Core Insights - The article discusses the promising initial results from the Phase I/IIa trial of AMT-191, a gene therapy for Fabry disease, highlighting significant increases in α-Gal A activity among patients [1][4][3] Company Overview - uniQure N.V. is a gene therapy company focused on developing transformative therapies for severe medical conditions, including Fabry disease [1][10] - The company has previously achieved a milestone with its gene therapy for hemophilia B, showcasing its commitment to advancing genomic medicine [10] Clinical Trial Details - The Phase I/IIa trial of AMT-191 includes multiple cohorts, with the first cohort (Cohort A) showing α-Gal A activity increases of 27- to 208-fold above normal levels [3][4] - All patients in the first cohort discontinued enzyme replacement therapy (ERT) and maintained stable plasma lyso-Gb3 levels [3][4] - A second cohort (Cohort B) has been enrolled with a lower dose, and no serious adverse events (SAEs) have been reported to date [5] Safety and Efficacy - Preliminary data indicate that AMT-191 has a manageable safety profile, with some SAEs observed that were unrelated to the treatment [4][5] - The trial aims to explore the safety, tolerability, and early efficacy of AMT-191, with updated results expected in the first half of 2026 [1][6] Disease Context - Fabry disease is a genetic disorder caused by α-Gal A enzyme deficiency, leading to harmful substrate accumulation affecting various organs [2][9] - The current standard treatment involves bi-weekly ERT, which has limitations in effectiveness [9] Regulatory Status - AMT-191 has received Orphan Drug and Fast Track designations from the U.S. FDA, indicating its potential significance in treating Fabry disease [7]

Group 1 - Shares of uniQure (QURE) have increased by 1.3% over the past four weeks, closing at $14.46, with a mean price target of $35.09 indicating a potential upside of 142.7% [1] - The mean estimate consists of 11 short-term price targets with a standard deviation of $17.1, where the lowest estimate is $13.00 (10.1% decline) and the highest is $70.00 (384.1% increase) [2] - Analysts show strong agreement on the company's ability to report better earnings, with a positive trend in earnings estimate revisions suggesting potential upside [4][11] Group 2 - The Zacks Consensus Estimate for the current year has increased by 1% due to one upward revision in the last 30 days, with no negative revisions [12] - QURE holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - While the consensus price target may not be a reliable indicator of potential gains, it does provide a directional guide for price movement [14]

Financial Data and Key Metrics Changes - Revenue for Q2 2025 was $5.3 million, a decrease from $11.1 million in Q2 2024, primarily due to a $7.1 million drop in collaboration revenue and a $2.1 million decrease in contract manufacturing revenue [18][19] - Research and development expenses increased to $35.4 million in Q2 2025 from $33.7 million in the same period in 2024, driven by a $6.3 million rise in external program spending [19] - Cash, cash equivalents, and investment securities totaled $377 million as of June 30, 2025, up from $367.5 million at the end of 2024, attributed to net proceeds of $80.5 million from a follow-on offering [20][21] Business Line Data and Key Metrics Changes - The company is advancing AMT-130 for Huntington's disease, with pivotal data expected in September 2025, and has received breakthrough therapy designation from the FDA [6][7] - AMT-191 for Fabry disease and AMT-260 for mesial temporal lobe epilepsy are also progressing, with initial data from AMT-191 expected at the ICIEM Conference in September [10][17] Market Data and Key Metrics Changes - The company has 14 clinical sites in the U.S. screening patients for AMT-260, with strong interest from the epilepsy community following early positive data [10][17] - There are approximately 35,000 diagnosed Huntington's disease patients in the U.S., with potentially three times that number undiagnosed [70] Company Strategy and Development Direction - The company is focused on preparing for a potential commercial launch of AMT-130 in 2026, with disciplined investments in commercial planning and recruitment for key roles [9][21] - The strategy includes leveraging prior knowledge from Hemgenics to validate the manufacturing process for AMT-130 [12][13] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming pivotal data and regulatory progress, indicating a transformational second half of 2025 [22][24] - The company is committed to delivering transformative therapies for patients with serious unmet needs, emphasizing the urgency of effective treatments for Huntington's disease [23][24] Other Important Information - The company has achieved alignment with the FDA on the statistical analysis plan and CMC requirements for AMT-130, which is crucial for the planned BLA submission [8][12] - The company is actively monitoring the safety and efficacy of AMT-130, including a new cohort for patients with lower striatal volumes [14][59] Q&A Session Summary Question: Does the FDA expect a minimum threshold for clinical benefit versus the enrolled HD on CUHDRS? - Management indicated that the FDA has not requested a minimum clinical effect and is optimistic about the three-year data supporting accelerated approval [26] Question: Can you walk us through the AMT-130 procedure from a patient's perspective? - The procedure is described as minimally invasive, with patients typically recovering quickly and returning to work within days [31][34] Question: What are the expectations for the fourth cohort in the AMT-130 trial? - The goal is to document the safety of administering AMT-130 to patients who would have otherwise been excluded due to lower striatal volumes [58] Question: Are there any differences expected in the regulatory path to approval in Europe versus the U.S.? - The company has not yet met with EMA for scientific advice and is currently focused on the U.S. regulatory path [61] Question: What are the next steps for AMT-260? - The company plans to increase the number of active sites for AMT-260 and is confident in patient enrollment in the second half of the year [59]

Company Performance - uniQure reported a quarterly loss of $0.69 per share, better than the Zacks Consensus Estimate of a loss of $0.89, and an improvement from a loss of $1.16 per share a year ago, resulting in an earnings surprise of +22.47% [1] - The company posted revenues of $5.26 million for the quarter ended June 2025, missing the Zacks Consensus Estimate by 26.23%, and down from $11.13 million in the same quarter last year [2] - Over the last four quarters, uniQure has surpassed consensus EPS estimates three times but has not beaten consensus revenue estimates [2] Stock Outlook - The stock has lost about 15.2% since the beginning of the year, while the S&P 500 has gained 8.6% [3] - The current consensus EPS estimate for the coming quarter is -$0.91 on revenues of $5.97 million, and for the current fiscal year, it is -$3.34 on revenues of $37.66 million [7] - The estimate revisions trend for uniQure was mixed ahead of the earnings release, resulting in a Zacks Rank 3 (Hold) for the stock, indicating expected performance in line with the market [6] Industry Context - The Medical - Biomedical and Genetics industry, to which uniQure belongs, is currently in the top 38% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

PART I – FINANCIAL INFORMATION [Item 1. Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) This section presents uniQure N.V.'s unaudited consolidated financial statements, detailing financial position, operations, equity, and cash flows [UNAUDITED CONSOLIDATED BALANCE SHEETS](index=5&type=section&id=UNAUDITED%20CONSOLIDATED%20BALANCE%20SHEETS) This section presents the company's financial position, detailing assets, liabilities, and equity at specific reporting dates Consolidated Balance Sheet Highlights (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :-------------------------------- | :------------ | :---------------- | | Cash and cash equivalents | $253,778 | $158,930 | | Current investment securities | $123,196 | $208,591 | | Total current assets | $408,573 | $390,289 | | Total assets | $584,890 | $556,536 | | Total current liabilities | $40,929 | $40,053 | | Total liabilities | $588,893 | $563,288 | | Total shareholders' (deficit) / equity | $(4,003) | $(6,752) | - **Cash and cash equivalents** increased significantly from **$158.9 million** at December 31, 2024, to **$253.8 million** at June 30, 2025, while **current investment securities** decreased from **$208.6 million** to **$123.2 million**[13](index=13&type=chunk) - The company's **total shareholders' deficit** improved from **$(6.8) million** at December 31, 2024, to **$(4.0) million** at June 30, 2025[13](index=13&type=chunk) [UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS](index=7&type=section&id=UNAUDITED%20CONSOLIDATED%20STATEMENTS%20OF%20OPERATIONS%20AND%20COMPREHENSIVE%20LOSS) This section details the company's revenues, expenses, and net loss over specific reporting periods Consolidated Statements of Operations and Comprehensive Loss (in thousands) | Item | 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 | $5,262 | $11,126 | $6,829 | $19,611 | | Research and development expenses | $(35,383) | $(33,655) | $(71,523) | $(74,347) | | Selling, general and administrative expenses | $(13,500) | $(15,767) | $(24,408) | $(29,704) | | Net loss | $(37,719) | $(56,299) | $(81,356) | $(121,917) | | Basic and diluted net loss per ordinary share | $(0.69) | $(1.16) | $(1.49) | $(2.51) | - **Total revenues** decreased by **52.7%** for the three months ended June 30, 2025, compared to the same period in 2024, primarily due to the absence of contract manufacturing and collaboration revenues following the Lexington Transaction[16](index=16&type=chunk) - **Net loss** improved by **33.0%** for the three months ended June 30, 2025, to **$(37.7) million** from **$(56.3) million** in the prior year, and by **33.3%** for the six months ended June 30, 2025, to **$(81.4) million** from **$(121.9) million**[16](index=16&type=chunk) [UNAUDITED CONSOLIDATED STATEMENTS OF SHAREHOLDERS' (DEFICIT) / EQUITY](index=8&type=section&id=UNAUDITED%20CONSOLIDATED%20STATEMENTS%20OF%20SHAREHOLDERS'%20(DEFICIT)%20%2F%20EQUITY) This section outlines changes in the company's shareholders' equity, including share issuances and accumulated deficit Shareholders' (Deficit) / Equity Movement (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :-------------------------------- | :------------ | :---------------- | | Ordinary shares (No. of shares) | 54,865,673 | 48,988,087 | | Additional paid-in capital | $1,262,971 | $1,173,068 | | Accumulated deficit | $(1,211,321) | $(1,129,965) | | Total shareholders' (deficit) / equity | $(4,003) | $(6,752) | - The number of **ordinary shares** issued and outstanding increased from **48,988,087** at December 31, 2024, to **54,865,673** at June 30, 2025, primarily due to a follow-on public offering[13](index=13&type=chunk)[21](index=21&type=chunk) - **Additional paid-in capital** increased by **$89.9 million**, reflecting proceeds from the public offering and share-based compensation[21](index=21&type=chunk) [UNAUDITED CONSOLIDATED STATEMENTS OF CASH FLOWS](index=10&type=section&id=UNAUDITED%20CONSOLIDATED%20STATEMENTS%20OF%20CASH%20FLOWS) This section presents the company's cash inflows and outflows from operating, investing, and financing activities Consolidated Statements of Cash Flows (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(83,995) | $(93,286) | | Net cash generated from investing activities | $93,172 | $141,922 | | Net cash generated from financing activities | $80,714 | $50 | | Net increase in cash, cash equivalents and restricted cash | $94,943 | $46,495 | | Cash, cash equivalents and restricted cash at end of period | $255,272 | $291,039 | - **Net cash used in operating activities** decreased to **$(84.0) million** for the six months ended June 30, 2025, from **$(93.3) million** in the prior year, primarily due to a lower **net loss** and changes in working capital[24](index=24&type=chunk) - **Net cash generated from financing activities** significantly increased to **$80.7 million** in 2025, driven by proceeds from a follow-on public offering, compared to **$0.1 million** in 2024[24](index=24&type=chunk) [NOTES TO CONSOLIDATED FINANCIAL STATEMENTS](index=11&type=section&id=NOTES%20TO%20CONSOLIDATED%20FINANCIAL%20STATEMENTS) This section provides detailed explanations of the company's accounting policies and specific financial statement line items [1 General business information](index=11&type=section&id=1%20General%20business%20information) This section provides an overview of the company's business, incorporation, and stock listing - uniQure N.V. is a gene therapy company incorporated in the Netherlands, focused on developing single treatments for rare and devastating diseases. Its **ordinary shares** are listed on the Nasdaq Global Select Market under the symbol "QURE"[26](index=26&type=chunk)[27](index=27&type=chunk) [2 Summary of significant accounting policies](index=11&type=section&id=2%20Summary%20of%20significant%20accounting%20policies) This section outlines the key accounting principles and policies applied in preparing the financial statements - The unaudited consolidated financial statements are prepared in compliance with U.S. GAAP and SEC interim financial reporting rules, presented in U.S. dollars, and reflect normal recurring adjustments[28](index=28&type=chunk)[29](index=29&type=chunk)[30](index=30&type=chunk) - There have been no material changes to the Company's significant accounting policies or new accounting pronouncements with a material impact during the six months ended June 30, 2025[34](index=34&type=chunk)[35](index=35&type=chunk) [3 Other investments](index=13&type=section&id=3%20Other%20investments) This section details the company's holdings in convertible promissory notes and non-publicly traded equity securities - The Company holds a **convertible promissory note** with a nominal amount of **$12.5 million**, bearing **8.0% interest**, with a balance of **$14.1 million** as of June 30, 2025. **Interest income** of **$0.5 million** was recognized for the six months ended June 30, 2025[36](index=36&type=chunk) - **Investments in non-publicly traded equity securities**, valued at cost less impairment, totaled **$15.6 million** as of June 30, 2025, with no recognized gains, losses, or impairments during the period[37](index=37&type=chunk) [4 Investment securities](index=14&type=section&id=4%20Investment%20securities) This section describes the company's investment in government debt securities, including their amortized cost and fair value Investment Securities (Government Debt, held-to-maturity, in thousands) | Item | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Amortized cost | $123,196 | $208,591 | | Estimated fair value | $123,364 | $208,755 | - The Company's **current investment securities**, primarily short-term U.S. and European government debt, decreased from **$208.6 million** at December 31, 2024, to **$123.2 million** at June 30, 2025[38](index=38&type=chunk) [5 Fair value measurement](index=14&type=section&id=5%20Fair%20value%20measurement) This section details the fair value measurement of financial instruments, particularly contingent consideration liabilities - The **fair value of contingent consideration** related to the uniQure France SAS acquisition increased from **$10.9 million** at December 31, 2024, to **$15.9 million** at June 30, 2025, primarily due to an unrealized change in fair value and currency translation effects[48](index=48&type=chunk)[50](index=50&type=chunk) - If AMT-260 were assumed to advance into a Phase III clinical study, the **fair value of contingent consideration** would increase to **$51.4 million**[49](index=49&type=chunk) [6 Accrued expenses and other current liabilities](index=18&type=section&id=6%20Accrued%20expenses%20and%20other%20current%20liabilities) This section provides a breakdown of the company's accrued expenses and other short-term liabilities Accrued Expenses and Other Current Liabilities (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :-------------------------------------------------------------------------------- | :------------ | :---------------- | | Accruals for goods received from and services provided by vendors-not yet billed | $13,878 | $10,109 | | Personnel related accruals and liabilities | $8,285 | $12,583 | | Liability owed to the Purchaser pursuant to the Royalty Financing Agreement | $5,248 | $4,951 | | Current portion of firm purchase commitment liability | $4,068 | $1,582 | | Total | $31,479 | $29,225 | - **Total accrued expenses and other current liabilities** increased to **$31.5 million** at June 30, 2025, from **$29.2 million** at December 31, 2024, driven by higher accruals for vendor services and firm purchase commitments[53](index=53&type=chunk) [7 Long-term debt](index=18&type=section&id=7%20Long-term%20debt) This section details the company's long-term debt obligations, including principal outstanding and interest expenses - The Company's total **principal outstanding** under the **Hercules debt facility** was **$50.0 million** as of June 30, 2025, following a **$50.0 million** prepayment in July 2024[55](index=55&type=chunk)[56](index=56&type=chunk) - **Interest expense** on the **Hercules debt facility** decreased to **$1.8 million** for the three months ended June 30, 2025, from **$3.7 million** in the prior year, primarily due to the principal repayment and lower market interest rates[58](index=58&type=chunk)[151](index=151&type=chunk) - The Company recognized a **foreign currency gain** of **$4.3 million** on the facility for the three months ended June 30, 2025, compared to a loss of **$0.7 million** in the same period in 2024[57](index=57&type=chunk) [8 Royalty Financing Agreement](index=19&type=section&id=8%20Royalty%20Financing%20Agreement) This section describes the terms and financial impact of the company's royalty financing agreement - Under the **Royalty Financing Agreement**, the Company received an **upfront payment** of **$375.0 million** in exchange for rights to the lowest royalty tier on HEMGENIX® sales, with the Purchaser receiving **1.85 to 2.25 times** the **upfront payment** depending on the date[61](index=61&type=chunk)[62](index=62&type=chunk) - The liability from the **royalty financing agreement** increased to **$460.5 million** as of June 30, 2025, from **$439.9 million** at December 31, 2024, reflecting **$27.1 million** in **interest expense** for the period and **$6.5 million** in royalty payments[67](index=67&type=chunk) - The **effective interest rate** for the **royalty financing agreement** is expected to be within a range of **12.0% to 13.5%** per annum[65](index=65&type=chunk) [9 Shareholders' (deficit) / equity](index=21&type=section&id=9%20Shareholders'%20(deficit)%20%2F%20equity) This section details changes in the company's share capital and additional paid-in capital from financing activities - In January and February 2025, the Company completed a follow-on public offering, raising **net proceeds** of **$70.1 million** and an additional **$10.4 million** from underwriters' option exercise, totaling **$80.5 million**[68](index=68&type=chunk)[69](index=69&type=chunk) [10 Share-based compensation](index=21&type=section&id=10%20Share-based%20compensation) This section outlines the company's share-based compensation expense and related unrecognized costs Share-based Compensation Expense (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $2,758 | $2,856 | $5,221 | $6,281 | | Selling, general and administrative | $2,326 | $3,334 | $4,273 | $6,755 | | Total | $5,084 | $6,880 | $9,494 | $14,071 | - Total **share-based compensation expense** decreased by **26.1%** to **$5.1 million** for the three months ended June 30, 2025, and by **32.5%** to **$9.5 million** for the six months ended June 30, 2025, primarily due to the divestment of commercial manufacturing activities and a restructuring in August 2024[72](index=72&type=chunk)[144](index=144&type=chunk)[149](index=149&type=chunk)[171](index=171&type=chunk)[176](index=176&type=chunk) - As of June 30, 2025, **unrecognized share-based compensation expense** related to unvested awards totaled **$38.4 million**, with a weighted-average remaining recognition period of **2.34 years**[74](index=74&type=chunk) [11 Segment Reporting](index=26&type=section&id=11%20Segment%20Reporting) This section describes the company's operating segments and their financial performance - The Company operates as a single operating segment, managing research and development activities for gene therapies due to common infrastructure and resources[82](index=82&type=chunk) - **Segment operating loss** for the three months ended June 30, 2025, was **$(32.3) million**, consistent with the prior year, and **$(66.6) million** for the six months, an improvement from **$(75.4) million** in 2024[84](index=84&type=chunk) [12 CSL Behring collaboration](index=27&type=section&id=12%20CSL%20Behring%20collaboration) This section details the financial impact and accounting treatment of the collaboration with CSL Behring - Following the divestiture of commercial manufacturing activities in July 2024, the Company now recognizes costs related to HEMGENIX® purchase from Genezen net of sales income to CSL Behring as 'Other expense'[86](index=86&type=chunk) - **Accounts receivable related to collaboration services and royalty revenue** decreased slightly from **$5.88 million** at December 31, 2024, to **$5.61 million** at June 30, 2025[87](index=87&type=chunk) [13 Other income](index=27&type=section&id=13%20Other%20income) This section provides a breakdown of the company's other income sources, including grants and reagent sales Other Income (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Sale of critical reagents to Genezen | $0 | $0 | $6,000 | $0 | | Research and development grants | $1,392 | $1,662 | $3,111 | $2,886 | | Sublease income | $801 | $173 | $1,259 | $325 | | Total | $2,597 | $1,983 | $10,903 | $3,359 | - **Total other income** increased significantly to **$10.9 million** for the six months ended June 30, 2025, primarily due to a one-time **$6.0 million** **sale of critical reagents to Genezen**[88](index=88&type=chunk) [14 Income taxes](index=27&type=section&id=14%20Income%20taxes) This section details the company's income tax expense and effective tax rate - The Company recorded **deferred tax expense** of **$0.4 million** for the three months and **$0.9 million** for the six months ended June 30, 2025, related to U.S. operations[89](index=89&type=chunk) - The **effective income tax rate** was **1.1%** for both the three and six months ended June 30, 2025, substantially lower than the Netherlands' enacted rate of **25.8%** due to valuation allowances against deferred tax assets[90](index=90&type=chunk) [15 Basic and diluted earnings per share](index=28&type=section&id=15%20Basic%20and%20diluted%20earnings%20per%20share) This section explains the calculation of basic and diluted loss per share, including anti-dilutive items - Due to **net losses**, all **potentially dilutive ordinary shares** (stock options, RSUs, PSUs) were anti-dilutive and excluded from the computation of loss per share for the three and six months ended June 30, 2025[91](index=91&type=chunk) Anti-dilutive Ordinary Share Equivalents | Item | Three months ended June 30, 2025 | Six months ended June 30, 2025 | | :-------------------------------- | :------------------------------- | :----------------------------- | | Stock options under 2014 Plans | 5,321,862 | 5,321,862 | | Non-vested RSUs and PSUs | 2,442,969 | 2,442,969 | | Total anti-dilutive ordinary share equivalents | 7,764,831 | 7,764,831 | [16 Subsequent events](index=28&type=section&id=16%20Subsequent%20events) This section reports on events occurring after the reporting period that may require disclosure - No subsequent events requiring disclosure were reported[93](index=93&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=29&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on uniQure N.V.'s financial condition and results of operations, highlighting business developments, financial performance, critical accounting policies, and liquidity. It covers the company's gene therapy pipeline, regulatory progress for AMT-130, and financial results for the three and six months ended June 30, 2025, compared to 2024 [Overview](index=29&type=section&id=Overview) This section provides a high-level introduction to the company's gene therapy focus and clinical pipeline - uniQure N.V. is a gene therapy leader focused on single treatments for rare and devastating diseases, advancing clinical candidates for Huntington's disease (AMT-130), refractory MTLE (AMT-260), Fabry disease (AMT-191), and SOD1-ALS (AMT-162)[96](index=96&type=chunk) [Business Developments](index=29&type=section&id=Business%20Developments) This section highlights recent strategic and operational advancements across the company's programs [Huntington's disease program (AMT-130)](index=29&type=section&id=Huntington's%20disease%20program%20(AMT-130)) This section details the clinical and regulatory progress of the AMT-130 program for Huntington's disease - **AMT-130 received Breakthrough Therapy designation** from the FDA in April 2025, supported by Phase I/II clinical data showing potential for meaningful slowing of disease progression in Huntington's disease[97](index=97&type=chunk) - The FDA also granted **RMAT designation** in June 2024, and previously **Orphan Drug and Fast Track designations** for AMT-130[98](index=98&type=chunk) - The company expects to present 3-year follow-up data from Phase I/II studies in Q3 2025 to support a potential Biologics License Application (BLA) submission[100](index=100&type=chunk) [Regulatory Alignment](index=30&type=section&id=Regulatory%20Alignment) This section outlines key agreements and designations received from regulatory authorities for AMT-130 - In December 2024, the FDA agreed that Phase I/II data for AMT-130, compared to natural history external control, may serve as the primary basis for an **Accelerated Approval BLA submission**, using **cUHDRS as an intermediate clinical endpoint** and **NfL reductions as supportive evidence**[102](index=102&type=chunk) - In June 2025, the FDA agreed on using ENROLL-HD as the external control dataset for the primary efficacy analysis of 3-year cUHDRS change in high-dose AMT-130 patients[103](index=103&type=chunk) - The FDA also agreed that **AMT-130 manufacturing process validation could leverage HEMGENIX® experience**, complemented by additional GMP batches and a single process performance qualification batch[104](index=104&type=chunk) [Financing](index=30&type=section&id=Financing) This section details recent capital raising activities, including public offerings - In January and February 2025, the Company completed a **follow-on public offering**, raising **net proceeds** of **$70.1 million** and an additional **$10.4 million**, respectively, totaling **$80.5 million**[106](index=106&type=chunk) [Organization](index=30&type=section&id=Organization) This section reports on key organizational changes and executive appointments - **Kylie O'Keefe was appointed Chief Customer and Strategy Officer** in June 2025, responsible for leading commercial and medical affairs[107](index=107&type=chunk) [Recent Developments of other Product Candidates](index=30&type=section&id=Recent%20Developments%20of%20other%20Product%20Candidates) This section provides updates on the clinical progress of other product candidates in the pipeline [Temporal lobe epilepsy program (AMT-260)](index=30&type=section&id=Temporal%20lobe%20epilepsy%20program%20(AMT-260)) This section details the clinical progress of the AMT-260 program for refractory MTLE - The **Phase I/IIa GenTLE clinical trial for AMT-260** in **refractory MTLE** dosed its first patient in November 2024[110](index=110&type=chunk) - Initial safety and exploratory efficacy data from the first patient showed a **92% reduction in seizure frequency** over five months with no serious safety events[110](index=110&type=chunk) [Fabry disease program (AMT-191)](index=32&type=section&id=Fabry%20disease%20program%20(AMT-191)) This section outlines the clinical and regulatory progress of the AMT-191 program for Fabry disease - The **Phase I/IIa clinical trial for AMT-191 in Fabry disease** dosed its first patient in August 2024, and received **Orphan Drug and Fast Track Designations** from the FDA in September and October 2024, respectively[112](index=112&type=chunk) - An **independent data monitoring committee recommended proceeding** with enrollment in the second cohort in February 2025, following a favorable safety review of the first two patients[113](index=113&type=chunk) [Amyotrophic Lateral Sclerosis (AMT-162)](index=32&type=section&id=Amyotrophic%20Lateral%20Sclerosis%20(AMT-162)) This section details the clinical progress of the AMT-162 program for SOD1-ALS - The **Phase I/II EPISOD1 trial for AMT-162 in SOD1-ALS** dosed its first patient in October 2024, with the **IDMC recommending proceeding to the second cohort** in January 2025 after reviewing safety data[116](index=116&type=chunk) - **Initial data from the EPISOD1 study is expected** in the first half of 2026[116](index=116&type=chunk) [Financial Overview](index=32&type=section&id=Financial%20Overview) This section provides a summary of the company's key financial performance indicators and position Key Financials (in thousands) | Item | 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 | $5,262 | $11,126 | $6,829 | $19,611 | | Research and development expenses | $(35,383) | $(33,655) | $(71,523) | $(74,347) | | Selling, general and administrative expenses | $(13,500) | $(15,767) | $(24,408) | $(29,704) | | Net loss | $(37,719) | $(56,299) | $(81,356) | $(121,917) | - **Cash and cash equivalents and investment securities increased** to **$377.0 million** as of June 30, 2025, from **$367.5 million** at December 31, 2024[118](index=118&type=chunk) - The Company's **net loss improved** to **$(37.7) million** for Q2 2025 and **$(81.4) million** for H1 2025, compared to **$(56.3) million** and **$(121.9) million** for the respective periods in 2024[118](index=118&type=chunk) [Critical Accounting Policies and Estimates](index=34&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) This section discusses the company's significant accounting policies and estimates that require management judgment - There were **no material changes to the Company's critical accounting policies** during the six months ended June 30, 2025[120](index=120&type=chunk) - **Research and development expenses are expensed as incurred** and include costs for preclinical and clinical trials, manufacturing development, and changes in fair value of contingent consideration[122](index=122&type=chunk)[123](index=123&type=chunk) - Following the Lexington Transaction, **contract manufacturing revenues are no longer recognized**, and **other expenses primarily consist of costs incurred under the commercial supply agreement with Genezen**[121](index=121&type=chunk)[127](index=127&type=chunk) [Results of Operations](index=37&type=section&id=Results%20of%20Operations) This section analyzes the company's financial performance for the reported periods, comparing revenues and expenses [Comparison of the three months ended June 30, 2025 and 2024](index=37&type=section&id=Comparison%20of%20the%20three%20months%20ended%20June%2030,%202025%20and%202024) This section compares the company's financial results for the three months ended June 30, 2025, and 2024 [Revenue (3 months)](index=37&type=section&id=Revenue) This section analyzes the company's revenue streams and their changes over the reporting period Revenue (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Change | | :-------------------------- | :------------------------------- | :------------------------------- | :----- | | License revenues | $5,262 | $1,869 | $3,393 | | Contract manufacturing revenues | $0 | $2,124 | $(2,124) | | Collaboration revenues | $0 | $7,133 | $(7,133) | | Total revenues | $5,262 | $11,126 | $(5,864) | - **Total revenues decreased by $5.9 million (52.7%)** due to the **absence of contract manufacturing and collaboration revenues** following the Lexington Transaction[130](index=130&type=chunk)[132](index=132&type=chunk)[133](index=133&type=chunk) - **License revenues increased by $3.4 million (181.5%)** to **$5.3 million**, driven by higher royalty payments on HEMGENIX® sales[131](index=131&type=chunk) [Cost of contract manufacturing (3 months)](index=39&type=section&id=Cost%20of%20contract%20manufacturing) This section details the costs associated with contract manufacturing activities - **Cost of contract manufacturing** was nil for the three months ended June 30, 2025, compared to **$7.2 million** in the prior year, due to the Lexington Transaction in July 2024[135](index=135&type=chunk) [R&D expense (3 months)](index=39&type=section&id=R%26D%20expense) This section analyzes the company's research and development expenses and their drivers R&D Expenses (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Change | | :--------------------------------------- | :------------------------------- | :------------------------------- | :----- | | Huntington's disease (AMT-130) | $10,517 | $2,894 | $7,623 | | Employee and contractor-related expenses | $9,523 | $13,035 | $(3,512) | | Fair value changes related to contingent consideration | $2,254 | $(1,786) | $4,040 | | Total research and development expenses | $35,383 | $33,655 | $1,728 | - **Total R&D expenses** increased by **$1.7 million (5.1%)** to **$35.4 million**, primarily driven by a **$7.6 million** increase in external costs for **AMT-130 BLA preparation**[136](index=136&type=chunk)[139](index=139&type=chunk) - **Personnel and contractor-related expenses** decreased by **$3.5 million** due to the Lexington Transaction and August 2024 restructuring[144](index=144&type=chunk) - A **$2.3 million loss** was recognized from an increase in the **fair value of contingent consideration** for uniQure France SAS, compared to a **$1.8 million** gain in the prior year[144](index=144&type=chunk) [Selling, general and administrative expenses (3 months)](index=42&type=section&id=Selling,%20general%20and%20administrative%20expenses) This section details the company's selling, general, and administrative expenses and their changes SG&A Expenses (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Change | | :--------------------------------------- | :------------------------------- | :------------------------------- | :----- | | Employee and contractor-related expenses | $5,397 | $5,669 | $(272) | | Professional fees | $3,428 | $4,053 | $(625) | | Share-based compensation expense | $2,326 | $3,334 | $(1,008) | | Total selling, general and administrative expenses | $13,500 | $15,767 | $(2,267) | - **SG&A expenses** decreased by **$2.3 million (14.4%)** to **$13.5 million**, primarily due to reductions in personnel, contractor-related expenses, and **share-based compensation** following the Lexington Transaction and restructuring[146](index=146&type=chunk)[149](index=149&type=chunk) [Other items, net (3 months)](index=42&type=section&id=Other%20items,%20net) This section analyzes other income and expenses not directly related to core operations Other Items, Net (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Change | | :--------------------------------------- | :------------------------------- | :------------------------------- | :----- | | Research and development grants | $1,392 | $1,662 | $(270) | | Sublease income / (expense), net | $347 | $(63) | $410 | | Supply of HEMGENIX® to CSL Behring | $(1,731) | $0 | $(1,731) | | Total other income, net | $412 | $1,747 | $(1,335) | - **Net other items** decreased by **$1.3 million**, primarily due to **$1.7 million** in net other expenses related to the purchase of HEMGENIX® from Genezen, net of sales to CSL Behring, following the Lexington Transaction[148](index=148&type=chunk) [Other non-operating items, net (3 months)](index=44&type=section&id=Other%20non-operating%20items,%20net) This section details non-operating income and expenses, including interest and foreign currency effects Other Non-Operating Items, Net (in thousands) | Item | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Change | | :--------------------------------------- | :------------------------------- | :------------------------------- | :----- | | Interest income | $3,524 | $5,805 | $(2,281) | | Interest expense - Royalty Financing Agreement | $(13,770) | $(12,438) | $(1,332) | | Interest expense - Hercules debt facility | $(1,821) | $(3,719) | $1,898 | | Foreign currency gains, net | $18,638 | $(989) | $19,627 | | Total non-operating expense, net | $6,571 | $(11,341) | $17,912 | - **Net non-operating income** significantly improved by **$17.9 million**, primarily driven by a **$19.6 million** increase in net foreign currency gains[150](index=150&type=chunk)[153](index=153&type=chunk) - **Interest income** decreased by **$2.3 million** due to lower cash and **investment securities** balances, while **Hercules debt interest expense** decreased by **$1.9 million** due to principal repayment and lower market rates[150](index=150&type=chunk)[151](index=151&type=chunk) [Income tax expense (3 months)](index=44&type=section&id=Income%20tax%20expense) This section details the company's income tax expense for the reporting period - **Income tax expense** decreased to **$0.4 million** for the three months ended June 30, 2025, from **$0.9 million** in the prior year[154](index=154&type=chunk) [Comparison of the six months ended June 30, 2025 and 2024](index=45&type=section&id=Comparison%20of%20the%20six%20months%20ended%20June%2030,%202025%20and%202024) This section compares the company's financial results for the six months ended June 30, 2025, and 2024 [Revenue (6 months)](index=45&type=section&id=Revenue) This section analyzes the company's revenue streams and their changes over the reporting period Revenue (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | Change | | :-------------------------- | :----------------------------- | :----------------------------- | :----- | | License revenues | $6,829 | $3,071 | $3,758 | | Contract manufacturing revenues | $0 | $6,114 | $(6,114) | | Collaboration revenues | $0 | $10,426 | $(10,426) | | Total revenues | $6,829 | $19,611 | $(12,782) | - **Total revenues decreased by $12.8 million (65.2%)** due to the **absence of contract manufacturing and collaboration revenues** following the Lexington Transaction[157](index=157&type=chunk)[159](index=159&type=chunk)[161](index=161&type=chunk) - **License revenues increased by $3.8 million (122.4%)** to **$6.8 million**, driven by higher royalty payments on HEMGENIX® sales[158](index=158&type=chunk) [Cost of contract manufacturing (6 months)](index=47&type=section&id=Cost%20of%20contract%20manufacturing) This section details the costs associated with contract manufacturing activities - **Cost of contract manufacturing** was nil for the six months ended June 30, 2025, compared to **$16.3 million** in the prior year, due to the Lexington Transaction[162](index=162&type=chunk) [R&D expense (6 months)](index=47&type=section&id=R%26D%20expense) This section analyzes the company's research and development expenses and their drivers R&D Expenses (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | Change | | :--------------------------------------- | :----------------------------- | :----------------------------- | :----- | | Huntington's disease (AMT-130) | $18,747 | $5,320 | $13,427 | | Employee and contractor-related expenses | $19,682 | $29,958 | $(10,276) | | Fair value changes related to contingent consideration | $3,470 | $(1,621) | $5,091 | | Total research and development expenses | $71,523 | $74,347 | $(2,824) | - **Total R&D expenses** decreased by **$2.8 million (3.8%)** to **$71.5 million**, primarily due to a **$10.3 million** reduction in **personnel and contractor-related expenses** following the Lexington Transaction and restructuring[163](index=163&type=chunk)[171](index=171&type=chunk) - **Direct R&D expenses for AMT-130 increased by $13.4 million**, driven by **BLA submission preparation activities**[166](index=166&type=chunk) - A **$3.5 million loss** was recognized from an increase in the **fair value of contingent consideration** for uniQure France SAS, compared to a **$1.6 million** gain in the prior year[171](index=171&type=chunk) [Selling, general and administrative expenses (6 months)](index=50&type=section&id=Selling,%20general%20and%20administrative%20expenses) This section details the company's selling, general, and administrative expenses and their changes SG&A Expenses (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | Change | | :--------------------------------------- | :----------------------------- | :----------------------------- | :----- | | Employee and contractor-related expenses | $10,882 | $11,888 | $(1,006) | | Professional fees | $5,331 | $6,094 | $(763) | | Share-based compensation expense | $4,273 | $6,755 | $(2,482) | | Total selling, general and administrative expenses | $24,408 | $29,704 | $(5,296) | - **SG&A expenses** decreased by **$5.3 million (17.8%)** to **$24.4 million**, primarily due to reductions in personnel, contractor-related expenses, and **share-based compensation** following the Lexington Transaction and restructuring[172](index=172&type=chunk)[176](index=176&type=chunk) [Other items, net (6 months)](index=50&type=section&id=Other%20items,%20net) This section analyzes other income and expenses not directly related to core operations Other Items, Net (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | Change | | :--------------------------------------- | :----------------------------- | :----------------------------- | :----- | | Sale of critical reagents to Genezen | $6,000 | $0 | $6,000 | | Research and development grants | $3,111 | $2,886 | $225 | | Supply of HEMGENIX® to CSL Behring | $(3,256) | $0 | $(3,256) | | Total other income, net | $6,759 | $2,889 | $3,870 | - **Net other items** increased by **$3.9 million**, primarily due to a one-time **$6.0 million** **income from the sale of critical reagents to Genezen**, partially offset by **$3.3 million** in net other expenses related to HEMGENIX® supply[174](index=174&type=chunk)[175](index=175&type=chunk) [Other non-operating items, net (6 months)](index=52&type=section&id=Other%20non-operating%20items,%20net) This section details non-operating income and expenses, including interest and foreign currency effects Other Non-Operating Items, Net (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | Change | | :--------------------------------------- | :----------------------------- | :----------------------------- | :----- | | Interest income | $7,651 | $12,313 | $(4,662) | | Interest expense - Royalty Financing Agreement | $(27,079) | $(24,839) | $(2,240) | | Interest expense - Hercules debt facility | $(3,621) | $(7,415) | $3,794 | | Foreign currency gains / (losses), net | $25,810 | $(2,134) | $27,944 | | Total non-operating expense, net | $2,761 | $(22,075) | $24,836 | - **Net non-operating income** significantly improved by **$24.8 million**, primarily driven by a **$27.9 million** increase in net foreign currency gains[178](index=178&type=chunk)[181](index=181&type=chunk) - **Interest income** decreased by **$4.7 million** due to lower cash and **investment securities** balances, while **Hercules debt interest expense** decreased by **$3.8 million** due to principal repayment and lower market rates[178](index=178&type=chunk)[179](index=179&type=chunk) [Income tax expense (6 months)](index=52&type=section&id=Income%20tax%20expense) This section details the company's income tax expense for the reporting period - **Income tax expense** decreased to **$0.9 million** for the six months ended June 30, 2025, from **$1.6 million** in the prior year[182](index=182&type=chunk) [Financial Position, Liquidity and Capital Resources](index=52&type=section&id=Financial%20Position,%20Liquidity%20and%20Capital%20Resources) This section discusses the company's financial health, cash management, and funding capabilities - As of June 30, 2025, the Company had **$378.5 million** in **cash, cash equivalents, restricted cash, and investment securities**[183](index=183&type=chunk) - **Existing cash resources** are expected to fund operations into the second half of 2027, but **additional funding will be required for AMT-130 commercialization and other late-stage clinical development**[183](index=183&type=chunk) - The Company incurred a **net loss** of **$81.4 million** for the six months ended June 30, 2025, and had an **accumulated deficit** of **$1,211.3 million**[191](index=191&type=chunk) [Debt](index=54&type=section&id=Debt) This section details the company's outstanding debt obligations and repayment schedules - As of June 30, 2025, the Company had **$50.0 million** in **outstanding principal** under the **Hercules debt facility**, with **$12.9 million** in **future interest and financing fees**, **$8.6 million** of which is payable within 12 months[184](index=184&type=chunk) - The **$50.0 million principal balance is due in full by January 2027**[184](index=184&type=chunk) [Leases](index=54&type=section&id=Leases) This section outlines the company's lease payment obligations and guarantees - **Fixed lease payment obligations** totaled **$23.2 million** as of June 30, 2025, with **$4.4 million** payable within 12 months[185](index=185&type=chunk) - The Company guarantees **$18.5 million** in **fixed lease payments for the Lexington Facility** until May 2029, despite assigning the lease to Genezen[185](index=185&type=chunk) [Commitments related to uniQure France SAS acquisition (nominal amounts)](index=54&type=section&id=Commitments%20related%20to%20uniQure%20France%20SAS%20acquisition%20(nominal%20amounts)) This section details potential milestone payments related to the uniQure France SAS acquisition - **Remaining commitments include EUR 160.0 million ($187.9 million) in potential milestone payments for AMT-260's Phase III development and approval**, expected between 2029 and 2033[186](index=186&type=chunk) - Up to **25%** of these milestone payments can be settled with **ordinary shares**[186](index=186&type=chunk) [Commitments related to licensors and financial advisors](index=54&type=section&id=Commitments%20related%20to%20licensors%20and%20financial%20advisors) This section outlines future payment obligations to licensors and financial advisors - The Company has **obligations for future payments to third parties upon achievement of development, regulatory, and commercial milestones**, and to a financial advisor related to CSL Behring Agreement payments[187](index=187&type=chunk) [Commitments related to the CSA and the DMSA with Genezen](index=54&type=section&id=Commitments%20related%20to%20the%20CSA%20and%20the%20DMSA%20with%20Genezen) This section details minimum purchase commitments under agreements with Genezen - **Remaining minimum purchase commitments to Genezen under the CSA for HEMGENIX® manufacturing services total $25.2 million**, with **$13.6 million** payable within 12 months[188](index=188&type=chunk) - **Minimum purchase commitments under the DMSA for development services total $9.8 million**, with **$3.8 million** payable within 12 months[189](index=189&type=chunk) [Sources of liquidity](index=56&type=section&id=Sources%20of%20liquidity) This section describes the primary sources of funding for the company's operations - Operations have been funded primarily through equity and convertible debt sales, venture loans, collaboration upfront payments, and **$370.1 million** from **royalty monetization** in 2023[192](index=192&type=chunk) - In January and February 2025, the Company raised **$80.5 million** in **net proceeds** from a follow-on public offering[193](index=193&type=chunk) - The **Hercules debt facility** was amended in July 2024, with a **$50.0 million principal repayment**, leaving **$50.0 million** outstanding due in January 2027[194](index=194&type=chunk) [Net cash used in operating activities](index=58&type=section&id=Net%20cash%20used%20in%20operating%20activities) This section analyzes cash flows from the company's core business operations - **Net cash used in operating activities** was **$84.0 million** for the six months ended June 30, 2025, an **improvement from $93.3 million** in 2024[197](index=197&type=chunk)[198](index=198&type=chunk) - Adjustments to **net loss** included **$8.2 million** in depreciation and amortization, **$9.5 million** in **share-based compensation**, and **$20.6 million** in **royalty financing agreement interest expense** (net of paid interest)[197](index=197&type=chunk) [Net cash generated from investing activities](index=58&type=section&id=Net%20cash%20generated%20from%20investing%20activities) This section details cash flows related to the company's investment activities Cash Flows from Investing Activities (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Proceeds from maturity of debt securities | $213,763 | $297,806 | | Investment in debt securities | $(120,205) | $(152,936) | | Net cash generated from investing activities | $93,172 | $141,922 | - **Net cash generated from investing activities** decreased to **$93.2 million** for the six months ended June 30, 2025, from **$141.9 million** in 2024[199](index=199&type=chunk)[200](index=200&type=chunk) [Net cash generated from financing activities](index=58&type=section&id=Net%20cash%20generated%20from%20financing%20activities) This section analyzes cash flows from the company's financing activities, including equity offerings Cash Flows from Financing Activities (in thousands) | Item | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Proceeds from public offering of shares | $80,511 | $0 | | Proceeds from issuance of ordinary shares related to employee plans | $203 | $50 | | Net cash generated from financing activities | $80,714 | $50 | - **Net cash generated from financing activities** significantly increased to **$80.7 million** for the six months ended June 30, 2025, from **$0.1 million** in 2024, primarily due to the follow-on public offering[201](index=201&type=chunk)[202](index=202&type=chunk) [Funding requirements](index=60&type=section&id=Funding%20requirements) This section discusses the company's future capital needs and factors influencing them - **Future capital requirements** depend on factors such as **AMT-130 commercialization**, **clinical trial progress**, **regulatory approvals**, and **intellectual property maintenance**[206](index=206&type=chunk) - **Additional funding will be needed to support AMT-130 commercialization and advance other clinical product candidates into late-stage development**[183](index=183&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=60&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section states that the Company's market risks and exposures, including currency, price, interest rate, credit, and liquidity risks, have not materially changed during the six months ended June 30, 2025, compared to the disclosures in its most recent Annual Report - The Company's **market risks and exposures**, including **currency, price, and interest rate risk**, **credit risk**, and **liquidity risk**, have not materially changed during the six months ended June 30, 2025[203](index=203&type=chunk)[204](index=204&type=chunk) [Item 4. Controls and Procedures](index=60&type=section&id=Item%204.%20Controls%20and%20Procedures) This section details the evaluation of the Company's disclosure controls and procedures and reports on any changes in internal control over financial reporting. Management concluded that disclosure controls and procedures were effective as of June 30, 2025, with no material changes to internal control over financial reporting during the period [Evaluation of Disclosure Controls and Procedures](index=60&type=section&id=Evaluation%20of%20Disclosure%20Controls%20and%20Procedures) This section reports on the effectiveness of the company's disclosure controls and procedures - As of June 30, 2025, the CEO and CFO concluded that the Company's **disclosure controls and procedures** were effective[205](index=205&type=chunk) - **Disclosure controls** are designed to ensure timely recording, processing, summarizing, and reporting of information required under the Exchange Act[205](index=205&type=chunk) [Changes in Internal Control over Financial Reporting](index=62&type=section&id=Changes%20in%20Internal%20Control%20over%20Financial%20Reporting) This section reports on any material changes to the company's internal control over financial reporting - **No changes in internal control over financial reporting that materially affected, or are reasonably likely to materially affect, the Company's internal control over financial reporting during the period**[208](index=208&type=chunk) PART II – OTHER INFORMATION [Item 1. Legal Proceedings](index=62&type=section&id=Item%201.%20Legal%20Proceedings) This section states that there are no legal proceedings to report - **No legal proceedings were reported for the period**[210](index=210&type=chunk) [Item 1A. Risk Factors](index=63&type=section&id=Item%201A.%20Risk%20Factors) This section outlines significant risks associated with an investment in uniQure N.V.'s ordinary shares, covering business operations, product development, regulatory approvals, commercialization, manufacturing, intellectual property, financial position, legal compliance, and market volatility. Key risks include dependence on AMT-130, need for additional funding, potential clinical trial delays, and intense competition in gene therapy [Summary Risk Factors](index=63&type=section&id=Summary%20Risk%20Factors) This section provides a concise overview of the most critical risks facing the company - The Company is **highly dependent on the success of its lead product candidate, AMT-130, for Huntington's disease**, with **potential failures in clinical development, regulatory approval, manufacturing, or commercialization posing significant risks**[213](index=213&type=chunk)[215](index=215&type=chunk) - **Additional funding will be required to advance product candidates and support the commercial launch of AMT-130**, which may not be available on acceptable terms[213](index=213&type=chunk) - **Risks include potential delays in clinical trials, failure to demonstrate safety and efficacy, challenges in commercialization, market acceptance issues, and negative public opinion regarding gene therapy**[213](index=213&type=chunk) [Risks Related to Our Business and the Development of Our Product Candidates](index=65&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20the%20Development%20of%20Our%20Product%20Candidates) This section details risks associated with the company's core business and product development pipeline - The Company's business is **highly dependent on the success of AMT-130** for Huntington's disease, with **risks including potential patient safety issues, insufficient clinical efficacy, and challenges in regulatory alignment or BLA submission**[215](index=215&type=chunk)[219](index=219&type=chunk) - **Drug development is expensive and uncertain**, with **significant risks of failure or delay in clinical trials** for all product candidates, including AMT-130, AMT-260, AMT-191, and AMT-162[223](index=223&type=chunk) - **Interim or preliminary clinical trial results**, especially from open-label or post-hoc analyses, **may not be predictive of long-term efficacy or final outcomes** and are subject to regulatory audit and verification[237](index=237&type=chunk)[238](index=238&type=chunk)[239](index=239&type=chunk) [Risks Related to Regulatory Approval of Our Products](index=82&type=section&id=Risks%20Related%20to%20Regulatory%20Approval%20of%20Our%20Products) This section outlines risks concerning the regulatory approval process for the company's product candidates - **Obtaining marketing approval for product candidates is expensive, time-consuming, and uncertain**, with **potential delays or rejections** due to changing regulatory policies, staffing limitations, or insufficient data[265](index=265&type=chunk)[266](index=266&type=chunk) - The **regulatory approval process is heightened for gene therapies** due to **limited FDA experience**, ethical concerns, and evolving guidance, potentially leading to **increased costs and delays**[270](index=270&type=chunk)[271](index=271&type=chunk)[274](index=274&type=chunk) - Leveraging specialized regulatory pathways (e.g., Breakthrough Therapy, RMAT, Accelerated Approval) **does not guarantee faster development or approval**, and **failure to meet post-marketing requirements could lead to withdrawal of approval**[280](index=280&type=chunk)[282](index=282&type=chunk) [Risks Related to Commercialization](index=96&type=section&id=Risks%20Related%20to%20Commercialization) This section details risks associated with the market acceptance and commercial success of approved products - **Successful commercialization** of approved product candidates depends on **market acceptance by physicians, patients, and third-party payers**, which is **uncertain due to factors like efficacy, cost-effectiveness, ease of administration, and potential side effects**[311](index=311&type=chunk)[314](index=314&type=chunk) - The **addressable market for orphan indications may be smaller than projected**, **impacted by factors like neutralizing antibodies, diagnosis criteria, and patient access**, which could **adversely affect product revenues**[316](index=316&type=chunk)[318](index=318&type=chunk)[319](index=319&type=chunk) - The **potential for long-term therapeutic benefit from a single administration of gene therapies presents challenges for pricing and reimbursement**, as **payers may be reluctant to provide significant upfront reimbursement**[301](index=301&type=chunk) [Risks Related to Manufacturing and Our Dependence on Third Parties](index=100&type=section&id=Risks%20Related%20to%20Manufacturing%20and%20Our%20Dependence%20on%20Third%20Parties) This section outlines risks related to product manufacturing and reliance on external partners - The **Lexington Transaction may not yield expected benefits** and could **expose the Company to additional costs and risks**, including **Genezen's ability to manufacture HEMGENIX® and other product candidates according to regulatory and supply requirements**[322](index=322&type=chunk)[324](index=324&type=chunk) - **Gene therapies are complex and expensive to manufacture**, and **third-party manufacturers (like Genezen) may face capacity, production, or technology transfer challenges, leading to delays or supply failures**[326](index=326&type=chunk) - **Reliance on third parties for manufacturing and clinical trials reduces control over these activities**, and **their failure to perform satisfactorily or comply with regulations could lead to delays, regulatory enforcement, or inability to obtain approvals**[331](index=331&type=chunk)[341](index=341&type=chunk)[342](index=342&type=chunk) [Risks Related to Our Intellectual Property](index=111&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) This section details risks concerning the company's intellectual property rights and protection - The Company **relies heavily on in-licensed intellectual property**, which **may not provide adequate rights**, **be subject to multiple interpretations**, or **be unavailable on commercially reasonable terms in the future**[350](index=350&type=chunk)[351](index=351&type=chunk)[353](index=353&type=chunk) - **Failure to obtain and maintain broad patent protection** for technology and products, or **successful challenges to existing patents**, could **impair the ability to commercialize products and prevent competitors from using similar technologies**[355](index=355&type=chunk)[356](index=356&type=chunk)[358](index=358&type=chunk) - **Involvement in intellectual property lawsuits**, whether to protect patents or defend against infringement claims, can be **expensive, time-consuming, and divert management resources**, potentially leading to **significant liabilities or loss of rights**[359](index=359&type=chunk)[361](index=361&type=chunk)[362](index=362&type=chunk) [Risks Related to Our Financial Position and Need for Additional Capital](index=118&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) This section outlines financial risks, including historical losses and the need for future funding - The Company has **incurred significant net losses and accumulated deficits**, **expecting future losses** as it funds late-stage development, commercialization preparations for AMT-130, and other product candidates[371](index=371&type=chunk)[375](index=375&type=chunk) - **Additional substantial funding will be required** beyond existing cash resources, and **failure to obtain capital on acceptable terms could force delays or termination of development and commercialization efforts**[373](index=373&type=chunk)[378](index=378&type=chunk) - **Strategic initiatives, including divestitures like the Lexington Transaction, may not achieve intended benefits**, could result in unanticipated problems, expenses, or liabilities, and **may divert management attention**[379](index=379&type=chunk)[381](index=381&type=chunk) [Risks Related to Other Legal Compliance Matters](index=124&type=section&id=Risks%20Related%20to%20Other%20Legal%20Compliance%20Matters) This section details risks associated with legal and regulatory compliance, including healthcare and data protection laws - **Relationships with employees, customers, and third parties are subject to anti-bribery, fraud and abuse, and other healthcare laws**, with **non-compliance potentially leading to significant penalties, damages, or operational restructuring**[389](index=389&type=chunk)[390](index=390&type=chunk) - The Company is **subject to complex data protection laws like GDPR**, with **non-compliance risking substantial penalties, regulatory enforcement actions, and private litigation**[393](index=393&type=chunk)[395](index=395&type=chunk)[396](index=396&type=chunk) - **Product liability lawsuits** related to clinical trials or approved products could result in **substantial liabilities, decreased demand, reputational damage, and diversion of resources**[397](index=397&type=chunk) [Risks Related to Our Ordinary Shares](index=129&type=section&id=Risks%20Related%20to%20Our%20Ordinary%20Shares) This section outlines risks concerning the company's stock performance and shareholder matters - The **market price of the Company's ordinary shares has been and may remain volatile**, **influenced by clinical trial results, regulatory developments, competition, and general market conditions**[407](index=407&type=chunk)[408](index=408&type=chunk) - **Directors, executive officers, and major shareholders collectively own approximately 33.8% of outstanding shares**, potentially influencing matters submitted for shareholder approval[411](index=411&type=chunk) - The Company **does not expect to pay dividends in the foreseeable future**, meaning **returns on investment will depend solely on future share price appreciation**[419](index=419&type=chunk)[420](index=420&type=chunk) [General Risks](index=136&type=section&id=General%20Risks) This section covers broader risks affecting the company, including economic conditions and operational controls - **Future success depends on the ability to attract, retain, and motivate key executives, technical staff, and other qualified employees** in a **highly competitive pharmaceutical field**[430](index=430&type=chunk)[431](index=431&type=chunk) - **Unstable market and economic conditions, including inflation, higher interest rates, and geopolitical issues, may adversely affect the business, financial condition, and share price**[433](index=433&type=chunk) - **Failure

[Executive Summary & Recent Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Recent%20Highlights) uniQure made significant clinical and regulatory progress for AMT-130 and AMT-260, strengthened its leadership, and maintained a strong cash position [Recent Company Progress Overview](index=1&type=section&id=Recent%20Company%20Progress%20Overview) uniQure achieved significant progress in Q2 2025, including FDA alignment for AMT-130 BLA submission, positive early clinical signals for AMT-260, and a strengthened leadership team - Achieved FDA alignment on AMT-130 statistical analysis plan and CMC requirements to support a planned Biologics License Application (BLA) submission in the first quarter of 2026[1](index=1&type=chunk)[3](index=3&type=chunk) - Company expects to present AMT-130 topline three-year data in September 2025[1](index=1&type=chunk) - Presented case study from first participant treated with AMT-260 for refractory mesial temporal lobe epilepsy showing **92% seizure reduction** with no serious adverse events through first five months of follow up[1](index=1&type=chunk) - Appointment of Kylie O'Keefe as Chief Customer and Strategy Officer[1](index=1&type=chunk) [High-Level Financial Overview](index=1&type=section&id=High-Level%20Financial%20Overview) The company reported a strong cash position of approximately $377.0 million as of June 30, 2025, which is expected to fund operations into the second half of 2027 Key Financial Highlights (Q2 2025) | Metric | Value | | :----- | :---- | | Cash, cash equivalents and current investment securities (as of June 30, 2025) | ~$377.0 million | | Expected Cash Runway | Into second half of 2027 | [Recent Company Developments and Updates](index=1&type=section&id=Recent%20Company%20Developments%20and%20Updates) uniQure advanced its gene therapy pipeline with significant regulatory and clinical progress for AMT-130, promising early data for AMT-260, and strengthened its leadership team [AMT-130 Program (Huntington's Disease)](index=1&type=section&id=AMT-130%20Program%20(Huntington's%20Disease)) uniQure achieved significant regulatory and clinical milestones for AMT-130, including FDA alignment on the BLA pathway, Breakthrough Therapy designation, and plans for a Q1 2026 BLA submission - FDA alignment on statistical analysis plan (SAP) and Chemistry, Manufacturing and Controls (CMC) requirements for BLA submission in Q1 2026. The primary efficacy analysis will evaluate the three-year change in cUHDRS[3](index=3&type=chunk)[4](index=4&type=chunk) - Submitted final SAP to FDA and initiated Process Performance Qualification (PPQ) campaign in July 2025[4](index=4&type=chunk) - AMT-130 was generally well-tolerated in Phase I/II study (third cohort); a short-term steroid regimen is expected to be incorporated as prophylactic immunosuppression[4](index=4&type=chunk) - Granted Breakthrough Therapy designation by FDA in April 2025 based on clinical evidence showing potential for slowing progression of Huntington's disease[4](index=4&type=chunk) AMT-130 Upcoming Milestones | Milestone | Expected Timing | | :-------- | :-------------- | | Present topline, three-year data from Phase I/II trials | September 2025 | | Initiate fourth cohort (high-dose AMT-130 in 6 patients with lower striatal volumes) | Q3 2025 | | Hold pre-BLA meeting with FDA and complete PPQ campaign | Q4 2025 | | Submit BLA with request for priority review designation | Q1 2026 | [Advancing Additional Clinical Programs](index=2&type=section&id=Advancing%20Additional%20Clinical%20Programs) uniQure is progressing other gene therapy candidates, including AMT-260 with promising early efficacy, and AMT-191 and AMT-162 which are actively enrolling patients with initial data expected in late 2025 and H1 2026, respectively - **AMT-260 (refractory mesial temporal lobe epilepsy):** Initial data from the first treated patient showed a **92% reduction in seizure frequency** through five months with no serious safety events. Clinical sites continue to screen patients[4](index=4&type=chunk) - **AMT-191 (Fabry disease):** Continues to enroll patients in the Phase I/IIa study; initial safety and exploratory efficacy data expected at the 15th ICIEM 2025 in September 2025[4](index=4&type=chunk) - **AMT-162 (SOD1 amyotrophic lateral sclerosis - ALS):** Continues to enroll patients in the Phase I/II EPISOD1 study; initial data expected in the first half of 2026[4](index=4&type=chunk) [Strengthening the Leadership Team](index=2&type=section&id=Strengthening%20the%20Leadership%20Team) uniQure strengthened its leadership team with the appointment of Kylie O'Keefe as Chief Customer and Strategy Officer, bringing decades of commercial experience to lead commercial and medical affairs - Kylie O'Keefe was appointed as Chief Customer and Strategy Officer in June 2025, responsible for leading all commercial and medical affairs. She previously served as Chief Commercial Officer at PTC Therapeutics[4](index=4&type=chunk)[11](index=11&type=chunk) [Financial Review](index=3&type=section&id=Financial%20Review) uniQure reported a strong cash position extending into H2 2027 and a reduced net loss in Q2 2025, driven by lower operating expenses and increased non-operating income [Cash Position and Runway](index=3&type=section&id=Cash%20Position%20and%20Runway) uniQure's cash, cash equivalents, and current investment securities increased to **$377.0 million** as of June 30, 2025, primarily due to a follow-on offering, extending its operational funding into the second half of 2027 Cash Position (in millions USD) | Metric | June 30, 2025 | December 31, 2024 | Change | | :----- | :------------ | :---------------- | :----- | | Cash, cash equivalents and current investment securities | $377.0 | $367.5 | +$9.5 | - The net increase in cash was primarily related to net proceeds of **$80.5 million** from a follow-on offering in January and February 2025[5](index=5&type=chunk) - Based on the current operating plan, including the planned U.S. launch of AMT-130, the cash position is expected to fund operations into the second half of 2027[5](index=5&type=chunk)[11](index=11&type=chunk) [Q2 2025 Operating Results Overview](index=3&type=section&id=Q2%202025%20Operating%20Results%20Overview) The company reported a reduced net loss of **$37.7 million** in Q2 2025 compared to **$56.3 million** in Q2 2024, driven by decreased revenue but also lower operating expenses and a significant increase in non-operating income Key Financial Results (Three months ended June 30, in thousands USD, except per share) | Metric | Q2 2025 | Q2 2024 | Change (YoY) | | :----- | :------ | :------ | :----------- | | Total revenues | $5,262 | $11,126 | -$5,864 | | Operating expenses | ($49,539) | ($56,883) | +$7,344 | | Loss from operations | ($43,865) | ($44,010) | +$145 | | Non-operating items, net | $6,571 | ($11,341) | +$17,912 | | Net loss | ($37,719) | ($56,299) | +$18,580 | | Basic and diluted net loss per ordinary share | ($0.69) | ($1.16) | +$0.47 | | Weighted average shares | 54,807,967 | 48,622,440 | +6,185,527 | [Revenues Analysis](index=3&type=section&id=Revenues%20Analysis) Total revenue decreased by **$5.8 million** year-over-year, primarily due to a significant drop in collaboration revenue and contract manufacturing, partially offset by an increase in license revenue Revenue Breakdown (Three months ended June 30, in millions USD) | Revenue Type | Q2 2025 | Q2 2024 | Change (YoY) | | :----------- | :------ | :------ | :----------- | | Total Revenues | $5.3 | $11.1 | -$5.8 | | License revenue | N/A | N/A | +$3.4 | | Collaboration revenue | N/A | N/A | -$7.1 | | Contract manufacturing (HEMGENIX®) | N/A | N/A | -$2.1 | - Following the divestment of the Lexington facility in July 2024, revenue from contract manufacturing is recorded net of cost within other expenses[6](index=6&type=chunk) [Operating Expenses Analysis](index=3&type=section&id=Operating%20Expenses%20Analysis) Operating expenses decreased by **$7.3 million** year-over-year, mainly driven by the absence of contract manufacturing costs and reductions in employee-related and professional fees, despite an increase in R&D external program spend Operating Expenses (Three months ended June 30, in millions USD) | Expense Type | Q2 2025 | Q2 2024 | Change (YoY) | | :----------- | :------ | :------ | :----------- | | Cost of contract manufacturing revenues | $0.0 | $7.2 | -$7.2 | | Research and development (R&D) expenses | $35.4 | $33.7 | +$1.7 | | Selling, general and administrative (SG&A) expenses | $13.5 | $15.8 | -$2.3 | - R&D increase of **$1.7 million** was due to a **$6.3 million** increase in external program spend and **$4.0 million** higher expenses related to an increase in the fair value of contingent consideration, offset by decreases in employee-related, facility, and preclinical supply expenses[8](index=8&type=chunk) - SG&A decrease of **$2.3 million** was primarily related to a **$1.6 million** decrease in employee-related expenses and a **$0.6 million** decrease in professional fees[9](index=9&type=chunk) [Other Income and Expense](index=3&type=section&id=Other%20Income%20and%20Expense) Other expense increased significantly due to non-cash amortization related to HEMGENIX® purchase rights, while non-operating items shifted from a net expense to a net income, primarily driven by foreign currency gains Other Income/Expense (Three months ended June 30, in millions USD) | Item | Q2 2025 | Q2 2024 | Change (YoY) | | :--- | :------ | :------ | :----------- | | Other expense | $2.2 | $0.2 | +$2.0 | | Other non-operating items, net | $6.6 (income) | $11.3 (expense) | +$17.9 (increase in income) | - Increase in other expense primarily related to **$1.4 million** of non-cash expense recognized to amortize the right to purchase HEMGENIX® from Genezen on favorable terms[10](index=10&type=chunk) - The **$17.9 million** increase in other non-operating items, net, was primarily related to an increase in net foreign currency gains of **$19.6 million**, partially offset by a decrease in interest income and reduction of interest expense[12](index=12&type=chunk) [Consolidated Financial Statements](index=6&type=section&id=Consolidated%20Financial%20Statements) The consolidated financial statements provide detailed figures for the balance sheet as of June 30, 2025, and the statement of operations for the three months ended June 30, 2025 and 2024 [Unaudited Consolidated Balance Sheets](index=6&type=section&id=Unaudited%20Consolidated%20Balance%20Sheets) As of June 30, 2025, total assets increased to **$584.9 million** from **$556.5 million** at year-end 2024, primarily driven by an increase in cash and cash equivalents, while total liabilities also increased, resulting in a reduced shareholders' deficit Consolidated Balance Sheet Highlights (in thousands USD) | Metric | June 30, 2025 | December 31, 2024 | Change | | :----- | :------------ | :---------------- | :----- | | Total assets | $584,890 | $556,536 | +$28,354 | | Total liabilities | $588,893 | $563,288 | +$25,605 | | Total shareholders' (deficit) / equity | ($4,003) | ($6,752) | +$2,749 | Key Balance Sheet Changes (in thousands USD) | Item | June 30, 2025 | December 31, 2024 | Change | | :--- | :------------ | :---------------- | :----- | | Cash and cash equivalents | $253,778 | $158,930 | +$94,848 | | Current investment securities | $123,196 | $208,591 | -$85,395 | | Prepaid expenses | $18,538 | $9,281 | +$9,257 | | Intangible assets, net | $75,604 | $71,043 | +$4,561 | | Goodwill | $25,340 | $22,414 | +$2,926 | | Liability from royalty financing agreement | $455,259 | $434,930 | +$20,329 | | Contingent consideration, net of current portion | $15,931 | $10,860 | +$5,071 | [Unaudited Consolidated Statements of Operations](index=7&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Operations) The detailed statement of operations shows a net loss of **$37.7 million** for Q2 2025, an improvement from the **$56.3 million** loss in Q2 2024, reflecting changes in revenues, operating expenses, and non-operating items Consolidated Statements of Operations (Three months ended June 30, in thousands USD, except per share) | Item | 2025 | 2024 | | :--- | :--- | :--- | | Total revenues | $5,262 | $11,126 | | Cost of license revenues | ($656) | ($234) | | Cost of contract manufacturing revenues | — | ($7,227) | | Research and development expenses | ($35,383) | ($33,655) | | Selling, general and administrative expenses | ($13,500) | ($15,767) | | Total operating expenses | ($49,539) | ($56,883) | | Other income | $2,597 | $1,983 | | Other expense | ($2,185) | ($236) | | Loss from operations | ($43,865) | ($44,010) | | Non-operating items, net | $6,571 | ($11,341) | | Loss before income tax (expense) / benefit | ($37,294) | ($55,351) | | Income tax (expense) / benefit | ($425) | ($948) | | Net loss | ($37,719) | ($56,299) | | Basic and diluted net loss per ordinary share | ($0.69) | ($1.16) | | Weighted average shares used in computing basic and diluted net loss per ordinary share | 54,807,967 | 48,622,440 | [Company Information](index=4&type=section&id=Company%20Information) This section provides an overview of uniQure's mission and pipeline, details investor relations, and outlines important forward-looking statements and associated risks [About uniQure](index=4&type=section&id=About%20uniQure) uniQure is a leading gene therapy company focused on developing single treatments with potentially curative results for severe medical needs, building on its success with a gene therapy for hemophilia B and advancing a pipeline for Huntington's disease, epilepsy, ALS, and Fabry disease - uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results[15](index=15&type=chunk) - Achieved a major milestone with the approval of its gene therapy for hemophilia B (HEMGENIX®)[15](index=15&type=chunk) - Advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases[15](index=15&type=chunk) [Investor Relations and Contacts](index=4&type=section&id=Investor%20Relations%20and%20Contacts) uniQure hosted an investor conference call and webcast on July 29, 2025, and provides contact information for investor and media inquiries - Hosted an investor conference call and webcast on Tuesday, July 29, 2025, at 8:30 a.m. ET[14](index=14&type=chunk) - The event webcast replay will be archived for 90 days under the Events & Presentations section of uniQure's website[14](index=14&type=chunk) - Contact information for investors (Chiara Russo) and media (Tom Malone) is provided[18](index=18&type=chunk)[19](index=19&type=chunk) [Forward-Looking Statements](index=4&type=section&id=Forward-Looking%20Statements) This section outlines forward-looking statements regarding the company's future expectations, including cash runway, regulatory interactions, clinical trial timing, commercialization plans, and potential risks and uncertainties that could cause actual results to differ materially - Forward-looking statements include those concerning the Company's cash runway, timing and outcome of regulatory interactions for AMT-130, plans for clinical updates (AMT-130, AMT-191, AMT-162), and commercialization plans[16](index=16&type=chunk) - Actual results could differ materially due to risks and uncertainties such as clinical trial results, regulatory approvals, ability to build infrastructure, intellectual property, and funding[16](index=16&type=chunk)[17](index=17&type=chunk) - These risks and uncertainties are more fully described in the Company's periodic filings with the U.S. Securities & Exchange Commission (SEC), including its Annual Report on Form 10-K and Quarterly Report on Form 10-Q[17](index=17&type=chunk)

Core Insights - uniQure N.V. has achieved alignment with the FDA on the statistical analysis plan and CMC requirements for AMT-130, supporting a planned BLA submission in Q1 2026 [1][4] - The company expects to present topline three-year data for AMT-130 in September 2025 [1][4] - Early clinical data for AMT-260 shows a 92% reduction in seizures for the first patient treated, with no serious adverse events reported [1][4] - The appointment of Kylie O'Keefe as Chief Customer and Strategy Officer is aimed at strengthening the leadership team [1][4] - As of June 30, 2025, the company has approximately $377.0 million in cash and equivalents, expected to fund operations into the second half of 2027 [1][5] Recent Developments - The FDA's alignment supports an Accelerated Approval pathway for AMT-130, with a focus on the three-year change in the composite Unified Huntington's Disease Rating Scale [4] - The final statistical analysis plan was submitted to the FDA in July 2025, and a PPQ campaign has been initiated [4] - AMT-130 has received Breakthrough Therapy designation from the FDA based on Phase I/II trial evidence [4] Financial Performance - Revenue for Q2 2025 was $5.3 million, a decrease from $11.1 million in Q2 2024, attributed to changes in license and collaboration revenue [6] - Research and development expenses increased to $35.4 million in Q2 2025 from $33.7 million in Q2 2024, driven by external program spending [9] - Selling, general and administrative expenses decreased to $13.5 million in Q2 2025 from $15.8 million in Q2 2024 [10] - The net loss for Q2 2025 was $37.7 million, compared to a net loss of $56.3 million in the same period in 2024 [13][21] Clinical Programs - AMT-260 is in clinical trials for refractory mesial temporal lobe epilepsy, with initial data showing significant seizure reduction [7] - AMT-191 for Fabry disease and AMT-162 for ALS are also in development, with initial data presentations expected in September 2025 and the first half of 2026, respectively [7] Leadership Changes - Kylie O'Keefe's appointment as Chief Customer and Strategy Officer is part of the company's strategy to enhance its commercial and medical affairs [1][4]

Core Viewpoint - uniQure N.V. is set to report its second quarter 2025 financial results on July 29, 2025, and will host a conference call to discuss these results [1]. Company Overview - uniQure is a leading gene therapy company focused on developing transformative therapies for patients with severe medical needs, including a pipeline for treating Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases [3]. - The company achieved a significant milestone with the approval of its gene therapy for hemophilia B, marking a historic achievement in genomic medicine after over a decade of research and clinical development [3]. Event Details - The earnings call will be available via webcast on uniQure's website, with a replay archived for 90 days [2]. - Participants wishing to join by phone must register online to receive dial-in details and a personal PIN number [2].

Core Insights - uniQure N.V. has appointed Kylie O'Keefe as Chief Customer and Strategy Officer to lead the commercialization of AMT-130 for Huntington's disease, effective June 6, 2025 [1][2] - The company is preparing for a potential U.S. commercial launch of AMT-130 in 2026, leveraging O'Keefe's extensive experience in rare diseases and gene therapy [2][3] - AMT-130 is positioned as a potential first disease-modifying treatment for Huntington's disease, with a clear path towards accelerated approval in the U.S. [3] Company Overview - uniQure is a leading gene therapy company focused on developing transformative therapies for patients with severe medical needs, including Huntington's disease, ALS, and Fabry disease [4] - The company has achieved significant milestones, including the approval of its gene therapy for hemophilia B, marking a major advancement in genomic medicine [4] Leadership Background - Kylie O'Keefe has a strong background in biopharmaceuticals, having previously served as Chief Commercial Officer at PTC Therapeutics, where she managed global commercial strategy for rare neurology and metabolic products across over 50 countries [2] - O'Keefe's experience includes leading significant commercial launches and developing reimbursement strategies, which will be crucial for uniQure's commercialization efforts [2]

Summary of Conference Call on AMT-130 for Huntington's Disease Company and Industry - **Company**: UniCure - **Industry**: Biotechnology, specifically focused on gene therapy for Huntington's disease Key Points and Arguments 1. **Regulatory Milestone**: UniCure announced alignment with the FDA on key components of the primary statistical analysis plan and CMC requirements for AMT-130, supporting a BLA submission planned for Q1 2026 [6][12][17] 2. **FDA Meetings**: Two Type B meetings with the FDA confirmed that validation of the AMT-130 manufacturing process is feasible using prior knowledge from Hemgenics, streamlining the path towards BLA submission [7][13] 3. **Efficacy Analysis**: The primary efficacy analysis will compare the three-year change in CUHDRS in high-dose AMT-130 patients to a propensity score adjusted external control group from the ENROL HD database [8][14] 4. **Unmet Medical Need**: Huntington's disease is a rare neurodegenerative condition affecting tens of thousands in the US and Europe, with AMT-130 positioned as a potential one-time treatment targeting the disease's root cause [9] 5. **Commercial Readiness**: UniCure is advancing its commercial readiness in phases to support the planned launch of AMT-130 in 2026 [10] 6. **Statistical Methodology**: The FDA supports the use of CUHDRS as an intermediate clinical endpoint, and the analysis will include sensitivity analyses using various datasets to ensure robustness [12][14][70] 7. **Patient Data**: Over 33,000 patients are enrolled in the ENROL HD study, providing a comprehensive dataset for analysis, which is expected to enhance the robustness of the propensity score model [15][36] 8. **Manufacturing Process**: The AMT-130 manufacturing process is similar to that of Hemgenics, with expectations for a process performance qualification to take approximately four to five months [48][49] 9. **Pre-BLA Meeting**: A pre-BLA meeting with the FDA is expected in Q4 2025 to align on submission requirements and confirmatory trial needs [92] 10. **International Strategy**: While prioritizing the FDA, UniCure is also engaging with the EMA regarding next steps for potential approval in Europe [99] Additional Important Content 1. **Forward-Looking Statements**: The call included forward-looking statements that are subject to risks, and actual results may differ materially from those anticipated [4] 2. **Community Engagement**: The support from the Huntington's disease community is acknowledged as instrumental in advancing AMT-130 [18] 3. **Statistical Analysis**: There is no specific P value threshold required by the FDA, but formal statistical analyses will be conducted [58][63] 4. **Sensitivity Analyses**: The consistency of results across various datasets is crucial for regulatory approval, and sensitivity analyses will be performed to validate findings [31][70] 5. **Patient Population**: The patient population for the study includes those with early-stage Huntington's disease, and any slowing of disease progression is considered significant for quality of life [63] This summary encapsulates the critical aspects of the conference call regarding UniCure's AMT-130 and its regulatory journey, highlighting the company's strategic focus and the importance of community and stakeholder engagement.