Ultragenyx Pharmaceutical Inc.

Good afternoon, and welcome to the Ultragenyx First Quarter 2024 Financial Results Conference Call. At this time, all participants are on 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. You may begin.

Thank you. We have issued a press release detailing our financial results, which you can find on our website at ultragenics.com. Joining me on this call are Emil Kakas, Chief Executive Officer and President, Eric Harris, Chief Commercial Officer, Howard Horn, Chief Financial Officer, and Eric Krambes, 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. This is the year that we're harvesting the exciting results of multiple years of focused execution across our key clinical programs, and we've shared a lot of meaningful data already this year. At the World Symposium meeting in February, we presented positive biomarker and long-term cognition data from our UX111 gene therapy in San Felipe syndrome. The data showed that treatment resulted in rapid and sustained production of CSF heparin sulfate and that this was correlated with improved long-term cognitive development. We also participated in a workshop on the heparin sulfate biomarker hosted by the Reagan Udall Foundation. This workshop brought together FDA representatives, patient advocates, scientists, and industry leaders to discuss the overwhelming body of data supporting the use of CSF heparin sulfate biomarkers. as a biomarker to enable accelerated approval in neuropathic MPS diseases. The support of Peter Marks and the FDA in recognizing this biomarker as a surrogate endpoint to support accelerated approval would be a profound benefit for the MPS communities and companies working on these diseases, and really to all companies working on gene therapies and other types of precision medicines. Shifting to citruzumab, just this week we announced that we've completed enrollment in our Phase II-III Orbit Study and our Phase III cosmic study in osteogenesis imperfecta. The Phase II data presented late last year was clearly compelling for the study investigators and led to accelerated interest and enrollment in the program. And two weeks ago, we announced strong positive interim data from the Phase I-II study of GTX1 and 2 in ANG1 syndrome. The interim data we shared confirmed in a larger body of data that GTX1 and 2 can fundamentally change the development trajectory of ANG1 patients. Importantly, the magnitude of the effect across all domains in the expansion cohorts was found to be similar or greater than what we observed previously with the dose escalation cohorts. Ongoing treatment with GTX1-2 resulted in continuous and sustained improvement in these patients, as evidenced by the long-term data in the dose escalation cohorts. And we have demonstrated the safety profile can be successfully managed. This Phase 1-2 study is valuing the most severe Angelman syndrome patients, those with genetic deletions, where there's typically no improvement on the Bayley scale. This is observed in both natural history and placebo-controlled studies. For example, our recent Angelman clinical study, after one year, their placebo group showed only a 0.8-point improvement in Bayley-3 cognition score. What we saw in our study was a 5-point improvement in the Bayley-4 score, beginning as early as day 170 in the dose expansion cohorts and almost double that at one year in the dose escalation cohorts. We also saw that this improvement continued through day 758 in the dose escalation cohorts. The magnitude of the change we observed with the Bayley was further supported in multiple other assessments, including angel severity assessments and the aberrant behavior checklist. The improvements in the domain of sleep and behavior or hyperactivity at day 170 were better than what we saw after a year or more in the prior cohorts. Families also talked about their kids being calmer, more attentive, more aware of the world around them. This allowed greater independence across multiple facets of development like eating, sleeping, and mobility. The improvements in cognition and motor function really came across in the videos that we showed on April 15th call, the patient was able to solve puzzles and navigate more challenging walking paths, which provide a small, real-world sample of the significant changes we're seeing in the charts and graphs. The combination of improvements across cognition, receptive communication, and motor function provide a real sense of the potentially transformative nature of this therapy. The Multi-Main Responder Nix, or MDRI, also resonated with physicians and families The MDI brings all the domain of movement across the study population together and is a great way to look at changes across individual patients for a heterogeneous patient group. MDI analysis across the four domains of cognition, receptive communication, behavior, and sleep resulted in a statistically significant median improvement of two domains across all cohorts at this early time point of day 170. Further, the majority of the patients in the expansion cohorts achieved improvements in at least two and up to all four domains. Importantly, the data we presented show that GTX1 and 2 has a tolerable safety profile. Lowered extremity weakness is now a rare, well-understood transient event that occurred in two out of 53 patients in the extension cohorts who had completed the loading phase. Both patients were in the cohort A and B, and no events observed in cohort C through E. The events were classified as mild and moderate and all resolved quickly with the patient remaining in the study. Six earlier patients with this safety issue from the beginning of the study are all on chronic dosing and received multiple doses without any issues. Given our understanding of this issue and recent feedback from regulators, we are comfortable that the current safety profile is acceptable and manageable and will continue providing routine safety updates only with our efficacy updates. We've heard strong enthusiasm from KOLs over the past couple weeks, including those reviewed by our analysts. Some of you might be on the call. These treating physicians expressed comfort with the safety profile and the route administration of these patient populations, and the broad agreement that treatment with GHTX1 and 2 resulted in clearly meaningful advocacy in these patients, where you just don't typically see any improvements. With all this put together, we have a strong product candidate and plan for Bay 3 development. We're confident this product candidate has potential to be a transformative treatment for patients with Angelman syndrome. Now I'll turn the call over to our Chief Commercial Officer, Eric Harris, to provide an update on our commercial efforts that led to another successful quarter.