somewhere in the city, weather-wise. Okay, welcome, everyone. We'll continue with the next session. My name is Paul Choi, and I cover the small and mid-cap biotechnology sector here at Goldman Sachs. It's my pleasure to welcome the management team from PTC. To my immediate right, we have Dr. Matt Klein, and at the far end there, we have Kylie O'Keefe. What we'll do is the usual format. Maybe I'll let Matt kick it off with a couple of high-level comments, and then we'll go into Q&A. If anybody in the audience has questions along the way, please feel free to raise your hand and we'll get a mic to you. Also, for those who are listening on the webcast, if you have any questions, please email them to us and we'll read them anonymously, if time allows.
Otherwise, with that, I'll let Matt kick it off here.
Great. Thanks so much, Paul. It's great to be here today. For those of you who don't know PTC, we are a global biopharmaceutical company that discovers, develops, and commercializes therapies for rare disorders. We just celebrated our 25th anniversary and are looking forward to a continuing successful next quarter century. We started with a focus on mRNA biology and have subsequently built several scientific platforms where we are able to leverage our unique knowledge to bring therapies forward for patients with high unmet medical need. We have a robust commercial portfolio with five marketed products, global, and a sixth product from which we receive collaboration royalty revenue. In 2023, we're projected to have between $940 million and $1 billion of revenue. Obviously, a key milestone for the company.
We also have a robust R&D portfolio with a number of clinical trials that are reading out in the first half of this year, and recently shared results from our phase 3, PKU APHENITY trial, where we had really transformative data that will allow us, we believe, to become standard of care and address the still significant unmet medical need in PKU, and represent another potential billion-dollar commercial opportunity. We have several additional trials still to read out in the next several weeks, including our PTC518, Huntington's disease program from our validated splicing platform, and a number of regulatory milestones coming up in the back half of the year. Really an exciting time at PTC, and look forward to answering any questions you have, Paul.
Great. Thank you. There's a lot to unpack there, but maybe we'll start with this, Matt, which is, you have been at the company for several years now, but only recently became CEO. Maybe my first question to you is, you know, from, from your new seat here, now, how do you know, I guess, think about PTC now from this new seat? You know, how do you. You know, how does the strategy and strategic vision for the company, perhaps, in your mind, change from having this new role?
Yeah. It's a good question. Obviously, it was an incredible, exciting opportunity for me to take over for Stuart Peltz after his 25 years as a founder, CEO, and really at a time where the company was ready to take its next step in growth. As I mentioned this year, we are projected to have between $940 million and $1 billion of revenue, and along with positive trial readouts, like from our APHENITY trial, we're really poised now to think about moving away from a company that has, you know, sort of opportunism in the strategy and needing to take a lot of shots on goal, where we can now be really focused.
We can focus our research efforts on things like splicing and Bio-e, which are two platforms that we built, that, quite frankly, we have scientific knowledge and expertise that very few other companies have, and can leverage that expertise in focused therapeutic areas such as neurology and metabolism and oncology. Also think about being much more strategic in how we deploy our capital and start thinking about, as we recently announced, a reduction in operating expenses and really thinking how with potentially $1 billion revenue this year and another $1 billion PKU revenue opportunity, we can think about moving towards the break-even and maybe even one day, profitability.
It's really, as I take over the role, the time in the company's development, where we can start thinking about taking that next step as a company and thinking about being more focused, in our strategy, more thoughtful in our capital structure and our deployment of capital, and how we, at the same time, can still remain that really, impressive, innovative, and entrepreneurial company that can continue to use pioneering science to deliver therapies to patients who desperately need them.
Right. Yeah, it's always a challenging balance. Maybe starting then or turning to the commercial piece side of things for either you, Matt or for Kylie. Your DMD franchise reported, you know, a very good consensus beat this past quarter. Can you maybe speak to what the recent trends have been for Translarna and for Emflaza in the U.S. and Europe? I had a couple follow-up questions on that as well.
Yeah, absolutely. As you said, we had a really strong quarter in the first quarter. We had $170 million for the DMD franchise, which was a 33% growth over the first quarter of last year. We're continuing that strong double-digit growth across the DMD franchise, despite being in market with Translarna for nine years and Emflaza for six. It's quite remarkable for a mature stage product. If I start with Translarna ex U.S., I think there's a number of different drivers that are contributing to the growth. One of the things that's really reassuring to us is we continue to see growth in existing geographies, so we're not at peak penetration in existing geographies.
We continue to find new patients, we continue to ensure that we're broadening access where possible, and we continue to ensure that we focus on high compliance. In addition to that, we're also looking at expanded geographic areas. We've spoke about, in the past, a number of areas like Brazil and Latin America, other countries in Latin America, Central and Eastern Europe, Middle East and North Africa, and also the Commonwealth of Independent States. That is starting to become a much larger growth driver for us as we continue to expand in these areas. There's still untapped potential for us with Translarna and geographic expansion, there's areas like Asia Pacific, which we're just starting to really scratch the surface on.
We continue to project double-digit growth over the next couple of years for Translarna, both in those existing geographies, but also as we continue to expand geographically as well.
Okay, that's great. I mean, it's fascinating because you have a mature, you know, what people characterize as a mature market between yourselves and Sarepta, yet these patients continue to be identified in other geographies. I guess, maybe just on the topic of Translarna now for either you, Kylie or Matt. The company has previously stated, you know, that you intend to reengage with the U.S. regulators on that front about a potential application. Can you maybe provide us some feedback on what's been happening on the FDA front there?
Yeah, absolutely. What following the readout of Study 041, which was our confirmational study for our European conditional marketing authorization, and also being a global placebo-controlled trial, we believe provided us with data that could support approval in the U.S. In particular, the fact that in the overall population, the intent to treat population, we, for the first time in a placebo-controlled study in DMD, demonstrated statistically significant benefit on the key functional endpoints of disease, including the six-minute walk test, North Star Ambulatory Assessment, and others. We believe that these data, along with the totality of evidence from, you know, three clinical studies and 700 boys, as well as our real-world registry evidence showing that we're able to slow loss of...
time to loss of ambulation and loss of pulmonary function, which are really the two key morbid transition points in the disease, providing us with a robust package, along with the drug safety, to meet the unmet medical needs in the U.S. for nonsense mutation DMD boys. We had a discussion with the agency, in the winter, at which time they suggested that we have a Type C meeting, where we present the totality of evidence that could be in support of an NDA resubmission in the U.S. We said we're gonna request that meeting.
We're in the process now of completing some analyses that will address some of the long-standing concerns in the data package, as well as provide really new evidence for the agency to consider that reflect the totality of evidence and the true benefit we're able to provide for nonsense mutation DMD. We look forward to having that discussion with the agency and, obviously, updating folks as we go through that, because clearly, there's a strong desire in the DMD patient community for this drug to get to children, as in the U.S., as Kylie explained. We've built this robust commercial organization, are able to provide this drug in nearly every other geography around the world, to Translarna, in nearly every other geography around the world.
Obviously, boys in the U.S. and their parents desperately want to get this therapy as well.
Great. Maybe just as a follow-up, any sort of rough framework for when that Type C meeting might occur, and when you might be able to provide an update to the market on that?
Yeah. Obviously, we're gonna work to get their request in as soon as possible. Obviously, it'll follow the FDA clocks for a Type C meeting request.
Okay.
We'll provide updates as we have them.
Great. Maybe staying on the topic of commercialization. obviously, you've partnered with Roche on SMA, but you also have recently started commercializing Upstaza as well. Can you maybe provide an update on or some color on how that launch is going? Any quantitative measures you can provide, like patients identified and treated, coverage and so forth, and just kind of where the state of the launch is?
Absolutely. Looking back to mid-2022, we received EMA approval for Upstaza, and then in the back half of last year, towards the end of last year, we also received MHRA approval. We're approved in Europe and also in the UK. We've talked a lot about the different access pathways that are available to us and how we can secure patients to be commercially treated, and we've been executing on a number of those pathways. The first is early access programs. We talked about France being a really good example of that. They have the AAP program, and that basically replaced the retired ATU program. We were able to treat patients very early on. We talked about treating the first patient through the AAP program in Q2 of last year, and we've treated additional patients in France since then.
There's a number of other countries that also have early access programs. Italy is a good example of that. Then also what we call named patient programs outside of Europe, that look to an approval in Europe to be able to have patients treated through named patient programs. The second pathway, that's obviously a pretty traditional one, is commercial access, and we've talked about Germany being the first country of launch through that, and we've obviously talked about treating patients in Germany with commercial access. We've also talked last quarter at earnings about securing a positive recommendation from NICE for Upstaza, and that will obviously help us move forward with treating patients in England and Wales, and we're focused on a number of other countries to bring them online with commercial access.
The third pathway, and somewhat uniquely, a little bit utilized for gene therapy, is cross-border health. That's where a patient is located in a country where there isn't a treatment center of excellence at this point, and they cross the border to an existing treatment center of excellence, and it's a commercially reimbursed patient. PTC is able to realize the revenue through that cross-border healthcare. We talked about at Q1 earnings as well, treating our first cross-border patient, that was from the Middle East and was treated in France. That has really realized the potential of that pathway, and we'll continue to focus on those areas.
Across the board, we're focused on bringing more countries online, so we're able to treat more patients in Europe and continued focus on named patient programs outside of Europe, for example, Brazil, Latin America, other parts of the world that allow that. Then also continued registrations. We've talked about a BLA. We're also looking at registration in Brazil and other parts of LATAM, then also in Asia Pacific as well. There's still continued growth. I think one of the things that people don't often understand is when it's a ex-U.S. launch first, despite it being a centralized registration process, country by country, pricing and reimbursement takes time. So we're working through that. We've seen really positive trends and positive discussions with NICE having a positive recommendation.
We've had strong ratings across Germany and France, and we're continuing to work through other countries off the back of that.
Okay, great. You brought up actually something that would be my next question, which is just on the U.S. BLA status. Matt, can you maybe just remind us of what's going on there and sort of what the key questions are before you continue with the BLA process?
We said we believe we'll be in a position to submit that application either by the end of this quarter or early in the third quarter. The last remaining dialogue with the agency has been around the data supporting comparability between the material that was used in the clinical studies and the material that we're gonna use commercially. Now, one thing that's very important is obviously to demonstrate that they're comparable in terms of key aspects of the therapy, including things like potency, infectivity, viral titer, infectivity, and empty and full capsids. We provide additional data to the agency to what we believe will fully address their residual concerns. We were just looking forward to their response to that, and once we have that in hand, we look forward to submitting the BLA.
While you're continuing, you know, and going forward to, you know, continue to work on commercializing Upstaza here in the gene therapy space, you also recently announced a decision from an R&D perspective to back off from continuing a gene therapy development. Can you maybe walk us through what were the inputs or that went into this cost-benefit decision and that you announced to the market recently?
Absolutely. Look, we're incredibly proud of the pioneering work we have done with Upstaza, being able to bring a truly transformative therapy to children and get approved the first-ever gene therapy that's administered through a neurosurgical procedure into the brain. We think that's incredibly important, not only for patients with AADC deficiency, but also for the entire field of gene therapy, particularly gene therapy targeting neurological disorders. We have also, as we said, gonna look very carefully at our use of capital and our R&D portfolio breadth. As I said earlier, sitting in a position now with the potential for up to $1 billion in revenue this year and the potential $1 billion product of sepiapterin for PKU moving forward, we really think we were in a position where we should say, where do we want to thoughtfully deploy capital?
You know, a lot has changed in the gene therapy space over the past few years. Actually, a lot hasn't changed, but I think we've learned a lot more about the gene therapy space in the past few years. A lot of the challenges, the cost that it takes to get a gene therapy into the clinic, the cost of development, what's in the clinic, the challenges of clinical development for a number of gene therapies, particularly ones for neurological disorders, and what may be, by the time you get a therapy approved, an uncertain commercial landscape and payer landscape in terms of funding for those types of products.
When we looked at the amount of spend we've had on gene therapies in the past few years, I think we've said and we've shared publicly around $570 million. That's a lot for therapies that are not yet in the clinic and may be very far off to approval. For us, it was really a decision of saying, we'd rather not invest any further in those programs. Obviously, look to put them in the hands of those who can develop them, and really use our resources to focus on our small molecule platforms, where again, we can uniquely discover and develop therapies for really meaningful therapies for patients with high net medical needs.
This was really a decision about how best to deploy resources, understanding what the return on a very, very large gene therapy investment would look like over the next several years, and being in the fortunate position that we have such a broad R&D portfolio and can do so many things, that we have to be very thoughtful about the opportunity costs of pursuing programs that may be incredibly capital intensive with a very low POS and an uncertain commercial viability.
Okay. You know, as part of the strategic prioritization, it sounds like you're definitely thinking a lot more about R&D productivity and to your point on capital allocation here. I guess, as you and the management team think about this and as well as the board think about it, you know, how are you thinking about balancing this, you know, effort to be, you know, productive in the clinic and in R&D versus the move to profitability? Is there a particular timeframe or metric that you guys are thinking around, in terms of, you know, shaping this narrative and communicating it to the investor in the community?
Yeah, absolutely. This is something we've talked about since the CEO transition. Look, it starts first with taking stock of what we're doing and what are the programs we should be doing, what should we be prioritizing, and what is really the strategic focus of the company. As I said, I think that really sits in scientific platforms, where we have the unique ability to bring forward really important therapies. It's really focusing down the platforms to things like splicing, which we can uniquely do, and things like the Bio-e platform, again, that we have unique expertise in, and saying: Okay, we focus that down. That obviously brings with it some savings in terms of OpEx, and also, quite frankly, a focus of intellectual capacity and intellectual resources so that we can optimize for success in those programs.
Look again across the entire development commercial portfolio as well, through this lens of focus and return on investment. I think you get into this situation where you obviously you walk before you run, and we want to think about what our optimal strategy is, how do we get moved towards break even? Obviously, on the other side of break even, is thinking how you move towards profitability, maintaining the balance, as you said, Paul, and critically important balance is that we are still be innovative and discover important therapies, which we believe we can, when you do that in a more focused way, that's how you do it.
Focus your resource spend on programs that have good return on investment, that we can uniquely do, and have reasonable probabilities of success, so that when we're deploying capital, it is done in a thoughtful way, and it can bring about transformative success in the long run.
Okay, great. Maybe turning to other aspects of the pipeline. Congratulations on your recent APHENITY results for sepiapterin in PKU. Can you maybe highlight some of the, you know, key takeaways from the data here, and, you know, just what you think what is most interesting from your Phase 3 results?
First, thank you. I think that we were incredibly excited about the results, as are the physician and patient communities. Given the fact that even though there's two approved therapies for PKU, there still remains a significantly large unmet medical need. The vast majority of patients are not well served by the current available therapies. The phase 3 trial was a placebo-controlled trial, sepiapterin versus placebo in adults and pediatric patients with PKU, in the full spectrum of disease, including mild, moderate, and severe patients. We first had a run-in phase during which we could identify responders to sepiapterin after two weeks of treatment with the drug and had a 66% responder rate. Just to benchmark that in a similar all comers responder study, Kuvan had about a 19% responder rate.
Right away, in that first 2 weeks, we again were able to demonstrate that we have an ability to provide a meaningful impact of many, many more patients than the standard of care, Kuvan or BH4. We took those patients that we had, the 65%, that the 66% that responded, and by the way, that included a number of classical PKU patients, 16 classical PKU patients that had a mean reduction of 60%. Again, a tremendous magnitude of reduction in the most difficult-to-treat patients.
We randomized those patients to receive sepiapterin or placebo for six weeks, we've had a highly statistically significant finding, with a overall reduction of 63%, mean reduction of 63% in the treatment group, obviously, minimal change in the placebo group that had a P value of 0.00001. Highly statistically significant and clinically meaningful magnitude of effect. When you dig deeper into that, you see really other pieces of impressive data. When you look at a subset of classical patients, we had a mean reduction of 69%. Again, a tremendous reduction, magnitude of reduction in the hardest-to-treat patients. We also were able to bring 84% of patients, 84% of patients, to below the clinical target guideline of 360 micromolar per liter.
That's really significant in its own right, when you compare that with the numbers from Kuvan, which is in the 30%, I think it's 34%. Furthermore, we had 11 patients who achieved normalization of phenylalanine levels. That's below the 160 micromolar per liter normal level. Those are really phenomenal data. The last piece that was really significant is we were also able, again, as we did in phase 2, look at how sepiapterin performed in patients who were on Kuvan. We had 27 patients who entered the study on Kuvan. We were able to get their Kuvan-associated phenylalanine levels.
They then got washed out and then treated with sepiapterin for two weeks, and what we found is that we had a 48% reduction in phenylalanine levels from their Kuvan treatment level. That, again, is saying that in patients who are on Kuvan, that sort of may be served by Kuvan, we're able to provide significantly greater benefit. When you put all these data together, they really support a product that was safe and well tolerated and can provide meaningful benefit, not only to those who aren't served by available therapies, but even those who may be, because we're able to achieve such greater reductions of phenylalanine, and that's really the name of the game in terms of providing neurological benefit to patients with PKU.
Okay, great. In the, in the wake of your data results, I think one of the debates of the investment community is trying to understand the data versus the approved therapies on a like-for-like basis, and given set the patient numbers and so forth, number of classical patients, different baselines, and, you know, maybe understanding what data looks like from your perspective on an apples-to-apples basis. To that regard, I guess, what would you say that the data suggests in terms of where sepiaterin would be most applicable? Just understanding, you know, how to contextualize maybe some of the data results, let's say, in the classical patients particularly.
Yes, may I make a couple comments, and Kylie, maybe you can cover the commercial ones, because I think you mentioned the different... You know, apples to apples is always hard. These studies were conducted years later, and that's why I think when you have data in patients who are on Kuvan and then look at what they do when they're on sepiaterin, are very impactful. Having that 48% greater reduction is really important. We also had a number of patients who were documented as Kuvan failures, who responded to sepiaterin. That's, that's pretty good, and not subject to maybe changes over time. You mentioned the question of, well, maybe our baseline levels of phenylalanine were a little lower than the Kuvan studies. That actually just raises the bar.
If you can have greater magnitude of reduction, both in absolute phenylalanine reduction and percent magnitude of phenylalanine reduction, that means that we performed better when the bar was higher. I think, again, all of these data put us in a position to address all the different segments of the population, and that's the feedback we're getting from physicians as well, even those who have patients on Kuvan. Kylie, I don't want to take-
Yeah, I think it's well said, Matt. I think across the board, what we're hearing from both physicians and patients is there's a substantial unmet need. We knew that going into the trial. Despite there being 2 therapies available, there's large proportions of patients and patient segments that are not being served. That might be because they're therapy naive. That includes that classical subsegment you just talked about. There's additional therapy-naive patients. That might be patients that have tried the standard of care but have failed. Patients that have tried the standard of care and tried to liberalize their diet and come off the drug because they've been not well controlled, right? There's many pockets of pretty large unmet need.
The question going into the study, from our perspective, was, what are the data points that we believe could be the proof in the pudding, so to speak, as to our ability to meet the needs of those patients? I think coming out the back of the APHENITY readout, I think consistent feedback has been that this is far exceeding the belief of what is required to meet the needs of those patients in many of the segments. If we think about, you touched on classical PKU, right? These patients have traditionally been unable to go on therapy. They're entirely managing the disease through diet management, and this is highly frustrating for a patient, particularly with very severe disease. They're desperate for therapies.
The ability for us to show a 69% Phe reduction or 523 micromolar in absolute Phe reduction, that's very substantial for those patients. You think about what 69% means if you're a patient with a baseline Phe level of 1,000, it's very substantial Phe reduction. From that perspective, it's a quick, and I would say, low-hanging fruit that has a lot of unmet need. We don't see that as the only opportunity, or we're stopping there, or we don't see it as the primary opportunity. We see also the patients with That have tried the standard of care and failed, so they've not shown a response. As Matt just talked about, we were able to show a 66% response rate.
There's a big gap of patients that have failed Kuvan, that would show a response on sepiaterin, and we had some of those patients in the trial, and that'll be another large opportunity in very quick succession at launch. The third is also those that are just not well controlled. You think about what control means to a patient, it's about liberalizing the diet. Phe reduction is one thing, but understanding what Phe levels you're able to maintain while you have an increased Phe intake is really important to the physician, to the patient, and to the payer. That's a big part of why we put Phe tolerance into our long-term extension study.
It's one thing to say we have 69% Phe reduction in a classical patient, or 63% in a broader patient population, but then if a patient comes down into target Phe levels, 360 micromolar, as an example, but they're not able to liberalize their diet, what does that really mean? Having an ability to show that we not only bring them into that target Phe level, but then over time, they're able to have an increased Phe intake and maintain those levels, is truly what's gonna be one of, in my opinion, from a commercial perspective, one of the most differentiating elements of this drug.
Okay. maybe just one more on this, which is, sort of what are the items left to check, you know, from a pre-NDA perspective? Secondly, as you think about the commercial rollout here, you know, what steps have you taken in terms of either, sales force build-out and/or payer engagement?
Just from the regulatory standpoint, we're, as we said, we're gonna get a meeting request ready, send it in, and look forward to the pre-NDA discussions, and have an NDA submission by the end of this year is the target.
Okay.
From a commercial infrastructure point of view, I think one of the things that we've been very deliberate about, Paul, is building a commercial infrastructure and engine that is plug and play for many of our opportunities, and PKU is no exception to that. We have a global commercial footprint that's been built to be able to commercialize not just the DMD franchise, not just Upstaza, not just Tegsedi or Librea, but also sepiaterin as it comes to the marketplace. Whether it's patient engagement, whether it's payer engagement, whether it's physician engagement, all of our customer-facing activities and infrastructure is built and ready to go. In many cases, we've started a lot of this work. We've been engaging with the well-known centers of excellence. We've been engaging with the patient advocacy groups.
To your question about payers, we've also been engaging with payers. We have done a number of different scientific advice meetings in advance of data readout to understand what does a package look like that payers would be interested in, and how does that differ from U.S. to ex-U.S.? I think one of the aspects that's reassuring to us is, as expected, payers were very interested ex-U.S. in Phe tolerance data, because they wanna understand how is a therapeutic operating alongside diet management. That was reassuring for us because, obviously, we'd made a deliberate decision to go forth with that. I think from a totality of evidence point of view, we have a phase 2 head-to-head study, and that gave us a lot of good data points and confidence. We have the phase 3 APHENITY study, as well as the long-term extension.
Within that data package, we also, as Matt talked about, have patients that were on Kuvan, were washed out and went on to sepiaterin. Across the board, we feel like we've got a really strong data package to be able to continue those payer discussions.
Okay.
There's nothing come up so far in payer engagement that would provide us any cause for concern.
Great. Maybe if we could discuss the MOVE-FA study results in particular for a moment here. While not meeting the primary endpoint, after you announced the top results, you did mention that you want to engage with regulators on a potential discussion here and exploring a path forward here. Can you maybe comment on what you've seen in the data that underpins this potential move to engage on a regulatory discussion here?
Absolutely. The primary endpoint in this study, MOVE-FA, which focused primarily in children, which we were able to do given the safety of the drug, was the disease rating scale, which has 4 parts to it. One of the 4 parts. Actually, we had nominal significance on 2 out of the 4 parts, and it turns out on the 2 parts that most reflect clinical meaning, fullness. One is upright stability, which has been shown to be very important in terms of time to loss of ambulatory function, which obviously is a key transition point of the disease, and the second is bulbar, which reflects speech and swallow. The fact that we had significance on the 2 key parts is element number 1.
Number two is, if you look at the pediatric patient population, the part of that scale that's actually moving, the one that actually progresses the most, over childhood and adolescence in FA, is upright stability. Now you're saying: Okay, on the most meaningful one to kids, you registered the strongest response. Obviously, we also had data on the fatigue scale, which met significance, fatigue being the number one complaint, symptom complaint of patients with FA, and at the external and Patient-Focused Drug Development day, was the number one symptom patients said they want a drug to target. Then, of course, the safety of the drug and the fact that Skyclarys is approved for basically adult patients.
There remains this unmet medical need, and in our discussion with the KOLs and the patient community leaders, they felt very strongly, given the unmet need in kids and the fact that we actually impacted the one thing that is important in kids on that scale, upright stability, certainly warranted a discussion with the agency. Whether that means they would view the upright stability data as an intermediate clinical endpoint, which is one of the pathways for accelerated approval, is a discussion worth having. Certainly when you think about what an intermediate clinical endpoint has to do, it has to say, one, that it is something that is known to be important in terms of the long-term clinical outcome of the disease, and then two, you made a movement on that that's significant.
Well, when you look at the literature, it clearly establishes the relationship between changes in upright stability and time to loss of ambulation. Obviously, it's an intermediate step on a very meaningful clinical endpoint. Then look at the magnitude of change we had. It's really consistent with that, about reducing by half what a patient would lose in a year. That actually, over the long term, could be quite meaningful. We believe it's worth then to just have a discussion to see if we could avail ourselves of a pathway.
Okay, very good. We're coming up on time here. I want to maybe spend our remaining time talking about Huntington's and 518 here. I think, you know, our conversations with investors suggest that, you know, they're very impressed by what they see in terms of the drug and the serum, but they have challenges connecting it to what it could translate to in terms of Huntington's changes, and then further, what that means from a clinical meaningfulness perspective. Can you maybe, you know, provide your view and help us connect the dots on how to think about that? This is a very important year in terms of updates in the Huntington space between yourselves and uniQure and so forth.
Yes.
You maybe just, you know, frame for us what we should expect from the data and how you'll present it.
Absolutely. Look, we're in a pretty unique position in the neurodegenerative disease, that we have an understanding of one of the key causes, which in the case of Huntington's disease, is the production of a mutant disease-causing toxic protein. To be in a position where you know what the cause is and to be able to target that effectively, really sets up a treatment hypothesis, which is quite sound. Obviously, this program where it comes from our splicing platform, where we've learned a great deal from the successful discovery and development of Evrysdi for SMA, in terms of what needs to be in a molecule to ensure that it is selective and specific, really important for splicing, gets to the brain and broadly bio distributes to the brain, which obviously is incredibly important for a whole brain disease like Huntington's disease.
Taking that path from being able to have something in a lab to something in human volunteers, to be able to translate that into ultimate clinical benefit, obviously, is a many-step path, and our whole development program is proceeding in that way. We've gone through phase 1, and now in the move, in the PIVOT-HD study, what we plan to show in the data before the end of June, is looking at the dose-dependent reduction of huntingtin mRNA and protein in the blood. Very important because we're in a position with a systemically administered therapy, that we can actually get a window into the brain from looking at the blood.
We can uniquely do that because it's an orally administered therapy, and we know that what's going on in the cellular machinery of a blood cell is the same as what's going on in the neuron. We know that. We've shown that preclinically. What we really have is a very special way to get a window into what's going on in a neuron. Those data will be very important, one, in terms of confirming what goes on in the cellular machinery, and then two, coupled with exposure data, showing that we're getting the drug across the blood-brain barrier in sufficient quantity, and it's not being efflux, tells us that it's getting into the brain, and we have every reason to believe then, at this early stage, that we're going to have an effect on huntingtin protein in the brain.
The next step comes when we start looking at biomarker data like NfL, which obviously is an important marker, not only of safety, but also effects on neuronal inflammation and neuronal cell loss, and ultimately, huntingtin protein in the CSF. Those biomarker data, we said will come at 12 months, will begin to tell that story of how we are doing in terms of having an impact on things that really matter in Huntington's disease. I think it's really a stage-gate approach that we need to walk along and get the most information we can at the right time. At 12 weeks, to be able to get important PK/PD peripheral data and CSF exposure data, which tells us that we're getting into the brain and affecting the cell machinery, are really critical first steps along that path.
Okay, great. Exciting times in Huntington. Okay, we've run over here, so my thanks to Matt and Kylie for joining us, and we'll end it on that note. Thank you very much.
Thank you, Paul.
Thanks for having us, Paul.