Summary of Ultragenyx Pharmaceutical Conference Call Company Overview - **Company**: Ultragenyx Pharmaceutical (NasdaqGS:RARE) - **Date**: March 11, 2026 - **Key Speaker**: Eric Crombez, CMO Recent Events and Priorities - **Commercial Success**: - Crysvita continues to show double-digit year-over-year growth - Significant growth in Dojolvi and Evkeeza, with Mepsevii contributing to revenue [4][4] - **Pipeline Focus**: - Emphasis on Angelman syndrome with data readout expected in the second half of the year - Progress in gene therapy pipeline, particularly for GSDIa and Sanfilippo [4][4] Angelman Syndrome Study - **Phase 3 Study Design**: - Primary endpoint will be measured without caregiver input to control for placebo effects [6][7] - Previous Phase 1/2 showed a Bayley Cognition Score improvement of over 10, with a clinically significant difference set at 5 [9][13] - **Statistical Considerations**: - Study powered to show a 10.9 difference in cognition scores from baseline in treated patients, with a flat natural history curve for the placebo group [11][12] - **MDRI Endpoint**: - FDA has agreed to consider the Multi-Domain Responder Index (MDRI) as a secondary endpoint, which captures broader developmental aspects [16][18] Gene Therapy Dosing and Efficacy - **Dosing Strategy**: - Initial dosing informed by animal models, with adjustments made based on clinical data from Phase 1/2 [20][21] - **GTX-102 Potency**: - Claimed to be the most potent ASO in development for Angelman, based on clinical data from 74 patients [22][22] - **Knockdown and Protein Restoration**: - Achieving over 80% knockdown is necessary for clinical benefit, with expectations of around 35% expression needed for efficacy [25][27] DTX401 Gene Therapy - **BLA Acceptance**: - BLA for DTX401 accepted, with a PDUFA date set for August [30][30] - **Manufacturing Control**: - In-house manufacturing facility established to ensure quality and control over production [32][33] - **Durability of Treatment**: - Strong durability observed in Phase I/II patients, supporting confidence in FDA review [34][35] Commercial Opportunity - **Market Potential**: - Approximately 6,000 patients in the U.S. with GSDIa, with high penetration expected due to the necessity of treatment [42][42] Wilson Disease Program - **Efficacy Differentiation**: - Aiming to show positive differentiation from existing chelator treatments, with a focus on the majority of patients coming off chelators [48][49] - **Biomarker Confidence**: - Heparan sulfate is considered a strong biomarker for clinical benefit, with a shift towards clinical approval based on patient outcomes [46][47] Conclusion - Ultragenyx is focused on advancing its gene therapy pipeline, particularly for rare diseases like Angelman syndrome and GSDIa, with promising commercial opportunities and a strong emphasis on clinical efficacy and safety in its studies.

Summary of Ultragenyx Pharmaceutical FY Conference Call Company Overview - **Company**: Ultragenyx Pharmaceutical (NasdaqGS:RARE) - **Event**: 46th Annual TD Cowen Healthcare Conference - **Date**: March 02, 2026 Key Points on Angelman Syndrome - **Aspire Study**: Focused on Angelman syndrome with 130 patients aged 4 to 17 years, primarily with full deletions, aiming for a primary endpoint of cognition based on the Bayley-4 scale [3][4] - **Clinical Significance**: The meaningful score difference (MSD) for cognition is set at +5, with a mean difference of 10.9 observed in actively treated patients compared to a maximum change of 1 in the control group [4][5][6] - **Statistical Power**: The Aspire study is powered for greater than 90% success based on the statistical modeling of natural history data [6] - **Patient Population**: The study enrolls only patients with full deletions to ensure a homogeneous and severe patient population, minimizing variability and placebo effects [10][11] - **Aurora Study**: A phase II/III study supporting the broader Angelman product, focusing on safety and efficacy across different genotypes [14][15] - **Regulatory Strategy**: The Aspire study will form the basis of the approval package, with the Aurora study providing additional safety and efficacy data [16] Insights on Multi-Domain Responder Index (MDRI) - **Endpoints**: The MDRI is a key secondary endpoint, with both cognition and MDRI being treated as primary endpoints in the study [20][22] - **MSD for MDRI**: The MSD for the MDRI is also set at five points, with individual domains having specific MSDs [28][29] Discussion on Setrusumab and Bone Mineral Density - **Setrusumab**: The drug shows benefits in vertebral fractures and bone mineral density, with a focus on translating these findings into functional outcomes [36][37] - **FDA Interaction**: The company is strategizing on how to approach the FDA for accelerated approval based on compelling vertebral data and the need for confirmatory studies [38][39] Sanfilippo Syndrome and Manufacturing Challenges - **FDA Feedback**: The FDA indicated that clinical data is sufficient for approval, but there are challenges related to manufacturing and additional paperwork [46][48] - **Validation Period**: A 2-week validation period is expected for resubmission, with no new clinical data required [49][52] Gene Therapy and Market Considerations - **Unmet Medical Need**: Sanfilippo syndrome represents a high unmet medical need, with a small patient population but significant potential for successful product launch [71][72] - **Pricing Strategy**: The company believes that accelerated approval will not significantly impact pricing, as the focus remains on the high unmet need [43] Future Outlook - **Clinical Data**: Anticipation of data readouts for various studies, including the potential for accelerated approval and the importance of patient-level understanding in ongoing trials [42][75] - **Launch Preparedness**: The company is prepared to launch therapies for Sanfilippo and GSDIa quickly, having prioritized these programs for resource allocation [74] Conclusion - Ultragenyx Pharmaceutical is actively advancing its pipeline for rare diseases, particularly focusing on Angelman syndrome and Sanfilippo syndrome, while navigating regulatory challenges and ensuring robust clinical data to support its therapies.

Core Thesis - Ultragenyx Pharmaceutical Inc. is viewed positively due to its diversified rare disease portfolio and upcoming gene therapy catalysts, despite recent setbacks in clinical trials [1][5]. Financial Performance - The company generates approximately $670 million in annual revenue from four approved products [2]. - Ultragenyx experienced a cash burn of roughly $446 million in the first nine months of 2025, indicating an annualized burn rate of about $600 million against $735 million in cash, providing roughly 1.2 years of runway [4]. Clinical Pipeline - The company has a credible pipeline with significant upcoming events in 2026, including two gene therapy PDUFA decisions for UX111 and DTX401, and Phase 3 data for GTX-102 [2][3]. - UX111 aims to deliver SGSH across the blood-brain barrier, while DTX401 focuses on restoring G6Pase activity in the liver, showing promising Phase 3 data [3]. - GTX-102 targets the UBE3A gene in Angelman syndrome, although it faces challenges related to a narrow therapeutic window [3]. Risks and Challenges - The recent Phase 3 failure of setrusumab highlights the risk that biomarker success does not guarantee clinical benefit [2]. - Manufacturing issues previously led to a Complete Response Letter (CRL) for UX111, indicating potential operational risks [4]. - The intellectual property landscape is mixed, with some gene therapies benefiting from technical barriers, while others face challenges from licensing and generics [4].

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]