Q2 2025 Ultragenyx Pharmaceutical Inc Earnings Call and Business Update
Good afternoon and welcome to the ultragenic, second quarter, 2025 Financial results conference call. At this time, all participants are in a listen-only mode. At the end of the, the prepared remarks, you will have an opportunity to ask questions during the Q&A portion of the call.
It is now my pleasure to turn the call to Joshua, Higa vice president of investor relations.
Thank you. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx cam. Joining me on this, call are AML cacus chief executive officer and president, Eric Harris, Chief commercial officer. Howard horn, Chief Financial Officer and Eric, crombez chief medical officer. I'd like to remind everyone that during today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties and are actual results May differ materially.
Please refer to the risk factors discussed in our latest SEC filings. I'll now turn the call over to Amor.
Thanks, Josh and good afternoon everyone.
In April 2025, we marked our 15-year anniversary of the company. Over that time, we've taken 4 programs all the way through approval, and multiple regions, and added a fifth that we are commercializing outside of the US.
Now have 53 clinical programs fully enrolled or at the belay submission stage and over the last 15 years. I'll Genex has been the most productive rate of these company in the industry across a broad range of modalities and therapeutic areas.
through the first half of 2025, continued, this moment with meaningful progress across our larger programs,
I'll begin with ux 143 ceitus map for our our fully human monicon, antibody for the treatment of osteogenesis imperfecta.
The orbit and Cosmic studies are continuing to the final analysis that will occur around the end of the year.
Well, I hope the studies might have stopped early at the interim time point last month, we remain confident in completing a successful study.
We're pleased to see profiles is as expected and that after looking at the day, the DMC recommend, we continue to the final analysis.
As we head to the final analysis, the continued treatment is basically should further strengthen bones of the treated patients, the additional 6 months of treatment for the treated subjects.
Along with the larger P, value threshold of 004 will help power the final assessment
We look forward to un blinding the phase 3 data sets and sharing the results.
Around the end of the year.
Now based on all the data we've seen in Phase 2. We're confident, the ux 143 will be a transformational treatment for pediatric and adult patients with osteogenesis. Imperfecta the combination mechanism of building bone, and reducing excess. Resorption is exact at the exactly the sites in their body where they need more bones. Will increase bone strength and reduce fractures.
While at the same time, improving overall bone health.
In addition to reducing fractures we're encouraged by the functional effect, we are seeing on increasing physical activity, ability.
It speaks to the long-term potential for this treatment.
Now shifting now, to GTX 102, our antisense of the nucleotide or ASO for the treatment of anger and syndrome.
GTX 102 received breakthrough therapy designation from the FDA in June.
BTD, aims to expedite the development of a review of drugs that are intended to treat serious or life-threatening diseases.
And whose preliminary clinical evidence indicates that the drug May demonstrate substantial improvement over existing Therapies.
Historically, it seems like there have been relatively few breakthroughs and designations granted in the field of neurology, because it can be challenging to demonstrate a meaningful potential clinical effect on neurologic disease symptoms.
But for G takes 1 and 2, we have been able to do that.
The BTD designation was obtained based on Phase 1 2, study data and 74 patients with a full maternal eb3a doing, deletion that showed consistent developmental gains with rapid sustained and continued improvements across multiple symptom. Domains, when patients have been on therapy for up to 3 years.
For GTX 102 the magnitude and durability of our Phase 1 2 Data. Indicate our ASO is meaningfully improving the lives of patients who have this neuro developmental disorder.
Last week, we also announced a GTX 102 phase 3 study Aspire completed enrollment ahead of plan with 129 patients in 7 months.
The interest for investigators and patience helped Drive the rapid enrollment. But I also applaud our team for their efforts to expeditiously enroll this study.
We're thankful for the support from the patient communities and investigators who helped to succeed our expectations.
We're now on track to read out, phase 3 data from this 48 week study, in the second half of 2026.
Now, switching to our commercial progress of the first half of 2025, our commercial teams continue their trend of delivering, double-digit, Revenue growth,
The 306 million in total revenue across the first 2 quarters represents, 20% growth versus the prior year and keep us on track to deliver 640 to 670 million of total revenue this year.
Graffiti is continuing to grow in line with our expectations from royalty, Revenue US and Canada and product Revenue in Latin American turkey.
And met cevey.
Also, continue contribute to our top lines. Each of these launches are progressing. Well,
I'll now hand it off to our commercial officer. Chief commercial officer Eric Harris to give us some additional details on his team's reason performance.
Thank you, ammo and good afternoon everyone.
This is ammo. Mentioned my team is continuing to successfully commercialize 4 products across the globe.
Starting with Chris Vita and Latin America. And the second quarter, our team generated, approximately 50, new start forms that led to approximately 50 patients on reimburse therapy.
We now have approximately 825 patients on Commercial product in the region as the team continues to exceed our expectations for Chris furrh.
Continue to receive positive feedback from healthcare providers. In the region, who tell us how much better their patients feel when on crispa which has led to an increasing number of doctors writing prescriptions for multiple
Patients.
We expect growth in the region to continue.
Following the successful negotiation of reimbursement from the Brazilian and Mexican authorities. The 2 largest payers in the region and continue to expansion in other Central and South American countries.
I'll now shift to Christina in the United States and Canada.
We are a partner Kawa Kieran. Has been leading commercialization for Chris Vita since the transition in April 2023.
Revenue in the second quarter, 2025 was supported by increasing new, start forms and new patients on reimbursed therapy.
we expect 2025 US and Canada, Chris Vita Revenue, to continue growing
As they work to identify new pediatric and adult patients with XLH.
And convert them to treatment.
Moving on to the Jovian in the United States, growth of new start forms in the second quarter. Continue to steadily increase.
Consistent with the patterns we have seen in Prior quarters.
Our team generated approximately 30 New Start forms and added approximately 30 new patients to reimburse therapy.
This brings the total since launched in 2020 to approximately 600 patients on reimburse therapy.
The split between pediatric and adult. Patients continues to be approximately 6, 65% peeds and 35% adults.
The total number of prescribers also continues to grow.
With a total of approximately 270 unique prescribers, at the end of the second quarter.
But the Jovi across the Emir region, there are approximately 280 patients treated under name patient cells across the region.
The majority of demand is from France, but we are continuous.
But we are seeing continuous growth across the Emir region including Kuwait, Saudi Arabia and Greece.
The demand for this product is quite strong across this region, especially given the fact that we are not actively marketing, the therapy.
And simply responding to name patient requests.
Before our clothes, I'll make a few comments on fisa, which we began commercializing in territories, outside the US with formal reimbursement, approvals in just the last couple of years.
In the air region. We now have patience on reimburse therapy from nearly all of the major countries and we have added almost 100 patients since the beginning of the year. With a total of total of approximately 285 patients across 15 countries.
We continue to successfully navigate the country by country pricing negotiations.
And respond to name patient treatment requests, across the whole and Mia region.
Our team in Japan continues to build on the launch momentum following the pricing and reimbursement, approval that we received last year.
In Canada, We are continuing pricing negotiations with government Health authorities, and recently added.
Younger pediatric patients to the label.
Over time, we expect if keys are Revenue to contribute, more meaningfully to the total revenue, as we continue to successfully launch. This transformative product for hofh patients with, with its high potency, due to a novel mechanism of action.
Regardless of background therapy.
as I have mentioned on previous earnings calls,
we continue to expect some quarter to quarter variability in Revenue, primarily due to uneven ordering patterns for Chris Vita and Latin America.
But we remain confident in the growing, underlying demand for all of our products around the world.
With that I'll turn the call to Howard to share more details on our financial results and guidance.
Thanks, Eric, and good afternoon, everyone. I'll focus on second quarter 2025 financial results and guidance for the year.
Starting with total revenue.
in the second quarter of 2025, we reported 166 million representing 13% growth over the second quarter of 2024
4.
Crispa contributed 120 million in the second quarter, including 79 million from North America. 35 million from Latin America and turkey and 7 million from Europe.
The Jovi contributed 23 million consistent with its expected steady growth trajectory.
At Kiesza contributed 15 million as demand continues to build following launches in our territories outside of the United States.
And mepsi contributed 8 million as we continue to treat patients in this ultra rare indication.
Total operating expenses for the quarter were 274 million, which included R&D expenses of 165 million, sgna expenses, of 87 million, and cost of sales of 23 million.
Operating expenses included, non-cash stock-based compensation of 39 million.
For the quarter. Net loss was 115 million or 1.17 cents per share?
As of June 30th, we had 539 million in cash, cash equivalents and marketable securities, which included 80 million of net. Proceeds raised through our ATM facility.
For the 3 months, ended June, 30 2025 net cash, used in operations, was 108 million and in total for the 6 months, ended June 30 2025, it was 275 million.
We now expect 2025 net cash used in operations to modestly increase compared to 2024.
Primarily driven by timing delays associated, with ux 111, DTS 401, and ux 143.
We will remain on our path, or excuse me, we remain on our path to GAAP profitability in 2027 and will continue to focus on growing revenues and rigorously prioritizing our spend, including stopping and delaying certain expenses prior to upcoming potential commercial launches.
Shifting the revenue guidance for 2025. We are reaffirming the guidance, we provided in February and May
total revenue is expected to be between 640 and 670 million. Which represents 14 to 20% growth over 2024.
Chris Vita revenue is expected to be between $460 million and $480 million, which includes all regions and all forms of Chris Vita revenue to Ultragenyx.
This range represents 12 to 17% growth over 2024.
The Jovi revenue is expected to be between 90 and 100 million which represents 2 to 14% growth over 2024.
With that, I'll turn the call to our CMO Eric crombez who will provide operational updates on the clinical programs.
Thank you, Howard and good afternoon, everyone.
I'll start with GTX 102 for the treatment of Angelman syndrome as a moment mentioned. We completed enrollment in the phase 3 Aspire study ahead of initial expectations enrolling 129 patients across 6 countries in a randomized. Controlled study in 7 months as a remarkable accomplishment, this would not have been possible without the incredible dedication and support from the Angelman Community study site teams and investigators. The Accelerated enrollment of the phase 3 study, underscores the urgent need and strong desire for an effective treatment for these patients.
We will now shift our enrollment efforts to the Aurora study, which will target younger and older patients with other genotypes.
This study is open-label and intended to provide supportive information on safety and efficacy. In the expanded patient population. The protocol has been finalized and we expect to begin enrollment in the second half of this year.
data from this ongoing study will be included in approval filings after successful, completion of the phase, 3 Aspire study,
shifting to ux 111 for the treatment of MPS 3A or Saint Saint Salo syndrome, type A
We received a Complete Response Letter for our BLA filing last month, and we are actively working with the FDA to resolve the observations through a plan type—a meeting that should lead to an understanding of what is required for refiling of the BLA.
Once resolution has been achieved, we expect to resubmit the bla and anticipate in up to 6 month review.
I think it's important to note that the clinical review had been ongoing and that the FDA acknowledged at the late cycle review meeting that the neuro developmental outcome data is robust and that the biomarker data provided additional support of evidence. The co crl did not note any review issues related to the clinical data package nor comment on the clinical inspection.
Clinical and biomarker, endpoints and safety to be included in the resubmission.
Next, DTX-401 for the treatment of Glycogen Storage Disease, Type 1A.
Where we are now on track to submit a bla. In the fourth quarter of this year, we have been working on the bla over the last couple of quarters and the non-clinical and clinical sections are ready to submit. We want to proactively resolve any relevant CMC and facility questions that derive from the ux 111 crl that could possibly impact the DTX 401 submission before we finalize the CMC section of the bla
We expect to resolve the observations of the next few months. And then finalize, the bla submission.
Finally ux 701 for the treatment of Wilson disease. Recall we are in the dose finding stage of the study and in cohort 4, we are evaluating a dose of 4313. All patients in this cohort will receive immuno modulation therapy with vertex and take. Relyus, in addition to the prophylactic oral cortical, steroid regimen, patients in quartz 1 through 3 received,
Enrollment in dosing and cohort 4 is underway. And we expect to complete enrollment in the next month or 2.
Um, I'll turn the call back to AML to provide some closing remarks.
Thank you, Eric. I'll quickly recap the milestones and catalysts over the second half of the year.
For ux 143 and osteogenic imperfecta, we expect to have Topline data from the final analysis of the orbit and Cosmic studies around the end of the year.
For Dia, G takes 102 and angels and drum will continue. Treating patients in the 40 week. 48 week, Aspire study and we'll begin enrollment in support of Aurora study in the second half of 2025.
For ux, 701 and Wilson.
We'll complete enrollment of the fourth cohort in the next couple of months. We expect to make a determination on the Stage 2 dose in 2026.
For ux1 11, in San Philip syndrome, we are working toward a type. A meeting with the FDA to get agreement on our plan to resolve their observations.
Which we believe we can address following this, we would work through the agreements that resubmit the pla, which we followed by a review period that could take up to 6 months.
Incredibly fulfilling and yet the best is still to come. Well, the news of last month did delay, our approval for ux1 11 and didn't accelerate the oi program. We're confident in the strong.
27.
With that, let's move on to your questions. Operator, please provide the Q&A instructions.
Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press start to to remove yourself from the queue for participants using speaker equipment. It may be necessary to pick up the handset before pressing the star Keys. We also asked all participants to limit themselves to only 1 question and 1 follow-up to allow ample time for others in the queue to ask their questions.
1 moment, please while we pull for questions.
Our first question comes from the line of Joseph Schwartz with L Partners, please proceed with your question.
Hey guys, this is Will on for Joe. Thanks for taking our questions today, and congrats on the progress this quarter. So, one question for us: considering the leadership at the agency has been rather fluid lately, could you provide a glimpse into any of your recent FDA interactions, especially at CBER? Are you noticing any meaningful changes in messaging and/or the folks that you're interacting with? Just trying to get a sense for how impactful these headlines we've all been seeing are on a day-to-day interaction.
Basis for alto Genex. Thank you.
Well, I think our interactions since the crl have lays been good. I think. Um, there are productive and we're working toward getting our type, a meeting package sent in. So we're we're pleased with how things are going. I know they've under a lot of duress at the agency, a lot of turmoil and change, but I think things have been going well, we're pleased with the progress so far.
Great. Thank you.
Thank you.
Our next question comes from the line of June Lee with Jewish Securities. Please proceed with your question.
Uh given GTX 10102 and rubiners and both use LNA, chemistry. Could you please, um, elaborate on non-target site dependent factors that drive. Um, very different dosing regimens that you you both have for, uh, these drugs
Well, the the LNA chemistry you're using is primarily chosen because it is substantially more potent.
It can have more toxicities.
And which is known by its potency is, was dramatically better for the Target on the or at least 1 or of magnitude or more.
In our hands when we compare it to nonla chemistry so there's a reason for it.
We think the potency gives us a dosing that's in the 5 to 14 milligram range, which I think is a distinct Advantage because the non-chemical or the chemical-based, off-target effects will be less since we're operating at a relatively low chemical concentration.
It's a little hard to compare all the different molecules the rougon earth. And the 1 from rosh is also an LNA, the 1 from IOS is a different chemistry.
Each of the chemistry has its upsides and downsides; we believe the LNA strategy, in this case for this target, gives us much better potency and a better therapeutic window. I think that's why we are seeing, we think, better results in our program so far and why we've been given breakthrough therapy designation based on the FDA's review of our data.
Thank you.
Thank you.
Our next question comes from the line of Jina Hwang with Barkley's, please, proceed with your question.
First, 1 is regarding Cosmic trial. Um, I mean, maybe can you remind us? Um, what's the reason to run Cosmic trial? And then, what is your assumption for this? Phosphate arm and if trials fail, but orbit is positive. How do you see the pear and the physician uptake of the draw? Um, my second question, if I may just also very quick. Uh, stats. Question regarding phase, 3 Aspire, uh, your secondary endpoint you allocate 10% of the alpha. Just want to confirm is that the 0.05? And the, why isn't it? That's just the hierarchy to uh have a full 0.05 Alpha alloy for the secondary endpoint?
Thank you, of course, you and I would not expect anything more than details statistical questions. So thank you for that diving deep. So the cosmic study, and the reason for it is to look at young patients, who have severe disease, who couldn't go in a placebo control trial and
In this case, they'd want to be on the drugs that they're on, which they're they're on. So they all have been on bisphosphate. So we're simply randomizing some to go on our drug versus standby.
We didn't assume a change in the um fracture rate for those patient with philosophy. We assume that they continue to sustain. The question is can we get a 50% Improvement? Which is what we were trying to power for
The 1 Advanced of the study. Although you would say a head-to-head may have less power. But I'd also argue that the population is very narrow. They're all very young patients that have a very rapid response to the drug
Very rapid bone marrow density production response to the drug and we think that that will help power the results. So if, for example, we believe the study as the power to succeed, if it perhaps just missed, for example, showed a difference, I think it still would provide supportive data in the age group and support of data, what they head to head looks like, I actually think the study should hit though because I think of the
Consistent responsiveness of patients of that age and the fact that bis fos have a relatively weak and variable bisphosphate response. We feel good about the fact that the combination mechanism of action of our drug
We will overcome whatever you might see with bisphosphate, and our read so far is that we are not worried about this phosphates as a competitor. But we want to have the data to prove to authorities, right?
That uh, the Trees of map is superior to this fascinates.
With regard to this fire at Aspire, we allocated the primary to...
Um, 90% of the power as to the Bailey and 10% to, to the uh mdri.
Which you called key secondary, but it's really the primary alpha split. The reason for that is the MRI is a very powerful method, which we see very strong statistical significance. So we didn't need to use much power to do that, but the idea was.
if if MGI hits, it gives us a way of having a successful study, no matter what happens to Bailey,
Then it's fine. Could be done sequential. You could do a sequential Bailey first then MRI or MGI first, then, Bailey, and kept all 005. But by doing them separately, it means that we're not dependent on Bailey, it doesn't have to hit in order to succeed in this design. You can still have a successful trial even with Bailey we're not to hit. I think it just provides.
A more secure approach to statistics here and but we appreciate sequential would be another way to do it but uh we think what we've picked gives us the best chance and brings forth a new message. The MRI method is a new method for FDA but it is a powerful method and we think will become
the dominant Superior. Way to look at complex multi-domain neurologic development disorders.
And once we start showing this in this study, I think people will understand
How much more powerful it is, when you're talking about a very heterogeneous population of patients? Um, so we're excited that the FDA has given us a chance to put that forth.
As one of the primary ways to assess our Phase 3 study.
Thank you. Our next question comes from the line, um, tazeen AMA AMAC with Bank of America. Please proceed with your question.
Hi uh good evening. Thanks for taking my question, ammo for the um the third and final read for orbit. Um there was some some debate among investors that if it is statistically significant at that final read at 18 months that the the level of clinical benefit will also matter more than it might have at 12 months because the argument is if it's taking that long to separate from this, phosphonates how much better is it than this? Phosphonates. So I wanted to get your thoughts on what what you think doctors would think about that particular argument doesn't matter the the as long as the statistically significant does it matter how much separation is getting at the 18th month time Point? Thanks.
Yeah, thanks Susan. I think if you look at the treatment effect estimates, the difference between patients, I think you could have the same difference but because of more variation it just might make more take longer to separate the groups. But the treatment effect size could very well be the same. What we had to try to caution people. That if it's 60% 67.40 50% in this range, it is substantially better than what certainly observed and I don't think that that percent number is going to have a dramatic impact. Exactly. And what happens, I think any number in that range is a strong benefit to patients. What we can see from Phase 2 though is that the effect on function.
Availability and other aspects of the patient health is substantial.
And really, that is what's going to drive the benefit to give you the parallelizing.
I always talk about um, xlh. You know, the Chris Vita story. We had an RSS score, there was a primary endpoint but there's no patient. Looking at the RSS score change percent telling us where they're going to put the kid on drug or not. The truth is that proves that it does improve Ricketts. But the reason is have so successful, the patients feel great are more functional, more active just like we're seeing with oi. That's what drives prescriptions. That's what drives patient. Demand, the numbers we have to hit, we will hit the numbers. I think the thing and utilization will come from the overall benefit. And we think what we're seeing in Phase 2 makes this drug at least as good as it's going to be to and it's that effect on oi. So that's why we're confident about where it goes.
Thanks operator. Let's move to the next question. Thank you. All right next question comes from the line of anomalies arama with JP Morgan. Please proceed with your question.
Hey guys, this is Billy on, for arom. Thanks taking a question just, um, well, appreciate the SDA acknowledged. The nerd developmental outcomes data or August. And the Bayou Market data are supportive evidence. What additional clinical data is like, between included in resubmission, is this small kind of longer duration data, we're thinking, or additional biomarkers, that would be
Thanks.
yeah, so what they specifically asked for was an update on the clinical endpoint data and the biomarker data just
Because time will have passed, they just wanted the latest data. We had which we have data, patients have been hongo in the study so we'll collect.
their Bailey data and their vinyl and data the data that sort of the developmental data they've seen which they considered robust,
And will include whatever, CSF, biomarker data. We have as well in that assessment as requested. So, it's pretty much a
Believe the patient's doing well and it'll be what I would call a routine update of the clinical data.
Thank you.
Thank you. Our next question comes from the line of Kristen kluska with cancerous Gerald. Please proceed with your question.
Hi. Good afternoon everybody for the orbit study, reading out later this year, I know you're you still very high conviction in the trial being successful but I wanted to talk about a hypothetical scenario where maybe the fractured data Falls slightly under what you were hoping for but you see really strong benefits on pain. Do you still think that there's a strong case to make for the FDA here? And could you argue that this will drive higher adoption for patients since they deal with this on a daily basis over the, uh, fracture aspects?
Well I you know, I think that your point is, maybe there's a lot of some variation in fractures and you just missed that and you have other supportive data, I think data, the FDA will always look at the total totality of the data in a rare disease program. We've had that many times in many programs.
Our sense here is that we're seeing a fundamental mechanistic effect on baral density. The effect it has in fractures. Depends on how many fractures that patient have their particular condition. We have a lot more type 3s and type fours in the study. They have a lot of complex problems. Uh,
And so I'm sure that the support of other data would help us in any situation um, whatever the statistical or treatment size is. And so that's just generally been the case, we feel confident, the fracture data will be what it is. We're seeing, what's going on in Phase 2. We know that as time goes on, there's very few fractures among patients after they've gotten established on the treatment so we feel good. We'll be able to do that. But hypothetically, I think the data will always be more than just fractures in this disease State and the body of data we have we think will support its use.
however, we come out with unfractured
Thank you.
All right, next question comes from the line of ego. Uh, Nico Vitz. With Citi group, please.
Proceed with your question.
Hey thank you. Hi, I'm Milan team. Uh I just had a clarifying question. Firstly regarding GSD 1A and the filing I think Eric you mentioned that you were making sure that you wanted to resolve any of the outstanding CMC issues on 111 before submitting uh GST 1. A could you just clarify? Is there a specific question that you're trying to
To answer, uh, on CMC, a Rel related to GST, 1A by virtue of, of clarifying, something on ux 111, or is this simply just a matter of taking extra precaution. Uh, to make sure that you, you've got everything, got everything, right, uh, before before filing the, uh, the GSB 1, AA.
Eric, did you want to answer that or you'd like me to answer? I'll, I'll give it a shot and I'm certainly happy for the follow-up, but, you know, it's important to remember that the manufacturing facility up in Bedford is producing uh, the gene therapy for MPS 3A as well. As for GST 3, uh, GST 1A. So, you know, any findings related to that manufacturing facility would potentially pull through to GST 1A. So we just want to make sure we work through all of that. Um, and any pulse any pulses to GST 1A
Okay, thanks. Um, and then on ROI. Uh, oh, hello.
Can you hear me?
Yep. Nope I think we're good. Go ahead.
Oh okay. I was going to say on oi. Um you know, given given the the first 2 in terms of passing know or we're looking at the final ones. I'm just curious. If you have any updated thoughts as far as what you believe the expected, uh, Placebo AFR, would be we've done some work. And there are a number of epidemiologic studies out there, both in the Scandinavia as well as the United States. Which point to various ranges for, uh,
AFR, um, I'm just wondering if you could comment on what you believe would be the the most likely scenario at this point as well as um, on some of the more specific aspects of the uh, the statistics again. Um, regarding this concept of um, variance or overdispersion, which as we know is a feature of this particular data set, given the way the, uh, the fractures are are distributed
Thank you. Yeah. So
you know, yes, we're aware of the, um,
Orbit and Cosmic to to do our modeling and we were really looking at those patients with a baseline AFR between 0.72 and 1 for our modeling to to support both of the work for the inner analysis. And obviously the the powering we did uh for the primary efficacy analysis period at at 18 months and with the dispersion. Yes. I mean I think you know while we did not change entry criteria for orbit Phase 2, going into orbit phase 3 on the strengths of the phase 2 data. We had really what I consider to be a self-enrichment of patients with type 3s and types 4. I think they needed to see that strong, uh, safety and efficacy data to take the risk to come into the clinic. Because remember, they're they really are at risk just from traveling into sites to sign consents and begin studying the participation. So I will say, you know, we did, you know, we have a greater number of patients with type 3 and type 4 oi in the phase 3.
Part of orbit compared to phase 2.
Okay, thank you.
Thank you.
Our next question comes from the line of saline rooster with Goldman Sachs, please proceed with your question.
Hi. Thanks for taking your question. This is Tommy on for Saline. How are you thinking about the bar for the Angelman data next year? Both from a regulatory and competitive standpoint and wondering if you've received any updated feedback about the use of Bailey for, as the primary endpoint? Thanks so much.
Yeah, so I mean, you know, again...
All right. Eric. You want to do it? Go for it. Oh no. Sorry Amal. I didn't know if you guys were back online or not,
um, but again, I guess I'll give it a
Start and you can certainly jump in. But, you know, the bar I think for Angelman, you know, it hasn't moved for us. So, you know, certainly we have our, you know, interactions with the FDA. We do feel like we have full Buy in with the study there, you know, we, we do work through our statistical analysis plans with them, as well. So, you know, have been in communication with, um, um, again, following back to the data, we generated in Phase 2, and that was quite a few number of of patients there. Who continue to see the attainment of new development developmental skills over time. We are not seeing a plateau, of fact, we are seeing them continue to gain new abilities. And that's very important to them and their parents. Um, you know, we have a lot of confidence in our primary endpoint with Bailey. Cognition again. Cognition is foundational to everything else you're looking at there, whether it be, um, expressive language, receptive, language motor or anything else, or it is following.
Foundation and we think inappropriate endpoint. Again, we talked about using mdri and, and really being an Ideal tool for these type of indications because you're really looking at all of these aspects on a very straightforward transparent scoring system to really look at the benefit, you know, in totality and and also allowing some some variability between individual patients. So again I think that rapid enrollment and really it's not just 129 patients over since 7 months it's 129 patients in a very complex study and that really speaks to the enthusiasm with sites with with patients and and their families to to Really gain access to this therapy.
Thank you.
Our next question comes from the line of Maxwell score with Morgan Stanley. Please proceed with your question.
Great. Thank you.
So much for taking my question. Um, I was just wondering, can you elaborate a bit on how prv proceeds are being factored into your path to 2027 Gap profitability. Uh, any insights into your relative confidence and receiving all 3 prv. Thank you.
Yeah, well obviously, peer B are important part of it. And I, I let, uh, Howard maybe talk through that the prvs and how we're working them into our cash plan. Yeah. We, we have prvs from 3 of our programs, so 1 11141 and 1 143 factored in, um, you know there there has been a shift in timing on those but we still think all of them come through
Um so I can't I think that's where I would stop. Yeah. If if it's reauthorized it makes it easier for the oi 1 but if it's not then the other 2 certainly could be will be done in time to achieve and we'd expect their value to be higher. So the net of of whether it's 3 with reauthorization or 2 without we think we're still up in the same place from a total cache.
Great. Thank you.
Thank you. Our next question comes from the line of yarn wber with TD Cowen. Please proceed with your question.
Of a prioritization on controlling spend including stopping and delaying certain expenses, can you give us a more granularity about what this entails and are you exploring the options in the event that responding to the crl for ux 111 takes longer than expected? Thank you so much.
Yeah, well thanks. I think.
A lot of this is practical stuff, you know, that we're focusing on. Maybe Howard can go through it with you, but our expectation on the CRL part is to get through. I mean, I don't...
We've looked through the whole list, we actually had a lot of feedback already and I've already done a lot of the changes and things, so uh, we don't really see. There's anything in there that is, undoable very doable stuff, so we're working through it. So we we're not really planning for us, not to get it done. I think it'll be done. And so far, we think the update has been responsive in our discussion since then, maybe. However, you can talk about how we're managing costs. Yeah. Our goal has been and remains to be, uh, Gap profitable for your Gap profitable, um, in 2027. And so how you get there, of course, is continuing to grow the Top Line, uh, but also making sure that we are good stewards of our cash. Um, and so with some of the delays that we've, uh, experienced this summer, uh, we did the natural thing which is to delay those expenses and make sure we're being prudent, um, and making sure we're using our money as well.
you know, involve not hiring people that would have been hired for launches and managing other headcount and addition to that just
Really scrubbing through all the spend that might be delayed as well and not just continue them ahead with momentum. So we'll help that bridge us to the.
the point in which we will get the cash and manage where we're at, but we're.
You know, I think it's just a prudent part of managing company in these situations and we've been through this before. So we're actually very fascinated making the moves. We have to make
Great, thank you so much.
Thank you. Our next question comes from the line of Sammy Corwin with William Blair. Please proceed with your question.
hey, congrats on the
questions. Um, I had 1 on ux 1111 and then a broader question on your aav platform. Um, do you think that The Fever leadership change will be helpful or kind of hinder the crl resolution for ux 1111? And then given the recent safety events with systemically administered aav? Are you thinking about modifying your immunosuppression regimen at all? Or are there any additional precautions? You've implemented to decrease the risk of aav related saes? Thank you.
so, um,
Look, I think there's a lot of very good people at the FDA. They're still there doing their jobs, and our sense was that,
They won't impact their ability to do their jobs. I think, in some ways, it might be simpler for the next period, because of the, the team that had down in the work can do their work and work with us in solving these things. So, I think it'll stick to a very practical matter of fact, line by line resolution of issues raised and I think it's very doable without having high level leadership for these kind of things. Uh, these kind of resolutions because the clinical data were felt to be robust and strong. That's a little, there's a little less uncertainty in judgment because the safety is excellent. There's no real question mark there. It's really more about getting the things boxes checked on all the CMC pieces, which we think we can do. So we're not so concerned about leadership for that particular aspect of it. With regard to the AV platform. We're highly supportive of the a as a treatment strategy, we obviously have a lot of investment in it but for many of the liver targeted ones we're doing at relatively lower doses. Compared to others, we have not seen substantial safety issues.
Like you were talking about either death or very serious liver indicate, um, complications the lower dose we use, we think are in a very safe range and we feel very good on them. Now, we are looking at enhancing immune modulation, but this is more about trying to alter or support more efficacy or managing anti-trans Gene responses. We are looking at that in our cohort for for aux1 11, to try to manage the immunological responses, but the drug wars was just a simple steroids, fine. That's what we can get approved on and our goal is always to continue to look to optimize but it's not a central thing to try to prevent a death. It's more about trying to optimize the outcomes and we will look at and be more FASA looking at immune modulation where needed. But so far we don't have any programs that are the high dose type that have put created more complexities. But I want to say that if you have a lethal disease as duchin is or others,
benefit, and we think that, um,
A lot of these horrible diseases are a death sentence and a horrible death sentence for families, and they should be given the opportunity to make their decision on what the best health care for their kid is. And, um, I think they are capable of making that decision with an approved product.
Thank you.
Thank you.
Our next question comes from the line of my Ray cross with Jeffrey's. Please receive with your question.
Hi. This is fising on for me, I wanted to clarify for citrus. I'm up. And if you can provide more granular timing on the street disclosure like last patient visit should be end of October as it sounds like there will be no DMC review and you'll be on blinded to the data. So technically it should be faster than 2 months and it took for I2
Hi. So, you'd like to know what day and time the data are coming out?
I'm sure we can print out that. Well yeah, the last patient. Now remember, there's this whole process of getting all the last data sets the x-rays reviewed finalized clean, no issues. We have to look at blind data to make sure there's nothing wrong with operations. It's a phase 3 study. So it's not something you want to rush through its the final assessments. We want to make sure we do it carefully. We've been saying this around the end of the year could be before the end of the year. It could be just after the end of the year, it's somewhere in there but we don't want to nail it down because frankly it's not possible to and we're not.
We're trying to be cagey here. It's just that we want to make sure we all get the time provided to close out the study absolutely perfectly. Every aspect of the study must be perfect; we owe it to the patients and our investors to ensure that everything is perfectly correct when we go out and release data.
Makes sense. And then for the Ancient Man, the demand is there clearly, and these are all DeLeon patients. But can you talk more about the patient baseline profile relative to your Phase 1 to enroll patients? And then should we expect more durability data from the Phase 1/2 cohort of patients maybe this year?
Well, the patients in the Phase 2 and now enrolled in the Phase 3 are essentially the same. There are 4- to 17-year-olds.
Deletion-only patients. So there are actually identical. The same criteria were used, so they're really very comparable. So whatever we saw at Phase 2 is probably pretty much what you should see in these Phase 3 patients.
So with the Aurora study, we're going to look at younger patients or older patients with deletion. We'll also look at patients that have missense mutation or the ICD UPD type.
So, we're going to gain knowledge. The idea was to gain sufficient safety data.
To show that you can administer the drug and then demonstrate that there is efficacy. Even though in an open-label format, the efficacy is comparable.
To the effect that we will demonstrate and prove as a cause and effect of the drug in the randomized control study. So that's the idea on the approach we're taking. Did I answer your question? Yep. And should we see more follow-up data from the Phase 1 to this year?
We haven't planned right now. I mean the team is working on two Phase 3 programs right now. That is our focus. And the last thing I want to do is put another item on their plate of running more. The patients continue to get drugged.
And are doing fine. And we're encouraged with it. But we hadn't planned. Another cut of data yet. We got to get the phase 3 done and do them well.
Got it. Thank you so much.
Thank you. Our next question comes from the line of Jack Allen with beard, please proceed with your question.
Great. Thanks so much for taking the questions, and congrats on the progress. I wanted to ask you a couple on the Satus Map program. As it relates to orbit, what kind of standard deviation are you seeing in any blinded data that you've seen? How confident are you in the existing statistical analysis plan that you have outlined? Do you think there are any needs to update that SAP? And then I have a quick follow-up as well.
Yeah, we haven't really talked to a standard deviation. I know everyone is trying to calculate the spreadsheet. You did say dispersions of. So, you know, but everyone sells the thing dispersion just to show their at the level of statisticians. Uh, operating here, I know everyone's trying to do the math for us. Um, we haven't put out the standard deviation, uh, and I don't really even know it off the top of my head right now. But there is a significant amount of variation because we've said about a third of the patients had fracture rate,
At Baseline up from 3 or above and about 2/3 below.
We also have an age range of, you know.
Five-year-olds up to 25, so there's a bit of range in those things. Those are all factors in the standard deviation, both the standard deviation of the AFR, but also bone BMD response, etc.
Actually is the best way to look at this kind of fracture data. And frankly today, I actually did a little AI search which you can do yourself and look up negative binomial and fractures. And it'll tell you, actually, this is the best method so you can do it yourself. And it says, among all the methods, there's some comparison papers, it's the best method. Now, there are things the details to that. Like what covariables, what are the items that contribute to variation then we can look at those are basically tweaks to the model that you can make. And usually in any stat plan, you are offer some flexibility and what coari you might use because you have to control for contributions of variation, which include the Baseline. AFR
It could include the type of OI. Could include the age, right. Those are 3 obvious ones that would be potentially included. So those are some of the tweaks you would do to a final analysis, uh, plan, but it the the basic negative, I know the model is set and we're confident in it as a strategy. And we just want to make sure we're using the right set of code variables to help control for Baseline variation. That's not related to the actual treatment effect and that will help ensure that we get the best result.
Great, great. That's super helpful contacts. And then you did mention, uh, that the Phase 2, uh, seems to be demonstrating a very durable effect and even a deepening of response over time, or at least that's how I would characterize some of your earlier comments from the situation. And I just wanted to ask if there are any, um, plans to present updated data from the Phase 2 cohort of 24 patients?
And when may we see that data set, if there are plans?
Well, we don't have plans yet—the studies are ongoing. The patients are doing really well, and we consider doing that at some point, but we haven't made a specific plan yet to do it.
Got it. Thanks so much. Congrats on the progress.
Thank you. Our next question comes from the line of Hannah way with green hot, Glen Partners, please, proceed with your question.
Hi, this is Hannah um for adoption and thanks for taking our questions. We have a question regarding oi program. Uh could you clarify which be sports for Nate therapy? For patients were on uh prior before entering the August study and the roughly how many patients were on reclast? Thank you.
Yeah, we have the schools which basically um, but we have said, the vast majority. I think it's created a 90% have had visas on board, like a large fraction, so um, it's permanent because it's enrolling patients with a higher fracture rate. You know, the higher ones are in the study. So the fraction has been on both sides worth, I think about 90%.
But we haven't said which ones. It's several different ones. So,
It wouldn't help you.
Got it. Thank you.
Thank you. All right, next question comes from the line of rager room, CU with HC Wayne Wright, please. Proceed with your question.
Good afternoon. This is Dan on Van. Thanks for taking our questions. Congrats on the beat. So, have you noticed, or has Karin mentioned anything notable about the U.S. or Canadian CEDA markets? The royalties appeared kind of flat on a Q1 year-over-year basis but increased over 17% in Q2 year-over-year. Do you have any rationalization for that? And how much of that increase do you expect to be sustainable in year-over-year quarter comparisons moving forward? Thank you.
Yeah. Well, you know I think there's always a little bit of lumpiness in those in regions because of the how the ordering and buying I haven't any particular explanation. I don't know. Eric if something.
of insight that you have, but
I think this is just for regional, you know, lumpiness and when the governments are managing, what goes on,
Yeah, no. We think the underlying demand has been pretty consistent, and the pull-through is able to mention the ordering patterns that have just been a little lumpy.
When I'm being more than that, for you.
Thank you.
Thank you. All right, the next question comes from the line of Luca EC with RBC Capital Markets. Please proceed with your question.
Oh, great. Hi team. This is Selvon for Luca, and thanks for taking our question. Emil, we have heard you in recent interviews noting that the FDA asked for things like more probes in your shipping validation for the sample LipaCRL, as well as an inspector who was particularly stringent with his review. Can you expand on that? And then maybe bigger picture, can you share your opinion on whether you think the FDA is missing the forest for the trees here? Any color there would be much appreciated. Thanks.
To actually check every tree in the forest, that's part of the rigor of the process. So if there's a CRL that has a lot of bits and pieces, it's because there are a lot of bits and pieces. I think I would say these are all things that need to get taken care of, and there are lots of parts and pieces to it. So I think they're doing their job with regard to that detail. Um, you know, what it should be CRL or could we have done it in time? You know, those are questions you could ask, but we're going to do the work to ask for it and, you know, the inspector and all that. I think it doesn't matter at the end of the day. We have a CRL listed issues to do, and we're going to do them, and we're doing them. I think we'll be able to work that out with the agency and get it done. But there are times when the FDA has to focus on certain details; it's part of the rigor they apply, and we appreciate that, particularly in CMC. Rigor is essential, and there are reasons for a lot of things that relate to things that have happened. And so, we are going to comply and improve what we can with everything we do.
Thank you. And ladies and gentlemen, we have reached the end of the question and answer session, and I'll now turn the call back over to Joshua Higa for closing remarks.
Thank you, this concludes today's call. If there are additional questions please contact us by phone or at IR ultragenyx calm, thank you for joining us.