Ultragenyx Pharmaceutical Inc. Q3 FY2024 earnings call

Clinical Pipeline Progress

• For UX-111 for Sanfilippo syndrome, reached agreement with the FDA that cerebrospinal fluid heparan sulfate is a reasonable surrogate endpoint for accelerated approval, and on track to file a BLA around the end of the year.
• UX-143 for osteogenesis imperfecta received breakthrough therapy designation from the FDA.
• DTX401 for GSDIa showed new data from cross-over patients with a 62% mean reduction in daily cornstarch requirement at 30 weeks post-treatment.
• UX701 for Wilson disease showed clinical activity and improvements in copper metabolism in the Phase 1/2/3 dose-finding study.

Commercial Portfolio

• Crysvita had strong global revenue growth, with 60% of US start forms from adult patients and 420 prescribers in the US. LatAm team added new Crysvita patients.
• Dojolvi saw increasing new start forms in the US and named patient sales in EMEA.
• Evkeeza had positive feedback and was being commercialized in various regions including Japan.

Future Plans

• Expect to have multiple BLA submissions, including UX-111 around the end of the year and DTX401 in mid-2025.
• Aim to launch three new therapies over the next couple of years, bringing first-ever approved treatments to patients.

In the third quarter of 2024, Ultragenyx reported total revenue of $139 million, a 42% increase from the prior year quarter. Crysvita contributed $98 million, with $56 million from North America, $36 million from Latin America and Turkey, and $6 million from Europe. Dojolvi contributed $21 million, Evkeeza contributed $11 million, and Mepsevii contributed $10 million. Crysvita's global revenue continued to grow, with strong demand in the US and Latin America. Dojolvi saw increasing new start forms in the US and named patient sales in Europe and MENA. Evkeeza had positive feedback from the HOFH community and was being commercialized in various regions including Japan.

Revenue Guidance

• Reaffirming total revenue range of $530 million to $550 million for 2024.
• Crysvita revenue expected to be towards the upper end of $375 million to $400 million, including all regions.
• Dojolvi revenue expected to be between $75 million and $80 million.

Risks

• Uncertainties related to regulatory approvals for BLA submissions.
• Variability in revenue growth due to uneven ordering patterns in certain regions.
• Operational challenges in clinical trial timelines and data collection for certain programs.
• Potential impact of market competition on commercial success of products.

Q: On the Wilson program, who is the ideal patient for the gene therapy?

A: The most addressable population for Wilson's disease is around 20% of patients who are not well-controlled or can't tolerate current medications. There's also a segment of patients who could do better than they are, but the main focus is on those with clinical symptoms not getting optimal copper management.

Q: Can you give more color on the negative binomial regression model used for setrusumab?

A: P. Tandon, Head of Biometrics, uses the negative binomial regression model as the best way for event-driven analysis, which the FDA has agreed to. It helps control for factors like baseline fracture, age, etc., and is a basic model suitable for rare disease programs.

Q: With regard to the near-term Angelman updates, what data should we focus on?

A: We'll provide more long-term data on the group, including data from patients on therapy for at least 338 days, showing the Phase 3 study is well-powered for primary and secondary endpoints, and update on overall safety in the Phase 3 plan.

Q: When could we expect to see data from the additional Stage 1 cohort for Wilson's disease?

A: Hoping to get the protocol in and set up early in the year, but it will take most of next year to get data as it depends on enrolling five patients and getting their data after at least 30 weeks of treatment. We're looking for a majority of patients to be off standard-of-care to make the gene therapy viable.

Q: What are key learnings from the Phase 2 14-month data update on setrusumab?

A: Learned that patients can have a profound degree of separation leading to most having no fractures over a significant period, and younger patients have a dramatic improvement in bone mineral density, giving confidence in the potential for early interim results.