Quarterly Report for Quarter Ending June 30, 2025 (Form 10-Q)

Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations

The following discussion and analysis of our financial condition and results of operations 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 and the related notes included in our Annual Report on Form 10-K for the year ended December 31, 2024, or Annual Report.

Overview

Ultragenyx Pharmaceutical Inc., we or the Company, is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare genetic diseases. We have built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

We were founded in April 2010 by our President and Chief Executive Officer, Emil Kakkis, M.D., Ph.D., and are led by a management team experienced in the development and commercialization of rare disease therapeutics. Our strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

Approved Therapies and Clinical Product Candidates

Our current approved therapies and clinical-stage pipeline consist of four product categories: biologics, small molecules, AAV gene therapy, and nucleic acid product candidates. The following table summarizes our approved products and pipeline of clinical product candidates:

Approved Products

Crysvita for the treatment of X-Linked Hypophosphatemia, or XLH, and Tumor-Induced Osteomalacia, or TIO

Crysvita is a fully human monoclonal antibody administered via subcutaneous injection, that targets fibroblast growth factor 23, or FGF23, developed for the treatment of XLH. XLH is a rare, hereditary, progressive, and lifelong musculoskeletal disorder characterized by renal phosphate wasting caused by excess FGF23 production. There are approximately 48,000 patients with XLH in the developed world, including approximately 36,000 adults and 12,000 children. Crysvita is the only approved treatment that addresses the underlying cause of XLH. Crysvita is approved in the U.S., the EU and certain other regions for the treatment of XLH in adult and pediatric patients one year of age and older.

Crysvita is also approved in the U.S. and certain other regions for the treatment of FGF23-related hypophosphatemia in TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older. There are approximately 2,000 to 4,000 patients with TIO in the developed world. TIO can lead to severe hypophosphatemia, osteomalacia, fractures, fatigue, bone and muscle pain, and muscle weakness.

We are collaborating with Kyowa Kirin Co., Ltd., or KKC, and Kyowa Kirin, a wholly owned subsidiary of KKC, on the development and commercialization of Crysvita globally.

Mepsevii for the treatment of Mucopolysaccharidosis VII, or MPS VII

Mepsevii is an enzyme replacement therapy administered intravenously, or IV, that replaces the missing enzyme (beta-glucuronidase), developed for the treatment of MPS VII or Sly syndrome. MPS VII is a rare lysosomal storage disease that often leads to multi-organ dysfunction, pervasive skeletal disease, and death. MPS VII is one of the rarest MPS disorders, affecting an estimated 200 patients in the developed world. Mepsevii is approved in the U.S., the EU and certain other regions for the treatment of children and adults with MPS VII.

Dojolvi for the treatment of Long-chain Fatty Acid Oxidation Disorders, or LC-FAOD

Dojolvi is a highly purified, synthetic, 7-carbon fatty acid triglyceride administered orally, designed to provide medium-chain, odd-carbon fatty acids as an energy source and metabolite replacement, developed for people with LC-FAOD. LC-FAOD represents a set of rare metabolic diseases that prevents the conversion of fat into energy and can cause low blood sugar, muscle rupture, and heart and liver disease. Dojolvi is approved in the U.S. and certain other regions as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed LC-FAOD. There are approximately 8,000 to 14,000 patients in the developed world with LC-FAOD.

Evkeeza for the treatment of Homozygous Familial Hypercholesterolemia, or HoFH

Evkeeza is a fully human monoclonal antibody administered by IV, that binds to and blocks the function of angiopoietin-like 3, or ANGPTL3, a protein that plays a key role in lipid metabolism, developed for the treatment of HoFH, a rare inherited condition. HoFH occurs when two copies of the genes causing familial hypercholesterolemia are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of low-density lipoprotein-cholesterol, or LDL-C, which is bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years. Evkeeza is approved in the U.S., where it is marketed by our partner Regeneron Pharmaceuticals, or Regeneron. It is also approved in the European Economic Area, or EEA, Brazil, Mexico, and Japan as a first-in-class therapy for use together with diet and other LDL-C lowering therapies. In these regions, Evkeeza is generally approved to treat adults and adolescents aged five years and older with clinical HoFH. There are approximately 3,000 to 5,000 patients with HoFH in the developed world outside of the U.S.

Clinical Product Candidates

UX143 (setrusumab) for the treatment of Osteogenesis Imperfecta, or OI

UX143 is a fully human monoclonal antibody administered by IV that inhibits sclerostin, a protein that acts on a key bone-signaling pathway by inhibiting the activity of bone-forming cells and promoting bone resorption. UX143 is being developed for the treatment of OI, or brittle bone disease, which is caused by variants in the COL1A1or COL1A2genes, leading to either reduced or abnormal collagen and changes in bone metabolism. There are an estimated 60,000 patients in the developed world affected by OI. UX143 has received orphan drug designation from the U.S. Food and Drug Administration, or FDA, and European Medicines Agency, or EMA, Rare Pediatric Disease designation and Breakthrough Therapy Designation from the FDA, and was accepted into the EMA's Priority Medicines, or PRIME, program. UX143 is subject to our collaboration agreement with Mereo and is the lead clinical asset in our bone endocrinology franchise.

GTX-102 (apazunersen) for the treatment of Angelman Syndrome

GTX-102 is an antisense oligonucleotide, or ASO, administered by intrathecal injection that inhibits expression of the paternal UBE3Aantisense. GTX-102 is being developed for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3Agene. There are an estimated 60,000 patients in the developed world affected by Angelman syndrome. GTX-102 has received Breakthrough Therapy Designation, Fast Track Designation, Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA and has been accepted into the EMA's PRIME program.

UX111 (rebisufligene etisparvovec) for the treatment of Sanfilippo syndrome type A or MPS IIIA

UX111 (formerly ABO-102) is an adeno-associated virus 9, or AAV9, gene therapy product candidate, administered by a one-time IV infusion that provides the cross-correcting enzyme that enables the breakdown of Heparan sulfate, or HS. UX111 is being developed for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease with no approved treatment, which primarily affects the central nervous system. There are an estimated 3,000 to 5,000 patients in the developed world affected by Sanfilippo syndrome type A. The program was acquired through an exclusive license agreement with Abeona Therapeutics, or Abeona, that was announced in May 2022. The UX111 program has received Regenerative Medicine Advanced Therapy, or RMAT, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations in the U.S., and PRIME and Orphan Medicinal Product designations in the EU.

DTX401 (pariglasgene brecaparvovec) for the treatment of Glycogen Storage Disease Type Ia, or GSDIa

DTX401 is an adeno-associated virus 8, or AAV8, gene therapy clinical candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of G6Pase-α, an essential enzyme in glycogen and glucose metabolism. DTX401 is being developed for the treatment of patients with GSDIa, and is the most common genetically inherited glycogen storage disease, with an estimated 6,000 patients in the developed world. A Pediatric Investigation Plan, or PIP, was accepted by the EMA. The DTX401 program has received Rare Pediatric Disease, RMAT, Fast Track, and Orphan Drug designations in the U.S., and PRIME and Orphan Medicinal Product Designations in the EU.

DTX301 (avalotcagene ontaparvovec) for the treatment of Ornithine Transcarbamylase, or OTC, deficiency

DTX301 is an AAV8 gene therapy product candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of the OTC, gene. DTX301 is being developed for the treatment of patients with OTC deficiency, which is the most common urea cycle disorder, and there are approximately 10,000 patients in the developed world with OTC deficiency, of which we estimate approximately 80% are classified as late-onset, our target population. DTX301 has received Orphan Drug Designation in both the U.S. and in the EU and Fast Track Designation in the U.S.

UX701 (rivunatpagene miziparvovec) for the treatment of Wilson Disease

UX701 is an AAV type 9 gene therapy, administered by a one-time IV infusion that is designed to deliver a truncated form of the ATP7Bgene. UX701 is being developed for the treatment of patients with Wilson disease, which affects approximately 50,000 patients in the developed world. UX701 has received Orphan Drug Designation in the U.S. and in the EU. UX701 has received a Fast Track Designation from the FDA.

Recent Program Updates

UX143 for the treatment of OI

In July 2025, we announced that the Phase 3 Orbitstudy is progressing to the final analysis expected around the end of 2025. In their review of the data at the second interim analysis for Orbit, the Data Monitoring Committee, or the DMC, informed us that UX143 demonstrated an acceptable safety profile and that we should continue the study to the final analysis. Patients in the Cosmic study also continue to be treated with either setrusumab or IV-BP therapy and will be evaluated in parallel with the final Orbitanalysis around the end of the year.

GTX-102 for the treatment of Angelman Syndrome

In July 2025, we announced that all patients in the 48-week Phase 3 Aspirestudy have been enrolled. In total, 129 patients, between four and 17 years of age, with a genetically confirmed diagnosis of full maternal UBE3A gene deletion were enrolled and randomized 1:1 to the GTX-102 or the sham comparator group. The primary endpoint will be improvement in cognition assessed by

Bayley-4 cognitive raw score, and the key secondary endpoint will be the Multi-domain Responder Index (MDRI) across the five domains of cognition, receptive communication, behavior, gross motor function, and sleep.

The Phase 2/3 Aurorastudy, which will evaluate GTX-102 in other Angelman syndrome genotypes and ages, is expected to initiate in the second half of 2025.

UX111 for the treatment of MPS IIIA

In July 2025, we announced receiving a Complete Response Letter, or CRL, from the FDA for UX111. The CRL cited specific chemistry, manufacturing and controls, or CMC, related observations that we expect to be readily addressable, related to facilities and processes, and are not directly related to the quality of the product. We will be working with the FDA over the next few months to resolve the observations. Once resolution is achieved with the FDA, we expect to resubmit the BLA and anticipate up to a six-month review period to follow the resubmission.

Clinical review had been ongoing and the FDA acknowledged that the neurodevelopmental outcome data provided are robust and the biomarker data provide additional supportive evidence. The CRL did not note any review issues related to the clinical data package nor clinical inspections, and asked that updated clinical data from current patients be included in the resubmission.

DTX401 for the treatment of GSDIa

In May 2024, we previously disclosed that the Phase 3 GlucoGenestudy for the treatment of patients aged eight years and older with GSDIa achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. At Week 48, patients entered a 48-week Crossover Period where patients previously treated with placebo were treated with DTX401. In May 2025 we announced data from this Crossover Period, that demonstrated greater reductions in total daily cornstarch were observed in both the ongoing DTX401 group (-60%) with a mean follow-up of 120 weeks and the Crossover Placebo to DTX401 group (-64%) with a mean duration on therapy with DTX401 of 69 weeks. As of the data cut-off, glycemic control was maintained in participants treated with DTX401 despite significant reductions in daily cornstarch intake. DTX401 has demonstrated a consistent and acceptable safety profile with no new safety signals identified as of the data cut-off.

These results will be included as part of a BLA submission which is now expected in the fourth quarter of 2025.

DTX301 for the treatment of OTC deficiency

In February 2025, we announced enrollment had been completed in the Phase 3 Enh3ance study of DTX301 for the treatment of OTC deficiency with a total of 37 patients randomized 1:1 to DTX301 or placebo. The co-primary endpoints are (i) the percentage of patients who achieve a response as measured by the change in 24-hour plasma ammonia levels and (ii) discontinuation or reduction ammonia-scavenger medications and protein-restricted diet. Based on an amended protocol, the change in 24-hour ammonia levels will be measured through Week 36, after which the study will unblind and patients will be followed for a total of up to 64 weeks to determine the complete responders able to move safely to both ammonia-scavenger medications and protein-restricted diet control.

UX701 for the treatment of Wilson disease

Enrollment is on track in Cohort 4 of the ongoing, dose-finding, stage of the pivotal Cyprus2+ study of UX701 for the treatment of Wilson disease. During Stage 1, the safety and efficacy of UX701 is being evaluated across four, sequential dosing cohorts (Cohort 1; 5.0 x 10^12 GC/kg; Cohort 2: 1.0 x 10^13 GC/kg: Cohort 3; 2.0 x 10^13 GC/kg and Cohort 4; 4.0 x 10^13 GC/kg). Enrollment in Cohort 4 is expected to be completed in the second half of 2025.

Financial Operations Overview

We are a biopharmaceutical company with a limited operating history. To date, we have invested substantially all of our efforts and financial resources in identifying, acquiring, and developing our products and product candidates, including conducting clinical studies and providing selling, general and administrative support for these operations. To date, we have funded our operations primarily from the sale of our equity securities, revenues from our commercial products, the sale of certain future royalties, and strategic collaboration arrangements.

We have incurred net losses in each year since inception. Our net losses were $115.0 million and $266.0 million for the three and six months ended June 30, 2025, respectively, and $131.6 million and $302.3 million for the three and six months ended June 30, 2024, respectively. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations.

Our total revenues were $166.5 million and $305.8 million for the three and six months ended June 30, 2025, and $147.0 million and $255.9 million for the three and six months ended June 30, 2024, respectively. The increase in revenue was largely driven by an increase in demand for our approved products.

As of June 30, 2025, we had $539.0 million in available cash, cash equivalents, and marketable debt securities.

Critical Accounting Estimates

Our management's discussion and analysis of our financial condition and results of operations is based on our Condensed Consolidated Financial Statements, which have been prepared in accordance with U.S. generally accepted accounting principles. The preparation of these Condensed Consolidated Financial Statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. There have been no material changes in our critical accounting policies during the six months ended June 30, 2025, as compared to those disclosed in "Management's Discussion and Analysis of Financial Condition and Results of Operations - Critical Accounting Policies and Significant Judgments and Estimates" in our Annual Report.

Results of Operations

Comparison of the three and six months ended June 30, 2025 to the three and six months ended June 30, 2024:

Revenue (dollars in thousands)

Our product sales increased by $7.0 million and $36.0 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024. The increase for the three months ended June 30, 2025 was primarily due to continued progress of the launch of Evkeeza in Japan and in several markets in Europe, Middle East and Africa territories, or EMEA, and the continued increase in demand for our other approved products, partially offset by a decrease in Crysvita product revenue related to timing of orders in Latin America. The increase for the six months ended June 30, 2025 is primarily due to continued progress of the launch of Evkeeza in Japan and several markets in EMEA and an increase in demand for Crysvita in Latin America resulting from an increase in the number of patients on therapy, and the continued increase in demand for our other approved products.

Our Crysvita royalty revenue increased by $12.5 million and $13.9 million for the three and six months ended June 30, 2025, respectively, as compared to the same periods in 2024. The increases were primarily due to an increase in the number of reimbursed patients on therapy.

Cost of Sales (dollars in thousands)

Cost of sales increased by $1.7 million and $12.9 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024. The increase for the three months ended June 30, 2025 was primarily due to an increase in demand for our approved products, partially offset by a decrease related to timing of Crysvita orders in Latin America. The increase in cost of sales for the six months ended June 30, 2025 was primarily due to an increase in demand for Crysvita in Latin America and Evkeeza in EMEA and Japan, and the continued increase in demand for our other approved products.

Research and Development Expenses (dollars in thousands)

Research and development expenses include internal and external costs incurred for research and development of our programs and program candidates and expenses related to certain technology that we acquire or license through business development transactions. These expenses consist primarily of clinical studies performed by contract research organizations, manufacturing of drug substance and drug product performed by contract manufacturing organizations and at our gene therapy manufacturing facility, materials and supplies, fees from collaborative and other arrangements including milestones, licenses and other fees, personnel costs including salaries, benefits and stock-based compensation, and overhead allocations consisting of various support and infrastructure costs.

Clinical programs include study conduct and manufacturing costs related to clinical program candidates. Translational research includes costs for preclinical study work and costs related to preclinical programs prior to IND filing. Upfront license, acquisition, and milestone fees include any significant expenses related to strategic licensing agreements. Approved products include costs for disease monitoring programs for post-marketing clinical studies, medical affairs activities to support scientific discovery efforts on existing programs, and regulatory costs for unapproved regions. Infrastructure costs include direct costs related to laboratory, IT, and equipment depreciation costs, and overhead allocations for human resources, IT, and other allocable costs.

We manage our research and development expenses by identifying the research and development activities we expect to be performed during a given period and then prioritizing efforts based on anticipated probability of successful technical development and regulatory approval, market potential, available human and capital resources, scientific data and other considerations. We regularly review our research and development activities based on unmet medical need and, as necessary, reallocate resources among our research and development portfolio that we believe will best support the long-term growth of our business. We allocate and analyze certain operational expenses by individual product candidates, specifically costs to conduct clinical studies, including expenses incurred with clinical research organizations, direct manufacturing costs, and salaries and benefits. Other operational expenses are not allocated and analyzed by individual product candidates. For instance, costs associated with Chemistry, Manufacturing and Controls, or CMC costs, are primarily purchases of materials for our internal gene therapy manufacturing activities that qualify as research and development expenses at the time of purchase but for which the allocation and consumption of such costs by a specific product candidate is not determined; accordingly, CMC costs for gene therapy programs are generally spread across multiple product candidates. Although we do track and allocate certain operational R&D costs at the individual product candidate level, as described above and as reflected in the table below, we do not fully track and allocate research and development expenses at the individual product candidate level.

The following tables provide a breakout of our research and development expenses by individual product candidate under each major clinical program type and other research and development categories:

Total research and development expenses increased by $3.2 million and decreased by $9.5 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024. The changes in research and development expenses were primarily due to:

We expect our annual research and development expenses to moderate in the future as we advance our product candidates through clinical development. The timing and amount of expenses incurred will depend largely upon the outcomes of current or future clinical studies for our product candidates as well as the related regulatory requirements, manufacturing costs, and any costs associated with the advancement of our preclinical programs.

Selling, General and Administrative Expenses (dollars in thousands)

Selling, general and administrative expenses increased by $6.0 million and $15.7 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024. The increases were primarily due to higher employee compensation costs and increased marketing expenses as we continue to plan for our future product launches, as well as the recognition of reimbursement for a cost share arrangement that reduced selling, general and administrative expenses for the three and six months ended June 30, 2024, which did not recur during the three and six months ended June 30, 2025.

We expect annual selling, general and administrative expenses to increase in the future as we continue to support our existing approved products, multiple clinical-stage product candidates, and planned launches of additional products.

Interest Income (dollars in thousands)

Interest income decreased by $1.6 million and $3.6 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024, primarily due to lower marketable debt securities balances.

Change in Fair Value of Equity Investments (dollars in thousands)

Change in fair value of equity investments increased by $4.0 million for the three months ended June 30, 2025, compared to the same period in 2024, primarily due to fluctuations in the value of our investment in Solid Biosciences Inc., or Solid, common stock.

Non-cash Interest Expense on Liabilities for Sales of Future Royalties (dollars in thousands)

The non-cash interest expense on liabilities for sales of future royalties decreased by $1.9 million and $3.4 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024, primarily due to a reduction in total royalty obligation balances as a result of increased royalties generated from our collaboration partner, KKC. To the extent the royalty payments are greater or less than our initial estimates or the timing of such payments is materially different than our original estimates, we prospectively adjust the effective interest rate.

Other Income (Expense) (dollars in thousands)

Other income increased by $4.0 million and $6.4 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024. These changes were primarily due to fluctuations in foreign exchange rates.

Provision for Income Taxes (dollars in thousands)

The provision for incomes taxes increased by $0.1 million and $0.9 million for the three and six months ended June 30, 2025, respectively, compared to the same periods in 2024. These increases were primarily due to increased foreign activities.

Liquidity and Capital Resources

To date, we have funded our operations primarily from the sale of our equity securities, revenue from our commercial products, the sale of certain future royalties, and strategic collaboration arrangements.

As of June 30, 2025, we had $539.0 million in available cash, cash equivalents, and marketable debt securities. We believe that our existing capital resources will be sufficient to fund our projected operating requirements for at least the next 12 months. Our cash, cash equivalents, and marketable debt securities are held in a variety of deposit accounts, interest-bearing accounts, corporate bond securities, commercial paper, U.S. government securities, asset-backed securities, and money market funds. Cash in excess of immediate requirements is invested with a view toward liquidity and capital preservation, and we seek to minimize the potential effects of concentration and credit risk.

In June 2024, we completed an underwritten public offering for the sale of shares of common stock and pre-funded warrants. The total proceeds that we received from the offering were $381.0 million, net of underwriting discounts and commissions.

In February 2024, we entered into a Sales Agreement with Cowen and Company, LLC, or Cowen, pursuant to which the Company may offer and sell shares of the Company's common stock having an aggregate offering proceeds up to $350.0 million, from time to time, in ATM offerings through Cowen. As of June 30, 2025, 2,217,138 shares have been sold under this agreement for net proceeds of $79.7 million.

The following table summarizes our cash flows for the periods indicated (in thousands):

Cash Used in Operating Activities

Our primary use of cash is to fund operating expenses, which consist primarily of research and development and commercial expenditures. Due to our significant research and development expenditures, we have generated significant operating losses since our inception. Cash used to fund operating expenses is affected by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable and accrued expenses.

Cash used in operating activities for the six months ended June 30, 2025 was $274.7 million and primarily reflected a net loss of $266.0 million, partially offset by non-cash items of $69.7 million, net, which consisted primarily of stock-based compensation, amortization of discounts on marketable debt securities, depreciation and amortization, non-cash royalty revenue, and non-cash interest expense related to the sale of future royalties. The change in operating assets and liabilities also reflected a net use of cash of $78.4 million, primarily due to a net decrease in accounts payable, accrued and other liabilities primarily due to the payout of the 2024 annual bonuses and decreases in accrued collaboration for payment of a milestone to a collaboration partner of $30.0 million, an increase in prepaid manufacturing expense, as well as an increase in accounts receivable related to timing of orders and collections.

Cash used in operating activities for the six months ended June 30, 2024 was $267.7 million and primarily reflected a net loss of $302.3 million, partially offset by non-cash items of $74.3 million, net, which consisted primarily of stock-based compensation, amortization of discounts on marketable debt securities, depreciation and amortization, change in fair value of equity investments, non-cash royalty revenue, and non-cash interest expense related to the sale of future royalties. The change in operating assets and liabilities also reflected a net use of cash of $39.7 million, primarily due to an increase in accounts receivable primarily related to an increase in sales of our approved products and timing of when orders were received, combined with a net decrease in accounts payable, accrued and other liabilities primarily due to the payout of the 2023 annual bonus and for the payment of Medicaid obligations.

Cash Provided by Investing Activities

Cash provided by investing activities for the six months ended June 30, 2025 was $191.1 million and was primarily related to $210.9 million from net activities in marketable debt securities, partially offset by the payment to a collaboration partner of $15.0 million for the achievement of a milestone under the collaboration agreement recorded as an intangible asset.

Cash provided by investing activities for the six months ended June 30, 2024 was $155.0 million and was primarily related to $174.8 million from net activities in marketable debt securities, offset by payments to a collaboration partner of $12.5 million for the achievement of milestones under the collaboration agreement recorded as an intangible asset.

Cash Provided by Financing Activities

Cash provided by financing activities for the six months ended June 30, 2025 was $83.8 million and was primarily related to net proceeds from our ATM offering.

Cash provided by financing activities for the six months ended June 30, 2024 was $384.9 million and was primarily related to net proceeds from the issuance of common stock and pre-funded warrants in connection with the underwritten public offering.

Funding Requirements

We anticipate that, excluding non-recurring items, we will continue to generate annual losses in the near term as we continue the development of, and seek regulatory approvals for, our product candidates, and continue with commercialization of approved products. We may require additional capital to fund our operations, to complete our ongoing and planned clinical studies, to commercialize our products, to continue investing in early-stage research capabilities to promote our pipeline growth, to continue to acquire or invest in businesses or products that complement or expand our business, including future milestone payments thereunder, and to further develop our general infrastructure and such funding may not be available to us on acceptable terms or at all.

If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may be required to delay, limit, reduce the scope of, or terminate one or more of our clinical studies, research and development programs, future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Our future funding requirements will depend on many factors, including the following:

We expect to satisfy future cash needs through existing capital balances, revenue from our commercial products, and a combination of public or private equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements, and other marketing and distribution arrangements. Please see "Risk Factors-Risks Related to Our Financial Condition and Capital Requirements."

Contractual Obligations and Commitments

Material contractual obligations arising in the normal course of business primarily consist of operating and finance leases and manufacturing and service contract obligations.

Future minimum lease payments under non-cancellable leases as of June 30, 2025, were approximately $43.7 million, of which $15.0 million is due within one year.

Manufacturing and service contract obligations primarily relate to manufacturing of inventory for our approved products. As of June 30, 2025, we had obligations of approximately $114.4 million, of which $100.0 million is due within one year.

We generally expect to satisfy these commitments with cash on hand and cash provided by operating activities. The terms of certain of our licenses, royalties, development and collaboration agreements, as well as other research and development activities, require us to pay potential future milestone payments based on product development success. The amount and timing of such obligations are unknown or uncertain.