Corporate Presentation February 2026 Confidential and Proprietary Forward looking statements Cautionary note regarding forward-looking statements: This presentation contains forward-looking statements, including, but not limited to, statements regarding our expectations, estimates, assumptions, and projections regarding our future operating results and financial performance, including our expectations for profitability in 2027, anticipated cost or expense management, including the company's expectations rel ...

Core Insights - Ultragenyx Pharmaceutical reported a third-quarter 2025 loss of $1.81 per share, which was wider than the Zacks Consensus Estimate of a loss of $1.23, and compared to a loss of $1.40 per share in the same quarter last year [1][6] - Total revenues for the quarter were $159.9 million, reflecting a 15% year-over-year increase, but fell short of the Zacks Consensus Estimate of $168 million [1][6] Revenue Breakdown - Crysvita generated total revenues of $111.9 million, up 14% year over year, with contributions of $57 million from North America, $47 million from Latin America and Turkey, and $8 million from Europe [4] - Mepsevii product revenues declined by 27% year over year to $7 million, while Dojolvi revenues increased by 14% to $24.3 million due to new patient demand [5] - Evkeeza recorded sales of $16.7 million, up 57% as the drug continues to be launched in territories outside the United States [5][6] Operating Expenses - Operating expenses for the quarter were $330.8 million, a 22% increase year over year, driven by higher investments in late-stage pipeline programs and marketing costs [8] - Research and development expenses were $216.2 million (up 27%), selling, general and administrative expenses were $86.6 million (up 8%), and cost of sales was $28 million (up 33%) [8] Financial Guidance - The company expects total revenues in 2025 to be between $640 million and $670 million, representing growth of approximately 14-20% compared to 2024 [10] - Crysvita revenues are projected to be in the range of $460-$480 million (up 12-17% year over year), while Dojolvi revenues are expected between $90 million and $100 million (up 2-14% year over year) [10] Pipeline Updates - Ultragenyx faced a setback with the FDA issuing a complete response letter for its biologics license application for UX111, requesting more information related to manufacturing [12] - The company plans to resubmit the BLA for UX111 early in 2026 [13] - GTX-102 received Breakthrough Therapy designation from the FDA for treating Angelman syndrome, with data expected in the second half of 2026 [14] - The company has begun the rolling submission of a BLA for its investigational gene therapy DTX401, expected to be completed in Q4 2025 [15]

Core Insights - Ultragenyx Pharmaceutical reported a second-quarter 2025 loss of $1.17 per share, which is an improvement from a loss of $1.52 per share in the same quarter last year and better than the Zacks Consensus Estimate of a loss of $1.27 [1][5] - Total revenues for the quarter reached $166.5 million, reflecting a 13% year-over-year increase, driven primarily by higher product sales, and surpassing the Zacks Consensus Estimate of $162 million [1][5] Revenue Breakdown - Crysvita generated total revenues of $120.4 million, up 6% year over year, with contributions of $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe [3] - Mepsevii product revenues increased by 35% year over year to $8.3 million, while Dojolvi revenues rose 20% to $23.2 million due to new patient demand [4] - Evkeeza recorded sales of $14.6 million in the first quarter, showing significant growth as the drug continues to be launched in territories outside the United States [4] Financial Guidance - The company reaffirmed its 2025 financial guidance, expecting total revenues between $640 million and $670 million, which represents a growth of approximately 14-20% compared to 2024 [9] - Crysvita revenues are anticipated to be in the range of $460-$480 million, reflecting a year-over-year increase of 12-17%, while Dojolvi revenues are expected to be between $90 million and $100 million, up 2-14% year over year [9] Operating Expenses - Operating expenses for the quarter were $274.4 million, a 4% increase year over year, attributed to higher investments in late-stage pipeline programs and marketing costs for approved drugs [7] - Research and development expenses were $164.7 million (up 2%), selling, general and administrative expenses were $86.6 million (up 7%), and cost of sales was $23 million (up 8%) [7] Pipeline Updates - The FDA issued a complete response letter for Ultragenyx's biologics license application for UX111, requesting additional information related to manufacturing processes, which the company plans to address promptly [11][12] - The company is also developing GTX-102 for Angelman syndrome, which received Breakthrough Therapy designation, with data expected in the second half of 2026 [14] - Ultragenyx plans to submit a BLA for DTX401, a gene therapy for glycogen storage disease type Ia, in the fourth quarter of 2025 [15]

Financial Performance & Projections - The company anticipates total revenue between $640 million and $670 million in 2025, representing a 14-20% increase from 2024[93] - The company projects full-year GAAP profitability in 2027, driven by revenue growth, expense management, and potential monetization of Priority Review Vouchers (PRVs)[94, 96] - Crysvita revenue is expected to be between $460 million and $480 million in 2025, a 12-17% increase[93] - Dojolvi revenue is projected to be between $90 million and $100 million in 2025, a 2-13% increase[93] - As of June 30, 2025, the company had $538 million in cash, cash equivalents, and marketable debt securities[96] Clinical Program Updates - Phase 3 data readout for UX143 in Osteogenesis Imperfecta (OI) is expected around the end of 2025[21, 32, 97] Phase 2 data showed a 67% reduction in annualized fracture rate (AFR) with UX143[33] - Enrollment for the Phase 3 Aspire study of GTX-102 for Angelman Syndrome (AS) was completed in July 2025, and the Phase 2/3 Aurora study is expected to begin in the second half of 2025[24, 49, 60, 97] - For DTX401 in Glycogen Storage Disease Type Ia (GSDIa), BLA submission is expected in Q4 2025, with a potential launch in 2026[75, 77, 97] Phase 3 data demonstrated a 41% statistically significant reduction in daily cornstarch intake at Week 48 (p < 00001)[80] - For UX111 in Sanfilippo syndrome (MPS IIIA), the company is actively working to resolve FDA observations in the Complete Response Letter (CRL)[66] - Stage 1, Cohort 4 enrollment completion for UX701 in Wilson Disease (WD) is expected in the second half of 2025[85, 87, 97] In Stage 1, 6 out of 15 patients were completely off chelators and/or zinc therapy[88, 90]

Core Viewpoint - Ultragenyx Pharmaceuticals faces a regulatory setback as the FDA issued a Complete Response Letter (CRL) for its biologics license application (BLA) for UX111, a gene therapy for Sanfilippo syndrome type A (MPS IIIA) [1][6]. Regulatory Update - The CRL requested additional information and enhancements related to chemistry, manufacturing, and controls, stemming from recent facility inspections. The issues are facility- and process-related, not linked to product quality, and can be addressed quickly [2][6]. - Ultragenyx plans to collaborate closely with the FDA to resolve the observations and expects to resubmit the BLA, which will initiate a review period of up to six months [2]. Clinical Data and Impact - The FDA acknowledged the robustness of the neurodevelopmental outcome data and supportive biomarker findings. However, updated clinical data from current patients is required for the resubmission [3]. - The regulatory delay has pushed the potential approval of UX111 for MPS IIIA to 2026. Year-to-date, shares of Ultragenyx have decreased by 30.5%, contrasting with a 0.9% decline in the industry [3]. Disease Context - MPS IIIA is a rare, fatal lysosomal storage disease affecting the brain, with no approved treatments available. Approximately 3,000 to 5,000 patients are affected, with a median life expectancy of 15 years [9]. Pipeline Overview - Ultragenyx has several other gene therapy candidates in its pipeline, including UX143 for osteogenesis imperfecta and UX701 for Wilson disease, with ongoing studies showing promising results [11][12]. - The investigational gene therapy UX111 has received multiple designations in the U.S. and EU, including Regenerative Medicine Advanced Therapy and Orphan Drug designations [10].

Core Insights - Ultragenyx Pharmaceuticals (RARE) has received FDA Breakthrough Therapy designation for its investigational therapy GTX-102 (apazunersen) aimed at treating Angelman syndrome (AS) [1][5]. FDA Breakthrough Therapy Designation - The Breakthrough Therapy designation accelerates the development and review of drugs for serious conditions, granted when early clinical evidence indicates significant improvement over existing treatments [2]. - Drugs with this designation benefit from enhanced guidance and support from senior FDA officials [2]. Clinical Study Results - GTX-102 demonstrated rapid and lasting improvements in AS patients during a phase I/II study lasting up to three years, involving 74 patients aged 4 to 17 with complete maternal UBE3A gene deletion [5][6]. - Participants showed consistent developmental progress and ongoing improvements across multiple symptom areas during treatment [6]. Current and Future Studies - Ultragenyx is currently enrolling patients for a phase III Aspire study and plans to initiate a phase II/III Aurora study to evaluate GTX-102 for a broader range of AS genotypes [8]. - The Aurora study is expected to start in the second half of 2025 [8]. Market Context - AS is a rare neurogenetic disorder affecting approximately 60,000 individuals in accessible markets, leading to severe developmental challenges with no approved therapies currently available [7]. Other Clinical Programs - Ultragenyx is developing other gene therapy candidates, including UX143 for osteogenesis imperfecta, which received Breakthrough Therapy designation in October 2024 [9]. - The company is also evaluating UX701 for Wilson disease and has achieved significant results in the phase III GlucoGene study for glycogen storage disease type Ia [10]. - A regulatory application for UX111, an AAV gene therapy for Sanfilippo syndrome type A, is under Priority Review, with a decision expected on August 18, 2025 [11].

Financial Data and Key Metrics Changes - In Q1 2025, Ultragenyx reported revenue of $139 million, representing a 28% increase compared to Q1 2024 [18] - The net loss for the quarter was $151 million, or $1.57 per share, with total operating expenses of $282 million [20] - Cash, cash equivalents, and marketable securities stood at $563 million as of March 31, 2025 [20] Business Line Data and Key Metrics Changes - Crysvita generated $103 million in revenue, with contributions of $41 million from North America, $55 million from Latin America and Turkey, and $7 million from Europe, marking a 25% growth over 2024 [18] - DeJolvi contributed $17 million, consistent with its expected growth trajectory, while EVKYSA generated $11 million as demand builds [19] - Mepsevii contributed $8 million as the company continues to treat patients in this ultra-rare indication [19] Market Data and Key Metrics Changes - In Latin America and Turkey, Crysvita revenue grew by 52% over 2024, driven by successful reimbursement negotiations [18] - The U.S. market for Crysvita is expected to continue growing as the company identifies new pediatric and adult patients [11] - The EMEA region saw over 260 patients treated with DERJOVY under named patient sales, with strong demand noted particularly in France [13] Company Strategy and Development Direction - The company is focused on expanding its commercial operations globally while preparing for new product launches in the U.S. and worldwide [5] - Ultragenyx is advancing multiple late-stage programs, including UX143 for osteogenesis imperfecta and GTX-102 for Angelman syndrome, with data expected in 2026 [7][26] - The company is on track to submit two Biologics License Applications (BLAs) in 2025, with one currently under review and another expected mid-year [8][9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence that 2025 will be a transformational year, with expectations of significant revenue growth and multiple clinical data readouts [32] - The company is optimistic about the demand for its products, particularly in Latin America and the pediatric and adult XLH markets in the U.S. [21] - Management acknowledged the evolving tariff landscape but does not expect material exposure for any products, including Crysvita [23] Other Important Information - The company is actively monitoring regulatory interactions and has scheduled inspections of manufacturing facilities and clinical sites [9] - The company expects net cash used in operations to decrease in the remaining quarters of 2025, aiming for full-year GAAP profitability by 2027 [21] Q&A Session Summary Question: Insights on setrusumab and the second interim analysis - Management discussed the variability in fracture rates among patients and the statistical methods used to analyze data, emphasizing confidence in achieving significant results [35][39] Question: Likelihood of success if the study moves to a third interim read - Management expressed confidence in hitting the p-value threshold based on observed data trends and the size of the study [46][49] Question: Impact of recent CBER nomination on the rare disease space - Management noted concerns about the nomination but emphasized the importance of maintaining accelerated approval pathways for rare diseases [51][54] Question: Enrollment status for the Angelman program - Management confirmed that all global sites for the Angelman program are active and screening patients [66][68] Question: Clarification on the timing of interim data release - Management indicated that data cleaning and analysis for the interim results would take approximately eight weeks, with a commitment to timely communication of results [90][92]

Pipeline & Approvals - Ultragenyx expects a PDUFA date of August 18, 2025, for UX111 in Sanfilippo syndrome (MPS IIIA) and a potential commercial launch in the second half of 2025[67, 98] - The company anticipates BLA submission for DTX401 in Glycogen Storage Disease Type Ia (GSDIa) in mid-2025, with a potential launch in 2026[78, 80, 98] - Phase 3 enrollment for GTX-102 in Angelman Syndrome (AS) is expected to be completed in the second half of 2025, with a Phase 2/3 Aurora study initiation planned for 2025[46, 49, 61, 98] - Ultragenyx plans to complete Stage 1, Cohort 4 enrollment for UX701 in Wilson Disease (WD) in the second half of 2025[88, 90, 98] - Phase 3 data readout for UX143 in Osteogenesis Imperfecta (OI) is expected in 2025[21, 28, 32] Financial Performance & Projections - Ultragenyx projects total revenue between $640 million and $670 million in 2025, representing a 14-20% annual revenue growth[94, 95] - Crysvita revenue is projected to be between $460 million and $480 million in 2025, a 12-17% increase[95] - Dojolvi revenue is expected to be between $90 million and $100 million in 2025, a 2-13% increase[95] - The company aims to achieve full-year GAAP profitability in 2027, driven by revenue growth, expense management, and monetization of Priority Review Vouchers (PRVs)[2, 96, 97, 99] - Ultragenyx reported $563 million in cash, cash equivalents, and marketable debt securities as of March 31, 2025[97]