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 ...

Summary of Ultragenyx Pharmaceutical FY Conference Call Company Overview - **Company**: Ultragenyx Pharmaceutical (NasdaqGS:RARE) - **Focus**: Development of treatments for rare diseases, with a strategy centered on potent biology and innovative drug development methods [1][2] Core Points and Arguments Product Development and Pipeline - **Commercial Products**: Since going public in 2014, Ultragenyx has four commercial products approved, generating revenue in over 30 countries [2] - **Setrusumab Program**: Recent trials for Setrusumab were disappointing, missing primary endpoints but showing improvements in bone mineral density and patient-reported outcomes [3][4][10] - **Trial Designs**: Two phase 3 studies (Orbit and COSMIC) were conducted, with Orbit being placebo-controlled and COSMIC being active-controlled for younger patients [5][6] - **Fracture Rates**: In the Orbit study, the fracture rates did not show significant differentiation between treatment and placebo groups, raising questions about the drug's efficacy [11][12] - **Bone Mineral Density**: Setrusumab demonstrated substantial improvements in bone mineral density, particularly in trabecular bone, but the expected reduction in fractures was not achieved [10][14] Future Developments - **Gene Therapy Programs**: - **Sanfilippo Syndrome**: A gene therapy program is expected to file for approval soon, with strong data supporting its efficacy [17] - **DTX401 for Glycogen Storage Disease**: A BLA filing was completed, showing significant demand and positive outcomes in reducing cornstarch needs for patients [18][19] - **GTX-102 for Angelman Syndrome**: Phase 3 data is anticipated in the second half of the year, with promising results in developmental improvements [20][21] Financial Outlook - **Revenue Growth**: Expected revenue of $62-$674 million, reflecting a 20% growth rate, with plans for expense and headcount reductions to maintain profitability goals by 2027 [24][25][26] - **Cash Position**: The company has $735 million in cash and anticipates receiving two PRVs before the sunset clause in September [26] Important but Overlooked Content - **Patient-Centric Focus**: Pain management and functional improvements are prioritized by patients, even if regulatory endpoints focus on fracture rates [30][31] - **Regulatory Navigation**: The company is working to understand the data better before approaching regulatory bodies, particularly regarding the discrepancies in fracture rates and patient activity levels [32][34] - **Long-Term Data**: There is an expectation for long-term follow-up data to provide further insights into the efficacy of treatments, particularly for Setrusumab [36] Conclusion Ultragenyx is navigating challenges in its product pipeline while maintaining a strong focus on patient outcomes and revenue growth. The company is poised for significant developments in gene therapy and aims to achieve profitability by 2027, despite setbacks in recent clinical trials.

Group 1 - Ultragenyx Pharmaceutical Inc. is considered a promising stock under $50, with Morgan Stanley lowering its price target to $50 from $55 while maintaining an Overweight rating [1][3] - The firm anticipates continued outperformance for US SMID-cap biotech in 2026, driven by commercial-stage companies transitioning from capital consumers to producers, alongside a patent cliff affecting large-cap biopharma revenues [1][3] - Ultragenyx completed its rolling BLA submission to the FDA for DTX401, a potential first-in-class gene therapy for Glycogen Storage Disease Type Ia, which could significantly improve treatment for approximately 6,000 patients worldwide [2][3] Group 2 - The BLA submission is supported by the Phase 3 GlucoGene study, which monitored 52 patients for up to six years, confirming that DTX401 is well-tolerated through 96 weeks [3] - DTX401 has received several high-priority designations, including RMAT and Fast Track, as it approaches a potential commercial launch [3] - Ultragenyx focuses on developing and commercializing novel products for rare and ultra-rare genetic diseases across multiple regions, including North America, Europe, and Asia-Pacific [4]

Company Overview - Ultragenyx Pharmaceutical Inc. is a biopharmaceutical company focused on developing and commercializing novel products for rare and ultra-rare genetic diseases across various regions including North America, Latin America, Europe, the Middle East, Africa, and the Asia-Pacific [4] Financial Performance - In Q3 2025, Ultragenyx reported total revenue of $160 million, reflecting a 15% year-over-year growth [2] - The company is projected to achieve full-year revenue between $640 million and $670 million, indicating a growth of 14% to 20% compared to 2024 [2] - Revenue from Crysvita accounted for $112 million in Q3, with full-year guidance expected between $460 million and $480 million, representing a 12% to 17% growth over 2024 [2] - AJOVY revenue for the quarter was $24 million, while Mepsevii revenue was $7 million [2] - The company reported a net loss of $180 million, or $1.81 per share, for Q3 [3] Analyst Insights - Barclays analyst Gena Wang lowered the price target for Ultragenyx from $81 to $50 but maintained an Overweight rating, citing analysis of the setrusumab COSMIC study while still indicating over a 70% chance of a positive result [1][3] - Despite the lowered price target, the company is advancing multiple late-stage clinical programs with significant commercial potential, including UX 143 (setrusumab) and GTX-102 [3]

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]

Financial Data and Key Metrics Changes - In Q3 2025, Ultragenyx reported total revenue of $160 million, representing a 15% increase compared to Q3 2024 and an 18% increase for the first nine months of 2025 over the same period in 2024 [14][15] - The net loss for the quarter was $180 million, equating to $1.81 per share [15] - As of September 30, 2025, the company had $447 million in cash, cash equivalents, and securities, bolstered by a recent $400 million financing [16] Business Line Data and Key Metrics Changes - Crysvita generated $112 million in revenue during Q3 2025, with contributions of $57 million from North America, $47 million from Latin America and Turkey, and $8 million from Europe [15] - Dojolvi contributed $24 million, maintaining steady growth, while Evkeeza and Mepsevii contributed $17 million and $7 million, respectively [15] - The company expects total revenue for 2025 to be between $640 million and $670 million, indicating a growth of 14% to 20% over 2024 [16][17] Market Data and Key Metrics Changes - In Latin America, approximately 875 patients are now on Crysvita therapy, with 50 new start forms generated in Q3 2025 [8] - Dojolvi has seen approximately 700 new start forms since its launch in 2020, leading to around 625 patients on reimbursed therapy, with a split of 65% pediatric and 35% adult patients [9] - Evkeeza has approximately 310 patients across 17 countries in the EMEA region, with 120 new patients added since the beginning of the year [10] Company Strategy and Development Direction - The company is focused on maximizing opportunities from its four commercial products and has two BLA submissions in progress for ultra-rare diseases [4] - Ultragenyx aims to maintain financial discipline while preparing for upcoming product launches and pivotal data readouts [14] - The company is positioned for growth with a strong balance sheet and plans to achieve profitability by 2027 [16][48] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming pivotal data readouts for GTX-102 and UX143, which are expected to be transformative for patients with Angelman syndrome and osteogenesis imperfecta [5][23] - The management team highlighted the importance of maintaining cash burn and prioritizing investments as they approach significant clinical milestones [5][16] - The company anticipates continued double-digit revenue growth from existing products and contributions from new launches [48] Other Important Information - The company received $400 million in non-dilutive capital through the sale of a portion of Crysvita royalties, with payments deferred until January 2028 [4][13] - The management team emphasized the unique value of Crysvita and its potential to deliver significant long-term value [14] Q&A Session Summary Question: Data update on Orbit and Cosmic studies - Management confirmed that data from both studies will be reported together, expected in December or January [27] Question: Open label extension from phase II for OI - Management stated that they have not released new quantitative data but are confident in the phase III expectations, aiming for a 40% to 70% reduction in fractures [31][32] Question: Clarification on UX111 and DTX401 submissions - Management explained that the timing of submissions was adjusted due to the need for additional reports, but both filings remain closely aligned [36] Question: Impact of OMERS transaction on financing needs - Management indicated that the $400 million raised will help address investor concerns regarding financing needs in 2026 and support upcoming product launches [42][48] Question: Length of treatment for Setrusumab - Management expressed confidence that Setrusumab will require chronic treatment to maintain bone health, suggesting bisphosphonates may become obsolete [70][73] Question: Loss of exclusivity for Setrusumab - Management highlighted the importance of orphan designation for exclusivity and mentioned ongoing patent protections that extend beyond 2030 [92]

Financial Data and Key Metrics Changes - In Q3 2025, the company reported total revenue of $160 million, representing a 15% increase compared to Q3 2024 and an 18% increase for the first nine months of 2025 over the same period in 2024 [14][15] - The net loss for the quarter was $180 million, equating to $1.81 per share [15] - Cash, cash equivalents, and securities as of September 30, 2025, totaled $447 million, bolstered by a recent $400 million financing [16] Business Line Data and Key Metrics Changes - Crysvita generated $112 million in Q3 2025, with revenue contributions of $57 million from North America, $47 million from Latin America and Turkey, and $8 million from Europe [15] - DOJOLVI contributed $24 million, maintaining steady growth, while EVKEEZA and MEPSEVII contributed $17 million and $7 million, respectively [15] - The company expects total revenue for 2025 to be between $640 million and $670 million, indicating a growth of 14%-20% over 2024 [16] Market Data and Key Metrics Changes - In Latin America, approximately 875 patients are now on Crysvita therapy, with 50 new start forms generated in Q3 2025 [8] - In the EMEA region, around 310 patients are receiving EVKEEZA across 17 countries, with 120 new patients added since the beginning of the year [10] Company Strategy and Development Direction - The company is focused on maximizing opportunities from its four commercial products and has two BLA submissions in progress for ultra-rare diseases [4] - A recent $400 million financing through the sale of Crysvita royalties is aimed at strengthening the balance sheet and supporting upcoming pivotal data readouts [4][13] - The company plans to maintain financial discipline while preparing for the launch of new products and managing cash burn [5][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming pivotal data readouts for osteogenesis imperfecta and Angelman syndrome, with expectations for significant commercial opportunities [5][23] - The company reaffirmed its path to profitability by 2027, supported by continued double-digit growth from existing products and potential new launches [16][48] Other Important Information - The company is preparing for the rolling BLA submission for DTX401, expected to be completed next month, and anticipates a BLA resubmission for UX111 in early 2026 [18][21] - Management highlighted the importance of patient support programs in influencing treatment decisions among caregivers and patients [62] Q&A Session Summary Question: Data update on Orbit and Cosmic studies - Management confirmed that data from both studies will be reported together, expected in December or January, with variability in timing due to data cleaning processes [26][27] Question: Open label extension from phase II for OI - Management stated that while no new quantitative data is available, they are confident in the phase II results and expect a fracture reduction of 40%-70% in phase III [30][32] Question: Clarification on UX111 and DTX401 submissions - Management explained that the timing of submissions was adjusted due to the need for additional reports, with DTX401 expected to be filed first [35][36] Question: Impact of OMERS transaction on financing needs - Management indicated that the $400 million raised will help address investor concerns regarding financing needs in 2026, particularly related to priority vouchers [42][48] Question: Commercial opportunity for Setrusumab in OI - Management believes the OI population is larger than XLH and expects similar pricing, indicating a significant commercial opportunity [58] Question: Loss of exclusivity for Setrusumab - Management highlighted orphan designation as a protective factor against loss of exclusivity, with additional patents in place to extend protection [90]

Financial Data and Key Metrics Changes - In Q3 2025, the company reported total revenue of $160 million, representing a 15% increase compared to Q3 2024 and an 18% increase for the first nine months of 2025 over the same period in 2024 [13][14] - The net loss for the quarter was $180 million, equating to $1.81 per share [15] - As of September 30, 2025, the company had $447 million in cash, cash equivalents, and securities, bolstered by a recent $400 million financing [16] Business Line Data and Key Metrics Changes - Crysvita generated $112 million in revenue during Q3 2025, with contributions of $57 million from North America, $47 million from Latin America and Turkey, and $8 million from Europe [14] - Dojolvi contributed $24 million, maintaining steady growth, while Evkeeza and Mepsevii contributed $17 million and $7 million, respectively [14] - The company expects total revenue for 2025 to be between $640 million and $670 million, indicating a growth of 14% to 20% over 2024 [16] Market Data and Key Metrics Changes - In Latin America, the company added approximately 50 new patients on reimbursed therapy for Crysvita, bringing the total to around 875 patients [8] - In the EMEA region, Evkeeza has approximately 310 patients receiving treatment across 17 countries, with 120 new patients added since the beginning of the year [10] Company Strategy and Development Direction - The company is focused on maximizing opportunities from its four commercial products and has two BLA submissions in progress for ultra-rare diseases [3] - A recent $400 million financing through the sale of a portion of Crysvita royalties is aimed at strengthening the balance sheet and supporting upcoming pivotal data readouts [3][12] - The company plans to maintain financial discipline while preparing for the launch of new products and managing cash burn [4][12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming pivotal data readouts for GTX-102 and UX143, which are expected to be transformative for patients with Angelman syndrome and osteogenesis imperfecta [4][23] - The company reaffirmed its path to profitability by 2027, supported by expected double-digit growth from existing products and new launches [12][48] Other Important Information - The company is preparing for a rolling BLA submission for DTX401, with expectations to complete this filing in December [23] - Management highlighted the importance of patient support programs in ensuring access to treatments, especially in a competitive landscape for Angelman syndrome therapies [64] Q&A Session Summary Question: Data update on Orbit and Cosmic studies - Management confirmed that data from both studies will be reported together, expected in December or January [26][27] Question: Open label extension from phase II for OI - Management stated that while no new quantitative data is available, they are confident in the phase III expectations, anticipating a fracture reduction of 40% to 70% [30][32] Question: Clarification on UX111 and DTX401 submissions - Management explained that the timing of submissions was adjusted due to the need for additional reports, but both filings remain closely timed [36][38] Question: Impact of OMERS transaction on financing needs - Management indicated that the recent financing strengthens the balance sheet and supports the path to profitability in 2027 [44][48] Question: Length of treatment for Setrusumab - Management expressed confidence that Setrusumab will require chronic treatment to maintain bone health, suggesting bisphosphonates may become obsolete [72][74] Question: Loss of exclusivity for Setrusumab - Management highlighted orphan designation and additional IP protections that extend exclusivity beyond 2030 [98][99]

Core Viewpoint - Ultragenyx Pharmaceutical Inc. has initiated a rolling submission of a Biologics License Application (BLA) for DTX401 AAV gene therapy to the FDA, aiming for approval as a treatment for Glycogen Storage Disease Type Ia (GSDIa) with full submission expected in Q4 2025 [1][2] Company Overview - Ultragenyx is a biopharmaceutical company focused on developing therapies for serious rare and ultra-rare genetic diseases, with a diverse portfolio of approved medicines and treatment candidates [5][6] - The management team has extensive experience in the development and commercialization of rare disease therapeutics, emphasizing efficient drug development to deliver safe and effective therapies urgently [6] Product Information - DTX401 is an investigational AAV8 gene therapy designed to provide stable expression of G6Pase-α, allowing liver cells to manage glucose levels effectively [3] - The therapy is administered as a single intravenous infusion and has shown promise in preclinical studies by improving G6Pase-α activity and reducing hepatic glycogen levels [3] Disease Context - Glycogen Storage Disease Type Ia (GSDIa) is a serious inherited condition caused by a defective gene affecting blood sugar regulation, leading to life-threatening hypoglycemia and potential organ dysfunction [4] - Approximately 6,000 individuals are estimated to be affected by GSDIa in commercially accessible regions, highlighting the unmet medical need for effective treatments [4] Clinical Development - The BLA for DTX401 includes data from a 96-week randomized, placebo-controlled Phase 3 study, showing significant reductions in daily cornstarch intake by 60% in the DTX401 group and 64% in the crossover group compared to baseline [2] - The company plans to address FDA observations from the UX111 program while completing the BLA submission [2]

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]