uniQure N.V. QURE on Wednesday released topline data from the pivotal Phase 1/2 study of AMT-130 for Huntington’s disease.Huntington’s disease is an inherited condition in which nerve cells in the brain break down over time. The disease affects a person’s movements, thinking ability and mental health.The study met its prespecified primary endpoint, with high-dose AMT-130 demonstrating a statistically significant slowing of disease progression as measured by the composite Unified Huntington’s Disease Rating ...

Summary of uniQure's AMT-130 Conference Call Company and Industry - **Company**: uniQure - **Industry**: Gene therapy for Huntington's disease Key Points and Arguments Clinical Trial Results - **Pivotal Data Announcement**: uniQure announced pivotal data from the Phase I/II clinical trials of AMT-130 for Huntington's disease, showing a statistically significant 75% slowing of disease progression at 36 months as measured by the Composite Unified Huntington's Disease Rating Scale (CUHDRS) [4][18] - **Total Functional Capacity (TFC)**: The study also demonstrated a 60% reduction in disease progression on the TFC, a key measure of a patient's ability to live independently [14][19] - **Neurofilament Light Chain (NFL)**: CSF neurofilament light chain levels were below baseline at 36 months, indicating a reduction in neurodegeneration [16][19] Regulatory and Commercial Plans - **Biologics License Application (BLA)**: uniQure plans to submit a BLA for AMT-130 in the first quarter of 2026, with a request for priority review [5][18] - **FDA Engagement**: A pre-BLA meeting with the FDA is scheduled to discuss the data and the content of the BLA [18][34] Patient Population and Market Opportunity - **At-Risk Population**: Approximately 200,000 Americans are at risk for Huntington's disease, with about 100,000 being genetically identifiable [26] - **Diagnosed Patients**: There are around 40,000 symptomatic HD patients in the U.S., with about 20,000 currently diagnosed [26][27] - **Initial Treatable Patients**: An estimated 6,000 patients could be considered initially treatable at launch [27] Treatment Characteristics - **Durable Treatment**: AMT-130 is designed as a durable, once-administered treatment, which is crucial for a slowly progressing disease [6] - **Targeted Delivery**: The treatment allows for precision-based delivery to affected brain regions, maximizing therapeutic concentrations and minimizing systemic exposure [7] - **Mechanism of Action**: AMT-130 targets the first exon of the Huntington gene, suppressing both the full-length mutant protein and toxic splice isoforms [7] Safety Profile - **Well Tolerated**: AMT-130 has shown a manageable safety profile, with no new treatment-related serious adverse events reported since December 2022 [17][19] - **Common Adverse Events**: Most adverse events were related to study procedures, such as headache and procedural pain [17] Expert Perspectives - **Clinical Impact**: Dr. Sarah Tabrizi emphasized the potential of AMT-130 to significantly impact the quality of life for patients and families affected by Huntington's disease [24] - **Long-term Benefits**: The slowing of disease progression could allow patients to maintain independence and work longer, potentially preventing symptoms from occurring [41] Future Considerations - **Payer Engagement**: Early engagement with payers is critical to educate them on the value of AMT-130 and its impact on patients' lives [51] - **Labeling and Eligibility**: Discussions are ongoing regarding the potential labeling of AMT-130, including whether it will be restricted to symptomatic patients [80] Additional Important Content - **Statistical Analysis**: The study's primary analysis showed a 75% reduction in disease progression with a p-value of 0.003, indicating strong statistical significance [18] - **Longitudinal Data**: The data from the Enroll-HD study provided a robust external control for comparison, enhancing the credibility of the results [55] This summary encapsulates the critical findings and strategic plans discussed during the conference call regarding AMT-130 and its implications for Huntington's disease treatment.

Pivotal Phase I/II AMT-130 Huntington's Disease Update September 24, 2025 Disclaimer This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to," "may ...

uniQure (NASDAQ:QURE) announced on Wednesday that its one-time gene therapy AMT-130 reached the main goals in a pivotal Phase 2/3 trial for patients with Huntington’s disease, a rare neurodegenerative disorder. Citing topline data from the trial, the Dutch biotech noted that ...

UniQure's experimental gene therapy significantly slowed the progression of a brain disorder in an early-to-mid stage study, it said on Wednesday. ...

Core Viewpoint - uniQure N.V. has secured a $175 million non-dilutive senior secured term loan facility with Hercules Capital to enhance financial flexibility for the potential commercial launch of its investigational gene therapy AMT-130 for Huntington's disease [1][2]. Financial Details - The loan facility includes three tranches: a first tranche of $50 million to refinance existing debt, a second tranche of $100 million available upon achieving regulatory and financial milestones, and a third tranche of up to $25 million subject to Hercules' approval [3]. - The interest rate for all tranches is floating, set at the greater of 9.45% or the prime rate plus 2.45%, with a current floating rate of 9.70%, down from a previous rate of 11.95% [3]. Company Background - uniQure is a leader in gene therapy, focusing on transformative therapies for severe medical conditions, including Huntington's disease, refractory temporal lobe epilepsy, ALS, and Fabry disease [5]. - The company has achieved significant milestones, including the approval of its gene therapy for hemophilia B, marking a major advancement in genomic medicine [5]. Partner Information - Hercules Capital is a prominent specialty finance company that provides senior secured venture growth loans to high-growth, innovative companies in technology and life sciences, having committed over $22 billion to more than 680 companies since its inception [6].

Core Insights - uniQure N.V. announced positive topline data from the pivotal Phase I/II study of AMT-130 for Huntington's disease, demonstrating statistically significant slowing of disease progression [1][2][3] Study Results - The pivotal study met its primary endpoint, showing a 75% slowing of disease progression at 36 months as measured by the composite Unified Huntington's Disease Rating Scale (cUHDRS) compared to a matched external control [3][4] - High-dose AMT-130 also achieved a statistically significant 60% slowing of disease progression as measured by Total Functional Capacity (TFC), meeting a key secondary endpoint [4][6] - Favorable trends were observed in additional clinical measures, including an 88% slowing of disease progression as measured by the Symbol Digit Modalities Test (SDMT) [4][6] Safety Profile - AMT-130 was generally well-tolerated with a manageable safety profile, and no new drug-related serious adverse events were reported since December 2022 [8][9] - The most common adverse events were related to the administration procedure, all of which resolved [8] Regulatory Plans - uniQure plans to submit a Biologics License Application (BLA) in the first quarter of 2026, with a potential U.S. launch later that year pending approval [1][9] - AMT-130 has received Breakthrough Therapy designation and Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA [9] Clinical Program Overview - The Phase I/II clinical program includes two multi-center, dose-escalating studies to explore the safety, tolerability, and exploratory efficacy signals of AMT-130 for Huntington's disease [11] - Data from the studies will be compared to a propensity score-matched external control derived from the Enroll-HD natural history dataset [11] Background on Huntington's Disease - Huntington's disease is a rare, inherited neurodegenerative disorder affecting approximately 75,000 people in the U.S., EU, and the UK, with no approved therapies currently available to slow its progression [15]

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]