Company Overview - Ultragenyx is a rare disease company focused on transformative treatments where none have existed in the past [2] - The company is 15 years old and is on a pathway to full year GAAP profitability in 2027 [2] - Ultragenyx has 4 current commercial programs that have significant and growing revenue [2] Upcoming Developments - The company has 3 near-term launches planned, including two gene therapies (401 program and 111 program) and an OI program (143) [3] - These upcoming programs are expected to transform the company [3] - The Angelman program is also a point of interest, receiving numerous inquiries [3]

Core Insights - Ultragenyx Pharmaceutical Inc. is focused on developing and commercializing therapies for serious rare and ultra-rare genetic diseases [5][6] - The company will participate in three upcoming investor conferences, providing opportunities for engagement with investors [1][2][3][4] Conference Participation - At the Cantor Global Healthcare Conference on September 4, 2025, Eric Crombez, M.D., and Howard Horn will participate in a fireside chat and host one-on-one meetings [2] - Eric Crombez will also participate in a fireside chat and host one-on-one meetings at the Morgan Stanley 23rd Annual Global Healthcare Conference on September 9, 2025 [3] - The Bank of America Global Healthcare Conference on September 23, 2025, will feature Eric Crombez in a fireside chat and one-on-one meetings, with webcasts available on the company's website [4] Company Overview - Ultragenyx has a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical needs [5] - The management team is experienced in the development and commercialization of rare disease therapeutics, focusing on efficient drug development [6]

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

Core Insights - Ultragenyx Pharmaceutical reported a second-quarter 2025 loss of $1.17 per share, which is an improvement from a loss of $1.52 per share in the same quarter last year and better than the Zacks Consensus Estimate of a loss of $1.27 [1][5] - Total revenues for the quarter reached $166.5 million, reflecting a 13% year-over-year increase, driven primarily by higher product sales, and surpassing the Zacks Consensus Estimate of $162 million [1][5] Revenue Breakdown - Crysvita generated total revenues of $120.4 million, up 6% year over year, with contributions of $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe [3] - Mepsevii product revenues increased by 35% year over year to $8.3 million, while Dojolvi revenues rose 20% to $23.2 million due to new patient demand [4] - Evkeeza recorded sales of $14.6 million in the first quarter, showing significant growth as the drug continues to be launched in territories outside the United States [4] Financial Guidance - The company reaffirmed its 2025 financial guidance, expecting total revenues between $640 million and $670 million, which represents a growth of approximately 14-20% compared to 2024 [9] - Crysvita revenues are anticipated to be in the range of $460-$480 million, reflecting a year-over-year increase of 12-17%, while Dojolvi revenues are expected to be between $90 million and $100 million, up 2-14% year over year [9] Operating Expenses - Operating expenses for the quarter were $274.4 million, a 4% increase year over year, attributed to higher investments in late-stage pipeline programs and marketing costs for approved drugs [7] - Research and development expenses were $164.7 million (up 2%), selling, general and administrative expenses were $86.6 million (up 7%), and cost of sales was $23 million (up 8%) [7] Pipeline Updates - The FDA issued a complete response letter for Ultragenyx's biologics license application for UX111, requesting additional information related to manufacturing processes, which the company plans to address promptly [11][12] - The company is also developing GTX-102 for Angelman syndrome, which received Breakthrough Therapy designation, with data expected in the second half of 2026 [14] - Ultragenyx plans to submit a BLA for DTX401, a gene therapy for glycogen storage disease type Ia, in the fourth quarter of 2025 [15]

Core Insights - Ultragenyx reported revenue of $166.5 million for the quarter ended June 2025, reflecting a 13.2% increase year-over-year and a surprise of +2.94% over the Zacks Consensus Estimate of $161.74 million [1] - The company's EPS was -$1.17, an improvement from -$1.52 in the same quarter last year, with an EPS surprise of +7.87% compared to the consensus estimate of -$1.27 [1] Revenue Breakdown - Dojolvi product sales reached $23.21 million, exceeding the average estimate of $22.38 million by analysts, marking a +19.9% change from the previous year [4] - Evkeeza product sales were $14.57 million, significantly surpassing the estimated $11.08 million, representing an impressive +85.5% increase year-over-year [4] - Mepsevii product sales totaled $8.31 million, slightly below the average estimate of $8.64 million [4] - Total Crysvita revenue was $120.41 million, exceeding the average estimate of $118.04 million by analysts [4] - Overall product sales amounted to $80.82 million, which was below the estimated $84.66 million, but still showed a +9.5% change compared to the previous year [4] - Royalty revenue reached $85.68 million, surpassing the average estimate of $77.43 million, reflecting a +17% increase year-over-year [4] Stock Performance - Ultragenyx shares have declined by -28.2% over the past month, contrasting with a +1% change in the Zacks S&P 500 composite [3] - The stock currently holds a Zacks Rank 4 (Sell), indicating potential underperformance relative to the broader market in the near term [3]

[CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS](index=4&type=section&id=CAUTIONARY%20NOTE%20REGARDING%20FORWARD-LOOKING%20STATEMENTS) This section highlights that the report contains forward-looking statements subject to risks and uncertainties, which may cause actual results to differ materially from expectations [Forward-Looking Statements](index=4&type=section&id=Forward-Looking%20Statements) This section details the nature of forward-looking statements, outlining inherent risks and uncertainties that could cause actual results to differ materially from projections - Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause actual results, performance, outcomes, or achievements to be materially different from any future results, performance, or achievements expressed or implied[9](index=9&type=chunk) - Key areas of forward-looking statements include commercialization strategy, timing of clinical study commencements and reporting results, regulatory approvals, market opportunities, financial performance (including **2027 profitability expectations**), and the impact of market and economic conditions[10](index=10&type=chunk) - The company assumes no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future[11](index=11&type=chunk) [PART I – FINANCIAL INFORMATION](index=6&type=section&id=PART%20I%20%E2%80%93%20FINANCIAL%20INFORMATION) This part presents the company's unaudited condensed consolidated financial statements and management's discussion and analysis of financial condition and results of operations [Item 1. Financial Statements](index=6&type=section&id=Item%201.%20Financial%20Statements) This section provides the core financial statements for Ultragenyx Pharmaceutical Inc., including the Condensed Consolidated Balance Sheets, Statements of Operations, Comprehensive Loss, Stockholders' Equity, and Cash Flows, along with detailed notes explaining the figures and accounting policies - The financial statements are presented on a condensed consolidated basis and include the accounts of the Company and its wholly-owned subsidiaries[29](index=29&type=chunk) - The unaudited interim financial statements have been prepared in accordance with U.S. GAAP for interim financial information and do not include all of the information and footnotes required by GAAP for complete financial statements[30](index=30&type=chunk) [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section presents the company's financial position, detailing assets, liabilities, and stockholders' equity at specific reporting dates ASSETS and LIABILITIES (in thousands) | ASSETS (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Cash and cash equivalents | $176,306 | $173,729 | | Marketable debt securities | $311,279 | $436,296 | | Total current assets | $719,788 | $817,123 | | Total assets | $1,306,265 | $1,503,456 | | | | | | LIABILITIES (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Accounts payable | $34,242 | $38,756 | | Accrued liabilities | $180,792 | $240,973 | | Liabilities for sales of future royalties | $63,863 | $49,847 | | Total current liabilities | $293,244 | $344,153 | | Total liabilities | $1,147,979 | $1,241,159 | | | | | | STOCKHOLDERS' EQUITY (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Total stockholders' equity | $151,286 | $255,297 | - Total assets decreased from **$1,503.5 million** at December 31, 2024, to **$1,306.3 million** at June 30, 2025[14](index=14&type=chunk) - Total liabilities decreased from **$1,241.2 million** at December 31, 2024, to **$1,148.0 million** at June 30, 2025[14](index=14&type=chunk) [Condensed Consolidated Statements of Operations](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) This section outlines the company's financial performance over specific periods, including revenues, operating expenses, and net loss Statements of Operations (in thousands, except per share amounts) | (In thousands, except per share amounts) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Total revenues | $166,496 | $147,026 | $305,788 | $255,859 | | Total operating expenses | $274,384 | $263,387 | $556,615 | $537,567 | | Loss from operations | $(107,888) | $(116,361) | $(250,827) | $(281,708) | | Net loss | $(114,951) | $(131,598) | $(266,031) | $(302,282) | | Net loss per share, basic and diluted | $(1.17) | $(1.52) | $(2.73) | $(3.54) | - Total revenues increased by **13%** for the three months ended June 30, 2025, and by **20%** for the six months ended June 30, 2025, compared to the same periods in 2024[17](index=17&type=chunk) - Net loss decreased for both the three-month (from **$(131.6) million** to **$(115.0) million**) and six-month periods (from **$(302.3) million** to **$(266.0) million**) ended June 30, 2025, compared to the prior year[17](index=17&type=chunk) [Condensed Consolidated Statements of Comprehensive Loss](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Comprehensive%20Loss) This section details the company's total comprehensive loss, encompassing net loss and other comprehensive income or loss components Statements of Comprehensive Loss (in thousands) | (In thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Net loss | $(114,951) | $(131,598) | $(266,031) | $(302,282) | | Other comprehensive income (loss): | | | | | | Foreign currency translation adjustments | $415 | $(219) | $807 | $(90) | | Unrealized loss on available-for-sale debt securities | $(342) | $(445) | $(432) | $(1,652) | | Total comprehensive loss | $(114,878) | $(132,262) | $(265,656) | $(304,024) | - Total comprehensive loss decreased for both the three-month (from **$(132.3) million** to **$(114.9) million**) and six-month periods (from **$(304.0) million** to **$(265.7) million**) ended June 30, 2025, compared to the same periods in 2024[18](index=18&type=chunk) [Condensed Consolidated Statements of Stockholders' Equity](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This section tracks changes in the company's equity over time, including common stock, additional paid-in capital, and accumulated deficit Statements of Stockholders' Equity (in thousands, except share amounts) | (In thousands, except share amounts) | Balance as of December 31, 2024 | Issuance of common stock in connection with at-the-market offering, net | Stock-based compensation | Issuance of common stock under equity plan awards, net of tax | Deferred compensation | Other comprehensive income | Net loss | Balance as of June 30, 2025 | | :--------------------------------- | :------------------------------ | :-------------------------------------------------------------------- | :----------------------- | :------------------------------------------------------------ | :-------------------- | :------------------------- | :------- | :-------------------------- | | Common Stock (Shares) | 92,484,330 | 2,217,138 | — | 1,652,166 | — | — | — | 96,353,634 | | Common Stock (Amount) | $92 | $2 | — | $2 | — | — | — | $96 | | Additional Paid-In Capital | $4,212,692 | $79,726 | $77,839 | $4,076 | — | — | — | $4,374,333 | | Accumulated Other Comprehensive Loss | $(643) | — | — | — | — | $375 | — | $(268) | | Accumulated Deficit | $(3,956,844) | — | — | — | — | — | $(266,031) | $(4,222,875) | | Treasury Stock | $(3,593) | — | — | — | $(4,398) | — | — | $(7,991) | | Deferred Compensation Obligation | $3,593 | — | — | — | $4,398 | — | — | $7,991 | | Total Stockholders' Equity | $255,297 | $79,728 | $77,839 | $4,078 | — | $375 | $(266,031) | $151,286 | - Total stockholders' equity decreased from **$255.3 million** at December 31, 2024, to **$151.3 million** at June 30, 2025, primarily due to the net loss incurred during the period[20](index=20&type=chunk) - The company issued **2,217,138 shares** of common stock through an at-the-market offering, generating net proceeds of **$79.7 million** during the six months ended June 30, 2025[20](index=20&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section reports the cash inflows and outflows from operating, investing, and financing activities over specific periods Statements of Cash Flows (in thousands) | (In thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------- | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(274,748) | $(267,690) | | Net cash provided by investing activities | $191,065 | $154,999 | | Net cash provided by financing activities | $83,806 | $384,881 | | Effect of exchange rate changes on cash | $4,362 | $(1,327) | | Net increase in cash, cash equivalents and restricted cash | $4,485 | $270,863 | | Cash, cash equivalents and restricted cash at end of period | $188,644 | $490,262 | - Net cash used in operating activities increased slightly to **$(274.7) million** for the six months ended June 30, 2025, from **$(267.7) million** in the prior year[23](index=23&type=chunk) - Net cash provided by investing activities significantly increased to **$191.1 million** for the six months ended June 30, 2025, compared to **$155.0 million** in the prior year[23](index=23&type=chunk) [Notes to Condensed Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) These notes provide detailed explanations and breakdowns of the figures presented in the condensed consolidated financial statements, covering the company's organization, significant accounting policies, financial instruments, revenue recognition, investments, collaboration agreements, liabilities for future royalty sales, stock-based awards, net loss per share, equity activities, related party transactions, and accumulated other comprehensive loss - The accompanying unaudited Condensed Consolidated Financial Statements have been prepared on the same basis as the annual financial statements and reflect all adjustments considered necessary for a fair presentation[31](index=31&type=chunk) [1. Organization](index=12&type=section&id=1.%20Organization) This note describes the company's business, its focus on rare genetic diseases, and its commercially approved products and clinical programs - Ultragenyx Pharmaceutical Inc. is a biopharmaceutical company focused on the identification, acquisition, development, and commercialization of novel products for the treatment of serious rare and ultra-rare genetic diseases[25](index=25&type=chunk) - The Company operates as one reportable segment and has four commercially approved products: **Crysvita®**, **Mepsevii®**, **Dojolvi®**, and **Evkeeza®**[25](index=25&type=chunk)[26](index=26&type=chunk)[27](index=27&type=chunk)[28](index=28&type=chunk) - The Company has several ongoing clinical development programs, including gene therapies (**UX111**, **DTX401**, **DTX301**, **UX701**), a monoclonal antibody (**UX143**), and an antisense oligonucleotide (**GTX-102**)[30](index=30&type=chunk) [2. Summary of Significant Accounting Policies](index=12&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) This note outlines the key accounting principles and methods used in preparing the interim financial statements, including segment reporting and cash management - The financial statements are prepared in accordance with U.S. GAAP for interim financial information and do not include all information and footnotes required for complete annual financial statements[30](index=30&type=chunk)[31](index=31&type=chunk) - The Company operates as one reportable segment, with its CEO acting as the Chief Operating Decision Maker (CODM) who reviews total revenues and expenses on a consolidated basis[33](index=33&type=chunk)[34](index=34&type=chunk) Cash, Cash Equivalents, and Restricted Cash (in thousands) | (In thousands) | June 30, 2025 | June 30, 2024 | | :---------------------------------------------- | :------------ | :------------ | | Cash and cash equivalents | $176,306 | $480,693 | | Restricted cash included in other current assets | $9,035 | $6,172 | | Restricted cash included in other non-current assets | $3,303 | $3,397 | | Total cash, cash equivalents, and restricted cash | $188,644 | $490,262 | [3. Financial Instruments](index=17&type=section&id=3.%20Financial%20Instruments) This note details the company's financial assets and liabilities, including fair value measurements and their categorization within the fair value hierarchy - Certain financial assets and liabilities are recorded at fair value, categorized into a three-tier hierarchy (**Level 1, 2, 3**) based on the observability of inputs[54](index=54&type=chunk) - The Company determines the fair value of its equity investment in Solid Biosciences Inc. using quoted market prices, classified as **Level 1** fair value measurements[55](index=55&type=chunk) Financial Assets and Liabilities (in thousands) | Financial Assets (in thousands) | June 30, 2025 (Level 1) | June 30, 2025 (Level 2) | June 30, 2025 (Total) | December 31, 2024 (Level 1) | December 31, 2024 (Level 2) | December 31, 2024 (Total) | | :------------------------------ | :---------------------- | :---------------------- | :-------------------- | :-------------------------- | :-------------------------- | :-------------------------- | | Money market funds | $106,529 | — | $106,529 | $113,894 | — | $113,894 | | Time deposits | — | $10,000 | $10,000 | — | $10,000 | $10,000 | | Corporate bonds | — | $288,273 | $288,273 | — | $391,731 | $391,731 | | Commercial paper | — | $300 | $300 | — | $21,194 | $21,194 | | U.S. Government Treasury and agency securities | — | $74,460 | $74,460 | — | $158,814 | $158,814 | | Investment in Solid common stock | $2,543 | — | $2,543 | $2,089 | — | $2,089 | | Deferred compensation assets | — | $16,816 | $16,816 | — | $15,337 | $15,337 | | Total financial assets | $109,072 | $389,849 | $498,921 | $115,983 | $597,219 | $713,202 | | | | | | | | | | Financial Liabilities (in thousands) | June 30, 2025 (Level 1) | June 30, 2025 (Level 2) | June 30, 2025 (Total) | December 31, 2024 (Level 1) | December 31, 2024 (Level 2) | December 31, 2024 (Total) | | :------------------------------ | :---------------------- | :---------------------- | :-------------------- | :-------------------------- | :-------------------------- | :-------------------------- | | Deferred compensation liabilities | — | $17,177 | $17,177 | — | $15,756 | $15,756 | [4. Balance Sheet Components](index=18&type=section&id=4.%20Balance%20Sheet%20Components) This note provides a detailed breakdown of specific balance sheet items, including cash equivalents, marketable debt securities, inventory, and accrued liabilities Cash Equivalents and Marketable Debt Securities (in thousands) | Cash Equivalents and Marketable Debt Securities (in thousands) | Amortized Cost (June 30, 2025) | Estimated Fair Value (June 30, 2025) | Amortized Cost (December 31, 2024) | Estimated Fair Value (December 31, 2024) | | :----------------------------------------------------------- | :----------------------------- | :----------------------------------- | :--------------------------------- | :--------------------------------------- | | Money market funds | $106,529 | $106,529 | $113,894 | $113,894 | | Time deposits | $10,000 | $10,000 | $10,000 | $10,000 | | Corporate bonds | $287,803 | $288,273 | $391,124 | $391,731 | | Commercial paper | $300 | $300 | $21,194 | $21,194 | | U.S. Government Treasury and agency securities | $74,355 | $74,460 | $158,414 | $158,814 | | Total | $478,987 | $479,562 | $694,769 | $695,776 | Inventory (in thousands) | Inventory (in thousands) | June 30, 2025 | December 31, 2024 | | :----------------------- | :------------ | :---------------- | | Work-in-process | $19,755 | $21,967 | | Finished goods | $26,743 | $23,040 | | Total inventory | $46,498 | $45,007 | Accrued Liabilities (in thousands) | Accrued Liabilities (in thousands) | June 30, 2025 | December 31, 2024 | | :--------------------------------- | :------------ | :---------------- | | Research and clinical study expenses | $19,895 | $24,437 | | Payroll and related expenses | $61,060 | $94,021 | | Revenue related reserves | $47,978 | $33,344 | | Manufacturing and related expenses | $30,995 | $25,143 | | Commercial and development milestones | — | $45,000 | | Other | $20,864 | $19,028 | | Total accrued liabilities | $180,792 | $240,973 | [5. Revenue](index=19&type=section&id=5.%20Revenue) This note disaggregates total revenues by product sales and royalty revenue, and by geographic region, for the reported periods Revenue by Product and Royalty (in thousands) | (In thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Product sales: | | | | | | Crysvita | $34,727 | $40,449 | $89,807 | $76,690 | | Dojolvi | $23,207 | $19,355 | $40,216 | $35,717 | | Evkeeza | $14,573 | $7,856 | $25,604 | $11,131 | | Mepsevii | $8,310 | $6,145 | $16,697 | $12,756 | | Total product sales | $80,817 | $73,805 | $172,324 | $136,294 | | Crysvita royalty revenue | $85,679 | $73,221 | $133,464 | $119,565 | | Total revenues | $166,496 | $147,026 | $305,788 | $255,859 | Revenue by Geographic Region (in thousands) | (In thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | North America | $102,926 | $88,889 | $160,718 | $146,571 | | Latin America | $32,967 | $38,929 | $87,855 | $74,107 | | Europe, Middle East, and Africa | $26,403 | $16,157 | $49,730 | $32,130 | | Asia-Pacific | $4,200 | $3,051 | $7,485 | $3,051 | | Total revenues | $166,496 | $147,026 | $305,788 | $255,859 | - The Company's largest accounts receivable balance was from a collaboration partner, accounting for **63%** and **70%** of the total accounts receivable balance as of June 30, 2025, and December 31, 2024, respectively[59](index=59&type=chunk) [6. Investment in Amlogenyx Inc.](index=19&type=section&id=6.%20Investment%20in%20Amlogenyx%20Inc.) This note describes the company's investment in Amlogenyx Inc., its consolidation as a Variable Interest Entity, and noncontrolling interest - In July 2024, Ultragenyx contributed intellectual property rights to Amlogenyx Inc., a subsidiary, and received **9.0 million shares** of common stock of Amlogenyx[60](index=60&type=chunk) - Amlogenyx was determined to be a Variable Interest Entity (VIE) and Ultragenyx is the primary beneficiary, consolidating its financial position, results of operations, and cash flows[61](index=61&type=chunk) Noncontrolling Interest (in thousands) | (In thousands) | Noncontrolling Interest | | :------------------------------ | :---------------------- | | As of December 31, 2023 | $0 | | Issuance of equity from noncontrolling interest | $7,000 | | As of December 31, 2024 | $7,000 | | Changes and adjustments | $0 | | As of June 30, 2025 | $7,000 | [7. License and Research Agreements](index=20&type=section&id=7.%20License%20and%20Research%20Agreements) This note details key collaboration agreements, including those for Crysvita, Evkeeza, and GTX-102, outlining revenue sharing and milestone obligations - The Company collaborates with Kyowa Kirin Co., Ltd. (KKC) on the development and commercialization of Crysvita, with Ultragenyx responsible for Latin America and Türkiye sales, and KKC for the Profit-Share Territory (U.S. and Canada) and European Territory[64](index=64&type=chunk)[66](index=66&type=chunk)[68](index=68&type=chunk)[71](index=71&type=chunk) Total Crysvita Revenue (in thousands) | Total Crysvita Revenue (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Product sales | $34,727 | $40,449 | $89,807 | $76,690 | | Royalty revenue (Profit-Share Territory) | $55,358 | $46,932 | $83,955 | $75,213 | | Non-cash royalty revenue (Profit-Share Territory) | $23,725 | $20,113 | $35,981 | $32,234 | | Non-cash royalty revenue (European Territory) | $6,596 | $6,176 | $13,528 | $12,118 | | Total Crysvita revenue | $120,406 | $113,670 | $223,271 | $196,255 | - Ultragenyx collaborates with Regeneron to commercialize Evkeeza for HoFH outside the U.S., having paid a **$30.0 million** upfront payment and recognized **$27.5 million** for regulatory and sales milestones as intangible assets[77](index=77&type=chunk) - The Company acquired GeneTx Biotherapeutics LLC in July 2022 for GTX-102 (Angelman syndrome), with obligations for up to **$85.0 million** in additional regulatory approval milestones and **$75.0 million** in commercial milestone payments[86](index=86&type=chunk) [8. Liabilities for Sales of Future Royalties](index=23&type=section&id=8.%20Liabilities%20for%20Sales%20of%20Future%20Royalties) This note explains the company's obligations from the sale of future Crysvita royalty rights to RPI Finance Trust and OMERS - In December 2019, the Company sold Crysvita EU/UK/Switzerland royalty rights to RPI Finance Trust for **$320.0 million**, with RPI receiving up to **$608.0 million** by December 31, 2030, or **$800.0 million** overall[93](index=93&type=chunk) - In July 2022, the Company sold **30%** of future Crysvita U.S./Canada royalty payments to OMERS for **$500.0 million**, capped at **$725.0 million**[94](index=94&type=chunk) Liabilities for Sales of Future Royalties (in thousands) | (In thousands) | RPI (Liabilities for Sales of Future Royalties) | OMERS (Liabilities for Sales of Future Royalties) | Total (Liabilities for Sales of Future Royalties) | | :------------------------------ | :---------------------------------------------- | :------------------------------------------------ | :------------------------------------------------ | | December 31, 2023 | $376,641 | $514,926 | $891,567 | | Royalty revenue | $(25,849) | $(59,088) | $(84,937) | | Non-cash interest expense | $23,747 | $39,294 | $63,041 | | December 31, 2024 | $374,539 | $495,132 | $869,671 | | Royalty revenue | $(13,528) | $(37,915) | $(51,443) | | Non-cash interest expense | $10,161 | $18,222 | $28,383 | | June 30, 2025 | $371,172 | $475,439 | $846,611 | [9. Stock-Based Awards](index=24&type=section&id=9.%20Stock-Based%20Awards) This note provides information on available shares under equity incentive plans and the total stock-based compensation expense recognized - As of June 30, 2025, there were **3,906,974 shares** available under the 2023 Incentive Plan, **6,290,812 shares** under the Amended & Restated 2014 Employee Stock Purchase Plan, and **109,696 shares** under the Employment Inducement Plan for future equity awards[99](index=99&type=chunk) Total Stock-Based Compensation Expense (in thousands) | (In thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :---------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Cost of sales | $420 | $269 | $923 | $685 | | Research and development | $21,420 | $21,674 | $42,226 | $42,215 | | Selling, general and administrative | $16,775 | $17,420 | $35,376 | $33,397 | | Total stock-based compensation expense | $38,615 | $39,363 | $78,525 | $76,297 | [10. Net Loss Per Share](index=24&type=section&id=10.%20Net%20Loss%20Per%20Share) This note details the calculation of basic and diluted net loss per share, including the treatment of antidilutive securities - Basic net loss per share is computed by dividing the net loss by the weighted-average number of shares of common stock outstanding, pre-funded warrants, and treasury stock for deferred compensation obligations[100](index=100&type=chunk) - Diluted net loss per share includes potential dilutive securities, but these were excluded from the computation for the periods presented because their inclusion would have been antidilutive[101](index=101&type=chunk) Weighted-Average Outstanding Common Stock Equivalents (Antidilutive) | Weighted-Average Outstanding Common Stock Equivalents (Antidilutive) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Options to purchase common stock, restricted stock units, and performance stock units | 17,364,770 | 16,992,495 | 17,021,469 | 16,031,785 | | Employee stock purchase plan | 27,734 | 24,405 | 13,943 | 12,002 | | Total | 17,392,504 | 17,016,900 | 17,035,412 | 16,043,787 | [11. Equity](index=25&type=section&id=11.%20Equity) This note describes the company's at-the-market offering of common stock and the net proceeds generated from these sales - In February 2024, the Company entered into a Sales Agreement for an at-the-market (ATM) offering of up to **$350.0 million** in common stock[102](index=102&type=chunk) - As of June 30, 2025, **2,217,138 shares** were sold under the ATM offering, generating net proceeds of **$79.7 million**[102](index=102&type=chunk) [12. Related Party Transaction](index=25&type=section&id=12.%20Related%20Party%20Transaction) This note discloses a contribution agreement with a non-profit foundation where certain board members also serve - In July 2022, the Company agreed to contribute **$1.0 million** over four years to a non-profit foundation for rare disease education, where two board members also served[103](index=103&type=chunk) - For the three and six months ended June 30, 2025, **$0.3 million** was recorded as research and development expense for this agreement[103](index=103&type=chunk) [13. Accumulated Other Comprehensive Loss](index=25&type=section&id=13.%20Accumulated%20Other%20Comprehensive%20Loss) This note presents the components of accumulated other comprehensive loss, including foreign currency adjustments and unrealized gains/losses Accumulated Other Comprehensive Loss (in thousands) | (In thousands) | June 30, 2025 | December 31, 2024 | | :---------------------------------------- | :------------ | :---------------- | | Foreign currency translation adjustments | $(843) | $(1,650) | | Unrealized gain on available-for-sale securities | $575 | $1,007 | | Total accumulated other comprehensive loss | $(268) | $(643) | - Total accumulated other comprehensive loss decreased from **$(643) thousand** at December 31, 2024, to **$(268) thousand** at June 30, 2025[104](index=104&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=26&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on the company's financial condition and results of operations, discussing revenues, expenses, liquidity, and capital resources, and highlighting key business developments and future outlook - The discussion and analysis should be read in conjunction with the accompanying unaudited Condensed Consolidated Financial Statements and related notes in Item 1 and with the audited Consolidated Financial Statements in the Annual Report on Form 10-K for the year ended December 31, 2024[105](index=105&type=chunk) [Overview](index=26&type=section&id=Overview) This section introduces Ultragenyx Pharmaceutical Inc., its mission in rare genetic diseases, and its product pipeline - Ultragenyx Pharmaceutical Inc. is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases[106](index=106&type=chunk) - The company was founded in April 2010 by Emil Kakkis, M.D., Ph.D., and is led by a management team experienced in rare disease therapeutics, focusing on time- and cost-efficient drug development[107](index=107&type=chunk) Products and Development Status | Products | Description | Indication | Phase 1 | Phase 2 | Phase 3 | Approved | | :------------------------ | :---------------------- | :--------- | :------ | :------ | :------ | :------- | | **Biologics** | | | | | | | | Crysvita® (burosumab) | Fully human monoclonal antibody | XLH | | | | ☑ | | Crysvita® (burosumab) | Fully human monoclonal antibody | TIO | | | | ☑ | | Mepsevii® (vestronidase alfa) | Enzyme replacement | MPSVII | | | | ☑ | | Evkeeza® (evinacumab) | Fully human monoclonal antibody | HoFH | | | | ☑ | | UX143 (setrusumab) | Fully human monoclonal antibody | OI | | | ☑ | | | **Small Molecules** | | | | | | | | Dojolvi® (triheptanoin) | Substrate replacement | LC-FAOD | | | | ☑ | | **AAV Gene Therapy** | | | | | | | | UX111 (rebisufligene etisparvovec) | AAV9 Gene Therapy | MPS IIIA | | | | | | DTX401 (pariglasgene brecaparvovec) | AAV8 Gene Therapy | GSDIa | | | ☑ | | | DTX301 (avalotcagene ontaparvovec) | AAV8 Gene Therapy | OTC | | | ☑ | | | UX701 (rivunatpagene miziparvovec) | AAV9 Gene Therapy | Wilson | | | | | | **Nucleic Acid** | | | | | | | | GTX-102 (apazunersen) | Antisense Oligonucleotide | Angelman Syndrome | | | ☑ | | [Approved Therapies and Clinical Product Candidates](index=28&type=section&id=Approved%20Therapies%20and%20Clinical%20Product%20Candidates) This section details the company's commercially approved products and their target patient populations, alongside its clinical development pipeline - Crysvita is approved for X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), with estimated patient populations of **48,000 for XLH** and **2,000-4,000 for TIO** in the developed world[109](index=109&type=chunk)[110](index=110&type=chunk) - Mepsevii is approved for mucopolysaccharidosis VII (MPS VII), affecting an estimated **200 patients** in the developed world[112](index=112&type=chunk) - Dojolvi is approved for long-chain fatty acid oxidation disorders (LC-FAOD), with an estimated **8,000-14,000 patients** in the developed world[113](index=113&type=chunk) - Evkeeza is approved for homozygous familial hypercholesterolemia (HoFH) outside the U.S., with an estimated **3,000-5,000 HoFH patients** in the developed world outside the U.S[114](index=114&type=chunk) - The clinical pipeline includes **UX143** (Osteogenesis Imperfecta, Phase 3), **GTX-102** (Angelman Syndrome, Phase 3), **UX111** (Sanfilippo syndrome type A, BLA submitted), **DTX401** (Glycogen Storage Disease Type Ia, Phase 3), **DTX301** (Ornithine Transcarbamylase deficiency, Phase 3), and **UX701** (Wilson Disease, pivotal Cyprus2+ study)[115](index=115&type=chunk)[116](index=116&type=chunk)[117](index=117&type=chunk)[118](index=118&type=chunk)[119](index=119&type=chunk)[120](index=120&type=chunk) [Recent Program Updates](index=29&type=section&id=Recent%20Program%20Updates) This section provides updates on the progress of key clinical programs, including study results, regulatory submissions, and enrollment statuses - UX143 (OI): The Phase 3 Orbit study is progressing to final analysis expected around the **end of 2025**, having demonstrated an acceptable safety profile at the second interim analysis[121](index=121&type=chunk) - GTX-102 (Angelman Syndrome): Enrollment for the **48-week Phase 3 Aspire study** has been completed with **129 patients**, and the Phase 2/3 Aurora study is expected to initiate in the **second half of 2025**[122](index=122&type=chunk)[123](index=123&type=chunk) - UX111 (MPS IIIA): The FDA issued a Complete Response Letter (CRL) citing specific chemistry, manufacturing, and controls (CMC) related observations, which are expected to be addressable, with BLA resubmission anticipated after resolution[124](index=124&type=chunk) - DTX401 (GSDIa): The Phase 3 GlucoGene study achieved its primary endpoint, demonstrating a statistically significant reduction in daily cornstarch intake, with BLA submission now expected in the **fourth quarter of 2025**[126](index=126&type=chunk)[127](index=127&type=chunk) - DTX301 (OTC deficiency): Enrollment has been completed in the Phase 3 Enh3ance study with **37 patients**, evaluating changes in plasma ammonia levels and discontinuation/reduction of ammonia-scavenger medications[128](index=128&type=chunk) - UX701 (Wilson disease): Enrollment is on track in Cohort 4 of the ongoing, dose-finding, stage of the pivotal Cyprus2+ study, expected to be completed in the **second half of 2025**[129](index=129&type=chunk) [Financial Operations Overview](index=30&type=section&id=Financial%20Operations%20Overview) This section summarizes the company's financial performance, including net losses, revenue trends, and available cash resources - The Company has incurred net losses in each year since inception, with net losses of **$115.0 million** and **$266.0 million** for the three and six months ended June 30, 2025, respectively[131](index=131&type=chunk) - Total revenues increased to **$166.5 million** and **$305.8 million** for the three and six months ended June 30, 2025, respectively, primarily due to increased demand for approved products[132](index=132&type=chunk) - As of June 30, 2025, the Company had **$539.0 million** in available cash, cash equivalents, and marketable debt securities[132](index=132&type=chunk) [Critical Accounting Estimates](index=31&type=section&id=Critical%20Accounting%20Estimates) This section discusses the significant judgments and assumptions made by management in preparing the financial statements - The preparation of Condensed Consolidated Financial Statements requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities[133](index=133&type=chunk) - Key estimates include clinical trial accruals, fair value of assets and liabilities, income taxes, stock-based compensation, revenue recognition, and liabilities for sales of future royalties[133](index=133&type=chunk) - There have been no material changes in critical accounting policies during the six months ended June 30, 2025, as compared to those disclosed in the Annual Report[133](index=133&type=chunk) [Results of Operations](index=31&type=section&id=Results%20of%20Operations) This section analyzes the company's revenues and expenses, explaining the drivers of changes in financial performance over the periods Revenue (dollars in thousands) | Revenue (dollars in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Dollar Change | % Change | | :----------------------------- | :------------------------------- | :------------------------------- | :------------ | :------- | | Product sales: | | | | | | Crysvita | $34,727 | $40,449 | $(5,722) | -14% | | Dojolvi | $23,207 | $19,355 | $3,852 | 20% | | Evkeeza | $14,573 | $7,856 | $6,717 | 86% | | Mepsevii | $8,310 | $6,145 | $2,165 | 35% | | Total product sales | $80,817 | $73,805 | $7,012 | 10% | | Crysvita royalty revenue | $85,679 | $73,221 | $12,458 | 17% | | Total revenues | $166,496 | $147,026 | $19,470 | 13% | | | | | | | | Revenue (dollars in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Dollar Change | % Change | | :----------------------------- | :------------------------------- | :------------------------------- | :------------ | :------- | | Product sales: | | | | | | Crysvita | $89,807 | $76,690 | $13,117 | 17% | | Dojolvi | $40,216 | $35,717 | $4,499 | 13% | | Evkeeza | $25,604 | $11,131 | $14,473 | 130% | | Mepsevii | $16,697 | $12,756 | $3,941 | 31% | | Total product sales | $172,324 | $136,294 | $36,030 | 26% | | Crysvita royalty revenue | $133,464 | $119,565 | $13,899 | 12% | | Total revenues | $305,788 | $255,859 | $49,929 | 20% | - Product sales increased by **$7.0 million (10%)** and **$36.0 million (26%)** for the three and six months ended June 30, 2025, respectively, driven by the launch of Evkeeza in Japan and EMEA and increased demand for other approved products, partially offset by timing of Crysvita orders in Latin America[134](index=134&type=chunk) - Crysvita royalty revenue increased by **$12.5 million (17%)** and **$13.9 million (12%)** for the three and six months ended June 30, 2025, respectively, primarily due to an increase in the number of reimbursed patients on therapy[135](index=135&type=chunk) Cost of Sales (dollars in thousands) | Cost of Sales (dollars in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Dollar Change | % Change | | :----------------------------------- | :------------------------------- | :------------------------------- | :------------ | :------- | | Cost of sales | $23,002 | $21,280 | $1,722 | 8% | | | | | | | | Cost of Sales (dollars in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Dollar Change | % Change | | :----------------------------------- | :------------------------------- | :------------------------------- | :------------ | :------- | | Cost of sales | $51,664 | $38,813 | $12,851 | 33% | - Research and development expenses increased by **$3.2 million (2%)** for the three months ended June 30, 2025, but decreased by **$9.5 million (3%)** for the six months ended June 30, 2025, primarily due to varying manufacturing costs and clinical progress across programs[141](index=141&type=chunk) Research and Development Expenses (dollars in thousands) | Research and Development Expenses (dollars in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Dollar Change | % Change | | :----------------------------------------------------- | :------------------------------- | :------------------------------- | :------------ | :------- | | Total gene therapy programs | $50,807 | $47,116 | $3,691 | 8% | | Total biologic and nucleic acid programs | $43,771 | $32,084 | $11,687 | 36% | | Translational research | $9,106 | $12,646 | $(3,540) | -28% | | Approved products | $9,292 | $6,269 | $3,023 | 48% | | Infrastructure | $18,627 | $21,459 | $(2,832) | -13% | | Stock-based compensation | $21,420 | $21,674 | $(254) | -1% | | Other research and development | $11,713 | $20,255 | $(8,542) | -42% | | Total research and development expenses | $164,736 | $161,503 | $3,233 | 2% | | | | | | | | Research and Development Expenses (dollars in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Dollar Change | % Change | | :----------------------------------------------------- | :------------------------------- | :------------------------------- | :------------ | :------- | | Total gene therapy programs | $93,220 | $99,791 | $(6,571) | -7% | | Total biologic and nucleic acid programs | $80,071 | $67,499 | $12,572 | 19% | | Translational research | $19,282 | $28,336 | $(9,054) | -32% | | Approved products | $17,850 | $16,297 | $1,553 | 10% | | Infrastructure | $41,574 | $42,341 | $(767) | -2% | | Stock-based compensation | $42,226 | $42,215 | $11 | * | | Other research and development | $36,285 | $43,511 | $(7,226) | -17% | | Total research and development expenses | $330,508 | $339,990 | $(9,482) | -3% | - Selling, general and administrative expenses increased by **$6.0 million (7%)** and **$15.7 million (10%)** for the three and six months ended June 30, 2025, respectively, due to higher employee compensation costs and increased marketing expenses[144](index=144&type=chunk) - Interest income decreased by **$1.6 million (22%)** and **$3.6 million (22%)** for the three and six months ended June 30, 2025, respectively, primarily due to lower marketable debt securities balances[146](index=146&type=chunk) - Non-cash interest expense on liabilities for sales of future royalties decreased by **$1.9 million (12%)** and **$3.4 million (11%)** for the three and six months ended June 30, 2025, respectively, primarily due to a reduction in total royalty obligation balances[148](index=148&type=chunk)[149](index=149&type=chunk) - Other income increased by **$4.0 million** and **$6.4 million** for the three and six months ended June 30, 2025, respectively, primarily due to fluctuations in foreign exchange rates[150](index=150&type=chunk) - Provision for income taxes increased by **$0.1 million** and **$0.9 million** for the three and six months ended June 30, 2025, respectively, primarily due to increased foreign activities[151](index=151&type=chunk) [Liquidity and Capital Resources](index=36&type=section&id=Liquidity%20and%20Capital%20Resources) This section assesses the company's ability to meet its short-term and long-term financial obligations, including funding sources and cash flow activities - The Company has funded its operations primarily from the sale of equity securities, revenue from commercial products, the sale of certain future royalties, and strategic collaboration arrangements[152](index=152&type=chunk) - As of June 30, 2025, the Company had **$539.0 million** in available cash, cash equivalents, and marketable debt securities, which are believed to be sufficient to fund projected operating requirements for at least the next **12 months**[153](index=153&type=chunk) - In February 2024, the Company entered into a Sales Agreement for an at-the-market (ATM) offering of up to **$350.0 million**, under which **2,217,138 shares** were sold for net proceeds of **$79.7 million** as of June 30, 2025[155](index=155&type=chunk) Cash Flows (in thousands) | Cash Flows (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------- | :----------------------------- | :----------------------------- | | Cash used in operating activities | $(274,748) | $(267,690) | | Cash provided by investing activities | $191,065 | $154,999 | | Cash provided by financing activities | $83,806 | $384,881 | | Effect of exchange rate changes on cash | $4,362 | $(1,327) | | Net increase in cash, cash equivalents and restricted cash | $4,485 | $270,863 | - Cash used in operating activities for the six months ended June 30, 2025, was **$274.7 million**, primarily reflecting a net loss of **$266.0 million**, partially offset by non-cash items[157](index=157&type=chunk) - Cash provided by investing activities for the six months ended June 30, 2025, was **$191.1 million**, primarily related to net activities in marketable debt securities[159](index=159&type=chunk) - Cash provided by financing activities for the six months ended June 30, 2025, was **$83.8 million**, primarily related to net proceeds from the ATM offering[161](index=161&type=chunk) [Contractual Obligations and Commitments](index=38&type=section&id=Contractual%20Obligations%20and%20Commitments) This section outlines the company's significant contractual obligations, including lease payments, manufacturing contracts, and potential milestone payments - Material contractual obligations include operating and finance leases, with future minimum lease payments of approximately **$43.7 million** as of June 30, 2025, of which **$15.0 million** is due within one year[165](index=165&type=chunk) - Manufacturing and service contract obligations totaled approximately **$114.4 million** as of June 30, 2025, with **$100.0 million** due within one year[165](index=165&type=chunk) - Future milestone payments under license and collaboration agreements are contingent upon various events, which have a high degree of uncertainty regarding amount and timing[166](index=166&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=38&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section discusses the company's exposure to market risks, specifically interest rate risk and foreign currency risk, and how these risks could impact its financial condition and results of operations - The primary objective of the Company's investment activities is to preserve capital to fund operations, with a secondary objective to maximize income from investments without assuming significant risk[167](index=167&type=chunk) [Interest Rate Risk](index=38&type=section&id=Interest%20Rate%20Risk) This section analyzes the company's exposure to fluctuations in interest rates, primarily on its cash equivalents and marketable debt securities - The Company's exposure to market risk for changes in interest rates relates primarily to interest earned on its cash equivalents and marketable debt securities, totaling **$539.0 million** as of June 30, 2025[167](index=167&type=chunk) - A hypothetical **100 basis point** change in interest rates would not have had a material impact on the fair market value of the Company's cash equivalents and marketable debt securities as of June 30, 2025, or December 31, 2024[167](index=167&type=chunk) [Foreign Currency Risk](index=39&type=section&id=Foreign%20Currency%20Risk) This section addresses the company's exposure to foreign exchange rate volatility and its potential impact on revenue and operating income - The Company faces foreign exchange risk from transactions denominated in currencies other than U.S. dollars but does not utilize forward exchange contracts due to the uncertain timing of expected payments[169](index=169&type=chunk) - Volatile market conditions or a weakening of foreign currencies relative to the U.S. dollar may negatively affect revenue and operating income[169](index=169&type=chunk) - A hypothetical **10%** change in foreign exchange rates during any of the periods presented would not have had a material impact on the Condensed Consolidated Financial Statements[169](index=169&type=chunk) [Item 4. Controls and Procedures](index=39&type=section&id=Item%204.%20Controls%20and%20Procedures) This section details management's evaluation of the effectiveness of the company's disclosure controls and procedures and confirms no material changes in internal control over financial reporting during the quarter - Management, under the supervision of the Principal Executive Officer and Principal Financial Officer, carried out an evaluation of the effectiveness of disclosure controls and procedures as of June 30, 2025[170](index=170&type=chunk) [Evaluation of Disclosure Controls and Procedures](index=39&type=section&id=Evaluation%20of%20Disclosure%20Controls%20and%20Procedures) This section confirms management's conclusion on the effectiveness of the company's disclosure controls and procedures as of June 30, 2025 - Management concluded that the Company's disclosure controls and procedures were effective and designed to provide reasonable assurance that required information is recorded, processed, summarized, and reported within specified time periods as of June 30, 2025[170](index=170&type=chunk) [Changes in Internal Control over Financial Reporting](index=39&type=section&id=Changes%20in%20Internal%20Control%20over%20Financial%20Reporting) This section states that no material changes occurred in the company's internal control over financial reporting during the quarter - There have been no changes in the Company's internal control over financial reporting during the quarter ended June 30, 2025, that have materially affected, or are reasonably likely to materially affect, its internal control over financial reporting[171](index=171&type=chunk) [PART II – OTHER INFORMATION](index=40&type=section&id=PART%20II%20%E2%80%93%20OTHER%20INFORMATION) This part includes disclosures on legal proceedings, risk factors, equity sales, defaults, mine safety, other information, and exhibits [Item 1. Legal Proceedings](index=40&type=section&id=Item%201.%20Legal%20Proceedings) This section details ongoing legal proceedings, including patent infringement suits related to Dojolvi and a breach of manufacturing agreement suit against Catalent - Ultragenyx filed a patent infringement suit under the Hatch-Waxman Act against Navinta LLC, Aurobindo Pharma Limited, and Esjay Pharma LLC in September 2024, in response to ANDA filings for a generic version of Dojolvi® (triheptanoin)[172](index=172&type=chunk) - The Dojolvi patent suit triggers a stay preventing the FDA from granting final approval to the ANDAs until **December 30, 2027**, and Ultragenyx intends to vigorously defend its intellectual property[172](index=172&type=chunk) - Ultragenyx filed a suit against Catalent Maryland, Inc. and Catalent Pharma Solutions LLC in October 2024, alleging fraudulent misrepresentation of manufacturing capabilities and breach of its manufacturing agreement, seeking monetary damages in excess of **$100 million**[174](index=174&type=chunk) [Item 1A. Risk Factors](index=41&type=section&id=Item%201A.%20Risk%20Fact

Financial Data and Key Metrics Changes - In Q2 2025, total revenue was reported at $166 million, representing a 13% increase over Q2 2024 and a 20% increase year-to-date [20] - The net loss for the quarter was $115 million, or $1.17 per share, with cash, cash equivalents, and marketable securities totaling $539 million as of June 30, 2025 [21][22] - The company expects 2025 total revenue to be between $640 million and $670 million, indicating a growth of 14% to 20% over 2024 [22] Business Line Data and Key Metrics Changes - Crysvita contributed $120 million in Q2 2025, with $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe [20] - Dajolvi generated $23 million, while Akiza and Mepsevii contributed $15 million and $8 million, respectively, reflecting steady growth trajectories for these products [20] - The commercial teams reported double-digit revenue growth, with total revenue across the first two quarters reaching $306 million, a 20% increase compared to the previous year [12] Market Data and Key Metrics Changes - In Latin America, approximately 825 patients are now on Crysvita, with positive feedback from healthcare providers leading to increased prescriptions [14] - In the U.S. and Canada, Crysvita revenue is expected to continue growing as new pediatric and adult patients are identified [15] - The EMEA region has seen approximately 280 patients treated with DERJOVY under named patient sales, with strong demand noted in France and other countries [17] Company Strategy and Development Direction - The company aims to achieve GAAP profitability by 2027 while focusing on revenue growth and managing expenses [22][30] - Ultragenyx is advancing its clinical pipeline with five Phase III programs fully enrolled or at the BLA submission stage, including UX143 for osteogenesis imperfecta and GTX102 for Angelman syndrome [6][10] - The company is committed to navigating pricing negotiations and expanding its market presence in various regions, particularly in Latin America and EMEA [19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical studies and the potential for transformative treatments, particularly for UX143 and GTX102 [9][10] - The company is optimistic about the upcoming data readouts and the overall strength of its product portfolio despite recent regulatory challenges [30] - Management highlighted the importance of maintaining a strong cash position while preparing for future commercial launches [22][30] Other Important Information - The company received breakthrough therapy designation for GTX102 from the FDA, indicating substantial improvement over existing therapies [10] - The Phase III ASPIRE study for GTX102 completed enrollment ahead of schedule, with results expected in 2026 [11] - The company is actively working with the FDA to address observations from a complete response letter for UX111, aiming for a timely resubmission [26][97] Q&A Session Summary Question: Recent FDA interactions and their impact - Management reported productive interactions with the FDA since the complete response letter, expressing confidence in the ongoing discussions [35] Question: Differences in dosing regimens for GTX102 - The company explained that the LNA chemistry used in GTX102 is more potent, allowing for lower dosing regimens compared to other drugs [38][39] Question: COSMIC trial rationale and assumptions - The COSMIC trial aims to evaluate young patients on bisphosphonates, with the goal of demonstrating a significant improvement in fracture rates [44][46] Question: Expected clinical benefit from the Orbit study - Management indicated that even if the fracture data is slightly under expectations, other supportive data could still make a strong case for FDA approval [62] Question: Additional clinical data for UX111 resubmission - The FDA requested updated clinical endpoint data and biomarker data for the resubmission of UX111, which the company is prepared to provide [57][58] Question: Financial management and cost control - The company is prioritizing cost control measures, including delaying certain expenses, to ensure a path to profitability by 2027 [90][91]

Financial Data and Key Metrics Changes - Total revenue for Q2 2025 was reported at $166 million, representing a 13% increase over Q2 2024 and a 20% growth year-to-date [19] - Crysvita contributed $120 million in revenue, with $79 million from North America, $35 million from Latin America and Turkey, and $7 million from Europe [19] - The net loss for the quarter was $115 million, or $1.17 per share, with total operating expenses of $274 million [20] Business Line Data and Key Metrics Changes - Crysvita continues to grow, with approximately 50 new start forms leading to around 50 new patients on reimbursed therapy in Latin America [12] - DERJOVY generated $23 million in revenue, with approximately 600 patients on reimbursed therapy since its launch in 2020 [14] - Efkesa has seen growth with nearly 285 patients across 15 countries in the EMEA region [16] Market Data and Key Metrics Changes - The company expects Crysvita revenue in the U.S. and Canada to continue growing as new pediatric and adult patients are identified [13] - The EMEA region shows strong demand for DERJOVY, particularly in France, Kuwait, Saudi Arabia, and Greece, despite not actively marketing the therapy [15] Company Strategy and Development Direction - The company aims to achieve GAAP profitability by 2027 while focusing on revenue growth and managing expenses [21][30] - The clinical pipeline is being refilled with five Phase III clinical programs fully enrolled or at the BLA submission stage [4] - The company is prioritizing the resolution of CMC issues related to UX-111 before submitting the BLA for GSD1a [65] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical studies and the potential of their pipeline, particularly UX-143 and GTX-102 [6][28] - The company is optimistic about the upcoming Phase III data readouts and believes they will support the efficacy of their treatments [28] - Management acknowledged the challenges posed by recent FDA leadership changes but remains confident in their interactions with the agency [33][92] Other Important Information - The company has $539 million in cash, cash equivalents, and marketable securities as of June 30, 2025 [20] - The company is reaffirming its revenue guidance for 2025, expecting total revenue between $640 million and $670 million [21] Q&A Session Summary Question: Recent FDA interactions and changes in leadership - Management reported productive interactions with the FDA since the CRL and is working towards a Type A meeting package [33] Question: Differences in dosing regimens for GTX-102 - The LNA chemistry used in GTX-102 is more potent, allowing for lower dosing regimens compared to other drugs [36][37] Question: COSMIC trial rationale and assumptions - The COSMIC trial aims to evaluate young patients on bisphosphonates, with the goal of demonstrating a 50% improvement in fracture rates [40][41] Question: Expectations for the Orbit study - Management believes that even if the fracture data is slightly under expectations, other supportive data will still be compelling for FDA approval [60][61] Question: Additional clinical data for UX-111 resubmission - The FDA requested updated clinical endpoint data and biomarker data for the resubmission of UX-111 [55] Question: Financial strategy and cost management - The company is prioritizing cost management and delaying certain expenses to maintain cash flow while working towards profitability [84][86]

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]

[Financial Highlights and Corporate Outlook](index=1&type=section&id=Financial%20Highlights%20and%20Corporate%20Outlook) Ultragenyx reported **$166 million** in Q2 2025 revenue, reaffirmed full-year guidance, and progressed key clinical programs including upcoming Phase 3 data for UX143 and full enrollment for GTX-102 Q2 2025 Financial Metrics | Metric | Q2 2025 | | :--- | :--- | | **Total Revenue** | $166 million | | **Crysvita® Revenue** | $120 million | | **Dojolvi® Revenue** | $23 million | - The company reaffirmed its full-year 2025 revenue guidance, projecting total revenue between **$640 million** and **$670 million**[1](index=1&type=chunk) - Management emphasized continued progress towards achieving GAAP profitability in **2027** through top-line growth and fiscal discipline[2](index=2&type=chunk) - Key clinical updates include expected Phase 3 data for UX143 by year-end and full enrollment of the Phase 3 Aspire study for GTX-102, which received FDA Breakthrough Therapy Designation[1](index=1&type=chunk) [Financial Performance](index=2&type=section&id=Financial%20Performance) Ultragenyx reported **$166.5 million** in Q2 2025 total revenues, a **13% year-over-year increase**, with a reduced net loss of **$115.0 million** and a quarter-end cash balance of **$539 million** [Revenues](index=2&type=section&id=Revenues) Total revenue for Q2 2025 increased **13% year-over-year** to **$166.5 million**, primarily driven by strong performance from Crysvita, Dojolvi, and Evkeeza Q2 2025 Revenue Breakdown | Revenue Source | Q2 2025 ($M) | Q2 2024 ($M) | YoY Growth | | :--- | :--- | :--- | :--- | | Total Crysvita Revenue | 120.4 | 113.7 | 6% | | Dojolvi | 23.2 | 19.4 | 20% | | Evkeeza | 14.6 | 7.9 | 85% | | Mepsevii | 8.3 | 6.1 | 35% | | **Total Revenues** | **166.5** | **147.0** | **13%** | [Operating Expenses and Net Loss](index=2&type=section&id=Operating%20Expenses%20and%20Net%20Loss) Q2 2025 operating expenses reached **$274.4 million**, resulting in a net loss of **$115.0 million** or **$1.17 per share**, an improvement from the prior year's net loss Q2 2025 Operating Expenses and Net Loss | Financial Metric | Q2 2025 ($M) | Q2 2024 ($M) | | :--- | :--- | :--- | | Total Operating Expenses | 274.4 | 263.4 | | Net Loss | (115.0) | (131.6) | | Net Loss Per Share | ($1.17) | ($1.52) | - Total operating expenses included **$39 million** in non-cash stock-based compensation[6](index=6&type=chunk) [Cash Position](index=3&type=section&id=Cash%20Position) As of June 30, 2025, Ultragenyx maintained a cash position of **$539 million**, with **$108 million** net cash used in operations for the quarter - Cash, cash equivalents, and marketable debt securities stood at **$539 million** as of June 30, 2025[8](index=8&type=chunk) - Net cash used in operations was **$108 million** for the second quarter and **$275 million** for the first six months of 2025[8](index=8&type=chunk) [2025 Financial Guidance](index=3&type=section&id=2025%20Financial%20Guidance) Ultragenyx reaffirmed its full-year 2025 financial guidance, projecting **14-20% total revenue growth** and maintaining its target for GAAP profitability in **2027**, despite anticipated increases in net cash used in operations 2025 Full-Year Financial Guidance | Guidance Metric | 2025 Full Year Range | | :--- | :--- | | Total Revenue | $640M - $670M | | Crysvita Revenue | $460M - $480M | | Dojolvi Revenue | $90M - $100M | - Net cash used in operations is now expected to modestly increase compared to 2024 due to timing delays and changes for UX111, DTX401, and UX143 programs[9](index=9&type=chunk) - The company reaffirms its path to GAAP profitability in **2027** by focusing on revenue growth and prioritized spending[9](index=9&type=chunk) [Clinical Pipeline and Regulatory Updates](index=4&type=section&id=Clinical%20Pipeline%20and%20Regulatory%20Updates) Ultragenyx provided significant updates on its late-stage clinical pipeline, including progress for UX143 and GTX-102, addressing the UX111 CRL, and advancing DTX401 and UX701 programs [UX143 (setrusumab) for Osteogenesis Imperfecta (OI)](index=4&type=section&id=UX143%20%28setrusumab%29%20for%20Osteogenesis%20Imperfecta%20%28OI%29) The Phase 3 Orbit and Cosmic studies for UX143 are progressing towards final data analysis by **year-end 2025**, with an acceptable safety profile confirmed for the Orbit study - Final analysis for the Phase 3 Orbit and Cosmic studies is expected around the end of **2025**[11](index=11&type=chunk) - A Data Monitoring Committee reviewed the Orbit study in July **2025**, confirmed an acceptable safety profile, and recommended the study continue to its final analysis[11](index=11&type=chunk) [GTX-102 for Angelman Syndrome](index=4&type=section&id=GTX-102%20for%20Angelman%20Syndrome) GTX-102 received FDA Breakthrough Therapy Designation in June **2025**, with its global Phase 3 Aspire study fully enrolled and data anticipated in the second half of **2026** - The FDA granted Breakthrough Therapy Designation for GTX-102 in June **2025** based on positive Phase 1/2 data showing consistent developmental gains[14](index=14&type=chunk) - The global Phase 3 Aspire study is fully enrolled with **129 patients**, with primary endpoint data expected in the second half of **2026**[15](index=15&type=chunk) [UX111 for Sanfilippo Syndrome Type A (MPS IIIA)](index=5&type=section&id=UX111%20for%20Sanfilippo%20Syndrome%20Type%20A%20%28MPS%20IIIA%29) The FDA issued a Complete Response Letter (CRL) for the UX111 BLA in July **2025**, requesting additional CMC information, which the company believes is addressable for resubmission - The FDA issued a Complete Response Letter (CRL) for the UX111 BLA, requesting more information on CMC procedures and validation[17](index=17&type=chunk) - The CRL did not note any issues with the clinical data package, and the company believes the observations are readily addressable[17](index=17&type=chunk)[18](index=18&type=chunk) [DTX401 for Glycogen Storage Disease Type Ia (GSDIa)](index=5&type=section&id=DTX401%20for%20Glycogen%20Storage%20Disease%20Type%20Ia%20%28GSDIa%29) Ultragenyx plans to submit a Biologics License Application (BLA) for DTX401 in Q4 **2025**, proactively addressing CMC observations from the UX111 review - A BLA submission for DTX401 is planned for the fourth quarter of **2025**[19](index=19&type=chunk) - The BLA will include updates to proactively address CMC observations from the UX111 CRL[19](index=19&type=chunk) [UX701 for Wilson Disease](index=5&type=section&id=UX701%20for%20Wilson%20Disease) Enrollment for the fourth cohort of the pivotal Cyprus2+ study of UX701 is ongoing and expected to complete in the second half of **2025** - The Phase 1/2/3 Cyprus2+ study is ongoing, with enrollment in the fourth cohort expected to complete in the second half of **2025**[20](index=20&type=chunk) [Appendix: Detailed Financial Statements](index=8&type=section&id=Appendix%3A%20Detailed%20Financial%20Statements) This appendix presents detailed unaudited financial statements for Q2 **2025**, including the Statement of Operations showing a **$115.0 million** net loss and the Balance Sheet with **$539.0 million** in cash and **$1.31 billion** in total assets [Selected Statement of Operations Financial Data](index=8&type=section&id=Selected%20Statement%20of%20Operations%20Financial%20Data) For Q2 **2025**, total revenues were **$166.5 million** and operating expenses **$274.4 million**, leading to a **$115.0 million** net loss Q2 2025 Selected Statement of Operations | Statement of Operations (Q2 2025, $ thousands) | Amount | | :--- | :--- | | Total revenues | 166,496 | | Total operating expenses | 274,384 | | Loss from operations | (107,888) | | Net loss | (114,951) | | Net loss per share, basic and diluted | ($1.17) | [Selected Balance Sheet Financial Data](index=9&type=section&id=Selected%20Balance%20Sheet%20Financial%20Data) As of June 30, **2025**, the company reported **$539.0 million** in cash, **$1.31 billion** in total assets, and **$151.3 million** in total stockholders' equity June 30, 2025 Selected Balance Sheet | Balance Sheet Data (as of June 30, 2025, $ thousands) | Amount | | :--- | :--- | | Cash, cash equivalents, and marketable debt securities | 539,039 | | Working capital | 426,544 | | Total assets | 1,306,265 | | Total stockholders' equity | 151,286 |