Core Insights - The upcoming year is a pivotal moment for the company, with two potential product launches and a crucial data readout expected to significantly boost commercial revenue [1] - A strategic restructuring plan is being implemented to lower operating expenses and align resources with high-impact opportunities in the rare disease sector [2] FDA Update - The company received an Incomplete Response Letter (IRL) from the FDA regarding its resubmitted marketing application for UX111 (rebisufligene etisparvovec) gene therapy for Sanfilippo syndrome type A, requesting additional documentation for resubmission [3] Earnings Snapshot - The company reported a fourth-quarter loss of $1.29 per share, missing the consensus estimate of $1.14, while sales increased to $207 million from $165 million year-over-year, surpassing the consensus of $196.97 million [4] - Revenue from Crysvita was $145 million, Dojolvi reached $32 million, and Evkeeza sales were $17 million [4] Strategic Restructuring - A strategic restructuring plan has been initiated, including a 10% workforce reduction affecting approximately 130 employees, aimed at reducing expenses and partially reinvesting to support future growth [5] - The company aims to achieve profitability by 2027 through significant cost discipline and revenue growth from current and new product launches [5] Outlook - The company forecasts fiscal 2026 sales between $730 million and $760 million, below the consensus of $786.93 million, with Crysvita revenue expected to be between $500 million and $520 million and Dojolvi revenue projected at $100 million to $110 million [6] Market Reaction - Following the announcements, Ultragenyx Pharmaceutical shares fell by 10.21% to $21.10 [7]

Core Insights - Ultragenyx reported $207 million in revenue for Q4 2025, marking a year-over-year increase of 25.6% [1] - The company's EPS for the same period was -$1.29, an improvement from -$1.39 a year ago, but below the consensus estimate of -$1.20 [1] - The revenue exceeded the Zacks Consensus Estimate of $202.92 million by 2.01%, while the EPS fell short by 7.32% [1] Revenue Breakdown - Dojolvi generated $32 million in revenue, surpassing the average estimate of $30.28 million, with a year-over-year increase of 2.9% [4] - Evkeeza achieved $17 million in revenue, exceeding the estimated $16.37 million, reflecting a significant year-over-year growth of 63.9% [4] - Mepsevii reported $13 million in revenue, above the average estimate of $10.81 million, also showing a year-over-year increase of 63% [4] - Total Crysvita revenue reached $145 million, exceeding the average estimate of $135.25 million [4] - Overall product sales were $102 million, which was below the estimated $114.76 million, but still represented a year-over-year increase of 41.9% [4] - Royalty revenue amounted to $105 million, surpassing the average estimate of $91.57 million, with a year-over-year change of 12.9% [4] Stock Performance - Over the past month, Ultragenyx shares have returned -0.8%, compared to a -0.3% change in the Zacks S&P 500 composite [3] - The stock currently holds a Zacks Rank 3 (Hold), indicating potential performance in line with the broader market in the near term [3]

Financial Data and Key Metrics Changes - Total revenue for 2025 was reported at $673 million, representing a 20% growth over 2024 and exceeding the upper end of guidance [11] - Net loss for the year was $575 million, or $5.83 per share [12] - Cash, cash equivalents, and marketable securities as of December 31 were $738 million [12] - Guidance for 2026 total revenue is expected to be between $730 million and $760 million, reflecting an 8%-13% growth over 2025 [12][13] Business Line Data and Key Metrics Changes - Crysvita contributed $481 million in revenue, with a 17% growth over 2024 [11] - Dojolvi generated $96 million, representing a 9% growth over 2024 [11] - Evkeeza saw significant growth, contributing $59 million, which is an 84% increase over 2024 [11] - Mepsevii contributed $37 million, continuing to treat patients in an ultra-rare indication [11] Market Data and Key Metrics Changes - The commercial business delivered a significant 20% year-over-year growth in 2025, with treatments reaching over 35 countries [8] - In Latin America, Crysvita's business is anchored in Brazil and Argentina, with solid reimbursement growth in Mexico and Colombia [16][17] - Dojolvi has seen continuous growth in EMEA, with regulatory wins in Kuwait and the U.K. [18] Company Strategy and Development Direction - The company aims for profitability by 2027, implementing a strategic restructuring plan to reduce operating expenses and align resources with high-impact opportunities [9][10] - The plan includes a 10% workforce reduction, impacting approximately 130 employees [10] - The company is focused on launching three additional treatments over the next two years while continuing to grow its base business of four commercial products [10][24] Management's Comments on Operating Environment and Future Outlook - Management highlighted 2026 as a significant year with potential approvals in MPS IIIA and glycogen storage disease type Ia, along with pivotal data readout in Angelman syndrome [4] - The management expressed confidence in the ability to deliver the next phase of growth required to reach profitability [20] - The company is addressing the FDA's incomplete response letter regarding UX111 and is working on resubmitting the BLA with additional documentation [7][21] Other Important Information - The company has a strong commercial infrastructure and experienced team to execute complex rare disease therapies globally [20] - The strategic restructuring is expected to enable the company to diversify its pipeline beyond gene therapy [54] Q&A Session Summary Question: What was the decision behind using cognition as the primary endpoint for the Angelman study? - The decision was based on the belief that cognition is fundamental and intertwined with communication, which takes more time to develop [27] Question: Can you provide insights on the patient baseline profile for the Angelman study? - The baseline data from the phase II trial is reflective of the phase III program, and the company is comfortable with the comparability [33] Question: How does the company plan to achieve profitability in 2027? - The pathway to profitability includes continued growth from current products and a reduction in combined R&D and SG&A expenses [40][42] Question: What is the timeline for the resubmission of the BLA in response to the IRL? - The resubmission is expected to take a couple of weeks for the FDA to determine if all required documents are included, with a PDUFA date set approximately six months after resubmission [72] Question: What is the expected launch trajectory for GSDIa? - The market for GSDIa is expected to develop steadily, with strong demand anticipated, but not as urgent as MPS IIIA [76]

Financial Data and Key Metrics Changes - For 2025, the company reported total revenue of $673 million, representing a 20% growth over 2024, exceeding the upper end of guidance [11] - The net loss for the year was $575 million, or $5.83 per share, with cash, cash equivalents, and marketable securities totaling $738 million as of December 31 [12] - Guidance for 2026 expects total revenue between $730 million and $760 million, reflecting an 8%-13% growth over 2025 [12][13] Business Line Data and Key Metrics Changes - Crysvita contributed $481 million in revenue, with a 17% growth over 2024, while Dojolvi generated $96 million, representing a 9% growth [11] - Evkeeza saw significant growth of 84% over 2024, contributing $59 million, and Mepsevii contributed $37 million [11] - The company anticipates Crysvita revenue in 2026 to be between $500 million and $520 million, with Dojolvi expected to generate between $100 million and $110 million [13] Market Data and Key Metrics Changes - The commercial business delivered a significant 20% year-over-year growth in 2025, with treatments now available in over 35 countries [8] - In Latin America, Crysvita's business is anchored in Brazil and Argentina, with solid reimbursement growth in Mexico and Colombia [17] - Dojolvi continues to grow steadily in the U.S. and EMEA, with recent regulatory wins in Kuwait and the U.K. [18] Company Strategy and Development Direction - The company is focused on achieving profitability by 2027 through a strategic restructuring plan that includes a 10% workforce reduction and realignment of resources towards high-impact opportunities [9][10] - The company aims to launch three additional treatments over the next two years while continuing to grow its existing commercial products [10][24] - The strategic restructuring will allow the company to maintain a diversified pipeline, not solely focused on gene therapy [54] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming year, highlighting key inflection points with potential approvals in MPS IIIA and glycogen storage disease type Ia, as well as pivotal data readouts in Angelman syndrome [4][20] - The management acknowledged the challenges posed by the FDA's incomplete response letter regarding UX111 but emphasized their commitment to providing the necessary documentation for resubmission [7][52] - The company remains optimistic about its ability to deliver meaningful growth and reach profitability, supported by a strong commercial infrastructure and ongoing product launches [20][42] Other Important Information - The company has implemented a strategic restructuring plan to reduce operating expenses and align resources with high-impact opportunities, aiming for profitability in 2027 [9][10] - The company expects R&D and SG&A expenses to decrease significantly in 2027, driven by the completion of clinical studies and reduced early-stage research efforts [15] Q&A Session Summary Question: Can you explain the choice of cognition as the primary endpoint for the Angelman study? - The decision was based on the fundamental nature of cognition and its interrelation with communication, with a focus on a broader assessment through the Multidomain Responder Index [27][28] Question: What is the baseline profile of patients in the Angelman study? - The baseline data from the phase 2 trial is reflective of the phase 3 program, and the company is comfortable with the comparability of the cohorts [33] Question: How does the company plan to achieve profitability in 2027? - The pathway to profitability includes continued growth from existing products, cost reductions, and contributions from upcoming launches [38][40] Question: What is the status of the DTX-301 program? - The DTX-301 program is ongoing, with data expected to be released this year [49] Question: Can you provide an update on the UX111 program and the IRL received? - The company is preparing to provide comprehensive documentation to address the IRL issues and is committed to resubmitting the BLA [52][53]

Financial Data and Key Metrics Changes - For 2025, the company reported total revenue of $673 million, representing a 20% growth over 2024, exceeding the upper end of guidance [10] - The net loss for the year was $575 million, or $5.83 per share, with cash, cash equivalents, and marketable securities totaling $738 million as of December 31 [11] Business Line Data and Key Metrics Changes - Crysvita contributed $481 million, with a 17% growth over 2024, exceeding guidance [10] - Dojolvi generated $96 million, reflecting a 9% growth over 2024 [10] - Evkeeza saw significant growth, contributing $59 million, representing an 84% increase over 2024 [10] - Mepsevii contributed $37 million, continuing to treat patients in an ultra-rare indication [10] Market Data and Key Metrics Changes - The commercial business delivered a significant 20% year-over-year growth in 2025, with treatments reaching over 35 countries [6] - The company anticipates total revenue in 2026 to be between $730 million and $760 million, representing an 8%-13% growth over 2025 [11][12] Company Strategy and Development Direction - The company is focused on achieving profitability by 2027 through a strategic restructuring plan that includes a 10% workforce reduction and realignment of resources towards high-impact opportunities [7][9] - The company aims to launch three additional treatments over the next two years while continuing to grow its existing commercial products [9][22] Management's Comments on Operating Environment and Future Outlook - Management highlighted 2026 as a significant year with potential approvals in key programs and pivotal data readouts [3] - The company is addressing the FDA's incomplete response letter regarding UX111 and is working to provide additional documentation for resubmission [5][20] - Management expressed confidence in the ability to deliver the next phase of growth required to reach profitability [19] Other Important Information - The company is implementing a strategic restructuring plan to reduce operating expenses while advancing its product pipeline [7][9] - The company expects combined R&D and SG&A expenses to be flat to down low single digits in 2026 compared to 2025 [12] Q&A Session Summary Question: Regarding the primary endpoint for the phase 3 Angelman study - The decision to use cognition over expressive communication was based on its fundamental importance and the complexities of communication development [24][25] Question: Can you provide insights on the patient baseline profile for the phase 3 study? - The baseline data from the phase 3 program is comparable to the expansion trial, providing confidence in the study's design [29][30] Question: How does the company plan to achieve profitability in 2027? - The pathway to profitability includes continued growth from current products and cost reductions, with expectations for combined R&D and SG&A expenses to decrease significantly by 2027 [35][36] Question: Can you clarify the timeline for the IRL resubmission? - The resubmission timeline is similar to the original submission, with a PDUFA date expected approximately six months after resubmission [68][69] Question: What is the expected launch trajectory for DTX-401? - The launch is expected to develop steadily, with strong demand anticipated, but not an immediate steep uptake [72]

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 Viewpoint - Ultragenyx Pharmaceutical Inc. is recognized as one of the best revenue growth stocks, with a focus on developing therapies for rare genetic diseases, particularly through its resubmission of the Biologics License Application for UX111 AAV9 gene therapy targeting Sanfilippo syndrome type A [1][3]. Group 1: Company Developments - The company resubmitted its Biologics License Application (BLA) to the U.S. FDA on January 30, seeking accelerated approval for UX111 AAV9 gene therapy [1]. - The resubmitted BLA addresses previous concerns from the FDA, with an anticipated review period of up to six months, expected to conclude in the third quarter [3]. - If approved, UX111 will be the first therapy available for Sanfilippo syndrome type A [3]. Group 2: Analyst Ratings and Market Position - Morgan Stanley analyst Maxwell Skor maintained a Buy rating on Ultragenyx Pharmaceutical with a price target of $50 [3]. - In the past month, Leerink Partners also issued a Buy rating, while Wedbush reiterated a Hold rating on the stock [3]. - The company’s product portfolio includes therapies such as Crysvita, Mepsevii, Dojolvi, and Evkeeza, emphasizing its commitment to rare and ultra-rare genetic diseases [3].

Core Insights - Ultragenyx Pharmaceutical Inc. reported preliminary total revenue for 2025 of $672 million to $674 million, exceeding the top end of guidance and representing approximately 20% growth compared to 2024 [1][3] - The company anticipates significant catalysts in 2026, including two potential gene therapy approvals and pivotal Phase 3 data for GTX-102 in Angelman syndrome [1][2] Financial Update - Preliminary revenue for 2025 is estimated at $672 million to $674 million, with Crysvita revenue projected at $480 million to $482 million, reflecting approximately 17% growth from 2024 [3] - Dojolvi revenue for 2025 is estimated at $95 million to $97 million, indicating approximately 9% growth compared to 2024 [3] - As of December 31, 2025, the company reported cash and investments of approximately $735 million [4] Clinical and Regulatory Catalysts - The company plans to present data from the Phase 3 Orbit and Cosmic studies of UX143 (setrusumab) at the J.P. Morgan Healthcare Conference on January 12, 2026 [7] - The rolling submission for DTX401 (pariglasgene brecaparvovec) for glycogen storage disease type Ia was completed in December 2025, with a PDUFA date anticipated in Q3 2026 [7] - UX111 (rebisufligene etisparvovec) for Sanfilippo syndrome type A is on track for BLA resubmission in early 2026 [7] - GTX-102 (apazunersen) data from the Phase 3 Aspire study is expected in the second half of 2026 [7] - Enrollment for UX701 (rivunatpagene miziparvovec) in the pivotal Cyprus2+ study is complete, with data expected in the first half of 2026 [7] Company Overview - Ultragenyx is focused on developing and commercializing therapies for serious rare and ultra-rare genetic diseases, with a diverse portfolio aimed at addressing high unmet medical needs [9] - The management team has extensive experience in the development and commercialization of rare disease therapeutics, emphasizing efficient drug development [10]

Summary of Ultragenyx Pharmaceutical FY Conference Call Company Overview - **Company**: Ultragenyx Pharmaceutical (NasdaqGS:RARE) - **Focus**: Development and commercialization of drugs for patients with rare diseases, particularly Osteogenesis Imperfecta (OI) and Angelman syndrome [2][26] Key Points Product Pipeline and Development - **Current Products**: Success with Crysvita, supported by Mepsevii, Evkeeza, and Dojolvi [2] - **Upcoming Data**: Anticipation for phase three data readouts, particularly for Osteogenesis Imperfecta [2] - **Setrusumab**: Expected to show significant results in both Orbit and Cosmic studies, with a focus on the probability of success [5][6] Financial Strategy - **Royalty Financing**: Initiated due to the delay in potential revenue from the Sanfilippo program, allowing for a stronger balance sheet without diluting stock [3] Clinical Trials - **Orbit and Cosmic Studies**: Both studies are designed to be reported together, with confidence in their success [4] - **Effect Size Expectations**: A treatment effect size of 30% to 40% is considered clinically meaningful, with a powered expectation of at least 50% [6][7] - **Rescue Treatment Protocol**: Ethical considerations in allowing patients to receive rescue treatment if they experience high fracture rates [9][10] Commercial Considerations - **Pricing Strategy**: Pricing for Osteogenesis Imperfecta will be informed by the successful launch of Crysvita [11] - **Duration of Treatment**: Setrusumab is expected to be a lifelong treatment due to its mechanism of action [12] Patient Demographics - **Trial Composition**: Orbit phase three includes approximately 50% type 3 and 4 patients, with a commercial mix of about 60% type 1 and 38% type 3 and 4 patients [14][15] Confidence in Data - **Confidence Level**: High confidence in the upcoming data readout for Setrusumab, supported by consistent results in earlier phases [16] Angelman Syndrome Program - **Phase 1/2 Study**: Enrollment of 74 patients, with ongoing discussions about data release prior to the next phase [17] - **Safety Monitoring**: Close monitoring of lower extremity weakness, with mild cases reported and resolved quickly [18][19] - **Dropout Rates**: Expected to remain low due to the nature of the study and the potential benefits for patients [19] Developmental Outcomes - **Cognitive Improvement**: Unique potential to improve cognition and communication in patients with Angelman syndrome, rather than just preventing deterioration [22] - **Primary Endpoint Focus**: Cognition is the primary endpoint, followed by communication and motor skills [25] Future Outlook - **Gene Therapy Programs**: Continued focus on gene therapy programs, with upcoming PDUFA dates for Sanfilippo and GSD1A expected to lead to successful launches [26]

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]