Good day, ladies and gentlemen, and welcome to the PTC Therapeutics 4th Quarter and Full Year 2018 Financial Results Conference Call. At this time, all participants are in a listen only mode. Later, and answer session. As a reminder, this call is being recorded. It is now my pleasure to introduce Head of Investor Relations, Ms.
Emily Hill. Please go ahead.
Hello. Good afternoon and thank you for joining us to discuss our 2018 fourth quarter and full year corporate updates and financial results. Joining me on today's call is our CEO, Stuart Peltz, our Chief Operating Officer, Marcia Souza and our Principal Financial Officer, Christine Utter. Before we start, let me remind presentation, which contains our forward looking statements. Our actual results could materially differ from these forward looking statements as any and such risks can materially and adversely affect our business and and uncertainties, we encourage you to review the company's most recent annual report on Form 10 K filed with the Securities And Exchange Commission as well as the company's other SEC filings.
We will disclose certain non GAAP information during this call. Information regarding our use of GAAP and non GAAP financial measures and a reconciliation of GAAP to non GAAP is available in today's earnings release. With that, let me pass the call over to our CEO, Stuart Peltz.
Thanks Emily, and thank you for joining us on today's call. 2018 was a transformative year for PPC. Going into the year, we set out several ambitious goals I'm proud to say that achieved a label expansion for Translarna and advanced our oncology pipeline with 2 potential products now in the clinic. Importantly, we also advanced our SMA program. Following a productive discussion with the FDA, we and our partners Roche in the SMA Foundation feel confident to submit the results of Firefish and SUNfish in an NDA later this year.
We are very proud that the SMA candidate resulted from PTC's internal splicing program. We have been utilizing this platform to identify other compounds that selectively and specifically modulate splicing. We have a number of other splicing programs that are solely owned by PTC. Besides achieving these goals, we also strengthened PTC with 2 business development deals adding the CNS gene therapy platform with multiple programs and in licensing two products that we plan to commercialize in Latin America you may recall that in the early 2018, we presented a 3 year vision for the company to become a fully integrated orphan drug company. Execution is at the core of everything we do at PTC and we are proud to have accomplished this 3 year plan in just 1 year.
Now looking forward, we have defined what we want to deliver over the next 3 to 5 years We describe these longer term goals at the beginning of this year, and I'd like to review them with you today. On the commercial front in 2018, we had $263,000,000 in revenue from the DMD franchise. Over the next few years, we anticipate 3 product launches Risdiplam, TEGSEDI and AADC gene therapy. As well as expanding for a U. S.
Approval of Translarna in 2020 based on the outcome of the dystrophin study that started at the end of last year. The combined potential revenue of these products that are currently in our pipeline is anticipated to grow in excess of $1,500,000,000 in potential revenues by 2023. We will continue to invest and expand our discovery clinical stage pipeline. We plan to accelerate 20 programs over the next 5 years through internal and external innovation sources across small molecule and gene therapy. In addition to outlining our 5 year vision, we have also recently provided updates on key programs that we'll cover in more detail later in the call, including patient identification efforts ahead of our plan BLA this year with AADC deficiency, the planned NDA submission this year for SMA and the anticipated launch of TEGSEDI in Latin America.
We are proud that PTC has positioned itself to be able to become a leading orphan drug company with diversified pipeline of innovating programs and products. We are leaders in DMD have built a solid revenue base and have strong talents with committed and motivated employees. We ended 2018 with a cash balance of $227,000,000 and recently completed an equity offering with net proceeds of approximately $225,000,000 we are in a very strong cash position to execute on our strategic vision. I'll now pass the call to review our
to serve patients with rare disease with the potential 2023 revenue in combined excess of $1,500,000,000 as Stu just discussed. Our expertise in all aspects We have spent considerable time and efforts to build cross functional teams that can rapidly increase disease awareness, identify the patients and bring differentiated therapies to the patients that need them. This includes a state of the art patient service which is a key components of rare disease treatments. As is to also mention, our DMD franchise has an exceptional 2018 reporting a combined revenue of $263,000,000. This includes sales of Translarna outside of the West which is now in over 40 countries and sales of M Plaza in the United States.
In 2018, DMA approved a label expansion for Translarna to treat nonsense mutation DMD patients age two to five. Importantly, this label expansion allows patients in all the countries that recognize DMA approval to gain access to therapy Additionally, there is an equal and very urgent unmet needs to treat non ambulatory patients. With that in mind, late last year, we have submitted to DMA, a label expansion application for the treatment and we expect to finalize the regulatory process later this year. All patients regardless of where they are in the disease progression. In the United States, we have begun our dystrophin study, which will lead to an expected resubmission of our Translarna NDA for accelerated approval later next year.
H5 and older in the United States. We continue to work hard to establish Emflaza as a standard of care in the U S. At the end of last year, we received a request from the FDA to file for pediatric label expansion for Emflaza. Yet they informed us that we have sufficient data to file the sNDA and that a study would not be required to demo rate safety and efficacy in this population. We have submitted the sNDA for Emflaza for patients 2 to five years old at the beginning of this year.
And the action date we received from the agency is July 4th. Our commercial team is diligently preparing for the launch Based on the expected continued growth of both Translarna and Emflaza, we have given 2019 DMD franchise revenue guidance of $285,000,000 to $305,000,000. We are proud to have established this strong commercial footprint globally. Which has made us the partner of choice Last year, we in licensed Latin America commercial rights to 2 products from Akcea. TEGSEDI and Waylivra.
To be successful in the region, it's essential to have the right process and the right team in place. Leveraging our Latin American infrastructure, we have completed all necessary additional hiring to support these products. Importantly, we have also established the necessary process to support patients. Including an exclusive partnership with our nursing support team. On the regulatory fronts, we have filed PEGSEDI with ANVISA, and we expect approval later this year.
We are eager to bring that study to the Latin America markets where the polyneuropathic form of hATTR is the most prevalent with approximately 6000 patients in that region. We're especially proud of this progress in a competitive market as this one is expected to be. It's teams and execution are critical for success and we believe we are ahead of the game there. I'd now like to highlight our CNS gene therapy platform. As you may recall, our strategy in pursuing CNS specific gene therapy includes some key advances.
The first is the ability to target the specific area where the disease process is occurring. Maximizing the benefits risk. Secondly, because cell turnover in the brain is so low that is the potential for durable effects and the potential to use a small amount the vector, which we call microdosing, which reduce the manufacturing burden for the process. Lastly, the combination of the target approach with the small dose reduces the potential for immunogenicity. Reducing the overall risk for the With AADC, we have started pre commercial efforts ahead of the anticipated filing of the BLA later this year.
As we said before, we have already identified approximately 100 ADC deficiency patients in the United States in Europe through early key opinion leader interactions. We continue to identify new patients steadily weak after week. But we're now moving to a more focused screening program at at risk populations. For instance, we have identified a cohort of approximately 100,000 apparently misdiagnosed patients in cerebral palsy clinics in the United States. Those patients present with normal MRIs.
We expect to have the screening programs in cerebral palsy implemented this quarter. We plan to share Beyond the agency, we plan to submit an IND by the end of this year for the next gene therapy program in the pipeline. To treat Friedreich's ataxia. FA is a devastating disease with no real underlying treatments at this point. We have all the elements in place to start the clinical trial in patients following the IND submission.
Next, the most advanced program is our gene therapy candidate for Engerman Syndrome. Which we plan to file an IND As we have said, we are developing a robust pipeline of gene therapy candidates. And to that end, we intend to declare new candidates later this year. In order to support this growth, in the gene therapy pipeline. We are also in Lastly, we continue to advance our oncology programs with several patients dosed in our diPG trial and having great progress We expect
Thanks, Marcio. The progress that's been made across our clinical and commercial fronts is impressive. I'd now like to highlight our splicing program, an area of innovation in which we are proud to be both the pioneers and leading the field. An emerging area of therapeutic focus is the ability to modulate splicing with a small molecule. In which our technology produce the most advanced compound Risdiplam.
We expect this compound, which is partnered with Roche and the SMA Foundation to be potentially approved next year for SMA types 1, 23. This is great news for patients with SMA, but it has a broader implication for PTC as a powerful validation of our splicing platform technology. It is now clear that we can identify selective and specific compounds that modulates splicing to treat disease. A small molecule also has the advantages of broad tissue distribution as well as ease of administration. We are applying our splicing platform to other diseases with higher medical needs and have programs across the R And D spectrum.
These include familial dysautonomia and Huntington's disease, I'm happy to report that and we expect to enter the clinic this
Thanks, Stu. Earlier today, we issued a press release summarizing the details of our financial results for the fourth quarter full year of 2018, and I refer you to the release for full details. I'll start with a few we reported $263,000,000 in combined revenue across our DMD franchise for the full year of 2018. Compared to $174,100,000 news were $171,000,000 for 2018. This compares to $145,200,000 in 2017, representing an 18 For Emflaza, we reported net product revenues of approximately $92,000,000 for 2018.
A revenue increase of over $60,000,000 from 2017. To continued commercial growth. Our 2019 DMD franchise revenue guidance is 285 to $305,000,000. As do mention, we have also outlined the potential combined revenues for products and our existing pipeline in excess of $1,500,000,000 by 2023. Non GAAP R and D expenses were $155,900,000 for 2018, Excluding $16,100,000 in non cash stock based compensation expense compared to $102,000,000 for 2017, excluding $15,500,000 in non cash stock based compensation expense.
This increase in R&D expense reflects costs associated with advancing our gene therapy platform and increased investment in our research programs as well as advancement of our clinical pipeline. Non GAAP SG and A expenses were $136,400,000 for 2018, excluding $17,200,000 in non cash stock based compensation expense compared to $106,200,000 in 2017 excluding $15,100,000 in non cash stock based compensation expense, reflecting continued investment in commercial activities to guidance for full year 2019 of $360,000,000 to $370,000,000 excluding non cash stock based compensation expense of approximately $35,000,000. This expense guidance reflects advancing gene therapy and supporting our commercial was $128,100,000 compared to a net loss of $79,000,000 for 2017. Cash, cash equivalents and marketable securities totaled approximately $227,000,000 at December 31, 2018, compared to $191,000,000 at December 31, 2017. I would also like to point out, we recently completed a public equity offering resulting in combined net proceeds of approximately $225,000,000.
I will now
Thank you. You. And our first question comes from the line of Ritu Baral with Cowen. Your line is now open.
Hi guys. Thanks for taking the question. I have one question and one follow-up. The first question is on Risdiplam and the submission. What indication or label are you going to be submitting for?
I know the 2 trials span type 1 and type 2, but do you anticipate, filing for a certain age range, a certain weight range, And then my follow-up question is on the patient identification activities for AADC. You mentioned that there was pool of about, a pool of 100,000 patients misdiagnosed with cerebral palsy with normal MRI Can you say like how many centers that's across and whether this is some sort of opt in program, that that, that the screening will use or, will you just sort of go through the centers and go through, blood spots? Thanks for taking the questions.
Hey, thanks, Ritu. Yes, so, in terms of the SMA, I think the plan is really, and it was based on our conversation with the FDA was to file based on Part 1 of both type 1, 23. So really to get a broad label within that as for AADC, maybe let Marcio, you want to?
Yes, absolutely. And maybe just, hey, Richard, just to finish on the what to start it right for that's no expected restriction on the age or way of those patients. Feel that we have very comprehensive program, several cohorts that examine that relationship. Roche did a really good job here on executing that. Trial.
And that's why we are reinforcing what our belief is that this is the most competitive SMA program globally. When we move to the AADC efforts for patient identification, there are basically 2 layers of clinics in the United States and Outside of the U. S, there's a lot of like difference dynamics in the U. S. There are like 65 or so main centers for cerebral palsy.
And then spend this cohort that is up to 200s given taken. The way we're doing this is through a multi pronged approach. So one is We are offering 4 centers if they want to conduct the screening as a research project, colon call. So that's basically a protocol driven going to go through the IRBs like contract with them, so on and so forth. And we have a very good uptake there.
There is a number of the centers that really wants do that way and go for their entire population. For the ones that either don't have the capacity right now or they don't have like the structure to run as a research, we have what we're calling known protocol, we're providing then the ability to screen their patients. And we have those centers opt in there as well. Currently, we're looking into like the sample as a whole bloods, but we are validating and finishing the steps or validation for a dry blood spot. So moving to that process is going to be faster as well, more productive throughout the year.
But pretty much all of them are on board, on the what we call tier 1, that's the majority of the patients are in. So it should start screening patients in the next couple of days. So in Q1, and expect to report the progress like later in the year in a more consolidated fashion. Does that help?
Yes, it does. And for the screening, is this something that sort of done in the background anonymously or is it something that you need sort of individual, family, individual patients parent, I guess, approval to run the assay?
Yes. No, that's a really great question. So for the one that is done with the protocol, So this is part of like a research clinical program, right. So it's that is a consent form and they're going to go through that and so on. For the other one, it's basically a 2 that's being offered to the families.
We are looking to this marker in the U. S, you can do like a 3 OMG. So it's a precursor of dopamine. That's a very simple and one that's elevated. We go and you genotype these patients.
Outside of the U. S. Is a little bit more country by country. Most of them, we are just providing the data they're going through and screening the patients they have. So it's more conversation with the family.
As you can imagine in every day, we learn more about this as well. This this family is really wants to know if it is not cerebral palsy, if that's something that can be done. So we're seeing like very motivated families sicking this and having positive conversations. So we don't see like any barrier there. The barriers were more on putting the process in place.
And now that we have that, it should go relatively quickly.
Great. Thanks for taking the questions.
Our next question comes from the line of Eric Joseph with JP Morgan. Your line is now open.
Hey guys, thanks for taking the questions. A couple from us. So the first on, on guidance for 2019, I just wanted to unpack, DMD sales a little bit. The top end of the range still looks as though you're tracking under the run rate for 4th quarter. So I know that you have talked a little bit about the expectation to see in seeing lumpy demand over the course of the year, but is there anything else that's implicated in the current guidance, anything in the and, with respect to pricing And if there are any expectation around pricing headwinds, where might they be coming from?
And then I have a follow-up. I'll start and then pass it on. I think you'll see I think we're adding on patients both for Emflaza and Translarna. They continue to grow. We do plan on some approvals in certain countries that can that can have transient aspects on the dynamics of the market, but I'll pass it to to Marcio to sort of go into what their thinking is on that.
Sure. Thanks, Duane. Hey, Eric. So couple dynamics here and I think they are important for everyone to understand. So one is the Stu just mentioned we are seeing patient growth.
So net patient growth in both products in all geographies. So the premise of the business and the base is quite positive. There are the way we're looking into this, right, to reach our goal, like a 2023 goal that we presented earlier this year is the dynamic of patients over time, increasing staying, on therapy. And to do that, in some of the countries, this year, we believe we're going to have to make some adjustments in terms of the pricing volume mix. So that is a little uncertainty, I would say, on that that we are accounting for in the guidance.
Specifically as it comes to Translarna since some of these markets became quite big, but there's still a lot of potential. So when you're looking into the amount of patients that are being treated versus the potential, it doesn't make sense for us to just like be stubborn and not try to gather as many patients because at the end of the day, that's why we're doing business is to treat these patients. So there might be a little bit of a negative impact on the pricemix throughout the year, which is going to correct once we get those patients, all on drug and then the other countries started. So that's one that might impact I think it's equally important to talk about is not in the guidance, right? So we don't have the 2 to 5 for Emflaza you might have noticed on the prepared remarks that we talked about the July 4th, approval by the FDA.
We received the notification by then that that's the action date. We hope it's an approval. And then with that, we're going to be executing the launch while patients between 2 and 5 are not necessarily fully diagnosed yet. There is a pool of patients there and we're going to be adding those and depending on how fast we can that might have a significant upside for the guidance. And the no ambulatory in Europe is not included either here since we're stealing regulatory conversations.
So we try to be, as we always are, like, quite responsible in the way we guide considering all the market dynamics.
Got it. And just a follow-up on Emflaza, if I could. We can see that the trial design is up on clinicaltrials dot gov. Just wondering how we should be thinking about recruitment timelines, also the level of input and discussion had with FDA and its design. And I'm also curious to know whether there are opportunities for to expand the exclusivity runway here, potentially through an additional orphan indication?
Thanks.
Sure. And are you referring to the
Limb Girdle Phase 3 study.
Yes, I thought so because 33 that was the 225 were actually removed because the FDA told us we don't need to conduct that anymore. So, we gave we got a lot of inputs from key opinion leaders here from the biggest center in the U. S. It's, to why, we're fairly constant with some of the natural history they gave to us. That was what drove the design.
Obviously, we filed that with the FDA and the recruitment we expect to be relatively fast because there's absolutely nothing approved or in developments for that specific subtype of limb girdle, which is the most prevalent type in caucasians, at least with the not so, best and expanded literature as of about there. So we're going to provide a little bit more updates later in the year on how it's going, but we feel really good about that. On the expansion of the runway in terms of the product, there's a number of things we are doing Some of them have to do with for some population. It's not that convenience to deliver. Maybe some other formulations would be more appropriate.
Here, there is a number of elements that are not quite ready to discuss publicly, but we should be at some point and you might see some things coming up at clinical trials log off as well in the near future in terms of how we are approaching that. Right now, we are the base case is the runaway that is present for the products, but we are as I just said, we're looking for a number of ways potentially expand that.
Our next question comes from the line of Jenna Wang with Barclays. Your line is now open.
First one is just wondering maybe follow Eric's question. What is the average pricing now for Translarna previously our understanding was like $300,000?
Hey, Gena, it's Marcio. So the prices been quite stable for Translarna Ravi. We haven't guided to a specific price. But one thing that we took a lot of care off is we don't want like countries to be parallel importing or patients to be treated differently in one country or another. So we kept the price fairly stable globally.
We have some like large markets like entering now with the potential to expand dramatically. So that's put a little bit of a negotiation dynamic on the table and it's the 5th year of the product as well. So we are looking into here where are the patients that are not being treated. So quite positive the dynamics so far, especially for an international product that starting the U. S, we're not talking when I'm talking about price mix, we're not talking about crazy erosion of value.
Just wanted to make that clear. But we believe there are some responsible adjustments that can be done in order to expand disproportionately the number of patients on drug.
Okay. So, but just wondering, are we talking about like 20%, 30% discount or are we talking about 50% discuss in the new territory?
Yes, yes. I think what you're talking about is depending on the size of the opportunity, on some of those markets. And the willingness of the payer, the governments to negotiate longer term contracts that you would be willing to give discounts like we the U. S. For CMS, for example.
That's the kind of thing we're talking about.
Question regarding a risk to plan. I'm just wondering, would early data of pivotal portions from both SUNFISH and FIFISH be part of the FDA final decision since both trials already complete enrollment now and should have initial data by the time FDA will take a look and then make a decision.
Yes. So no, the plan though is really is based on part part 1 of the of of the both SUNFISH and Firefish trial to make that sufficient for we thought that we had very good discussions and that this would be would be sufficient for approval. So that's the game plan of what we're planning on.
Okay. And then very quick last question regarding the Latin America commercial preparation, just wondering how much investment in terms of dollars would need to set up a sales force NAB commercial ready for Ameluz, TEGSEDI and will incur?
Yes. Of course, So, first thing is, just to say, we hired everyone we had to hire in Latin America, could those 2 Eric and his team who are like very ready to do these executed in a matter of weeks. So we don't actually expect to add anyone else to support TEGSEDI. We obviously don't have anyone dedicated to a Libra since the product is not approved elsewhere. We are not putting any efforts right now.
There are basically 3 major components, right? It's the commercial, medical, then the patient supports. And we see them kind of equally. Like in this space right now, it's mostly unsolicited requests or medical fares folks are in the fields. We have neurologists on staff.
We have like great healthcare professionals on our medical staff that are giving that support. Equally important is the patient monitoring both to help them maximize the standard of care the testing get familiar with the testing program we're going to have later, but then understands this connection with PTC. And that's in place as well. It's a third party, in our view, it's the best provider of this kind of service in Latin America and it's an exclusive contract with us. And then the 3rd part is we did not create a special field force for TEGSEDI.
We actually pending what I normally call, solve for zip codes, meaning we are with reducing the areas of COBRA produces a very large country, Argentina, it's large country. We're reducing the area of coverage. So we have more people doing both products. Because what we've seen is there is about 50% to 70% overlap between the locations and the key opinion leaders and treaters with Translarna and TEGSEDI. So it's highly complementary.
And so I believe the good point there is as well is that these are already ongoing efforts
Correct.
That all this is already we've already started working and so physicians are aware of this and we've also submitted for approval already. So which we anticipate will be this year. So there's already a lot of effort that's been ongoing to get ready for this.
And our next question comes from the line of Joel Beatty with Citi. Your line is now open.
Hi, thanks for taking the questions. The first one is on TEGSEDI and kind of a follow-up question of what was just asked. What do you see as a reasonable expectations for the shape of the launch curve there in terms of the key steps that need to be taken towards ramping up sales?
Sure. Hey, Gerald. So the beginning of the launch or the beginning, even pre launch We expect to have a number of patients as we to be perfectly honest, we are seeing this already requesting TEGSEDI for the different channels. Right? The more they hear about it, the more they hear the fact that actually PTC is involved since we have, thankfully, a very positive reputation with the physicians starting to get a request and this has been treated as name patient requests and going through the process.
This takes several months. So it's going to be fairly slow in the 1st few months. What we expect is right after the approval, and I'm not going to answer too much on the strategy here because these are potentially competitive markets, but to actually accelerate real quick, we're entering next year with a potential substantial gain of market share and then growing on the following years. So it's low I would say on the next 12 to 18 months and then starting to have like a hockey stick type of so it's an unusual launch. If you were to think about major geographies like the U.
S. And Europe, but fairly usual for rare disease in the geographies in Latin America.
We do think there's a lot of advantages here. As a consequence of just the properties of TEGSEDI that it's injectable that, you know, there'll be, it'll be ease of instance of patients that come as a consequence of that and we're out there now. Exactly.
Okay. And then maybe one other question on Translarna. You have the new Phase III trial that initiated late last year. Could you discuss the design of that trial and what needs to be shown to support an approval in the U. S?
Sure. Of
course. So that we call that I-thirty 44 45, sorry, I just got the number wrong there. So, it's basically it's an open label study with 20 patients aged 4 to 7. We're taking a biopsy at baseline, a single center in California and another at 9 months. We're not going to read any of this before all the samples are collected, right?
So that becomes the block control internally in the trial. We were using 2 methodologies, which were discussed and agreed with the FDA to measure dystrophin. So the expectation is that we would see a statistical difference between the baseline and the 9 months in terms of increase of the amount of protein as measured by an ELISA type method that's called ACL and a secondary measure that is ICH is a modified ICH actually on pallets where we would see the localization in the sarcolemma as you expect to. So that's the trial we're enrolling right now. We have a couple of patients on the trial.
We're like, have a good interest or that we expect to enroll like this year in the next several months with a potential resubmission Obviously, we expect the trial to be positive. We hope it's going to be positive and you're going to resubmit to the FDA under the old NDA early next year.
And our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is now open.
Okay. Hi guys. Thanks for taking my questions. Maybe one about Risdiplam. I think, Stu, in your current dollars in the first quarter of 2019.
So, that's a very good question. So, I think that's a very good question. So, I think that's a very good question. So, in the first half of the year. So, we're going to have a little bit of a reduction in the plan.
I was wondering if you could give us some color on how you came up with that number vis a vis either priced or market penetration into the SMA market?
Yes. So we looked at what we thought would be in terms of an excess of $2,000,000,000, where and it was based on that. And I think you could see in the previous in the previous press release, we've put out precisely what was the royalties Whereas, for example, it was in the excess of 14 percent above $1,000,000,000 in excess 60 percent above $2,000,000,000. And so it was based on that sort of mix that we looked at the numbers to be around $200,000,000.
And based on early doctor checks that we've done, it certainly seems that physicians would be excited for an oral. Could this number be conservative if the switch rate potentially from SPINRAZA faster?
That's funny you said that. We've had meetings where Sometimes people think that that is conservative is what we what it can be. So yes, I think, we thought we'd start out where we are today and then discuss and grow it as we as time goes on.
It may be Steve, if I may, jump in. Hey, zinc. So there are a couple of dynamics that are really very important as well, right? So there is obviously a debate on drug price internationally we try to take like a relative conservative stance on that. So that's one point of, I would say, upsides on the model in general.
We know that type 3s, for example, are largely unserved right now. Our own internal checks and it seems like yours as well show that physicians and patients would be very excited to go from like the teens percents that is being treated right now with the current treatment available. To a vast majority of the patients with risdiplam. That market is not competitive. We expect to really dominate that.
Similarly in Type 2 and then the Type Gs type ones are probably going to be the most competitive of all at the time of launch. When you look into a normal molecule, that is durable in the facts. It's being safe to date. It's obviously very easy to administer. Then it comes to access.
The beauty of this model is everyone knows globally how to get access to small molecules for chronic treatments. So this is a plug and play. And to that point, you're right, we have a starting point here for 200, but we're not going to stop there. And I'm sure Roche, why all the conversations we have with them are not going to stop that either trying to maximize this value.
More product that it really came out of our it really came out of our splicing platform and that when we think about it from the competitive nature of the This really can be a really competitive globally as a consequence, not only because of its ease, the broad distribution, but as Marcio said, how people understand how to get access to drugs like this.
Okay. Thanks. And then maybe, Marcio, on AADC, you have talked about finding about 100 patients or so in the U. S. And EU.
Over what period of time has that taken you?
Yes, so that they took about, I would say, 10 weeks for us, I'm going to say though the efforts, like we built the team to do that, right? So that took a few weeks. Like we have a very clear strategy on countries that are priority and no one's going to be surprised that U. S, Germany, for example, like few countries in Europe like these are our priorities right now. So we're putting extra efforts there.
Interesting thing is like we're just in a Congress, and we put like a symposium on AGC right after that, we got some new docs that we didn't really have relationships with and we got a number of patients that they had genotyped before in couple labs in Europe. That are so we are seeing this I would say every week in different geographies, both in our core geographies that we are reporting here but in non core geographies as well. You might have seen this. I know do a lot of really diligent work on this disease is The number of mutations reported at the time we did the acquisition was about 50. Now it's more than 80 So we're seeing like a huge efforts there and it's diversifying the pool.
So I believe that teases that the patients were not there. There's a founder mutation. It's pretty much dead right now. You can't have 80 founding mutations well theoretically you can, but then it would be in 80 different pools and actually it would be a good thing for us. But that's not what is happening.
So the last 10 weeks or so, the screening programs barely started. So we expect to see a good acceleration throughout the year as well. I think
that's a really good point to it. Well, not that there was an effort to find the patients, but it really was finding those that people already actually already knew what's there that we're able to find them and haven't taken yet the efforts of looking for the unidentified patients yet. So that's just started. So it wasn't that in a sense, I know it's always tough to find patients, but relatively speaking, we're able to find them but they've already been genotyped. Now there's a whole bunch that will be in these that will be in those clinics that we'll be able to find who are just misdiagnosed.
So that's the next step.
You have made quite a bit of progress. So in terms of your target, you know, 5000 to 6000 patients potentially, how long do you think it'll take you to get to that or close to that number?
Great question, right. And you can imagine that I'm being quite pushy with my team and working very hard here to get there. Like we see this is going to be a little bit of a class rare disease launch or really focusing on the U. S. And some key geographies, as I mentioned, we believe it's going to be a very success launch we did, but on the pie that we were mentioning before, substantial number of patients to be treated in 2023.
But even by then, I don't expect to have like all the patients identified. What we expect to see is about, for example, 100 new patients per year in the U. S. And as we move towards like 2022, 2023, that's the incidence patient population is going to be more obvious and you're going to start to get those patients who are normally colon call laws. I think it's a great day to discuss this, right?
So rare disease day rare diseases are so under diagnosed globally and there is so much push now to include genotyping panels and so on. So in the space of I would say 5 to 7 years, you would expect to have a very good number, percent of those patients and the majority of the incident patients. So it's going to be a substantial markets the way we see it.
And we're working hard to make sure we got a strong launch upon approval. So the patients are lined up and ready to enroll.
Okay. And if I might squeeze a last question in really quickly on your oncology portfolio. You are doing a study in AML with PTC299. Can you just give us an idea of what type of patients that's going to be in within AML?
Yes, of course. So, so 299, right, DHODH inhibitor, I think that the body of literature showing that that's a key pathway for hematologic malignancies in general, but it's specific KML is being growing. We have some goods preclinical and clinical data showing that the mechanism is being activated. It's a 3+3 design with 3 cohorts, in refractory relapsed patients. So we are really getting very severe patients.
We are starting, as we normally do in trials like this, right, with a dose that is relatively small in sub therapeutic, moving on to therapeutic levels, it is a relatively small, sorry, slow design a sense. So we expect to enroll during the year all cohorts and to move into an expansion early next year, depending on what we are seeing, because this is open label. We are seeing the methodological data for adult patients. We're being able to learn as well in the kind of patients with once on the expansion. To maximize the probability of success there.
All right. Thank you. Ladies and gentlemen, Our next question comes from the line of Alethia Young with Cantor Fitzgerald.
Past couple of months. I guess 2 sets them up all the trend line here. 1, can you just talk a little bit more specifically about with the AADC gene therapy? What's kind of left to work through in the manufacturing? And I mean, do you view that as like a big hurdle as far as getting to the finish line with the FDA or is it just kind of business as usual.
And then the second question, as far as SMA recipients readouts over the year, I mean, are we looking at basically every medical meeting? We'll have some sort of update on the Part 1 of the study. I just wanted to kind of get characterization of like what data we should expect over the year. Thanks.
Thanks, Alethia. In terms of the second question, first, yeah, we'll obviously the next meeting is AAN and we'll be having a full presentation of the results then. So we're excited to be there for that. And we'll do it at the upcoming meetings that continue on after that as well. So we'll continue to update you on that as well.
In terms of the second question?
ADC manufacturing.
ADC manufacturing, why don't you Yes.
Let me give you. So I would say, Alexia, business, as usual, when manufacturing for gene therapy, I don't think belong on the same sentence this day, right? So I'm gonna I'm going to I'm not going to be cocky there and say that it is. We take extremely seriously all the feedback we got from the We've been pleased and blessed for having the interactions we had with them and get the guidance on the Type C meeting. We had late last year We're following all these steps and beyond as our CGMO is being great to work with giving a lot of attention to everything.
And right now, all these steps that we have to move to get to the BLA later this year are occurring. And hopefully, and Neil and his team are working extremely hard to get there, everything is going to continue in place. We continue to expense part of what's, is consideration for us here is obviously we want to have a successful launch. So you have to have several commercial beds manufactured to that commercial launch. So We're looking to that capacity.
We're looking to continue to add the material. And I know we discussed this in one of our calls, but just for the broader groups, view, we had 2 manufacturing CDMOs before, both in the United States. That did the clinical trial product. So we are able to use that process at NBL on the commercial And now we are in the late stage of implementing the methods and everything else the FDA discussed with us. For a BLA later this year, as I mentioned.
Yes. And the from just to remind everybody as well, it's one of the advantages of what we're doing is is it's it's stereotactic surgery. So the level that we need and this is one of the reasons, when we went with Agilis is that the the requirement of manufacturing is much smaller. We're around it 2 times 10 to 11 viral particles total. So it's Well, like Marcio said, we never take it for granted.
They're different in terms of what other programs are. It's a different level of what you need for it to manufacture.
Thank you. And our next question comes from the line of Raju Prasad with William Blair. Your line is now open.
Thanks for taking the question. Just a quick clarification on something you previously said to The NDA submission is only going to be based on part 1 of SUNFISH and Firefish. And I guess just that first time a follow-up?
Yes, that's right. That the it was based on our interactions with the FDA where they saw the results of both SUN Fish and Firefish that we're submitting based on that.
And I guess was there any amount of time that they wanted to see those patients out before you could submit or is it just when the CMC package and the rest of the packages put together that you can submit it?
Yes, when we're putting our plan is to put together the package and have it submitted, but this year, later this year. So it's really based on that. And most of this is just getting ready to be able to submit in the NDA. So that's what that's more about, not about it longer term necessarily.
Okay. I guess what would, if the part 2 of the study didn't show 5 5 patients, what would the are there any discussions there or how is Part 2 going to factor into kind of regulatory discussion moving forward?
So, so, Raju, basically, the conversation with the FDA was centered under like some of the data they're seeing is not being public. Because this was at the different time points than the one we showed at WMS. And based on that, I believe the best interpretation of the feedback we got from them is that they're looking to proportions, right? We always use absolute numbers, but the proper way to look into this is like for part 2 firefish that was 12.5% of the babysitting. What we are looking to right now, if you were to apply that proportion to Part 1, that's about 2.5 babies, right?
So three babies would be to that thresholds. When they look into this, they're like, look, that's robust data and the chopping tens and few other things. With the some fish is similarly, right? We're seeing patients that normally decline on the MFM32 base on the natural history increasing. So the package and we never got definitive answers before a full review from any regulatory agency.
But based on the briefing book data, they receive they're like, this is look sufficient for the file. The both trials completed 1 year or more of exposure right now for part 1. So it meets the normal, I would say, non codified in the statutes, but normally used threshold of 1 year of exposure, 100 patients a year of exposure, things like that. So Roche feels very confident. We feel very confident with the package and it's now more procedural documents that have to be put in place for an upcoming submission.
Great. That's helpful. And then just a clarification question on the milestone payments, I think it says $400,000,000 in the press release approximately what percent of those are regulatory and milestones versus sales milestone payments?
So we posted some slides today, in the, our SEC filings. There's a very detailed scheduled of all the payments, but maybe, Christina, you want to like Yes.
So there's about $87,000,000 related to, regulatory milestones and the remaining our sales based milestones. And as Marcio said, all the details as well as the theater royalties are also in those schedules.
Great. And then one question on AADC. Any color you can provide on the U. S. Versus ex U.
S. Split between those 100 patients?
Sure. Happy to. So it's about half and half right now like give and take. And so the as I mentioned before, right, we're putting effort on both regions. The in Europe is relatively easy as physicians request the kids test this.
So we're probably going to see a little bit of an uptake in Europe over the next couple of months potentially, I don't know because we haven't run, but potentially faster than the U. S. But it's equal, right now, it we expect that this is pandemic, so we don't expect, to have a concentration in one region, another obviously putting a lot of emphasis to get all the screening up and running the U. S. Because the U.
S. Is our first launch. It's the most important pharmaceutical markets in the world. We want to be very asphalt here.
Great. And then just a quick last one. What's the age range between those patients?
They are right now, the information we have, we don't have age for all of them, but they are within the age that were exposed to the treatments before.
All right. Great. Thanks. Thanks for the questions.
You bet.
Thank you. Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.
Thank you for taking my questions. My first question is on the AADC program. Among the patients you identified, can you talk about what proportion we should be thinking about as being eligible for treatment with the gene therapy? Would all of them be eligible or just a small part?
Yes. Thanks, Brian, for the question. What we've seen is that and what we anticipate is that all patients would be eligible for the gene therapy treatment. We've seen actually an interest in regardless of age we've seen improvement in all the patients thus far.
Got it. And then bigger picture, just to hear a little bit more about your plans to build out the in house gene therapy franchise. With respect to what type of manufacturing platform you plan to use. What's the progress been like to date? Any specific timeline goals or milestones we should be thinking about and potential associated costs there as you build out that emerging franchise?
Yes. Thanks for that. I think on one front, we're going to have our own internal gene therapy group, building out vectors and things like that as well. And then I think as we talked about in terms of We thought that it's important to control the manufacturing ourselves. We've been looking hard to be able to bring it in house.
And I think probably within the next 60, 90 days, we'll have probably more to talk about that.
Okay, fair enough. And then last one for me. I'm curious your latest views on use of capital. For continued external business development versus investing in the internal pipeline and other capabilities like manufacturing, where do you stand? What's your thoughts?
So I'll start and then you have Christine. Our view is obviously we're as we've talked about in the vision of what we'll be doing, we'll be expanding both our research and clinical programs internally And so we said we'll be as we said in our vision of what we would be. And so we're doing that as well, but we've always said we'll continue to look externally as well. Obviously, you can't do everything in house. And so we continue the search and try and see if there's other things that are compatible fit for us.
In terms of capital, maybe Christine, you want?
Yes, just to remind you, we had $227,000,000 in cash at year end. We recently completed the equity offering of approximately $225,000,000. So with our solid revenue base and our diversified pipeline, we'll continue to invest both internally and also continue to look externally what fits our strategic vision.
Thank you.
Thank you. And our next question comes from the line of Martin Auster with Credit Suisse.
Hi, everyone. This is Mark on for Marty. Thanks for taking my questions. I guess looking at Risdiplam, I have a couple of questions on that particular product. When should we expect to see functional data for the Juulfish study?
And can you outline what specific data you may provide? And similarly, when should we expect to see initial rainbow FISH results? And what do you expect the initial debt updates into? Thank you.
Yes, I don't know if we've So the Jules but I guess a couple of points here. The one is the JEWELFISH has been expanded to include patients that are treated with gene therapy. And so, so while that's relatively new, we would probably have data at the Cure SMA meeting, is probably when we would be talking more about that.
And maybe if I may, it's true. So Duo Fish is a safety trial at its core. Obviously, there's some measures there. We're looking into the PK and the exposure protein levels. I will show some of that data at WMS, which is extremely positive in my view.
When you're seeing patients switching from other therapies and having an increase in sustainable levels of SMN protein. So that's going to continue. QRSMA is the next expected because the cohort was just expanded to include other type of treatments Rainbow Fish is on the beginning of enrollment. So we're not quite ready to give like an estimate on when that's going to be reading out But as you can imagine, there's a lot of interest with physicians being more and more constant with risdiplam on treating presymptomatic patients with it.
Perfect. Thank you.
Thank you.
Thank you. And that concludes our question and answer portion. I would now like to turn the call back over to CEO, Mr. Stuart Peltz, for closing remarks.
Thank you. So it is and thank you all for joining the call today. And as you know, today is rare disease day and I think it's a report reminder of what drives us here at PTC, where we're focused on rare disease really every day. And as you've seen is after a transformative 2018, we're now really now executing on our vision to be a leading company with a diversified portfolio on the scientific cutting edge to treat rare genetic disorders. With an expected BLA for gene therapy treatment, of AADC and a planned NDA for Spinal Muscular atrophy treatment both this year will be advancing towards this goal.
We look forward to delivering on the and will enable us to achieve the potential $1,500,000,000 revenues by 2023. Thank you all for joining the call today.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone, have a wonderful day.