Ultragenyx Pharmaceutical Inc at Leerink Partners Global Healthcare Conference Transcript

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

Question: Joseph Schwartz - Leerink Partners - Analyst : You obviously have a lot of irons in the fire. And maybe you can just start us off with your view of the catalyst path we can look forward to for those programs which you would expect to have the biggest potential to impact patients.

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, great. So if we could start with setrusumab, no surprise there probably. I know the company previously mentioned there was less than a 50% chance that the first interim analysis would hit. How are you thinking about the probability that IA2 might be triggered?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And can you help us contextualize the range of an effect size on fracture reduction that would be needed to hit the second interim? I know it obviously depends on things like variability and the timing of fractures, of course, but given the statistics and how they work, but any brackets that you can place around the range of fracture reduction?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And I guess one question we get all the time is based on the mechanism of action for setrusumab and given not all patients are of the subtype that have low insufficiency, and they just need more bone, but they have collagen defects that result in poor quality bone. A lot of folks wonder about how relevant the mechanism can be in those subtypes of patients. Can you help us understand the therapeutic logic?

Question: Joseph Schwartz - Leerink Partners - Analyst : Across the spectrum.

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, interesting. And how integral are the Cosmic data to the setrusumab story given many patients are on bisphosphonates now and that trial is head to head versus placebo after discontinuing bisphosphonates?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And I guess we hear that so many people are on these and some docs say if patients are stable, whatever that means, that they might not switch or add setrusumab necessarily. How do you view the flow of patients in the community if and hopefully when setrusumab is available given the presence of bisphosphonates already as standard of care, I guess?

Question: Joseph Schwartz - Leerink Partners - Analyst : Right. Yeah, that makes sense. And then how should we think about treatment duration? Are there any signals out of your existing data or will there be data out of the Orbit or Cosmic programs that will inform whether this is -- whether setrusumab is likely to be given with the same schedule forever, whether maintenance schedule might look a little bit different, or maybe another paradigm might take shape?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And how should we expect the Cosmic data to be disclosed? Will that be triggered? Will an announcement or look at that study be triggered when Orbit is triggered, or is there some other plan there?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. That's very helpful. So what about -- are there any other end points that we should keep an eye out for such as pain or quality of life? I mean, some of the stories that we heard about in the past out of the Phase 2 were pretty striking. How are you -- can you quantify any of those other benefits? 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 12, 2025 / 5:40PM, RARE.OQ - Ultragenyx Pharmaceutical Inc at Leerink Partners Global Healthcare Conference

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, great. And then, what's the best? Is there is there a good comp for how we should think about potential market uptake? Is there a good comp in perhaps Crysvita or any other bone or other types of agents?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, great. Well --

Question: Joseph Schwartz - Leerink Partners - Analyst : Oh yeah, please. Unidentified Participant (inaudible - microphone inaccessible)

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. So can we just talk briefly about how the statistics work in a general sense with your model waiting when fractures happen as well as the number of fractures? How much incremental power does that contribute? Is there any way to envision that?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, great. And then how should we think about or how is the company thinking about the value equation and how much -- what is your payer research imply is a good price for us to think about?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay.

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. Great. So shifting to Angelman, if we could. Outside of the study design and endpoints, has the FDA provided you with any color on the bar for success for approval of GTX-102?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And what is a clinically meaningful change or benefit relative to placebo on that endpoint?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And kind of a related question, how is the trial powered to show a difference on that end point?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And given it's a placebo-controlled trial, how are you maintaining the blind given how the drugs administered? And does the placebo or the inclusion of a placebo, could that make enrollment any bit of a challenge?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, interesting. And then we noticed that the clinical trial listing for the Phase 3 study states that the primary endpoint is changed from baseline Bailey-4 Cognitive raw score without caregiver input at day 338. Can you just talk about what is the significance, if any, of that caregiver input component and how that compares to how the data was collected in the Phase 1/2?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, great. And what should we expect for the Sanfilippo A gene therapy launch? It seems like we haven't seen too many really strong gene therapy launches, although the need here is pretty big. So what will really get the the rate of uptake there in your view?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, and then it seems like DTX401 is a real sleeper. Based on our checks, there's some enthusiasm out there because of that need. How would you view that potential uptake ultimately?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, super. Unfortunately we're out of time, but thank you so much for the update.