Material Event (Form 8-K)

Item 8.01 Other Events.

On March 12, 2026, Ultragenyx Pharmaceutical Inc. (the "Company") issued a press release announcing positive results from its Phase 3 Enh3ancestudy of DTX301, an investigational AAV8 gene therapy for the treatment of ornithine transcarbamylase ("OTC") deficiency. At Week 36 in the randomized, double-blind placebo-controlled period of the trial, DTX301-treated patients (n=18) demonstrated a statistically significant and clinically meaningful 18% (p=0.018) reduction in 24-hour plasma ammonia ("AUC0-24") compared to placebo (n=19) and maintained average ammonia AUC0-24 in the normal range through Week 36. Eight of nine patients with abnormal ammonia AUC0-24 at baseline despite optimal current drug treatment and diet restriction reached normal ammonia levels rapidly, which were generally maintained during this treatment period.

Baseline 24-hour ammonia AUC levels were normal in 50% of DTX301-treated patients and 68% of placebo patients, who were all on current care of scavenger medications and strict dietary control of protein intake. Patients treated with DTX301 (n=18) experienced reductions in 24-hour ammonia rapidly by Week 6 and were decreased by 18% (p=0.018) compared to placebo (n=19) at Week 36. Ammonia was generally maintained in normal range in treated patients despite their mean 27% reduction in ammonia scavenger medications at Week 36 (n=18) and an approximately 13% increase in protein intake relative to no change in placebo (n=19).

Assessed at Week 24, patient global impression scale ("PGIC") for OTC symptoms (total n=15 reporting) overall showed 71% of treated patients were much improved (equivalent to +3) versus 0% of placebo. For Week 24, PGIC evaluations of OTC deficiency symptoms and OTC impact on daily living (total n=30 reporting), both showed 64% were either much improved (43%) or moderately improved (21%) and on placebo only 19% were moderately improved (none were much improved).

DTX301 was well tolerated with an acceptable safety profile, consistent with prior Phase 1/2 safety data. The most common treatment-emergent adverse events were mild to moderate transient hepatic reactions managed with steroids. One serious adverse event ("SAE") of acute hepatitis was assessed as treatment-related and resolved with steroids. No SAEs or AEs related to thrombotic microangiopathy, dorsal root ganglion toxicity, malignancies, or other complex immune reactions. Hyperammonemic crises requiring hospitalization occurred five times in the placebo group with one death, and only one such event in the treated group and no deaths. Two patients in the placebo arm discontinued, including one death due to hyperammonemia crisis and one patient who became AAV8 antibody positive prior to crossover. One patient in the DTX301 arm discontinued after Week 36 for non-clinical reasons.

As planned, the study is continuing to its second primary endpoint which evaluates reduction in treatment burden, including use of ammonia scavengers and dietary management, across both the treatment and placebo-crossover groups following treatment with DTX301 through 64 weeks of follow-up. Data are expected in the first half of 2027. The conduct of the program is reflected in the Company's February 2026 guidance on 2026 spend and will be managed within the company goals of 2027 profitability.