Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics Fabry disease transaction call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you would need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Dr. Matthew Klein, Chief Executive Officer. Please go ahead.
Thank you all for joining this afternoon's call. Before I begin, I refer you to our forward-looking statements on the slide posted on our website, as well as our risk factor section in our most recent 10-K. I am excited to share the details of our planned acquisition of the ST-920 Fabry gene therapy asset. This was an opportunity to advance our strategy of leveraging our accomplished existing rare disease global commercial infrastructure and accelerate short- and intermediate-term revenue growth. Our customer-facing teams have repeatedly demonstrated the ability to deliver rare disease therapies to patients worldwide regardless of treatment modality, including oral small molecule, ASO, and gene therapy. The ST-920 Fabry gene therapy program provided a unique opportunity to acquire a potentially transformative therapy at BLA stage without the need for significant investment or build-out of development, regulatory, or commercial capabilities.
This is a potential value-creative transaction that puts another innovative and valuable product in the demonstrated capable hands of our customer-facing teams. In fact, we have several commercial leaders at PTC with specific experience in marketing the existing approved Fabry therapies. We see the potential here for significant return on investment without impacting our potential to reach cash flow breakeven in 2026. PTC was selected as the winning bidder for the ST-920 asset through a competitive bankruptcy auction. The terms include a $111 million cash payment at deal closing and regulatory milestones of $80 million for FDA acceptance, FDA accelerated approval, and $20 million for FDA full approval. Of course, deal closing is subject to certain conditions. As one of the few companies to have gained FDA approval for an AAV-based gene therapy, we applied that knowledge and experience to a detailed diligence process.
In addition to review of the clinical efficacy and safety data, our teams focused on various aspects of product manufacturing and quality that we know are critical to regulatory approval. We are confident in the demonstrated safety and clinically differentiated profile of ST-920, as well as in the manufacturing and related quality processes. In addition, we believe there is clarity on the regulatory path and that our experience in gaining FDA approval for an AAV gene therapy product increases the probability of success. ST-920 is a one-time intravenously administered AAV gene replacement therapy that enables the production of the alpha-gal A enzyme deficient in Fabry disease. Notably, treatment administration does not require pre or concomitant immunosuppression. The BLA for accelerated approval is based on the findings of meaningful effect on alpha-gal A enzyme production, renal function, and other aspects of clinical benefit recorded in the phase I/II STAAR study.
The STAAR study included 33 adults with Fabry disease, both men and women, with a variety of subtypes and ERT treatment history. Based on discussions with FDA, the key efficacy endpoint for the BLA is the mean positive eGFR slope from baseline to week 52 following gene therapy administration. The finding of positive eGFR slope over 52 weeks is differentiated from other Fabry therapies which demonstrated improved renal function but still negative eGFR slope from baseline. Furthermore, all 18 study participants on enzyme replacement therapy at study start were withdrawn from ERT. Durability of effect has been demonstrated with sustained increased alpha-gal A activity maintained for up to four and a half years for the earliest treated study participant, with evidence of maintained improvements in renal function. Importantly, ST-920 has been demonstrated to be safe and well-tolerated.
The most common adverse events in the STAAR study were fever, COVID-19, and headache. ST-920 has received Regenerative Medicine Advanced Therapy designation as well as Orphan and Fast Track designations from FDA. As I mentioned, the BLA submission for accelerated approval is based on the intermediate clinical endpoint of annualized eGFR at week 52, as aligned with FDA, with 104-week results from the STAAR study planned to provide confirmatory evidence to support full approval. The non-clinical and clinical BLA modules have already been submitted as part of a rolling submission, with the CMC package expected to be submitted in Q4 2026. PTC also plans to pursue regulatory approval outside of the U.S., again leveraging existing regulatory and commercial rare disease infrastructure. From a commercial standpoint, we see this as a potential meaningful global opportunity.
There are an estimated 11,000 individuals with Fabry disease in the U.S., and a similar prevalence rate worldwide in countries where we intend to pursue registration. In addition, the disease community is well aggregated, and there are Fabry centers of excellence where the majority of patients are treated. Furthermore, there are several U.S. states and countries in which Fabry disease is included as part of newborn screening programs. In summary, we are excited to bring another meaningful rare disease therapy to patients in need worldwide. The terms of this transaction preserve our firepower as we pursue our strategy to leverage business development to complement our existing product portfolio and demonstrated rare disease development and commercial capabilities. I'll now turn the call over to the operator for questions on this transaction. Operator?
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. The first question comes from Kristen Kluska with Cantor. Your line is now open.
Hi, everyone. Congrats on this deal. Thanks for taking my questions. I wanted to ask, normally, when we see gene therapies approved for indications where standard of care is already existing, these therapies don't do as well as some of the ones where there's no options at all. Why don't you believe this is going to be the case with this asset? Maybe it sounds like the kidney benefits in particular are going to drive a lot of the events. Then separately, does this program have rare pediatric disease designation, and is there potential for PRV associated with that? Thank you.
Hi, Kristen. Let me take the second question first and then the first question second. The study included only adults. We clearly realize that there's the potential, and one of the things we'll think about as we advance the program forward is to go into younger Fabry patients, certainly adolescent patients. So for right now, the main study included adults, so did not have rare pediatric designation. Again, I think we see a potential here to explore that following the completion of the transaction. Fabry is a pretty diverse and large population that includes individuals on ERT, not on ERT, as well as Galafold, and I think one of the things as we were doing diligence here that was very attractive to us is how differentiated this therapy is. The trial included all patients with different ERT history, different genetic subtypes, men and women.
As I mentioned in the prepared remarks, when we actually look at the patients who were on ERT during the study, 18 of them, they were withdrawn from the ERT during the study. So that's our way of saying that we believe it's a very differentiated therapy and has the potential to make meaningful impacts for all patients, whether those who are on existing therapies, not on existing therapies, and have different treatment histories.
Thank you. Our next question will come from Tazeen Ahmad with Bank of America. Your line's open.
Hi, guys. Thanks for taking my questions. I wanted to get a better sense about how you're thinking about eligibility of ST-920 based on patients who have pre-existing antibodies, level of severity of disease. If there is, what proportion of the Fabry population do you think would be particularly amenable to 920? What's your view of, it seems like the low-hanging fruit would be switch patients, but how are you thinking about newly diagnosed patients and what it would take to make this the first treatment that they get? Thanks.
Yes. Thanks, Tazeen. I'll start, then I'll turn part of the question over to Eric for his comments. I think if you look at the inclusion criteria for the clinical trial, they were pretty broad, again, in terms of treatment history, men or women, genetic background. There was certain, an important limitation is an AAV6 gene therapy. So clearly, if you have demonstrated history of AAV6 antibodies, you would not be eligible for the therapy, and the inclusion criteria also included those with GFR of over 40. Now, that's the clinical trial inclusion. Obviously, one of the things we'll do as we dig further into this and work on our commercial planning, we'll look to understand broadening potential eligibility, ensuring, as always, which is very important with all gene therapies, that safety first.
But we believe that given the differentiated characteristics of this therapy, it could have broad utility across the full spectrum of patients. Eric, do you want to comment? I'll also comment that Eric himself has experience having launched Fabry nine years ago, and a lot of his team, a lot of our existing commercial team, including leaders in market access and other parts of the organization, have specific Fabry gene therapy commercial experience, which again, made this sort of such a nice fit for the company. Eric?
Yeah. Tazeen, thanks for the question. Yeah, I was involved in some of the very first launches, as you know, globalizing Replagal and what I think Matt described is really begins with clinical differentiation. If we look at the data, the durability in kidney and cardiac is incredibly important and meaningful, and they're hard endpoints. This one-time infusion with no pre-medication is also something critically important, and we see durable, meaningful improvements both in the kidney and the heart. What we've learned about Fabry is early diagnosis and early treatment means better outcomes.
The data that we saw showed that this durability happens irrespective of sex, whether it is prior ERT, Fabry subtypes. We believe that ultimately the label will be the label, but we look at this in the long term as a broad use for Fabry patients.
Okay, and how are you thinking about switch versus newly diagnosed?
Well, and to Matt's point, we looked at the market, and the marketplace is really segmented with ERTs in some markets, particularly if you look at the key ones, U.S., Japan, Europe, Latin America, particularly Brazil, about two-thirds of those markets are ERT. Okay. There is a burden behind that. There is pre-medication involved. There are infusions that require every two weeks. There are people that have to travel to the clinics. Those are a number of different things that have to happen compared to a one-time infusion in the clinic. Then what you are doing is monitoring, if you will, kidney function and cardiac function. So, I think the target here is a broad use. We have been able to show that irrespective of Fabry subtypes, that this is effective, and we will be looking at this in a broader context.
I think ERT is potentially a lower-hanging fruit, but earlier treatment will be the better choice. That is something we will be going after.
Okay. Thanks, guys.
Thank you. The next question comes from Eric Joseph with Citi. Your line's open.
Hi. Hey, guys. Thanks for taking the questions. Just two from us. I'm wondering if there's potential for, as part of the planned BLA or completion of the planned BLA submission, I'm wondering if there's potential for perhaps full approval, given that I think about two-thirds of patients have already completed their 104-week follow-up. Just coming back to the point around expected durability, could you share some thoughts on what you think the ultimate durability of ST-920 to continuously express alpha-galactosidase A would be? Just appreciating that some other AAV programs have resulted in attenuated gene product expression over time. Thank you.
Eric, so look, there was pretty good alignment with the FDA in our review of the regulatory documents that this would be an accelerated approval based on 52-week data. Those data, the clinical module has been submitted. I think once all the data are available longer term, it will obviously be a process of going through that, analyzing that, and at the right time, discussing with the FDA. I think our base assumption and operating case right now is continuing with the plan as it was designed, which is that this clinical set would serve for accelerated approval, and then we would look to bring long-term data for full approval. Clearly, we'll get a better idea of what that time looks like and whether that could be accelerated as we go a little further into the process.
And as you know, typically in the BLA process, you will have your mid-cycle meetings and other opportunities to share what data may be available that could influence how the agency thinks about it. In terms of durability, look, what we have seen so far in this product is really encouraging. To have the four-and-a-half year maintenance of enzyme production levels, I think is really, really important. And while one could say, sure there could be changes over time, what we have seen so far has been really impressive to us, and again, that durability effect we have seen, I think gives us greater confidence in the strength of this therapy and what it could provide for patients.
Thank you. The next question is going to come from Ben Burnett with Wells Fargo. Your line is open.
Hi. Hello, guys. This is Chen Su calling in for Ben. We just have a quick one. So what kind of CMC information can you share with this asset? I assume that this is probably working with a CDMO. What kind of information do you know? Thank you.
Yeah, sure. Look, as I mentioned, having taken a gene therapy across the finish line for approval, as we did with our AADC program, we have a very good understanding not only of the importance of the CMC package, the quality characteristics, CDMO, all that, but how difficult and challenging this is. So clearly one part of diligence that was particularly important to us was ensuring that the CMC package looked good, which it does. There is a very clear process with specifications well thought out and PPQ lots being conducted. And then the CDMO. CDMO for the production of this product is Thermo Fisher, which I think is a best-in-brand CDMO. And again, not surprisingly, in preparation for the file, there has already been mock inspections, and we will continue to do those and make sure everything is in order for any potential inspection.
But again, I think what we've seen of the CMC program based on our experience and the quality work that the Sangamo team has done gives us a lot of confidence on the CMC package, and it's always reassuring to have a best-in-brand CDMO responsible for the manufacturing of the gene therapy.
Thanks. Congrats on the deal.
Thank you. And the next question is going to come from Ellie Merle with Barclays. Your line's open.
Hey, guys. Congrats on the deal. Just a question on sort of the commercial landscape. I guess how would you characterize the heterogeneity of the disease severity in Fabry? And I think of the 11,000 patients you cited, I guess which of those do you think would be the most interested in gene therapy? Is it patients that are progressing on their current ERT or Galafold, or are showing symptoms, or is it more of the burden of the administration of ERT? And if you can elaborate on sort of how you're thinking about that segmentation of the patients. Thanks.
Thanks for the questions, Ellie. Again, I think what we see here is a pretty broad opportunity. That was one thing that came through in the clinical data. I will let Eric talk a little about how his team is starting in these very early hours, thinking about the population market segmentation and a plan of attack. Yeah, Eric?
Yeah. Thanks, Ellie, for the question. From the commercial landscape, first of all, we have a footprint right now across multiple markets, and we know how to market not only gene therapy but rare disease, but also really get inside these clinics, and these clinics have a variety of patients. When I launched Replagal, in the very early days, what we thought in terms of severity were males, adult males that had symptomatic. What we found out over time was that this is X-linked, and of course, females, perhaps less symptomatic, were also on enzyme replacement therapy. I think there is a natural progression to think that there is definitely severity, and severity will certainly drive this. But with the durability of this data and the durability that we see not only in kidney function and heart function, this really is fit for a broader use.
With Galafold, obviously, there is only a segment of the market that can actually utilize this, so there is only certain Fabry subtypes. So far, what we have seen is the vast majority of subtypes may be able to respond to gene therapy and have a durable treatment, not having to take oral therapy every single day. Again, all of these factors play into broad use for Fabry.
Great. Thanks.
Thank you. Our next question is going to come from Brian Cheng with JP Morgan. Your line's open.
Oh, hey, guys. Thanks for taking our questions here this afternoon. Just a quick one. As we think about the launch, can you talk a little bit about how much work needs to be done for the build-out of the commercial capacity? Do you have a sense of the capacity that you will have in place at the time you launch this product? Thank you.
Hi, Brian. For us, I think one of the key factors here is the fact that we have the existing infrastructure globally with capacity. Obviously, we have a number of different products in the commercial portfolio at different stages of their lifespan. We really believe that we have the capability to really set this in with the existing infrastructure. That includes not only commercial in terms of launch, but also regulatory and global regulatory capacity and understanding, because getting this across the finish line, we have that experience, and I think we're very well-suited to do that. Again, this is what made this a pretty special opportunity for us. We have existing capacity, existing expertise, and this is something that we could set in to what we have without any significant build needed.
Great. Thank you, guys.
Thank you. The next question is going to come from Judah Frommer with Morgan Stanley. Your line's open.
Yeah. Hi, guys. Congrats on the deal. Maybe you could just help us with a little more detail on the process here and the due diligence, the competitive nature of the process. Did you have a chance to speak with Sangamo, or was due diligence done in sort of a clean room environment? What could FDA interactions look like from here? Did you get a good sense of what they were previously and what the next ones will be? Thanks.
Hi, Judah. Thanks for the questions. I'll say we did a pretty thorough diligence process here. There was sufficient time prior to the auction. There was several weeks' time that, again, this was a matter for us of taking our team who knows this stuff inside and out, clinical team, CMC, quality, CMC regulatory. Generally, all of those folks were involved. We had a number of conversations with the appropriate folks on the Sangamo team to get questions answered. Again, we were very impressed by the Sangamo team, who've worked incredibly hard and passionately to get this program and product forward to patients. Again, we made the decision to participate in the auction and clearly to make sure we had the winning bid because we believed in the potential here.
We carefully considered the clinical data, the safety data, CMC package, and the like, and we're very comfortable with the promise of this therapy and our ability to get this across the line based on the quality of the package, the data, combined with our experience. So that was really an important part of it. It was a competitive process. There were multiple bidders. In fact, the auction took over two days, just to give you an idea of how competitive it was and how much interest there was in this asset. Look, for us, as I said, this was really a pretty good opportunity, unique opportunity for us to say the ability to get this asset, we think we can generate a significant return on investment based on what we think the potential market opportunity here is.
We can integrate it into the existing teams and existing infrastructure, existing expertise. Again, being one of the few companies who've gotten an AAV gene therapy approved, we have the know-how to navigate the regulatory pathway. Also, I think the other thing that's attractive here is we're able to bring in such a potentially valuable asset while still maintaining a significant amount of our firepower, given the economic upfront consideration. In terms of FDA interactions, the process is going on. We obviously carefully reviewed all the previous regulatory correspondences, and that made us comfortable that there was an aligned-upon path forward for the submission for the confirmatory evidence.
We expect going forward, the submission would get completed, then it would follow a fairly standard review process where you have the typical agency back and forth, sometimes information requests, formal meetings around the mid-cycle or late cycle parts of the review period. Thanks.
Thank you. The next question comes from Brian Abrahams with RBC Capital Markets. Your line's open.
Hey, guys. Thanks so much for taking our questions. When you were able to review some of the FDA interactions, can you clarify just how much of the dialogue was with the contemporary administration versus in 2024 when Peter Marks was running CBER? Should we be expecting a potential AdCom? Where do you stand on scale-up and materials here? Any expected pre-approval production costs that could impact the near-term R&D line? Thanks.
Yeah, absolutely, Brian. The Fabry program has been in progress for a number of years, so there's FDA correspondence that goes back several years as well as correspondence with the current administration. In fact, I believe there's correspondence confirming with current leadership the plan to submit the BLA based on the intermediate clinical endpoint of eGFR slope at 52 weeks, as well as for the confirmatory evidence to be eGFR slope at 104 weeks. Again, we were comfortable there based on the correspondence. In terms of predicting AdCom, I don't know. I can't really predict that. I think one of the things that's attractive here in our diligence is when you're dealing with things like eGFR slope, that's pretty objective. This is something that's calculated based on objective clinical data. So there's not a lot of room for interpretation. It's a pretty standardized calculation.
And I think when you look at the change in slope or the slope value from baseline to week 52, you see a consistent, steady benefit emerging over the weeks post-treatment. So that is to say, this 52-week finding wasn't the single one that looked good. No, these look consistent. You see exactly what you'd expect to see with an efficacious therapy, that you have a gradual improvement in function over time. So a lot of that gave us comfort that these data are clear, consistent, and interpretable, which, as you know, is always very important in considering the potential ways that the agency could think about the review.
Thank you. The next question will come from Faisal Khurshid with Jefferies. Your line's open.
Hey, guys. Thank you so much for taking the question. Two slightly related questions. We were trying to do the math on how large the market is U.S. versus ex-U.S., and it looks like the ex-U.S. market here is pretty considerable and larger than the U.S. market. Just wanted to see, is that true? And can you talk about the capability of filing this data package as it currently stands ex-U.S. and whether Sangamo had pursued any regulatory conversations related to that?
Yeah, sure. I just want to come back and finish answering the second part of Brian's question. Sorry, Brian, and then Faisal, come to yours about scale-up and production. I think one of the good things here is as part of all the PPQ batches, we're getting enough supply to be ready to launch this. We'll clearly look at any additional supply that would be needed ahead of launch or near time for launch. But as we said, I think we're pretty comfortable that this doesn't change any of our thinking about expense and our ability to meet our goal of cash flow breakeven this year. Faisal, to your question, sorry about that. Obviously, there's a large global market.
There's patients in the U.S., and then when we look at our global capabilities and the presence we have from both regulatory and commercial standpoint in Japan and Europe, Middle East, South Africa, Russia, Commonwealth of Independent States, Brazil, there's a lot of patients here. One of the things we'll be doing now over the next few weeks is really finalizing our launch sequence. What comes along with that is our thinking about regulatory planning. As we've said, not only do we have commercial capabilities in all these regions, we have experienced regulatory teams and regulatory expertise that could allow us to be successful in getting this across the line.
I know there were some discussions that Sangamo had in Europe and with European authorities, but again, one of the things we're going to be doing in our regulatory work stream here is understanding what data we have, what the regulatory path could look like, how do we leverage the U.S. data, how do we leverage U.S. approval for main patient programs, all the things we typically do in the PTC Global Rare Disease playbook.
Thank you.
Thank you. The next question will come from Joseph Thome with TD Cowen. Your line's open.
Hi there. Good afternoon, and congrats on the transaction, and thank you for taking my question. You kind of addressed this maybe, but can you just maybe specifically talk about the meta-analysis that I think the FDA wanted to see from Sangamo comparing their data to prior phase III's in the space and your level of comfort that that was done maybe appropriately? Then second, just on the milestones I think that are related, can you go into a little bit more detail as to what those are related to if they're accelerated approval or full approval, U.S., international? Anything you can do to provide color on that would be great. Thank you.
Yeah, absolutely. So, this was a single-arm phase I/II gene therapy trial. We found that the evidence here is very compelling for a number of reasons. One, you have the objective evidence of the improvement in the enzyme, the reduction in the substrate that deposits in different organs causing organ damage, and then seeing the clinical benefit in terms of renal function also objectively related. As you mentioned, Joe, there was a request in discussions with FDA to provide some context for the improvement observed in renal functions by way of having some sort of control or comparison of the treatment data. Again, this was very encouraging on several levels. First of all, the natural history of Fabry disease in terms of renal function decline is very well characterized. You lose renal function over time, and you have a negative slope of annual eGFR.
Here again, not only is there improvement here over what the natural history is, there's actually improvement. There's a positive slope over time. This also is quite differentiated from the other approved Fabry therapies, which slow progression in terms of loss of renal function, but there's still a negative eGFR slope. It's just less negative. Again, this is just in such stark contrast that it's positive. So the meta-analysis really tried to formalize this analysis. Again, as you expected, to us, it seems fairly clear here that you've got a group of folks who are negative slope, and then you have a treatment that's positive slope. To us, it was pretty clear-cut that this was a differentiated therapy, and we believe the team did a very careful and thoughtful job of doing the analysis. In terms of the milestones, there's two of them.
The first one is $80 million on accelerated approval in the U.S. The second is $20 million on full approval in the U.S. with no additional other regulatory milestones, no sales milestones, and no royalties.
Perfect. Thank you.
Thank you. The next question is going to come from Joseph Schwartz with Leerink. Your line is open.
Hello, this is Leona Nease on for Joe. Congrats on the update, and thanks for taking our question. Just a couple of things from us. What learnings from your prior gene therapy launches can you apply to ST-920? How much work do you need to do to activate centers and identify eligible patients? Also, can you clarify whether commercial product will be manufactured by the same CDMO as what was used in the STAAR study? Thank you.
Yep. Hi, Leona. Thanks for the questions. On your first question, look, I think anyone, there's not that many people who've gotten AAV gene therapies approved, but anyone who has knows that it's a pretty heavy lift. Not only do you have the traditional clinical issues, non-clinical issues, but the CMC manufacturing quality, all of that is super critical. And we have that same team here that brought the AADC product to PTC 's ability following all here, all brought that expertise to the assessment of ST-920, as well as having the confidence and continuing to work with the folks at Sangamo to get this across the line. In terms of commercial preparation, I think this is not gene therapy specific. This is what we do in rare disease, and I'll let Eric comment on that.
Thanks for the question. I think what we've been doing over the last decade or so is we have a geographic footprint that helps not only find patients, work with centers of excellence, but as gene therapy has evolved, we look for the value proposition. Our market access teams have been able to negotiate not only favorable pricing and reimbursement, but also ensure that patients are able to be treated across multiple geographies. As the previous question came up about how big is the Fabry market ex-U.S. is very important, and we have a geographic footprint that will be able to address that. Importantly, we also have the mechanisms such as name patient programs. Once the U.S. approval happens, we can begin that process in many of the countries to treat patients in Europe and Latin America, in the Middle East and Russia, and different places right now.
We're going to be applying a lot of what I think is the playbook that we have been doing for decades with the portfolio of drugs that we've had, and especially applying a lot of what we've learned about gene therapy in terms of getting patients not only on drug, but getting access to these treatments.
Leona, let me answer your other question about product manufacturing. As I'm sure you're aware, which is probably why you asked the question, a lot of gene therapies over the course of the development may have different manufacturers, different manufacturing processes, and this one did as well. But clearly, one of the most important parts of our CMC diligence was this idea to ensure that the product that's been used in trials, the product that's been used in the earlier parts of the trial, later part of the trial, and in the commercial product comes from processes that are comparable. Of course, we looked through the comparability assessments, the comparability analyses, and again, this was an area where our team got confidence that very common feature of gene therapies would not be an issue here.
Great. Thank you.
Thank you. The next question will come from Paul Choi with Goldman Sachs. Your line's open.
Hi. Good afternoon, and congratulations on the deal. Matt, I was wondering if you could maybe provide some framework for how you're thinking about potential pricing here versus multiple years of patients being on ERT. Is that maybe the right way to think about it? As you look at sort of historical sales estimates for ST-920, do you find these estimates to be reasonable, or how are you thinking about potential upside scenarios versus what had been sort of consensus estimates at the time? Thanks for taking our questions.
Yeah. Hi, Paul. Let me take the second one, then I'll turn it over to Eric to talk a little bit how we were thinking about pricing relative to the clear value proposition differentiation here. We, of course, saw some of the previous sales estimates from previous analyst coverages. I would say, look, I think one thing that has certainly evolved over time and one of the things that PTC, we believe, can bring to the commercial opportunity is really the global aspect of this. We're clearly aware from a commercial standpoint that there is a significant potential U.S. opportunity, and I think that's included in some of the previous analyst estimates, perhaps some has incorporated global as well.
But I think we really think about this as an important global opportunity, much as we're doing with Sephience and the ability to bring this to Japan, which is a pretty special rare disease market. Obviously, we have Europe and we have LATAM, we have all the different regions. So I think the opportunity and our team's demonstrated ability to execute here, I think brings even greater potential value here to the opportunity. Eric, do you want to talk a bit about access?
Yeah, Paul, thanks for the question. I think it all starts with differentiation. Pricing is going to be a very important component based on how we differentiate the product, the final label that we have, as well as the addressable population. We'll be looking at all these factors. As Matt said, the U.S. will be our primary market, but we also see Japan as a very important market where we can get premiums. I don't think it's a bad thing to actually look at what ERT is doing over a period of time and look at where the durability of the treatment could be. So that certainly is an option.
As we demonstrate the value proposition, particularly around durability around the kidney and heart functions, these are hard endpoints that Europeans really do like, and they want to see things that are going to be improving quality of life, replacement of various therapies, reduction in hospitalization and costs and infusions, things like that. So developing the value proposition in many of these markets, which are what I would call HTA or health technology-sensitive markets, is going to be part of our strategic goal as well. For us, really, we believe that pricing will be a factor of all of these things. So stay tuned. We believe this is a really important opportunity for us.
Thank you. There are no further questions in the queue at this time.
All right.
I would now like to turn the call back to Dr. Matthew Klein, Chief Executive Officer, for closing remarks.
Thank you all again for joining the call today. As I said, we are incredibly excited about this opportunity. It really fits very well with what we have articulated as our strategy to leverage our accomplished rare disease commercial infrastructure to accelerate short-term and intermediate-term revenue growth. I think there are some particularly unique characteristics of this opportunity that made it even more attractive to us.
We are able to generate, we believe, significant value creation here while leveraging the unique regulatory and commercial expertise that we have. We preserve significant firepower in terms of being able to continue to pursue business development as a component of our strategy of strengthening our product portfolio. And finally, we really look forward to an opportunity to bring something we believe could be a meaningful therapy to patients who really need one. With that, I thank you all, and I wish you a good evening.
This does conclude today's conference call. Thank you for participating, and you may now disconnect.