Ultragenyx Pharmaceutical Inc Q3 2024 Earnings Call Summary

The following is excerpted from the question-and-answer section of the transcript.

Question: Chris Raymond - Piper Sandler Companies - Analyst : Congrats from us on all the progress. Maybe two questions. I guess, first on the Wilson program, maybe Emil, what is -- who is the ideal patient for this gene therapy? Would this be -- as you guys are envisioning a commercial rollout suited for patients that are well controlled maybe on copper chelators or zinc? Or would this be targeted only for those most severe patients? And then maybe also a follow-up on setrusumab. Can you give a little bit more color on this negative binomial regression model that you're using? Just to explain a little bit about what that means, what you're doing there?

Question: Tazeen Ahmad - BofA Global Research - Analyst : On OI, Emil, given the timelines that you've provided for the different interim reads, if the study has to continue past the first interim, is there a calculation that you've made about likelihood of success of the trial? That's the first question. And then secondly, with the timeline to when this would become commercial very significantly depending on which at the time point the study would eventually stop assuming that it would be successful at one of those stops if that question is clear.

Question: Malcolm Kuno - JPMorgan - Analyst : This is actually Malcolm Kuno on for Anupam. So what data should we focus on with regard to the near-term Angelman updates coming at the near-term medical conferences?

Question: Malcolm Kuno - JPMorgan - Analyst : Great. Thank you.

Question: Gena Wang - Barclays - Analyst : Maybe just quickly follow the previous questions. Will data at the FAST and the CNS meeting, the same data set. And I have one question regarding setrusumab Phase III study. I mean, you did actually provide a little bit more clarity regarding the timeline. I remember last time was more likely beginning of 2025. Now is at year-end beginning of 2025. And second interim, very definitive is 1Q '25, is that because the event is already picking up and you have more clarity regarding when this will happen? And then also, will you share the baseline characteristics of Phase III trial at some point? If not, could you comment on patient baseline attack rate range? And also the breakdown of the patients, specifically between age 5 to 12, 12 to 18 and 18 to 25. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 05, 2024 / 10:00PM, RARE.OQ - Q3 2024 Ultragenyx Pharmaceutical Inc Earnings Call

Question: Lydia Erdman - Goldman Sachs - Analyst : This is Lydia on for Salveen. Congrats on the progress. Just on Wilson's disease, when could we expect to see data from this additional Stage 1 cohort? And I guess, what would you want to see from this data set to gain confidence in the regulatory and commercial outlook?

Question: Maury Raycroft - Jefferies - Analyst : Congrats on progress. For setrusumab, just wondering what are key learnings from the Phase II 14-month data update at ASBMR that help you triangulate around fracture rates and chances of success for the first interim or second interim updates. And maybe just a quick follow-up. If you can clarify if you'll have new patients with less follow-up in the Angelman data updates that you have.

Question: Maury Raycroft - Jefferies - Analyst : Got it, thanks for taking my questions.

Question: Mehdi Goudarzi - Truist Securities - Analyst : This is Mehdi on for Joon. So on Angelman, could you please provide some color on the RR study, given the patients age from 2 to 64 in diverse mutation type that are included, so what should be the optimal endpoint for patient study? And would Bayley-4 Cognition be the one for this study?

Question: Mehdi Goudarzi - Truist Securities - Analyst : Thank you.

Question: Yaron Werber - TD Cowen - Analyst : I got a couple of questions. Maybe the first one, just on setrusumab, and I totally understand the need to -- when you finish the study to have a couple of further assessments. At the time in which this goes to a committee, independent committee and, let's say, based on the events they decided to recommend to you to terminate the study, I think they will do based on the fracture rates and statistics and the hazard ratio, can you at least let us know hopefully, when that hits and becomes positive that you hit and the hazard ratio is X, Y, Z at a certain p-value is the first question? Or would you really just not say anything until later. And then secondly, just on 401. Did you complete the tech transfer to your own facilities now that you have a filing around mid next year? And anything you can share with us initially on margin in COGS because you're going to be obviously scaling a whole facility? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 05, 2024 / 10:00PM, RARE.OQ - Q3 2024 Ultragenyx Pharmaceutical Inc Earnings Call

Question: Yigal Nochomovitz - CITI - Analyst : Maybe I missed it, but just with regard to DTX401, it doesn't appear that you gave us the specific reduction for cornstarch for the patients that were on the treatment in the 48-week primary period, you have that information? And just the way I'm thinking about it is, I would think, that they would catch up given we know that they received the gene therapy and should catch up to the ones that were the crossovers.

Question: Yigal Nochomovitz - CITI - Analyst : Okay. I guess what I was driving at is will there become a point in time where you'll share the 78-week data from the ones that were originally on therapy from the very beginning in terms of the total cost structure.

Question: Yigal Nochomovitz - CITI - Analyst : And then more just a corporate picture in terms of the cash and the profitability. I recall at the R&D Day just over a year ago in New York, you had a sort of a qualitative slide on the path to profitability. It wasn't too specific as far as numbers in the exact year. So now that you're burning $400 million in cash a year and a little over $800 million in the bank. I'm just wondering if you could comment any further on revised thoughts around the time to profitability? I know you mentioned that the launch in Japan could accelerate that.

Question: Yigal Nochomovitz - CITI - Analyst : Thank you.

Question: Thomas Yip - H.C. Wainwright & Co., LLC - Analyst : This is Thomas Yip asking a couple of questions for Ed. So first, a question for GTX-102 for Angelman syndrome, the Phase III EXPR study. So recorded preliminary design that was discussed in April was incorporate 12-week or 84 days primary efficacy time point period. Can you discuss the significance of this duration? And then second question for 143, can you discuss development status progress? What next step that we can expect from this program in 2025?

Question: Thomas Yip - H.C. Wainwright & Co., LLC - Analyst : Yes. That was just wanted to understand the duration of the data measurement so that helps. Thank you again for taking our questions.

Question: Jack Allen - Robert W. Baird & Co., Inc. - Analyst : Congratulations to the team on the progress made over the course of the quarter. I know there's been a lot of discussion on setrusumab and the interim analysis on the call, but I was hoping we could just step back and provide some more context around what triggers the interim analyses. I think there was a comment made by Emil previously about an estimation of time to fracture rate. And I just want to understand, are the interims set in stone as it relates to when those interims occur? Or is there still incoming data that needs to be accrued to determine the timing of the interim analysis?

Question: Jack Allen - Robert W. Baird & Co., Inc. - Analyst : That's very helpful. Can I just ask one brief follow-up. I guess, how did you think about the potential time for onset of setrusumab when you were making those fracture estimates, and I guess, that's all I'm really interested in. Maybe when operationally did you make that change in the thinking as it relates to estimating the fact rate rather than going off a bit, yes. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 05, 2024 / 10:00PM, RARE.OQ - Q3 2024 Ultragenyx Pharmaceutical Inc Earnings Call

Question: Joe Schwartz - Leerink Partners - Analyst : Great. I also have a couple of questions on setrusumab, I was wondering, first, on ORBIT, if you could talk a little bit more about how you're calculating the effect size in ORBIT, how that compares to how you did in Phase II and then the range of effect size separations that might be needed in order to hit (inaudible) at the different interim analyses would be very helpful. And then I have a follow-up on COSMIC.

Question: Joe Schwartz - Leerink Partners - Analyst : Okay. And then what kind -- sorry, sorry, go ahead.

Question: Joe Schwartz - Leerink Partners - Analyst : Okay. So in terms of COSMIC, what kind of a treatment effect do you assume in your powering relative to bisphosphonates, what do you hope to see for the setrusumab arm? Are there any nuances in terms of how the endpoints in COSMIC are calculated versus ORBIT?

Question: Joe Schwartz - Leerink Partners - Analyst : Thanks again.

Question: Michael Riad - Morgan Stanley - Analyst : This is Michael Riad on for Jeff Hung. For UX111 for (inaudible), given reductions in heparan sulfate and their association in Bayley, is it safe to assume like HS is the sole biomarker data in the BLA? Or do you expect to include other measurements like maybe more downstream markers like NFL, just in case? I have a follow-up. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 05, 2024 / 10:00PM, RARE.OQ - Q3 2024 Ultragenyx Pharmaceutical Inc Earnings Call

Question: Michael Riad - Morgan Stanley - Analyst : That's helpful. And then as a follow-up for the interim setrusumab analysis, like if you see a similar fracture like you would have seen in ORBIT, would that treatment effect have been like sufficient enough to like winding back to ORBIT with the like ORBIT have detected a cleared enough separation at like representative first interim analysis?

Question: Michael Riad - Morgan Stanley - Analyst : No, that's very helpful. Thank you.

Question: Kristen Kluska - Cantor Fitzgerald - Analyst : On setrusumab, I was hoping to get a little bit more color around at about the placebo arm. We know that the five bisphosphonates studies had diverse readouts. So can you give us some context about how you developed that 20% figure. And then is there any possibility in this trial that because patients are used to being quite inactive that we could see more fractures on placebo if the protocol requires them to go to the clinic.

Question: Dae Gon Ha - Stifel Nicolaus and Company, Incorporated - Analyst : I wanted to -- we'll take a different angle to the setrusumab line of questions that have dominated the call today. I wanted to ask about manufacturing for setrusumab. Just if you can maybe remind us what scale is it at? Does that plant actually have some precedent or regulatory success track record when it comes to getting a drug approved and similarly, when it comes to burosumab or Crysvita, it was, I guess, as of 2023, transmission over as more of a royalty-based commercialization activity in the US. So just wondering from a sales force standpoint, how ready are you -- if you were to hit the interim number one, would there need to be a massive hiring spree that would need to get done.