Core Viewpoint - Ultragenyx Pharmaceutical Inc. released its 2024 Impact Report, emphasizing its commitment to corporate responsibility and its mission to transform the lives of individuals affected by rare diseases [1][2] Group 1: Corporate Responsibility Approach - The company's corporate responsibility is structured around six key pillars: Innovation, Patients, People, Communities, Planet, and Governance, aligning with its vision to lead in rare disease medicine [2] - The 2024 Impact Report includes updates for all six pillars and references Sustainability Accounting Standards Board (SASB) and Global Reporting Initiative (GRI) indices [2] Group 2: Innovation - Ultragenyx is dedicated to developing transformative treatments for rare diseases where no options currently exist [3] Group 3: Patients - The company supports the rare disease community by developing novel therapies, sharing scientific expertise, ensuring access to screening and treatment, and collaborating with policymakers for impactful changes [4] Group 4: People - Ultragenyx focuses on maintaining an inclusive, safe, and healthy work environment, along with fair and equitable compensation practices [5] Group 5: Communities - The company is committed to initiatives that positively impact the rare disease community, including public health access, STEAM education, and support for at-risk local communities [6] Group 6: Achievements and Recognition - In 2024, Ultragenyx successfully transferred the manufacturing process of its DTX401 gene therapy and advanced several key clinical programs for rare diseases [7] - The company supported over 80 clinical and non-clinical investigator-sponsored trials globally and assisted more than 650 patients in 50 countries through various access programs since 2013 [7] - Ultragenyx received multiple accolades in 2024, including being named one of the 100 Most Sustainable Companies by Barron's and recognized as one of the Top Places to Work in the USA for the second consecutive year [11]

Summary of Ultragenyx Pharmaceutical Conference Call Company Overview - **Company**: Ultragenyx Pharmaceutical (RARE) - **Industry**: Rare Disease Biotech - **Profitability Goal**: Targeting full year GAAP profitability by 2027 driven by growth from four commercial programs and three upcoming launches [5][6][79] Key Points and Arguments Financial Projections - **2025 Revenue Forecast**: Expected total revenue between $640 million to $670 million [7] - **Upcoming Data Releases**: Data from the Osteogenesis Imperfecta (OI) program expected this year, with multiple gene therapy programs under review and filing [7][13] Regulatory Environment - **FDA Interactions**: Ongoing positive interactions with the FDA, particularly for the 111 gene therapy program, with inspections on schedule [13][14] - **Impact of Executive Orders**: Uncertainty regarding the impact of new executive orders on the rare disease sector, with market sentiment suggesting minimal impact [8][9] Product Pipeline - **Osteogenesis Imperfecta (OI)**: - Phase three trial ongoing with interim analyses planned [17][18] - Market opportunity estimated at 60,000 patients globally, with a significant portion in the US [29] - Anticipated faster ramp-up compared to previous products due to existing relationships with physicians [30][50] - **Angelman Syndrome**: - Phase three trial enrollment expected to complete this year, with data anticipated next year [58][72] - Market opportunity comparable to OI, with around 60,000 patients globally [76] - **Wilson Disease**: - Currently in phase two, with enrollment of a fourth cohort expected by year-end [83][84] - Market size estimated at 50,000 patients globally [84] - **Sanfilippo Syndrome**: - Market opportunity of 3,000 to 5,000 patients globally, with no approved therapies currently [93] - Potential pricing in the range of $2 to $4 million due to the disease's severity [93] Competitive Landscape - **Market Positioning**: Ultragenyx aims to be a leading therapy in the rare disease space, leveraging existing relationships with healthcare providers [49][50] - **Competition in Angelman**: While the market can support multiple players, success will depend on clinical data outcomes [81][82] Manufacturing and Cost Structure - **Manufacturing Facilities**: Gene therapy manufacturing located in the US, with plans to leverage existing infrastructure for cost efficiency [16][89] - **Cost of Goods Sold (COGS)**: Expected to be lower due to proprietary manufacturing methods [89] Pricing Strategy - **Value Proposition**: Emphasis on responsibly pricing products, particularly in cases where current standard care is inferior but cheaper [90][91] - **Market Acceptance**: Anticipated acceptance of gene therapy pricing due to the urgency and life-threatening nature of certain conditions [91] Additional Important Insights - **Patient-Centric Approach**: The company emphasizes its mission to help rare disease patients globally, which guides its strategic decisions [12] - **Future Investments**: Plans for future R&D investments will depend on the success of current programs and their market performance [80][81] This summary encapsulates the key points discussed during the Ultragenyx Pharmaceutical conference call, highlighting the company's strategic direction, product pipeline, and market positioning within the rare disease biotech industry.

Core Viewpoint - Broad Arrow Auctions, a subsidiary of Hagerty, is set to auction a rare 2003 Honda NSX-R, one of fewer than 140 produced, at the inaugural Concorso d'Eleganza Villa d'Este Auction on May 24-25, 2025, highlighting its significance in the collector car market [1][5][8]. Company Overview - Broad Arrow Auctions is a leading global collector car auction house, founded in 2021, and has rapidly expanded its presence, including launching its first European auction in May 2025 [9]. - Hagerty, the parent company of Broad Arrow, is a prominent brand in automotive enthusiast culture, providing specialty vehicle insurance and car valuation services, with a community of over 875,000 car enthusiasts [10]. Auction Details - The auction will feature the Honda NSX-R, which is celebrated for its engineering excellence and performance, including a 3.2-litre VTEC V6 engine producing 290hp [3][4]. - The NSX-R is noted for its rarity and is the first of its kind to be auctioned publicly outside Japan in many years, expected to attract significant interest from collectors globally [6][8]. Event Context - The auction will take place at the Concorso d'Eleganza Villa d'Este, a prestigious event in Italy, further enhancing the profile of the auction and the vehicles presented [9]. - The Gelleråsen Arena in Sweden, where the NSX-R was showcased, has a rich motorsport history, adding to the allure of the vehicle being auctioned [2][8].

Company Overview - Ultragenyx Pharmaceutical Inc. is a biopharmaceutical company focused on developing and commercializing novel therapies for serious rare and ultra-rare genetic diseases [3] - The company has established a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical needs [3] Management and Strategy - The management team of Ultragenyx is experienced in the development and commercialization of rare disease therapeutics [4] - The company's strategy emphasizes time- and cost-efficient drug development to deliver safe and effective therapies to patients urgently [4] Upcoming Events - Howard Horn, the chief financial officer and executive vice president of Ultragenyx, will participate in a fireside chat at Bank of America's 2025 Healthcare Conference on May 13, 2025, at 8:00 a.m. PT [1] - A live and archived webcast of the panel will be available on the company's website [2]

Core Viewpoint - Ultragenyx Pharmaceutical reported a wider-than-expected loss in Q1 2025, despite a year-over-year revenue increase driven by higher product sales, but missed consensus estimates for revenue [1][3]. Financial Performance - The company reported a loss of $1.57 per share, compared to a loss of $2.03 per share in the same quarter last year [1]. - Total revenues for the quarter were $139.3 million, reflecting a 28% increase year over year, but falling short of the Zacks Consensus Estimate of $142 million [1]. - Operating expenses increased to $282.2 million, up 3% year over year, attributed to investments in late-stage pipeline programs and marketing costs [4]. Product Performance - Crysvita generated revenues of $102.9 million, a 25% increase year over year, with significant growth in Latin America and Turkey [2]. - Mepsevii revenues rose 27% year over year to $8.4 million, while Dojolvi revenues increased 4% to $17 million [3]. - Evkeeza recorded sales of $11 million, showing significant growth as the drug is launched in territories outside the U.S. [3]. Financial Guidance - Ultragenyx expects total revenues for 2025 to be between $640 million and $670 million, indicating a growth of approximately 14-20% compared to 2024 [6]. - Specific revenue expectations include Crysvita between $460-$480 million (up 12-17% year over year) and Dojolvi between $90 million and $100 million (up 2-14% year over year) [6]. Pipeline Developments - The company is developing UX143 for osteogenesis imperfecta in collaboration with Mereo BioPharma, with updates expected in mid-2025 [8]. - UX701, an investigational gene therapy for Wilson disease, is in a phase I/II/III study, and a BLA submission for DTX401 is planned for mid-2025 [10]. - The pivotal phase III Aspire study for GTX-102, targeting Angelman syndrome, is ongoing, with an additional open-label study planned for 2025 [11]. - The company submitted a BLA for UX111 for Sanfilippo syndrome type A, with a decision expected on August 18, 2025 [12].

Group 1 - Ultragenyx reported revenue of $139.29 million for the quarter ended March 2025, reflecting a 28% increase year-over-year [1] - The earnings per share (EPS) for the quarter was -$1.57, an improvement from -$2.03 in the same quarter last year [1] - The reported revenue was a slight miss of 1.90% compared to the Zacks Consensus Estimate of $141.99 million [1] Group 2 - Key metrics indicate that Ultragenyx shares have returned +20.9% over the past month, outperforming the Zacks S&P 500 composite's +11.5% change [3] - The stock currently holds a Zacks Rank 3 (Hold), suggesting it may perform in line with the broader market in the near term [3] Group 3 - Product sales for Mepsevii reached $8.39 million, exceeding the average estimate of $7.63 million from seven analysts [4] - Dojolvi product sales were reported at $17.01 million, below the estimated $21.47 million, but showed a 4% increase compared to the previous year [4] - Evkeeza product sales were $11.03 million, surpassing the average estimate of $10.58 million, with a significant year-over-year increase of 236.8% [4] - Total product sales amounted to $91.51 million, exceeding the average estimate of $75.76 million based on four analysts, representing a year-over-year change of 46.4% [4]

Company Performance - Ultragenyx reported a quarterly loss of $1.57 per share, slightly worse than the Zacks Consensus Estimate of a loss of $1.54, but an improvement from a loss of $2.03 per share a year ago, indicating a year-over-year improvement in loss figures [1] - The company posted revenues of $139.29 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 1.90%, but showing an increase from $108.83 million in the same quarter last year [2] - Over the last four quarters, Ultragenyx has surpassed consensus EPS estimates two times and topped consensus revenue estimates three times [2] Stock Outlook - Ultragenyx shares have declined approximately 7.6% since the beginning of the year, compared to a decline of 3.9% for the S&P 500 [3] - The current consensus EPS estimate for the upcoming quarter is -$1.27 on revenues of $160.05 million, and for the current fiscal year, it is -$5.14 on revenues of $653.73 million [7] - The estimate revisions trend for Ultragenyx is mixed, resulting in a Zacks Rank 3 (Hold), suggesting the stock is expected to perform in line with the market in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Ultragenyx belongs, is currently ranked in the top 31% of over 250 Zacks industries, indicating a favorable industry outlook [8] - Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact Ultragenyx's stock performance [5]

Product Portfolio - Ultragenyx Pharmaceutical Inc. has a diverse portfolio of approved therapies and clinical product candidates targeting serious rare and ultra-rare genetic diseases[106]. - Crysvita is the only approved treatment for X-Linked Hypophosphatemia (XLH), with approximately 48,000 patients in the developed world, including 36,000 adults and 12,000 children[110]. - Mepsevii is approved for Mucopolysaccharidosis VII (MPS VII), affecting an estimated 200 patients in the developed world[113]. - Dojolvi is approved for Long-chain Fatty Acid Oxidation Disorders (LC-FAOD), with approximately 8,000 to 14,000 patients in the developed world[114]. - Evkeeza is approved for Homozygous Familial Hypercholesterolemia (HoFH), with an estimated 3,000 to 5,000 patients in the developed world outside the U.S.[115]. - DTX401 for Glycogen Storage Disease Type Ia (GSDIa) achieved its primary endpoint, showing a statistically significant reduction in daily cornstarch intake compared to placebo at Week 48[126]. - The Phase 3 study for GTX-102 in Angelman Syndrome is currently enrolling approximately 120 patients, with completion expected in the second half of 2025[123][124]. - UX111 for MPS IIIA received Priority Review from the FDA, with a Prescription Drug User Fee Act action date set for August 18, 2025[125]. - DTX301 for OTC deficiency targets approximately 10,000 patients in the developed world, with 80% classified as late-onset[120]. - UX701 for Wilson Disease is being developed for approximately 50,000 patients in the developed world and has received Fast Track Designation from the FDA[121]. Financial Performance - Total revenues increased to $139.3 million for the three months ended March 31, 2025, up 28% from $108.8 million in the same period of 2024, driven by increased demand for approved products[133]. - Product sales rose by $29.0 million, with Crysvita sales increasing by 52% to $55.1 million, and Evkeeza sales surging by 237% to $11.0 million[135]. - Net losses for the three months ended March 31, 2025, were $151.1 million, compared to $170.7 million for the same period in 2024, reflecting ongoing R&D and administrative costs[132]. - Research and development expenses decreased by $12.7 million to $165.8 million for the three months ended March 31, 2025, primarily due to reduced costs in gene therapy programs[142]. - Selling, general and administrative expenses increased by $9.6 million to $87.8 million for the three months ended March 31, 2025, mainly due to higher employee compensation costs[143]. - Cash, cash equivalents, and marketable debt securities totaled $563.0 million as of March 31, 2025, providing a solid financial foundation for ongoing operations[133]. - Interest income decreased by $2.0 million to $8.8 million for the three months ended March 31, 2025, primarily due to lower marketable debt securities balances[145]. - Other income increased by $2.4 million, or 152%, to $0.8 million for the three months ended March 31, 2025, compared to $(1.6) million in 2024, primarily due to fluctuations in foreign exchange rates[149]. - Provision for income taxes increased by $0.9 million, or 188%, to $(1.3) million for the three months ended March 31, 2025, compared to $(0.5) million in 2024[150]. - Cash used in operating activities was $166.5 million for the three months ended March 31, 2025, reflecting a net loss of $151.1 million[156]. - Cash provided by investing activities was $119.9 million for the three months ended March 31, 2025, primarily related to $137.0 million from net activities in marketable debt securities[158]. - As of March 31, 2025, the company had $563.0 million in available cash, cash equivalents, and marketable debt securities, down from $745.0 million as of December 31, 2024[166]. - Future minimum lease payments under non-cancellable leases as of March 31, 2025, were approximately $46.6 million, with $13.9 million due within one year[164]. - The company anticipates continuing to generate annual losses in the near term as it develops and seeks regulatory approvals for product candidates[161]. - The company may require additional capital to fund operations, complete ongoing clinical studies, and commercialize products[162]. - A hypothetical 10% change in foreign exchange rates would not have had a material impact on the company's financial statements for the periods presented[167]. Clinical Development - The pivotal Stage 2 protocol for UX701 was amended to a 52-week design, focusing on safety and efficacy comparisons with active control groups[130]. - Enrollment in Cohort 4 of the UX701 study is expected to complete in the second half of 2025, with five patients receiving immunomodulation therapy[129]. - Non-cash interest expense on liabilities for sales of future royalties decreased by $1.5 million, or 9%, to $(15.8) million for the three months ended March 31, 2025, compared to $(14.3) million in 2024[148].

Financial Data and Key Metrics Changes - In Q1 2025, the company reported revenue of $139 million, representing a 28% increase compared to Q1 2024 [15] - The net loss for the quarter was $151 million, or $1.57 per share, with total operating expenses of $282 million [18] - Cash, cash equivalents, and marketable securities stood at $563 million as of March 31, 2025 [18] - The company reaffirmed its 2025 revenue guidance of $640 million to $670 million, indicating a growth of 14% to 20% over 2024 [19] Business Line Data and Key Metrics Changes - Crysvita generated $103 million in revenue, with significant contributions from North America ($41 million), Latin America and Turkey ($55 million), and Europe ($7 million), marking a 25% growth over 2024 [16] - DeJolvi contributed $17 million, while EVKYSA and Mepsevii contributed $11 million and $8 million, respectively [17] - In Latin America and Turkey, Crysvita saw a remarkable 52% growth over 2024 [16] Market Data and Key Metrics Changes - The commercial team in Latin America reported approximately 775 patients on reimbursed therapy for Crysvita, with expectations for continued growth following successful reimbursement negotiations [8] - In the U.S., the adult patient population for Crysvita has exceeded initial expectations, contributing to revenue growth [9] - The EMEA region showed strong demand for DERJOVY, with over 260 patients treated under named patient sales [11] Company Strategy and Development Direction - The company is focused on expanding its commercial operations outside the U.S. and preparing for new product launches [3] - The development pipeline includes multiple late-stage programs, with significant progress in Phase III studies for various treatments [5] - The company is working on two separate Biologics License Applications (BLAs), with one under review and another expected to be submitted mid-2025 [6] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in 2025 being a transformational year, with expectations for substantial revenue growth and successful clinical data readouts [29] - The company is actively monitoring regulatory changes and does not anticipate material exposure from tariffs affecting its products [21] - Management highlighted the importance of continued demand for products in Latin America and the U.S. pediatric and adult markets [19] Other Important Information - The company is on track for a PDUFA action date of August 18 for the UX-111 BLA under review by the FDA [7] - The company expects net cash used in operations to decrease in the remaining quarters of 2025, aiming for full-year GAAP profitability by 2027 [19] Q&A Session Summary Question: Discussion on setrusumab and fracture reduction - Management explained the concept of variation in fracture rates among patients and its impact on study outcomes, emphasizing confidence in achieving significant results [34][36] Question: Likelihood of success in the third interim read for OI - Management expressed optimism about meeting the p-value threshold based on the study's design and patient data [44][46] Question: Impact of recent FDA appointments on the rare disease space - Management indicated that while there are concerns, they remain confident in their clinical data supporting their programs [50][52] Question: Growth drivers for Crysvita in Latin America - Management noted that patient experiences and physician engagement are key factors driving growth in the region [116]

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