal recessive lysosomal storage disease, the primarily affects the brain and the spinal cord, causing severe cognitive decline motor disease.

He's year old decline and unfortunately data young age.

Douglas S. Ingram: AVANCE is a single-arm trial evaluating the safety and efficacy of an RH10-mediated gene therapy to deliver the missing SGSH gene with the goal of robustly expressing the missing enzyme in the brain that is the cause of MPS3A. Moving to Charcot-Marie-Tooth, or CMT, Dr. Zarif Sahank of Nationwide Children's Hospital intends to commence dosing of the proof-of- CMT is the largest inherited neuromuscular disease in the world, and CMT1A, a devastating peripheral nerve disease, is also the most prevalent form of CMT.

Advances a single arm trial evaluating the safety and ethic efficacy and our each 10 mediated gene therapy to deliver the missing SG as H. gene.

With the goal of robustly expressing the missing enzyme in the brain that is the cause of MPS three yet.

Moving to Chicago Murray to work CMT.

Doctors the reached a headache nationwide children's hospital intends to commence dosing of the proof of concept study.

For C.M.T., one day subject only to obtaining final release of trials material for that study.

CMT is the largest inherited neuromuscular disease in the world and CMP workday devastating peripheral nerve disease is also the most prevalent form of CMT.

Douglas S. Ingram: Dr. Sahank's gene therapy is an AAV1-mediated construct to deliver the neurotrophic factor 3, NT3. In animal models, MT3 has been shown to promote nerve regeneration, improve motor function, histopathology, and electrophysiology of peripheral nerves, and in early proof-of-principle studies, NC3 has shown markers of clinical benefits in patients with CMT1A when administered subcutaneously. In summary, we have made great progress in the third quarter and over the course of 2019 toward our ambitions, advancing our RNA and gene therapy platforms, advancing our many development programs, building out our gene therapy manufacturing capacity, and Building Out Our Town. However, as with any ambitious strategy, our progress this quarter was met with an obstacle in the form of the Vyonda CRL. The breadth of our ambition inevitably comes with challenges and obstacles to address and overcome.

Doctors, Thanks gene therapy.

Is it a b one mediated construct to deliver the neurotrophic factors three and T. Three.

In animal models and T. Three has been shown to promote nerve regeneration improved motor function is to pathology and electrophysiology of peripheral nerves and in early proof of principle studies.

NT three has shown markers of clinical benefits in patients with CMT, one hey, when administered subcutaneously.

In summary.

We've made great progress in the third quarter and over the course of 2019.

Toward our ambitions advancing our our day of gene therapy platforms advancing our many development programs.

Building out our gene therapy manufacturing capacity.

And building out our town.

As with any ambitious strategy our progress this quarter was met with an obstacle.

In the form of buying out the by on the CRL.

The breadth of our ambition and ambition inevitably comes with challenges.

And obstacles to address and to overcome.

Douglas S. Ingram: But to those who might at times feel discouraged or disheartened by the need to overcome the occasional barrier, we should keep top of mind that what we are doing with all of this, if we are successful in our mission, we will not merely be among the most significant gene therapy and genetic medicine biotechnology companies in existence. But we will have, more importantly, extended, improved, and saved the lives of countless patients who would otherwise have been left hopeless. And with that, I will turn the call over to Sandy to provide an update on the financials. Sandy?

But to those who might at times feel discouraged where does heartened by the need.

To overcome the occasional barrier, we should keep top of mind.

What we're doing with all of this if we are successful in our mission, we will not merely be among the most significant gene therapy and genetic medicine biotechnology companies in existence.

But we will have more importantly extended proved and save the lives of countless patients who would otherwise have been left tubeless.

And with that I'll turn the call over to Sandy to provide an update on the financials Sandy.

Sandy: Thanks, Doug. Good afternoon, everyone. Let me start by saying that we had another strong quarter, both in terms of financial performance and progress towards the pipeline and manufacturing capabilities. With a current top-line run rate of approximately $400 million and a cash balance of over a billion dollars, we are in a strong position to continue to accelerate our strategic imperatives and invest in the growth of Sarepta. Net product revenue for the third quarter of 2019 was $99 million, compared to $78.5 million for the same period of 2018.

Thanks, Doug Thanks, good afternoon, everyone.

Let me start by saying that we had another strong quarter, both in terms of financial performance and in progress towards the pipeline and manufacturing capabilities.

The current topline run rate approximately $400 million on a cash balance over a billion dollars. We're in a strong position to continue to accelerate our strategic imperatives and invest in the growth of Sarepta.

Net product revenue for the third quarter of 2019 was 99 million compared to 78 and a half million for the same period of 2018.

Sandy: The increase primarily reflects higher demand for Exondus 51. On a GAAP basis, the company reported a net loss of $126.3 million and $76.4 million, or approximately $1.70 and $1.15, for the third quarter of 2019 and 2018, respectively. We reported a non-gap net loss of $84.4 million, or $1.14 per share, compared to a non-gap net loss of $37.1 million, or $0.56 per share, in the third quarter of 2018. In the third quarter of 2019, we recorded approximately $13 million in cost of sales, compared to $8.7 million in the same period of 2018.

The increase primarily reflects higher demand for EXONDYS 51.

On a GAAP basis, the company reported a net loss of 126.3 million and 76.4 million or approximately $1.70 on $1.15.

But share for the third quarter of 2019 and 2018, respectively.

We reported a non-GAAP net loss of 84.4 million or $1.14 per share compared to non-GAAP net loss of 37.1 million or 56 cents per share in the third quarter of 2018.

In the third quarter of 2019, we recorded approximately 13 million in cost of sales compared to 8.7 million in the same period of 2018.

Sandy: The increase was primarily driven by inventory costs related to higher demand for Exonis 51 during the third quarter of 2019, as well as accrued royalty payments to Biomarin and the University of Western Australia. On a gap basis, we recorded $133.9 million and $86.6 million of R&D expenses for the third quarters of 2019 and 2018, respectively, which is a year-over-year increase of $47.3 million. R&D expenses were $110.5 million for the third quarter of 2019 compared to $64.2 million for the same period of 2018.

The increase was primarily driven by inventory costs related to higher demand for EXONDYS 51 during the third quarter of 29 team.

As well as a crude royalty payments to Biomarin and the University of Western Australia.

On a GAAP basis, we recorded 133.9 million, an 86.6 million of R&D expenses for the third quarters of 2019 and 2018, respectively.

Through the year over year increased 47.3 million.

R&D expenses were 110.5 million for the third quarter of 2019 compared to 64.2 million for the same period 2018.

Sandy: An increase of 46.3 million. The year-over-year growth in non-GAAP R&D expense was driven primarily due to the continuing ramp-up of our microdistribution program, our ESSENCE program, and the initiation of certain post-marketing studies for Exandus 51. Turning to SG&A, on a GAAP basis, we recorded $75.4 million and $53 million of expenses for the third quarters of 2019 and 2018, respectively, a year-over-year increase of $22.4 million. On a non-GAAP basis, SG&A expenses were 59.6 million for the third quarter of 2019, compared to 42.5 million for the same period of 2018.

An increase of 46.3 million.

The year over year growth in non-GAAP R&D expense was driven primarily due to continuing ramp up off our micro dystrophin program, our essence program and initiation of certain post marketing studies for EXONDYS 51.

Turning grades yanni on a GAAP basis, we recorded 75.4 million and 53 million up expenses for the third quarters of 2019 and 18, respectively.

Year over year increase of 22.4 million.

On the non-GAAP basis do you have you any expenses were 59.6 million for third quarter 2019.

Compared to 42, and a half million for the same period of 2018.

Sandy: An increase of $17.1 billion. The year-over-year increase was primarily driven by significant organizational growth and continued expansion to support our commercial launch plans globally and almost 30 therapies in various stages of development across several therapeutic modalities. On a GAAP basis, we recorded $2.5 million in other expenses for the third quarter of 2019, compared to $7 million for the same period of 2018. This favorable change is primarily driven by the payoff of certain dead instruments during the third quarter of 2018, as well as a high return on investments during the third quarter of 2019. We had approximately $1.1 billion in cash, cash equivalents, and investments.

An increase of 17.1 billion.

The year over year increase was primarily driven by significant organizational growth and continued expansion.

<unk> commercial launch to support our commercial launch plans globally, and almost 30 therapies in various stages of development across several therapeutic modalities.

On a GAAP base is recorded two and half melamine other expenses for the third quarter 2019, compared to 7 million for the same period of 2018.

The favorable changes primarily driven by the payoff of certain debt instruments during the third quarter 2018.

As one of the high return on investment over the third quarter of 2019.

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

Sandy: As of September 30, 2019, With that, I'd like to turn the call over to Bo for a commercial update. Bo?

As of September Thirtyth 2019.

With that I'd like to turn the call over to both for commercial update both.

Bo: Thank you, Sandy. Good afternoon, everyone. To begin, we are pleased with the continued strong performance of Exodus 51 in the third quarter. Total revenues reached $99 million. We were also pleased to be in a position to increase our 2019 Revenue Guidance Range from $365 to $375 million to a range of $370 million to $380 million, for example, because sales have increased quarter over quarter for over three years. And we continue to see consistent demand for Exodus 51 as we... Clients and adherents have remained high and stable since launch, and to date, continue to remain steady. It should be noted that in the past two years, we've experienced ordering volatility at the end of the year. I suspect that we could see a change in ordering patterns with both Christmas and New Year's falling in the middle of the week.

Thank you Sandy good afternoon, everyone.

She began we're pleased with continued strong performance EXONDYS 51 third quarter.

Total revenues reached 99 million.

We were also pleased to be in position to increase our 2019 revenue guidance range from 365 to 375 million to a range of 370, just 380 million for EXONDYS 51.

Sales have increased quarter over quarter for over three years now and we continue to see consistent demand for EXONDYS 51, as we speak today.

Compliance and adherence have remained high in stable since launch and to date continue to remain steady.

It should be noted that the past two years, we've experienced ordering volatility at the end of the year.

And suspect that we could see a change in ordering patterns with both Christmas and new years following in the middle of the week.

Bo: Internally, we are assuming the pattern from previous years could be more extreme this year due to both holidays falling mid-week. With that said, we feel comfortable with the guidance provided. The success we achieved this year reflects the impact Exonis 51 continues to have on patient lives. We remain the leading voice with KOLs and payers across the world in support of Duchenne patients and are recognized as the leader in RNA and gene therapies within Duchenne. Our strategy to advance the very best science...

Internally, we are assuming the pattern from previous years could be more extreme this year due to both holidays following mid week.

With that said, we feel comfortable with the guidance provided.

The success, we achieved this year reflects the impact EXONDYS 51 continues to have on patient lives.

We remain that leading boys with AOL and payers across the world. It's important addition patients.

And our recognized as the leader in our in HIV therapy is within the Duchenne deal.

Our strategy to advance the very best science build awareness and appreciation for Duchenne and paid new pathways are duchenne patients gain access to therapy have resulted in successful trajectory of EXONDYS 51 since its approval just over three years ago.

Bo: Building awareness and appreciation for Duchenne and pave new pathways so Duchenne patients gain access to therapy has resulted in the successful trajectory of Exondus 51 since its approval just over three years ago, and will play a role for future therapy. As for Golda Durson, if approved, we will be ready to launch, leveraging our knowledge and experience to facilitate rapid access to individuals amenable to access. Our work is focused and deliberate, grounding us in all we do as the patient. That journey begins with identifying patients in our core therapeutic area. Shushen, Limberl Mustard Dish Feast, and MPS3A; Patient identification will be central to the commercial organization for the balance of 2019 and leading into 2020 and beyond. The genetic testing program DECODE-DUCEN, which we started with PP&D many years ago, consistently identifies patients.

And we'll play a role for future therapy.

As for go wonders if approved we will be ready to launch leveraging our knowledge and experience to facilitate rapid access to individuals amenable to exon 53.

Our work is focused and deliberate and grounding ethanol, we do as the patient.

That journey begins with the identifying patients in our core therapeutic areas Duchenne limb girdle muscular dystrophy Nm Dsthree AG.

Asia identification will be central to the commercial organization for the balance of 2019, and leading into 2020 and beyond.

Genetic testing program decode Duchenne, which we started with PPD many years ago consistently identified patients.

Bo: We are also in the process of building genetic testing programs for other disease states we are working on as well. We believe patient identification will always be one of our primary commercial goals, and we will continue to place resources on these programs. Another important goal will be gene therapy site readiness. We are already working on global site readiness for our DMD microdistrict program and working with many of these Oljensma and Spinraza sites treating SMA. Based on the very strong results Novartis demonstrated with their recent launch of Zolgenspil and understanding the label and the differences in patient population sizes between the two diseases, we believe having a strong network of sites ready and trained to handle gene therapies will be critical. We will continue to focus on this as we move through worldwide development and, if successful, commercialization. We also believe it is critical to focus on access and reimbursement as early as possible.

We're also in the process of building genetic testing programs for other disease stage, we're working on as well.

We believe as shown diversification will always be one of our primary commercial goals and we will continue to place resources on these programs.

Another important goal will be gene therapy site readiness, we're already working on mobile site readiness for DMD Micra Dystrophin program and working with many of these old Genzyme spinraza sites treating estimate.

Based on very strong results the BARDA demonstrated with their recent launches xeljanz, Bob and understanding the label and the differences in patient population size is between the two to these days.

We believe having a strong network the sites ready and train to handle gene therapies will be critical.

We will continue to focus on this as we move through worldwide development and if successful commercialization.

We also believe is critical to focus on access and reimbursement as.

As early as possible.

Bo: We're already speaking to and educating large to mid-sized insurance plans, as well as CMS and Medicaid providers, on the differences between chronic therapies and one-time gene therapies and the importance of quickly gaining access to these therapies for diseases like Duchenne. We have built constructive relationships with payers over time and look forward to continuing to work with them to support broad access. In the limb-vertebral muscular dystrophy, we are focused on disease education and identifying patients. The limb girdle muscular dystrophies are a family of diseases, with over 30 subtypes in all.

We're already speaking to and educating March to mid size insurance plans as well as CMS and Medicaid providers on the differences between chronic therapy.

Therapies and the important weekly gaining access to these therapies for diseases like to shed.

We have built constructive relationships with payers over time and look forward to continuing to work with them to support broad access.

In Liberal muscular dystrophy, we're focused on disease education Indentifying patients.

Hey, limb girdle must produce therapies, our family of diseases over 30 sub types and all.

Bo: Therefore, patient identification is of critical importance. Our plan is to leverage our knowledge and experience to ensure that we're able to serve these communities as we have in Duchenne. We've already attended limb-verbal muscular dystrophy conferences, held educational symposiums at major neuromuscular conferences, held advisory boards to understand how physicians identify and treat patients, and already have additional presence. All of this will help us prepare for the potential to support multiple launches.

Therefore patient identification is of critical importance.

Our plan is to leverage our knowledge and experience to ensure that we're able to serve these communities as we haven't you shed.

We've already intended linked girl muscular dystrophy conferences held educational symposium that major neuromuscular conferences LT advisory boards to understand how physicians identify and treat patients and already have a digital presence within community.

All of this will help us prepare for the potential to support multiple launches in the years to come.

Bo: Sarepta's prospects to transform the lives of patients with rare diseases are unparalleled in the industry. We have the largest neuromuscular RNA and gene therapy pipeline in the industry, and we understand the responsibility that comes with such an important mission. With that, I will turn the call back to Doug for closing remarks. Thank you both.

Surreptitious prospects to transform the lives of patients with rare diseases is unparalleled in the industry.

The largest there must be or are in AG therapy pipeline and the industry and we understand that responsibility that comes with such important mission.

With that I'll turn the call back to Doug for closing remarks.

Thank you both so looking forward.

Douglas S. Ingram: So looking forward... We have a number of significant milestones to achieve. For the rest of 2019 and through 2020, first, we intend to complete dosing of our SRP 9001 Study 2, that is, our microdistrophin study, by year-end, with functional readout 48 weeks thereafter. We soon intend to lock process development for SRP 9001 manufacturing for purposes of conducting our next clinical trial, gain insight from the agency on CMC and on our trial itself, And then to commence study 301 by mid-2020. We intend to dose an additional high dose cohort for limb girdle 2E and then make a dose selection. We intend to gain regulatory and manufacturing insight and to present an update on the development pathway and timeline for our entire Lynn Girdle program in 2020. Dr. Sahank intends to commence a proof-of-concept study for CMT gene therapy MT3. And we intend to obtain safety and dosing insights for our PPMO program in the first half of 2020. So we obviously have a lot to do, but we have a lot of milestones as well over the coming months and quarters. Thank you all for joining us tonight.

We have a number of significant significant milestones to achieve.

Well for the rest of 2019 through 2021st we intend to complete dosing of our SRP Niger Zero. One study to that's our micro dystrophin study by year end with functional read out.

40 weeks thereafter.

We still intend to lock process development for SRP nine 001, not manufacturing for purposes of conducting our next clinical trial data insights from the agency arms CMC and on our trial itself.

Then to commence study three one by mid 2012.

We intend to those an additional high dose cohort for lived girdle to even make a dose selection.

We intend to gain regulatory and manufacturing insight.

And to present, an update on the development pathway and timeline for our entire link girdle program.

In 2020.

Dr say sake intends to commence a proof of concept study.

For CMT gene therapy.

Mt three.

And we intend to obtain safety and dosing insight for our PMO program in the first half.

Of 2020, so we obviously have a lot to do but a lot of milestones as well over the coming months at quarter's. Thank you all for joining US Tonight I'll open up the lives for questions.

As a reminder to ask a question you would need to press star one on your telephone to withdraw your question press. The pound key we ask that you limit yourself to one question. Each please standby why the composite queuing they roster.

Operator: I'll open up the floor to questions. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.

Our first question comes from elite Young of Cantor Fitzgerald. Your line is open.

Alicia Young: We ask that you limit yourself to one question each. Please stand by while we compile the Q&A roster. Our first question comes from Alicia Young of Cancer Fitzgerald. Your line is open.

Hey, guys. Thanks for taking my question and congrats on all the progress over the quarter, that's maybe a symbol on but I was just curious to get your perspective.

Douglas S. Ingram: Hey guys, thanks for taking my question, and congrats on all the progress over the quarter. This may be a simple one, but I was just curious to get your perspective on the Bill Jensman partial hold, and like, are there any reads to potentially make to, you know, other gene therapy programs? Thank you for that question, Alethea.

In some partial hold that Mike Chile is there any are there any read potentially make taking the other gene therapy program. Thanks.

Thank you for that question, yes, Okay. So a book first let me say this well, let's make sure all of the same page for those who.

Maybe on awareness suspect everyone is aware Novartis recently announced that their clinical trial for their 89 mediated SMH gene therapy for Intrathecal administration was placed on a partial clinical hold due to neurotoxicity that we've seen an animal models.

Douglas S. Ingram: Okay, so first let me say this. Let's make sure we're all on the same page for those who, maybe unaware, and I suspect everyone is aware, Novartis recently announced that their clinical trial for their AAV9 mediated SMA gene therapy for intrathecal administration was placed on a partial clinical hold due to neurotoxicity that was seen in animal models. So first understand this; we do not have any unique insight into the Zolgensma clinical trial itself or the Zolgensma program. Certainly, one should look to Novartis to gain accurate insight into that program and those issues. I should tell you we see no read-through to our program, and there's a host of reasons for that. First, understand that we are dosing peripherally with IV administration; we're not dosing intrathecally as was the issue as announced by Novartis regarding that partial clinical hold, and second of all, understand that we're not using a benign. Dr. Louise Rodino-Klepec, who was with One of the significant ones was that Rh74, unlike AB9, as an example, does not promiscuously cross the blood-brain barrier. Unlike SMA, where that would be a value.

So first I understand this we do not have a unique insight into the sole Jensen, that's going to gold itself, where there's still Jens not program certainly one should look to novartis to gain accurate inside on that program those issues with that said.

I should tell you we see no read through to our program and there was a host of reasons for that first I understand that we are dosing peripherally with idea administration were not dosing intra equally as was the issue as announced by Novartis regarding that partial clinical hold and second of all understand that were not use.

Being 89.

Dr will be Sergio quite back it was witness Tonight and Dr., Jerry Mendell chose our each 74 for a number of specific attributes.

One of the significant ones was that our each 74.

Unlike a benign as an example does not promiscuity cross the blood brain barrier, Unlike SDMA, where that would be a value.

There is absolutely no value to these micro dystrophin constructs in the CNS at all they have promoters that wouldn't turned on in this again CNS again, it would be no value. There. So this seems to have been a very wise choice. I also know this that we have an enormous amounts of preclinical animal model evidenced with respect to our a 74 and even.

Doses that are multiples hot multiples higher then.

Then we're using in our clinical trial, we have never see jumps up neurotoxicity as relates to a the Rx seven before.

Douglas S. Ingram: There is absolutely no value to these microdisturbing constructs in the CNS at all. They have promoters that wouldn't turn on in the CNS, so there would be no value there. So this seems to have been a very wise choice. And also know this, that we have an enormous amount of preclinical and animal model evidence with respect to RA-74, and even at doses that are multiples higher than we're using in our clinical trial. We have never seen a case of neurotoxicity as related to AAV RA-74.

Great. Thanks.

Thank you.

Next question comes from Whitney item of Guggenheim. Your line is open.

Hey, guys. Thanks for taking the questions and.

Also congrats on all the progress.

A question on the original for Microdisplays inpatient curious if we'll get an update on them in 2020, either in an update from your possibly a publication from document though.

Yeah. Thanks for that question. Thank you fear for your.

Whitney Igem: Great. Thanks. Our next question comes from Whitney Igem of Guggenheim. Your line is open.

The comments so yes document Dell has always had a keen interest in publishing the one your data on the for patients and he is working on manuscript even as we speak so I am I feel very confident they will have a publication in 2020 on the first for patients.

Douglas S. Ingram: Hey guys, thanks for taking the questions and also congrats on all the progress. I'll ask a question on the original four microdistricts and patients. Curious if we'll get an update on them in 2020, either in an update from you or possibly a publication from Dr. Mandel. Yeah, thanks for that question.

Great. Thanks, and then maybe one quick follow up thanks for your comments on gold or can I guess I'm just curious if you're willing to comment on the type of anything else.

You know whether or not there.

Douglas S. Ingram: Thank you for your comments. So, yes, Dr. Mandel has always had a keen interest in publishing the one-year data on the four patients, and he is working on the manuscript even as we speak. So I feel very confident that we'll have a publication in 2020 on the first four patients. Great, thanks.

Based on that.

I missed the end of your question, but I still have the Ashley the answer wealthy frustratingly.

I'm not going to provide updates.

I as I've said, we're going to work with the agency and if there is a rapid pathway will work in the agency to see if there is one.

What I would like not to do is to provide.

Interim comic so I don't want to provide updates along the way there our meetings that were having where the past with pathway there were considering or the views of the agency, but I will make a promise to everyone. When we have submitted a clarity I will very rapidly provide an update not only to the investment community, but also obviously the patient.

Douglas S. Ingram: And then maybe one quick follow-up. Thanks for all your comments on Goal Adherence, and I guess I'm just curious if you're willing to comment on the type of meeting you'll be having with the FDA and, you know, whether or not their timing is safe based on that. I missed the end of your question, but I still have the answer.

The physician community as well.

So thank you for that.

Our next question comes from Christopher Mariah Monomer. Your line is open.

Douglas S. Ingram: The answer will be, frustratingly, I'm not going to provide updates. As I said, we're going to work with the agency, and if there is a rapid pathway, we'll work with the agency to see if there is one. What I would like not to do is to provide interim comments. So I don't want to provide updates along the way, either on meetings that we're having or the pathway that we're considering or the views of the agency. But I will make a promise to everyone.

Hey, good afternoon. Thank you for taking my question on really quickly maybe.

Yes.

Hi.

You bet.

Yes.

Yes.

Pardon.

Yes.

Study.

And then.

[laughter].

Thank you.

I'm going to really apologize we were unable to hear your question.

Douglas S. Ingram: When we have definitive clarity, I will very rapidly provide an update, not only to the investment community but also, obviously, to the patient and the physician community as well. So thank you. Our next question comes from Christopher Mirai of Namur. Your line is open. Hey, good afternoon.

I'll try to answer what I think made but your question. Joe is a question about limb girdle dosing for the T., we program will be dosing patients.

Over the course of this quarter it will have that insight Bob glamour to perspective.

Early next year and that's when we'll be able to make the decision is the question in part was what what are the choices on dosing. We don't start our original dose was five times either the 13th the protocol itself cold for a dose escalation to talk to you. The 14, that's what we will be doing in the next three patient cohort will be getting that done very soon.

Christopher Mirai: Thank you for taking the question. Um, really quickly, maybe thinking about, www.kenhub.com and then regarding the PPFO, www.kenhub.com/blog/and when should we see that update? I am really going to really apologize; we were unable to hear your question. I'll try to answer what I think may have been your question. I think there was a question about limb girdle dosing for the 2E program. We'll be dosing patients over the course of this quarter, and we'll have that insight from a biomarker perspective early next year, and that's when we'll be able to make the decision. If the question in part was what the choices were on dosing, we dosed our original dose was 5 times e to the 13th, but the protocol itself called for a dose escalation to 2 times e to the 14th.

And we'll have that dosing inside early next year armed with that will make a decision we've seen great results in our five times either the 13th to remind one we had expression levels of just over 50% and of course, we've seen very good signals. Its three patients I'm gonna be careful but we've seen very good signals.

A functional efficacy in these first three patients. So we're in a good place now and then we'll compare both the the tolerability in the safety profile for a higher dose as well as the expression levels from that higher dose and we'll make a decision regarding that and then I think you asked a question about the PMO I'm going to apologize I Didnt get the first part of the quest.

And I think one of the question part of the question May have been when should we expect an update regarding the PMO program that will happen I'm certainly before the middle of 2020 and should be actually significantly earlier than that hopefully in and what are we looking for their remember what the PMO is our current technology the PMO.

Douglas S. Ingram: That's what we will be doing in the next three-patient cohort. We'll be getting that done very soon, and we'll have that dosing insight early next year. Armed with that, we'll make a decision. We've seen great results in our 5 times e to the 13th.

Our R&D technology that forms the basis of the tougher sidner scientists and Gunderson Academy person and alike.

Douglas S. Ingram: To remind you, first, we had expression levels of just over 50 percent, and, of course, we've seen very good signals. It's three patients, so I want to be careful, but we've seen very good signals of functional efficacy in these first three patients. So we're in a good place now, and then we'll compare both the tolerability and the safety profile for a higher dose as well as the expression levels from that higher dose, and we'll make a decision regarding that. And then I think you asked a question about the PPMO. I'm going to apologize.

Is this more fleet technology. The pp about was a peptide conjugated version of that same technology, the peptide which is positively charged.

At least in animal models drags that therapy into the cell with much greater abundance and it should result, if if we get to the right doses in much significant increases in both exon skipping and therefore dystrophin production and presumably additional functional benefits.

Douglas S. Ingram: I didn't understand the first part of the question. I think one of the questions, part of the question may have been, when can we expect an update regarding the PPMO program? That will happen certainly before the middle of 2020.

And.

So by.

Before the middle of next year, we're going to essentially get.

The one big question is can we tolerably increased doses to significant level. So far things are going very well, but we have more works to do so we'll be getting dosing insight and safety signals before the middle of next year. So that will include things like.

Douglas S. Ingram: It should actually be significantly earlier than that, hopefully. And what are we looking for there? Remember what the PPMO is. Our current technology, the PMO, our RNA technology that forms the basis of the Keflerson or Saunders and Golunderson and Kazimierson and the like, is this morpholino technology. The PPMO is a peptide conjugated version of that same technology. The peptide, which is positively charged, at least in animal models, drags that therapy into the cell in much greater abundance, and it should result, if we can get to the right doses, in much greater increases in both exon skipping and therefore district production and presumably additional functional benefits.

Tissue levels skip levels, and perhaps even dystrophin production levels I'm getting a thumbs up from our from Dr. aneel, suggesting that I'd I Havent made a mistake in there and we'll have that before the middle of next year I apologize. If there are parts of the question that I was unable to hear and therefore I haven't answered.

Our next question comes from Brian Abrahams of RBC capital. Your line is open.

Hi, Thanks, very much for taking my questions.

Micro dystrophin anything you're seeing so far with the additional cohort of patients to suggest that this new batched might be any different from the batch used to dose that first 24, I guess 12 patients perhaps.

Douglas S. Ingram: And so before the middle of next year, we're going to essentially get the one big question: can we tolerateably increase doses to significant levels? So far, things are going very well, but we have more work to do. So we'll be getting dosing insight and safety signals before the middle of next year. And that will include things like tissue levels, skip levels, and perhaps even district production levels. I'm getting a thumbs up from Dr. O'Neill, suggesting that I haven't made a mistake there. And we'll have that before the middle of next year.

With respect to manufacturing competition the way the second center administers it or Stabilities your transportation out to L.A., and then secondarily I recognize you're not giving play by play updates on your update feedback, but we did see recently that cedar is going to reorganize the off the center of science and other areas. The office of new drugs between now and your Ren just wondering did that might mean to change.

And leadership group, that's responsible for the goal of application or any other implications. This might have for your ongoing dialogue with the agency and go lumped or some CASM or send your future gene therapies. Thanks.

Taking the first question regarding whether dystrophin. Please understand this is a blinded placebo controlled trial. So we'll await those results, but with that said also understand that the material for this trial is the same process and the same manufacture both of our clinical material coming.

Douglas S. Ingram: I apologize if there are parts of your question that I was unable to hear and, therefore, I haven't answered. Our next question comes from Brian Abrahams of RBC Capital. Your line is open.

Brian Corey Abrahams: Hi, thanks very much for taking my questions. On microdystrophin, anything you're seeing so far with the additional cohort of patients to suggest that this new batch might be any different from the batch used to dose that first 24, I guess, 12 patients, perhaps, with respect to manufacturing composition, the way the second center administers it, or stability through transportation out to LA? And then, secondarily, I recognize you're not giving play-by-play updates on your FDA feedback, but we did see recently that CDER is going to reorganize the Office of Neuroscience and other areas of the Office of New Drugs between now and year-end. And I'm just wondering if that might mean a change in leadership for the group that's responsible for the GOLO application, or any other implications this might have for Thanks.

From the same hide from GMP hyper stack, the Neely and adhering process at nationwide children's hospital. So in the face of they we have no concerns regarding material itself and we're very cognizant of things like you know the supply chain and.

The wage transported so we're very confident on those regard so things are going well I don't want to where it is a blinded trial. So we'll we'll see the function of the old results and other related issues.

Once all the dosing is done we unblind that portion at the end of 48 weeks, but we certainly are very confident that's material itself.

The process for the trials, both with the Doctor Jerry Mendell and also with Dr. Perry Shane can you.

Talking about the reorganization the short answer on that if that were not going to then I'm certainly not going to speculate on what that could mean for go Inder Singh at all I will say this we have had a very productive relationship.

Douglas S. Ingram: Taking the first question regarding microdistribution, please understand this is a blinded, placebo-controlled trial, so we'll await those results. But with that said, also understand that the material for this trial is the same process and the same manufacturer, both of our clinical materials coming from the same GMP hyperstack mammalian adherent process at Nationwide Children's Hospital. On the face of it, we have no concerns regarding the material itself, and we're very cognizant of things like the supply chain and the way it's transported, so we're very confident in those aspects. So things are going well. I don't want to, you know, it is a blinded trial, so we'll see the functional results and other related issues. Once all the dosing's done, we unblind that portion at the end of 48 weeks, but we certainly are very confident in the material itself.

Both with Dr., Billy dynamic and Dr. base things both of whom we have considerable regard for so we think this is certainly a good answer for those in Neurosciences and neuromuscular across the industry.

Our next question comes from Septima set a pad of H.C. Wainwright. Your line is open.

So.

Hey, good afternoon.

So.

Given the tools on the toolbox currently would you consider factorized exon skipping the products or are you limited by manufacturing capacity as far as you've got to rise to exon skipping a concern and just a follow up on the same question in terms of compatibility between wise type just took an expression and micro district.

Is there a correlation or conversion say for example, if you have 8%.

Does that expression that.

Should have the same kind of puncture benefits as day at 30% Micra discipline, especially I guess how much.

Douglas S. Ingram: And the process for the trial, both with Dr. Jerry Mandel and also with Dr. Perry Shea at UCLA. Talking about the reorganization, the short answer on that is that we're not going to, and I'm certainly not going to, speculate on what that could mean for Rola Durson at all. I will say this; we have had a very productive relationship with both Dr. Billy Dunn and Dr. Baystings, both of whom we have considerable regard for. So we think this is certainly a good answer for those in neuroscience and neuromuscular across the industry. Our next question comes from Debjit Chattopadhyay of H.C. Wainwright. Your line is open. Hey, good afternoon. Given the tools in the toolbox currently, would you consider a vectorized exon skipping approach, or are you limited by manufacturing capacity as far as vectorized exon skipping is concerned?

So on the first question, we have significant programs focused on Duchenne muscular dystrophy, both priority perspective, as well sure a gene therapy for perspective, others have different approaches we are.

Generally not focused on nor do we intend to have a focus and anytime in the near future on the concept of.

Using gene therapy to to deliver exon skipping modalities, where it's not something we're we're interested at the gene transfer therapy I should also note. However that as it relates to CRISPR Casnine, which itself is a form of exon skipping it is not in the aren't.

It actually is.

Directly at its the genome itself that is an approach that dr. Charlie jurist block is taking now he's taking a different approach than others in that regard. His CRISPR casnine approach actually does a fairly significant time and if it is successful and this is a research program at this point this is not a.

Debjit D. Chattopadhyay: should have the same kind of functional benefits as, say, a 30% microdiscipline expression. Thank you so much. So, on the first question, you know, we have significant programs focused on Duchenne Muscular Dystrophy, both from an RNA perspective as well as from a gene therapy perspective. Others have different approaches we are generally not focused on, nor do we intend to have a focus any time in the near future on the concept of using gene therapy to deliver an exon skipping modality. It's not something we're interested in as a gene transfer therapy. I should also note, however, that as relates to CRISPR-Cas9, which itself is a form of exon skipping. It is not in the RNA side.

Development stage program that we are some ways away from a development stage program, but is that words, they would be an approach that could that could.

Be available perhaps to as many as 50%.

Patients that have DMD, but that is a research.

Program in some ways out as it relates to the the first choice. The basic question about the concept of using an 80 mediated approach through some other mechanisms that you seven mechanism or the like to insert exon skipping agent.

This is our focus and frankly it isn't something that we're we're obviously excited about as an organization.

On that second issue I'll.

Douglas S. Ingram: It actually, you know, directly edits the genome itself. That is an approach that Dr. Charlie Gerspach is taking. He has a different approach than others in that regard.

Turning to the we should be no clay back you might have some views based on the animal model. They conduct the any correlates in one sees between expression the microbus with that one might see of expression of wild type disturbance.

Douglas S. Ingram: His CRISPR-Cas9 approach actually does a fairly significant cut, and if it is successful, this is a research program at this point. This is not a development stage program, and we are some ways away from a development stage program. But if that works, it would be an approach that could be available, perhaps to as many as 50%, of patients that have D&D. But that is a research program in a sense. As it relates to the basic question about the concept of using an AAV mediated approach through some other mechanism, a U7 mechanism or the like, to insert an exon skipping agent, it isn't our focus, and frankly, it isn't something that we're enormously excited about as an organization. On that second issue, I'll turn to Louise Rodino-Kleypak, who might have some views based on the animal modeling on any correlates that one sees between the expression of microdistrophin and what one might see of the expression of wild-type dystrophin.

Alright, Thank you Doug in our preclinical studies, we did an extensive dose escalation and we found that as little as 20% dystrophin micro dystrophin positive fibers.

Let the clinical benefit and if you think about our clinical results that were about 80% micro dystrophin positive fibers are well beyond that level, we really based on extensive efficacy studies and and yet mdx mouse model for the disease.

As a reminder, we'd like to ask a question. Please press Star then one.

And please remember to limit yourself to one question. Our next question comes from the thing in a lot of Bank of America. Your line is open.

Hi, good afternoon guys.

Thanks for taking my question I, just wanted to get a sense that about the timing of the read out for the confirmatory study that you're starting this quarter I think on clinical trials that it has a 2024 days for read out, but just wanted to get some clarity if that's round about the timeline Eric thanks. Thanks.

Louise R. Rodino: Thank you, Doug. In our preclinical studies, we did extensive dose escalation, and we found that as little as 20% of microdystrophin positive fibers led to clinical benefit. And if you think about our clinical results that were about 80%, the fibers were well beyond that level. So we really based it on extensive efficacy studies in the MDX mouse model for the disease. As a reminder, if you'd like to ask a question, please press star then 1. And please remember to limit yourself to one question.

Before I go too far into the high dose.

We will come up with more Clare will provide an update and in.

Probably later in 2020 about timelines associate with the confirmatory trial. The good news on the trial just over on the same pages that this was this a little more complicated as a confirmatory trial. The one might normally imagine this is not a trial with a placebo arm versus the approved dose. It was as I've noted in my comments.

Operator: Our next question comes from Tazeen Ahmad of Bank of America. Your line is open. Hi, good afternoon, guys.

It is a confirmatory trial that actually test thislife a different stake thesis, which is the current dose first as a significantly higher personnel that goes to do that before you could commence the try the main trial you have to start with LT human volunteer trial, and we've done that we've completed that's read out that justified moving to.

Tazeen Ahmad: Thanks for taking my question. I just wanted to get a sense, Doug, about the timing of the readout for the confirmatory study that you're starting this quarter. I think in clinical trials that it has a 2024 date for readout, but just wanted to get some clarity if that's roughly the timeline you're expecting. Thank you. We'll come up with more, Claire.

To this higher dose study as I said before there really are three arms. There's the 30 makes for K, which are currently approved dose there's an arm at 100 mixed for Chegg, There's an arm at 200 mixed for keurig It gets a little bit more complicated than that over time, but that's essentially the study and that study is initiating now will be dosing now we can provide updates on that probably.

Douglas S. Ingram: We'll provide an update probably later in 2020 about timelines associated with the confirmatory trial. But the good news on the trial, just so we're on the same page, is that this is a little more complicated as a confirmatory trial than one might normally imagine. This is not a trial with a placebo arm versus the approved dose. It was, as I've noted in my comments, a confirmatory trial that actually tests a different hypothesis, which is the current dose versus a significantly higher version of that dose. To do that, before you can commence the main trial, you have to start with a healthy human volunteer trial, and we've done that. We've completed it. That's read out. That justified moving to the higher dose study. As I've said before, there really are three arms.

Toward the end of 2020, or so give you some additional sometime wins.

Our next question comes from Gena Wang of Barclays. Your line is open.

Thank you for taking my question and the first one is assets trial. Just wondering if you can remind us when the data will lead out and also do you think if you want it data in order to.

Person and customers.

And then my second question is a very quickly regarding the one year to date for patients.

Wondering what will be included in that one year data update would that include biomarker data, especially like canned approaching level as well as a function or the.

Douglas S. Ingram: There's 30 mg per kg, which is our currently approved dose. And there's an arm at 100 mg per kg. There's an arm at 200 mg per kg. It gets a little bit more complicated than that over time, but that's essentially the study, and that study is initiating now and will be dosing now. We can provide updates on that, probably toward the end of 2020 or so, and give you some additional information. Our next question comes from Gena Wang of Barclays. Your line is open. Thank you for taking my questions. The first one is the absence trial.

Yes.

So as it relates to essence essence will be I will read out light. Obviously, we're recruiting now that we've recruited over 70% so assets is coming along very well.

We should have a readout in essence around 2023.

As I've said I I'm not going to comment on the pathway for Golar Dirksen until we have more clarity from the agency then I'll come back and provide definitive clarity.

And then I think the second question was as it relates to.

Dr. Midtown.

When you're like I was wondering data will be it'll be inclusive of functional biomarker safety will be there will be.

Inclusive of the down a bit that he has on the first for patients at the one year.

Gena Wang: Just wondering if you can remind us when the data will read out. And also, do you think FDA will want absence data in order to approve Golders? And then my second question is very quickly regarding the one-year data for four patients. Just wondering, what will be included in that one-year data update? Will that include biomarker data and the protein level, as well as functional data?

Our next question comes from Salveen Richter of Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking my question, so with regard to the gene therapy manufacturing can you detail the progress you've made on yield optimization and ask they work on essentially where you stand right now with the overall tech transfer from Nch. If you look to start the commercial grade pivotal trial.

Douglas S. Ingram: So as relates to essence... Essence will be, we'll read out, you know, obviously we're recruiting now, but we've recruited over 70%, so Essence is coming along very well. We should have a readout in Essence around 2023. As I've said, I'm not going to comment on the pathway for Gola Dursun until we have more clarity from the agency. Then I'll come back and provide definitive

Oh, you week, so let's go through a couple of things, there's obviously elements.

That's for competitive reasons, and I will provide numerically, but broadly speaking the other falling first we long ago Tech transferred the process from the switch over to hospital.

Due to us into this hybrid.

Approach, we have so remember they really are.

Collection of three groups working on process development analytical development, mostly here and that is where our own group. We've got a significant group, we've got 10 ice Dallas units.

Douglas S. Ingram: And then I think the second question was, as it relates to... Dr. Mendel, 1-year data will be it'll be inclusive of functional biomarkers safety, it'll be it'll be you know inclusive of the data that he has on the first four patients at the one-year mark. Our next question comes from Salveen Richter of Goldman Sachs. Your line is open. Good afternoon, thanks for taking my question. So with regard to gene therapy manufacturing, can you detail the progress you've made on yield optimization and assay work, essentially where you stand right now with overall tech transfer from NCH as you look to start the commercial grade pivotal trial? So let's go through a couple of things. There are obviously elements that, for competitive and other reasons, I won't provide numerically, but broadly speaking, know the following.

Here actually wrapped and then we've got our partners at Paragon, We've got our partners at Brammer. So that we pay a lot of progress first just from a pure capacity perspective as I said, we are fully belts with brand are biased sciences, a single use facility in Lexington, and it is dying and ready to go.

We have.

At Paragon, we actually have even more significant that well that a significant capacity, we have even more significant capacity at paragon and that then I sell this units are there and and getting ready to go as well led by Dr. reach work at Sarepta, We've made great strides on.

Assay development there now as it relates to process development, we've made significant strides on our Microdisplay program, we actually made significant strides on some of our limb girdle programs as well in fact as relates to yields for the clinical trial, we will be logging I'm not going give you exact date, but it will be in the near term will be locking processing beginning.

Salveen Jaswal Richter: First, we long ago transferred the process from Nationwide Children's Hospital to us and to this hybrid approach we have. So remember, there really are a collection of three groups working on process development and then analytical development, mostly here. Here at Sarepta, and we've got our partners at Paragon, and we've got our partners at Brammer.

Information right. So that we're in a position by the middle of 2020 to commence.

What we study three one which is our commercial process supply trial. So all in all I'd say, we're making great progress around capacity and assay development and we're making good good progress on process development to yield optimization as well.

Douglas S. Ingram: So, we've made a lot of progress. First, just from a pure capacity perspective, as I've said, we have fully built, with Brammer Biosciences, a single-use facility in Lexington, and it is done and ready to go. We have, at Paragon, we actually have even more significant, well, that is significant capacity.

We still have a lot less to do.

I think we we started this process you know we got ahead of this early got the capacity as soon as we realize the opportunity in front of us and I think the team is very focused weve got a lot of great expertise here and we're making good progress.

Our next question comes from Daniel Brims with Piper Jaffray. Your line is open.

Douglas S. Ingram: We have even more significant capacity at Paragon, and the Nicellus units are there and getting ready to go as well. Led by Dr. Reid Clark at Sarepta, we've made great strides on assay development, and as it relates to process development, we've made significant strides on our microdiscipline program, and we've actually made significant strides on some of our lymph granule programs as well. In fact, as it relates to yields for the clinical trial, we will be locking, I'm not going to give you the exact date, but it will be in the near term, we'll be locking process and beginning confirmation runs so that we're in a position by the middle of 2020 to commence study 301, which is our commercial process supply trial.

Hi, guys.

Good afternoon. Thank for the question Doug have you done any of the additional one girl to each patient you said that you'll have the dose selected by early next year and safe to assume that they will be goes by the end of this year. Thanks.

They should be goes by the end of this year, we havent material. The patients are all screen. So I'm not give details on on who's scheduled for Wang but they are the three patients should all be done by the end of this year and we should have insight in that it should be around that at the end before the end of the first quarters, Yes, yes, yes.

Our next question comes from Joel Baby of Citi. Your line is open.

Hi, Thanks for taking my question.

Douglas S. Ingram: So, all in all, I'd say we're making great progress around capacity and assay development, and we're making good progress on process development. We still have a lot left to do, but I think we started this process early, we got ahead of this early, we got the capacity as soon as we realized the opportunity in front of us, and I think the team is very focused, we've got a lot of great expertise here, and we're making progress. Our next question comes from Danielle Brill of Piper Jeffries. Your line is open.

One is on exon skipping agents, including your ppm olefin development as well that competing companies.

Right now.

Children expression from those agents that kind of get so high that it would be competitive, whereas the gene therapy.

Anthony in terms of competitive from a marketing standpoint, and that's if so could you help characterize what of that maybe.

Well, if you look it's hard to characterize in advance I will say that isn't enormously high bar, so to remind wine with respect to our microdisplay them program, we're seeing.

Over 90% expression and as Dr. with Luis Moreno Clay back mentioned.

Danielle Brill: Hi guys, good afternoon, thanks for the question. Doug, have you dosed any of the additional limb girdle 2E patients? You said that you'll have the dose selected by early next year, so is it safe to assume that they will be dosed by the end of this year? Thanks.

In response to a question earlier, you get transformative functional improvements in animal models.

And even at lower than that number so we should we.

To ask whether there's a possibility that PMO and I think it really would only be the peptide conjugate UPPI PMO, whether it could be at a place where could actually be in some ways competitive with a gene therapy I think we'll we'll await the results of our study and 2020, but.

Douglas S. Ingram: They should be dosed by the end of this year. We have the material, the patients are all screened, so I don't have details on who's scheduled for when, but the three patients should all be dosed by the end of this year, and we should have insight into that, it should be around the end, before the end of the first quarter. Yeah.

That is a high bar I think the real interesting question for our Pbms program.

Assuming the success of our gene therapy is that if we got we had such significant.

And robust expression and I will say at least in animal models and I don't we will await the data from our multi ascending does stay but at least in animal models.

Joel Beatty: Our next question comes from Joel Beatty of Citi. Your line is open. Hi, thanks for taking the question. The question is on exon skipping agents, including your PPMOs in development as well as competing companies. Is there an amount of distributed expression from those agents that could get so high that it would be competitive with the gene therapy agents in terms of, you know, competitive from a marketing standpoint? And if so, could you help characterize what that may be?

Getting to the right. Those you could have an order of magnitude more exon skipping we're disciplined production and then significant increases in function.

The real question in that scenario or whatever the number questions. The first is is there a place where a cognitive therapy very transformative gene therapy.

With a potential follow on P. PMO and obviously, there's also the opportunity of gene therapy successful for them. So for those patients who would otherwise screen out of.

Douglas S. Ingram: Well, you know, it's hard to characterize in advance, but I will say that it is an enormously high bar. So to remind you, with respect to our microdistribution program, we're seeing over 90% expression. And as Dr. Louise Rodino Clayback mentioned in response to a question earlier, you get transformative functional improvements in animal models at even, you know, lower than that number. So we, you know, ask whether there's a possibility that a PPMO, and I think it really would only be the peptide conjugated PPMO, could be in a place where it could actually be in some ways competitive with gene therapy. I think we'll await the results of our study in 2020. But that is a high bar.

The gene therapy, and then if the PBM hours is and again, let's let us await the data before we before we get too far over our skis, but if that PMO data was able to get to very high doses and was.

Was significant and well tolerated then obviously the next question for US and we're looking at this right now as well what other areas could we take this therapy to to provide benefits to patients.

Who would benefit from stair blockage at significant doses.

As a reminder, we ask that you. Please limit yourself to one question. Our next question comes from Ritu Baral of Cowen Your line is open.

Hey, guys. Thanks.

Question so.

Douglas S. Ingram: I think the real interesting question for our PPMO program is, The real question in that scenario, well, there are a number of questions. The first is, is there a place for a combinative therapy of a very transformative gene therapy with a potential follow-on of PPMO, and obviously, there's also the opportunity for gene therapy to be successful for PPMO for those patients who would otherwise screen out of gene therapy. And then if the PPMO is, again, let us await the data before we get too far ahead of ourselves, but if the PPMO data was able to get to very high doses and was significant and well tolerated, then obviously the next question for us, and we're looking at this right now, is what other areas could we take this therapy to provide benefits to patients who would benefit from stair-clocking at significant doses. As a reminder, we ask that you please limit yourselves to one question. Our next question comes from Ritu Baral of Cohen.

You mentioned that you have I get locked in a placebo controlled.

Design aspect to the phase three three a one trial.

Can you describe your current thinking on patient numbers randomization, you didn't mention younger patients and it sounded like you said that your sequestering older patients in a different study and just to clarify your answer to sell Deans question.

Yes.

So have you finished assay validation.

And if not when you think you might nail that down with the FDA and start those engineering once you mentioned.

After the second question first we still have work to do on assay validation.

But we're making great progress under the guidance and Dr. read Clark and obviously, our goal and targeted and every intention is to have that done well in advance of the commencement of our.

Ritu Baral: Your line is open. Hey guys, thanks for taking the question. So, Doug, you mentioned that you have, I guess, locked in a placebo-controlled design aspect of the Phase 3, the 301 trial. Can you describe your current thinking on patient numbers, randomization? You didn't mention younger patients, and it sounded like you said that you're sequestering older patients in a different study.

Study three which he is going started the middle of 2020. So obviously, we made great progress so far and assay development as it relates to our study three there a number of elements of it that we'll disclose later as we have further discussions with the agency. So we're all clear about the goals of that study. It's our it's our intention in that study to have data.

Okay.

And results sufficient both from approval perspective, as well as from an access and reimbursement perspective to serve a broad population for duchenne muscular dystrophy and by broad of course, we think both in terms of age we went from the youngest children to to the oldest patient with DMD.

Douglas S. Ingram: And just to clarify your answer to Salveen's question, and so have you finished assay validation? And if not, when do you think you might nail that down with FDA and start those engineering runs you mentioned? Answering the second question first, we still have work to do on assay validation, but we're making great progress under the guidance of Dr. Reid Clark, and obviously, our goal and target and every intention is to have that done well in advance of the commencement of study three, which is going to start in the middle of. So, obviously, we've made great progress so far on asset development. As it relates to our study three, there are a number of elements in it that we'll disclose later as we have further discussions with the agency.

And we also mean the bride in regard to mutations we want to ensure that patients across all mutations have an opportunity to benefit from this and the studies that were designing.

Our designed would that intention our main study the study that with the primary study.

Proposed for the functional results.

Is the age for seven year olds, and that's a one to one placebo controlled trial double blinded et cetera, multi site multi country trial.

But we have other studies as well with will we will have we will have some study for younger patients to your very good questions that we will have older patients and online money ambulatory patients as well in a separate study and we're planning does as well so.

Douglas S. Ingram: So we're all clear about the goals of that study. It's our intention in that study to have data and results sufficient, both from an approval perspective as well as from an access and reimbursement perspective, to serve a broad population with Duchenne muscular dystrophy. And by broad, of course, we think both in terms of age, we want from the youngest children to the oldest patients with DMD, and we also mean broad in regard to mutations.

So that that is our goal and our goal is to have this all commence by mid 2020.

Our next question comes from Brian Scorning of Baird. Your line is open.

Hey, good afternoon, guys. Thanks for taking the call.

You are on track for a mid 2020 start to study three but on last quarter's call you guided for first half 2020, you're actually said that you might do it is early in 2020 as possible first quarter possible. So I'm just trying to square away, if manufacturing's up online Lexington, somebody's running feeling good about your yields what sort of a change your between this quarter.

Douglas S. Ingram: We want to ensure that patients across all mutations have an opportunity to benefit from this. Our main study, the primary study proposed for the functional results, is in age four to seven-year-olds, and that's a one-to-one placebo-controlled trial, double-blinded, et cetera, multi-site, multi-country trial. But we have other studies as well. We will have some studies for younger patients, to your very good questions, and we will have older patients and non-older patients. Non-ambulatory patients, as well, in a separate study, and we're planning those. So.

This quarter.

I'm sorry, it's more mid 2020 as opposed to targeting first quarter possibility.

This is not so we're clear that you shouldn't read into my comments delay there's no delay here just to understand our goal is to lock. What's one locks process development. Then you have to go through an entire process of confirmatory runs and the like just to be it a in a.

Douglas S. Ingram: So that is our goal, and our goal is to have this all commence by mid- Our next question comes from Brian Skorney of Baird. Your line is open. Hey, good afternoon, guys.

Positioned to commence the trial now of course, you've got we've got site radius insight I or be approvals. So we've always guided to mid 2021st half between 20 to 2020 and that continues to be our plan. So to lead that at read My my current statements as a positive development that we continue to make good progress.

Brian Peter Skorney: Thanks for taking the call. You said that you're on track for a mid 2020 start to study three. But on last quarter's call, you got it for first half 2020, you actually said that you might do it as early in 2020 as possible, first quarter possible. So I'm just trying to square away if manufacturing's up online, Lexington facilities running, feeling good about your yields, what's sort of a change here between this quarter and last quarter to say it's more mid 2020, as opposed to targeting a first quarter possibility. This is not, so we're clear that you shouldn't read into my comments about delay. There's no delay here.

On analytical development capacity and process development. So that we will be in a position to fulfill our goal starting this trial by mid 2020.

Our next question comes from on you Palm ROM of JP Morgan Your line is open.

Hi, this is tough well now Karen.

No. Thank you for the updating for taking my questions.

Oh, one demo from now confirming light commercial supply we are one trial.

Somebody if indeed, there will be that lucky I have agreed to buy will be among chairman mouse. Unlike are different from expression.

Douglas S. Ingram: Just understand, our goal is to lock, once one locks process development, then you have to go through an entire process of confirmatory runs and the like, just to be in a position to commence the trial. And then, of course, you've got site readiness and site IRB approval. So we've always guided to mid-2020, you know, first half of 2020 to mid-2020, and that continues to be our plan. So read that at, read my current statements as a positive development that we continue to make good progress on analytical development capacity and process development so that we will be in a position to fulfill our goal of starting this trial by May. Our next question comes from Anupam Rama of J.P. Morgan. Your line is open. Hi all, this is Tess Romero filling in for Anupam tonight.

Body.

I think again comes from and what that this would readout in 2020.

Just one we'll keep reached agreement on how many patients will be went on like a month.

And then my second question, if I could on that sarcoma 18th program.

But from all that stuff, how mind for dosing ball.

Oh really how women kit went all the patients will be dealt with.

Just trying to think about potential pipeline for data on that on that program. Thanks. So much.

Yes on the first question, we have meetings planned with the agency across a number of programs, including about CMC and the studies. We are one design will have had done certainly plans in time to commence study three one by mid 2020.

On the effective sorry.

Yeah.

Out of respect for every analyst trying to get a question on the call. We're asking everyone that song Caf one question.

Anupam Rama: Thank you for the updates and for taking our questions. Just one thing left on the confirmatory commercial supply 301 trial. I wanted to confirm that, if indeed there will be, the FDA has agreed that there will be an interim analysis on microdystrophin expression in this study and that I think the intention was that this would read out in 2020.

Thats happy to follow up afterwards.

Our next question comes from Tim Lugo of William Blair. Your line is open.

Hi, This is John on for Tim. Thanks for the question I was just wondering if you can provide any additional details on the sanfilippo program, maybe specifically around the commercial prospects or the safety expectations from dosing directly into the brand.

Well I.

Douglas S. Ingram: Just wondering if you've reached agreement on how many patients will be in this. And then my second question, if I could, on the Charcot-Marie-Tooth program. Can you just remind us of the timelines for dosing here? Really, when they should, when all the patients should be dosed? Just trying to think about potential timelines for data on that. Thanks so much, guys.

I guess broadly speaking I can I can turn to we see by provide some insight on the.

Second that the two questions on the first of the two questions is obviously very rare disease, but we're very excited to serve.

This community this is a devastating disease that.

Historically has been bereft of any help these children.

Vincent Chin: On the first question, we have meetings planned with the agency across a number of programs, including about CMC and the Study 301 design. We'll have that done, certainly planned in time to commence Study 301 by mid-2020. [inaudible] We're just out of respect for every analyst trying to get a question on the call.

Degenerate, both cognitively behaviorally, and then neuro must surely rapidly commencing at about four or five years old and.

So you know there there is obviously, we're very excited by the commercially we're very excited about for our mission and then as it relates to the safety and scientific issues Luis if you have any insight into that.

I would just that as we've mentioned 13 patients have been does this is a direct delivery. There's the preclinical data is that's all that's the point that approach and that were getting very robust delivery into the parts of the brain that are meaningful for herb bylaw.

Douglas S. Ingram: We're asking everyone to only ask one question, so Taz is happy to follow up. Our next question comes from Tim Lugo of William Blair. Your line is open. Hi, this is John. On for Tim.

Tim Lugo: Thanks for the question. I was just wondering if you can provide any additional details on the San Filippo program, maybe specifically around the commercial prospects or the safety expectations from dosing directly into the brain. Well, I guess, broadly speaking, I can turn to Louise, who might provide some insight on the second of the two questions. On the first of the two questions, this is obviously a very rare disease, but we're very excited to serve this community. This is a devastating disease that historically has been bereft of any hope. These children degenerate both cognitively, behaviorally, and then neuromuscularly rapidly, commencing at about four or five years old.

Nickel and functional.

Efficacy so.

And this is that you'll need here I think I can speak about the New York.

Research filled out of the procedure for human patients.

So our it seems bye.

And.

I should say that gives you posted things or the concept of injecting addresses the brain is actually.

And experience has been developed over many years into context made therapeutic interventions and.

Well tolerated stage and we anticipate.

Douglas S. Ingram: So, you know, we're obviously very excited about it commercially, we're very excited about it for our mission, and then as relates to the safety and scientific issues, Louise, if you have any insight. I would just add, as we've mentioned, 13 patients have been dosed. This is direct delivery. The preclinical data is exceptional, that supports this approach in that we're getting very robust delivery into the parts of the brain that are meaningful for biological and functional. [inaudible] This is Gil Ronit here.

That said the benefit risk.

If I could be positive in the context of what is very serious disease.

Our next question comes from Liisa Bayko of JMP Securities. Your line is open.

Hi, Thanks.

But the couple of pertain to the model so how many patients on therapy and what's your sense everything our genotype right now and then also what viagra and that thanks.

Well for.

Gil Blum: I think I can speak about the neurosurgical elements of the procedure for human patients. So far, it seems fine. I should say, it gives you pause to think, or the concept of injecting, directing it to the brain. This actually...

So we're not we don't typically provide typically we don't provide.

Information on patients on therapy for the commercial product axon dates.

Sandy Sandy of a comment on gross to net.

Gil Blum: This is an experience that has been developed over many years in the context of many therapeutic interventions, and it's been well tolerated to date. Our next question comes from Lisa Bayko of JMP Securities. Your line is open. Hi, thanks for taking my question. Just a couple for change to the model.

Well, we haven't provided specific guidance on gross to net either I mean, when you look at our commercial and noncommercial split it hasn't really changed in the recent past.

But that's about all we have set so far on that topic.

Yeah.

We are now we are we're obviously very pleased with.

Lisa Bayko: So, um, how many patients are on therapy and what? is our genotype right now, and then also what's the... We don't typically provide information on patients on therapy for the commercial product Exondys. Sandy, I assume Sandy, you have a comment on GrossDNet? Well, we haven't provided specific guidance on gross net either. I mean, when you look at our commercial and non-commercial split, it hasn't really changed in the recent past.

The performance of of our products since its approval in 2016 as you saw we were continuing to grow in the last quarter, which means we're continuing to serve.

Additional patients with Exxon deserve a tough worsen and I should know there's some people I'm sure people know this but to the extent you don't know this we don't take price increases are and we certainly haven't in the past, though when you see growth on sales you're obviously seeing.

Additional patients being served by this therapy.

Unknown Executive: But that's about all we have said so far on that topic. We are obviously very pleased with the performance of our product since its approval in 2016. As you saw, we were continuing to grow in the last quarter, which means we're continuing to serve additional patients with Exondus or Teplersen. And I should note this, so people, I'm sure people know this, but to the extent you don't know this, we don't take price increases, or we certainly haven't in the past, so when you see growth in sales, you're obviously seeing additional patients being served by Our next question comes from Yun Zong of Janney. Your line is open.

Our next question comes from young song of Janney. Your line is open.

Hi, Thank you very much puts you kind of questions. So can you remind us sure. How you were going to leverage the data from the now 40 patients study to help you get a few approval now that you have a placebo controlled study plan to be initiative.

2020, apparently you won't be able to see any data from the 40 patients study before you initiate the pivotal study.

Correct, so one possibility and this will require.

First additional conversations with the agency and then obviously all of this will be considered in the context of the data when it actually develops.

Yun Zong: Hi, thank you very much for taking the question. So can you remind us how you were going to leverage the data from the Now 40 Patients Study to help you get FDA approval now that you have a placebo control study planned to be initiated in mid 2020? Apparently, you won't be able to see any data from the 40 Patients Study before you initiate the Pivotal Study. Correct.

But.

Again will be done dosing, if all goes well and things are going very well right now will be done dosing, we call study to the 40 patient placebo controlled trial by the end of this year, we'll have a read out on that 48 weeks thereafter.

Which will provide safety as well as functional.

Benefits of our micro dystrophin therapy.

Out of before that time.

Douglas S. Ingram: So one possibility, and this will require... First additional conversations with the agency and then obviously all of this will be considered in the context of the data when it actually develops. Again, we'll be done dosing if all goes well and things are going very well right now, we'll be done dosing what we call Study 2, the 40-patient placebo-controlled trial by the end of this year. We'll have a readout on that 48 weeks thereafter, which will provide both safety as well as functional benefits of our micro dystrophin therapy At or before that time, we will have expression related information from the next study, which is study 301, which is our commercial supply trial, at least we'll have that in a significant subset of the 301 trial itself, which means that at the time that there is a readout from our study two on function and safety, we will also have insight from both the CMC, and from biopsy data on the comparability of our commercial supply and our clinical supply.

We will have expression related.

Information from the next study, which is studies, we are one which is our commercial supply trial at least will happen in a significant subset of the three or one.

Trial itself, which means that the time that there is a read out from our study to on function and safety. We will also have insight from both the CMC.

Add from biopsy data.

On the comparability of our commercial supply.

And our clinical supply.

Certainly at that time.

We'll approach the agency and discuss the pathway for the fastest possible approval consistent with regulations and good signs and good safety.

Our next question comes from Vincent Chen of Bernstein. Your line is open.

Hi, guys. This is Brian on for Vincent I guess I just have a CLO.

The future manufacturing model for your gene therapy programs is it will eventually to bring some capacity in house or is your sense, but primarily relying on the CMO says that the long term strategy.

I think it's a great question so.

Douglas S. Ingram: And certainly, at that time, we'll approach the agency and discuss the pathway for the fastest possible approval consistent with regulations and good science. Our next question comes from Vincent Chin of Bernstein. Your line is open. Hi guys, this is Brian on for Vengeance. I guess I just have a question about the future manufacturing model for your gene therapy programs. Is the goal eventually to bring some capacity in-house, or is your sense that primarily relying on CDMOs is the long-term strategy? Yeah, I think it's a great question.

You know as you know you can see through what we're doing from a platform perspective that I understand here. Even now I think we have one of if not be deepest gene therapy specific pipelines and it's because we intend to be.

A durable enduring gene therapy Biotechnology company treating recipes for a long time that means we're going to be looking at lots of things. We have a we're very excited and we're very pleased right now with our hybrid manufacturing model. That's allowed us to move rapidly to gain expertise quickly and to work with somebody the best and brightest and we're pleased with that and that's why we have great relationship.

With that I'll never on him with Braver now Thermo Fisher Paragon Catalent.

Douglas S. Ingram: So... You know, as you know, you can see from what we're doing from a platform perspective that as we stand here, even now, I think we have one of, if not the deepest gene therapy specific pipelines, and it's because we intend to be a durable, enduring gene therapy biotechnology company treating rare diseases for a long time. That means we're going to be looking at lots. We're very excited, and we're very pleased right now with our hybrid manufacturing model. It's allowed us to move rapidly, to gain expertise quickly, and to work with some of the best and brightest, and we're very pleased with that. And that's why we have great relationships with Aldebaran and with Brammer, now Thermo Fisher at Paragon, now Catalan. But we're looking at other things as well down the road. We'll certainly do feasibility studies on whether additional capacity internally makes sense, and we'll look at other modalities even beyond the approaches we're taking right now.

But we're looking at other things as well down the road, we'll certainly do feasibility studies on whether additional capacity internally makes sense.

And we'll look at other modalities, even beyond the approaches were taking right now, but as it relates to our micro dystrophin program at least with girdle programs that were working on right. Now. This is the approach, we're taking and it's it's working well for us.

Our next question comes from Tim Chiang BTI G. Your line is open.

Hi, Thanks.

I don't know if you mentioned the number of patients that are enrolled and study to.

Just wondering if you had account.

Up to 40 patients that you're targeting.

Studying how many of them have already have rolled and then how many patients you expect Dr shape to enroll up to 40 patients.

I don't have detailed on the split between document Dell and Dr. Jay can tell you, there's a significant inventory of patients both sides. So.

Douglas S. Ingram: But as it relates to our microdistribution program and these loyalty programs that we're working on right now, this is the approach we're taking, and it's working well for us. Our next question comes from Tim Tang of BTIG. Your line is open.

Being able to fulfill our our need to get everyone does by the end of year shouldn't be an issue I don't have an update or count on the number of patients dosed site. When we know that the first 24 patients were all dosed before the last time, we spoke on our earnings call were dosing patients even as we speak in fact I want to get to over my skis on these things in a patient with.

Tim Lugo: Hi, thanks. Doug, I don't know if you mentioned the number of patients that enrolled in Study 2. I was just wondering if you had a count of the 40 patients that you're targeting for that study. How many of them have already enrolled? And then how many patients do you expect, Dr. Shea, to enroll among the 40 patients? I don't have details on the split between Dr. Mendel and Dr. Shea.

Those today. So we're on track to had everyone dose by the end of this year.

Our next question comes from Joseph Schwartz of SPP Leerink. Your line is open.

Hi, good evening, Thanks for taking my questions. This is.

Moving on for Joe So Doug just sorry, if I missed this I'm just thinking about the timeline going forward I briefly contra talking about study to being complete enrollment wide body ended the year with 40 week data towards the year end of next year.

Douglas S. Ingram: I can tell you there is a significant inventory of patients at both sites, so being able to fulfill our need to get everyone dosed by the end of the year shouldn't be an issue. I don't have an update or count on the number of patients dosed. We know that the first 24 patients were all dosed before the last time we spoke on our earnings call. We're dosing patients even as we speak. I don't want to get too over my skis on these things, and a patient was dosed today. So we're on track to have everyone dosed by the end of the week. Our next question comes from Joseph Schwartz of SBB Lyric. Your line is open.

Think about the calendar or the timeline of studies, three which is anticipated to study in mid 2020.

I guess given the competitive landscape somebody other guys that are.

Our using back tried and if that's all that goes for example, as well as your commercial product and somebody other micro dystrophin players also entering a larger phase three trial in 2020.

Joseph Patrick Schwartz: Good evening. Thanks for, Dog, just, uh, sorry if... Timeline going forward. Think about the calendar or the timeline of Study 3, which was anticipated to study in mid-2020. Um, can you maybe talk about, Well, I'll say some broad stroke statements and Dr. O'Neill may want to comment on things like trials. We don't take for granted the leads that we have, but we do have a lead right now versus other folks, and we've already, by the end of this year, we'll have 40 patients dosed in our placebo-controlled trial, our proof-of-concept study with our first four patients, of course, we've done some time ago, we'll have data on those first four patients in the publication in the near term, and we're very confident about the progress we're making towards study 301, and I think we're very confident about where we'll be at the end of 2020 as we're reading out the functional data from study two and the opportunity to have biopsy and CMC-related data from study 301, but with that said, Dr. O'Neill, if you want to make any additional comments. We are already actively engaged with sites through our prior and ongoing efforts with our PMO programs, and we are actively engaged with sites around the world.

Can you maybe talk about comfort level in terms of your enrollment how many trial sites are you anticipating and whats your target enrollment here that can actually get you through to that year end biopsy data.

Matched the concurrent.

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Well I was just in broad strokes statements and Dr. on the only want to comment on things like trial site numbers and Allied just broadly I understand the following week.

We are we don't take for granted the region, we have but we do have lead right now versus other folks and and we.

We've already deal by deal this year, what 40 patients dosed placebo controlled trial I proof of concept study with our first where based of course has done some time ago will have data on those first for patients and the publication in the near near term and we're very confident about the the progress we're making toward study three one we're very very confident about where we.

We'll be at the end the 2020 as we're reading out the functional data from study too and.

The opportunity to have biopsy and CMC related data from study three alignment with that said Dr. Deal. If you want to making additional comments. So all I would say is that we're very conscious of issues raised around competition or that's not read right of way of putting it but you know patients actually times decides on side to side the across different study we are.

Gauging, we already obviously actively engaged with sites through our our prior an ongoing efforts with.

Our at PMO programs, and we are actively engaged at sites around the world.

You know looking and evaluating an interest expense landscape and the capacity and participation and she will say so we actually confidence that we can enroll.

Douglas S. Ingram: [inaudible] But I'd say we are very conscious of the issues you've raised, and that's why we are being very careful and... There are no further questions. I'd like to turn the call back over to Doug Ingram for any closing remarks. Thank you very much, and thank you all for joining us this afternoon and this evening for our update. We look forward to executing against our plans for the remainder of 2019 and, obviously, to providing a further update at our next conference call early next year. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect. Thanks for watching!

As is required to meet the timelines we got line.

But I'd say, we are very conscious of issues you raised and that's why we're being very careful and precise and how do we evaluate engagement so you'd sites.

There are no further questions I like to turn the call back over to Doug anger for any closing remarks.

Thank you very much as they do all for joining us this afternoon's evening for our uptake we look forward to.

Beginning with our plans for the remainder of 2019, obviously, the providing a further updated our next conference call.

Early next year.

Thanks.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participating you may now disconnect.

Right.