Financial Data and Key Metrics Changes - In Q2 2025, total revenue was reported at $166 million, representing a 13% increase over Q2 2024 and a 20% increase year-to-date [20] - The net loss for the quarter was $115 million, or $1.17 per share, with cash, cash equivalents, and marketable securities totaling $539 million as of June 30, 2025 [21][22] - The company expects 2025 total revenue to be between $640 million and $670 million, indicating a growth of 14% to 20% over 2024 [22] Business Line Data and Key Metrics Changes - Crysvita contributed $120 million in Q2 2025, with $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe [20] - Dajolvi generated $23 million, while Akiza and Mepsevii contributed $15 million and $8 million, respectively, reflecting steady growth trajectories for these products [20] - The commercial teams reported double-digit revenue growth, with total revenue across the first two quarters reaching $306 million, a 20% increase compared to the previous year [12] Market Data and Key Metrics Changes - In Latin America, approximately 825 patients are now on Crysvita, with positive feedback from healthcare providers leading to increased prescriptions [14] - In the U.S. and Canada, Crysvita revenue is expected to continue growing as new pediatric and adult patients are identified [15] - The EMEA region has seen approximately 280 patients treated with DERJOVY under named patient sales, with strong demand noted in France and other countries [17] Company Strategy and Development Direction - The company aims to achieve GAAP profitability by 2027 while focusing on revenue growth and managing expenses [22][30] - Ultragenyx is advancing its clinical pipeline with five Phase III programs fully enrolled or at the BLA submission stage, including UX143 for osteogenesis imperfecta and GTX102 for Angelman syndrome [6][10] - The company is committed to navigating pricing negotiations and expanding its market presence in various regions, particularly in Latin America and EMEA [19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical studies and the potential for transformative treatments, particularly for UX143 and GTX102 [9][10] - The company is optimistic about the upcoming data readouts and the overall strength of its product portfolio despite recent regulatory challenges [30] - Management highlighted the importance of maintaining a strong cash position while preparing for future commercial launches [22][30] Other Important Information - The company received breakthrough therapy designation for GTX102 from the FDA, indicating substantial improvement over existing therapies [10] - The Phase III ASPIRE study for GTX102 completed enrollment ahead of schedule, with results expected in 2026 [11] - The company is actively working with the FDA to address observations from a complete response letter for UX111, aiming for a timely resubmission [26][97] Q&A Session Summary Question: Recent FDA interactions and their impact - Management reported productive interactions with the FDA since the complete response letter, expressing confidence in the ongoing discussions [35] Question: Differences in dosing regimens for GTX102 - The company explained that the LNA chemistry used in GTX102 is more potent, allowing for lower dosing regimens compared to other drugs [38][39] Question: COSMIC trial rationale and assumptions - The COSMIC trial aims to evaluate young patients on bisphosphonates, with the goal of demonstrating a significant improvement in fracture rates [44][46] Question: Expected clinical benefit from the Orbit study - Management indicated that even if the fracture data is slightly under expectations, other supportive data could still make a strong case for FDA approval [62] Question: Additional clinical data for UX111 resubmission - The FDA requested updated clinical endpoint data and biomarker data for the resubmission of UX111, which the company is prepared to provide [57][58] Question: Financial management and cost control - The company is prioritizing cost control measures, including delaying certain expenses, to ensure a path to profitability by 2027 [90][91]