On June 11, 2024, Ultragenyx Pharmaceutical Inc. (the Company), together with its collaboration partner, Mereo BioPharma Group plc, announced positive 14-month results from the Phase 2 portion of the ongoing Phase 2/3 Orbit study (NCT05125809) demonstrating that, as of a May 24, 2024 data cut-off date, treatment with setrusumab (UX143) continued to significantly reduce incidence of fractures in patients with osteogenesis imperfecta (OI") with at least 14 months of follow-up. Treatment with setrusumab also resulted in ongoing and meaningful improvements in lumbar spine bone mineral density at month 12 without evidence of plateau. The large reduction in annualized radiologically confirmed fracture rate previously reported in patients treated for a minimum of six months was sustained in patients treated for at least 14 months with a high degree of significance.

The median annualized rate of radiologically confirmed fractures across all 24 patients in the two years prior to treatment was 0.72. Following a mean treatment duration period of 16 months, the median annualized fracture rate was reduced 67% to 0.00 (p=0.0014; n=24). As of the data cut-off, there were no treatment-related serious adverse events observed in the study.

Reported adverse events were generally consistent with those observed in the Asteroid study with infusion-related events and headache determined to be the most common adverse events related to the study drug. As of the data cut- off, there were no reported hypersensitivity reactions related to setrusumab. More detailed 14-month data will be presented at a future scientific meeting.

The Company is developing setrusumab in pediatric and young adult patients across OI sub-types I, III and IV with two late-stage trials: the pivotal Phase 2/3 Orbit study and Phase 3 Cosmic study. The global, seamless Phase 2/3 Orbit study is evaluating the effect of setrusumab on clinical fracture rate in patients aged five to 25 years. In the Phase 2 portion, 24 patients were randomized 1:1 to receive setrusumab at one of two doses to determine the optimal dosing strategy for Phase 3. All patients from the 40 mg/kg dosing cohort have been transitioned to 20 mg/kg of setrusumab.

The pivotal Phase 3 portion of the study has enrolled an additional 158 patients at 45 sites across 11 countries, with subjects randomized 2:1 to received setrusumab or placebo, and a primary efficacy endpoint of annualized clinical fracture rate. All patients will transition to an extension period and receive open-label setrusumab after the Phase 3 primary analysis is complete. The global Phase 3 Cosmic study is an open-label, randomized, active-controlled study in patients aged 2 to <7 years.

Patients are randomized 1:1 to receive settingrusumab or intravenous bisphosphonates (IV-BP) therapy to evaluate reduction in total fracture rate. The Cosmic study has enrolled 69 patients at 21 sites across seven countries.