Q3 2025 Ultragenyx Pharmaceutical Inc Earnings Call
Speaker #1: Good afternoon and welcome to the ultra Gen-X third Quarter 2025 Financial Results conference call . At this time , all participants are in a listen only mode .
Speaker #1: At the end of 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 .
Speaker #2: Thank you . We've issued a press release detailing our financial results , which you can find on our website at Ultragenyx Pharmaceutical Inc .
Speaker #2: Joining me on this call are Emil Kakkis Chief Executive Officer and President , Eric Harris , chief commercial officer . Howard Horn Chief Financial Officer and Eric Crombez chief Medical officer .
Speaker #2: 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 our actual results may differ materially .
Speaker #2: Please refer to the risk factors discussed in our latest SEC filings . I'll now turn the call over to Emil .
Speaker #3: Thanks , Josh , and good afternoon , everyone . Today , is on the cusp of significant evolution and We have four commercial products that have delivered consistent and substantial double digit annual revenue growth over many years .
Speaker #3: We have two submissions in progress for programs that are poised to address significant medical need for patients with ultra rare diseases . We also have multiple late stage clinical programs with transformative commercial potential that are approaching pivotal data readouts .
Speaker #3: We're in a defining moment for the company , and I'm pleased to report that our team is ready to maximize the opportunities ahead .
Speaker #3: We announced earlier today that we took an important step to strengthen our financial position , receiving $400 million of Non-dilutive capital from Omers through the cap sale of a portion of our Vita royalties .
Speaker #3: Importantly , we were able to defer the start of payments under this financing until January 2028 . These funds and this timing bolster our balance sheet as we approach pivotal data readouts for our most significant commercial opportunities and osteogenesis imperfecta and Angelman syndrome .
Speaker #3: Importantly , we continue to focus on managing our cash burn and prioritizing our investments . Shifting to clinical . We continue to see exciting momentum across our late stage programs , beginning with GBT one and two .
Speaker #3: Our investigational antisense oligonucleotide for syndrome . In July , we announced the pivotal 48 week Aspire study , completed enrollment with 129 patients and is expected to readout data in the second half of 2026 .
Speaker #3: Last week , we announced the first patient dosed in the phase two three aurora study , which evaluates GTX 102 in additional ages and genotypes .
Speaker #3: This study , along with the fully enrolled phase three study , will generate data across the spectrum of genotypes and ages . Turning to UX 143 for the treatment of osteogenesis imperfecta .
Speaker #3: The conduct of the phase three orbit and cosmic study continues to go well . We hear stories from investigators who have patients in the open label .
Speaker #3: Phase two about how well their patients are doing . The improvement in their bone density , bone mineral density , and the profound effect of the drug is having on their lives .
Speaker #3: Data from the phase three studies are on track to readout around the end of the year , which to us means December or January .
Speaker #3: As we move into the final analysis , we remain confident that Mab's mechanism of action , its ability to make more bone in the places that need more strength , which should reduce fractures .
Speaker #3: If successful , this will lead to a transformational treatment for pediatric and adult patients with osteogenesis imperfecta . For our existing approved products , our global commercial organization continues to deliver meaningful revenue and cash flow every year .
Speaker #3: This year , they are on track to deliver total revenue between 640 and $670 million , which would be 14 to 20% growth from last year .
Speaker #3: Graffiti is the largest product in the portfolio , and we expect revenue to continue growing in the US , Canada , Latin America and Turkey as more and more patients initiate this important medicine , Dojolvi Mepsevii also meaningfully contribute to our financial base and provide a steady , diversified source of revenue .
Speaker #3: Is also expected to grow over time . I'll now turn the call over to Erik Harris to share more details on his team's efforts .
Speaker #3: Last quarter .
Speaker #4: Thank you , and good afternoon , everyone . As mentioned , the commercial organization is continuing to successfully launch four products across the globe , starting with Vita in Latin America in the third quarter .
Speaker #4: Our team generated another 50 new start forms that led to approximately 50 more patients on reimbursed therapy . We now have approximately 875 patients on commercial product in the region .
Speaker #4: As the team continues to meet the growing demand for this important product , healthcare providers continually share positive feedback on how well their patients feel when on Vita , and this has led to an increasing number of doctors writing prescriptions for more than one patient .
Speaker #4: I'll now shift to Vita in the United States and Canada , where our partner , Kyowa Kirin has been leading commercialization since the transition in April 2023 .
Speaker #4: While the third quarter 2025 royalty revenue was impacted by expected seasonality , we also know that there has been continued underlying growth in new start forms and new patients on reimbursed therapy .
Speaker #4: We expect strong fourth quarter revenue growth consistent with prior quarters . Moving on to the Jovian , the United States growth of new start forms in the third quarter continued to steadily increase , consistent with patterns we have seen in prior quarters .
Speaker #4: Since launching this product in 2020 , our team has generated approximately 700 new start forms , leading to approximately 625 patients on reimbursed therapy .
Speaker #4: The split between pediatric and adult patients continues to be approximately 65% PEDs and 35% adults . The number of new prescribers also continues to grow , with a total of approximately 275 unique prescribers .
Speaker #4: At the end of the third quarter . For the Jovian across the EMEA region , we are approaching 300 patients treated under named patient sales across the region .
Speaker #4: We continue continue to be pleased with this demand , especially since we are not actively marketing the therapy and simply responding to named patient requests .
Speaker #4: The majority of demand has been in France, but we also see increasing interest from patients and families in other EMEA countries, including Kuwait, Saudi Arabia, and Greece.
Speaker #4: In closing , I'll make a few brief comments on Evkeeza , which we began commercializing in our territories outside of the US with formal reimbursement approvals in just the last couple of years .
Speaker #4: And the EMEA region. We now have patients on reimbursed therapy from nearly all of the major countries, and we have added approximately 120 patients since the beginning of the year.
Speaker #4: In total , there are there are approximately 310 patients across 17 countries who are receiving fxa . I want to recognize the tireless efforts from my European team as they continue to successfully navigate the country by country pricing negotiations and respond to patient treatment requests across the whole region .
Speaker #4: As I have mentioned in previous earnings calls , we continue to expect some quarter to quarter variability in revenue . But we remain confident in the growing underlying demand of all of our products around the world .
Speaker #4: With that , I'll turn the call to Howard to share more details on our financial results and guidance .
Speaker #3: Thank you . Eric .
Speaker #5: And good afternoon , everyone . Before I go through our financials and guidance , I want to touch on the financing we announced earlier today .
Speaker #5: Additional details are in the press release . And 8-K . But the essence is that we received $400 million through the sale of an additional 25% of our royalty interest on the future sales of Crysvita and the United States and Canada .
Speaker #5: Payments to Omers will start in January 2028 and are capped just like our prior royalty financing agreement with Omers . We were fortunate to have many financing tools at our disposal and monetizing another strip of royalty with Omers proved to be the best option .
Speaker #5: We went through a competitive process and Omers provided an attractive cost of capital and a beneficial payment holiday in a cap transaction . These terms helped us minimize the impact on our PNL and maximize liquidity .
Speaker #5: Importantly , Crysvita has proven to be a unique and highly valuable asset , one that we expect will continue delivering meaningful value after the cap on this agreement is hit and the royalty stream is returned to Ultragenyx , adding 400 million to our balance sheet will help us deliver on our expected launches .
Speaker #5: Setting us up for our next stage of growth and on our path to profitability in 2027 . We will also continue to maintain our financial discipline , leveraging our existing infrastructure to launch UX .
Speaker #5: 111 and DBT 401 if they are approved and remain focused over the next year on delivering phase three results for UX one , four , three and GBT 102 .
Speaker #5: Now turning to the financials for the quarter . I'll start with total revenue in the third quarter of 2025 . We reported 160 million , representing 15% growth over the quarter of 2024 .
Speaker #5: And 18% growth for the first nine months of 2025 . Over the first nine months of 2024 . Crysvita contributed 112 million in the third quarter and 57 million from North America , 47 million from Latin America and Turkey , and 8 million from Europe .
Speaker #5: Dojolvi contributed 24 million , consistent with its expected steady growth trajectory . Evkeeza and 17 million as demand continues to build following launch in our territories outside of the United States and Mepsevii contributed 7 million .
Speaker #5: As we continue to treat patients in this ultra rare indication . Total operating expenses for the quarter were 331 million , which included R&D of 216 million in investments in pre-launch inventory , manufacturing expenses of 87 million and cost of sales of 2028 million .
Speaker #5: Creating expenses also included non-cash stock based compensation of 1 million for the net loss was 180 million , or $1 , $0.81 per share .
Speaker #5: As of September 30th , we had 447 million in cash . Cash equivalents and securities , which has been further strengthened by the 400 million raised through the royalty trends we announced today .
Speaker #5: For the three months ended September 30th , 2025 , net cash used in operations was 91 million in total for the nine months ended September 30th , 2020 .
Speaker #5: It was $366 million. We expect 2025 net cash used in operations to increase compared to 2024, and we also reaffirm our path to full-year GAAP profitability in 2027.
Speaker #5: Shifting to revenue guidance for 2025 . We are reaffirming the guidance we previously provided . Total revenue is expected to be between 640 and 670 million , which represents 14 to 20% growth over 2020 .
Speaker #5: Revenue is expected to be to be between 460 and 480 million , which includes all regions and all forms of revenue to Ultragenyx .
Speaker #5: This range change represents 12 to 17% over 2024 . Dojolvi revenue is expected to be between 100 million , which represents 2 to 14% over 2024 , growth with that , I'll turn the call to Eric Crombez , who will provide updates on the clinical programs .
Speaker #6: Thank you . Howard , and good afternoon , everyone . I'll touch on UX 111 for the treatment of MPs three and DT 401 for the treatment of glycogen storage disease .
Speaker #6: Type one a , starting with UX 111 , we have had constructive , formal and informal interactions with the FDA since receiving a complete response letter in July .
Speaker #6: We have also reviewed the additional longer term data that the FDA requested , and we continue to see a durable treatment effect based on multiple biomarkers related to MPs three with further separation and multiple clinical endpoints from natural history .
Speaker #6: While maintaining an acceptable safety profile . The FDA interactions and internal progress we have made to address the observation give us confidence in a Bla resubmission in early 2026 , followed by an FDA review of up to six months .
Speaker #6: Shifting to DBT 401 . In September at the International Congress of Inborn Errors of Metabolism in Japan , we presented final 96 week results from the pivotal Glucagen study .
Speaker #6: These results showed durable , clinically meaningful and statistically significant improvement in cornstarch reduction while maintaining good glucose control . At week 96 , study patients originally treated with DTE 401 had been on study for nearly two years , and patients originally randomized to placebo had 48 weeks of treatment with dtc401 after crossover to study drug at week 96 , patients saw a 61% reduction in daily cornstarch intake across both the DBT 401 and placebo to DT 401 .
Speaker #6: Crossover groups . This also corresponded to a mean decrease in the number of daily doses of cornstarch , with the DT 401 group reducing by almost two doses at week 96 , the placebo to DT 401 crossover group on average dropped 1.6 daily doses by week 96 .
Speaker #6: The improved glucose control and reduction in dependence on cornstarch is particularly important overnight , with the increased risk of hypoglycemia . Hyperglycemia , and why patients are sleeping and less able to detect symptoms .
Speaker #6: Reducing overnight cornstarch doses also helps to alleviate the burden of needing to wake to take cornstarch , and the real risk of missed doses at week 96 , 67% of patients were able to eliminate at least one nighttime dose of cornstarch .
Speaker #6: The DTC401 group saw a 70% reduction of nighttime cornstarch when compared to baseline, and the crossover group saw a similar mean reduction of 75% compared to week 48.
Speaker #6: These clinical results were also supported by improvement in patients impressions of their disease , as measured by a global impression of Change scale , or Pgic , and patient interviews in the DT 401 group , ten of 12 or 83% of patients felt that their disease management was improved , 96 weeks after receiving DT 401 for the placebo to dtc401 crossover group , 18 of 19 , or 95% of patients had improved disease management .
Speaker #6: Just 48 weeks after receiving DT 401 . What is most important is that patients were able to reduce their dependence on day and nighttime cornstarch , feeling better while doing so , all while maintaining good glycemic control .
Speaker #6: This is why we believe this could be a transformative and life changing treatment for these patients . In August , the FDA granted us the ability to begin a rolling submission of our Bla , which is underway and going well .
Speaker #6: The complete application will include the 96 week clinical data and the CMC updates that are in process based on the UX 111 feedback .
Speaker #6: We expect to complete the DT one rolling submission next month . I'll now turn the call back to Emil to provide some closing remarks .
Speaker #3: Thank you Eric , I'll quickly recap the milestones and catalysts as we head toward the end of the year for UX 143 and osteogenesis imperfecta , the last patients in both the orbit and Cosmic studies have had their final visits , and we are on track to share top line data from these studies in December or January .
Speaker #3: For GBT 102 and Angwin syndrome, we continue treating patients in the 48-week Aspire study and continue enrollment in the supportive Aurora study for Dtc401 and Gstt1.
Speaker #3: The rolling Bla submission continues , and we are on track to complete this filing in December . Lastly , UX 111 and Sanfilippo Syndrome .
Speaker #3: We are responding to observations noted in the serial and expect to resubmit the BLA early in 2026. We are well positioned to deliver transformative therapies for rare disease patients.
Speaker #3: While generating meaningful long term shareholder value . We have a growing base of global revenue with strong balance sheet and focus to execute on our top priorities .
Speaker #3: We look forward to sharing the truth . The truth about data and reading out the GBT 102 phase three data in the second half of 2026 , with that , let's move on to your questions .
Speaker #3: Operator . Please provide the Q&A instructions .
Speaker #1: Thank you . And at this time , we'll conduct our question and answer session in order to get through as many questions as we can in the time allotted .
Speaker #1: Please limit yourself to one question and one follow up question per each time that you queue up for a question . So if you'd like to ask a question , press star one on your telephone keypad .
Speaker #1: A confirmation tone will indicate that your line is in the question queue . You may press star , followed by the number two .
Speaker #1: If you would like to remove your question from the queue for participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
Speaker #1: Our first question comes from Gena Wang with Barclays . Please state your question .
Speaker #7: Thank you for taking my questions . I know you were very important . Data update on orbit and Cosmic . You said it around year end 2025 .
Speaker #7: So maybe if you can walk us through the logic there , you know , like , should we actually more likely expecting the data will be at the JP Morgan giving the so close to holiday time and also when you share the data , I assume will be both cosmic and orbit data .
Speaker #7: And if you can also talk about the different scenario , how would you take to the next level ?
Speaker #3: Great . Well , first I'll say that we it's going to include cosmic and Orbit both together . So both will come out together .
Speaker #3: We're saying December or January because we're doing the cleaning process and the finishing of the database locking analysis . And we don't have the precise timing .
Speaker #3: We're providing some variability . There because of the process is not defined , but we will expect to report on both at either in December or in January .
Speaker #2: Good . Let's move on to the next question .
Speaker #1: Thank you . And your next question comes from Maury Raycroft with Jefferies . Please state your question .
Speaker #8: Hi . Thanks for taking my question . Maybe just following up on Gina's question for O-i . Well , I guess to start off , can you comment on what you're seeing in the open label extension from the phase two ?
Speaker #8: And you provided some anecdotal perspective there , but can you provide more quantitative perspective and just anything additional on how we should think about the range of effect sizes on fracture reduction and what would be needed to succeed for the final analysis ?
Speaker #3: Okay . Well , we we haven't put out another cut of the phase two data , so I can't give you any more quantitation .
Speaker #3: I think what we've been observing the style is trials consistent . What we've put out before . And we decided to focus our work on the phase three .
Speaker #3: So we don't have any more quantitative data . But we're comfortable with what you've seen on phase two is consistent as we move forward .
Speaker #3: Now , with regard to what we expect in phase three , we've said that anywhere between 40 and 70% reduction of fractures and that range is a very good fracture reduction level .
Speaker #3: And I don't think that the exact percentage within that range matters as much as how patients feel and how they're functioning . And from the phase two study , it's pretty clear that the the way patients are functioning is quite important in terms of their ability to take on exercises , to walk better , get out of wheelchairs or using walkers , etc.
Speaker #3: . So we think anywhere in that range , and I think most kols have suggested something better than 40% . We've seen 67% in the phase two study .
Speaker #3: I think anywhere in that range is I think would be a clinically meaningful change for these patients . But the effect on the overall function , I think , will ultimately be even more important than how the product launches .
Speaker #3: And I would tie that back to XLA , because in zsh , the score change didn't really change people's views . It shows the drug worked , but how patients felt on the drug that drove the adoption of that drug .
Speaker #3: So we're speaking from experience there on what we expect . But everything we've seen in phase two says that this drug has potential for it to be transformative in changing not only the fracture rate , but how patients feel and how they function on a day to day basis .
Speaker #1: Thank you . And your next question comes from Yigal Naumovich with Citi . Please state your question .
Speaker #9: Hi . Thank you very much . Could you just clarify with regard to the UX 111 and the 401 submissions ? I thought the idea was to to to sort out the CMC related questions on UX 101 first and then and then get that submitted , and then do 401 .
Speaker #9: But now it seems like you're going to do four one . And then one , one , one . And you mentioned something about an observation .
Speaker #9: So maybe that's the reason . But or is there another reason please . Thank you .
Speaker #3: Well the filings were always very close to each other . I mean there were always within a month of each other . So what we there are some aspects of the program that involve the inspection facility that need to be in common to both .
Speaker #3: But there were certain things that were specific to 111 and our in our type A meeting . The FDA made some accommodations , but did require us to have full reports , and some of those reports took a little bit more time , which is why 111 is now following 401 .
Speaker #3: But there was no real change , just the exact timing of when the final reports for things could be put together that are needed for each 400 .
Speaker #3: One doesn't have some of those things because it is a new filing . And so we felt we could get the things that are in common done in time , and kept 401 on track to file this next month .
Speaker #3: So it's a slight change , but I don't think it's a fundamental change . It's just what we have to get done . And when .
Speaker #9: If you if you could comment on that , on that aspect of it .
Speaker #3: Well , I'll let Howard go through it . But we sent we at that time . We sold 30% and we had a cap , and now we're selling a little bit extension of that , plus another piece .
Speaker #3: But the cap ultimately is going to cover both pieces . But maybe , Howard , you can explain it simply for them .
Speaker #5: Yeah . Thank you for the question . We can't actually tell you how we're tracking to the cap , but I think what Amel said was important that the prior deal with Omers .
Speaker #5: So the 2020 agreement with the 30% that has its own cap once it's hit , it will then flow into this new deal and together that piece , plus the additional 25 that we announced today , will together have its own cap of 1.55 times the 400 million that we raised .
Speaker #5: There's actually a really helpful page in our corporate deck that's either on our website or will be there soon . That that describes this .
Speaker #1: Thank you . And your next question comes from Tazeen Ahmad with Bank of America . Please state your question .
Speaker #10: Hi , guys . Good evening . Thanks for taking my questions . Just to stay on the point of this Omers topic , that 400 million that you announced today , how far does that go in helping to address any concerns investors might have about the potential for financing needs coming up in 2026 , especially as it relates to September , when your priority vouchers would need to be renewed .
Speaker #10: If you could give some color on that and then secondly , on the scenarios of orbit and Cosmic , how are you thinking about if one of the studies is positive and the other is not ?
Speaker #10: So let's say that that orbit is positive and cosmic is not , and vice versa . How would that impact you think your chances of getting approved in ?
Speaker #10: Okay , thanks .
Speaker #3: Well , let me answer the orbit cosmic first , then I'll let Howard talk about the Omers transaction being the cash . Cash runway story with regard to cosmic .
Speaker #3: We think both studies have have are powered to succeed . So we're expecting both to succeed . If on the outside chance that one doesn't and one does , I think that we'll have enough data to help support the full range of the indication .
Speaker #3: Remember, Orbit is against placebo and involves older kids. Cosmic involves younger kids and is against the control. If we show good bone mineral density improvements in the younger kids.
Speaker #3: But versus maybe the p values and hit for versus bisphosphonates , for example . But we show that the effect is still happening .
Speaker #3: I think we can manage that in terms of getting the age indication by showing the treatment effect is occurring, and then safety is good down into young ages.
Speaker #3: If the cosmic study is smaller , but the one advantage of it is that it's a narrower population because they're young patients only of 2 to 7 , rather than excluding adults .
Speaker #3: So even though it's smaller , it also is a narrower population . So it could also achieve with a narrower population . Maybe there's less variation .
Speaker #3: It could come out positive and show a good effect if the orbit turned out to have too much variation and was missing slightly.
Speaker #3: But we can then show that the older patients are seeing the same effect . We saw before . So I think if we get one or the other study positive , we'll be able to work forward and how we'd solve the issue of the age range and the indication .
Speaker #3: I don't expect there to be differences in how the drug works . I think both studies should show a substantial bone marrow density benefit and improvement , and should show improvement in fractures .
Speaker #3: So we're confident the program . But I think we can make it work with either combination of results . Now , let Howard talk about the Omers deal and cash runway question .
Speaker #5: Yeah . So I guess maybe I'll couch this in the in the term in terms of our pathway to profitability in 27 , there are a number of assumptions that go into that .
Speaker #5: First of all , the recent changes in timing are all factored into what I'm about to say . But on the revenue front , we expect to have continued double digit growth from our current products and some contributions from launches on the expense side , we will continue to manage expenses , but we will incorporate some select investments to to maximize our launches .
Speaker #5: As we talked about today with pre-launch inventory , build and then on the financial side , we do incorporate monetization of three prvs .
Speaker #5: So from UX 111 DT 401 and UX 143 , we've talked about in the past , if one of those wasn't to come to pass , that we think that the aggregate value of the others would get us to the same cash point .
Speaker #5: And of course , today's today's financing that we announced bolsters the balance sheet . But in aggregate , we think that all of those levers will put us on our path to profitability in 27 .
Speaker #1: Thank you . And your next question comes from Maxwell Score with Morgan Stanley . Please state your question .
Speaker #11: Great . Thank you very much for taking my question . So based on your Kol interactions , how do physicians think about potentially initiating Sacituzumab , for example , prioritizing younger patients versus those with more advanced disease ?
Speaker #11: Some checks we've done indicated earlier use in younger patients , but just wondering your thoughts and feedback from the community . Thank you .
Speaker #3: I think if we demonstrate the strong fracture effect across the age ranges, I think that it's very likely the earliest adopters will be patients with the most severe disease.
Speaker #3: And I think for many , that will be the type three and type four patients . We'd expect a higher fraction of those patients to get treated .
Speaker #3: And many of them are affected at a younger age . But really at any age , if they're type threes and fours where they have a more severe phenotype within type one population , there may be a range of spectrum .
Speaker #3: There's a significant fraction , maybe half or more , that have enough fractures to be a really a detriment . And for which , even if they're not having fractures , their change in behavior , their avoidance of activities or the sedentary activities are are a problem that they would still want to get treated .
Speaker #3: So I think the area where most Cles would wonder about is on the milder type one patients , but a lot of those patients are not even diagnosed very efficiently .
Speaker #3: So we do think that it could shift younger , but I would say from our experience that Crysvita we see growing and growing use in adult patients , because even in Ojai , there are substantial effect .
Speaker #3: They may have less fractures , but they still have bone dysfunction . That is hurting their ability to enjoy life well . So I think it'll be used across the spectrum , but I would expect younger and more severe patients to get more immediate access compared to others .
Speaker #11: Thank you .
Speaker #1: Your next question comes from Jack Allen with Baird . Please state your question .
Speaker #11: Great .
Speaker #12: Thanks so much for taking the questions . And congrats to the team on the progress made over the course of the quarter . Two quick ones from me .
Speaker #12: The first of which was on R&D . Howard , I apologize , but I think your remarks were a little choppy for those on the line .
Speaker #12: At the top of the call , I was hoping you could dive in a little bit more on the third quarter . R&D , and you referred to some pre-launch , pre-launch manufacturing spend there .
Speaker #12: How should we think about that in the quarter ? And then the runway moving forward on R&D and then just briefly on on osteogenesis imperfecta ?
Speaker #12: I was wondering how you guys are thinking about the commercial opportunity there as compared to maybe Xlh and your pre-launch efforts ? And I guess analysis of that market .
Speaker #3: Okay . Thank you . I I'll touch on the commercial . Excuse me if that's right . Actually , Howard , why don't you do the R&D first ?
Speaker #5: Yeah . Jack , you got it . My my point that I was trying to make there is in the quarter , the 216 million for R&D expense .
Speaker #5: It came up a little bit . I mean , I guess it was a diversion from our trend . And I wanted to explain that that was related to investments in pre-launch inventory and getting ready for these launches .
Speaker #5: So that's the point . I was trying to call out and apologies if the line had garbled over to you on O-i .
Speaker #3: Yes . So in O-i , we look at the population in our view of the Oi population is that there's probably 50% to 100% larger than Xlh based on our discussion with Kols , who see a lot of patients and have a big sample size , we think of pricing as probably similar to our Crysvita program .
Speaker #3: So we'd expect that that the opportunity is larger than our Xlh program . Okay .
Speaker #1: Thank you. And your next question comes from Joseph Schwartz with Leerink Partners. Please state your question.
Speaker #13: Hey , guys . This is Will on for Joe . Congrats on the progress this quarter . I just have one question on the Angelman program , considering there are multiple Asos in development here , we might be in an environment in a few years where there are multiple approved options .
Speaker #13: While it's difficult to envision how the competitive landscape might shake out , can you help us understand how the patients , parents and caregivers for this disease may be making their treatment decisions ?
Speaker #13: Is this something purely driven by the overall data , or are there other attributes such as dosing , schedule specific endpoints , safety , etc.
Speaker #13: that are driving these decisions ? Thank you .
Speaker #3: Thank you . Interesting question . Of course , there's a lot of unknowns and what will actually play out in our mind right now .
Speaker #3: Our Aso is the most potent and is shown the best long term data . I think in the end , the data will speak to parents as to what what is important with regard to how they make decisions .
Speaker #3: We're certainly talked to a lot of parents and and understand what their views are of patients . I would say to you , there's there's no interest in knowing what the primary versus secondary endpoint or other endpoint .
Speaker #3: They want to know how their kids are doing . And it's broader than picking one thing . We will have all the endpoints .
Speaker #3: And I think the endpoints across the different programs are broad enough to cover enough of the same domains for parents to be able to tell with regard to the schedule .
Speaker #3: You know, I think that both programs, in the long term, are ending up in at least the Ionis program. Our programs are both in Q3, kind of scheduling down the road.
Speaker #3: I think it's going to be more about I don't think the schedule itself is going to matter , or if there's a load or not , I don't think that's going to really alter .
Speaker #3: It's going to be more about potency . The other thing I think will important is , you know , our patient support programs and how we help patients with treatments .
Speaker #3: And we have, I think, one of the best support programs to ensure that people can get access to drugs. They maintain access even when they change insurance and other things.
Speaker #3: So, we'll help support patients to achieve their access goals and get treated. At the end of the day, I think the potency and safety will matter.
Speaker #3: Be the most important thing . But if there's multiple products out there , it's how we handle the administration . And support for our patients will have a big impact on what works .
Speaker #3: And the last thing I'll point out is that we are are rolling , rolled our phase three and moving along very quickly . And I feel we will have the potential to be out ahead of other Asos .
Speaker #3: But let's see which one is best. I think patients will probably opt for the best one when the trial is all done.
Speaker #13: Great. Thanks so much.
Speaker #1: Thank you . Your next question comes from Anand Rama with J.P. please state your question .
Speaker #14: Hi . This is Joyce on for Anna . Thanks for taking our question . Maybe just one from us or GTX 102 following up on Angelman .
Speaker #14: Realize here that the Aurora Supportive study has only just started enrolling . But how should we think about the enrollment curve for that trial relative to what you observed with the pivotal Aspire trial ?
Speaker #14: Thank you .
Speaker #3: Thank you . The Aurora trial . We actually expect enroll pretty quickly . There's a lot of patients lined up for it . We haven't set a precise timeline for enrollment , but we were impressed with the speed .
Speaker #3: I am enrolling in a sham-controlled trial. This trial is actually open-label. I think that I'm expecting competition to get enrolled in the trial.
Speaker #3: And so we expected to go pretty quickly . I think it's going to be an important study , though , for open up our understanding of treatment , safety and efficacy , both in a wider array of genotypes .
Speaker #3: So we do think it'll go quickly , but we haven't set right now a timeline specifically for it .
Speaker #1: Thank you . Your next question comes from Yaron Werber with TD securities . Please state your question .
Speaker #15: Congratulations on a great quarter. This is Steven on for your own. Just one question: how are you thinking about the length of a course of treatment for Citrus?
Speaker #15: We've heard different kols say different things about exploring bisphosphonates in combination or in cycles with cetuximab , just based on the relative effect .
Speaker #15: Because citrus might build more bone mass , whereas bisphosphonates have a more , you know , freezing effect . Do you expect the majority or , you know , all patients to be on citrus and Mab continuously and then secondly , whether there's any other concern about bone pain from folks switching off of bisphosphonates that you've heard of anecdotally .
Speaker #15: Thanks .
Speaker #3: Yes . Well , I'll give you my more personal opinion is that I think bisphosphonates are going to become obsolete . I think they don't create good bone .
Speaker #3: They hold bone density that exists . But I think the anti-sclerostin approach is enabling normal bone metabolism . Bone creation , and bone resorption .
Speaker #3: But better balanced . And I think in the long run , the paradigm of building bone with an anti-sclerostin and then capturing or locking it in with bisphosphonates , which has been established in the osteoporosis world , will not be the right answer for why we have patients now on a couple of years , and we are confident that chronic therapy is actually necessary in order to maintain the gains in bone they have achieved and to keep bone healthy .
Speaker #3: I think the FDA even has own concerns about bisphosphonates because of long term bisphosphonate use seems to result in more fractures or problems because of the altered structure .
Speaker #3: So we're trying to break through the paradigm of one year of anti-sclerostin . And then bisphosphonate lock in . I think that that model is for a different disease state and a different time .
Speaker #3: And I think everything we're seeing says this is a chronic treatment . And that by maintaining anti-sclerostin treatment , what you're really doing is dialing up the balance between bone production and bone resorption to the proper place in a disease that drives that dial normally down toward resorption and away from bone production .
Speaker #3: And that dial needs to stay where it needs to stay in order to keep patients with a steady state of high quality bone without losing , you know , a bone poison to prevent breakdown of bone as a strategy .
Speaker #3: So in my view , that is future and bisphosphonates should probably become obsolete for .
Speaker #1: Thank you . Your next question comes from Salveen Richter with Goldman Sachs . Please state your question .
Speaker #16: Hi . This is Lidia on for Salveen . Thanks for the update and for taking our question . Maybe just another on could you just speak to any statistical work or study design changes you've made ?
Speaker #16: Post the second interim analysis ? Thanks so much .
Speaker #3: Well , I don't believe we made any , but Eric , I don't know if you if you wanted to have any any thoughts .
Speaker #3: I don't think there were any . I'm not familiar with any changes at all .
Speaker #6: No , no , the statistical plan remains in place . We , you know , did take the opportunity , you know , to really verify our assumptions , verify our statistical plan and all of our modeling and rework really told us the plan we had in place is the right plan .
Speaker #6: And really giving us a lot of confidence going into final data readout .
Speaker #16: Thanks so much .
Speaker #1: Your next question comes from Mehdi Goudarzi with Truist Securities . Please state your question .
Speaker #17: Hi . Good afternoon , and thanks for taking our question . This is Marion for June . Following a previous question on given cosmic is superiority studies in younger , narrower population .
Speaker #17: What are the scenarios if it misses and even if orbit hits , what are the impacts on adoption of the drug ?
Speaker #3: Yeah , well , the trial . Thank you . So the point is that cosmic is head to head against bisphosphonates and has to be superior .
Speaker #3: First of all , I don't think bisphosphonates were in those patients . Had to be they were on bisphosphonates before they started . So we're crossing over onto our drug I , I believe that bisphosphonate benefit , which is only about 20% , is relatively modest .
Speaker #3: So we actually are not concerned about it . But the question is the trial being smaller for whatever reason misses ? What does it do ?
Speaker #3: We'll still have the safety and mineral density data from that population , which I think would be supportive for allowing a label that includes that age group .
Speaker #3: Even if we can't be superior to bisphosphonates , particularly remember in the US there is no requirement to be superior to another treatment for approval .
Speaker #3: The treatment that what it would have an effect on adoption . I actually don't think it would . I think people will see what's happening .
Speaker #3: I think the little kids have terrible bone density problems , and I think seeing the big picture across group , I think will drive adoption in all age groups .
Speaker #3: So I appreciate the question , but I do think that this time I don't think we'll have a major impact either way .
Speaker #3: So I appreciate the question , but I do think that the age
Speaker #17: you .
Speaker #1: Your next question comes from Raj Selvarajah with H.C. Wainwright . Please state your question .
Speaker #18: Hey , this is Mitchell on for Raam . Thanks for taking the question . I wanted to ask about if you could just talk us through how the Crispr to transaction came to be and if there's a threshold at which you view a mature product as better used for monetization for capital recycling into the pipeline versus the recurring income from the product .
Speaker #3: Well , I'll start and then let Howard talk . I mean , we're always looking for the most efficient cost of capital and in this case , the valuation people place on the royalty was excellent .
Speaker #3: And we did that way . But I , I think in general , we'd want to try to keep our revenue streams and not do this .
Speaker #3: But I think we're just as critical moment here . But for us , with three potentially four products launching in the next couple of years , we're going to be in a very different place very soon and we won't be need to be talking about this , but maybe , Howard , you can touch on how the transaction came together .
Speaker #5: Yeah . You know , we evaluated a number of different things . This was a competitive process ultimately , where we were looking what
Speaker #5: capital well to minimize the impact of interest expense , while also maximizing our cash preservation . The payment holiday helps with that . And these other terms help with it .
Speaker #5: But as AML mentioned , we thought that we could take some future dated revenues and pull them into today to bolster our balance sheet to make sure we we had what we needed to , you know , to launch up to four programs in the near future and to put us on our growth path that we expect .
Speaker #5: .
Speaker #11: Great .
Speaker #18: Thank you .
Speaker #1: Your next question comes from Laura Chico with Wedbush. Please state your question.
Speaker #19: Hi . Good afternoon . This is Thomas on for Laura . Chico , thank you very much for taking my questions today . Perhaps one question for 701 and Wilson disease , can you discuss what you will need to see from the fourth cohort to have confidence in advancing the fourth to the 13 power dose into future studies ?
Speaker #19: Thank you .
Speaker #3: Yeah . Thank you . So I'll touch on it . And Eric , I don't know if when you add a little bit more , but I think if you could do a gene therapy you want to see , you know , a substantial effect in the majority of patients .
Speaker #3: Right . We want to see something that's , that's compelling . And what we're doing right now is increasing the dose to try to help enhance the fraction of patients that see that kind of effect .
Speaker #3: We're excited about what we're seeing . And there's some data being presented soon . But Eric , maybe you can talk about what you want to look for in the data for Wilson , as we make that decision to go to phase three .
Speaker #6: Yeah , no . And I think it's important to stress that , you know , first and foremost , we are looking for the majority of patients to come off of current standard of care , which is chelators and zinc .
Speaker #6: And Emil mentioned increasing dose . We are are changing our Immunomodulation program . So we think that those changes will be at least additive , if not synergistic with improving or really maximizing the efficacy .
Speaker #6: We see with this gene therapy . So , so great results that we've presented externally so far . And we were close to that .
Speaker #6: Mark . You know , we did think it was worth taking this extra time to do this . This cohort to to try to get the off of patient .
Speaker #6: And what's nice with Wilson and looking at copper is you have a lot of different ways to measure copper. So I think, you know, we will be able to make a clear decision there.
Speaker #19: Okay . Thank you again for taking my question .
Speaker #1: Your next question comes from Luca Issa with RBC Capital Markets . Please state your question .
Speaker #20: Hi , team . This is Shelby on for Luca and thanks for taking our question . Can you just remind us how we should think about loss of exclusivity for Sotrovimab ?
Speaker #20: This is obviously been a long journey for this molecule . Given it was originally developed by Novartis , then Mario , and finally you guys .
Speaker #20: So I believe some of the initial IP actually expires at the end of the decade in 2028 . Is that the foundational IP ?
Speaker #20: So a biosimilar can , in theory , come soon after that ? Or do you have additional IP assay that can maybe push out the loss of exclusivity to a later time point ?
Speaker #20: Any color there much appreciated . Thanks .
Speaker #3: Well , thank you . I think we've always looked at the whole story as being really important . I think we have , of course , orphan designation , which would give us certain protection , which is well past 2030 .
Speaker #3: So I would start with that . So that's the first part of the story . The second thing , even if there are , if there were no patents , the truth is that biologics like that rarely change in the following biologics may occur .
Speaker #3: But I think that it would be different from what typical loss exclusivity the . I don't think I can go through all the details of the patents that protect us .
Speaker #3: Now for the program . There are also additional things we're putting together related to our discoveries of how to treat , how to do chronic treatment and other things .
Speaker #3: So, we feel pretty good about where we're at right now. But you're right. Molecule has been around a while, and it was being developed for AI.
Speaker #3: I mean osteoporosis in the past. But I think a combination of drugs and our expectation to have some IP protecting it should put us in a good place to take this program forward.
Speaker #1: Thank you . And your next question comes from Sammy Corwin with William Blair . Please state your question .
Speaker #21: Good afternoon . Congrats on the progress , and thanks for taking my questions . I was curious if you could walk us through again the rescue arm in orbit and how that's factored into the statistical analysis plan .
Speaker #21: And then as you've had conversations with neurologists , how are they kind of viewing utility of the Bailey for cognition versus Bailey for communication ?
Speaker #21: Thank you .
Speaker #3: So the rescue arm , the point of the rescue arm is that if a patient was having a lot of fractures and a lot of PiS were worried if they come in the trial after bisphosphate , they have a lot of fractures .
Speaker #3: They're sort of stuck in the trial . They'd have to withdraw if the kid was doing badly . So we'd offer them that they could rescue if they if they have a large number of fractures , seeing a certain number of fractures .
Speaker #3: But they do have to be in the trial . At least one year . And then after that they could rescue the idea then is that with a one year sample time and a higher number of fractures , we'll have had enough time to assess their AFR .
Speaker #3: Right and determine their their analyze fracture rate . Right . If you have a lot of fractures in a one year time frame is enough to make that the estimate of the AFR .
Speaker #3: So if a patient goes into the rescue arm , we include all the time that they've been on drug as included in their analysis .
Speaker #3: And estimate their AFR from the time , the sampling time , does that make sense to you . So because we're doing an analyze fracture rate reduction , we just need a sample time that's adequate estimate of their true fractures .
Speaker #3: So that's the way it's working. But it was an essay part of doing the trial. And because doctors couldn't keep patients off bisphosphonates indefinitely and have a tremendous amount of problems, rather than have them withdraw, it would be better to find a way to keep them in the trial and cross them over.
Speaker #3: So thank you for that question . The next question was on the utility of Bayley for versus cognition versus communication . I , I will say to you , honestly , it doesn't matter what the primary endpoint is because I've never talked to parents .
Speaker #3: And had they don't ask me what the primary endpoint of trials are . They might talk about what you're measuring , but they are never going to depend on primary or secondary to make decisions .
Speaker #3: They want to look at all the whole story , and that is what we're going to provide . The whole story . We will have receptive and expressive communication in our program .
Speaker #3: We'll have answers for that . We compare them and the idea of what you position first . It's more of a regulatory thing .
Speaker #3: As I think limited value and at least in rare , I know in other big market diseases , the primary endpoint and its exact crafting turns out into a big deal .
Speaker #3: But in rare cases, I've not seen it happen. It's not really mattered because people will look at all the data and incorporate it.
Speaker #3: Our plan then is to focus on the Bailey for cognition . We saw the best effect . It's a fundamental brain function issue , but we're also looking at the rest of the communication and other endpoints , one through the multi main responder index and then through individual , secondary and tertiary endpoints .
Speaker #3: So we'll be able to speak to all the issues, all the endpoints, and be able to provide comparisons between the products as well.
Speaker #3: So I think that's why I'm not as concerned about what people choose as primary. We have to do that for regulatory purposes.
Speaker #3: But in the real world , I never went to my doctor and said , you know , my primary endpoint is this . But my secondary is this , and what can you do for me ?
Speaker #3: And no one ever speaks that way . So I'm really comfortable . What we have , we're covering every domain . And I think I feel good about the type of data we've seen so far in our expansion study .
Speaker #3: Patients make me comfortable that we're going to see China's changes in communication and cognition and sleep and behaviors and fine motor and expressive that will be , I think , an amazing future for Angelman patients , frankly , because who could have thought we could change a kid with severe developmental delay and actually start causing the brains to develop ?
Speaker #3: I think it's a miraculous situation. We're really proud to be part of it.
Speaker #21: Great . Appreciate all the color .
Speaker #1: Thank you. And your next question comes from Gavin Clark, Gartner with Evercore ISI. Please state your question.
Speaker #15: Hey , guys .
Speaker #22: Thanks for taking the question . Just wanted to ask on the ongoing Aspire Angelman study . Is there any commentary you can make on the variability you're seeing ?
Speaker #22: Any of the blinded data , any of the baseline characteristics , really just anything that gives you a confidence in the ongoing study ?
Speaker #22: Thanks .
Speaker #3: Well , the study's going well and we're confident we normally do not talk about data on a trial when it's gone . Going I don't know , Eric , if there's any high level color you can provide and the patient population , I believe they're very similar to the expansion patients .
Speaker #3: We've already reported on .
Speaker #6: Yeah . No , exactly . And I think , you know , that's important . We don't bring untested things into phase three .
Speaker #6: And really caring over our learnings . And understanding from phase two . So , you know , same entry criteria , same endpoints , same patient population .
Speaker #6: And again , looking in aspire for patients with full deletion . So you know those those are patients really expressing no protein very consistent phenotype .
Speaker #6: And you know the most severe the most severe . And and of that spectrum . So we do an anticipate very consistent results to what we saw in phase two .
Speaker #22: Great . Thanks .
Speaker #1: Thank you . And there are no further questions at this time . So I'll hand the floor back to Joshua Higa for closing remarks .
Speaker #2: Thank you . This concludes today's call . If there are additional questions , please contact us by phone or at IR at ultragenyx .
Speaker #2: Thank you for joining us .