Ultragenyx Pharmaceutical Inc. Q2 FY2025 earnings call

• Ultragenyx marked 15 years as a company in April 2025, with 5 approved programs and 5 Phase III clinical programs. - UX143 (setrusumab) for osteogenesis imperfecta: Orbit and Cosmic studies continuing to final analysis end of year, safety profile expected, confident in successful study. - GTX-102 (Angelman syndrome): Received Breakthrough Therapy designation, Phase III Aspire study completed enrollment ahead of plan, on track to read out data H2 2026. - Commercial progress: Double-digit revenue growth, Crysvita growing in regions, Dojolvi, Evkeeza, and Mepsevii contributing to top line.

In the second quarter of 2025, Ultragenyx reported total revenue of $166 million, representing a 13% growth over Q2 2024. For the first half of 2025, total revenue was $306 million, a 20% growth compared to H1 2024. Crysvita contributed $120 million in Q2 2025, including $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe. Dojolvi contributed $23 million, Evkeeza contributed $15 million, and Mepsevii contributed $8 million. Total revenue guidance for 2025 is reaffirmed at $640 million to $670 million, with Crysvita revenue expected to be $460 million to $480 million and Dojolvi revenue $90 million to $100 million.

• Reaffirmed 2025 total revenue guidance of $640M-$670M (14%-20% growth YOY). - Crysvita revenue expected $460M-$480M (12%-17% growth YOY). - Dojolvi revenue expected $90M-$100M (2%-14% growth YOY). - Path to GAAP profitability in 2027, managing cash burn and expenses.

• Regulatory risks related to FDA interactions, including CRL resolution for UX111. - Timing delays in clinical programs (UX111, DTX401, UX143). - Potential impact of leadership changes at FDA on CRL resolution.

Q: Considering the leadership at the agency has been rather fluid lately, could you provide a glimpse into any of your recent FDA interactions, especially at CBER?

A: Well, I think our interactions since the CRL of late has been good. I think they are productive, and we're working toward getting our Type A meeting package sent in. So we're pleased with how things are going.

Q: Given GTX-102 and rugonersen both use LNA chemistry, could you please elaborate on nontarget site-dependent factors that drive very different dosing regimens that you both have for these drugs?

A: The LNA chemistry we're using is primarily chosen because it is substantially more potent. It can have more toxicities and which is known, but its potency is -- was dramatically better for the target on the -- or at least one order of magnitude or more in our hands when we compare it to non-LNA chemistry. So there's a reason for it. We think the potency gives us a dosing that's in the 5- to 14- milligram range, which I think is a distinct advantage because the nonchemical or the chemical-based off-target effects will be less since we're operating at a relatively low chemical concentration.