Edison International Q1 2023 Earnings Call Transcript

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Provided by Quartr
April 27, 2023

There are 15 speakers on the call.

Operator

Good day and thank you for standing by and welcome to the PTC First Quarter 2023 Financial Results Call. All participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. Please be advised that today's conference is being recorded. I would now like to turn the call over to Kiley O'Keefe, Chief Commercial Officer, you may begin.

Operator

Hello, speakers.

Speaker 1

Yes.

Speaker 2

Good afternoon and thank you for joining us today to discuss PTC Therapeutics' Q1 2023 corporate update and Financial Results. I am joined today by our Chief Executive Officer, Matthew Klein our Chief Business Officer, Eric Powells and our Chief Financial Officer, Emily Hill. Today's call will include forward looking statements based on our current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward looking statements. Our actual results could materially differ from these forward looking statements.

Speaker 2

As such, statements are subject to risks that can materially and adversely affect our business and results of operations. For a detailed description of applicable risks and uncertainties, We encourage you to review the company's most recent annual report on Form 10 ks 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. With that, let me pass the call over to our CEO, Matthew Klein.

Speaker 1

Matt? Thanks, Kiley. Good afternoon and thank you for joining the call. I'm pleased to share PTC's 1st quarter results and our expectations for continued strong performance and Formative 2023. PTC is a leader in developing and commercializing innovative therapies to treat rare disorders.

Speaker 1

I am incredibly excited to lead PTC into its next quarter century as we continue to utilize pioneering science Deliver therapies to patients with high unmet medical needs. We had a very productive Q1, achieving $220,000,000 in total revenue, our highest quarterly revenue ever. This represents 48% growth over the Q1 of 2022. Our DMD franchise revenues in the quarter totaled $170,000,000 which represents a 33% increase over the Q1 of 2022. ARISD also had a strong Q1 providing royalty revenue of $31,000,000 The Auryxia revenue growth continues to be driven by both therapy naive patients and those previously treated with ZOLGENZA and SPINRAZA.

Speaker 1

In addition, U. S. Growth is being driven by patients less than 2 months of age following the recent sNDA approval. This robust Q1 performance puts us in a strong position to achieve our total 2023 revenue guidance of $940,000,000 to $1,000,000,000 which would represent up to 43% year over year growth. In addition, as we previously shared, we expect to use the study results to be reported in the Q2 to inform a strategic portfolio review and likely OpEx reduction on which we will provide further details once available.

Speaker 1

Moving to our pipeline, We remain on track to report results from 4 clinical studies in the Q2, 3 of which are registration directed. Let me provide a brief overview of each study and the results we expect to share. I'll begin with our APHINITY study. AFFINITY is our Phase 3 global placebo controlled study of sepiotarum in children and adults with PKU. The placebo controlled portion of the study was 6 weeks in duration with the primary endpoint of reduction in blood phenylalanine levels.

Speaker 1

To enrich the randomized population for cepiaterin responders, there was a run-in phase during which all screened subjects received cepiaterin for 2 weeks. Only those subjects who demonstrated a reduction in phenylalanine levels of 15% or more from baseline in Part 1 were randomized for Part 2, with the primary analysis population consisting of those who had a greater than 30% reduction in phenylalanine levels from baseline during the run-in phase. At 4th quarter earnings in February, we shared the encouraging data from Part 1 run-in phase in which approximately 2 thirds of treated subjects demonstrated a greater than 30% reduction in phenylalanine levels. The mean phenylalanine reduction for all subjects with at least 30% reduction was 66% and the mean reduction for classical PKU subjects was 61%, supporting the concept that a more bioavailable and potent cofactor therapy, sepiaterin, can provide a clinically meaningful and differentiated response for the full spectrum of PKU patients. We look forward to sharing results from the placebo controlled portion of Affinity in May.

Speaker 1

Let me now move to the 2 registration directed trials of vatiquin. MITEI is a global registration directed trial of aticuinal in patients with mitochondrial disease associated with seizures. The study included a 24 week placebo controlled phase with the primary endpoint being changed from baseline in frequency of observable 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 Q2. The MOVE FA trial is a global Phase directed study of vatiquinone in pediatric and adult patients with Friedreich ataxia.

Speaker 1

The study included a 72 week placebo controlled phase with the primary endpoint being changed from baseline in the validated MFAR score. Last patient's last visit to the placebo controlled phase has also occurred and we continue to expect results for Move FA in the Q2. Moving to our PTC 5.8 Huntington disease program. Pivot HD is a 12 month placebo controlled trial that consists of 2 parts. Part 1 is 12 weeks in duration and focuses on PTC-five eighteen pharmacology and pharmacodynamic effects, as well as biodistribution.

Speaker 1

Part 2 is 9 months in duration and focuses on blood based, DSS based and radiographic biomarkers of disease. The study initially includes 2 dose levels, 5 milligrams and 10 milligrams, with the ability to include a 3rd dose level of up to 20 milligrams, leveraging the titratability of the molecule. We initially included patients with Stage 2 Huntington disease and we recently expanded the trial to include early Stage 3 patients will be studied initially at the 5 milligram and 10 milligram dose levels. We continue to expect interim data from the 12 week portion of the trial in the Q2 of These data will include safety, pharmacology, pharmacodynamics and biodistribution data from the 5 milligram and 10 milligram doses. With results of these 4 studies expected in the next several weeks, beginning tomorrow, we will not be discussing these programs until results are reported for each study.

Speaker 1

Turning to Translarna, we continue to expect the CHMC opinion for the Type 2 variation to convert the European conditional marketing authorization to standard authorization in the Q2. In the U. S, we are preparing a Type C meeting request to review with the FDA the totality of data collected to date that could support an NDA resubmission for Translarna. Finally, for Stata, 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 data 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 Q3 of 2023 rather than the Q2 as previously planned.

Speaker 1

Overall, I'm incredibly proud

Speaker 3

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 twenty twenty two. 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 AUSTAYSA launch in Europe. We also have launched WAYLIVRA for 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.

Speaker 3

Let me start with the DMD franchise. Translarna and Emflaza continue to be an important engine for growth, delivering an impressive $170,000,000 in 1st quarter net revenue, which is up 33% compared to the Q1 of 2022. For Translarna, we achieved $115,000,000 In revenue this quarter, we continue 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 unpredictable government ordering patterns in these markets, we expect to see ongoing lumpiness in quarterly revenue throughout the year.

Speaker 3

We remain confident that we will achieve our 2023 DMD franchise revenue guidance of $545,000,000 to $565,000,000 As our growth fundamentals remain solid with continued new patient starts, high compliance, low discontinuation and proper weight based dose adjustments on an ongoing basis. The fundamentals of the Emflaza business continue to be solid. Quarterly net revenue was $55,000,000 We have seen a significant number of new patient start forms in the Q1, 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 UPSTAZA, 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 1st cross border commercial patient.

Speaker 3

We see the steady rollout of UPSTAYZA 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. And we have received positive final guidance from NICE in England and Wales for AADC patients 18 months and older. We expect to Treat more patients in more countries in Europe and other international markets throughout 2023.

Speaker 3

Now moving to TEGSEDI and WAYLIVRA in Latin America, where we continue to successfully grow these franchises in Q1. Following WAYLIVRA's approval for familial partial lipodystrophy by ANVISA in December last year, We officially launched this new indication in Brazil and have already generated our first prescriptions. We also received our 1st group purchase order for WAYLIVRA for familial chylomicronemia syndrome, which was completed and delivered in Q1. As mentioned in our last call, For TEGSEDI, we received our 2nd group purchase order from the Brazil Ministry of Health. In conclusion, The Q1 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.

Speaker 3

Now, let me turn the call over to Emily for a financial update. Emily?

Speaker 4

Thanks, Eric. I'll take

Speaker 5

a few minutes to review our Q1 financial results. Please refer to the earnings press release issued this afternoon for additional details. Beginning with top line results, total revenues for the Q1 were $220,000,000 This consisted of net product Revenue across the commercial portfolio of $187,600,000 EVRISD royalty revenue of $30,800,000 And manufacturing revenue of about $2,000,000 Translarna net product revenues in the quarter were $115,100,000 reflecting strong growth across All geographies. Emflaza had net product revenues of $54,600,000 representing 12% growth in the quarter compared to the first As Matt mentioned, the Q1 performance puts us in a strong position to achieve 2023 total revenue guidance of $940,000,000 to $1,000,000,000 including $100,000,000 milestone expected when Aversity surpasses $1,500,000,000 in annual revenue. Non GAAP R and D expenses were $179,800,000 for the Q1 of 2023, excluding $15,300,000 in non cash stock based compensation expense compared to $127,000,000 for the Q1 of 2022, excluding $13,000,000 in non cash stock based compensation expense.

Speaker 5

The year over year increase in R and D expenses reflects additional investment in research programs and advancement of the clinical pipeline as well as the $30,000,000 cepiabteran clinical development milestone paid predominantly in common stock. Non GAAP SG and A expenses were $73,400,000 for the Q1 of 2023, excluding $13,500,000 in non cash stock based compensation expense, compared to $59,700,000 for the Q1 of 2022, excluding $13,600,000 in non cash stock based compensation expense. Cash, Cash equivalents and marketable securities totaled approximately $286,300,000 as of March 31, 2023, compared to $410,700,000 as of December 31, 2022. I'll now turn the call over to the operator for Q and A. Operator?

Operator

And thank you. And one moment for Q and A. Please stand by while we compile the Q and A roster. And our first question comes from Kristin Kluska from Cantor. Your line is now open.

Speaker 6

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?

Speaker 6

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 could leverage this should some of these candidates end up crossing the finish line soon?

Speaker 1

Great. Thank you very much, Kristen, for the questions. We're incredibly proud of the global commercial infrastructure rebuilds and the ability to continue To grow the DMD franchise revenue year over year being that we've been on the market now for almost 9 years. So that's really a tremendous accomplishment. And obviously, there have been a number of key learnings in building that infrastructure That will come into play as we look forward to launching new products.

Speaker 1

Let me turn the call over to Eric, who can give some more color on the global franchise.

Speaker 3

Yes. Thanks for the Kristen, thanks for the question. I think we're really pleased with the fundamentals and the execution across all geographies. I We achieved $170,000,000 of sales and that's the highest ever for our DMD franchise. To your question about what's driving growth, we see growth in a lot of different areas.

Speaker 3

Of course, geographic expansion has helped with new patients, but also early diagnosis of patients and the rapid time from the time they're diagnosed to commercial treatment and the execution that 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 a non ambulant patient prevalent pool that we have on drug through dose adjustments. That's really important. And of course, we've been seeing across the board for both Emflaza as well as Translarna improved and better payer And that's really important as well. Now for Translarna, we did see $115,000,000 and That is also from growth from all of our major markets and that's incredibly important.

Speaker 3

But we also Did receive some large government orders from our CIS region, our Central and Eastern Europe, Brazil and from 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 sizable 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 we're managing. We are expecting orders government orders like this in the second half as well.

Speaker 3

And as Matt reiterated, We are reiterating our guidance for the DMD franchise to $545,000,000 to 565,000,000 So I hope that provides you the color that you need, Kristen.

Speaker 6

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.

Speaker 6

But thinking about the different therapeutics out there and recognizing the mechanisms How are you thinking about an oral agent's ability to really target the right areas in the brain versus Some other routes of administration that are being evaluated.

Speaker 1

Yes, Kristen, thank you for the question. We think route of administration and biodistribution are Incredibly important elements to the development of a successful therapy for Huntington's disease. Obviously, the development of PTC C-five eighteen comes on the heels of the successful discovery and development of a RISD for SMA. And obviously, we made a number of important learnings about how to molecule that can effectively cross the blood brain barrier and not get efflux and globally by distribute throughout the CNS, which is not only essential for The optimal treatment of SMA, but obviously it is similar, similarly critical for Huntington's disease. So in the design of PTC-five eighteen, We put into play all of those lessons, have a molecule that's highly selective, highly specific, gets across the blood brain barrier and blood and bio distributes every region of the brain, Which is incredibly important given that Huntington's disease is a whole brain disease.

Speaker 1

So the mechanism drug obviously is targeting The cause of the disease, which is the production of the mutant Huntington protein that is toxic to cells and leads to neurodegeneration. And so what we're able to do with our splicing molecules is Essentially decrease the production of the disease causing toxic protein and therefore having the ability to Get to every region of the brain which contributes to disease is an incredibly important advantage of PTC-five eighteen over other therapies that are limited in their biodistribution by DinkaV, it could be locally delivered in the case of the gene therapy. Obviously, local delivery into the brain gene therapy is something we know a whole bunch about from our successful development of AUSTAYSA. And then also has significant advantages over intrathecaly administered There are therapies which are just can't get all to all the locations in the brain that are contributing to disease. So in this case, we have an oral molecule That was designed to get across the blood brain barrier or they buy distribute, which we'll be able to confirm in terms of the CSF exposure in our Phase 1 study.

Speaker 1

We'll The share data again is mostly due to the PTHC readout in the Q2. And then also, we have other advantages because of the oral molecule is titratable. So we're also leveraging our tight treatment in our clinical study to identify the optimal dose to achieve the target whole brain volume of

Speaker 6

Great. Thanks. Looking forward to catching up with you once these Data readout.

Operator

And thank you. And one moment for our next question. And our next question comes from Brian Abrahams from RBC. Your line is now open.

Speaker 7

Hi, this is Joe on for Brian. Thank you for taking our question. Just on Huntington's, can you tell us more about Which data might be shared 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 desired level of HTT NowTOWN and CSF?

Speaker 7

Thank you.

Speaker 1

Thanks, Joe, for the question. So the PIVOT HD study is a 12 month placebo controlled study that's in 2 parts. Part 1 is 12 weeks in duration and focuses on PKPD in blood as well as biodistribution, looking at the relative exposure in the CSF and in the plasma. These are important data points to inform optimal dose that gets us towards the target reduction in the brain of 30% to 50% of Huntington protein. The 2nd 9 months of the study is focused on biomarkers of disease, including Huntington protein levels in the CSF, radiographic markers including brain volume changes as well as NfL levels in the plasma and The data we plan to share in the Q2 is an interim analysis from the 1st 12 weeks of PIVOT HD.

Speaker 1

We'll be sharing information on The PKPDNF blood, so looking at blood looking at drug levels in the blood and the reduction in Huntington's mRNA protein blood and then looking at the relative exposure of the CSF in the plasma. As you recall from our Phase 1 healthy volunteer study, we were able to We were getting excellent CNS exposure and in fact we're achieving greater exposure in the CSF than in the plasma. So that's a very important Findings that we'll seek to confirm in the 12 week data. The biomarker data, including the CSF hunting and protein levels, NfL levels and volume changes will come in the readout from the 12 month data. To your second question regarding patient populations.

Speaker 1

As I shared in answering Kristen's question, the mechanism of the drug is targeting the production of the disease causing mutant Huntington protein. That is by leveraging splicing, we're able to introduce Stop codon that effectively decreases the production of that disease causing protein. Obviously, that holds promise for the full Spectrum of HD patients and whether they be juvenile or adult patients given that the disease cause is the same in all cases. However, it's obviously incredibly important in conducting a clinical trial that we try to include the right study population in whom we could Practically capture clinical effect and in the case of the PPDHT study biomarker effect along in the time limited constraints of a clinical trial. So we put a lot of effort into identifying the attributes of what we thought would be that optimal population.

Speaker 1

We've availed ourselves in the robust Huntington disease natural history databases will work closely with Huntington's disease experts and biostatisticians who support these databases to come up with what we thought were the essential attributes of the study population that would likely to decline over the course of a clinical trial. Obviously, we want patients who are not so advanced in their disease that by targeting the upstream cause of the disease, we can't practically deliver a benefit. And we certainly don't want patients who are so early in the disease that they're not progressing at all, therefore making it impossible to show that we're slowing disease progression. So we put these, attributes to play as our inclusion criteria for the study. These were essentially stage 2 HD patients.

Speaker 1

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 TSC score of 13, which would be initially acquired. The reasons for this were because there were a number of these patients who were identified and prescreened and prepared to participate in other clinical trials that were no longer being conducted. So we were in a situation where patients identified ready to be in clinical trials and incredibly eager to participate in clinical trials and whom we obviously believe we could have provide benefit with this therapy. So we made the decision to introduce additional dosing cohorts, 5 milligram, 10 milligram dosing cohorts in these early stage 3 patients because this will provide us additional important data on potential benefit of PTC-five eighteen and also allow us to test our hypothesis In terms of the population that we initially set out to enroll.

Speaker 1

So I hope that answers your question on the adjustments or the addition of new patients.

Speaker 7

Yes, that was super helpful. Thank you, Matt.

Operator

And thank you. And our next question comes from Eric Joseph from JPMorgan. Your line is now open.

Speaker 8

Hi, good evening. Thanks for taking the question. Just a quick one from me on vatiquinone. And if you could just briefly talk about the Pat in the state of the compound, I guess what claims are covered on IP where you maintain exclusivity and then for what duration? Thanks.

Speaker 1

Thank you for the question, Eric. So the protection for particular note is principally going to be on the working With Civity, 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.

Speaker 8

Okay, great. Thanks. Maybe just a quick follow-up, if I could. As it relates to Move FA, can you just talk about sort of the range of patients Entering by age and I guess within that patient ages that will comprise the Primary analysis for mPharmacy on the top line readout. Thanks.

Speaker 1

Yes, absolutely. So when we constructed the MOVE FA trial, we leveraged a number of learnings that we made from our own Phase 2 trial as well as a number of the important learnings from other clinical studies. We also were in a position where given the safety of the teprinone and the large volume of exposure in children, This opened up the opportunity to enroll the full spectrum of FA patients in terms of age. And so in this trial, our primary analysis population consists of patients aged 7 to 21. Now the majority of FDA patients are usually diagnosed In early adolescence, late childhood early adolescence.

Speaker 1

And the idea here is if you look at the natural history of disease, The younger patients tend to have a more uniform and more rapid decline. So as we talked about the last question regarding Huntington's disease, Getting that right clinical trial population that will move enough over the course of the clinical trial for indomodentine placebo group puts you in the best position to CAPTURE treatment benefit. And so we cut the lower age limit at 7 because if patients get younger than 7, First of all, there's very few of them, but second of all, it's harder for those young children to comply with a number of the study assessments. So that means ascertainment of clinical events is difficult. So we set the lower age at And then the requirement analysis group goes up to 21.

Speaker 1

Again, we believe that this is a population in whom, one, we can has less of a chance of a placebo effect. We're also in a situation where these patients tend to have a greater decline of the course of trial, which makes it easier to register clinical benefit. And also as is commonly the case in neurodegenerative disorders, if you're going to intervene, It helps 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 of the drug in the newly enrolled younger patients.

Speaker 1

We're also including additional adult patients, if not part of the primary analysis population, We previously studied the drug in adults. We believe we can hold benefit for, again, patients of all ages and the opportunity to enroll adult patients will give us a chance also to look at the relative It's in the pediatric patients relative to the adult patients, but we would fully expect that with a positive trial that if we can move towards approval that we would have a label that would

Operator

And thank you. And one moment for our next question. And our line is open, Robyn Karnauskas from Chuyen. You're now available.

Speaker 9

Great. Thanks for taking my questions. So I have 3 of them. So the first one is around PKU. So I know the bar you gave the responder analysis 30% from the decline, the improvement fee reduction for those lead in patients.

Speaker 9

But since The bar for entering Phase 2 is 15%. Presumably, you're going to get some lower responders going into this Part 2 that Might actually reach the 30% at the end of the Part 2 phase. And I was just wondering, how do you set the expectations for Part 2? Do you think it will look as good as just the lead in phase considering there may be some slower responders entering that? So I just wanted you to really flush it out and set up for expectations for investors.

Speaker 9

Second question is for FA, given the drug is TID dosing, do you think the bar for success has to be better than Reata? And Maybe flush out how much that TID dosing might impact the market? And then third, you mentioned like The range of patients like the you're doing younger patients and you're confident that they might have a lower placebo effect, but also maybe Maybe progress more rapidly. What's 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 over time with older patients.

Speaker 9

What about younger patients and decline of the efficacy of these drugs? Thank you.

Speaker 1

Okay, Robin. Thank you for those questions. We'll take them in turn. So the first question is regarding the APHINITY trial. And so as we said, we have We run a phase in which all screened subjects were treated for 2 weeks of severe tear and we randomized all subjects who had a greater And 15% reduction in fee.

Speaker 1

However, importantly, the primary analysis population for the trial includes only those subjects We had a greater than 30% reduction during the run rate. So in terms of the primary analysis and success in the trial That there'll be no interaction of those like 15% reduction or between 15% and 30% reduction during the run-in versus those that had 30% reduction. Just to give you a few of the numbers as we shared in the past, we had 102 of the 156 subjects who were In the run rate, they've had over 30% reduction and there were additional 13 subjects who had between 15% and 30%. That's important because what you're basically seeing is that of 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, the mean reduction in all comers was 66% from baseline.

Speaker 1

So really Impressive reductions in those numbers. To answer your question also about what we would expect to see in terms of reduction in the patients as they move from the Run-in phase to the placebo controlled phase, look, these patients are treated for 2 weeks, they're washed out, return to baseline and then the Same patients are again treated with the same drug. So those who get randomized to active, we fully expect to see similar magnitude of reduction. And obviously, those who were randomized to placebo given that historically the placebo patients in PKU trials tend not to have very much of any placebo response. That gives us a great deal of confidence to not only achieve the primary analysis, the success of significant Greater reduction in the treatment relative to placebo, but again, you're confident based on the data from Part 1 that we'll be able to demonstrate not only clinically meaningful response, but one that would Strongly differentiate, Stephanie and Karen for the treatment of PKU.

Speaker 1

In terms of FA, Your first question was regarding the TIV dosing. Look, we've never seen a problem with Compliance with TIE dosing and it's a breakfast, lunch and dinner. So it's actually with meals, it's not Q8 hours, which makes a very big difference. And we believe that there's several other important aspects that differentiate the therapy. I can turn it over to Kylie.

Speaker 1

I don't know if you want to add anything to that

Speaker 2

Yes, I think that's well said, Matt. I think There's a number of factors that are taken into consideration, particularly in disease of high unmet need and progressive diseases like Friedreich ataxia. Efficacy, 1st and foremost, is obviously a key priority. And so it will be interesting to see as we come out of the Move FA study where both our primary and secondary endpoints land. In addition to that, safety is obviously really important.

Speaker 2

And so there's a number of Two differentiation factors from a safety point of view that we've seen with vatricuinone. And then obviously dosing comes into play. And as Matt said, with Dosing around meals, it's 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 as they're eating the meals. So across the board from the discussions we've had both with KOLs and with patients, There's not been any concerns raised around that, Robin.

Speaker 1

Yes. And then Robin, in terms of your third question regarding the 7 to 21 year olds and concerns there. And then how do why do we think that those patients will move more in the course of the clinical trial in the placebo group. So the natural history of disease is very clear when you look at age groups and changes in the MFAR score over time. If the patients Who are diagnosed earlier and are younger at the time of disease presentation tend to have a more uniform and greater magnitude of decline over the course of the study.

Speaker 1

In terms of the concept that by interviewing early And 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 at the RAYADA data, it was in their young they had patients 16 to 45 of those in the 16 to 17 year old cohort, those younger patients where they had the greatest, over 5 points placebo corrected Which I think lends further support to the notion that if you intervene early, you're going to be able to capture a greater treatment effect on those patients. In terms of reduction in effect over time or still progression over time, look, none of these therapies are curative, But to be able to slow progression, slow progression by a year, by 2 years is incredibly meaningful and a slowly progressive disease such as future cataxia that is relentless in its progression. So I think we expect there Meaningful effect in children that will alter and modify the disease course.

Speaker 1

They may one could still expect there being some progression all the time, Being able to slow the progression of disease would be incredibly meaningful impact of particular.

Speaker 9

Thanks so much.

Operator

And thank you. And one moment please. One moment for our next question. And our next question comes from David Lebowitz from Citi. Your line is now open.

Speaker 10

Hi. This is Devanjana on behalf of David. So thanks for taking our call. The first thing we wanted As was like if you could share any further details on the nature of FDA queries regarding UxTASA like feedback you received? And do you anticipate any additional delays like that could push back the FDA sorry, the BLA submission beyond Q3?

Speaker 10

And one other thing we wanted to know is that like, given like the although omav and pivotal trials are both using MFRS as endpoint. There are, of course, differences in like the patient demographics and time points. So How should we benchmark vaticoinone results when they come out against the omav like label efficacy? Thanks.

Speaker 1

Thank you very much for the question. So first on Asteyza, as we had previously shared, the agency had We requested that we provide some additional data on comparability between the clinical drug product and the commercial drug product, As is commonly the case in drug development and particularly the case in gene therapies, the manufacturing process for a gene therapy drug product can evolve 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 it's apples to apples. The key attributes of the commercial drug product are analogous to The attributes of the clinical drug product and the agency had asked us to provide some additional data, essentially analyze additional We have a few examples 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 asked for some additional Questions around one specific area, which is differences in empty fill capsids between clinical product and commercial product. They are quite similar and we were able to easily provide that data.

Speaker 1

We have stated that we believe the Submission of BLA could be delayed to Q3 of this year from Q2 and that's simply because of the potential cadence of interactions back and forth between the agencies. We'll then submit responses to their queries. We expect to hear back from them and then be in a position submit the BLA, but we just wanted to communicate that it's possible given the cadence of the back and forth with the agency that the submission could be delayed until the Q3. Regarding differentiation between omav and vatikinone, obviously, there's not the past Trial is a bit longer than the omav trial, so that's going to allow for the possibility of capturing a longer term impact on 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 appreciate The relative benefits of betikinone and obviously secondary endpoints are really, really important. I mean, I think that's an important part of The Epi story is also important part of the regulatory pathway.

Speaker 1

Our discussions with the agency have been similar to those that we had, which is they'd like to understand not only the effects on the primary endpoint, but other aspects of disease morbidity, which are captured in some of the secondary endpoints.

Speaker 10

Okay. Thanks. Very helpful. Thank you.

Operator

And our next question is Joseph Toome from Cowen. Your line is now open.

Speaker 1

Hi there. Good afternoon and thank you for taking our questions. Maybe first one on the PKU trial. When you think about what constitutes Success here, is it really just a static benefit or do you want to see a certain proportion of patients under 360 micromole per liter or that have a 30% reduction from baseline or what have you? And do you have the sufficient safety database to file off this program if the study works?

Speaker 1

And then I have one quick follow-up. Thanks for the question, Joe. I'll start and then I'll let Kiley talk a little bit about the commercial differentiation. So Obviously, one of the couple of things that were really impressive from the Phase 1 run-in data. One was the proportion of patients that responded seeing Nearly 2 thirds of the patients have over 30% reduction is really impressive and certainly when you benchmark it to the Kluban Allcomer a study where the proportion of responders over 30% was only 20%.

Speaker 1

The second is the magnitude of the fact not only in the overall Treated 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, it says that regardless of your disease severity, we're able to provide in that running phase of real on market reduction in phenylalanine. Our expectations with the placebo controlled study would not only provide evidence of clinical benefits sufficient to But also would it be able to provide evidence of differentiation? I'll comment quickly on the regulatory, but then I'd like to highlight a comment on the differentiation.

Speaker 1

So on the regulatory front, we're going to have data from the 6 week placebo controlled study, but obviously we've been Patients roll over from the placebo controlled study into a long term open label extension study, which is going to provide data not only on durability effect, but obviously Longer term safety, 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. Kylie, do you want to hand the commercial differentiation question?

Speaker 5

Yes, absolutely. Thanks, Matt, and

Speaker 2

thanks, Joe. I think from that perspective, Joe, it's 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 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, but those being And I think even in that 15% to 30% population showing benefit in classical PKU is going to be a powerful differentiation.

Speaker 2

Outside of those that classical PKU population looking more broadly, I think, In those that have already trialed and failed Kuvan, showing a stat sig benefit, I think will be key. And even looking at those that are poorly controlled over And ultimately well controlled, I think looking at a 40% plus greater fee reduction will give us an opportunity for the number of different patients in those Different segments. I think obviously anything higher above and beyond that opens up more and more patients that would be looking to try sepiaptra.

Speaker 1

Great. Thank you. And then just real quickly on UBSAZA, I know it's mentioned that several patients were treated. I don't think I saw it in the press release, but are you able to provide some of the revenue contribution for This quarter or if not, are you anticipating breaking that out going forward? Thank you.

Speaker 1

Mark, do you want to talk a little bit about the launch and progress in treatment?

Speaker 3

Yes. Well, we haven't actually broken out Yes, specific patient numbers or revenue, but we're really pleased with the way the launch is progressing. It's going according to plan and what we see is patients are being treated We actually have treated patients in both Germany and France And we in the quarter. And we also have treated our 1st cross border patient, which came from the Middle East and was treated in Europe. So Proof of concept of treating cross border patients commercially was achieved.

Speaker 3

We continued our patient finding activities And we've been able to continue to find patients in the Q1 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

Speaker 1

I call early access programs as well.

Speaker 3

On the payer engagement side, it's It's gone extremely well. We've had strong HTA assessment in Germany and France, which now is 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 and that's important for patients in England and Wales We'll 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 a really steady Cadence of patients and we're the overall cadence of those patients that are being treated means that there will be more patients treated in Europe.

Speaker 3

And as the year goes by, we're going to see patients via early access in the Middle East and Brazil. So, so far I would say we're really pleased with the progress.

Speaker 1

Great. Thank you very much.

Operator

And thank you. One moment please. And one moment for our next question. And our next question comes from Kelly Hsieh from Jefferies. Your line is now open.

Speaker 11

Thank you for taking my questions. For vitecanal in assay, my question is, the Phase 2 study showed a treatment effect at a point 5 points difference over placebo arm on FARS NeuroStar at 24 weeks And the first for Phase 3, it's 72 weeks and you said about at 4.5 I'm just curious what data you rely on to model how the treatment effect will trend from 24 weeks to 72 weeks And make this decision on the primary endpoint. Thank you.

Speaker 1

Yes. Thank you very much for the question, Kelly. So a number of important points Here and that you brought up. So the Phase 2 study was 6 weeks in duration and had the difference that you noted. And part of that Magnitude of that difference was driven by a placebo effect that was present even after 6 months and this is something that was important lesson we learned.

Speaker 1

And If you look at the REATA data as well, you still see a persistent placebo effect at 6 months that had that study only been 6 months in duration. They would not have achieved Statistical significance as they did, more time is needed for that placebo effect to abate. So our selection of the 18 month Our duration or 72 week duration of the placebo control phase was to allow for complete washout of any placebo effect and allow for the placebo patients To more closely mimic the natural history of the disease, which is on average a 2.5 point loss on the mpar score per year. So you would expect that based on natural history, the change in the placebo group should be closer to 3 and perhaps even higher. The magnitude of treatment benefit was based on the hypothesized magnitude of treatment benefit was based on the long term extension of the Phase 2 study.

Speaker 1

Now we did do the 6 week placebo portion, right, but all patients were continued to be treated For an additional 18 months, which allowed then for a comparison of 18 months to 24 months of treatment with an age, stage and sex matched natural cohort, Natural History cohort. The magnitude the difference between those two groups between the Natural History And the natural history cohort and the treated cohort was actually much more market. There was a 4.8. Worsening and an 8.1.8 treatment benefit. So the difference over the 18 24 months was 6.6.

Speaker 1

So we're starting to see a magnitude of effect from the Phase 2 study that's greater than what you mentioned as a hypothesized effect 4.5. So we believe That 4.5% estimate and power on that difference puts us in a strong position to capture significant benefit in the study.

Speaker 11

Super helpful. And I also have a quick follow-up in PKU, if I may. Do you think 16 classic patients are sufficient To ensure a broad label in both mild and classic PKU patients, all this might require expanded enrollment.

Speaker 1

Yes. It's a good question. We have 15 patients in the running phase with a mean reduction of 22%. So you're seeing pretty meaningful reductions now across 20 patients, which in classical PKU is a lot. I would also say and keep it a couple of things to keep

Speaker 3

in mind.

Speaker 1

One is that we also capped the number of classical PKU patients. So you're seeing a good proportion of those treated who are having those meaningful levels of reduction. The other important thing to think about with classical PKU is not only the Threshold response is having a greater than 30% reduction, but also the absolute change in phenylalanine. When you think about PKU, it's that Levels of phenylalanine that are most significant in terms of the clinical effects of the disease, including cognitive effects. And it's well known that reductions And phenylalanine by even 100 points can impact IQ.

Speaker 1

So if you think about a 15% or 20% reduction in phenylalanine levels For classical PKU patients, obviously, those could be quite meaningful when one considers the benefits of reducing the overall Level of that, finally. So we believe that the data set we're generating will have not only a number sufficient number of patients The classical PKU to be included in the label, but the magnitude of effecting in these patients is also quite important and impactful.

Speaker 11

Terrific. Thank you.

Operator

Danielle, if your phone is on mute, could you please unmute it?

Speaker 1

Yes. Hey, sorry. This is Alex on for Danielle. Just a couple of quick ones from us just to clarify, my audio went out. Just wondering what was up with the FDA Type C meeting request for Translarna.

Speaker 1

Has that been requested or scheduled? And then secondly, just curious about the order of the upcoming readouts. You're trying to back into it a little bit. Is it fair to assume that PKU What comes first? We were trying to guess May and maybe June for the others.

Speaker 1

Thanks so much. Thanks for the questions, 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've not provided more specific timing because we don't have the more specific timing beyond Q2 at this time. In regards to your first question and the Type C meeting for Translarna, as we had previously shared, we had a meeting with the FDA, a Clarification meeting following up the written response only that we had received from them in the fall.

Speaker 1

In that meeting, the Agency suggested that we request the Type C meeting to review with them the totality of data from Translarna, including mechanistic data, dystrophin data and the Data that we've generated over the clinical studies done to date and then be able to have a robust discussion on the totality of data and its potential to support an NDA re submission. So we're obviously, there's a lot of data to be presented. We're in the process of preparing that meeting request and the briefing book. We're going to be able to include not only the mechanistic data they asked for, but the data that we collected in the 3 placebo controlled trials and that was 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 this data package is that we're having a clinically meaningful effect that's not due to chance.

Speaker 1

And the Consistency of effect that we're seeing across the 3 studies, the volume of data that we've collected in over 700 boys, the ability to look across these three studies and see statistically significant benefit across a number of the key endpoints of the disease, the safety of the drug as well as the Context of these, which is non sensitization DMD remains a significant unmet medical need. So we look forward to putting together all these data in a briefing We're also conducting some additional analyses to address some of the previous concerns that the agency has raised, so we can come in to the agency at the right time and have a robust discussion about the path to NDA resubmission. Great. Thanks so much.

Operator

And our next question comes from Joe Swartz from SVB Securities. Your line is now open. Great.

Speaker 12

Hi. This is Will on for Joe today. Thank you for taking our questions. So to start, I just want to pivot back to the MOVE FA study. And based on the powering, it looks like there is the potential for the study to miss on Statistical significance while also showing the benefit over Reata's omaveloxolone.

Speaker 12

So in this event, how are you thinking about next steps on the regulatory side? And I have a quick follow-up. Thank you.

Speaker 1

So Will, thanks for the question. We believe That we will have sufficient power to detect the difference that was recorded in the ARIADA study. So we don't see that as our risk here, If we capture the same magnitude and investment similar there.

Speaker 12

Okay, great. And then I guess following up here, Now has the agency provided you guys with any specific guidance in terms of what they want to see either from an efficacy standpoint or a stats perspective? And how is your thinking, if at all changed on this since the approval of omaveloxolone and kind of any insight into the agency's views

Speaker 1

Yes, sure. It's an interesting question, Will, because historically the agency has very much Wanted to not only see a significant effect on the mfAR scale, but given that it's a composite scale that doesn't Clearly communicate the impact of a therapy on how a patient feels or functions in everyday life, which is those are really the buzzwords that FDA likes to see for clinical benefit. They typically wanted to have a key secondary endpoint that more directly assesses the other function move along with the primary endpoint so that you can contextualize appropriately contextualize the recorded changes and ours as being clinically meaningful. Obviously, that was a source of a lot of the discussion that went on over from the time Rayator shared their data in October 2019 till NDA approval. And I would I think that some of the back and forth was based on The fact that their key secondary endpoint, which is the clinical global impression scale did not achieve statistical significance.

Speaker 1

So be that as it may, The approval of the FDA on essentially a specifically significant NBARs change set a threshold that we believe others can now follow. I think while it's unclear and challenging sometimes to predict how the FDA will act or the reasoning behind their decision, they tend to be quite consistent when they set a precedent So I think it's clear. I think if we believe that being able to achieve a statistically significant effect on the MFARs, particularly in a longer study But 72 weeks relative to 48 weeks and in a larger patient population that we had in MoveSA relative to The MOXI study would put us in a strong position. Nonetheless, we did spend a lot of time Planning at a key secondary endpoint for this study, which is the FA activities of daily living scale, which is something that the agency has shared that they believe Adequately captures feeler function and everything like we selected this as the key secondary endpoint because if you look at the national history data, MRs changes Tend to move along with changes in the ABL scale. They tend to move similarly and across as the disease progresses.

Speaker 1

And in fact, if you look at the results of the MOXVI study, the one secondary endpoint on which There was nominal statistical significance. It was the ADL scale. Unfortunately, I believe that was listed as the last of several secondary endpoints in the MOXI study. So again, just to answer your question, I think the statistical significance on Ampharas is the benchmark that's now been set for approval, but we'll also obviously be Looking to see if we can capture secondary endpoint benefit as well.

Speaker 12

Very helpful. Thank you.

Speaker 3

Our next caller is Jeff Hung with Morgan Stanley. Jeff, your line is open. Please go ahead.

Speaker 13

Thanks for taking my questions. For Maity, 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 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.

Speaker 1

Thanks for the question, Jeff. So the powering in the MIGHTY study was based on a couple of things. Obviously, on the placebo side, we tried to hypothesize a change in observable motor seizure frequency that was consistent with the placebo response that's been shown in other pediatric epilepsy syndrome trials. And there's not been any Previous placebo controlled trials in children with myometriosis associated with seizures, but we believe the hypothesized effect of placebo effect 10% was reasonable given what's been seen in other studies, which is generally ranging between 3% 19%. On the efficacy side, a 50% reduction.

Speaker 1

So first, let me say we absolutely agree given this to be Refractory nature of these seizures, their highly morbid nature, the fact that they could be life threatening in many cases, I think most KOLs and regulators would agree that 25% reduction would be clinically meaningful as population. That 50% hypothesis is driven a bit by the previous Seizure reductions we've quantified in other studies, particularly in the treatment series of children with ponticernodar hypoplasia type 6, which seems to be 1 of the most virulent mitochondrial disease associated with seizures subtypes. So again, we believe that we 20% to 25% would be incredibly meaningful, but again, the numbers are based on our previous experience as well as the experience of others.

Speaker 13

Great. Thanks. And then for PTC-five eighteen, did the FDA specify where the additional data for supporting dosing and duration needed to come from geographically? I know that you've been enrolling patients outside the U. S.

Speaker 13

And just wanted to see if FDA had given any indication on whether they wanted data from patients in the U. S. For additional data and if they may care at the end of the study if more patients end up coming from other geographies. Thanks.

Speaker 1

Yes. So just as a reminder, Jeff, the FDA asked for additional data to support the dosing and duration proposed in the PIVOT HD study was based on non clinical data. This is based on data from the toxicology studies, the same toxicology studies that were used to support the approvals of the conduct of the study in The other geographies around the world where the study is being conducted, it was the FDA uniquely had asked for additional data to support the dosing and duration And they said those data could be clinical data that were collected as part of the Kedahashi study. Obviously, as the study has only been conducted in countries outside of the U. S, they would naturally And that those data are going to come from patients outside of the U.

Speaker 1

S. And so we will plan as we do this first interim data cut to use those data to take those data to the agency and continue discussions about opening enrollment again in the U. S. But In terms of the patients coming from outside of the U. S, they naturally expect that and there shouldn't be any other impact on how these data are looked at, Whether they were collected in the U.

Speaker 1

S. Or elsewhere. Okay. Thank you. One moment.

Operator

And our next question comes from Gena Wang from Barclays. Your line is now open.

Speaker 4

Thank you. Very quick few

Speaker 3

First one is

Speaker 4

regarding the 4 datasets, we see each individual datasets with press release and the conference call in the second And the second question is regarding AFFINITY trial in KiU. There's some patient had prior Kuvan experience. I know you cannot comment on the percentage of patient, But would these are Kuvan non responders in the study or simply just Kuvan experienced patient? And then lastly, very quickly on Pivot HD, what is your bar for the lot hunting team knockdown level?

Speaker 1

Gina, thank you for the questions. Unfortunately, I didn't clearly hear your first question. I heard a second and third. Would you mind repeating the first question?

Speaker 4

Sure. First question is basically for the 4 datasets, will you report individually with press release and the conference call In Q2?

Speaker 1

Yes. So as we've guided that the data from Ophineo will be in May, the other We haven't given details yet on the exact nature of whether there will be all releases and calls or So we haven't made those decisions yet. And we plan to share the data as they become available. There's not a plan now Can match them in any way. On your second question, we do have patients who entered the study who had previously been treated with Kuvan, who are I see.

Speaker 1

So that obviously will give us the opportunity to understand in specific subjects what was their Kuvan effect relative to what we observed today, Epiaterin effect during the run phase. And we'll plan to break out some of those data in with the data release when available. So to directly answer your question, it's a mix. There's folks who've been on Kuvan in the past has failed and others who were taking it and washed out to 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%.

Speaker 1

We're in a difficult position. Obviously, we can't directly measure Changes in neuronal Huntington protein levels because we simply can't 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 that's a compartment that we can easily access And that was one of the nice findings, some important findings from Phase 1 that we were able to record evidence of target engagement and dose dependent splicing activity with dose dependent reduction in huntingtin mRNA and protein in the blood. That gives us a very good window into The target engagement and splicing activity.

Speaker 1

Now the next important element is the relative exposure of the drug between the blood and the brain, which we can measure by looking at blood levels of drug and measure by looking at CSF levels of drug. We know that splicing activity is directly related to exposure. So by understanding what the reduction is in the blood at a certain exposure Relative and then understanding the relative exposure between the blood and the brain can give us an estimate of what is going on inside the brain cells. So the decision to start with 5 10 milligrams in the Phase 2 study was based on what we saw in Phase 1 in terms of blood huntingtin protein lowering, which what we saw in the NAD was roughly 40% reduction at 15 milligrams and roughly 60% reduction at 30 milligrams. We noted that the ratio of free drug in the CSF to plasma was 2.7:one.

Speaker 1

So we were getting twice as high exposure in the brain to the blood. So therefore, we said that 5 10 milligrams, if those exposure ratios hold, we could very well be at the necessary dose level to achieve the desired 30% to 50% low rate. So we'll look at when we get the PIVOT H2 data at the levels of reduction recording in the blood at 5 10 milligrams will also look at the relative exposure from the blood to the brain and use those data to help guide the decision of whether we want to Our dosing in that higher dose level of 20 milligrams, which based on the Phase 1 data would represent roughly 50% reduction in the blood. And therefore, if we were closer to a 1 to 1 ratio of blood and brain exposure, would suggest that we're achieving roughly 50% reduction in the brain. I know there's a lot of numbers and a little more complicated, but just to answer your question.

Speaker 4

Very helpful. Thank you.

Operator

And our next question comes from Collyn Bristow from UBS. Your line is now open.

Speaker 14

Hi, this is Yi Han on for calling. Thanks for taking our question and congrats on the quarter. So the first question is For the Translarna, it seems to have a very big beat this quarter. And you just noted the government order would continue to be expected in the 2nd Q. Just wondering about this government order in terms of the longer time and also because you didn't really update your DMD guidance.

Speaker 14

Just wondering if we should potentially expect more revenue for this whole year versus our current guidance. Can we have more color on that? And the second Q, just a very quick clarification question. So for the Avisa Do a filing delay in the Q3? You previously said you have already provided the additional requested data to Yes.

Speaker 14

Is that correct? Thank you so much.

Speaker 1

Thank you, Yihai, for the question. Let me first say on Translarna revenue. We're Incredibly excited about the performance in the Q1. As Eric stated in the prepared remarks, we remain on target to meet franchise guidance this year. But let me turn it over to Eric and Embers to provide additional color on the Translarna franchise.

Speaker 3

Hey, Hass. As we mentioned earlier, Translarna 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 We have compliance rates in many countries at 90%. We've seen a lot of the geographic expansion take hold over the last three 4 years as we've developed these in places such as Central and Eastern Europe, in the Middle East, our CIS region and of course in Latin America. So many of these orders that come in are central government orders and it's for new patients as well as the existing ones.

Speaker 3

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're adding new patients every quarter, especially seeing from these geographic expansion markets. So this strong performance that we've seen across Translarna is going to continue. We'll have some lumpiness in the quarter, but we anticipate government orders to continue because the base that we have, including new patients that are coming in and Managing the compliance and the load discontinuations are incredibly important. We're not going to change the guidance at this point in time and we'll just continue to provide an update as we see these orders Coming in, but I'd like to reiterate that we have a 545 to 565 D and D franchise right now that we are very confident in achieving this year.

Speaker 1

And then I'll just also that's why we don't typically give quarterly guidance. We tend to give And your guidance for just that reason. Regarding the BLA, I will say that, as we commented before, they had the FDA had asked For additional data in support of comparability analyses, 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 and we'll send back in shortly. And again, the Timing, the potential delay in submissions in the Q2 to Q3 is just a possibility based on the potential cadence of Responses from the agency, the query responses.

Speaker 14

Okay. Thank you.

Operator

And our next question comes from Kaye Cruz. Your line is now open.

Speaker 1

Hi. This is Kate on for Paul Choi. Thanks for taking our questions. Two quick ones for us. First, we wanted to see what the impact of inventory or stocking was throughout the quarter.

Speaker 1

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 as the pipeline progresses here. Thanks so much. Yeah, Absolutely. Thanks for your questions.

Speaker 1

I'll start, Kay, and then I'll turn it over to Emily. So first, regarding OpEx, Look, as we mentioned in the prepared remarks and as we've talked about previously, we've been building our R and D and Commercial infrastructure over the past several years and quite proud of what we've achieved. Obviously, the performance of the commercial performance in the Q1 is Incredibly impressive and 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 cards of these clinical trials, we'll 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 operating expenses. Obviously, we'll 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 and the revenue growth we desire to achieve over the coming years.

Speaker 1

Emily, do you want to comment on OpEx or further on OpEx and on stocking?

Speaker 5

Yes. On OpEx, Obviously, put it best, we look forward to after the readout of data, analyzing our program priorities and Looking for opportunities to narrow our OpEx guidance. On the revenue side, there was no stocking. We Saw some large government orders, as Eric has pointed out, which contributed to the growth in the Q1 and put us in a position to reiterate

Operator

I would now like to turn the call back over to Chief Executive Officer, Matthew Kline.

Speaker 1

Well, I want to thank everyone for joining the call today. I'm incredibly pleased with the productive and successful Q1 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.

Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.

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Earnings Conference Call
Edison International Q1 2023
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