Q4 2019 Earnings Call
[music].
Ladies and gentlemen, thank you for standing by welcome to the PC Therapeutics fourth quarter in your end 2019 financial results Conference call. At this time all participants are in listen only mode. After the speakers presentation. There will be question and answer session to ask a question. During this session will need to press star one on your telephone.
As a reminder, trees program, maybe recorded and now I'd like to introduce your host for today's program Alec Skate head of Investor Relations. Please go ahead Sir.
Good afternoon, and thank you for joining us to discuss the PTC Therapeutics 2019 fourth quarter and your and corporate I'll see if some financial results joining me on today's calls are cheap.
Second of Officer, Stuart Peltz, our Chief operating Officer, Marcio Souza, our Chief Financial Officer Emily Hill.
Before we start let me remind you that today's call will include forward looking statements based on current expectations. Please take a moment to review the slides posted on our Investor Relations website in conjunction with the call which contain forward looking statements and other details share during this call.
Our actual results could materially differ from these forward looking statements any such risks can materially and adversely affect our business the results of operation.
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 Exchange Commission as well as the company's other actually see Fox.
We will disclose certain non-GAAP information during this call information regarding our use of GAAP and non-GAAP financial measures reconciliation of GAAP to non-GAAP Isabel today's earnings release with that let me pass the call over to our CEO Stewart.
Thanks, Alex.
Thank you for joining us. This afternoon, we provide our update for the 2019 fourth quarter and ended the year route.
Significant progress was made across our platform and programs in 2009 tea, which has continued in 2020.
Our vision is to continue to grow with the diversified rare disorders company with multiple finds platforms with the goal of at least $1.5 billion in rather like 2023.
Ptcs recent transformation has been remarkable to experience.
Over the past five years, we've transitioned from a single product company with Translarnas.
To treat nonsense mutation duchenne muscular dystrophy issue to company with two Duchenne muscular dystrophy products trends lawn and garden Plaza to where we are now.
Now selling for products globally and have the capabilities to bring therapies to patients in 50 countries.
With potential approval for roof to plan to treat Esa nave patients in our gene therapy Ray do you see deficiency, our commercial portfolio is expected to further expand our pipeline is also expected across multiple scientific platform, which we will continue to drive innovation and lead to value.
Creation.
Let's start with ours, placing platform.
We recently presented the results from our successful SUNFISH part two pivotal trial.
This trial when road enrolled the broadest population of type two and three estimate Peyton ever study and and more closely represent the type of pacing. That's his mission typically see in practice.
Importantly, the vast majority of type two or three patients are not currently on disease modifying treatment.
The positive and statistically significant results observed in this trial confirmed the potential of routes. The plan would be the most competitive global product for a broad range of estimate patient.
SUNFISH part two study non ambulant estimate HM 225 years, so big without any limitation to their motor function capabilities as evidenced by the baseline Hammersmith scores.
We believe that you results further support potential approval and reimbursement for a broad patient population.
We also recently announced successful topline results from the pivotal fire pits study in type one and somebody patient.
This trial met its primary endpoint it was statistically significant.
Complete results Empire fish part two will be presented here yet in late April.
With these studies now completed we anticipate <unk>, what do you have maybe next quarter and look forward to the upcoming produced a date on may 24th.
The next or slightly modify your moving towards the clinic is for Huntington disease.
We were selected a development candidate, which isn't GLP safety toxicology studies and expect to have an I'd be filed by the end of the year.
As a reminder, there are no currently approved therapies for the treatment upon needed to be.
In preclinical studies are Huntington disease development candidate demonstrated uniform Huntington lowering systematically and throughout the whole brain, including in the stride Rite aid them Cortech Syncera belem.
This is critically important as hamid into these effects virtually all parts of the break.
Similar to our estimate program, where we mentioned FM in two M.R.M. R&D and protein levels in healthy volunteers.
We will also have the ability to measure Huntington lowering blood.
And Mike we've shown that the level of Huntington lowering observed in blood reflects the level of Huntington lowering and all tissue in the brain was near one to one brain the blood Huntington lowering ratio.
This is exciting because it will allow us to rapidly demonstrate target engagement.
Typically you back early phase one clinical program.
Moving on our next scientific plant form like.
Like late last year, we acquired assets from buyer electronic focused on re docs pathways, which we now refer to our buyer we platform.
These compounds are all small molecules orally bioavailable highly selective and efficiently cross the blood brain barrier similar to our other small molecule therapy.
We're very excited about the progress in our body or you platform with to potentially Registrational studies to begin later this year.
I wanted to take a moment to discuss the science behind this platform PTC seven for three and <unk> five seven well both entered the clinic later this year.
Hi, good 15 with boxes, you need a key regulator box distress lifted taste neuro inflammation, Apple Mcqueen oxidation an aggregation in cell death.
Inhibition of 15, the Pocs, it's usually leads to the reduction of key disease markers, such as real cell activation that Google filing depletion.
These critical modulators underpin package Genesis across broad range of nurtured agenda and mitochondrial diseases Marci were five additional details I'm just like on this platform later in the call.
Turning to our gene therapy platform, our strategy is to replace genes of interest by targeting specific teachers, which limits systemic exposure and potentially lessons immunogenicity blame it administering small doses, we also reduce our manufacturing burden. Furthermore, we're pursuing diseases.
Tissue with lower sell turnover, such isn't the CNS and the yard which may lead to improved durability of response.
Being able to control our manufacturing state is key to our gene therapy strategy.
2019, we entered into a long term lease for state of the art Biologics manufacturing facility. We expect to begin in house gene therapy manufacturing efforts in the facility. Later this year importantly, we were able to retain the vast majority of biologics manufacturing factory talent at this was still.
We are now well positions the start gene therapy men factory on her own would be a central facilities equipment and talents in place.
I want to highlight our most advanced gene therapy program for a D.C. deficiency, which is shown impressive clinical results in 28 basis.
<unk> D C deficiency marketing authorization has been filed an accepted in the M-, we plan to submit the B.L.A. to the F.D.A. into second quarter up this year, our patient identification efforts are ongoing and we continue to identify patients globally with a D.C. deficiency.
Hey, D.C. deficiency is a rare and devastating inherited disorder. The globally affects roughly 5000 patients with an annual incidents of approximately 300 patients.
Well originally there was a concept that age you see was confined to a genetically defined population in southeast Asia, approximately 80 different mute millennials have been identified globally. This highlights. The age you see deficiency is a genetic disorder that affects patients all across the world, we anticipate more than three.
800 addressable patients will be identified by launch across the U.S. Europe and Latin America.
Taking all these updates indoor com, we are not well position to drive continuous value creation with a number of exciting upcoming milestones and a deep pipeline to drive sustainable innovation moving forward.
Look forward to shoot and more detailed information on our platform in pipeline on our analyst day on June 16.
With that let me turn the Mike over to Marcio RCM.
Hey, Thanks just to.
Let me start just the commercial side of the business our GMT franchise remains the foundation for our girl.
For Translarna, there's growth potential from multiple ongoing efforts.
We expect increased penetration in existing territories, including Brazil for which we recently received M P's approval.
Geographic expansion into new territories.
Chris disease awareness in order to diagnose we also contributes to growth moving forward.
For in Florida, We expect continued positive momentum with new patient and those switching from prides itself.
Just a real sense label expansion, we are now able to treat all GMT patients two years in older and continue to increase treatment with some plaza in this younger patients.
Our beaches seek care scene is actively engaged with physicians and payers to ensure that patients receive access to treatment as quickly as possible.
In Florida clinical differentiation border supported with new data recently published in the Jarno of comparative effectiveness.
In that study treatment with the plastic or was associated with a more than two years delay in law the combination relative to two its mentally friends on.
In addition jumps out the publications like scoliosis, what's significantly delayed among patients treated with the slots at par sports to spread himself and for their functional benefits were absorbed into fly the core patients.
The data also demonstrate its defaults to risk benefits of switching to that fly the cost trend fragile.
Beaches sequel genius to leverage our strong Latin America infrastructure to support ongoing and upcoming launch.
Detect Sadie launch continues to trend well with hundreds of newly diagnosed patients genetically Colm funds for Pete you see supported problems.
We are finding entreating, new patients and due to do you already have a natured off the disease the process is likely to accelerate into future.
As a reminder, that Saudi wants to force approves H.E.R. silence or.
Treatment 40 stage, one and 2.0, Patrick adult patients by M Pesa.
Yeah at an estimated 6000 patients with H. yard in Latin America, the vast majority of Dan in Brazil.
We believe that Doug said, he is well differentiated and the best fits participations.
That said is a some good 10 years at home injection performance by patient.
In that region, while infusion clinic us are often asked on your capacity and then which travel requirements can be challenging self administration is the best solution for patients in the healthcare professionals.
Through our early access program.
Patients are able to enter our patient service interrupting access and other kinds of supports allowing us to be able to strong rent loyalty and lasting relationships.
Let me now touch up on the bio eat platform that is to reference or.
As mentioned, we're very excited about this problems and they are fits within our current portfolio and the future with both the platforms and Standalone therapies.
To reiterate beaches cseven for three and 857 art advancing into clinic and they both targets 15 Lybrook seasoning.
An additional compounds, we just see five eight night targets a different set up enzymes and he has been partnered with a Japanese company Sumitomo Dainippon pharma.
Currently being developed for the treatment of a elas and potentially alder neurological disease.
Following the recent completion of a positive proof of concept study Sumitomo is plenty to move forward with the developments are you just see 589 40 Elas.
So we don't want has commercialization rights in North America, and Japan, why would be just to remains commercialization rights under wraps up toward including Latin America in Europe.
Moving back to our lead compounds Ptcs seven for Threed.
First indication using refractory mitochondria black sea.
And it would be initiating a potential registrational trial next quarter.
Seven for three years, rather unique in that it has already being used to treat over 400 patients with mitochondrial disease for a series of compassion use any indication specific studies.
Oh, no, but just your seven for to be wall. Just started in an expanded access program from 2009, 2012, where 94 patients throughout the U.S. Europe in Latin America with insurance adds mitochondrial disease and within 90 days.
Oh and up Lifecare wanting roles that was the specific criteria.
43 of the is 94 patients remain alive and on treatments today.
Which is remarkable considering the expectations at the beginning of treatment of survival off only 90 days or less.
Speeches has also experienced a meaningful reduction in seizure frequency.
The upcoming 743 trial, we roll approximately 60 patients globally.
Who have inherited mitochondrial disease and associated with <unk> refractory epilepsy.
All patients will be followed for one month to ensure a baseline seizure frequency and then we'd be randomized to receive either beaches cseven for three or placebo for six months.
The end points for the trial is reduction in seizure.
We expect that there are five to 6000 addressable mitochondria slaps you patients in the U.S. in Europe combined.
We also plan to initiate a nod their registrational trial with 743, either shut that step in the following quarter that door to part it off this year.
Would you complements our gene therapy approach.
You know your phase two trial in 63 at Feight patient seen day last treatment with 743, well the associated with an improvement in long term disease severity and neurological function when related to natural history.
The primary endpoint team that trial was measured at six months, which now understands is not sufficient to show a separation from placebo.
From a safety perspective, 743 has been dosing hundreds of patients and has generally being well tolerated in the clinic.
Incorporating the understanding stone to fields that have the more since the initial proof of concept trial.
Yep calming trial of 743 in that phase, we enroll approximately 100 patients we will be focusing on the younger cohorts and run a trial for one year you know once you want randomization scheme with placebo.
As a reminder, we expect that there are 25000 addressable at Feight patients globally.
Finally, we just see 857 would you believe is ideally suited both for larger patient populations, we entered into the phase one healthy volunteer trial in the third quarter.
Based on a very strong pre clinical rationale we are targeting GBP eight define Parkinson's as the first indication.
No I wanted you provide some perspective and the Translarna on you read that trial.
For background on you read is a genetic disorder often cause by a nonsense mutation in the fact 16.
Which is associated with awkward the facts and typically leads to blindness.
Just try was randomized placebo controlled study that falls patients for 48 weeks with an additional nine six weeks open label extension.
39 patients were randomized.
And the primary endpoints will that change from baseline to weak 48 in the maximum reading speeds as measured by the N. reads acuity charts.
Only inpatients older than eight years of age.
While the trial did not meet statistical significance, a trend of the absorbed in favor of up Laurent.
For reference the data has to be included in our slide that bolstered in conjunction with this call.
As the next step we tends to discuss the results with experts on this following weeks and decide that that forward for the program.
Importantly, this safety profile in and you read their patients was similar to that of previous studies and the ongoing commercial use off at Dolores.
Moving onto G.M.D.
We expect results from the flooring U.S. dystrophin trial in the second quarter off this year.
This is a 40 week open label single study into when see nonsense mutation mutation DMD boys H future seven.
Needle biopsies weren't they can at baseline and 40 weeks following treatment with fossil Laurent.
The primary endpoint is the per cents dystrophin change from baseline as measured by E C out.
We saw positive and statistically significant results as we expect we dense just submit for celebrated approval in the U.S., which would be in conjunction with the Q1 clinical data for out to Lauren from other studies.
Moving now to our agency deficiency program.
We continue to make good progress and patient identification.
Using a multi prong approach.
No cost blood testing has been deployed go globally it'll have absorbed increased patient identification for this simple blood test after launching last year.
Particularly for patients with symptoms that mimics cerebral palsy in epilepsy, which was across all regions, including Europe and Latin America.
As we can see did you see is poised for continued growth with upcoming clinical regulatory and commercial catalyst across all platforms.
I'll now hand to call Overcharge CFO Emily Hill, So she can review the financial progress and leap.
Thank you I see on steel outlined our several development and commercial product place us in a strong financial position have revenues in royalties that fund our ongoing innovation to drive us toward our 1.5 billion target in 2023.
We made good progress toward that goal in 2019.
Last release issued earlier this afternoon summarizes the details about fourth quarter and year end 2019 financial result, and I will take a few minutes now to review key details for the here and our guidance for the full year 2020, please refer to the press release for additional details.
Starting with our topline results, we reported 307 million in combine that revenue for the full year 2019, compared to 264.7 million for the full year 2018. This includes a 15 million milestone payments of PTC femoral triggered by the acceptance of the rest of plan India.
Translarna net product revenues were 190 million for the year compared to 171 million for the full year 2018.
This growth reflects the extended commercialization of Translarna as a reminder, translarna was the first therapy approved in Brazil for DMD last April within your current price impact, which should result in long term expanded market access.
Friends Plaza, we reported net product revenues of approximately 101 million for the full year, 2019, which compared to 92 million for the full year 2018.
And Plaza sales were impacted by an increase in the utilization of Medicaid, which changed our first tonight assumption and the transition to a new specialty pharmacy distributor. These factors can pack it implies a sales in the third quarter 2019 in particular and we saw improvements in the fourth quarter and have continued through early 2020.
Total DMD franchise net product revenue was 291 million for 29 team and we anticipate full year 2020, DMT franchise net product revenues to be between 320 in 340 million.
New product launches, including take study revenue and potential risk depend milestones and royalties are also expected to contribute in 2020.
Non-GAAP R&D expenses were 236.6 million for the full year 2019, excluding 20.8 million a noncash stock based compensation expense.
Paired to 155.9 million for the full year, 2018, leading 16.1 million and noncash stock based compensation expense.
The increase in R&D expense reflects cost associated with advancing the gene therapy platform increased investment in research programs. The advancement of the clinical pipeline and the upfront 10 million dollar payment for the acquisition of the bio Elektron assets.
Non-GAAP EPS DNA expenses were 181.2 million for the full year 2019, excluding 21.3 million and noncash stock based compensation expense compared to 136.4 million for the full year 2018, excluding 17.2 million and noncash stock based compensation expense.
The increase in actually in a expenses, primarily due to continued investment to support our commercial activity.
We anticipate non-GAAP R&D and I see an expense for the full year 2020 to be between 545, and 575 million, excluding approximately 65 million an estimated noncash stock based compensation expense.
The anticipated increase in R&D and I see an expense are based in part on highly leverageable and scalable investment towards the 1.5 billion projected revenue target in 2023, including gene therapy manufacturing and increasing the number of programs advancing into the clinic and commercial launches.
Net loss for the full year 2019 was 251.6 million compared to a net loss of 128.1 million for the full year 2018.
Cash cash equivalents, a marketable securities totaled 686.6 million as of December 31st 2019, compared to 227.6 million as of December 31st 2018.
Ill now hand, the call over to the operator to start our questions and answers session operator.
Certainly ladies and gentlemen, if you have a question at this time. Please press Star then one you touched on telephone. If your question has been answered and you'd like to move yourself from the Q. Please press the pound key our first question comes the line up Alethia Young from Cantor Fitzgerald. Your question. Please.
Hey, guys. Thanks for taking my question then congrats to out I'm not the progress over this last quarter I guess I just wanted that maybe ask you to questions. One just kinda wind your perspective on how you guys kind of think about the rest of 'em data as it relates to maybe the fire fish upcoming read out lets you know some may believe may lead to more comparable dataset of sorry, and then.
Second line just as did you talk about the synergies between on freighters, Botoxia and gene therapy, and what the Redux platform. Please thanks.
Sure Hey, Thanks, Louise Thanks for the.
Good question.
From the perspective, I think you're absolutely right in terms of both the notion of you know the assumptions trial that we recently had data.
That was a very broad trial with.
Thanks, Jason Segel 25 years of age with a very broad inclusion criteria. So it looks like a patient population.
But that real that really see day to day in their patients.
And we Didnt putting people that's what we wanted to see how the the drug would function that line and we're you know obviously, we've Oh Oh women.
Oh point difference that was statistically significant and we're pretty happy with it.
In terms of Oh.
Okay.
In summary from Oklahoma.
Oh population, although there are different but did you saw even part one oh, well acquire them Oh function.
There isn't anybody did quite well and from my perspective was really so to be the most competitors of drugs, where we anticipate well part two of the same of that we already.
Historically significant.
And that you know, we expect as you'll see in coming up in the.
And the results of that more clearly and so we're excited about that I don't think you'll be able to more clearly.
A little better comparison, when you say, how well that we do versus level. So I think oh, that's probably a you know well nothing that's perfect in sort of apples to apples, that's probably as close as you can get and I think you'll soon but.
Oh, well do quite well.
In terms of the thing about gene therapy.
The drug what one is obviously gene therapy that will be of directly into the into the directly into the brain, whereas the other ones.
Molecule different mechanism may be.
Marci wants to go through a little bit more similar things too in a highly Joe. Thanks for the question. So we mentioned before right that our interest on the company. Our goal at the end of that they stood Swiss things are patients. When you look into odd disease like goods written about yeah. Oh, you have a component that is systemic toxicity.
Before death amongst many others the hard you start the effect.
And then you have to deterioration or launch for the duration that sure what the stations over time I, specifically on their teenage years and later, what you're looking into what the two modalities, which is why she wants that most if not all patients. This patients both through buying Jackson directly to the dentate nucleus officer about.
We expect to stop the progression of synergies and hopefully I will start some function to add neurological leap and by keeping 7.3 would have a more systemic madron, including the horse so see both approaches but complementary they are people our development timelines, although seven ports.
He is more fancy goes off the stage of the trial. So it wouldn't be starches trial later this year.
Holding rolling doubles compensation or we expect.
After one year and the result is would be pivotal trial. So we should be able to register 7.3 before our gene therapy Cabot.
Great. Thank you.
Thank you.
Thank you. Our next question comes on line of Jones from Cowen and company. Your question. Please.
Sure There and then you for taking my question.
The first one is is on the the anybody a data that were that were presented today I guess the placebo arm perform as you would have expected with that 3.3% change and is there anything different about sort of the patients that did respond to translarna therapy and.
And those that Didnt in terms of their.
Current disease severity and then one more on on a follow up to the first question and presence Akcea in order to use the two products in combination if if they are going to be cautionary mechanisms do you have to study those.
From a clinical study or or just achieved independent registration. Thank you.
Yeah, it's like so for the Oh Blue Cross and maybe the first one on I mean, the radio let me just say, but you know you pointed to the <unk>, what we're back in sort of in a way we didn't know necessarily what to expect in principle for trial really every bombing and iridium terms Oh following.
The real natural history and understanding of that will be.
Welcome all that well Hmm back.
Recently happened trials into a sort of early trial <unk> safety study compared to placebo treatment. We just thought that uplift when things are looking at Enron.
To.
To be able that if we saw something that we'd be able to go and talk to the so to regulate but I think at the end of the day.
At the end that they you know it was hard to be able to power directly what we thought the trial would be because there wasn't just enough information, but that being said in the way we learned a lot about system and I think as you grow as you go and look at the data.
In the debt you'll see why.
We think that the well the drug was effectively.
So when you compare the number of cases that were that's all benefit versus placebo why did that change.
And reliability of the assets I think that.
I would prevent it from being statistically significant I mean, that's how we look at a marketable yeah just a.
Little detail to complement that thanks.
The business will know randomized stays on this criteria right. So we have some congrats Mike BARDA Bill it's coming all the randomization south that was not that well balance. So your question about placebo odd to placebo behave similarly to our works back that was one patient. That's just saw there that have a responsible some wants an expected buddy.
General and that was not the issue it's more of that size up the trial and the path for the more dumisani balance at baseline is once not the regional endpoints that it's still a bad.
You are looking for states and some biomarkers originally so.
We learned a lot you that's what this size of the trial, what the point that makes moving into right direction.
He does not Maggie the effect, where it's back to what you see and very importantly, since launch in the markets. In several calls is large and be the safety profile is exactly why we are expecting here.
And then the Oh, it to product, but okay, a gene therapy versus maybe small molecule. We're gonna have to independent trials that will be probably not so I'm, hoping you initially.
We.
Do them both together so I don't think that would be an issue we're gonna be happy to product.
Mike you know with very different met one would be underlying causes the but oh.
Oh the law.
Approaching itself would simplify the from the Petro one really affect.
Most likely inflammation and so the combination of those to rethink obviously when you have information you have a problem, but reducing them is often good, especially with chronic inflammation the sector one in terms of bringing the.
The protein that is not Megan will be important so it so there can be work.
Together, but we don't think right now that would do a combination studies.
Great. Thank you congrats on the progress.
Thank you. Our next question comes on line of Martin Auster from Credit Suisse. Your question. Please.
Well, thanks for taking my call had a couple of questions for you as well.
From the entering a pivotal data I'm curious if you see any read through to the ongoing districts and study.
I don't know if you as you look through maybe more of the secondary endpoints you get a chance to analyze some of those if there's anything in there that kind of elevate your conviction in the drugs them away and kinda supports an expectation for for a demonstration dystrophin expression of study in age.
From a fairly granted expectations around that one and then the second you guys have generally standard I would say incrementally more exciting about the by re platform since that deal was was all signed and closed.
And I'm curious than at the R&D day, they're gonna be any new data presented them or will we be seen just until presentations of preclinical and clinical results you've I wonder what's already thanks.
Sure.
You're entering into this person I don't think or.
I would say one from the other one is trying to understand the clinical manifestations that would occur treaty, which we're where we learn in terms of and which we learned as a consequence of that in book.
The visibility of the of the coupon I'm quite sure.
Disciplined we feel pretty comfortable that we've done all we can do in terms of ensuring that as best we can but this will be a possible Bobby.
We think that the assay that we have is.
So.
Incredibly sensitive and maybe your well and so we think were pretty good shape in terms of getting that and we're hopeful that oh that we're going to see your networks, we have big already from from the Oh for study in this Oh, we think can you know it was more sensitive after that can replicate but that being.
I'm sorry, we booked at this level of being able to have a positive results.
Good for approval in the United States in terms of the bio <unk>.
Platform yet.
Good about that.
Important platform in the novel settled problem of that working on different ways that that no. Other companies have worked out before so we're pretty excited about that another thing you'll see on handle the right we'll talk more about.
Not only the mechanism, but more in detail some of the things. We studied we alluded to and so the talk here today in terms of other work.
With the summer Tomo and films.
Oh, we'll talk more about that and so you are more in terms of preclinical clinical data in that as well. So I think there'll be a lot, but you'll learn.
Consequently, so the buyer platform on the.
As of June 16th.
Yeah.
Great. Thanks.
Thank you. Our next question comes from the line of instead Chen from <unk>.
And Steve Your question please.
Great. Thank you very much for taking my question. Congrats on the progress I was wondering if you could just.
Following up on Translarna in a in DMD, that's where you can describe the powering assumptions around the Translarna U.S. study and what gives you confidence of the trolls adequately powered for example, what are your assumptions around the variability in dystrophin levels in the in the absence of drug and in the expected effect size.
Sure.
Mostly once you look yeah Havent monster here. So the powered the we believe that in all the scenarios that we had lots of interesting likely.
Since we've been looking to just one scenario here, what's an absolute change.
We are power at more than 90% or walk to show a different states such as the significance on that trial.
The way, we can throw the viability or that's exactly the point that has to be control. That's true up here is off studies.
Leading to an validation work leading to that where multiple cores were analyzed and different biopsies. Thus, while we were able to really control that so we're not oh, sorry that would be a nice year. The there obviously scenarios where few patients show a large increase and then my job.
Patients who are very small increase versus another one of them I would say more likely that you see an increased while split up smaller magnitudes neither of them.
We can you describe meanwhile, powered to show benefit and as such as the significance of course as a baseline the manager.
Based on or about additional work as well one thing that the vast majority of the patients are going to be below the low level classification.
That is to be replicated wouldn't have a problem in terms of like the noise that we've seen call. Some of the other measures one of the reasons why we're left with this method Andy both from the acquisition of the biopsy and a bunch allocation of discipline as we did.
Yes.
[laughter].
Great. Thank you.
Our next question comes online Robin can ask is from Suntrust Robinson Humphrey Your question. Please.
Hi, Thanks for taking my question is on track progress I'm, just so a couple but number one big pictures here you you've guided and you have before you 1.5 billion over the next few years I'm what are your thoughts on making sure that that can help you achieved some profitability just when you take your guidance, what's your thought on your goal there.
And how you how you're going to think about business development now versus you have in the past I.
Second question is on.
And you see for the patient population or that you have identified to can you give us a little bit more clarity as far as more recently left in the United States and actually last.
And then third on the Enormity idea if you would exclude that Hypatia, hi, responder piece. It is there any different she placebo and I'm the treatment arm. Thanks.
Robin This is I'm only talk to you.
And that's due to your question about reaching that 1.5 billion revenue target by signing 23, you know what you've seen in the past couple of years, we've really invested in driving innovation to continue to grow our rationale and we'll plan to do that actually have.
Just coming on board here with me study in Wales rise on HBC and the rest of family LP.
No nothing I read off platform or gene therapy platform, and our citing platform. Obviously, you know as you get towards that 1.5 billion target there is likely a threshold of profitability, but I wouldn't say enough our priority our priority right now, it's really invest and accelerating those pipelines continue to drive innovation.
We've done that in the possible through internal innovation on as you mentioned through business development, while we have a lot on our freight I'm internal side really past that might not landscape for business development opportunities I'm, hoping we selectively opportunistic as I say right.
Yes.
So now the antibodies are the all HBC deficiency I think the big picture is we've been finding patients.
In all the areas.
Well more focus Sierra Leone.
So there you know where so many in the sense one of the questions people had is a little small population told me founders effect that's turns out.
Surely not typically.
Okay.
And so I think the split I think.
Okay. What your team is working pretty hard on that so once again.
What we're looking for him, but very well area of course, so the they certainly been seems pretty even I would say between the Wow and the Curations all five of the last just to remind you were focusing on five calls we've got this first wave.
So, Brazil that you out and be the three largest markets in Europe.
So, France, Italy, and Germany with secondary looking to a number of other markets when youre seeing as while the increase in the number of patients there, but it's fairly balanced in terms of the key results that we definitely want to 15.
Yes, that's how we are not performance and how we're putting the source again is it the split between the last Melphalan. They left so we expect about half the patients to continues to become somebody from the Americas region and the other box on European region between like Eric can adra leaderships there.
Huh.
The in terms of these things we're doing is while we just thought to that number are you problems as we learn more the things are happening in that are working or not working very well weve cycled through them very quickly and get the problems includes the having more people into field in the West for example in some of the point of contact.
Seeing are we starting more patients. So as we learn were able to again focus the resource and refocus the resource walks, though.
Mmm annual reveal a problem in terms of looking at two cents sensitivity analysis of removing we already have a pretty small patient population, but.
Yes.
Yeah. So it's a it's a small patient populations to adjust that like it's obviously, if we remove the one patient people with the large resolved we.
People in fact would be seen a larger separation here in the reaching Domino's is supposed to discuss.
But I don't think it would be appropriate for us to speculate because we don't always that patient is an outlier or not.
What you're seeing is in the distribution of one of the reasons, we put the waterfall slide we see the just sufficient clearly skewed toward increased with up Lauren So gave us confidence not only for this study, but also some expense to deal with the overall platform with applaud you know.
Again, we look at that study when you looked at the waterfall plots, which I think probably in the small population is a nice way.
It's pretty apparent the affects of run on these patients over Oh placebo.
So no we listened system you know so we're going to be policies for position from the company <unk> and the key opinion leader and you know so I think we've learned a lot of listen I think.
No that's really different people complement some from book reflective of the drug.
Great. Thank you.
We do you think you. Our next question comes from the line, though right you person from William Blair. Your question. Please.
Hi, there Sammy entourage Hugh.
I was wondering if.
Format, you might be presenting at the odd dystrophin results, what kind of one I O presenting them and whatever it'll be a medical conference why press release, and if you have had any discussion or if you plan on having any discussions with the FDA how did that resubmission.
Yeah, we haven't yet defined.
You know, whether we'll do another meeting or press release, but you know our goal is that when we notice to get this out as rapidly as possible. So there's a good chance. So if you will put something out as a press release so people know.
And then we could be able to percent either that or call, even well, we'll figure that out.
Then the second part was.
I see what's yeah sure. So they in terms of interactions with FDA. So I'd be happy interactions through all the planning phase and execution up they study Oh intends to have a PNG a meeting as while we would come what should that when they said it's Bob.
It's been discussed already with the agency should be on the books, a pre selling land that is many all that matters as you can imagine other than they start itself right. There the update up the safety database the update on the other studies.
Additionally, the G. I started is the war dawn between the two submission. So a number of things that we've been talking to the agency and having productive discussions with that.
Great and then I was wondering if you could just discussion of the potential outcomes for next steps for the and Iridium program, depending on your conversations with experts you guys kind of thinking in the program like a table or running another study and having power differently just what your thoughts are.
Well I think you know, but that's the question I don't think that's why we're going to.
Oh go and talk to the key opinion leaders from talk among ourselves, but with that amendable will if we come with a plan I think we talk about net stuff but.
Okay.
Thank you. Our next question comes from the line of Gena Wang from Barclays. Your question. Please.
Thank you for taking my questions. My first question is also regarding the ball market data for Translarna I'm, just wondering how could you remind us which must fill a with the thought they'd be PK and then would that be taken from the same side of the piceance and how many biopsies pekin from each pacing.
Each time.
Sure, Hey, Jim and I am RCR here. So we're taking tissue samples for every patient you buy off to a three course for biopsy. So so would have thought all six.
As a base as an alternate muscle as loud.
Before in case that is already SAP coming for the sake. So we have enough sampled coming there and as I mentioned on the answer to you Vincent on your we have run some of the yes in terms of the validation we know based on the dairy kinds of nation that assignments fits in that would happen different space.
And that it shouldn't be a problem, where do the biceps isn't the gas rights for despite define reciting the T.A. as a secondary Cybercoders Genericized me I'd say here. So the primarily is really to read this six course that it would have.
One of the nice things answering the validation as was that when we compare decor.
We've seen very very small variability there. So we can use annual spend a lot to measure.
Does that answer.
Yeah, Yeah, so, but we do you have an individual detail you were poor the.
Basically all that together.
Yes, so that's a very good question. So we will show so there's a way down that is that is a difference for being digitalization solve their baseline right.
Obviously, we're going to confuse that enough there assassinate or statistically, but each one of those patients are going to be looking versus their baseline because why we expect that the baseline who's going to be very very small or even below the level of education, we cannot guarantee that that's the case so simple.
Oh, it's an admin change could skew the results. So each one of denim gonna be looking to easily a and then going to compute the difference in different while divisions I'm sorry, My Shai I was I'm wondering you know to see each individual patient they have a six samples would these examples oh I gather.
Oh, well be individualistic baseline no. So just one or so it's a bath sample for baseline and four weeks 44 that each one of the patient that's going to be used for deanna.
Okay, Great and then I have a questions regarding the microcontroller epilepsy trial.
Just wondering was the primary endpoint.
Is that based on the if the discussion feedback and also how do you measure the seizure and then do you can capture both generalized your old Pasha seizure and how do you hold to seizure events, especially for those seizure. If you wanted to copy them.
Sure no absolutely I would say the trial design just it to some extend to better similar to other drugs that was there were just thrilled with our genetic lefties a in general like I'm sure you know, they're the ones I imagine Oh, we are developing like a buyer specifics I report this trial that's.
Going to account for this patient population so looking to generalize features at this point in time.
Participation.
And looking for for the change like there were obviously, especially the difference regulatory agencies here. The key design off the sidelines agrees under our budgets advise important Bharti protocol, we deal with DNA and we're using the same for part yes. They of course.
Okay. That's fine just one more question regarding generalize seizure. So in a Keystone teaching I'm just wondering what caregiver also it'll have a follow a ended slightly if a patient have a general anesthesia and then the piece actually wasn't aware Uh huh.
You had to seizures, because he was passed out and we couple of how Roger was called events like that.
Well, that's going to be recorded by the caregiver actually should have made that clear right. So most of the stations were talking about what's our infants are thought leaders are young kids. So we're talking about the judge recorded a dialogue.
Okay.
Okay. Thank you.
Thank you.
Thank you. Our next question comes on the line of Brian Abrahams from RBC capital markets. Your question. Please.
Hey, guys. Thanks, very much for taking my questions.
Can you just a sense of the agencies comfort around the easy I'll ask say on just in terms of validation and quantitative ability for dystrophin measurement relative to other techniques first as western secondly.
Can you characterize in general.
The regulatory interactions have been going for redeployment initially in your level of confidence in a timely approval with broad label and then lastly to maybe ask at an earlier question a different way on Unrisked. A plan now that you guys have had an opportunity to further explore the fire fiction SUNFISH data and looking at potentially comparative.
Subgroups and endpoints, what's your level of confidence that the magnitude of benefit is comparable to spinraza in types, one two or three patients and are there any some types, where you think efficacy maybe better. Thanks.
Yes sure.
So maybe we'll start with the dystrophin measurement that was welcomed.
Obviously, we've had substantial discussions with the.
Okay and that some of the it wasn't one where we said.
But in essence, we actually thought I remember of scrapping for.
And how you I'm sure you would want to western blot and they said no not really nicely. They don't like western blot Oh, they understand the limitation, both though if you have a better I say would be interested in so we had been working on we have been using in our own laboratories, so there's a unique form or but over the life.
No.
And so and they say they like that so they we worked with them and largely on the team have worked for quite some time them. So maybe you want to talk a little bit football.
Sort of that it was favorable heat month interaction.
And they were pretty much screens I think very much room.
With the work in the sensitivity I mean, I think they're very excited about disaster, let's rights decides to so we watch very closely with the FDA and that's what the golf or is there a on the validation of yesterday and they are they are completely on the same age us as we are in terms of imaginary felt like obviously the result.
Im going to see after the trial is we the adult soon but the assay south of defensive it turned away what validate it was obviously on a concern I would think general formats and for the FDA from the beginning because if its full length dystrophin, a very different than a war.
Those were doing O. hatch, rather than sterno standards. Once you are doing the salvia Santander has to be hyper you're.
And so once we get all this work with that and then to the satisfaction off the agent then obviously, our self as while we decided to use our third party lab to do this you eliminate any potential biased that'd be talking a lot because that could add Q2, such matters not on black Friday, so that was a hobby Dod again I think well.
Is it took about alongside true to validate that just doesn't the agents, but well get that there's no no no instead of of the Arista play Oh in terms of the broad label I think we're you know I think we're actually in terms of the having fire person some things and so the part that we part one for park too I think both.
The them actually help.
Really understand them further of the the drug itself and how how effective the can be I think in terms of the fund.
Oh trial really it's hard to you know prepared concerns that no one else. It's almost a two to 25 year old Oh try a weird in such a broad label abroad.
Criteria that we got station.
Scoliosis with them and things like.
Hammersmith, they place or less than 10, I should point out that that goes in the real life hasten even in that the the to the five year old 20% of the pace of had Hammersmith scores.
Less than 10 number probably old system of contractual so you're really going to have a hard times. So we're pretty excited with the fact that they're working [laughter] significant improvement in this broad population and we think that give us a leg up in that no. One else has bigger when you talk not only took the solution, but the sort of pay.
Sure, but you've actually study the <unk> the types of patients that you're going to but you're going to be treating them and in fact, no. One else outside my thing in terms of you think about buyer pools.
And it firefighters I think because I think were comparable I think that becomes clearer and I think in terms of looking at age. It probably is probably the most determine the thing where you could see and I think you can look at the real question, Dave can you give a paycheck.
Oh, great over five months of age is still saw increases in shop in 10 had and that wasn't theme and all the other trials as well. So at the end of the day I think when you're going to computer you want to do a comparison goes on to close with them you can look at the other trials when they have basically far younger patients than what we saw.
Yes, we felt very strong Dave another lever early picks up.
But also in though even though the type one patients that were even older.
So.
We're pretty well.
We're pretty happy about that we look forward to actively talking far more about that at the hey at both I feel pretty.
Really strongly but that Rupert planned. This though is a highly efficacious drug or that will be quite broadly in the population.
Thanks, so much to thanks, Marci and congrats on all the progress.
Okay. Thank you.
Thank you aren't next question comes in a line of Joel Beatty from Citi. Your question. Please.
Hi, guys. This is Sean Egan, calling in for Joel or two questions for me today first few on Latam franchise, but I potrero getting anvisa approval can you talk about what advantages, having you know and establish Latin them infrastructure give you guys. Her for marketing Tech study and and then on away lever following a positive phase three broadening study.
And I feel a wanting if that data be included when you guys summit in the second half and then all of one follow up on the Redoctane Jim.
Sure. So thanks for the question talking to the become I'll, let them right. So the approval types that he left you're giving us a lot of that this year in terms of the overall I mean force.
A lot of things worked on in between so want to spend obviously you have to gas price I agree with it all but man I. Just decide you that takes some time and where are well underway here. The second is the general thought infrastructure as mentioned on my prepared remarks hundreds of patients now with general typically homes.
Farms Asia, TTR, not only in Brazil, and Argentina, Colombia in other places.
So we're way ahead of the gang there and then that the last one that is not the lads importance I would say together with the infrastructure that will happen to coffee that is very robust since we have substantial say a box from learn up on the reason is a is the fact that the health system like and look at the situation, we all right.
Now testing health system got fasting awards in General I don't think you wants to overload hospitals with I'd be a bit neighbors in general so the Dallas should the need for this on People's home the ability to your money toward Dan or as we have the nursing enough work had the white who demand though.
And I really positive I'll get back. So the launch is now underway and we were expecting to see you should expect to see more and more updates on us in relation to that your second question in relation to weigh Libra all right. So the first approval, we expect frac yeah.
Sharply doctor to complements that data sat with half the also wouldn't be at least our base case right now it's not to have that you all indications are problems.
Got it. Thank you must feel and then on the 743 Redux age and epilepsy for that pivotal study can you maybe talk about how you plan to enroll will it be an all comer study for.
For patients with metabolic mutations or will you be enrolling any kind of particularly mutations more or less and then kind of going one step further what could if this study is successful oh, what could be indication look like in or is there any potential for if it feels like a clear benefit in some genetic sub populations for like a smaller approval.
Yeah. No. This is a great question. The so it's kind of both like that as we went through the scientific advice, what we heard very loud and clear I, specifically can be amazed that they want that both a very general population comes off does that imply any mitochondria lapped the with seizures.
On a whole Jones, so we could potentially three any patient and E commerce out after the approval. If the approval is to come but also do you have the most common mutations the revpas assets, so whether it be discussing that a little bit more detail, but there are four major group.
Oh mutations that he's going to have a balance.
For those patients want us Dan one of the most common is mid tens around how we might be familiar and they lost as well amongst others. So on the June 16, I'm going to be like well underway on on planning gas and hopefully executing as well but to be discussing exactly what is the expectation on the trial.
The market potential and so on the mentioned on the on the prepared remarks is while we do expect about five to 6000 patients should be got Graspable population here. So it's very large and these stations because of the type of ramp they have they did not respond well to any commentary.
All right now so just would be really liking for that and we we really expect them or power Viper system.
Great. Thanks, Marci I appreciate it.
Oh, thank you.
They do you aren't next question comes on line of its Chen from Bernstein. Your question. Please.
Great. Thanks, Thanks for taking a few follow up questions Oh, It's just a few on the on the DMD trial for Translarna personal is simply a does your correctly that you'll be comparing the best sample of baselines. The best sample at the end to How's the best sample determined that why not you why not use the average.
Second is I was wondering you alluded to a very low variability in the validation test that's where do you could quantify the degree of their believes the it and how were those run and then well maybe a third actually a gift giving them. The FDA has shown comfort with using western blot historically, even with the even have hasn't imperfections well.
The rationale for going through to warrant to absorb.
Due to easier ill, rather than using western blot, given that regulator seem to be willing to use western world.
Yeah.
Oh, no subgroup allow for <unk>, but.
Well they've been I don't think directly all they're comfortable with about symbolic thing.
But that they probably had but they don't think that it.
Great. Thank for a large protein the bubble up lot very well and that you're not in so and so we thought also gives you that you know I think that.
Situation it could give you depending on how it how it works greater variability more chance for potential missing things that are positive. So at the end of the day, we think about.
A lot more reliable Uh huh.
Good for better chance for success.
In them onto a more suitable for sure. So so the decision about you'd be out fasting right. So one is obviously was all simulated ER and the way the most reliable for one or you can have a situation a one off the cars I want to see some bose, it's contributing to things like that.
So that's one of the reasons not to average because it wouldn't be a through athletes like we just I'm lucky to some extent I think when you look into other studies.
Our study.
One example, all these mcf game by Marine lines with that in some of the other bizarre in the market you do see samples that cannot use oh would have to be happy compensated because of a fast. So that's one of the reasons to use the other Uh huh.
In terms of off the validation so the expectation we didn't know where the sample from Paul I'll stop right. There were asking the question can I buy occupation move on PPI and the results that are beverage formula and the answer is yes with the math. It one more reason not to use on the Americas like if you're looking to both.
All types of biopsy that will use before our number one when substation masses that when his before you see insert a interest sample variability like 40% somebody.
And that's obviously not acceptable.
She is bad one U blox approaching that yeah, you gonna have intrinsic Maria Lazarus looking for Super truncated part of the protein methodically like are we looking into pool like yes.
Hi, Thank you very much.
Thank you.
Thank you. This does conclude the question and answer session of today's program I'd like to hand to program back to Stuart Peltz CEO.
Thank you.
You know thanks for joining us today on the call.
<unk> as you may be a weird the real nice day over this past Saturday and.
I think it's a good progress to take stock of where we are at the company.
The importance of the work that we do that ultimately would benefit patients so with them in mind quite proud to be a global commercial diversified.
Our pharmaceutical company, that's focusing on these therapies, so a pretty rare genetic disorders.
So with that let me. Thank you again, and we look forward to senior without Abu Ghraib.
Later this year. Thank you.
Thank you ladies and gentlemen few participation in today's conference. This does conclude the program you may now disconnect good day.
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