Ultragenyx Pharmaceutical Inc. Q4 FY2024 earnings call

2024 was a pivotal year with advancement of 6 late-stage programs in serious genetic conditions. International growth was strong with EVKEEZA launches in Europe, Canada, and Japan, and expanded access in other regions. UX111 program for Sanfilippo syndrome showed promising clinical data with sustained reduction in CSF HS and improved cognitive scores. CRYSVITA franchise had strong results in various regions, with DOJOLVI seeing growth in start forms and new prescribers. EVKEEZA had increasing demand in EMEA and Japan. The company focused on expense management and advancing Phase 3 programs, with an eye toward full year GAAP profitability in 2027.

For 2024, total revenue was $560 million, representing a 29% growth over 2023. CRYSVITA contributed $410 million, with $249 million from North America, $135 million from Latin America and Turkey, and $26 million from Europe, showing 25% growth over 2023; Latin America and Turkey CRYSVITA sales grew 78% over 2023. DOJOLVI contributed $88 million, a 25% growth over 2023. EVKEEZA contributed $32 million as demand built outside the U.S. MEPSEVII contributed $30 million in the ultra-rare indication.

2025 total revenue is expected to be between $640 million and $670 million, representing 14% to 20% growth over 2024. CRYSVITA revenue is anticipated to be between $460 million and $480 million. DOJOLVI revenue is expected to be between $90 million and $100 million. There is an expectation of reduced net cash used in operations compared to 2024, with the first quarter including $45 million in payments for milestones achieved in the fourth quarter of 2024.

Uncertainties exist in clinical trial outcomes, including variability in fracture rates in OI studies which could impact results. There are also uncertainties regarding regulatory approval timelines and potential variation in revenue due to uneven ordering patterns for some products.

Q: Tazeen Ahmad from Bank of America inquired about confidence in the second interim read for the OI study.

A: Emil Kakkis stated that they believe the second interim has a much greater chance of hitting than the first due to the 0.01 threshold and patients having at least 12 months of treatment. If it doesn't hit, they would communicate the status at that time.

Q: Salveen Richter from Goldman Sachs followed up, asking about risks if the second interim doesn't hit.

A: Emil Kakkis said large variation in fracture rates could be a reason, and if the second interim doesn't hit, they would release final analysis data by the end of the year.

Q: Anupam Rama's team asked about filing after the Orbit study hits.

A: Emil Kakkis said if Orbit hits, they would file more quickly as the database is locked and the Data Monitoring Committee (DMC) would inform them, and it would be relatively sooner to share results.

Q: Gena Wang from Barclays asked about the timeline for the second interim of the OI study and communication.

A: Emil Kakkis said midyear is the range, the DMC would meet, and if the second interim hits, they would share results sooner as the database is locked; if not, they would communicate the status.

Q: Yaron Werber from TD Cowen asked about stratification in the Orbit study.

A: Emil Kakkis said they stratify mainly by fracture rate and age, and look at total fractures as the endpoint.

Q: Yigal Nochomovitz's team asked about retrospective analysis in the OI study.

A: Emil Kakkis said they look at Phase 2 data as a model, and the data from Phase 2 is a reasonable model for what's happening.

Q: Maury Raycroft's team asked about the final analysis if the second interim for OI hits.

A: Emil Kakkis said if the second interim hits, they would share results sooner as the database is locked and the DMC would inform, and they wouldn't hold up filing for 18-month data.

Q: Joon Lee from Truist Securities asked about the OI study completion and competitiveness.

A: Emil Kakkis said it doesn't mean the effect is less, and they think the drug is far better than bisphosphonates.

Q: Jeff Hung from Morgan Stanley asked about Phase 2 patients with fractures.

A: Emil Kakkis said Phase 2 patients with fractures weren't only type 3s and 4s, and bone mineral density improvement was comparable across types.

Q: Joseph Schwartz's team asked about learnings for UX111 launch.

A: Emil Kakkis said they would look at other launches, focus on urgency, and work with payers upfront, with Erik Harris adding close contact with treatment centers.

Q: Kristen Kullka's team asked about the OTC deficiency protocol amendment.

A: Emil Kakkis said they allowed up to 200 micromolar ammonias, expected a rapid drop to normal range, and endpoints would be monitored; Erik Harris added parallels to GSDIa.

Q: Luca Issi from RBC Capital asked about OI therapy duration and Angelman study design.

A: Emil Kakkis said OI patients need chronic therapy as they continue to benefit longer, and for Angelman, sham was chosen over placebo due to ethical/regulatory considerations.

Q: Liisa Bayko from Evercore ISI asked about variability in OI study.

A: Emil Kakkis said there was a wide range of baseline fractures, younger patients have more fractures, and the study is powered to handle variation.

Q: Ed Arce's team asked about the Aurora study for GTX-102.

A: Emil Kakkis said Aurora will study younger/older patients and other mutations, support labeling, and be done in other territories.

Q: Yaron Werber from TD Cowen asked about data timing for DTX401 and interim analysis on Cosmic.

A: Emil Kakkis said data timing for DTX401 wasn't specified yet; for OI, Orbit and Cosmic interims are run in parallel with a 0.01 p-value, and if Orbit hits, Cosmic data is also considered