Q1 2023 PTC Therapeutics Inc Earnings Call
Good day, and thank you for standing by and welcome to the P. T C first quarter 2023 financial results call.
All participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question. During the session you will need to press star one on your telephone.
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Please be advised that today's conference is being recorded I would now like to turn the call over to Kylie O'keefe Ah.
Chief commercial officer.
You may begin.
Okay.
Hello speakers.
Yeah.
Yes.
Good afternoon, and thank you for joining us today to discuss PTC Therapeutics first quarter 2023, corporate update and financial results I'm joined today by our Chief Executive Officer, Matthew Klein, our Chief business Officer.
Eric Powell, and our Chief Financial Officer, Emily Hill.
Today's call will include forward looking statements based on our current expectation.
Please take a moment to review the slides posted on our Investor Relations website in conjunction with the call which contains our forward looking statements.
Actual results could materially differ from these forward looking statements.
Such statements are subject to risks that can materially and.
Adversely affect our business and results of operations for.
For a detailed description of applicable risks and uncertainties. We encourage you to review the company's most recent annual report on Form 10-K filed with the Securities and Exchange Commission as well as the company's other SEC filings.
We will disclose certain non-GAAP information during this call.
Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in today's earnings release.
Thanks, Carey good afternoon, and thank you for joining the call I'm pleased to share <unk> first quarter results and our expectations for continued strong performance and a transformative 2023.
<unk> is a leader in developing and commercializing innovative therapies to treat rare disorders that are incredibly excited to lead PTC Intuit next quarter century, as we continue to utilize pioneering science deliver therapy to patients with high unmet medical need.
We had a very productive first quarter, achieving $220 million in total revenue our highest quarterly revenue at this represents 48% growth over the first quarter of 2022.
<unk> franchise revenues in the quarter totaled $170 million, which represents a 33% increase over the first quarter of 2022.
It will be also had a strong first quarter, providing royalty revenue of $31 million. The <unk> revenue growth continues to be driven by bulk therapy naive patients and those previously treated with old Gen y and spin route.
In addition, U S growth being driven by patients less than two months of age.
Following the recent NDA approval.
This robust first quarter performance puts us in a strong position to achieve our total 2023 revenue guidance of $940 million to $1 billion, which would represent 43% year over year growth.
In addition, as we previously shared we expect to use the study results to be reported in the second quarter to inform a strategic portfolio review and likely Opex reduction on which will provide further details once available.
Moving to our pipeline we remain on track to report results from four clinical studies in the second quarter three of which are registration directed.
Let me provide a brief overview of each segment and the result, we expect to shape I'll begin with our affiliate leaseback.
Affinity is a phase III global placebo control study of Cepheid parents and children and adults with PK.
The placebo controlled portion of the study was six weeks in duration with the primary endpoint of reduction in blood phenylalanine levels.
<unk> reached the randomized population for Cepheid, Karen responders, there was a running phase during which all screen subjects receive stepping a tariff for two weeks.
Legal subject, we demonstrated a reduction at Kendall alanine levels of 15% or more from baseline in part one were randomized for part two with the primary analysis population consisting of those who had a greater than 30% reduction in panel <unk> levels from baseline during the run in phase.
At fourth quarter earnings in February we shared the encouraging data from part one running phase in which approximately two thirds of treated subjects demonstrated a greater than 30% reduction in phenylalanine levels.
The meaningful alanine reduction for all subjects with at least 30% reduction with 66%.
In the mean reduction for classical PKU subjects with 61%.
According to contract and a more bio available and potent co Packers Cherokee Cepheid terror can provide a clinically meaningful and differentiated response, the full spectrum of PKU patients.
We look forward to sharing results from our placebo controlled portion of Academy in May.
Let me now move to the two registration directed trials in particular.
Miami is a global registration directed trial of <unk>, particularly in patients with mitochondrial disease, but the seizures.
That included a 24 week placebo control phase with the primary endpoint being changed from baseline and frequency of observed both motor seizures.
The last subject last visit for the placebo controlled phase occurred in March as planned and we continue to expect results in the second quarter.
It moved up a trial is a global phase III registration directed study, particularly in pediatric and adult patients with retracted taxis.
The study included a 72 week placebo control phase with the primary endpoint being changed from baseline in the validated <unk> score.
Last patient last visit for the placebo control phase is all quicker and we continue to expect results for move assay in the second quarter.
Moving to our PTC five eight Huntington disease program.
HD is a 12 month placebo controlled trial that consists of two parts.
One is 12 weeks in duration and focuses on PTC, <unk> pharmacology, and pharmacodynamic effects as well as bio distribution.
Part two is nine months in duration, where focus about blood based DSS base and radio graphic biomarkers of disease.
Study initially include two dose levels five milligrams and 10 got brands with the ability to include a third dose level of up to 20 milligrams leveraging the titrate ability of the molecule.
We initially included patients with stage two Huntington's disease, and we recently expanded the trial to include early stage III patients who will be study initially at the five milligram and 10 milligram doses.
We continue to expect interim data from the 12 week portion of the trial in the second quarter of 2023.
These data will include safety pharmacology pharmacodynamic by distribution data from the five milligram and 10 milligram doses.
With results of these four studies expected in the next several weeks beginning tomorrow, we will not be discussing these programs until results are reported for each study.
Turning to trends, we continue to expect that the HMP opinion for the type two variation to convert the European conditional marketing authorization the standard authorization in the second quarter and.
In the U S. We are preparing a type C meeting request to review with the FDA that totality of data collected to date that could support an NDA submission for <unk>.
Finally.
As we previously shared the FDA requested additional bioanalytical data in support of comparability analyses between the clinical and commercial drug product.
We have received initial feedback from the agency on these days and are in the process of responding to additional FDA queries prior to submitting the BLA, which could result in a BLA submission occurring in the third quarter of 2023, rather than the second quarter as previously planned.
Overall, I'm incredibly proud about productive and successful first quarter.
Now I'll hand, the call over to Eric to provide an update on our commercial portfolio Eric.
Eric.
Thanks, Matt our global customer facing team has kicked off 2023 with an extremely strong quarter capitalizing on the significant momentum we created in the second half of 2022.
Our team is focused on driving significant growth with our commercial portfolio of products for neurological and metabolic disorders.
We continue to make good progress with the stage of the launch in Europe .
We also have launched we lever up our familial partial lipodystrophy FPL in Brazil. Following the approval of this new indication in the fourth quarter of last year.
Our strategy and execution of geographic expansion continues to progress in Latin America, and our future growth markets in Asia, and we are in a strong position to achieve our 2023 revenue guidance as Matt previously mentioned.
Let me start with the DMD franchise, Trans Lara and Plaza continues to be an important engine for growth delivering an impressive $170 million in first quarter net revenue, which is up 33% compared to the first quarter of 2022.
Fortran, Florida, we achieved $115 million in.
In revenue this quarter, we continued to see strong growth across the major markets internationally.
And there were some large government orders contributing to our revenue in Latin America, Central and Eastern Europe , and the Middle East regions.
Given the unpredictable government ordering patterns in these markets.
We expect to see ongoing lumpiness in quarterly revenue throughout the year.
We remain confident that we will achieve our 2023 DMD franchise revenue guidance of 545 million to $565 million as our growth fundamentals remain solid with continued new patient starts high compliance low discontinuation.
And proper weight base dose adjustment on an ongoing basis.
The fundamentals of the employees the business continued to be solid.
Quarterly net revenue was $55 million we.
We have seen a significant number of new patients start forms in the first quarter, which will provide important momentum as we progress through the year, along with continued high compliance appropriate weight based dosing and broader insurance access.
Now turning to upstage, the first and only gene therapy approved to be infused directly into the brain.
We continue to see the transformative effects as new patients have been treated in Europe this quarter, including our first cross border commercial patients.
We see the steady rollout of upstage or commercially in Europe , and will leverage early access programs and cross border treatment in other international markets.
Importantly, patient identification continues to accelerate and new treatment centers of excellence are being opened in markets internationally.
Additionally, market access discussions are progressing well with Germany and France.
We have received positive final guidance from nice in England, and Wales for HCC patients 18 months or longer.
We expect to treat more patients in more countries in Europe and other international markets throughout 2023.
Now moving to take steady and where libre in Latin America, where we continue to successfully grow these franchises in Q1.
Following way leavers approval for familial partial lipodystrophy by visa in December last year.
We officially launched this new indication in Brazil, and have already generated our first prescriptions.
We also received our first group purchase order for Libre for familial Kylo microbial <unk> syndrome, which was completed and delivered in Q1.
As mentioned in our last call protect study we received our second group purchase order from the Brazil Ministry of Health.
In conclusion, the first quarter was our strongest quarter ever at PTC and an excellent start to 2023 with substantial progress across all our commercial products and in all major regions setting us up to achieve our 2023 revenue guidance now let me turn the call.
Over to Emily for a financial update Emily.
A few minutes to review our first quarter financial results. Please refer to the earnings press release issued this afternoon for additional detail.
With topline results total revenues for the first quarter were 220 million. This consisted of net product revenue across the commercial portfolio of $187 6 million.
<unk> royalty revenue of $30 8 million and manufacturing revenue of about $2 million.
Translarna net product revenues in the quarter were $115 1 million, reflecting strong growth across all geography.
<unk> had net product revenues of $54 6 million, representing 12% growth in the quarter compared to the first quarter of 2022.
As Matt mentioned, the first quarter performance puts us in a strong position to achieve 2023 total revenue guidance of $940 million to one dose.
Including $100 million milestone expected one of risky surpasses one 5 billion in annual revenue.
non-GAAP R&D expenses were $179 8 million for the first quarter of 2023, excluding $15 3 million in noncash stock based compensation expense.
Compared to 127 million for the first quarter of 2022.
Excluding $13 million in noncash stock based compensation expense.
The year over year increase in R&D expenses reflects additional investment in research programs and the advancement of the clinical pipeline as well as the 30 million cepheid certain clinical development milestones pay predominantly in common stock.
non-GAAP SG&A expenses were $73 4 million for the first quarter of 2023, excluding $13 5 million in noncash stock based compensation expense.
Compared to $59 7 million for the first quarter of 2020 to.
Excluding $13 6 million in non cash stock based compensation expense.
Compared to $410 7 million as of December 31, 2020.
And thank you.
And one moment for Q&A as.
As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced so withdraw. Your question. Please press star one again, please standby, while we compile the Q&A roster.
And one moment by first question.
And our first question comes from Kristen <unk> from Cantor. Your line is now open.
Hi, good afternoon. Thanks for taking my questions. The first one is for your DMD portfolio could you talk specifically about what's been the biggest driver in new patient starts and is this also related to the specific geographies with more patient adds.
And then just kind of on top of that bigger picture question here. Given you have a few registrational trials on deck, what's been the biggest learning factors in being able to expand your footprint globally and how do you think you can leverage this should some of these candidates end up crossing the finish line soon.
Great. Thank you very much Kristen for the questions.
Credibly proud of.
Global commercial infrastructure, we built and the ability to continue to grow so DMD franchise revenue year over year being that we've been on the market now for almost nine years. So that's really a tremendous accomplishment and obviously there have been a number of key learnings and building that infrastructure that will come into play as we look forward to.
Launching new products, let me turn the call over to Eric who can give some more color on the global franchise.
Yes, thanks for the Chris Kristen. Thanks for the question I think we're really pleased with the fundamentals and the execution across all geographies, we achieved $170 million of sales and thats the highest ever for our DMD franchise to your question about what's driving growth, we see growth in a lot of different areas of course geographic expansion has helped.
New patients, but also early diagnosis of patients in a rapid time from the time, they're diagnosed to commercial treatments in the execution of our commercial team has been able to work on in addition to that we're also focusing on maintaining if you will the ambulance as well as the non ambulant patients prevalent pool that we have on drive thru.
Dose adjustments, that's really important.
And of course, we've been seeing across the board for both and Plaza as well as trends, Florida improved and better paid payer access and that's really important as well now for trans Lorna, we did see a $115 million and that that is also from growth from all of our major market.
And that's incredibly important but we also did receive some large government orders from our CIS region, our central and Eastern Europe , Brazil, and some of the middle East the timing and the size of those orders sometimes are a little hard to predict.
And that creates some levels of lumpiness, but.
The most important thing is that these sizeable orders have confirmed that there is underlying growth fundamentals and so we have a very strong base of new patients as well as existing patients that were managing we are expecting orders Gov.
Government orders like this in the second half as well and as.
$545 million to $565 million. So I hope that provides you the color that you need Kristen.
Yes. Thank you that's helpful. And then maybe just one quick one on Huntington's disease.
An oral drug obviously comes with benefits in terms of compliance and adherence but.
About the different therapeutics out there recognizing the mechanisms are different how are you thinking about an oral <unk> agent ability to really target the right areas.
The brain versus some other relative administration that are being evaluated.
Okay, Chris Thank you for the question.
Think route of administration and bio distribution are incredibly important elements to the development of a successful therapy for Huntington's disease.
Honestly.
The development of <unk> $5 eight comes on the heels of the successful discovery and development of a Wednesday for SMA and obviously, we've made a number of important learnings about how to design a molecule that can effectively cross the blood brain barrier not get eplex and globally by distribute the CNS, which is not only essential.
The optimal treatment of SMA, but obviously there is a similar stimuli critical for Huntington's disease.
The design of PTC 518, we've put into play all of those lessons at our molecule is highly selective highly specific gets across the blood brain barrier and broadly by distributions every region of the brain, which is incredibly important given that huntington's disease is a full bringing whole brain disease. So the mechanism drug obviously it was targeting the cause of liver disease, which is the <unk>.
<unk> share of the mutant Huntington protein that is toxic the cells and leasing.
<unk> and so what we're able to deal with our splicing molecule is essentially decrease the production of the disease causes toxic protein and therefore, having the ability to get to every region of the brain, which contributes the disease is incredibly important advantage of PTC 518 over other therapies that are limited.
And thereby distribute ship I think that needs to be locally delivered in the case of the gene therapy, obviously local delivery into the brand gene therapy, something a whole bunch of out from our successful development of data and then also has significant advantages over.
Equally administered therapies, which are just can't get to all the locations and the brands that are contributing to disease. So in this case, we have an oral molecule that was designed to get across the blood brain barrier broadly by distribute which we were able to confirm in terms of the.
Yes that exposure in a phase one study will obviously.
Sure David again, when we do the pivotal HD readout in the second quarter and then also.
Other advantages because an oral molecules titratable. So we're also leveraging our titrated ability hit our clinical studies to identify the optimal dose to achieve the target Holdco loan Huntington protein that we think is optimal for disease treatment.
Great. Thanks, looking forward to catching up with you once these data readout.
And thank you.
And one moment our next question.
And our next question comes from Brian Abrahams from RBC. Your line is now open.
Hi, This is Joe on for Brian . Thank you for taking our question just Huntington's.
You tell us more about <unk>.
What which data might be might be share data from the 12 week portion of the study and it seems like there.
May have been some changes in your target population to include earlier Huntington's patients can you share your thinking around it and if it speaks to any possible changes in your thinking around 10.
The level of the HGT now town in CSF. Thank you.
Thanks, Joe for the question so.
The pivot <unk> study is a 12 month placebo controlled study that some cheap parts part one is 12 weeks in duration and focuses on PK PD.
Blood as well as bio distribution looking at the relative exposure in the CSF and in the plasma.
Important data points to inform optimal dose that gets us towards the target production of the brain with 30% to 50% of Huntington protein.
Nine months of the study is focused on biomarkers of disease, including Huntington protein levels and CSF radiographic.
Markers, including bringing volume changes as well as NFL levels in the plasma and the CSS. The data we plan to share in the second quarter is an interim analysis for the first 12 weeks of activity, which we'll be sharing information.
Maybe PK PD and applied so looking at blood looking at drug levels in the blood and R&D reduction in Huntington Tomorrow protein in the blood and then looking at the relative exposure in the CSF in the plasma as you recall from our phase one healthy volunteer study, we were able to confirm that we were getting excellent CNS exposure in <unk>.
<unk>.
Achieving greater exposure in the CNS.
That said in a plasma so that's a very important finding that will seek to confirm the 12 week data the biomarker data, including the CSS Huntington protein levels NFL levels and bring balance changes will come in the readout from the 12 month data.
To your second question.
Regarding patient populations.
I shared answering Christian's question the mechanism of the drug is targeting the production of the disease, causing mutant Huntington protein that is by leveraging slicing, we're able to introduce a stop codon that affected the decreases the production of that disease, causing protein.
Obviously that hold promise for the full spectrum of HD patients.
Whether they'd be juvenile or adult patients given that the disease causes the same as in all cases. However, it's obviously incredibly important and conducting a clinical trial that we tried to include the right study population, who we can practically.
Tactically capture clinical effect and in the case of the pivot to HD study biomarker effect, along with invoking a time limited constraints Amit clinical trial. So we put a lot of effort and to identify the attributes of what we thought would be that optimal population availed ourselves of the robust Huntington disease.
History databases to work closely with all contingencies experts and Biostatistician to support these databases to come up with what we thought were the essential attributes of a study population that would likely to decline over the course of a clinical trial. Obviously, we want patients who are not solid ancillary fees that by targeting.
The upstream causal disease, we can't practically deliver benefit and.
Certainly don't want patients who are so early in disease, if they're not progressing at all therefore, making it impossible to shelves that were slowing disease progression. So we put these.
Accidents to play at the inclusion criteria for the study and these were essentially stage two HD patients. We shared at the Jpmorgan conference in January that we were adding additional cohorts of slightly later stage patients. We were now including patients with who had a total functional capacity score of 11 and 12, rather than just simply.
Having a TLC square 13, which will be initially acquired.
The reasons for this one because there were a number of these patients who are identified some pre screened.
Prepared to participate in other clinical trials that were no longer being conducted so we have a situation where there are patients identified ready to be in clinical trials incredibly eager to participate in clinical trials and when we we obviously believe we could have provided benefit with this therapy.
The decision to introduce additional dosing cohorts five milligram single Grand dosing cohorts and these early stage III patients because this will provide us additional important data on potential benefit of PTC 508, and also allow us to test our hypothesis in terms of the population that we initially set out to enroll so.
So I hope that answers your question Amit.
Adjustments are the addition of new patients.
Yes that was super helpful. Thank you Matt.
And thank you.
And one moment our next question.
Okay.
And our next question comes from Eric Joseph from Jpmorgan. Your line is now open.
Hi, good evening, thanks for taking the questions just a quick one from me.
Particularly.
If you could just briefly talk about the patent estate for the compound I guess what claims are covered.
On IP for your where you maintain exclusivity and then for western Rishi. Thanks.
Yes. Thank you for the question Eric.
The protection for a particular note is principally going to be on the orphan exclusivity as is always the case, we are exploring other potential ways to strengthen and extend the patent life, obviously in the U S and Europe as well as in other markets.
Okay, great. Thanks, and maybe just a quick follow up if I could.
As it relates to move assay.
Can you just talk about sort of the.
The range.
Patients.
By age and.
And I guess within that.
Patient ages that will comprise the.
Primary analysis.
FERC farce.
Thanks.
Yeah, absolutely. So when we constructed to move ethane trial, we leveraged a number of borrowings that we made from our own phase II trial as well as the number of the important learnings from other clinical studies.
Also we are in a position where given the safety in particular.
A large volume of exposure in children.
This opened up the opportunity to enroll the full spectrum of applications in terms of age.
So in this trial are primary analysis population consists of patients patient gained 7% to 21.
Majority of that pay patients usually diagnosed in early adolescence play childhood early adolescence and the idea here is that for years. If you look at the natural history of disease.
Younger patients tend to have a more uniform and more rapid decline. So as we've talked about in the last question part of Huntington's disease getting the right clinical trial population that will move enough over the course of the clinical trial is randomized to the placebo group puts you in the best position to capture treatment benefit and.
So we cut the lower age limited seven because of patients that are younger than seven first of all there's very few of them second of all it's harder for those young children and tests comply with a number of the study assessments. So that makes ascertainment of clinical benefit difficult. So we said the lower age at seven and then the primary analysis group goes up to 21.
We believe that this is the population income one we can have less of a chance of a placebo back we're also.
Situation, where these patients tend to have a greater decline over the course of a clinical trial in which makes it easier to register clinical benefit and also as is commonly the case of our degenerative disorders, if youre going to intervene.
It helps to intervene earlier in the disease, you have a better chance of affecting disease progression. If you Act earlier and so we were able to do that again, given the safety that drove the majority of all the younger patients. We're also including additional adult patients and not part of the primary analysis population. We previously studied the drug in adults. We believe we can hold benefit again.
Patients of all ages.
The opportunity to enroll adult patients will give us a chance also to look at the relative benefits in the pediatric patients relative to the adult patients, but we would fully expect that with a positive trial, but if we are seeing a move towards approval that we would have a label that would include pediatric and all adult population.
Okay.
Great. That's very helpful. Thanks for taking the questions.
And thank you.
And one moment our next question.
Okay.
And our line is open Robin <unk> from TUI.
You are now available.
Thanks for taking my questions I have three of them. So the first one is around.
PKU.
So I know the bar you gave the responder analysis of 30% and the decline the improvement Steve reduction for the lead in patients but since.
The bar for urgent PC is 15%, presumably youre going to get.
Lower responders going into the queue.
It might actually reached the 30% at the end of the party.
And I was just wondering how do you set the expectations for part two do you think it will look as good as just the lead <unk> considering there may be some.
Lower responders entering that so I just wanted to really flesh it out and set for expectations for investor.
Second question.
It's for us a given the drug is.
Tid dosing.
Do you think the bar for success has been better than reata, and maybe flesh out.
How much that tid dosing might impact the market.
And then third you mentioned Mike.
The range of patients like Youre doing younger patients and you are confident that they might have a lower placebo effect, but also maybe.
I mean, the progress more rapidly whats your confidence in that over the timeline and also what's your confidence that the decline in the efficacy.
In that population because we've seen decline in reata overtime with older patients what about younger patients the decline of the efficacy of these drugs. Thank you.
Okay. Thank you Robin. Thank you for those questions, but we'll take that in turn so the first question is regarding the has been in trial and so as we said we have been running phase in which all screen subjects were treated for two weeks study of tariffs and we randomize all subjects, who had a greater than 15% reduction. However, importantly.
The primary analysis population for the trial includes only those subjects, who had a greater than 30% reduction during the run in terms of the primary analysis and success in the trial that there'll be no interaction of those like 15% reduction between 15 and 30% reduction during the running versus those that had 30.
Production and just to give you a few of the numbers as we shared in the past we have.
102 of 156 subjects, who are in the run rate base had over 30% reduction and there are additional 13 subjects, who had between 15 and 30% that's important because what you're basically seeing is that.
Those who responded to the drug by and large the vast majority had a tremendous response of over greater than 30% response and as we shared a mean reduction in all Congress was 66% from baseline so really impressive reductions in.
Those numbers to answer your question also about what we would expect to see in terms of reduction with patients as they move from the running phase.
Two the placebo control phase.
Patients are treated for two weeks they are washed out return to baseline <unk> patients are getting treated with the same drug so those who get randomized to active we fully expect to see similar magnitude.
<unk> and.
And obviously, those who were randomized to placebo given historically the placebo patients from PK trials turn out to have very much of any placebo response activities.
That gives us a great deal of confidence to not only achieved.
The primary analysis success.
Success significantly greater reduction in inventory relative to placebo, but again.
Based on the data from part one that we will be able to demonstrate not only clinically meaningful response, but one that would strongly differentiate.
<unk> for the treatment of PKU.
In terms of SA.
Your first question was regarding the <unk>.
Tid dosing look we've never seen a problem with compliance with tid dosing.
<unk>.
It's a breakfast lunch and dinner, so it's actually with meals and snacks, you eight hours, which makes a very big difference.
We believe that there are several other important aspects of a differentiate the therapy, let me turn it over to Cary I don't know if you want add anything to that in terms of the effective dosing.
Yes.
Great.
Yes, I think Thats, well said, Matt I think there's a number of factors that are taken into consideration, particularly in diseases of high unmet need and progressive diseases like Friedrich ataxia.
Efficacy first and foremost obviously, a key priority and so it'll be interesting to see as we come out of the mood that by study where both our primary and secondary endpoint plans. In addition to that safety is obviously really important.
There's a number of key differentiation key differentiation packages from a safety point of view that we've seen with the <unk>.
And then obviously deicing comes into play and as Matt said with with dosing around meals it easy to comply and adhere to particularly in the younger ages, where we see our differentiation where parents are obviously, providing the tablets to these kids Asbury and EMEA, let's say across the board from the discussions we've had both with Kols and with patients.
It has not been any concerns raised around that Robyn.
And then Robert in terms of your third question regarding the 721 year olds and concerns there.
Why do we think that those patients will move more and of course of the clinical trial in the placebo group. So the natural history of disease is very clear when you look at age groups.
Changes in the AG parcel overtime at the patients who are diagnosed earlier and our younger.
The title of disease presentation tend to have a more uniform and greater magnitude of decline over the course of the study in terms of the concept that by age or too early.
Disease course.
We're likely to be able to deliver a meaningful benefit I think that's well understood reality in treating neurological or neurodegenerative disorders and in fact, if you look past the readout of data.
It was in there.
Patient, 16% to 45 of those in the 16 to 17 year old cohort those younger patients where they had the greatest over five point placebo corrected response, which I think will in service supports the notion that if you intervene early it's going to be able to capture a greater treatment effect on those patients.
In terms of.
<unk> seen an effect over time or are still progressing overtime, but none of these therapies are curators, but to be able to slow progression slow progression by year by two years isn't credit incredibly meaningful and a slowly progressive disease, such as future pretax relentlessness progression. So I think we.
Spect, there to be a meaningful effect in children that will alter and modify the disease course.
One can still expect to gain some progression all the time, but being able to slow the progression of the disease have been incredibly meaningful impact.
Great.
Thanks, so much.
And thank you.
And one moment please.
One moment our next question.
And our next question comes from David Leibowitz from Citi. Your line is now open.
Hi, this is the bonds and on behalf of David So thanks for taking my call.
The first thing we wanted to ask was like if you could share any further details on the nature of <unk>.
Scott.
Feedback you received.
And do you anticipate any additional delays that could push back baby.
Sorry, the BLA submission beyond third quarter.
And one other thing we wanted to know is that like.
Steven.
<unk> and <unk>.
I think we own five of those trials are both using an endpoint.
And.
And then of course differences being like the patient demographics and pipeline so.
Should we benchmark that they going on results when they come out in Omaha efficacy. Thanks.
Thank you very much for the questions. So first time of stays up as we have previously shared the agency had requested that we provide some additional data on comparability between the clinical drug product in the commercial drug product as is commonly the case in drug development and particularly in <unk>.
Europe is the manufacturing process for a gene therapy drug product evolved over the course of development and the process used to generate commercial drug product often is different than clinical drug product and it's important.
To show the agency that is.
Apples to apples the key attributes of the commercial drug product are analogous.
The attributes of the clinical drug product and the agents had asked us to provide some additional data essentially analyze additional samples of the clinical drug product to demonstrate that it's comparable to the commercial drug product, which we were able to do they have come back and ask for some additional questions around one specific area, we'll just defer.
<unk> and detailed capsid between clinical product and commercial product. They are quite similar and we were able to easily provide that data.
<unk> has stated that we believe the submission of the BLA could be delayed to Q3 of this year from Q2, and thats simply because of the potential cadence of interaction back and forth between the agents.
Net responses to queries, we expect to hear back from them in an enviable position and submit the BLA, but we just wanted to communicate that as possible given the cadence of the back and forth with the agency that the submission could be delayed until the third quarter.
Regarding differentiation between <unk> and particularly known.
Obviously.
Theres not as trial is a bit longer than any one lab trials, that's going to allow for the possibility of capturing a longer term impact.
John .
Patients obviously, the patient populations are slightly different but nonetheless, we'll be able to look over the longer term over all different age groups and appreciates the relative benefits of particular note and obviously secondary endpoints are really really important I think thats an important part.
The.
Story, it's also important part of the regulatory pathway.
Our discussions with agencies.
Been similar to those that reata Tuesday, right to understand that all of the effects on the primary endpoint, but other aspects of disease morbidity, which are capturing some of the secondary endpoints.
Okay. Thank.
Thank you.
And thank you.
Okay.
And one moment our next question.
Okay.
And our next question is Joseph Thome from Cowen. Your line is now open.
Hi, there good afternoon, and thank you for taking our questions here first one on the.
The PKU trial, where do you think about what constitutes success here is it really just a stat sig benefit or do you want to see a certain proportion of patients under 360 micro mill per liter.
Or that have a 50% reduction from baseline or what have you and do you have the sufficient safety database to file off this program. If the study works and then I have one quick follow up.
Thanks for the questions Joe I'll start and then I'll I'll, let Kelly talk about about the commercial differentiation. So obviously a couple of things that were really impressive from the phase one run in data one was the proportion of patients that respond and his team.
Nearly two thirds of the patients have over 30% reduction is really impressive and separately the bench markets.
All comer.
February the proportion of responders over 30% was only 20% considering the magnitude of effect not only in the overall treating patients who had over 30% reduction which was 66% but in the classical PKU patients who had an average reduction of 61%.
And that's really impressive and again says that regardless of your disease severity.
We're able to provide it.
Phase of real market reduction in federal Halloween.
Expectation is that the placebo controlled study would not only provide evidence of clinical benefit sufficient to achieve registration, but also would it be able to provide evidence of differentiation.
I'll comment quickly on that I, just wanted to turn it over to <unk> to comment on the on the differentiation on the regulatory products, we're going to have data from the six week placebo controlled study, but obviously, we've been patient rollover from the placebo controlled study into a long term open label extension study, which is going to provide data not only on durability of effect, but obviously longer term.
50, which we believe along with all the other data collected to date would put us in position to be able to submit following positive data.
Joining in the.
The commercial differentiation.
Yes, absolutely.
Thanks, Jay I think from that perspective sort of about looking across the different patient segments that have high unmet medical need in PKU, which we've talked about in the past I think having an ability to demonstrate benefit in classical PKU is extremely important and Matt just touched on that I think that.
<unk> historically been a very difficult to treat patient population being able to demonstrate benefit there I think it's strong.
As we've talked about we have the primary analysis population being in the 30% or greater fee reduction.
Thanks <unk>.
15% or greater and I think even in that 15% to 30% population showing benefit in classical PKU is going to be a powerful differentiation outside of those that Costco PKU population looking more broadly I think.
And those that have already tried and failed to then.
Showing a stat Sig benefit I think will be key and even looking at those that are poorly controlled over time, and ultimately well controlled I think looking at a 40% plus greater fee reduction will give us an opportunity a number of different patients in those different segments, I think obviously anything higher above on that item.
More and more patients that would be looking to trust that the upturn.
Great. Thank you and then just real quickly on <unk> I know you've mentioned that several patients were treated I don't think I saw it in the press release, but are you able to provide the revenue contribution for <unk>.
Sure.
This quarter or if not are you anticipating breaking that out going forward. Thank you.
Mark do you want to talk a little bit about the launch and progress and treatments.
Yes, well, we haven't actually broken out.
Specific patient numbers or revenue, but we're really pleased with the way. The launch is progressing it's good it's going according to plan and what we see is patients are being treated in the transformative effects.
We actually have treated patients in both.
Germany and France.
In the quarter and we also have treated our first cross border patient, which came from the middle East and was treated in Europe .
Proof of concept of treating cross border patients commercially was achieved.
We continued our patient finding activities and we've been able to continue to find patients in the first quarter and new patients in all major geographies, where we've we know that there is access for gene therapy. So the surgical centers as well, we've been working very closely with them and establishing them.
In key countries, particularly multiple centers in Europe , and we anticipate having centers in the middle East and Brazil. During the course of the year to set up and take full advantage of what I call early access programs as well on.
On the payer engagement side, it's gone extremely well we've had strong HCA assessments.
In Germany, and France, which which now supporting ongoing price negotiation and I remind you that sort of Europe is a step by step process with access and reimbursement, but we hope to conclude some of those pricing negotiations in the second half of the year.
And importantly, we have nice recommendation in the UK.
That's important for patients in England, and Wales, who will have access to the treatment soon and we anticipate treating these patients in the coming weeks or months.
In the UK.
And as a reminder, I would say that what we're seeing right now is it really steady cadence cadence of patients and.
The overall.
Cadence those patients that are being treated means that there will be more more patients treated in Europe and as the year goes by we're going to see patients.
Via early access in the Middle East Britain, Brazil, So so far I would say, we're really pleased with the progress.
Great. Thank you very much.
Yes.
And thank you.
One moment please.
And one moment our next question.
And our next question comes from Kelly <unk> from Jefferies. Your line is now open.
Thank you for taking my questions.
With Docomo assay. My question is at the Phase two study showed a treatment effect that to quantify them.
Points difference over placebo arm.
They are asking Euro star at 24 weeks and the final.
<unk> phase III is a 72 weeks and then side about a full point of five points difference I'm. Just curious what are the data we rely on to model. How the treatment is back to trend from Tony for weeks towards 72 weeks and the make of this new standard on the primary endpoint. Thank you.
Yes. Thank you very much for the question Kelly.
There are important points here and that you brought up sort of in the phase II study with six weeks in duration and had the difference that you've noted and part of that Magna.
Magnitude of that difference was driven by a chain placebo effect that was present, even out to six months and this is something that was important lesson, we learned and if you look at the reorder data as well and we still see a persistent placebo effect at six months that had that study only been six months in duration. They would not have achieved statistical significance as they did.
Time is needed for that placebo effect to abate so our selection of the 18 months.
Our duration, our 72 week duration placebo controlled phase was to allow for a complete wash out of any placebo effect and allow for the placebo patients to more closely mimic the natural history of the disease, which is an average of two and a half point loss on the MLR score per year. So you would expect that based on that.
Actual history the change in the placebo group should be closer to three and perhaps even higher the magnitude of treatment benefit was based on the <unk>.
The size of attitude of treatment benefit was based on the long term extension of the phase two study that we did do the six week placebo portion right but.
All patients will continue to be treated for an additional 18 months, which allowed them for a comparison of 18 to 24 months of treatment with an aim staging techs match natural cohort natural history cohort the magnitude difference.
In between those two groups between the natural history.
And the.
The natural history cohort in the treated cohort was actually much more.
Market.
There was $4 $8 worsening of that 818 treatment benefits. So the difference over the 18 to 24 months was six six so we're starting to see a magnitude of effect.
Phase II study Thats greater than what you mentioned is that hypothesize effect for five so we believe that $4 five estimate and powering on that difference puts us in a strong position to capture significant benefits in the study.
Very helpful and I also have a quick follow up if I may do you think 16 clasico patients are sufficient.
To ensure a broad label in both mild and the classic with PKU patients.
My require expand data.
Enrollment.
Yes.
It's a good question, but we have 16 patients who are in that greater than 30% reduction than we had previously shared that we had five additional classical patients who had between 15% to 30% reduction in the run in phase with a mean reduction of 22%. So you are seeing pretty meaningful reductions to our cros.
Many patients which in classical PKU is a lot I would also say thank you a couple of things to keep in mind. One is that we also captured a number of classical PKU patients. So youre seeing a good proportion of those treated who are having those meaningful levels of reduction.
The important thing to think about classical PKU is not only the thresholds responsive having a greater than a 30% reduction but also the absolute change in phenylalanine. When you think about PKU is debt levels of <unk> that are most significant in terms of the clinical effects of the disease, including cognitive effects and it's well known that.
Reductions in <unk> by even 100 points can impact IQ. So if you think about a 15 or 20% reduction in phenylalanine levels for classical PKU patients, obviously those could be quite meaningful.
And considers the benefit of reducing.
The overall level of fertile so we believe that the data set we are generating will have not only a number a sufficient number of patients with classical PKU to be included in the label, but the magnitude of effect in the quarter was patient recorded in these patients is also quite important and impactful.
Terrific. Thank you.
Yes.
Okay.
Yeah.
Yeah.
Okay.
Danielle.
If your phones on mute could you please on mute it.
Oh, Yeah, Hey, sorry, this is Alex on for Danielle.
Quick one from US just to clarify my audio went out just wondering what was up with the FDA type C meeting request for Trans Florida has that been requested or scheduled and then secondly, just curious about the order of the upcoming Readouts you were trying to back into it a little bit is it fair to assume that PKU.
We'll come first we were trying to guess Meg.
And maybe June for the others. Thanks, so much.
Yes. Thanks for the question Alex So let me take the second question first we've been able to provide the specific guidance for PKU with Readouts in May and obviously the others. We have not provided more specific timing because we don't have any more specific timing.
Beyond second quarter at this time.
In regards to your first question in a type C meeting refrigerated warehouse. We had previously shared we had a meeting with the FDA a clarification meeting following up the written response only that we have received from them in the fall in that meeting. The agency suggested that we request a type C meeting to review.
With that in the totality of data from Translarna, including mechanistic data district, and data and the data that we've generated over the clinical studies done to date, and then be able to having a robust discussion on the totality of data and its potential to support an NDA resubmission.
Obviously theres a lot of data to be presented we're in the process of preparing that meeting request and briefing book, we're going to we're going to be able to include that on the mechanistic data they ask for but the data that we've collected windstream placebo controlled trials amendments over 700 boys, where we've been able to demonstrate consistent clinically meaningful.
Benefit in these boys and when you think about what the FDA really needs to see in the data package that we're having a clinically meaningful effect exactly the chance and the consistency of effect that we're seeing across the three study is the volume of data that we've collected over 700 boys the ability to look across these three studies in skin statistically significant benefit.
Across a number of the key endpoints would be the safety of the drug as well as the <unk>.
Context of abuse, which is nonsense mutation DMD remains a significant unmet medical need. So we look forward to putting together all these data in a briefing package. We're also conducting some additional analysis to dress some of it a previous concerns that the agency in that range. So we can come in to the agency at the right time and have a robust discussion about a path to NDA resubmission.
Great. Thanks, so much.
And thank you.
And one moment please.
And our next question comes from Joe Schwartz from SBB Securities. Your line is now open.
Great Hi, this is will on for Joe today. Thank you for taking our questions. So to start I just want to pivot back and move FAA study and based on the powering it looks like there is the potential for this study to Miss on statistical significance.
<unk> shown a benefit over <unk> <unk>. So in this event how are you thinking about next steps on the regulatory side and I have a quick follow up thank you.
So well thanks for the question, we believe that we will have sufficient power to detect a difference that was recorded in <unk> study. So we don't see that as.
Our next year, if we can capture the same magnitude of effect in similar areas.
Okay, Great and then I guess following up here has the agency provided you guys. If any specific guidance in terms of what they want to see either from an efficacy standpoint, or stats perspective, and how is your thinking if at all changed on this since the approval of <unk>.
And kind of any insight into the agency's views here would be helpful.
Yes sure.
Interesting question, well because historically the agency has very much.
Wanted to not only see a significant effect on the <unk> scale, but given that it's a composite scale that doesn't clearly communicate the impact of a therapy on how a patient feels and functions in everyday life, which is those are really the buzzwords that FDA likes to see preclinical benefit typically wanted to have a key secondary end.
<unk> got more directly assessment CLO function move along with the primary endpoints or if you can contextualize appropriately contextualize that recorded changes and ours as being clinically meaningful.
Obviously that was a source of a lot of the discussion that went on over time.
Right out of share their data in October 2019 to NDA approval.
Hi.
I think that's some of the back and forth was based on the fact that there are key secondary endpoints such as the clinical global impression scale did not achieve statistical significance.
Be that as it may the approval of the SBA on essentially a statistically significant and bars change set a threshold that we believe others can now follow I think while it's unclear or challenging sometimes to predict how the FDA will anchor the reasoning behind that decision they tend to be quite consistent when they set a precedent for approval.
So I think its clear I think.
We believe that being able to achieve a statistically significant effects on the employers, particularly in a longer study was 72 weeks relative to 48 weeks and in a larger patient population that we haven't moved assay are relative to the.
The Moxie study will put us in a strong position, but nonetheless, we did spend a lot of time.
Planning a key secondary endpoint for the study, which is the FAA activities of daily living scale, which is something that agency.
The agency has shared that they believe adequately capture CLO function in everyday life. We selected this as the key secondary endpoint because if you look at the natural history data and ours changes tend to move.
Along with changes in the ADL scale, there they tend to move suddenly and across.
As it progresses and in fact, if you look at the results of the Moxie study the one secondary endpoint on which.
There was statistic nominal statistical significance. It was the ADL scale unfortunate I believe that was looked at as the last of several secondary endpoints.
In the marketing side.
Again, just to answer your question I think the statistical significance on Empire.
Benchmark that has now been set for approval, but we will also obviously be looking to see if we can capture secondary endpoint benefit as well.
Very helpful. Thank you.
Okay.
Yeah.
Okay.
Yeah.
Our next caller is Jeff hung with Morgan Stanley Jeff. Your line is open. Please go ahead.
Thanks for taking my questions for <unk> can you remind us of why the study was powered for a 40% placebo adjusted difference in seizure reductions when $20 to 25 reduction can be important would you consider the study's success. If you see a 20% to 25% reduction or do you need to see.
A 40% reduction and then I have a follow up.
Thanks for the question, Jeff So the.
The powering and the Navy study was based on a couple of things obviously, the placebo side, we tried to hypothesize that.
Change in observable motor seizure frequency that was consistent with the placebo response, that's been shown in other pediatric epilepsy syndrome trials have not been any previous placebo controlled trials in.
Children with my apologies.
But we believe the hypothesized effective placebo effect of 10% was reasonable given what <unk> seen in other studies, which is generally ranging between 2% and 19% on the efficacy side of 50% reduction or.
So first let me say, we absolutely believe given this.
The refractory nature of these seizures theyre highly morbid nature of the fact that they can be life threatening in many cases, I think most kols aggregators and agree that a 2025% reduction would be clinically meaningful as population at 50% hypothesis has driven a bit by the previous.
Seizure reductions we've quantify them in other studies, particularly in the treatment series chosen Hypothesised Lawler hyperplasia top six which tends to be one of the most virulent.
Concho disease associated seizures subtypes.
So again, we believe that we are.
<unk>.
2025% would be incredibly meaningful but again.
The numbers are based on our previous experience as well as experienced some others.
Great. Thanks, and then for PTC <unk> did the FDA specify where the additional data for supporting dosing and duration needed to come from geographically.
I know you've been enrolling patients outside the U S and I just wanted to see if you had given any indication on whether they wanted data from patients in the U S for additional data and if they make here at the end of the study if more patients end up coming from other geographies. Thanks.
Yes, so just as a reminder, jeff's the the FDA has asked for additional data to support the dosing and duration of proposal activity. HD study was based on non clinical data. This was based on data from a toxicology studies. The same toxicology studies that will be used to support the approvals of the conduct of the study in the other geographies around.
In a world where the studies being conducted it was the FDA had asked for additional data to support the dosing and duration as I said those data could be clinical data that we've collected as part of the Kennedys instead. It obviously as the study has already been conducted in countries outside of the us naturally understand that those data are going to come from patients outside of the U S.
And so we will plan as we do this first interim data cuts to use those data to.
Take those data to the agency and continue discussions about.
Opening enrollment to get in the U S. But in terms of the patient's colloquy outside of USDA naturally expect that and there shouldnt be any other impact on how these data looked at.
Whether they were collected in the U S or elsewhere.
Okay. Thank you.
And thank you and one moment our next question.
Yeah.
Yeah.
One moment.
And our next question comes from Gena Wang from Barclays. Your line is now open.
Thank you.
Yeah.
Questions Chris.
Yes.
Okay.
Thank you Danielle.
This press release conference call second quarter.
Second question is regarding synergy trial.
Hi.
Some patients had.
Prior experience I know you cannot comment on the percentage of patients, but would you saw.
Proven now responders in the study or simply just coolant experienced patients.
And then lastly, very quickly pivot HD or what is your box of Huntington knockdown levels.
Gena, Thank you for the questions. Unfortunately.
Clearly hear your first question I heard the second and third would you mind repeating the first question sure. First question is basically for the four datasets will you report individually with press release on the conference call.
The second quarter.
Yes so.
As we guided that the data from <unk> in May and the others need to occur in the second quarter, we haven't given details yet on the exact nature of.
Whether there'll be all releases and calls.
So we haven't made those decisions yet.
<unk>.
<unk> to share the data as they become available because there's not a plan now to batch them at any in any way.
On your second question, we do have patients who entered the study who had previously been treated with Kogan, who are Kuban failures CF patients in the study who were on Cougar and when they came into the study who had been washed out from <unk> and then.
So that obviously will give us the opportunity to understand.
Specific subjects what was there.
Kuban effects relative to what we observed today's that'd be a tear in effect during the London phase and we will plan to breakout some of those data.
With the data released.
Quite available so to directly answer your question. It's an exodus focuses folks who've been on <unk> in the past and sale than others, who are taking it and washed out to come on and come into the affinity study.
On the pivot HD study in terms of magnitude of Huntington reduction as we've talked about the goal of this program is to achieve a lowering of Huntington protein in the brain of 30% to 50%.
In a difficult position, obviously, we can't directly measure changes in Iran. All Huntington protein levels, because we simply cant biopsy brain tissue.
So what we're doing to understand and guide dosing is a couple of things first we're obviously looking at the changes in blood levels of Huntington protein because it's a compartment that we can easily access.
And that was one of the nice finding some important findings from phase one that we were able to record evidence of.
Target engagement and dose dependent splicing activity with dose dependent reduction in Huntington mrna and protein in the blood that gives us a very good window into can you talk <unk> target engagement spicing activity at the.
The next important element is the relative exposure of drug between blood and brain, which we can measure by looking at blood levels of drug and measured by looking at CSF levels of drug we know that splicing activity is directly related to exposure. So by understanding what the reduction in the blood that is certain.
Exposure relative and then understanding the relative exposure between the blood in the brain can give us an estimate of what is going on inside the brain cells.
So the decision to start with five and 10 milligrams in the Phase <unk> study was based on what we saw in phase one in terms of blood Huntington protein borrowing which what we saw in the <unk> was roughly 40% reduction at 15 milligrams.
Roughly 60% reduction at 30 milligrams, we noted that the ratio of free drug in the CSF plasma was two seven to one so we've been getting.
Twice as high exposure in the brain the blood. So therefore, we said that five and 10 milligrams. If that was exposure ratios hold we could very well be.
The necessary dose level to achieve the desired 30% to 50% lowering so we'll look at when we get to activity. Some data at the levels of reduction recording in a blood at five and 10 milligrams will also look at the relative exposure from a blood to the brain and use those data to help guide the decision of whether we want to start dosing in that.
Higher dose level of 20 milligrams, which based on the phase one data will represent roughly 50% reduction.
The blood and therefore, if we were closer to a one to one ratio of blood and brain exposure would suggest that we're achieving roughly 50% reduction in the brain. So I know, there's a lot of numbers and the more complicated.
Answer to your question.
Very helpful. Thank you.
And thank you.
And one moment our next question.
And our next question comes from Colin Bristow from UBS. Your line is now open.
Yeah.
Hi, This is <unk> on for Colin Thanks for taking our questions and congrats on the quarter.
The first question is for the quiz Lana seems to have a very big beat this quarter.
And you just know that the government alterra with continue to be expected in the second Q just wondering about this German alterra in terms of the longer time.
And also because you didn't really update Jim.
Guidance.
Wondering if we should potentially be more revenue for this whole year versus I'll turn to guidance.
Can we have more color on that and the second Q Jessica just a very quick clarification question so far.
A BLA filing delay the so called her you previously said you have already provided the additional.
Additional request data to FDA.
Thank you so much.
Thank you you have for the question, let me first say on entrees on our revenue.
Sure.
Credibly excited about the performance in the first quarter as Eric stated in the prepared remarks, we remain on target to meet our.
Franchise guidance this year, but let me turn it over to Eric and Emily will provide additional cover.
<unk> on the trend line in franchising revenues.
As we mentioned earlier.
<unk> continues to grow and it's growing in all major markets. So we're seeing growth, particularly as we're adding new patients managing the prevalence pool and particularly.
Working on dosing adjustments and higher compliance we have compliance rates in many countries, 90%. We've seen a lot of the geographic expansion take hold over the last three years to four years as we develop these in places such as central and Eastern Europe , and the Middle East Our CIS region and of course in Latin America. So many of these <unk>.
Or has that come in our central government orders.
For new patients as well as the existing ones and so it's kind of hard to predict the timing and the size of some of these larger orders we anticipate.
That we will continue to get those orders in the second half because some of these we are adding new patients every quarter.
Especially.
Seeing from these geographic expansion markets. So this strong performance that we've seen across trade is Florida is going to continue we will have some lumpiness in the quarter, but we anticipate government orders to continue because of the base that we have including new patients that are coming in and managing the compliance and the low discontinuation.
Generations are incredibly important.
We're not going to change the guidance at this point in time and we'll just continue to provide an updates as we as we.
We see these orders coming in but I would like to reiterate that we have a $545 to $5 65, DMD franchise right now that we are very confident in achieving this year.
And then I'll just also address why we don't typically give quarterly guidance, we tend to give annual guidance for just that reason on regarding the BLA I will say that as we commented before the FDA had asked for additional.
Data is supportive comparability analysis, we provided those data and they've come back with a follow up with follow up questions that we're now in the process of answering it will send back and shortly.
And again.
<unk>.
Timing the potential delay in submission from the second quarter third quarter is just a possibility based on the potential cadence of.
Responses from the agency.
Query responses.
Okay. Thank you.
And thank you and one moment our next question.
Okay.
Yes.
And our next question comes from J crew.
Your line is now open.
Hi, This is Kate on for Paul Choi. Thanks for taking my questions. Two quick ones for US first we wanted to see what the impact of inventory or stocking was throughout the quarter and then second we noticed you took out your full year operating expense guidance. We wanted to see what the rationale was for removing that and how to think about go forward operating expenses.
The pipeline progresses here. Thanks, so much.
Yeah, absolutely. Thank you for your questions I'll start and I'll turn it over to Emily.
First.
Regarding opex look as we mentioned in our prepared remarks, and as we've talked about previously we've been building, our R&D and commercial infrastructure over the past several years.
And quite proud of what we had achieved obviously the performance the commercial performance in the first quarter is incredibly progressive incredibly impressive and it is clearly a result of the infrastructure that we've created and we're now well positioned to launch additional products on positive data.
We've also said that when we turn over the card to these clinical trials. We will then be in a very good position to do a strategic portfolio review, which we plan on doing as a result of which we expect that there'll be reduction in Opex and therefore, we will come back once that analysis performed and share any changes to the <unk>.
Operating expenses, obviously, we will undertake this review of the portfolio clearly guided by return on investment and probability of success and ensuring that we focus on things that we think will bring.
Success in kind of revenue growth, we desire to achieve over the coming years.
Do you want to comment on Opex or further on Opex and on stock.
Yeah.
On Opex, obviously put it best be look forward to after the readout of data analyzing I program priorities and looking for opportunities to narrow our opex guidance on the revenue side. There was no stocking we saw some large government or Christmas that Eric has pointed out which contributed.
Two the growth in the first quarter and put us in a position to reiterate both our.
Our DMD franchise guidance as well as our overall revenue guidance for the year.
And thank you.
Okay.
I would now like to turn the call back over to Chief Executive Officer, Matthew climb.
Well I want to thank everyone for joining our call today I'm incredibly pleased with the productive and successful first quarter that we have and we look forward of course to sharing the upcoming study readouts with you all as soon as they become available. So thank you all again for joining the call and have a good evening.
This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
[music].