Key Takeaways RARE resubmitted its UX111 BLA to the FDA seeking accelerated approval to treat Sanfilippo syndrome type A.Ultragenyx addressed prior CRL CMC issues, citing facility and process fixes unrelated to product quality.RARE added long-term neurologic and CSF biomarker data. FDA review could take up to six months.Ultragenyx Pharmaceutical (RARE) announced the resubmission of its biologics license application (“BLA”) to the FDA seeking accelerated approval for AAV gene therapy candidate UX111, which i ...

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 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].

Company Overview - Ultragenyx (RARE) shares increased by 5.1% to $41.44 in the last trading session, with a notable trading volume [1] - The stock has also gained 5.1% over the past four weeks [1] Pipeline Progress - The rise in stock price is linked to positive investor sentiment regarding Ultragenyx's late-stage pipeline, particularly the regulatory application for FDA approval of UX111, a gene therapy for Sanfilippo syndrome type A, currently under Priority Review with a decision expected on August 18, 2025 [2] - Ultragenyx plans to submit a biologics license application for DTX401, an AAV8 gene therapy for glycogen storage disease type Ia, which could further enhance revenue if approved [2] Financial Expectations - The company is projected to report a quarterly loss of $1.27 per share, reflecting a year-over-year increase of 16.5%, with expected revenues of $161.61 million, up 9.9% from the previous year [3] - The consensus EPS estimate for the quarter has remained unchanged over the last 30 days, indicating that stock price movements may not sustain without trends in earnings estimate revisions [4] Industry Context - Ultragenyx operates within the Zacks Medical - Biomedical and Genetics industry, where another company, Fortress Biotech (FBIO), saw a 3.1% increase in its stock price, closing at $1.99, although FBIO has returned -7.2% over the past month [4] - Fortress Biotech's consensus EPS estimate for its upcoming report is -$0.31, which is a 57.5% improvement from the previous year, and it also holds a Zacks Rank of 3 (Hold) [5]

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].