Ultragenyx Pharmaceutical Inc.

Good afternoon, and welcome to the Ultragenyx fourth quarter and full year 2025 financial results conference call. At this time, all participants are in a listen-only mode. At the end of the prepared remarks, you will have an opportunity to ask questions during the Q&A portion of the call. It is now my pleasure to turn the call to Joshua Higa, Vice President of Investor Relations.

Thank you. We've issued a press release detailing our financial results, which you can find on our website at Ultragenyx.com. Joining me on this call are Emil Kakas, Chief Executive Officer and President, Howard Horn, Chief Financial Officer, Eric Harris, Chief Commercial Officer, and Eric Cromdes, Chief Medical Officer. I'd like to remind everyone that during today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please refer to the risk factors discussed in our latest SEC filings. I'll now turn the call over to Emil.

Thanks, Josh, and good afternoon, everyone. 2026 is poised to be a significant year for the company as we reach key inflection points across multiple programs. This includes two potential approvals in MPS3A or Sanfilippo type A syndrome and glycogen storage disease type 1A, and a pivotal data readout in Angerman syndrome. These programs are excellent examples of our mission to bring important first-ever treatments to patients and families while also delivering meaningful long-term value to shareholders. Just last week, we presented updated data at the World Symposium from the UX111 for MPS3A program. The new data reflect an additional year of follow-up and continue to demonstrate sustained and significant further separation of early treated patients in multiple neurologic endpoints, including the Bayley cognitive and communication scores when compared to the decline observed in MPS3A natural history. The data also show a significant and durable reduction in the toxic substrate heparan sulfate and other disease-caused biomarkers that show a restoration of lysosomal function, regardless of age or stage of disease. This reduction in CSF-HS can be effectively measured by any of a number of different assay methods available, and all HS measures correlate significantly to stabilization or improvement in clinical function. These results in humans and animal models were thoroughly discussed, substantiated, and ratified by highly trained and qualified academics, clinicians, and industry leaders that are the internationally recognized experts in this field at a Reagan-Udall convened workshop in 2023. For the entire UX111 study program, we now have more than eight years of follow-up, and overall, these data continue to support a clinically meaningful and durable clinical effect of UX111 regardless of age or stage of disease, all supported by consistent improvement in the multiple relevant direct measures of disease activity, including CSFHS. We resubmitted the UX111 BLA to FDA late last month, and earlier today received an incomplete response letter. We had provided complete responses to each CRL item, but now the FDA is requiring additional details within supportive documentation on the CMC-CRL responses made and their impact. This information is typically provided during an inspection, and we were prepared to do so, but we'll now provide this supportive documentation as a part of our BLA resubmission. Our efforts to bring these transformational therapies to patients are supported by our established and still growing commercial business, which again delivered significant 20% year-over-year growth in 2025. We're now bringing treatments to patients in more than 35 countries, each of which contributed revenue in 2025. This commercial infrastructure will power our growth into 2026 and beyond as we leverage the investments, expertise, and relations we have established around the world to commercialize three additional treatments over the next two years. Eric Harris will outline for you our results across programs last year and discuss our vision to expand and deepen our global commercial footprint in the coming years. As noted in our press release earlier today and following the UX111 CRL last year and the data from the UX143 trials, we made the necessary decision to implement a strategic construction plan to reduce our operating expenses and ensure our resources are squarely aligned with our highest impact opportunities going forward. Howard will now go through some of the details But these actions were necessary to keep us on path to profitability in 2027 while still advancing a meaningful pipeline of new products.