Ultragenyx Pharmaceutical(RARE) - 2025 Q2 - Quarterly Report

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS 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 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] - 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] - 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] PART I – FINANCIAL INFORMATION 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 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] - 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] Condensed Consolidated Balance Sheets 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] - Total liabilities decreased from $1,241.2 million at December 31, 2024, to $1,148.0 million at June 30, 2025[14] Condensed Consolidated Statements of Operations 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] - 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] Condensed Consolidated Statements of Comprehensive Loss 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] Condensed Consolidated Statements of Stockholders' Equity 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] - 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] Condensed Consolidated Statements of Cash Flows 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] - 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] Notes to Condensed Consolidated Financial Statements 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] 1. Organization 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] - The Company operates as one reportable segment and has four commercially approved products: Crysvita®, Mepsevii®, Dojolvi®, and Evkeeza®[25][26][27][28] - 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] 2. Summary of Significant Accounting Policies 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][31] - 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][34] 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 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] - 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] 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 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 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] 6. Investment in Amlogenyx Inc. 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] - 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] 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 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][66][68][71] 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] - 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] 8. Liabilities for Sales of Future Royalties 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] - 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] 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 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] 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 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] - 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] 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 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] - As of June 30, 2025, 2,217,138 shares were sold under the ATM offering, generating net proceeds of $79.7 million[102] 12. Related Party Transaction 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] - For the three and six months ended June 30, 2025, $0.3 million was recorded as research and development expense for this agreement[103] 13. Accumulated Other Comprehensive Loss 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] Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations 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] 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] - 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] 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 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][110] - Mepsevii is approved for mucopolysaccharidosis VII (MPS VII), affecting an estimated 200 patients in the developed world[112] - 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] - 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] - 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][116][117][118][119][120] Recent Program Updates 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] - 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][123] - 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] - 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][127] - 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] - 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] Financial Operations Overview 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] - 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] - As of June 30, 2025, the Company had $539.0 million in available cash, cash equivalents, and marketable debt securities[132] Critical Accounting Estimates 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] - 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] - 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] Results of Operations 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] - 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] 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] 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] - 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] - 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][149] - 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] - 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] Liquidity and Capital Resources 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] - 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] - 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] 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] - 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] - 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] Contractual Obligations and Commitments 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] - Manufacturing and service contract obligations totaled approximately $114.4 million as of June 30, 2025, with $100.0 million due within one year[165] - 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] Item 3. Quantitative and Qualitative Disclosures About Market Risk 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] Interest Rate Risk 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] - 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] Foreign Currency Risk 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] - Volatile market conditions or a weakening of foreign currencies relative to the U.S. dollar may negatively affect revenue and operating income[169] - 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] Item 4. Controls and Procedures 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] Evaluation of Disclosure Controls and Procedures 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] Changes in Internal Control over Financial Reporting 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] PART II – OTHER INFORMATION This part includes disclosures on legal proceedings, risk factors, equity sales, defaults, mine safety, other information, and exhibits Item 1. Legal Proceedings 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] - 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] - 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] [Item 1A. Risk Factors](index=41&type=section&id=Item%201A.%20Risk%20Fact