Ultragenyx Pharmaceutical Inc at TD Cowen Healthcare Conference Summary

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

Question: Yaron Werber - TD Cowen - Analyst : <_ALACRA_META_ABSTRACT>So a lot to talk about. We're going to focus on OI then Angelman and we definitely want to talk about the pipeline as well. Maybe let's start by -- you talked about doing the second interim analysis for the Orbit study based on the April data cut, which is the 12-months data cut. And at the same time, you're going to do now an interim analysis, which I think is also based roughly about 12 months into the Cosmic study, but that's going to be your first interim, and you're only going to do that interim if the interim and Orbit works, right? At that point, you'll trigger the interim analysis on Cosmic. Do I have that correct? Is that how you're going to determine?

Question: Yaron Werber - TD Cowen - Analyst : So you will do the interim analysis from Cosmic regardless of whether -- I mean, you're going to do the second IA for Orbit, but you only release that if it hits, obviously. But with Cosmic, you announce regardless, you'll do that IA regardless?

Question: Yaron Werber - TD Cowen - Analyst : But if -- okay, so let's play it out. If Orbit hits, I mean, you'll discuss that, and then it sounds like you'll just continue with Cosmic.

Question: Yaron Werber - TD Cowen - Analyst : So with Cosmic, it sounds like you did not do the first -- you didn't do a first interim, right? What was the reason for that? And to do it in Orbit and it sounds to me like and its own words, that you did it at around 6 months and kind of what extends to the second is going to be 12 months and not doing a similar analysis for Cosmic. Is it because of the washout on BPs and how long they might have an effect for?

Question: Yaron Werber - TD Cowen - Analyst : Got it. And with Cosmic, I guess, in the very unlikely situation, which Orbit does not meet what can Cosmic get you? And I imagine it's got its own statistical plan separately? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 03, 2025 / NTS, RARE.OQ - Ultragenyx Pharmaceutical Inc at TD Cowen Healthcare Conference

Question: Yaron Werber - TD Cowen - Analyst : And so maybe just remind us as you just did, Orbit is 159 patients. What age groups is that, and it's obviously low, high versus placebo. Cosmic is 50, right? Head-to-head against standard of care. So maybe give us a sense of the age groups? And then how is Cosmic powered as well?

Question: Yaron Werber - TD Cowen - Analyst : And for Cosmic, is it sufficiently powered on the primary endpoint statistically?

Question: Yaron Werber - TD Cowen - Analyst : And what's the -- I remember with Orbit, you're looking for 50% delta sort of an absolute. What about at Cosmic?

Question: Yaron Werber - TD Cowen - Analyst : And what time point?

Question: Yaron Werber - TD Cowen - Analyst : 24 months. With Cosmic in general, you would expect to see more fractures, right, than Orbit as patients are younger age. Am I thinking about this correctly?

Question: Yaron Werber - TD Cowen - Analyst : Okay. So the difference is, Cosmic, you stay on BPs and Orbit you wash out. And just remind us how long is the wash out for?

Question: Yaron Werber - TD Cowen - Analyst : But they stopped them, is it 30 days or at least 30 days?

Question: Yaron Werber - TD Cowen - Analyst : So we were in some simulations and statistical and it's obviously all about sort of what you know and how you set it up. But we took sort of everything we knew. It sounds like the fracture rate was 0.7 before. It sounds like the rates were higher in Orbit, at least relative to what it was in the Phase II. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 03, 2025 / NTS, RARE.OQ - Ultragenyx Pharmaceutical Inc at TD Cowen Healthcare Conference And so once we started kind of looking at the first interim analysis, I mean, to really stop it at that point, you had to have been sort of in the 60%, 70% plus absolute treatment effect. In the second one, with we think you have ample power based on 40% to 60% delta. And then you can probably hit on the third, if you're in the 30% to 40% delta. Are we in the ballpark?

Question: Yaron Werber - TD Cowen - Analyst : And by the way for the audience. If you have any questions, just raise your hand, we're happy to take them on your behalf. The -- I guess the one thing that we're getting a lot of questions on, is it sounds like you'll do the second IA based on April data. Let's say, if you -- you announced the last one in January, but if we're correct, and it was based on a six-month look, that was based on an October data cut, which took about two to three months sort of the clean. Is Orbit going to take just as long in the second eye to clean the data? Or did you already present some of it, it's going to be faster?

Question: Yaron Werber - TD Cowen - Analyst : And at that point, at the time in which you announced that hopefully, it hit, the patients at that point, they still need to come back for a last visit, last safety visit before you can announce,? Or they could do that afterwards?

Question: Yaron Werber - TD Cowen - Analyst : Okay. And you can do that you just need all the patients to come in maybe an extra visit right before you do that second look.

Question: Yaron Werber - TD Cowen - Analyst : Okay. We can come back to -- yeah, go ahead. Unidenified Participant Just really quickly, some KOLs are saying that type 3 specifically is severe than either 4 or 1. Just remind us what you saw from the Phase II if you add type 3s? And is it helpful to have more type 3s in these studies? And did you try to get more type 3s in these studies?

Question: Yaron Werber - TD Cowen - Analyst : I'm sorry, it's 50%?

Question: Yaron Werber - TD Cowen - Analyst : That's in the Phase III. And what was in the Phase II? I'm sorry if I missed it.

Question: Yaron Werber - TD Cowen - Analyst : Yes. Okay. We're going shift -- we're going to shift over to Angelman. And the -- we're going to do a panel actually. I think it's tomorrow

Question: Yaron Werber - TD Cowen - Analyst : I'm sorry, for cognition. Did I say communications?

Question: Yaron Werber - TD Cowen - Analyst : And so how does that again, we'll discuss this in the panel a little bit more detail tomorrow. But literally, how does these -- the nice thing about Bayley-4 it's literally fairly subjective, right? It's given by the same reviewer at the office. It's not dependent on retrospective sort of patient feedback. But how do you assess communication versus cognition.

Question: Yaron Werber - TD Cowen - Analyst : And so one of the challenges, these are phasic kids with developmental delay with a motor component. So even as part of communications, some of it is there's a box test, right, move cubes around and all kinds. These are inevitably motor. So it does require some interface between motor skills as well. How does that handled?

Question: Yaron Werber - TD Cowen - Analyst : And so when you powered the Phase III, can you remind us how that was done? And what's the delta you're looking for?

Question: Yaron Werber - TD Cowen - Analyst : And you're looking specifically cognition based on raw scores from baseline, right? Can you tell us why that's important?

Question: Yaron Werber - TD Cowen - Analyst : Any questions from the audience? It sounds like the study is ongoing, and it sounds like you're expecting enrollment fairly rapidly, right? And how many sites do you expect to have open and how many are open right now?

Question: Yaron Werber - TD Cowen - Analyst : And would you have sites in Australia as well? And how about Japan?

Question: Yaron Werber - TD Cowen - Analyst : Right, Jane, over to you.

Question: Yaron Werber - TD Cowen - Analyst : Perfect. Eric, thanks so much, and Josh. Really appreciate your comments.