Material Event (Form 8-K)

On December 29, 2025, Ultragenyx Pharmaceutical Inc. (the "Company") announced results from the Phase 3 Orbit and Cosmic studies for setrusumab (UX143) in Osteogenesis Imperfecta ("OI"). Neither study achieved statistical significance against the primary endpoints of reduction in annualized clinical fracture rate compared to placebo or bisphosphonates, respectively. Both studies achieved the secondary endpoints of improvements in bone mineral density ("BMD") against comparators. There was no change in the safety profile observed.

Orbit and Cosmic Results

In the Orbit study, participants experienced statistically significant and substantial improvements in BMD compared to placebo, at levels consistent with the treatment effect observed in the Phase 2 portion of the study. These BMD changes were not accompanied by a corresponding reduction in annualized fracture rates and there was a low fracture rate in the placebo group.

In the pediatric Cosmic study, patients had a substantially higher baseline fracture rate compared to the patients enrolled in Orbit. In this younger patient population, meaningful improvements in BMD were associated with a reduction in annualized fracture rate for setrusumab treated patients compared to bisphosphonate treated patients, though the reduction did not meet statistical significance.

The Company is conducting additional analyses on the data across both studies, including on other bone health and clinical endpoints beyond fractures to assess next steps for the program given the totality of these data.

The Company will implement expense reductions

The Company is evaluating its planned operations and will promptly define and implement significant expense reductions.