Q3 2022 Sarepta Therapeutics Inc Earnings Call
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Good afternoon, and welcome to the selection of Therapeutics third quarter 2022 earnings call.
A reminder, today's program is being recorded to ask a question during the Q&A session you will need to press star one one on your telephone and you'll then here an automated message advising that your hand is raised at this time I'll turn the call over to Mary Jenkins Senior manager of Investor Relations. Please go ahead.
Thank you Cathy and thank you for joining today's call earlier today, we released our financial results for the third quarter 2022 press releases available on our website after up to Dot Com and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.
Joining us on the call today are Doug Ingram, and Astra patents, Alan Murray and Dr. Louise Ricky I'll play back after our formal remarks, we'll open the call for Q&A.
Like to note that during this call we were making a number of forward looking statements. Please take a moment to review our site on the webcast, which contains our forward looking statements. These forward looking statements involve risks and uncertainties many of which are beyond its control actual results could materially differ from these forward looking statements and any such risks can materially and adversely.
Back to the business the results of operations and trading prices for <unk> common stock.
For a detailed description of applicable risks and uncertainties. We encourage you to review the company's most recent quarterly report on Form 10-Q filed with the SEC as well as the company's other SEC filings.
<unk> does not undertake any obligation to publicly update its forward looking statements, including any financial protections provided today based on subsequent events or circumstances.
And now I will turn the call over to our President and CEO , Doug Ingram, who will provide an overview of our recent progress.
Thank you Mary good afternoon, everyone and thank you for joining interrupted therapeutics.
Third quarter 2020, <unk> financial results conference call.
So let's start with performance as you will have seen in our release, we had another strong quarter, serving the community with our three approved therapies exon 51 by on this 53 and the bond is 45.
As we mentioned on our second quarter call.
About $5 million anticipated for the third quarter came in and was booked in the second quarter and even with that total revenues for the third quarter was approximately $233 million and net product revenue was $207 8 million, representing a nearly 25% growth.
For the same quarter last year.
Remind you in the second quarter, we raised our full year total revenue guidance to between 905.
$920 million and our net product revenue guidance to between 825 and.
$840 million and in light of our continuing strong performance, we remain comfortable with that guidance.
So, let's move now to our gene therapy platform and specifically to SRP 9001.
Our gene therapy for Duchenne muscular dystrophy.
Just wondering if you wanted to it's been a momentous one for SRP 9001, and for the Duchenne community that we serve over the course of the first half of 2022, we discussed with the FDA the possibility of submitting a biologics license application or BLA for the approval of SRP 9001 on an accelerated basis.
As a result of those those discussions in the written feedback that we received we announced on our second quarter call that we intended to submit a BLA for the approval of SRP 9001 to treat ambulatory duchenne patients and in the third quarter, we did indeed submit our BLA for <unk>.
001 now.
Now if all goes to plan the FDA will accept the BLA for filing at the end of November of this year.
We anticipate that the <unk> date on our BLA in May of 2023, and a successful launch by the middle of 2023.
So those who have asked why we are trying to move so urgently, let me talk for just a moment.
Why seeking accelerated approval here is not merely appropriate but as compelled by good science.
Where justified by appropriate disease therapy, and evidenced the accelerated approval pathway as an innovative modern tool that is extended and saved countless lives, including patients living with HIV AIDS patients living with cancers and patients living with Duchenne It brings therapies to patients in time.
And actually intervene and do good and at the same time it results in an explosion of innovation and the FDA itself has repeatedly noted the opportunity for accelerated approval in gene therapies were approved appropriate and from our perspective SRP 9001 is an ideal candidate for accelerated approval review let's.
Consider first patients need this therapy now not someday or eventually.
Is the enemy of those living with Duchenne it irreversibly robs children of their muscle and nerve function on an hourly and daily basis.
Ultimately, killing.
Preventing further disease progression is the greatest need of every duchenne family and patients should not have to have irreversibly suffer when a well established regulatory pathway exists to bring that therapy to them now.
Duchenne is a well characterized monogenic disease and the shortened functional dystrophin robustly produced by SRP 9001.
As an upstream surrogate endpoints for accelerated approval, one addressing the proximate cause of disease.
<unk> founded on a wealth of scientific evidence supported by preclinical.
Related biomarker.
Clinical functional benefits.
One based on a well established precedent as the FDA has approved for therapies to date using shortened functional dystrophin as a surrogate endpoint and finally, we are well underway to confirm the results of that accelerated approval or proposed confirmatory trial embarked isn't fully rolls and.
Fully dosed so children can get this treatment rapidly and the accelerated approval will be expeditiously confirmed through embark.
The risk of granting accelerated approval is leading the small while the risk of harm to duchenne patients. If we did not seek accelerated approval.
Certain as severe and is available.
So planning for the success of our BLA, we are ramping up manufacturing.
We have bolstered our commercial medical affairs patient services and access teams.
And we are focused on site and launch readiness.
Additionally, we have already commenced the study to narrow the early exon mutation exclusions currently and embark and thus if successful to <unk>.
We expand the availability of SRP 90012, a larger percentage of the Duchenne population.
Likewise, we are finalizing the protocols of the commencement of envision.
Our study for non ambulatory patients as we look to expand the label for SRP 9001.
Non ambulate ambulatory patients as soon as possible.
And continuing on the theme of expanding the addressable population next year, we intend to start a study with our partner <unk> Biopharma.
Explore the use of <unk> to cleave IGT in RH 74 positive duchenne patients with the goal of safely and effectively permitting dosing with SRP 9001.
Dr. <unk> will provide further commentary on our gene therapy plans and those will include our plans for <unk> in 2023 as well.
Now moving to our RNA franchise as you are aware, we have three approved PMA was today and Saunders my arms instead of months. The first of those approvals Exxon just 51 came in the fall of 2016.
Nearly six years ago.
So in addition to continuing to prosecute our two main post marketing commitments for those approval essence submission. We have had the opportunity with respect to Exxon is to evaluate the world evidence of the effect of our PMO therapies over time.
At the World Muscle Society Conference in Halifax, Nova Scotia in October we presented study results on the benefits of exogenous versus natural history controls.
For those interested you will find the poster on the Investor page of our website, including the survival benefit associated with the axons.
Doctor Rodino Clat <unk> will discuss these findings in her remarks momentarily.
<unk> was approved on an accelerated basis using internally shortened functional dystrophin as encouraging as the early data was to support its approval and that of my honest and a bond as well with a degenerative disease those full benefits mature and reveal themselves only over time and that is the VAT.
When you have an accelerated approval to the lives of patients living with a deadly degenerative disease.
Without it patients would have been denied this therapy at least by additional years and perhaps we would never have been able to generate this long term data without that approval.
So moving to our next generation RNA therapy, the peptide conjugated PMO or P. P. M. A S R.
<unk> hundred $50 51.
We are dosing momentum part D and we are on track to complete enrollment this year and we'll have a data.
Data readout on that trial in 2023.
Finally, commenting on our management transition.
Were announcing Tonight, the Bill Sham Brown, our head of technical operations and manufacturing will be retiring I would like to give a big thank you to bill without whom we would not be in a position to launch SRP 9001 next year.
After an impressive career bill had been largely retired when I approached them in 2019.
But given our mission and our science.
And I'd like to believe some fair amount of persuasion for me I was able to coax bell out of retirement and given three important goals first to complete the process and analytical development for SRP 9001, and to ensure we had capacity to launch SRP 900 wanted to fully meet the need of the computed.
Second to build a robust sustainable technical operations function that has the talent and the focus to scale with <unk> ambitions and.
And third to prepare his successor as Dow had intended to make a large a large impact in a relatively short period of time.
I am proud to say that bill achieved every one of those goals we have the process the people and the capacity to launch SRP 900 wanted to make it a success.
Built a best in class organization, and we now have over 300 technical operations personnel driving us forward.
Bill has prepared an ideal successor.
Bill will transition leadership of the technical technical operations organization to below reached at the end of this year and then he will stay with US as both an advisor to me and to the manufacturing organization through June 2023. After the presumed <unk> date for SRP nine years or one.
The law was done with <unk> and intimately involved in all aspects of our manufacturing activities, including SRP 9001 from the beginning of 2019. He has well over 20 years of experience, including over eight years at Shire, where he worked for and close we would bill I'm absolutely.
Confident that as the law, we could not have a more aligned successor to bill someone who will continue our progress without missing a beat who will continue to drive our technical operations and it was intimately familiar with our strategic priorities and the tactical requirements for success.
Bill has made an enormous impact.
<unk> and he's been a great thought partner for me and for all of my colleagues on the Executive Committee and I know that sentiment is shared by our board as well.
I am very pleased that he will remain involved in advisors through the approval of SRP 9001. So thank you bill for all that you've done and for what you will do for <unk> and for putting us in this great position to be successful.
And with that let me turn the call over to our head of R&D and Chief Scientific Officer, Dr. Louise Rodino quite back Luis.
Okay.
In the third quarter, we achieved two critical milestones for the <unk>.
<unk> nine.
Okay.
The completion of enrollment and dosing.
Mark.
Many of our BLA to the SEC ahead of schedule.
Cannot be prouder of my team.
R&D and regulatory for their commitment perseverance and execution, while keeping duchenne community and our mission at the forefront.
On a personal note these accomplishments I, both personally and professionally meaningful and bring us closer to realizing the potential of SRP 901, as a treatment for duchenne.
What we've accomplished thus far with gene therapy for Duchenne is just the beginning.
Leveraging our learnings from SRP 901, and are applying them to the candidates in our deep genetic medicine pipeline.
Nearly the entirety of my professional career has been dedicated to genetic therapy research my team and I have never been singularly focused on bringing just one trying to market.
Instead, finding a way to shift the paradigm and creative platform that shortens the development time, producing multiple targeted therapies.
In parallel and align to our strategy and things like the best therapies to treat the widest array of patients with genetic diseases. We are pleased to announce the advancement of our Milo AAV platform with the broad Institute and my team and hybrid mile. AZ is a new group of Adenosis data viruses that uses a modified capsid.
Other protein shelf easy to deliver genetic therapies with greater efficiency and at lower doses.
The platform has the potential to offer another breakthrough in genetic medicine delivery with early research showing significantly greater gene expression at lower doses comparison natural thorough type capsid.
Now moving to our PMO therapy.
One of the highlights corrupt is impressive presence at the 2022 World Muscle Society conference that took place in October .
In total we had 14 posters and presentations several containing new data from across our genetic medicine portfolio.
I'd like to focus for a moment on a key late breaking real world evidence presentation on the type of person and treated patients with Duchenne amenable to exon 51 skipping.
This new analysis showed that treatment with a 10% resulted in statistically significant survival benefit compared to control natural history comparator occurred additional patient.
The analysis found that patients treated with a 10% per annum 579 patients survive five four years longer when compared to untreated reproduced patient level data from dish and natural history study, which had an end of 1224 patient.
Additionally longer exposure to 10% was associated with increased survival benefit.
Patients treated with a couple of things for less than 10 years.
Survival consistent with the natural history arm, but the hazard ratio of <unk>, eight nine and a P value of 0.64.
Patients on therapy for two to four years showed increased benefit, but the hazard ratios 0.36, and a P value of point. There is there are five and.
In patients on therapy for four plus years had the greatest benefit with a hazard ratio of 0.11, and a P value of less than <unk> one.
The findings were generally robust sensitivity analysis conducted across cohorts, including natural history controls.
The $5 four year survival benefit was observed in the most conservative of the analytical models.
Other findings from the analysis concluded accomplishment patients appear to have a 66% higher survival compared with dish and natural history control or P is less in point. There is there is there one.
Also established in patients experienced prolong survival and has been.
Significantly longer survival from baseline compared with Duchenne natural history control, where P. S equaled 2.0011.
This finding is consistent in the subgroup of patients is 10 to 28 years at baseline.
Guests are most likely to be observed for P is equal to point to is there was there a one.
And finally predicted mortality rates were lower for Tesla and treated patients compare sufficient natural history controls for all patients between the ages of 10 to 30 years.
These new data on survival as a totality of evidence we have our type of thing.
It also includes a $2 seven year delay in the time to loss of ambulation, a significant milestone for patient physician and a slower rate of decline in lung function, leading to a difference of five seven years free of ablation.
As Doug noted full details of the posters are available on the Investor page of our website.
Now turning to gene therapy, and beginning with SRP 900.
As I mentioned at the outset of my remarks, we are thrilled to have completed the enrollment and dosing for the phase III embark study and submitted our BLA to FDA.
I'd like to take a moment to acknowledge the tremendous effort undertaken by our team. Many activities are done in parallel. So we can move quickly, but we were able to accomplish so much critical work in a short period of time because of the team's deep commitment to execution.
Our BLA with the plethora of an approval based on the expression of <unk> wanted to start off with <unk>.
Certain functional version of disruption as a surrogate endpoint reasonably likely to predict clinical benefit.
Among other things is supported by positive preclinical biomarker and clinical functional results.
In clinical trials SRP 9001 demonstrated positive results at multiple time points, including one two and four years. After treatment. In addition to the consistent safety profile.
L. A for SRP 9001 includes the efficacy and safety data from studies, one O 100 to 103 for endeavour as well as an integrated analysis across these three studies comparing functional results to propensity score matched external control.
Importantly, the functional data reinforce the consistency of NSA a improvement across across the three independent trials and show mean improvement across key secondary functional endpoints, such as time to rise and 10 meter walk run.
Quantification of the SRP 9001 protein expression and that's it.
Western blot and supported by any of the.
The expression data from across our clinical studies demonstrate consistency from both our clinical and commercial manufacturing process.
In particular, the clinical results from endeavor.
They showed that our <unk>.
Unintended commercial process material crews motor function and further confirms our confidence in the treatment effects of our therapy.
Facing the probability of success for a phase of the framework.
Additionally, these study serve to increase our level of conviction fern park, because both endeavor and embarked are being conducted using the same material.
Importantly, 101.
One one or two one O three an integrated analysis of the safety profile of SRP 9001 remains consistent and manageable with no evidence of clinically relevant complement activation.
As I've mentioned, we completed the embark and are encouraged because at over one month.
One dosing completion.
Safety profile remains consistent with our previous experience.
I wanted to note that as we prepare to enter a new period with the agency, we do not anticipate publicly sharing additional data cuts leading up to our 2023 regulatory milestones and the Embarq data read out.
We are committed to reaching as many individuals living with Duchenne as possible, which is why as Doug mentioned, we've commenced a new cohort as part of the endeavor study designed to narrow the Exxon it.
Early exon mutations that are currently <unk> and embark.
Also working to finalize the protocol for envision a placebo controlled study evaluating SRP 9001, and non ambulatory patients.
Additionally, we are in the process of starting an extension study for a gene therapy study, enabling us to follow patients out for a minimum of five years.
Our commitment to our limb girdle muscular dystrophy programs has not wavered and continues to be a key priority for scrap that we are pleased that our natural history study journey continues to enroll and represents a key component of our <unk> development pathway.
We will soon be conduct convincing an additional study for SRP 9003, he's been clinical material for <unk>.
And our book screens, and more ambulatory and Nonambulatory patients.
It's also our goal to start a study with commercial process material for SRP 9003 and 2023.
And finally in addition, soon we plan to commence a systemic pilot study for SRP stick was there is there are four dual vector or a 74 mediated gene therapy to treat <unk>, which is characterized by the absence of the protein just for Olin.
Our progress into the third quarter exemplifies our commitment to advancing the best science in the interest of individuals living with rare diseases. We are enormously grateful to the patients who are <unk> to participate in our clinical trials and their families to support them.
Our clinical investigators and experts to guide us to where we stand today again. Thank you again to our extraordinary team of scientists and professionals worked tirelessly dedicated for admission to Greenfield.
Got it.
Turn the call over to Don.
Activities Alan.
Thank you Louise.
The third quarter of 2022 represented another strong quarter of execution for <unk>. This RNA based PMO franchise net product revenue totaled 207 8 million in the third quarter with roughly $122 million for example, 50 $155 million for a modest 45.
And $31 million for <unk> 53.
As Youll recall from the second quarter and as Doug mentioned upfront.
We guided a $5 million pull forward due to ordering patterns, resulting from the timing of the July 4th holiday in Q2.
The results for the third quarter.
Including the pull forward played out exactly as we had expected and guided.
The pull forward had a disproportionate impact on your modest 45 net revenue in the third quarter.
We see the third quarter.
Emily for a modest 45 and expect the quarter over quarter growth rate to modestly rebound in the fourth quarter.
Overall, a modest 45 is very much on track with our expectations.
And we continue to actively identify and gain access to the Duchenne population amenable to exon 45 skipping.
It's also important to note that the exon 51 net revenue has been positively impacted by our ex U S sales growth in 2022.
X U S revenue continues to grow year over year and the vast majority of these ex U S. Revenues are currently coming from <unk> 51.
This is becoming an important contributor to net product revenue growth.
But at the same time introduces some quarter to quarter fluctuations as the order ordering patterns are different than what we see in the U S.
As it relates to the third quarter revenue, while exotic 51 U S revenues grew modestly.
<unk> revenue for the quarter was impacted by the Lumpiness in ex U S ordering patterns.
Taken as a whole the $207 8 million in total net product revenues for the third quarter represents nearly 25% growth over the third quarter of 2021.
We remain on track to achieve our full year net product revenue guidance of between $825 million to $840 million.
Moving on now to the performance of each of our three RNA based PMO therapy during the quarter.
For example, 51, we delivered $122 million and net revenue in Q3.
The third quarter net revenue for example is 51 represents nearly 6% growth from the third quarter of last year.
For a modest 45, particularly in light of the effect of the pull forward.
We're very pleased with the nearly $55 million and net revenue representing nearly 106.
Compared to the third quarter.
Only 21.
My honest 53 grew more than 24% over the third quarter of 2021 with net revenue of.
$31 million.
We have continued our market leadership position for the exon 53 of medical population and our team is continuing their efforts to get new patients on therapy and maintain existing patients.
As we've mentioned on the second quarter call. We don't expect any substantial changes for buy on this in the coming quarters.
In addition to another strong quarter of execution and revenue generation, we've accelerated our efforts to be launch ready for SRP 9001 by mid 2023.
As leaders in Duchenne, we feel the urgency of the patient community and will ensure that our deeply experienced team will be ready on day, one of SRP 930 one's approval.
Just as we were for each of our three PMO launches.
In the third quarter as our R&D colleagues, we're executing on our BLA submission ahead of schedule the customer organization ramp up for the SRP 9201 launch hit full stride.
Currently we are building out all of our field and head office teams, who the lead what we believe will be the most successful gene therapy launched to date.
Further we have started engaging with key sites, so that we and they are ready to support patients approval.
The magnitude of this opportunity is not lost on us.
We are the Duchenne market leader with three of the four approved RNA therapies.
To be poised to launch the first Duchenne gene therapy with the data that our R&D colleagues have generated is absolutely incredible.
We are ready to take the torch built on the efforts of our R&D colleagues and.
And deliver this important therapy to the Duchenne community.
On a personal note I want to share that I recently celebrated my years with disruptive.
During this time it has been a privilege to witness unwavering dedication to our mission and commitment to serving patients.
I am proud of our team's strong performance.
And execution since launching our first PMO six years ago.
The extensive experience we've gained has prepared us well and I feel that no. One is in a better place than we are to take on the launch of SRP 901.
With that I'll turn the call over to E&S depend for an update on our financials.
Thanks, Alan and good afternoon all.
This afternoon's financial results press release provided details for the third quarter of 2022 on a non-GAAP basis as well as the GAAP basis. Please refer to our press release available on our website for a full reconciliation of GAAP to non-GAAP financial results.
For the three months ended September 32022, the company reported total revenues of $233 million, which consisted of net product revenue and collaboration revenues compare to revenues of $189 $4 million for the same period of 2021, an increase of $49 million net.
Product revenue for the third quarter of 2022 from our PMO exon skipping franchise with $207 8 million compared to $166 9 million for the same period of 2021.
The third quarter of 2022 individual net product sales were $122 $3 million for example.
$54 9 million for a minus 45% and $36 million for <unk> 53.
The increase in net product revenue, primarily reflects the increasing demand for our product in the U S and around the world.
And each of the quarters ended September 32022, and 2021, we recognized $22 $5 billion of collaboration revenue, which relates to our collaboration arrangement with Roche the Reimbursable co development costs under the Roche agreement totaled $22 million for the third quarter of 2022 compared to $29 four.
<unk> million dollars for the same period of 2021.
On a GAAP basis, we reported a net loss of $257 $7 million or $2 94.
$48 1 million or <unk> 60 per basic and diluted share for the third quarter of 2022 and 2021, respectively.
We reported a non-GAAP net loss of $70 million or <unk> 80 per basic and diluted share in the third quarter of 2022 compared to a non-GAAP net income of $2 4 million or <unk> <unk> per basic and diluted share in the third quarter of 2021.
Third quarter of 2022, we recorded approximately $40 million and cost of sales compared to $23 $4 million in the same period of 2021.
The increase in cost of sales is primarily due to increasing demand for our products and an increase in write offs of certain batches of our products not meeting the quality specifications for the three months ended September 32022, as compared to three months ended September 32021, partially offset by a decrease in royalty payments during the three months.
And at September 30, due to changes in the Biomarin royalty terms.
On a GAAP basis, we recorded approximately $216 $7 million and $139 $1 million and R&D expenses for the third quarter of 2022, and 2021, respectively. A year over year increase of $77 $6 million. The increase is primarily due to increases in manufacturing expenses.
The continuing ramp up of our SRP nine here or there one manufacturing.
On a non-GAAP basis, R&D expenses were $193 7 million for the third quarter of 2022 compared to $119 6 million for the same period of 2021, an increase of $74 $1 million.
Now turning to SG&A on a GAAP basis, we recorded approximately $104 8 million and $61 $1 million of expenses for the third quarter of 2022, and 2021, respectively, an increase of $43 $7 million the.
The increase was driven primarily by an increase in stock based compensation expense, primarily due to an additional expense recognized through the CEO Grant modification agreement executed in the three months ended June 32022, which records, which is recognized over the service period.
On a non-GAAP basis, the SG&A expenses were $66 8 million for the third quarter of 2022 compared to $43 6 million for the same period of 2021, an increase of $23 $2 million.
On a GAAP basis, we recorded $6 $3 million in other expenses net for the third quarter of 2022 compared to $26 million in other expenses net for the same period of 2021.
The decrease is primarily due to an increase in interest income due to the investment mix of our investment portfolio as well as the reduction of interest expense incurred as a result of the repayment of our December 2019 term loan for the three months ended September 32022.
In the third quarter, we had proceeds of $1 $1 billion from issuing convertible senior notes due in 2027.
Additionally, we repurchased a portion of our outstanding 2024 convertible notes and prepaid in full the amount of outstanding related to the 2019 term loan.
The repurchase and prepayment of the existing debt resulted in a loss on debt extinguishment of $125 $4 million.
Being an approval a ninth or there one we anticipate that along with our current cash and our projected revenue that this offering will be sufficient to fund our operations to profitability.
We had approximately $2 $1 billion in cash cash equivalents and investments as of September 30 of 2022, and therefore, we are well capitalized to support the launch of FRP <unk>, one if approved and now I'll turn the call back over to Doug to start the Q&A Doug.
Thank you Ian for that Kathy, let's open the call for question and answers.
Thank you at this time, we will have the question and answer session as mentioned.
As a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced also please note to limit your questions to just one.
Standby, while we compile the Q&A roster.
Our first question comes from the line of Gena Wang from Barclays. Your line is open.
Thank you for taking my question.
I have one question regarding the SRP 9001.
Doug you mentioned that you expect <unk> D likely in May 2023, any concern that the review could be standard review and do you think if it's possible. The FDA would like to see three year study one with two data that will mature in January 2023.
So we.
In connection with our submission of our BLA of course, we have requested.
Priority review, we are planning for that and that's why we've mentioned.
The may deadline for the <unk> data at least that's our current expectation. So that is what we're planning for and that's what we assume.
And we haven't received any information for the agency or any.
Commentary from the division that would lead us to believe anything differently right now.
Okay. Thank you for a moment for our next question.
Our next question comes from the line of <unk> Ahmad of Bofa. Your line is now open.
Hi, Good afternoon, guys. Thanks for taking my question.
I just wanted to get some detail from you on where you are with your manufacturing commitments, what do you need to show FCA and if you do get a priority with this allow enough time for you to complete whatever commitments you have agreed upon before the launch with Christina Thanks.
Thank you very much <unk>. So obviously, we'll have all of this dialogue with the division during the review itself, but we're in great shape.
You will recall that summer before last in connection with the commencement of our.
Embark study the placebo controlled trial that we fully dose now.
We were required to and then.
Basically the <unk> CMC completed.
Assay work done as well so I think we're in very good shape right now to respond to any of the agency's questions.
Our submission that we made.
Is very detailed and has an enormous amount of CMC. So I think we're in very very good shape right now.
Okay. Thank you.
Our next question.
Our next question comes from the line of Gil Blum of Needham <unk> Company. Your line is now open.
Hi, everyone and thanks for taking our question so Doug.
Just helpful for US can you put in context, a six month difference for a <unk> patient.
Sure.
Okay.
Every day is first of all just so we're clear because I think probably underlying your question was sort of an assumption that the delta between a non accelerated approval submission and approval versus <unk> versus traditional versus accelerating would be about six months it would be much longer than that.
Because let's just remember if we if we were not seeking accelerated approval pathway didn't exist as it has existed.
Formerly since the nine these we would have to wait for the end of embark compile that information QC all of that.
By the time, we were all done with that we might be ready to start working on the BLA, we submit that BLA, sometimes in 2024, assuming we get priority review, we'd probably be getting approval in the <unk>.
Back half of 2024, if not the very end of 2024. So this is a.
Very significant delta in the lives of patients with Duchenne, but even six months. So let's be very clear is it is monumental in the life of Duchenne patient remember and I've said this before and it's not an exaggeration.
Every day when the Sun comes up and then the Sun goes down at the end of that day of Duchenne patients has been damaged and damage in ways that neither our therapy or any other therapy currently envisioned.
Would rectify that's not what therapies like this do what the what this therapy does is arrest decline.
And that's that.
It means that they would get damage on a daily basis that will not be reversed. It also means over a six month time, some in the United States, probably 200 or so of those children would have died and some other significant number of hundreds would be confined to a wheelchair for the rest.
Over their lives and some other group of them will lose additional milestones that they wouldn't have and some will be on a ventilator, maybe a few hundred will be on a ventilator and just that six month period, and then compound that because it is six months its upwards of 15 to 17 months Delta and the difference.
<unk> an accelerated approval.
<unk> approval is enormously valuable and it's not a valuable to a 200 or 400 or 600, it's valuable to the 10000 to 15000, because every one of those children is going to be damaged every single day that we wait and unfortunately with respect to science, sometimes science takes a long time and that damage is.
But when it is inevitable.
When there is a pathway there.
That provides an opportunity to bring a therapy.
<unk> are really good signs for patients.
We should be doing that and we should certainly be fighting for that and speaking of accelerated approval here as I've mentioned in my script again. This is sort of I would argue and I realize that that is the argumentation that this is this is <unk>.
Purpose built accelerated approval for something like Duchenne. It said it is a devastating life ending neuro degenerative disease. It is not well served right now there are only about 29% of the duchenne population that have any real therapy available to them.
We have a surrogate endpoint that is in some downstream correlated endpoint, but actually direct row directly relates to the proximate cause of this monogenic disease and we know why these children are dying we've known it since 1986, when the Duchenne the dystrophin gene and eventually it's <unk>.
Protein, where discovery or die because they are missing the shock absorber in their muscles that protects their muscles and then the final thing I will say on why it's so compelling from our perspective at least be seeking accelerated approval now is that we can confirm these results.
Relatively rapidly embark our placebo controlled trial as you know as we sit here today is fully enrolled.
Fully dose and so there isn't some argument about when the confirmatory trial will be complete it will be complete basically on a day search and <unk>.
So it would be as I said in my script and I really mean, it I think it would border on on the ethical which we had <unk>.
<unk> accelerated approval certainly after we had very detailed evidence rich discussions with the F D. A.
But thank you very much for that question. Okay. Thank you one moment please.
Our next question comes from that line of calling <unk> P. B S. You're mine is now open.
Good afternoon, and thanks for taking my questions. Just a couple from my side first on the case of my car devices. You have I think it was in cohort to Windsor three just any update here any further info it's around the call and then settled on file. This recent approach will change the screen other patients with <unk>.
<unk> and the reason for <unk> 50, 271, I believe to spend with the region <unk> region.
So to any index of concern of neuroscience around sort of potentially immunogenicity issues for patience lacking Nathan Crazy Internet region. Thanks.
Thank you no to the latter question, but I'm Gonna turn both of those questions over Dr. <unk> quite back I could provide additional color.
Thank you for that question, obviously, we are continuing to follow our patients as you recall, the patient and comfort K lift myocarditis.
Had a sustained cardiac function in normal cardiac function <unk> baseline there was a trip on an increased also as you know and and <unk>. These increases can occur and and natural history as well as a patient continues to do well and continue to follow them, but now.
Other.
Other updates other than that.
Uhm, it's terms of the genetic exclusions as leaves mentioned <unk> excluded want to 17 and embarked but we're conducting a cohort 530 to.
Narrow that down we have not had any concerns with the the C 10 minutes for a program.
Okay. Thank you [noise].
One moment links.
[noise]. Our next question will come from the line is helping rector from Goldman Sachs minus now open.
Thanks for taking the question and congratulations on the progress. This is Tommy on for solving and we're wondering if you've discuss the scenario where you get accelerated approval for nine O. One by embark is not starts vague on and I say, a potentially do the variability or other factors and.
Went on what it could be like the likelihood of them that you would get an odd calm things.
Sure. So let me start with the first one first before I comment on that hypothetical let me be very clear we're very confident.
Well Powell.
Howard well into the nineties. It is very well informed that entire studying it's design is very well informed now dealing with the issue directly and I think the question.
Underlying all of that is.
You know essentially what do you would you would you commit to removing the therapy from the market is embarking hit single that's not the actual staggered. The actual standard is look at the entire totality of the evidence and if the totality of the evidence been justified the continued.
Available any of it there. The then would you commit to remove it gives me answer to that is of course, yes that is the standard for accelerated approval and we would certainly do that notwithstanding. The fact, you were very confident and we're confident based not just on the power of that study, but on all of the data that we already have.
On the therapy, and I I apologize perhaps.
Someone could remind me of the second question.
Dot com.
Apologies yeah.
The short answer is that we haven't heard yet from the agency or whether or not we're going to get an AD com. We will know that probably shortly after the agency accepts our BLA, which should occur in late November but given that this is the first in his class, we're certainly planning for and assuming that we would get in.
Add common that would occur in the spring of 2023.
As for that.
Okay. Thank you.
One moment for our next question.
Our next question comes from Matthew.
With Morgan Stanley .
Mine is now open.
[noise] great. Good afternoon. Thanks for thanks for taking my question I just wanted to ask about some some of the some of the real world data that you presented in some of your thoughts just around the.
The time point for the primary endpoint and embark [laughter] you know I think one of the things a lot of investors are concerned about his potential variability from.
From patients I wonder if you've if you've considered I'm looking at a longer time point in that study and just your confidence that one year is the right time for the primary endpoint in that study.
Yeah. Thank you the real world evidence for embark first of all I mean for scientists. This is very exciting for us and we've had the opportunity to really follow those <unk>.
Over a number of years to see it emerge now remember of course that the Pmo's and and Niger is or what are very different right. The pmo's make a reliably make quantifiable amounts of disturbing and it does it very consistently across all of our therapy.
All of our studies, but it's making a much smaller amount of truncated functional district, and then 9001 bag. So the impact on the life of a child is different over a different time frame. It and just so we're clear cause I think there've been misunderstanding 9001 again makes a.
Truncated functional version of full length dystrophin as does Becker dystrophin are Becker type of Duchenne as well as the P M out.
And they're all kind of reasonable approximations of the same thing.
Then as we look to the 9001 study I would say again that we've taken into account the variability in the head originator of the of the patient population in the design of this study you've been very rigorous and well informed about it as everyone knows we have an additional wealth of natural history data in our own experience and.
I don't think anyone at least from an organizational perspective has been kind of experience. We have we have the one O. One data at a one O. Two data one data to data one O three multiple got worse. So we're well informed in the design of that study and I think relatively conservative in the assumptions that we make around the powering of.
Study and based on all of that including the amount of variability that we're assuming and the standard deviation we're assuming.
Feel very confident in the power of that study, which as I've said as well over 90% even conservatively assess assume so we feel very good about where we are and we feel very good about 52.
Week timeframe now I will also say that 52 weeks in the life of of.
<unk> patient is or is it a short period of time, but that's what makes 9001. So exciting that you can actually already see the fairly significant delta in the trajectory of disease. When you look at the trial that's been on 90014 52 weeks versus <unk>.
That's real history, and if you keep reading that out you see it expanding and expanding in two years you see at the four year Mark with the one O. One kids truly transformative as you would expect from something that deals with the root cause of the disease and changed the trajectory of the disease and a disease modify way where you're literally.
Over nine points on the 34 point scale when you get up to four years. So.
Two things about it one we're very comfortable with the power even bark and we are very confident and have a lot of conviction around those results.
It is one of the largest studies of its kind that exists right now and we're very excited about the what this mutation kids now one year two years three years four years five years 10 years, and I think you know far beyond that hopefully if we get approved.
Thank you one moment.
Our next question is from the line of Joe Schwartz That's S. B E Security. Your line is now open.
Hi, This is <unk>. Thank you for taking our questions today for S. R. P 9001 filing for ambulatory patients and we were just wondering if you have a sense from the F. B I asked her current data package insufficient to support us in ambulatory patients broadly regardless of age Justin.
Doc tax congested desire to initiate gene therapy, you sooner than later I also was curious if you'd maybe consider giving a study in D. M D patients younger than four to support their kind of similar to what size receiving with there are two to three year old study. Thank you.
So we you know to feel joy.
Confident about the approach, we're taking seeking approval for the ambulatory patient population remind us that the regulatory standard as well as the legal standard for extrapolate into greater parts of the population is well understood. When you have a presumed mechanism of action that would be applicable to a broader population you have.
The ability to study in a narrow population to see the effect as we were discussing a moment ago.
<unk> with the heterogeneity that it comes from a larger population than expect expand it to broader population. So that's why we've chosen the ambulatory population we want to get started as soon as possible on a placebo controlled trial for the non ambulatory population, we are actually an ongoing dose.
<unk> non ambulatory kids today, but uhm and our one O three protocol and we wanted to expand it to the non ambulatory patient population as soon as possible because you know those kids need this therapy rapidly and then to your point. We are I think we are in the planning stages for a study to.
Go uhm significantly lower but I'll turn that totally we sure do you know if I can talk about going even lower than the four year old population embark.
[laughter].
Thanks for that.
<unk> to say that we've done that.
<unk> <unk> for <unk>.
<unk> and <unk> My name is Stephanie to go even.
Younger than three years old as well that's certainly we are.
A therapy.
Primary address population.
Thank you.
Our next question.
Comes from the line of Brian Abrahams, a R B C.
Hey, thanks.
Thank you so much for for taking my question, maybe shifting gears limb girdle uhm, what's the latest on the C. M C assays and process development, there and then perhaps I misheard it but it sounds like there's gonna be a I guess a plan for two studies now with clinical materials, and then material and have subsequently with commercial scale.
<unk>, just any sense of conduct timelines and maybe how these two studies my combined to support a potential pivotal past next.
Yeah, I was trying to Luis can provide additional color, but I'll say it in the broadest strokes were still working on the <expletive> is or the commercial process release assays for 9003 to remind everyone that the start study that could form the basis of an approval. The current standards of the agencies to have those.
Assays, essentially done and ready for commercial use clinically use isn't sufficient so we're working on that it does take time and we're we're continuing that but our goal was to have all of that dynamic commend staff study in 2000 twenty-three as you pointed out we have two different studies, they're not the intention is not.
To have them done sort of serially, but they can be done concurrently. These are these are really in a very real sense unrelated studies, both of which should occur in 2023 and then the question is why are you doing two studies why not just do your study with your commercial processed material when the athletes are complete and the answer.
For that is that we have clinical material available to us that is very usable and we think would significantly benefit patients and would give us them really additional interesting insight in other parts of the population than the study population for purposes of our what will be <unk>.
[noise] pivotal trial next year with commercial process and so from our perspective. It only makes sense that we use that material and do a study and and gain additional insight wall at the same time from our perspective at least benefiting patients that Luis.
Okay.
Oh at <unk> Dot D X.
Okay, <unk> <unk> <unk> adaptation.
Have more destiny.
Non ambulatory patient that'll give a significant insight into the entire population.
And my chance not sure.
Sure.
Commercial processes.
Making sure that we're capturing the whole population with <unk>.
Okay. Thank you.
One moment please.
Our next question comes from the line of.
Peace corny at <unk>.
Your line is Hamilton.
Hey, good afternoon. Thanks for taking my question I, just really think about potential launch honestly clinical sites or <unk> with us and patient demand would presumably.
Presumably be pretty high I guess, one of your conversation has been like so far with tires I know the players are sort of pushback recently on some portage approvals just trying to think about the the the curb of the launch your obviously in negotiations what kind of pet, Arizona accomplishment and have some idea of utilization of the old <unk>, but do you think that there's.
Gonna be hurdles hold off until you got the Mark David out or do you think that parents will be relatively flexible initial so I'm pretty comfortable.
So it's actually a couple of things and down if I Miss anything ready, though first I'll say, what Darwin is probably too humble to say, which is the good news is there'll be lots of hurdles to overcome but we're battle hardened and the ability to work with payers and overcome obstacles and get kids on therapy I would you know.
Remind everybody that we've been with three approved therapies stomach Saunders, we've been growing yet what is you know between 35 and 40 per cent kagera now for nearly six years, our compliance and adherence rates well over 90% of our ability to get these kids on therapy, Uhm and with respect to a chronic therapy keep them on.
Therapy has been you know just tremendous we've been able to go to the prior off process in the reauthorization process wouldn't be it wouldn't be relevant for gene therapy that makes the point, we definitely know what we're doing the good news is that we are working significantly with payers, even as we speak we've been doing it for a <unk>.
Number of years to make sure we really understand their perspective, and what day one cause to your very good point I think that if you think about the things that can constrain demand or or open up demand. Let's go first from the patient perspective, it will be enormous we're not at all concerned patients or.
Are are desperate to get up there would be like this from our perspective, I think physicians will be equally in the same place. The third thing is capacity related issues at the sites are they well prepared to infuse as it relates to that our goal ultimately is to.
Have 70 experts sites available to infuse and in fact about 80 per cent of patients are served by about 50 sites. So we should be in very good shape and the vast majority of these sites already have significant experience with gene therapy were benefiting from the launch of Zolgensma and then the fourth one is payers.
Then I think we're working very.
Very well and very thoughtfully with payers very proactively repairs and that you know.
Thinking of some very innovative approaches and our goal is simply to get let's be clear I said earlier I know I'd get a little straightened about this but I feel strongly about it. These kids don't have the luxury of waiting they need therapy and they needed now and waiting three or four months for therapy is inappropriate. So we're working with payers on that exact issue, which is we don't just one <unk>.
Access we want access.
In a timely manner and I think well informed payers are gonna be not suggested it won't be challenges and the pairs are gonna be supportive and certainly when you look at our value proposition for our therapy and we've got a lot of work on the value of the.
The objective value of this therapy I think it's gonna be very compelling down from an uptake perspective, let me be very clear. It takes some time to get through the process. So you know.
Assuming we get approved the timeline, we envision it will take a couple of quarters to get through the process and start getting kids is used in the like but then I think the uptake is gonna be very robust if we've done our job well and I do think <unk> have the ability to do this very well probably second to none.
Down on my forgotten something that I shouldn't comment and no I think I think you've covered it does I I you know I think there's a couple of things that the payers, we've had constructive dialogue with the payers and there is a real high <unk>.
Level of receptivity to gene therapy number one secondly, and this last six years, thanks to the <unk> community and particularly R. K O L. So muscular kalo.
I think the Payor communities learned a lot about <unk> and then there's we're in a different place now than we were at the <unk> in the launch of.
In 2016 of exotic is 51, and then I think the last and very important thing I would say here is that thank you to.
<unk> R. R. D colleagues the data that we're gonna be launching with the publications that will have to support the value and in the work of our health.
Health outcomes folks as well <unk> valued framework that Doug was talking about we've learned a lot as well <unk> and this will be a very different we're well prepared.
To engage in constructive dialogue here.
[noise] Okay. Thank you.
Our next question comes from the line of 10, Lucco Williams Blair.
Your line is now open.
Thank you so much and congratulations on the progress I know, we're all laser focused on the end.
Even the Embarcadero next year. However, we haven't heard much about Europe in a while can you just give us an update on your relationship with rose.
The timeframe for Oh, we're making an impact in Europe and beyond I assume it's going to be embarked dependent no matter what occurs with the <unk>.
Yeah. Thank you for that so first we have a great working relationship with Roche I think you can.
I think you'll see it revealed in their public statements that a <unk>.
It seems to be about as bullish as we are about this therapy publicly and that certainly is reflective of the very positive working relationship we have with our colleagues at Roche and then we got a very good.
Uhm collaborative approach across all aspects of this development program commercial plan, a regulatory and the like yeah, I I I'm in on Europe , and beyond Europe to other parts of the world outside the United States I will leave it to my colleagues that Roche to inform the external world on the timing of thing.
Other than to know what you've noticed sandwiches that that I think that Roche. His public statements have been they will rely upon the embark read out as the pathway for their approvals and then the H T. A discussion, but they'll have in Europe and around the world. So I think that unless we get something different from Russia, I think that they are a public statement.
And that's why we shouldn't rely upon.
Okay. Thank you.
One moment for our next question.
Which comes from <unk> Rama F. J P. Morgan Your line is now open.
Hey, guys. Thanks, so much for taking the question I wanted to follow up on <unk> question earlier, and I think you've kind of highlighted this a little bit but on the manufacturing side what are the 901.
Apply some areas that you're planning for looking to mixture pending approval and are there any sort of constraints or hurdles, we should be considering when it comes to supply axis as we think about this large cokes. Thanks so much.
Yeah. Thank you so I think with cause he knows answering a slightly different question, which was your point, which was you know are we in good shape from a C. M. C perspective, do we have the assays done in the quick and the data is supported in the answer to that is yes, we've done a ton of work and in fact, we did a ton of work before embark. So we were in very good shape and then I think.
Your question is a very good one which is how 'bout capacity or are you in good shape from a capacity perspective before we launch and the answer is yes, we're gonna be in very good shape, we're planning to launch for the Uhm ambulatory patient population that is our current working assumption broadly speaking and our goal is to fully serve.
Community without delay and even assuming fairly aggressive uptake and even assuming which I think is at this point a very fair assumption that we will be launching this alone.
Okay. Thank you.
Our next question comes from hearted sang F.
That's often hammer your.
Your line is now open.
Great. Thank you and thanks for all the updates and I just had a quick question. The <unk> program I don't need you and your colleagues. When you were a nationwide have been working <unk> 74 for over a decade and it seems you have a best in class movies after their.
What really attracted you to my O E V and you know I guess is is it significantly better than our 74 and lastly, you know how do you see it kind of getting into the clinic in D. M. D. L. G. M D. Thanks for the question.
Sure.
Luis the combo.
Yeah. Thank you for that question.
And.
Certainly where we love our 74.
Okay.
Hi, Bullishness about it my Lady and very exciting research phase and <unk> <unk> <unk>.
<unk> <unk> <unk> <unk>.
Okay.
Okay.
Yeah.
Uhm.
Uhm.
Once we continue to validate.
Clinical path alright, well that is all.
I I apologize.
<unk>.
Oh I'm sorry.
Okay, Let me just cutting out a little bit.
August August .
Pete less artfully, what Luis was saying, which was but first I will repeat what Luis said firmly we love already 74. We are excited that is that is really the the platform right now for our gene therapy focused on neuromuscular or a neuro and frankly Carter.
How may I help with these as well and there is no from our perspective at least there is no better current stereotypes.
From a safety perspective, coupled with a trope as in perspective, then alright 74. So this isn't about any negativity on already 74, we are thrilled with it obviously there is an enormous amount of future value to patients and to the breath of patients.
Patients if one can find ways to decrease dose, which would make therapies more affordable around the world et cetera, and probably increase safety and the like we have a long way to go we haven't dose any patience or even healthy human volunteers with my old Navy, but at a preclinical an antique.
Model perspective, we're seeing some things that really excited about the potential at least for my way or it could be literally and.
An order of magnitude more <unk> than any of the current Sarah times, which would really be extraordinarily meaningful it would be meaningful around.
Around the World and places like India, and Africa, Other places, where we're going to have to find a different kind of cost of goods to really have the full breadth of of the benefits of our therapies, including 9001 and it probably takes system. Many other kinds of disease states that would be challenging today and.
These cost of goods with gene therapy. Currently today, there are probably certain kinds of ultra rare diseases that become very difficult.
And that's.
Frankly, that's not acceptable that's tragic because we have the ability to treat even very very rare diseases, we ought to be thinking about ways to do it and.
<unk>, maybe some other captured the currently the best thing we've seen her we've seen everything is my way via it could really be a transformative next generation.
<unk> two gene therapy.
So we are we are in love with our 874, but we are excited about the potential of my mileage do down the road.
Mhm thankfully it.
Thank you one moment alright next <unk>.
Questioner.
She comes from the line of <unk> Gupta as calling your mind [noise].
Hi, <unk> I wanted to continue questioning on the mile Easy program. So are you guys seeing any transaction of satellite much of a chance to hopefully get a sense of potentially improve your ability in in any indications.
Oh alright.
Hope get store.
Well I'm certainly we will we will explore.
Satellite cells into like I don't know asleep have yet.
Luis was Mike is working.
I've seen that one <unk>.
Uhm.
But just the mentioned we have also exploit I'm sorry.
The transaction that without a lifestyle not.
That's something we hardly think that one finally evaluate it with a mile a day as well.
Okay.
Thank you.
Moment for our next caller.
Which comes in the line of <unk> <unk>.
T I G. Your line is now open.
Hi, Good afternoon. Thank you for taking a question. It's actually an old question that had been asked before but now that you were talking about the long lunch of gene therapy program was strong confidence so probably more related so what kind of impact you expect that wants to have on your exxon's skipping revenues and are you going to be.
Build that into your lunch strategy. Please thank you.
Yeah. So you know one of the things we've talked about often as an organization is that we are patient driven patient mission driven organization. So let's start with the first premise. If indeed, we have a therapy that is as beneficial as we believe 9001 isn't it has an impact or greatly cannibalizes.
The current excellent skipping platform and the children as a result of that are benefiting from it. We're thrilled so I just let it be very clear about that from our perspective, we lean into the best technology for kids. We do believe first of all though that there will be a significant place for both actually.
Gene therapy, and our Exxon skipping therapy here PMO or our next generation P. P. M. L for a very long time take up first I would remind everybody and we won't see significant cannibalization in the in the near term in any event for a number of reasons. So the first thing to notice that we are over for.
50 per cent of our current therapies are about 50 per cent of our current patient population on our Exxon escaping as non ambulatory so they need they.
They need this therapy, while they're waiting for us to get 9001 approve second of all there until we do something about it there are strict neutralising any body related kids, maybe 14% or so that won't have availability for gene therapy, we're trying to do.
Something about that as I mentioned in the opening remarks, we're going to start a study with a partner Honda and we're very encouraged by the preclinical data that we've seen and we may very well be able to address that but until that is addressed the that therapy will continue to benefit those kids and then of course around the world there'll be a lot.
And places both of the U S and around the world whether it is may be the availability for a P. M O or P. P M O where gene therapy or not so I do think they will co exist for some time and then of course that doesn't even consider.
The issue of the co administration of gene therapy, and then a P. P M O or P. P M out, which at least and some of the preclinical models and even some literature would suggest is an an additive value to have both together and if that's the case then we're doing some basic research on that to continue to explore it then you would have a long.
Term answer for kids with a one time therapy and then you know over the long run a chronic therapy, but I will go back to the statement I made at the beginning if eventually this 9001, it's so significant as we believe it is and that it results in cannibalization of our Exxon skipping therapy.
And kids are benefiting enormously will be thrilled with that answer correctly and you'll be thrilled to let's be honest as an investor you'll also be thrilled because this is the population that can be addressed with 9001 is is.
Right now it's enormous even with the current restrictions and then we're reducing actually started dosing already a study to reduce the amount of early exxon's. It would have to be excluded we're focusing on the neutralizing antibody positive patients and we're gonna start a study on that that if it works.
Would bring another 14% of the kids and then frame for US and then of course the biggest of all is getting to the non ambulatory kids and we're gonna work like Mad to get that done and get the the label expanded to not ambulatory kids as fast as possible.
Thank you.
[noise]. Our next question comes from the line of Christian <unk> I've Cantor Fitzgerald.
Line is now open.
Hi, This is Rick on for Christian Thank you for taking our questions for the real World <unk> data presented at the World Muscle Society could you talk about how you're specifically thinking about the importance of these data in the high unmet need known ambulance population. Thanks.
Well, let's.
Beauty, but.
With respect to districts. It. So I guess, that's an interesting question. The question is you know what what package you have an automobile first of all understand all this data is equally applicable across all of the population because.
Every kid is there may be a different.
Part of the journey or place in the journey, but they're all suffering from exactly the same issue they are missing.
Functional dystrophin as a result of which they are damaging their muscles every time, they move them and the value of this real world evidence is it as proof over a very long period of time that what we saw at the beginning with the song this really reveals itself over time.
So I think it's really it's really important in that regard and it's important for scientists if it's important it's important for August it of course.
No metaphorically as in and sort of by example makes the point of the value of accelerated approval.
You can just imagine what we will see you over time with 9001, let me think about the amount of dystrophin that is induced with 9001 and then finally, let me be very clear cause I want to move back to something that's important which is with respect to restart my honest I'm honest, we have a significant number of postmarketing commitments, we have literally invested already <unk>.
Words of millions of dollars and progressing those studies and two of them are really top provide estimates admission and I do want to be very very clear to everybody that notwithstanding what we're very excited about with respect to railroad evidence, it's our obligation and our absolute commitment to continue and.
Sure that we complete both of those studies as timely as possible.
The railroad evidence is is it's very encouraging and we need to continue to work or post Margaret cause that much as well.
Okay. Thank you.
One moment for our next question, which comes from the line of <unk> Ah Barringer. Your line is now open.
Great. Thank you very much for taking my question I'd like to ask about that the the external control that it that that if he could of Igor integrated analysis and the gene therapy package, it's 10 minutes, what kind of approval.
I Wonder have you got any alignment with the F D.
On the control external control faithful and natural history. Obviously, we are aware that recently there was.
Cause an active opinion from an oncology products from me.
The furniture Committee just wondering if you have.
Any.
There.
And how how important it is to have that that data.
To support you accelerated approval.
Very much.
Mmm well so first of all I think the the totality of evidence is extraordinarily important so the design why it exists the way it exists the extent to which it's a reasonable approximation of a becker dystrophin the preclinical work all of the related.
Bio Margaret work and then all of the clinical data that we have include any of the integrated analysis. We have one O. One those kids are one year two years three years now four years out we've got one or two part one and part two of those kids are one and two years out.
One O three abroad.
Look at kids from a safety perspective on one O three very broad age range is very broad weights and the like and certainly the integrated analysis pulling it all together is additionally, valuable what I would say on the F. D. A is that they have they've seen all of this data we've shared all of this information with them obviously all.
What their views all that's gonna reveal itself and the review classes itself, but we feel very good I don't I'm not sure. How one does an external control more rigorously the way we've done it just to remind people it's not as simple external control, we used a well matched external control, but then we mashed on for <unk>.
[noise] covariates, not simply one kilbury uhm.
Uhm age NSA a baseline.
10 meter walk run I believe rise time, if I'm not I'm not misremembering and then we we didn't even stop there we got that very closely matched but to ensure that we added tight correlation between the as closely a representative external crucial was our actual group as possible. We did this regression analysis.
<unk> and his propensity matching which essentially essentially synthetically makes the distribution not simply the means of the distributions identical across the two so within the limitations associated with extremist controls. This is about as rigorous as one get and then on top of that I should note that many of the page.
<unk> and the external control actually came from placebo controlled trial, so to the extent that people might wonder about that they actually came from a very similar approach that you'd have to a placebo controlled trials because they were on a placebo at the time of their information was developed so yeah. We will have this full review of the agency I don't think it's any one piece of data I think it's.
All of the data that's gonna go into the discussion because remember with respect to accelerated approval. The fundamental question is does this surrogate endpoint in this case, we're talking about functional shorten district.
Is it reasonably likely based on all of this data reasonably likely to predict a clinical benefit.
We are obviously the sponsors that you can imagine what our perspective is but we believe it's very compelling.
Okay. Thank you.
A moment for our last question, which comes from the line of Gavin Clark Gardner.
Evercore ISI your line is now open.
[noise] Hey, thanks for taking my question.
<unk> I'm just wondering if you're planning to include a placebo arm for either of those next trials and what your current thinking on Registrational influences.
Luis two on it.
Texas.
Yeah.
Now that we.
And political thing about that is.
<unk> <unk> <unk>.
<unk> <unk>.
How can I help you.
More severe ambulatory and non ambulatory and talk about the three.
Yeah, I don't really.
By that.
[laughter] agreement.
Just to remind everybody with respect to 9003, so where you've seen in our we've done two cohorts with clinical material, you'll see we've gotten a.
Very similar safety profile to 9001, not surprising it's already 74 and it's the same promoter.
Seem very good expression across both of the code words, and I would remind you of two additional things when we think about what that study design ought to look like the first is to remember that the northern lights, Duchenne muscular dystrophy, uhm nine years or three treats TUI, which is it's the lack of data circled like in.
By a bit of sort of like an apathy. It is well characterized in that regard, we know exactly what's causing the demise and that the generation of these kids. It's the lack of data for hours before I can properly localized to the sarcolemma their muscle and 9003 induces an enormous amount of the native protein properly localized and.
In addition, with signals on the functional side associated with all of the addition of being functional.
Functional protein upregulation of the dystrophin associated protein complex reduction in C. K and the wife, so with all that in mind and given the fact that it is an ultra rare disease or.
Our view is that the the registration on trial for this needs to be.
It needs to be thoughtful and take that into account and be lean enough to get this trial done rapidly and get this therapy, the kids without undue delay or unnecessary.
Hi.
Okay. Thank you with no further questions I'd now like to turn it back into came from for closing remarks.
Alright, well. Thank you all very much for spending time with us This evening and thanks, everyone for your very insightful.
I have some questions obviously the next seven months.
Are among the most consequential in our history.
And we have a fairly long history and more than that I believe at least that are probably among the most consequential for <unk> patients, perhaps since the discovery of the dystrophin gene back in 1986, if I'm remembering correctly and so with that with that said, we're looking forward to all of the work that we have ahead of us.
And we're looking forward to updating you as we pass through these important milestones and would that I would ask anyone to have a lovely evening.
Yes. Thank you for your participation in today's conference. This does conclude the program. So you may now disconnect.
The conference will begin shortly to raise your hand during Q&A you can dial 911.
[music].
[music].
[music].
[music].