We can get started. Welcome, everyone. I'm Yigal Nochomovitz, one of the biotech analysts at Citi, and welcome to our Global Healthcare Conference in Miami. So our next session is with Ultragenyx. We have the Chief Medical Officer, Eric Crombez. Eric, welcome. Thank you for making the trip. We've been covering you for many years, and there's been a lot of progress. So maybe we could start out just at a high level. You obviously have a very important catalyst coming up, essentially imminently, with setrusumab. So before we get into the details of that, just kind of set the stage as far as what is the opportunity there. You had and are continuing to have a lot of success with Crysvita, another genetic disease. So talk about what the opportunity is in Osteogenesis Imperfecta and how you're setting up for a market launch there.
Yeah, great. And thanks for having me. So Osteogenesis Imperfecta is our near-term value driver. We've been talking about final data readout around end of year, and we've defined that as December or January. So we're certainly within that period now, and it's about as near-term as it gets. So Osteogenesis Imperfecta, also known as brittle bone disease, and I think really illustrates the disease and the opportunity. The only currently available treatment to really stopping these patients from fracturing with very little to no trauma is bisphosphonates. Those are used off-label in the U.S. and most parts of the world. The truth is, it's better than nothing, I think, as a treating physician making a diagnosis like this. With children and adults really fracturing on a very regular basis, multiple times a year, sometimes with no trauma, it helps. We certainly think we can do better with this antibody.
This antibody takes out sclerostin, which really affects the balance between osteoblasts and osteoclasts to build and break down bone as children grow and remodel, then as adults remodel. So we really think shifting the balance towards osteoblasts, having the ability to lay down more collagen, increase bone mineral density, and then the resulting reductions and fractures really will not only improve the fracture rate for these children, but quality of life. It keeps them from leading a very protected, sedentary lifestyle, allows them to become more active and not fracture. For us, for rare, it's a big indication. We think at least 60,000 patients in the geographies we cover. And really, for us, and really for anyone, a very unique opportunity to really repeat what we were able to do with the launch of Crysvita.
Similar type of bone disease, similar type of effort we would need to launch and support that program. And certainly, while Crysvita was a very, very successful launch, we do think with those lessons learned and the opportunity here with the Osteogenesis Imperfecta, we could potentially even do better.
Okay. So you've generated, obviously, a lot of data. You had data from Mereo, and now you have your own data. So maybe you can just kind of walk us through, summarize what that data is telling us and how that helps as far as looking at probabilities of success for what we'll get into the two studies, Cosmic and Orbit.
Yeah. So for us, this program did start with Mereo. They did a small adult study called ASTEROID. That study, while technically not successful for them, did provide a lot of learnings. And importantly, it provided us the opportunity to partner with them and bring this forward. So we started the development plan with Orbit. Orbit is a phase II/III study. So we designed that to be a seamless study, which did mean we needed to design the phase III part of that II/III study at the same time we designed phase II. So it was with the strength of that phase II data, 24 patients originally designed to understand safety better, pick a dose to take into phase III. That allowed us to take a fresh look at that phase III with that data.
It's what led us to plan for those interim analyses and now brings us to final data readout. With those 24 patients, we did see a 67% reduction in fracture rate from baseline. All patients did respond very well. All of them had an improvement in the biomarkers we're tracking, an increase in bone mineral density that did correlate and led to a decrease in fracture rate in all patients.
Okay. Can we kind of walk through what you've seen so far with the Orbit trial and how the design is different and what the goals are, Orbit versus Cosmic? Because as I understand it, we're going to get both of those very soon.
Yeah. So with the success of the phase II part of Orbit that immediately transitioned into the phase III part, we selected our dose. We brought that forward into phase III and enrolled an additional 159 patients into that study, two-to-one randomization setrusumab to placebo, and have been following those patients throughout. This study enrolled patients five to 26 years of age. And importantly for us, same entry criteria, same overall study design, same endpoints that we did in the phase II part of Orbit . So we weren't bringing anything unknown or untested into phase III. We did think with the results and the safety profile, which has been very strong from the beginning, we could go down to two years of age. And that's what really initiated, in part, the second phase III study, Cosmic.
Importantly, and what I'm looking forward to with Cosmic is the generation of a head-to-head data set of setrusumab compared to bisphosphonates. Bisphosphonates is not approved in most parts of the world. There haven't been really well-designed conducted phase III studies. So you're forced to do a meta-analysis on the effect of bisphosphonates. So if anyone wants to have a conversation on the effect, the value of setrusumab versus bisphosphonates, we'll now have a well-designed phase III data set to have a data-driven conversation on the difference between those two products. So in total, we'll be looking at really a full label, children and adults. We haven't talked about the different types, types 1, types 3, and 4. So a really full label between Orbit and Cosmic at time of launch with both being successful.
Do you need both of these studies to work, or are there ways where if one of them worked, you would have sufficient evidence for success? Can you just kind of talk through the differential thinking there as far as what you'd like to see or need to see to have a strong package?
Yeah. So I think, I guess maybe I'll start from a regulatory perspective. And I think with two phase III studies, you obviously have the scenario where both are positive. Two scenarios where one is positive, the other is not, and then the scenario where neither works. In the scenario where Orbit hits and Cosmic has positive trends but doesn't hit, you still have a very, very successful product. Orbit still gives you a very full label. What you would lose without Cosmic hitting statistical significance is you would likely lose the ability to claim superiority in the label. So you would still be having a discussion on the totality of data on Cosmic on the benefit of setrusumab versus bisphosphonates, but it would be very hard to make that claim in a label without hitting statistical significance.
In the scenario where Cosmic is positive, Orbit technically misses statistical significance, but again, has positive trends. The totality of the data tells you this drug works. You still have a positive phase III study, and that's what you need to have a path forward with the FDA. So certainly, you're going to depend on hitting statistical significance in Cosmic . That's your positive pivotal trial. You're going to want Orbit to still have very strong trends, to still be able to see enough evidence from the totality to have a compelling discussion with the agency to still achieve a full label there.
Okay. Now, given you're comparing to the bisphosphonates with Cosmic, what is the expectation as far as the benefit that bisphosphonates can bring to the table? And given the data that you'd spent a little bit of time talking about before, the early data, what's the sense as to how much better you can do on AFR?
Yeah. So it is always challenging to try to understand the benefit of bisphosphonates. When we really kind of look at all of the data out there, try to do a meta-analysis, if you will, we're thinking that the benefit of bisphosphonates is maybe somewhere around 20%. I've never heard anyone attribute anything near 30% treatment effect from bisphosphonates. So that's kind of the ballpark we're working in. Looking at change from baseline for the 24 patients enrolled in phase I/II, we saw consistently a 67% fracture reduction rate, which is obviously great, and no one's going to debate you on clinical significance of that. We did power the study with the 159 patients enrolled in the phase III part of Orbit. That gives us greater than 80% power to detect at least a 50% treatment effect.
So that does give us some room between 50% and 67% for something unexpected to happen, something we couldn't plan for or control for to happen. Certainly clinically significant. I haven't heard, and I haven't heard anyone tell me of people they're talking to that that wouldn't be meaningful to them. I think 30%-40% is kind of the lower range of what I've been hearing physicians say would be clinically meaningful to them. But certainly, with that consistent above 60% fracture reduction rate, we're expecting to be firmly within that clinically meaningful range for Orbit .
Okay. And as you know, there's been a ton of debate as far as the interim analyses, which you did, the first one and the second one. And there's this back and forth as to whether, from a statistical perspective, whether if they miss, they miss, but it shouldn't impact the final. What's your view on that? How do you think about this final analysis in terms of the power and whether those two data points, which could have been very close and just missed by a hair's breadth, we don't know, maybe we'll know at some point, how does that impact your thinking or does it impact your thinking as far as the ultimate likelihood of success?
Or is it just, that's the way the study was designed, and that's how it was done that way intentionally to give you those looks, and you didn't necessarily know they were going to hit or not hit?
Yeah. No. And I think, to be honest and to be fair, I think in retrospect, I wouldn't support doing interim analysis one. I think, again, a lot of, well, this really was driven on the really compelling data we saw at a phase II. And it was a surprise to us. And we certainly thought with those 24 patients, these types of results with 159 patients enrolled two to one, that maybe we could do even better. So I think we can kind of set IA1 aside. Certainly, a lesson learned there. But focusing on IA2, we did see a very good probability of success. To me, that probability of success hasn't changed. In retrospect, I would still do IA2. Having a positive data readout, being able to file and gain approval that much earlier would have made a difference to the NPV of the program.
And importantly to us, and I'm sincere in this, we have always been concerned about the patients randomized to the control groups for both studies who are out there fracturing, and we don't want them to fracture any longer than necessary. So if we could have been successful at IA2, gotten all patients on setrusumab, that would have been great. My guess, and I don't know, is that we came really close, but with an alpha spend of 0.01, we just didn't hit it. And certainly, if it was 0.05 or 0.02, maybe we would have been successful. So when we were modeling our probability of success for the interim analysis, our probability of success for final data readout, we took that all into account. We still like the negative binomial regression model. We think that's the right overall study design.
We did take the opportunity to look in a blinded manner at the total fracture number we saw at IA2. We can model out what we would expect based on phase II results to see in the treated patients. We can model out from natural history from patients randomized to control in their baseline what we would expect to see for fracture numbers. It is what we wanted to see going into final data readout. So the truth is our probability of success, and my confidence hasn't changed since IA2.
Just to make sure I understand correctly, so you looked at the blinded fracture rate at IA2.
Yes.
It looked consistent with what you would believe would support a positive outcome at the end of the study or at some point.
Correct. At end of study.
Did you do that at the IA1 too or no?
No. So I didn't look at IA1. Again, IA1, it was a high bar. I think at that time, people said it was fine. People weren't really necessarily expecting it to hit. I think we were disappointed to miss IA2, and it was one thing we were confident that we could look at without introducing bias, without having the FDA or anyone else be concerned that we are introducing bias. So it was one thing we thought we could look at.
Okay. And now speaking, of course, an important question, you referenced the NPV of the product. Assuming you hit on final, and you talked about scenarios, but you have sufficient data to support filing the BLA, there's an important deadline potentially in the fall of 2026 with the unclear situation with the PRV program. If it gets renewed, it gets renewed, great. But are you angling to get that filed before so you could potentially have that third PRV, which could be valued as much as the latest trades? It's $150 million.
Yeah. So you mentioned the third. So certainly, I'm happy to come back to it, but we are confident with Sanfilippo and GSDIa.
Yeah. We'll get to those.
We will be comfortably within that end of September deadline for approval. OI, that gets hard.
Right. It's hard.
It gets really tight. So the one thing we have said is that given the importance of OI to us overall as a company, given the value driver there, we are not going to rush, cut corners, if you will. We're not going to compromise the quality of that data package to hit that date. So we certainly have risen to the occasion. I think that was exemplified by what we were able to do with the Angelman Aspire enrollment and try to get things done very, very fast. Certainly, there are tools, and we are very seriously looking into the use of AI to really analyze big data sets, do first drafts of documents, and can that give you a head start?
So we're looking at that, but it is fair to say that it's ambitious to try to hit approval by end of September, and we will not compromise the quality of that file.
Okay. But just to reaffirm, the data for both of those studies are end of this year. Is it definitively end of this year, or could it be like beginning of January or?
Well, so we've defined, and we've been very clear, and we're going to be very clear while we're out here talking that we've defined end of year as December or January. So certainly, we're in it. So I guess to me, it's about as near- term as we can get.
In the locking, have you locked the data? Are you still in the, what, exact step are you in right now?
Yeah. So we have acknowledged that the last patient has had their last visit. And we have this conversation internally too with the executive leadership team because it always sounds like a lot of time. But when you map out how long it takes to chase down long lead time labs globally, chase down every query, sometimes queries trigger another query, and everything has to be chased down. And these are two phase III studies. So once you map it all, it takes this time to do it. So we haven't said exactly where we are in the process, but we are in the process.
Okay. All right. Well, let's talk about some of the other programs because you started to mention the other. So just tell us about the other PRVs. So those are more, I don't know if I should use the word assured, but likely or highly likely.
Yeah. No. And I think for me, when I kind of talk about our lead gene therapy programs for Sanfilippo and GSDIa, I'm actually not positive which one is going to come first because we filed for Sanfilippo. We did receive the complete response letter. But with that response to the CRL, it's up to a six-month clock. It's not the full eight-month review period. We've said we're going to refile that in the beginning of next year. We have said that we started the rolling BLA for GSDIa, and we would finish that this month. So that starts an eight-month clock. So both of those would give us PDUFA dates comfortably within that last day of September deadline to achieve the PRVs. I'm not sure which one will come first. The PDUFA dates should be very close together.
But if there's an upside to this, any CRL, but the CRL for Sanfilippo is that the FDA makes it explicitly clear what they require for refiling, and they will not accept your package without really completing that to the letter of the letter. So we have a lot of confidence in exactly what we need to do that, and we're on track to do that. And then it really did inform the manufacturing CMC for GSDIa because both of those drugs are made at our gene therapy facility outside of the Boston-Cambridge area in Massachusetts. The clinical data for both Sanfilippo and GSDIa has always been very strong. The FDA has actually remained and gone out of the way to be complimentary on the data set for Sanfilippo. So with the strength of the clinical data at the end of the day, that's what the label is.
That's what the approval is. We definitely needed to work through the CMC and other findings, but to me, really de-risk those programs and makes them both with a very high probability of success.
I mean, without getting into too many specifics on manufacturing and, of course, trade secrets, but just at a high level, what were some of the learnings from the CRL for 111 that you've fed into 401 that kind of improved the quality for that one?
Yeah. And we had the opportunity. We took the opportunity, and it was accidentally during COVID to build from a green site that new manufacturing plant from the ground up. So any findings, any learnings from the Sanfilippo CRL that has to do with the facility itself exactly is applicable to GSDIa. And we knew all of it was fixable. We just needed to take the time to complete everything.
Okay. Can you give us a snapshot of the market opportunities for both of those, please?
Yeah. So for Sanfilippo, we've been a little softer on patient numbers with that. We do think it's a little less well- understood. It is a smaller rare indication. So we've been saying between 3,000 and 5,000 patients within the territory we cover. GSDIa, a little larger at 6,000 patients. So smaller compared to OI and Angelman, but I think important. And to me, if you think about as a leg for the organization going forward, not to discredit or set aside what we've done commercially so far, but OI being a leg, Angelman being a leg, collectively, the gene therapies can be another leg for this organization. And with Sanfilippo specifically, looking at what makes a successful gene therapy and what doesn't, I don't think it's that hard or that complex.
To me, it goes back to unmet medical need and real unmet medical need and not kind of hand waving there, but it's really these patients without any therapy or things that really don't work, and to me, the comparison is SMA. I mean, I think Sanfilippo is directly comparable with the unmet need and with those patients really stopping developing between two and three years of age and then really starting to lose ground with death in their teens or early 20s, really high need, and there's no motivated family or parent than a child with Sanfilippo, so I do think that'll be a very successful launch. GSDIa may be just a little bit below that with unmet medical need, but these patients are still dependent on cornstarch to avoid hypoglycemia, and that's hypoglycemia that can be life-threatening, especially in the childhood years.
So again, we think the right programs to bring forward first for our gene therapy pipeline.
You had a lot of interesting data on the cornstarch and how it evolved was interesting as far as the greater reductions in cornstarch as people became, as I understand it, more comfortable and more confident in the effect of the gene therapy. Is that basically correct? Can you kind of summarize that data and how that evolved? Because I think that's an important aspect of the value proposition.
Yeah. No, absolutely. And we talk about the reduction of cornstarch, and to me, it's always important to talk kind of in full sentences because it's the reduction of cornstarch while maintaining good glucose control. And that's what's important there. That's what gets these patients in trouble. And we really saw that clearly illustrated in the phase III trial because it was a blinded phase III trial. That is still the gold standard. That really is the expectation for the FDA: to do blinded phase III trials. These patients are told at diagnosis, parents, children, and then once these children grow up to adulthood, they cannot miss their doses of cornstarch. They need to wake during the night to take cornstarch because it can be life-threatening. And now you're telling them you're in a blinded study.
I don't know if you've been randomized to gene therapy or placebo, but I'm going to try to take your cornstarch away, so the families were afraid. The treating physicians were hesitant, if not afraid, so in the beginning of the phase III, it was gentle titration off of cornstarch because it was blinded, and they were really afraid of that real risk of hypoglycemia. Once we managed through that and we got into the open- label part of that, everyone knew they were on gene therapy. We saw really great increases in reduction of cornstarch, much better results, and most recently, we had a new cohort of patients in Japan to support the approval in Japan. It was a defined cohort of patients. We had learned everything from phase II, phase III. All of those patients quickly came off of cornstarch. They're doing great.
They're feeling fine, great glucose control. So we were able to take all of those lessons learned after many, many years and really show when we can do this in an unblinded fashion and apply these learnings, we can do it very quickly, and these patients can do very well off of cornstarch. So again, really great efficacy, and then the safety has held up very, very strong as well.
Okay, so that one is getting filed imminently.
This month.
This month. And then 111, Sanfilippo, what's the exact timing?
Yeah. We've said beginning of year, but we've also said comfortably within the PRV window within six months. So it gives us a couple of months, but it's the beginning of next year.
Okay. And let's stay on gene therapy. There's another one, which is also super interesting, the excess copper storage disease, Wilson disease. So 701. So summarize that. You're now in the pivotal study or you're close to it, Cyprus.
Yeah. So Cyprus is a seamless phase I/II/III study. So that seamlessly goes through the phases of development. And we've taken our time because we've learned. And what that allows us to do once we get to what's the equivalent of the phase I/II part of it, this is similar to what we did with Orbit. As long as we feel comfortable with safety, the safety holds up with what we've seen so far, and we have the dose. And in this case, really the immunomodulation regimen we want to bring forward to the phase III part of this trial, we can seamlessly move through and not having to go through into phase II, not needing to do scientific advice in Europe. It saves you honestly about a year, and you're not standing up a whole new study. So overall, it does save time.
We took the opportunity with the data we saw out of the original cohort, which did have a good number of patients coming off of their chelators, doing very well. But here is exactly what I was talking about with successful versus something less than successful for gene therapy. With chelators doing a reasonably good job with Wilson disease, we want to make sure we're really bringing forward a gene therapy at a dose that can get the majority of patients off of chelators, that we're really offering something better. I mean, certainly with a gene therapy, if you're getting to the heart of the disease, the gene affected here is a transporter that either loads copper onto ceruloplasmin, which allows it to traffic normally in the body, or pumps it into the bile system for excretion out of the body.
That gets at the heart of the disease versus chelators, which has to wait for excess copper to leak out of unhealthy hepatocytes, inflamed hepatocytes, in order to bind that copper and pull it out of the body. But we want to see the majority of patients coming off of chelators before we move into phase III.
Okay. And you're getting close to that goal or you're at that goal or?
Yeah. So that's what Cohort 4 is. We went up on dose and increased the immunomodulation to include rituximab and sirolimus. It's an unblinded study. So we have not done a formal full analysis of the data, but I like what I'm seeing so far from those patients. And we'll see results from that new cohort next year.
Okay. And just kind of go into the immunomodulation a little bit more. I mean, the reason to choose rituximab and sirolimus, what was the rationale for that? And what are you aiming to? Is it just liver injury or what exactly are you aiming to prevent?
Yeah. And so it's this whole, I mean, yes, we can talk about safety events that have been important particularly for muscle when you're in those types of dosing. But we're really now, for what we're doing here, talking about liver-directed gene therapy. And the increase in LFTs we see here, for me, are really a concern, something to think about for preserving efficacy and not really something we're worried about as a true safety event. So for GSDIa, OTC, Wilson, we have seen that increase in LFTs with the gene therapy liver-directed. And to me, if you have an increase in LFTs, you're telling me that the immune system is attacking these hepatocytes that have taken up the transgene and they're damaged, and you're possibly losing the gene therapy because you have these LFTs leaking into the bloodstream. And steroids, while helpful, do not completely eliminate it.
So if we can fully really damp down that immune response, retain as much of the transgene within these hepatocytes as possible, you're going to see better efficacy in the near- term. I also think it's going to help with durability in the long- term as liver cells divide and grow. So there's a lot of different combinations, a lot of different B-cell and T-cell depleting drugs out there. I think a lot of people like this combination. It's being used in other cases. I think at a certain point, you need to do your studies and figure out what's best and then do the experiment. But we're happy with the results that we've seen so far with this combination.
Is this layered on top of a low dose, like 5 mg prednisone or not?
Yeah. So this is in addition to the several-month-long course of steroids.
And then is this the similar regimen for the other programs you mentioned for 401 and OTC?
Yeah, so we have not introduced this into GSDIa and OTC.
I didn't think so. Yeah, I didn't think so.
I mean, we could if we needed to.
Yeah, why not?
I think we want to do the experiment with Wilson. I think we want to make sure this is the right combination. It's safe. It's the right thing to do. I do think this is certainly worth going up on dose with Wilson and the better immunomodulation, it should be at least additive, if not synergistic, to really get the best efficacy possible. We'll take these lessons learned.
But there's nothing you saw for OTC and 401, there was nothing you saw in the liver signal that suggested that would have been necessary.
No, but we're still seeing some LFTs, and again, anytime you're seeing a rise in LFTs, I'm seeing an immune response that could be better controlled. Maybe it's not necessary in these diseases, but I think it's the right thing to do to continue to look at ways to optimize all of these gene therapies.
Okay. I mean, sirolimus is quite a strong immunosuppressant. There's been some concerns around opportunistic infections. Is that a worry or is that the way you're doing this is that you don't expect that to be an issue?
Yeah, it's not a worry. I mean, I think that is why it's been hard for a lot of people to move away from steroids because steroids are a blunt instrument and work on really all parts of the immune system, but that also makes them a good choice. And yes, all of these other immunomodulating drugs have their own benefit-risk profile, and some of them can have some safety findings, even if rare, that I don't think we need to worry about, but we need to understand and study them in studies. So doing this in a well-controlled design phase III trial where you're following these patients very, very closely is a right place to introduce this and learn.
And if it's helpful and it does what you intend, would it be something you'd layer in post-approval on some?
It's possible.
Potentially.
Absolutely. Yeah.
Okay. OTC, that one is getting close to data. Tell us just the quick timelines on that one.
Yeah. So that's also fully enrolled, that phase I/II part of that study earlier this year. We'll be looking for first ammonia data readout earlier next year and then looking for a response with the patients who are fully able to come off ammonia scavenging drugs later. It's the second step.
Okay. Now, if we were having this conversation five or six years ago, we would have started with 102, but let's do the 102 questions now.
Probably become late Q1 or Q2. We'll be back to Angelman, which will be good. We'll come full circle.
Okay. But you are getting closer. I mean, isn't the phase III Aspire study enrolled now? So kind of just walk us through the design of that one, please. And then the other one is the Aurora trial, which is just starting, if I'm not mistaken.
Yep.
So how are those different?
Yeah.
Goals of each?
Yeah. So Aspire leads, and Aspire really as a phase III study could stand alone. And again, similar to OI, we don't like to and really don't bring untested things into phase III. So to me, most importantly for phase I, II, we were studying patients with full deletions. So that means these patients are making no UBE3A. That means that yes, they're going to be severe, but also very homogeneous in their expression of the disease. So it's going to give you consistent results and clear signals in your phase III study. So Aspire patients with full deletions, but certainly and importantly, and we would never want to leave out a meaningful segment of patients. And patients with other genotypes, missense mutations, uniparental disomy, imprinting defects make up somewhere between 20% and 30% of the total patient population.
So we brought along Aurora as an open-label basket study to evaluate this AS in that group of patients. So with the two studies together, have a very full label of patients affected with Angelman.
Okay. So the endpoints, can we walk through that? So you had explored your own sort of novel endpoint at one point, this multi-domain endpoint, and you had some conversations with the FDA, and they steered you in, I believe, a more classical direction to look at the Bayley-4, if I'm not mistaken. So just walk us through what the endpoints are and what you want to see on those to have a really strong data set.
Yeah. No, and I think, I guess potentially where we're going next is and then the comparison to what Ionis is doing. And I think it's important for us to understand that we're both going forward with primary endpoints out of the Bayley, cognition versus expressive communication, both evaluated by the Bayley. You need to choose your primary endpoint. You want to power your study based on the primary endpoint and obviously be successful there. When we looked at the results from our phase I/II study, we took the opportunity to enroll a total of 74 patients. So for us, for rare, that is a lot of patients in phase II because we wanted to make sure we got dosing right and we understood what primary endpoint was best to bring forward because it is neurology and neurology is always hard.
The truth is we could have made other choices from language, behavior, gross motor, etc. Cognition looked best to us. I also like cognition because it is foundational to the other skills you learn, like language, behavior, sleep, gross motor. So you need that improvement in cognition as a foundation for all of those additional skills. Obviously, Ionis made the choice to bring forward expressive language, and that's what their results must have shown them. The truth is if we're both successful in our primary endpoint, no payer, no parent, no treating physician is going to care, as long as we have the same data set, whether it was primary, secondary.
So if we both have results from the Bayley on cognition and expressive language and then the other tools for the other endpoints, and you can look at the data head to head, no one's going to care what's primary, secondary. You just need to make sure you win on your primary for the FDA and other regulatory agency perspectives.
Okay. And what is the filing strategy? I know you don't have the data yet, but what's the strategy? Aspire leads, as you said. And Aurora is supportive or does it come later or is it just?
Yeah. So Aurora is open- label. Again, you do want that gold standard phase III trial, blinded controlled study, which Aspire is. And then with Aurora, foundationally, you need to show that it is safe in these additional patient population. And then you can bridge with the safety and efficacy data you generate in those patients. You can bridge back to Aspire, and the results we generate there to really go for a very full label and able to treat all patients.
So if they both look good, you would hope for the deletion and mutation?
Yeah. Our plan is for a full label. And I think, again, it's important because I would never want to be in a scenario where we have this really successful drugs and then it's limited to patients with deletions. You're excluding these other patients who also have Angelman and could benefit. So our plan is for a full label.
Two other important topics. One is, of course, pricing of these. I know Emil has talked in the past about pricing, not necessarily to maximize price, but to maximize access and to provide good value for investors, but also good value for physicians and for patients. So just broadly, can you talk about how you might think about pricing some of the ones we've talked about, the gene therapies, setrusumab? And then also with the FDA and the push to sort of accelerate some of the rare disease approval timelines, how much of that is intersected with your direct dialogue with the agency as far as advancing some of these programs and gene therapy on an even faster timeframe?
Yeah. I mean, so I guess we're in the process for Sanfilippo. I mean, that original filing still is active and we'll get that response in. And then they have, per PDUFA, up to six months to review. They can certainly do better than six months. We'll see. With GSDIa, that's a standard priority review. They can always go faster. I will say, particularly the patients who are really, truly doing the day-to-day work, they've been very engaged. They've been very responsive. We have had high-quality interactions with people who truly understand these diseases, understand our filings. And again, it was nice to see at our most recent meeting with Sanfilippo that they remain very complimentary of the clinical data, and that's been important. We'll see.
We certainly know that they're all very busy and stretched, but certainly if they can beat those PDUFA dates, great.
Okay. I know you're not the CFO, but anything you want to just quickly say, snapshot on the financial situation of the company? You had the recent monetization deal, obviously, with OMERS for Crysvita. Anything you want to add there?
Yeah. No, I mean, I think from what I've heard, people have thought that was a good deal. The terms were good. Certainly, not having to start payments until January of 2028 gives us room to benefit from that revenue during that period. We've talked about achieving profitability within that timeframe, and that's important to us. So it was non-dilutive. We didn't have to make any decisions dependent on the stock price on any given day. And I think a lot of it was with the CRL for Sanfilippo that did push out the monetization of the PRV. So with that type of opportunity, which was a very competitive opportunity and a competitive process there, we thought was the right deal at the right time to allow us to do what we need to do.
While we always want to be disciplined and mindful, we are looking forward to launching Sanfilippo, GSDIa very close together. OI will be very close behind that. And then with data for Angelman coming in the second half of next year, it's going to be, in a very, very good way, a very busy, transformative time for us.
All right. Thank you very much, Eric.
Right on the nose.
Covered everything.