Ultragenyx Pharmaceutical Inc at Piper Sandler Healthcare Conference Summary

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

Question: Christopher Raymond - Piper Sandler - Analyst : <_ALACRA_META_ABSTRACT>Excellent. Okay. So maybe let's dive into the pipeline. Setrusumab obviously, is top of mind. This is when I speak to investors, everyone asked about this. So for osteogenesis imperfecta. So you announced earlier this year, maybe Eric, you fully enrolled the COSMIC study and then the Phase III portion of the ORBIT study. Maybe for those who aren't maybe familiar with this program, just give us a quick overview here of OI and the setrusumab sort of unmet need and the value proposition.

Question: Christopher Raymond - Piper Sandler - Analyst : And so you've provided 14-month data from ORBIT that's the Phase 2 portion of the study. Maybe speak to how these data evolved since the previous update before that? And help us understand how this sort of has a derisking perhaps potential for the Phase 3?

Question: Christopher Raymond - Piper Sandler - Analyst : Yes. Let's talk about that setup because I get you a lot of questions on that. So you've got a really high p-value bar and first interim analysis. The second one, I think, is a p-value of 0.01, and then you go on to the final analysis at the end of next year with 18-month data. Just maybe talk about the step and the -- I guess, the next -- sequencing of events as you go through those interim opportunities and into the data, the final data.

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. Excellent. Okay. So you also noted -- I think you won't provide baseline characteristics until you disclose the data. What we do know is the study has a population of about 50% have subtypes 3 and 4 and which tend to have more fractures and therefore, would you have a higher rate of fractures than you saw in maybe the Phase 2. This would arguably have been part of the statistical plan, but maybe just talk about that dynamic?

Question: Christopher Raymond - Piper Sandler - Analyst : Sorry. You haven't disclosed the baseline characteristics, but I think you had mentioned that you've got a subtype 3 and 4 in there, which would tend to have higher fracture rates.

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. Excellent. Maybe for Howard, so you're going to get this readout next year sooner or later, this would arguably be the perfect time to start market development, KOL development. Trying to understand with your partner, Mario, how to really attack the commercial effort. Maybe just talk a little bit about the market prep that you guys have ongoing right now in front of the data? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 05, 2024 / 2:00PM, RARE.OQ - Ultragenyx Pharmaceutical Inc at Piper Sandler Healthcare Conference

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. Excellent. All right. Let's maybe pivot to Angelman, which actually it's heartening to talk about something before Angelman actually for a change, but we have to talk about it. So obviously, that's still relatively top of mind, especially as you guys move into Phase 3 in that program. So you recently presented positive data from your dose expansion cohort and showed what I think is pretty impressive data that shows that it works. Maybe just let's talk a little bit about the Phase 3 study powering. So I think you said you'd expect the study to have greater than 95% power to detect a treatment effect. Help us understand how you arrived at this measure?

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. So maybe let's talk about the enrollment dynamics. So the Aspire study, you're looking for 120 patients aged 4 to 17. And with the enrollment criteria. Do you foresee being any sort of impact to enrollment dynamics given, like you said, it's relatively similar to your previous patient population? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 05, 2024 / 2:00PM, RARE.OQ - Ultragenyx Pharmaceutical Inc at Piper Sandler Healthcare Conference

Question: Christopher Raymond - Piper Sandler - Analyst : And especially with -- you're not the only company trying to enroll patients of this population. So you're feeling relatively confident?

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. So maybe on safety. So the modifications, I guess, to the dosing protocol seem to have addressed the lower extremity weakness issues that you observed in this -- early on in the study. But maybe talk about the sort of follow-up, I guess, from regulators that you think that they're going to be looking for?

Question: Christopher Raymond - Piper Sandler - Analyst : So this is a question I get a lot. [Ionis] had their data if you look at the efficacy sort of measures, they seem, at least from our vantage point, relatively comparable. And then, of course, the 582 drug did not have the AEs, especially that you saw early on. Obviously, that's just a snippet. There's many other attributes to the drug, but maybe just talk about the competitive set up specific to that drug. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 05, 2024 / 2:00PM, RARE.OQ - Ultragenyx Pharmaceutical Inc at Piper Sandler Healthcare Conference I'm not asking you to throw shade necessarily but as you're having this discussion with an investigator who's looking at enrolling in one of the two, how do you make that argument?

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. And then maybe for Howard, another commercial question. So this is not the most straightforward administration. There's training involved. You also have infrastructure transfusions, drug supply, other stuff. Maybe talk a little bit about as you get closer to the readout, the pivotal readout, the commercial sort of preparation activities.

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. All right. Maybe let's pivot to the Wilson Disease program, which I think is a very interesting program. So this is obviously you're in the midst of a Phase 1/2/3 program and getting more and more questions, but we actually heard some chatter from investigators and patients that were in your trial, there seems to be some, I guess, more if you will, I guess, inconvenience may be involved with the immunosuppressive regimen and the requirements to -- in preparation for the therapy. I don't know, any sort of -- sort of feedback you might have on that and your patient experience so far?

Question: Christopher Raymond - Piper Sandler - Analyst : To your statement on one and done, there's always a question on long-term durability with any gene therapy, right? I mean, we've seen this with a commercial gene therapy in hemophilia with one of your cohort companies where that is a real sort of barrier, I guess, to uptake. But what are you guys doing to sort of address maybe that concern if it comes from investigators or patients about really how long is this runway of benefit? I know you need to have the clinical data, but is there anything you can do with preclinical work that sort of helped sort of give a picture of how long the durability picture is going to look?

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. Great. So maybe one question on DTX401. This is your AAV gene therapy for GSD-1a. Sort of new, I guess, in your last earnings presentation, you guys talked about a crossover patient cohort that it's kind of got our attention. It looked like these patients did maybe a bit better than actually a lot better than the original treatment arm. Is there a hypothesis for why this happened?

Question: Christopher Raymond - Piper Sandler - Analyst : Okay. Maybe if I could switch to back to the commercial setting. A couple of questions there. Howard, I heard your commentary around path to profitability 2026. And I know you're not in a position to maybe give 2025 guidance just here. But just maybe talk about the setup as we get -- go in this 2025, obviously, a very important year if you're talking about GAAP profitability the year after. Just talk about in broad terms sort of the setup as we get into next year.

Question: Christopher Raymond - Piper Sandler - Analyst : Excellent. Okay. Lots going on, but we're out of time. So anyway, thanks for the great presentation.