Executive Summary & Recent Progress [First Quarter 2025 Highlights](index=1&type=section&id=First%20Quarter%202025%20Highlights) uniQure announced its Q1 2025 financial results and highlighted significant progress, including FDA Breakthrough Therapy designation for AMT-130, positive safety data from its Phase I/II study, and a strong cash position expected to fund operations into the second half of 2027. - **AMT-130** granted Breakthrough Therapy designation by FDA[1](index=1&type=chunk) - Initial safety data from the third cohort of the Phase I/II study indicate **AMT-130** continues to be generally well-tolerated, with no treatment-related serious adverse events reported[1](index=1&type=chunk) - Cash, cash equivalents, and current investment securities totaled approximately **$409.0 million** as of March 31, 2025, projected to fund operations into the second half of 2027[1](index=1&type=chunk) [CEO's Statement](index=1&type=section&id=CEO%27s%20Statement) CEO Matt Kapusta highlighted constructive interactions with the FDA for AMT-130, emphasizing the significance of its Breakthrough Therapy designation and upcoming regulatory and clinical data updates. He also noted continued progress across the broader gene therapy pipeline and the company's strong financial position. - CEO anticipates providing a regulatory update in **Q2 2025**, including guidance on potential timing of BLA submission for **AMT-130**, and expects to share new clinical data from **AMT-130 Phase I/II trials** in **Q3 2025**[3](index=3&type=chunk) - Initial data for **AMT-260** (refractory mesial temporal lobe epilepsy) from the first treated patient is expected later this quarter, with **AMT-191** (Fabry disease) initial data on track for the second half of the year[3](index=3&type=chunk) Recent Company Developments and Updates [Advancing AMT-130 Toward Accelerated Approval for Huntington's disease](index=1&type=section&id=Advancing%20AMT-130%20Toward%20Accelerated%20Approval%20for%20Huntington%27s%20disease) uniQure has made significant strides with AMT-130, securing FDA Breakthrough Therapy designation and engaging in Type B meetings to advance Biologics License Application (BLA) preparations. Clinical trials show AMT-130 is generally well-tolerated, with further data expected in Q3 2025. - In **April 2025**, the FDA granted **Breakthrough Therapy designation** to **AMT-130**, based on Phase I/II clinical evidence indicating potential to slow Huntington's disease progression[4](index=4&type=chunk) - In **March 2025** and **Q2 2025**, the Company conducted Type B meetings with the FDA to discuss CMC requirements and the pivotal statistical analysis plan for a planned BLA submission[7](index=7&type=chunk) - In **February 2025**, enrollment of all 12 patients in the third cohort of the Phase I/II study was completed, with **AMT-130** generally well-tolerated at both dose levels and no treatment-related serious adverse events reported[7](index=7&type=chunk) [Advancing additional clinical programs to proof-of-concept](index=2&type=section&id=Advancing%20additional%20clinical%20programs%20to%20proof-of-concept) uniQure is progressing its pipeline with upcoming data presentations for AMT-260 (refractory mTLE) in May 2025 and AMT-191 (Fabry disease) in H2 2025, following favorable safety reviews. Enrollment for AMT-162 (SOD1 ALS) is also advancing, with initial data anticipated in H1 2026. - Initial safety and exploratory efficacy data from the first treated patient for **AMT-260** (refractory mTLE) are expected to be presented at the Epilepsy Therapies & Diagnostics Development Symposium on **May 29, 2025**[7](index=7&type=chunk) - For **AMT-191** (Fabry disease), a favorable recommendation from the independent data monitoring committee (IDMC) was announced in **February 2025**, with initial study data planned for the **second half of 2025**[7](index=7&type=chunk) - For **AMT-162** (SOD1 ALS), enrollment in a second dose cohort is complete, with the third dose cohort expected in **Q3 2025**, and initial study data anticipated in the **first half of 2026**[7](index=7&type=chunk)[8](index=8&type=chunk) Financial Highlights [Cash Position](index=3&type=section&id=Cash%20position) uniQure's cash, cash equivalents, and current investment securities increased to $409.0 million as of March 31, 2025, primarily due to $80.5 million net proceeds from a follow-on offering, extending its operational funding into the second half of 2027. Cash, Cash Equivalents and Current Investment Securities | Date | Amount (Millions USD) | | :--- | :--- | | March 31, 2025 | $409.0 | | December 31, 2024 | $367.5 | - The increase in cash was primarily driven by **net proceeds of $80.5 million** from a follow-on offering in **January and February 2025**[9](index=9&type=chunk)[16](index=16&type=chunk) - Based on the current operating plan, cash, cash equivalents, and current investment securities are projected to fund operations into the **second half of 2027**[9](index=9&type=chunk) [Revenues](index=3&type=section&id=Revenues) Total revenues for the first quarter of 2025 significantly decreased to $1.6 million from $8.5 million in the prior year, primarily due to reductions in collaboration revenue and contract manufacturing revenue for HEMGENIX®. Total Revenues (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $1.6 | -$6.9 million | | 2024 | $8.5 | - | - The **$6.9 million decrease** in revenue stemmed from a **$0.4 million increase** in license revenue, a **$3.3 million decrease** in collaboration revenue, and a **$4.0 million decrease** in contract manufacturing revenue for **HEMGENIX®**[10](index=10&type=chunk) [Operating Expenses](index=3&type=section&id=Operating%20expenses) Total operating expenses decreased by $16.6 million to $47.2 million in Q1 2025, driven by the nil cost of contract manufacturing revenues (due to facility divestment), and reductions in R&D and SG&A expenses. Total Operating Expenses (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $47.2 | -$16.6 million | | 2024 | $63.9 | - | [Cost of Contract Manufacturing Revenues](index=3&type=section&id=Cost%20of%20contract%20manufacturing%20revenues) Cost of contract manufacturing revenues was nil for Q1 2025, a $9.1 million decrease from Q1 2024, following the divestment of the Lexington facility in July 2024. Cost of Contract Manufacturing Revenues (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $0.0 | -$9.1 million | | 2024 | $9.1 | - | - Following the divestment of the Lexington facility in **July 2024**, the cost of contract manufacturing is recorded net of revenue within other expenses[11](index=11&type=chunk) [Research and Development (R&D) Expenses](index=3&type=section&id=R%26D%20expenses) R&D expenses decreased by $4.6 million to $36.1 million in Q1 2025, primarily due to lower employee-related and facility expenses, partially offset by increased external program spend. R&D Expenses (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $36.1 | -$4.6 million | | 2024 | $40.7 | - | - The decrease was primarily attributed to a **$7.7 million reduction** in employee-related expenses, a **$2.5 million decrease** in facility expenses, and a **$1.1 million decrease** in preclinical supply costs, partially offset by a **$7.1 million net increase** in external program spend and **$1.1 million higher expenses** from an increase in the fair value of contingent consideration[12](index=12&type=chunk) [Selling, General and Administrative (SG&A) Expenses](index=3&type=section&id=SG%26A%20expenses) SG&A expenses decreased by $3.0 million to $10.9 million in Q1 2025, mainly due to reductions in employee-related expenses and intellectual property fees. SG&A Expenses (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $10.9 | -$3.0 million | | 2024 | $13.9 | - | - The decrease was primarily due to a **$2.2 million reduction** in employee-related expenses and a **$0.3 million decrease** in intellectual property fees[13](index=13&type=chunk) [Other Income and Expense](index=3&type=section&id=Other%20income%20and%20expense) Other income significantly increased in Q1 2025 due to a one-time gain, while other expense also rose. Non-operating items, net, showed a reduced expense compared to the prior year, driven by lower interest expense and higher foreign currency gains. [Other Income](index=3&type=section&id=Other%20income) Other income increased by $6.9 million to $8.3 million in Q1 2025, primarily driven by a one-time gain of $6.0 million from the sale of critical reagents. Other Income (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $8.3 | +$6.9 million | | 2024 | $1.4 | - | - The increase was primarily attributable to a **one-time gain of $6.0 million** from the sale of critical reagents[14](index=14&type=chunk) [Other Expense](index=3&type=section&id=Other%20expense) Other expense increased to $2.0 million in Q1 2025 from $0.2 million in Q1 2024, mainly due to a $1.4 million non-cash expense for amortizing the right to purchase HEMGENIX®. Other Expense (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | $2.0 | +$1.8 million | | 2024 | $0.2 | - | - The increase was primarily due to **$1.4 million** in non-cash expense recognized for amortizing the right to purchase **HEMGENIX®** from Genezen on favorable terms[15](index=15&type=chunk) [Other Non-Operating Items, Net](index=4&type=section&id=Other%20non-operating%20items%2C%20net) Other non-operating items, net, decreased as an expense by $6.9 million to $3.8 million in Q1 2025, driven by a reduction in interest expense and an increase in net foreign currency gains. Other Non-Operating Items, Net (Three months ended March 31) | Year | Amount (Millions USD) | Change (YoY) | | :--- | :--- | :--- | | 2025 | -$3.8 (expense) | +$6.9 million (less expense) | | 2024 | -$10.7 (expense) | - | - The **$6.9 million decrease** in other non-operating items, net, was primarily due to a **$2.4 million decrease** in interest income, a **$1.0 million reduction** in interest expense from the **$50.0 million repayment** of Hercules debt in **July 2024**, and an **$8.3 million increase** in net foreign currency gains[17](index=17&type=chunk) [Net Loss and EPS](index=4&type=section&id=Net%20loss) uniQure significantly narrowed its net loss for Q1 2025 to $43.6 million, or $0.82 per ordinary share, compared to a $65.6 million net loss, or $1.36 per ordinary share, in Q1 2024. Net Loss (Three months ended March 31) | Year | Amount (Millions USD) | Basic and Diluted Loss Per Ordinary Share | | :--- | :--- | :--- | | 2025 | $43.6 | $0.82 | | 2024 | $65.6 | $1.36 | Corporate Information [Investor Conference Call and Webcast Information](index=4&type=section&id=Investor%20Conference%20Call%20and%20Webcast%20Information) uniQure hosted an investor conference call and webcast on May 9, 2025, at 8:30 a.m. ET, with replay available on their website for 90 days. - uniQure management hosted an investor conference call and webcast on **Friday, May 9, 2025, at 8:30 a.m. ET**[19](index=19&type=chunk) - The event was webcast under the Events & Presentations section of uniQure's website, with a replay archived for **90 days**[19](index=19&type=chunk) [About uniQure](index=4&type=section&id=About%20uniQure) uniQure is a leading gene therapy company focused on developing single treatments for severe medical needs, having achieved a historic milestone with its approved hemophilia B gene therapy and advancing a pipeline for Huntington's disease, epilepsy, ALS, and Fabry disease. - uniQure is a leading gene therapy company developing transformative therapies for patients with severe medical needs[20](index=20&type=chunk) - The approvals of uniQure's gene therapy for **hemophilia B** represent a major milestone in genomic medicine[20](index=20&type=chunk) - uniQure is advancing a pipeline of proprietary gene therapies for **Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease**, and other severe diseases[20](index=20&type=chunk) [Forward-Looking Statements](index=4&type=section&id=uniQure%20Forward-Looking%20Statements) This section contains forward-looking statements regarding uniQure's future expectations, including its cash runway, regulatory outcomes for AMT-130, commercialization plans, and clinical updates for various programs. It also highlights inherent risks and uncertainties that could cause actual results to differ materially from these projections. - Forward-looking statements encompass the Company's cash runway into the **second half of 2027**, regulatory outcomes for **AMT-130**, commercialization plans, and clinical updates for **AMT-130, AMT-260, AMT-191**, and **AMT-162** programs[21](index=21&type=chunk) - Actual results may differ materially due to risks and uncertainties related to clinical results, regulatory interactions, infrastructure development, clinical trial management effectiveness, continued development and acceptance of gene therapies, intellectual property, and funding operations[21](index=21&type=chunk)[22](index=22&type=chunk) [Contacts](index=5&type=section&id=uniQure%20Contacts) Contact information is provided for investor relations (Chiara Russo) and media inquiries (Tom Malone). - For investors, contact **Chiara Russo** at c.russo@uniQure.com[24](index=24&type=chunk) - For media, contact **Tom Malone** at t.malone@uniQure.com[24](index=24&type=chunk) Unaudited Consolidated Financial Statements [Unaudited Consolidated Balance Sheets](index=6&type=section&id=UNAUDITED%20CONSOLIDATED%20BALANCE%20SHEETS) As of March 31, 2025, uniQure's total assets increased to $605.4 million, driven by a rise in cash and cash equivalents. Total liabilities also increased, but shareholders' equity moved from a deficit to a positive balance, reflecting improved financial positioning. Key Balance Sheet Figures (in thousands USD) | Item | March 31, 2025 | December 31, 2024 | Change | | :--- | :--- | :--- | :--- | | Cash and cash equivalents | $217,229 | $158,930 | +$58,299 | | Current investment securities | $191,782 | $208,591 | -$16,809 | | Total current assets | $435,421 | $390,289 | +$45,132 | | Total assets | $605,403 | $556,536 | +$48,867 | | Total current liabilities | $36,310 | $40,053 | -$3,743 | | Total liabilities | $571,717 | $563,288 | +$8,429 | | Total shareholders' equity / (deficit) | $33,686 | $(6,752) | +$40,438 | [Unaudited Consolidated Statements of Operations](index=7&type=section&id=UNAUDITED%20CONSOLIDATED%20STATEMENTS%20OF%20OPERATIONS) uniQure reported a significantly reduced net loss of $43.6 million for Q1 2025, down from $65.6 million in Q1 2024. This improvement was primarily due to lower operating expenses and higher other income, despite a decrease in total revenues. Key Income Statement Figures (in thousands USD, three months ended March 31) | Item | 2025 | 2024 | Change (YoY) | | :--- | :--- | :--- | :--- | | Total revenues | $1,567 | $8,485 | -$6,918 | | Total operating expenses | $47,245 | $63,855 | -$16,610 | | Other income | $8,306 | $1,376 | +$6,930 | | Other expense | $1,959 | $234 | +$1,725 | | Loss from operations | $39,331 | $54,228 | -$14,897 | | Non-operating items, net | $3,810 | $10,734 | -$6,924 | | Net loss | $43,637 | $65,618 | -$21,981 | | Basic and diluted net loss per ordinary share | $0.82 | $1.36 | -$0.54 | | Weighted average shares | 53,110,580 | 48,384,510 | +4,726,070 |

Core Insights - uniQure N.V. has received Breakthrough Therapy designation from the FDA for AMT-130, indicating significant progress towards a potential disease-modifying treatment for Huntington's disease [3][4] - The company reported a cash position of approximately $409.0 million as of March 31, 2025, which is expected to fund operations into the second half of 2027 [7] - Financial results for Q1 2025 show a revenue decrease to $1.6 million from $8.5 million in Q1 2024, primarily due to reduced collaboration and contract manufacturing revenues [8] Company Developments - AMT-130 is advancing towards a planned Biologics License Application (BLA) submission, with regulatory updates expected in Q2 2025 [3][4] - Initial safety data from the third cohort of the Phase I/II study of AMT-130 indicate it is generally well-tolerated, with no treatment-related serious adverse events reported [5][6] - The company plans to present initial clinical data for AMT-260 at the Epilepsy Therapies & Diagnostics Development Symposium on May 29, 2025 [4][9] Financial Highlights - The cash position increased from $367.5 million at the end of 2024 to $409.0 million by March 31, 2025, largely due to net proceeds of $80.5 million from a follow-on offering [7] - Research and development expenses decreased to $36.1 million in Q1 2025 from $40.7 million in Q1 2024, reflecting a reduction in employee-related and facility expenses [11] - The net loss for Q1 2025 was $43.6 million, or $0.82 per share, compared to a net loss of $65.6 million, or $1.36 per share, in the same period of 2024 [16][25]

Core Insights - The focus is on sustainable wealth growth through investments in R&D biotech [1] - The author expresses a personal beneficial long position in QURE shares, indicating confidence in the company's potential [1] Company and Industry Summary - The article emphasizes the importance of research and development in the biotechnology sector as a means to achieve sustainable investment returns [1] - The author highlights the relevance of their academic background in Cell Physiology and Bio-organic Chemistry to their investment strategy in biotech [1]

Core Insights - uniQure N.V. will report its first quarter 2025 financial results on May 9, 2025, before market open, and will host an earnings call at 8:30 a.m. ET to provide updates on its pipeline and AMT-130 [1] - The company is initiating quarterly earnings calls to enhance engagement with the investment community as it progresses towards a BLA submission and potential commercialization [1] Company Overview - uniQure is a leading gene therapy company focused on delivering transformative therapies for patients with severe medical needs, including a gene therapy for hemophilia B, which marks a significant milestone in genomic medicine [3] - The company is advancing a pipeline of proprietary gene therapies targeting Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases [3]

Company Overview - uniQure (QURE) shares increased by 38.5% in the last trading session, closing at $13, following a notable volume of shares traded, contrasting with a 33.1% loss over the past four weeks [1] - The stock's rally was driven by the FDA granting Breakthrough Therapy designation to its pipeline candidate, AMT-130, for treating Huntington's disease, a rare neurodegenerative disorder [1] Financial Performance - The company is expected to report a quarterly loss of $1.07 per share, reflecting a year-over-year increase of 21.3%, while revenues are projected to be $6 million, down 29.3% from the same quarter last year [2] - The consensus EPS estimate for uniQure has remained unchanged over the last 30 days, indicating that stock price movements may not sustain without trends in earnings estimate revisions [3] Industry Context - uniQure is part of the Zacks Medical - Biomedical and Genetics industry, where Kiniksa Pharmaceuticals, Ltd. (KNSA) experienced a 1.6% decline in the last trading session, with a -11% return over the past month [3] - Kiniksa Pharmaceuticals has a consensus EPS estimate of $0.06 for its upcoming report, representing a 124% increase from the previous year, and currently holds a Zacks Rank of 2 (Buy) [4]

Core Points - The U.S. FDA has granted Breakthrough Therapy designation to AMT-130 for treating Huntington's disease, highlighting the urgent need for effective treatments in this area [2][3] - AMT-130 has also received multiple designations from the FDA, including Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug, and Fast Track designations, indicating its potential significance in addressing unmet medical needs [2] - Interim data from ongoing Phase I/II trials show a dose-dependent slowing of disease progression in treated patients, with 45 patients having received AMT-130 to date [3] Company Overview - uniQure is a gene therapy company focused on developing transformative therapies for severe medical conditions, including Huntington's disease, ALS, and Fabry disease [6] - The company has previously achieved a significant milestone with its gene therapy for hemophilia B, marking a major advancement in genomic medicine [6] Huntington's Disease Context - Huntington's disease is a rare, inherited neurodegenerative disorder affecting approximately 70,000 diagnosed individuals in the U.S. and Europe, with no approved therapies currently available to slow its progression [5]

Core Insights - The U.S. FDA has granted Breakthrough Therapy designation to AMT-130 for Huntington's disease, highlighting the urgent need for effective treatments and the promising interim data indicating potential disease progression slowing [1][2] - The Breakthrough Therapy designation is in addition to other FDA designations previously granted to AMT-130, including RMAT, Orphan Drug, and Fast Track [1] - The company anticipates additional regulatory updates and guidance on the Biologics License Application submission in the second quarter of 2025 [1] 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 [5] - The company has made significant progress in gene therapy, evidenced by the approval of its gene therapy for hemophilia B, marking a milestone in genomic medicine [5] Huntington's Disease Context - Huntington's disease is a rare, inherited neurodegenerative disorder affecting approximately 70,000 diagnosed individuals in the U.S. and Europe, with no approved therapies available to slow its progression [4] - The disease is characterized by motor symptoms, behavioral abnormalities, and cognitive decline due to a genetic mutation in the huntingtin gene [4] Clinical Data and Development - Interim data from ongoing Phase I/II trials of AMT-130 presented in July 2024 showed dose-dependent slowing of disease progression based on the cUHDRS scale, with 45 patients treated to date [2][3] - The Breakthrough Therapy designation aims to expedite the development and review of investigational therapies that show substantial improvement over existing treatments [3]

Core Insights - The FDA has granted Breakthrough Therapy designation to AMT-130 for Huntington's disease, highlighting the urgent need for effective treatments and the promising interim data indicating potential disease progression slowing [1][2] - The designation is supported by clinical data from ongoing Phase I/II trials, with interim data showing dose-dependent slowing of disease progression based on the cUHDRS after 24 months [2] Regulatory Updates - Additional regulatory updates and guidance on the Biologics License Application (BLA) submission for AMT-130 are expected in the second quarter of 2025 [1] - The Breakthrough Therapy designation allows for expedited development and review processes, including intensive guidance on drug development and senior management involvement from the FDA [3] Huntington's Disease Overview - Huntington's disease is a rare, inherited neurodegenerative disorder affecting approximately 70,000 diagnosed individuals in the U.S. and Europe, with no approved therapies to slow its progression [4] - The disease is characterized by motor symptoms, behavioral abnormalities, and cognitive decline due to a genetic mutation in the huntingtin gene [4] Company Background - uniQure is focused on advancing gene therapies, including AMT-130 for Huntington's disease, and has previously achieved significant milestones with its gene therapy for hemophilia B [5] - The company is developing a pipeline of gene therapies for various severe diseases, including ALS and Fabry disease [5]

UniQure (QURE) came out with a quarterly loss of $1.50 per share versus the Zacks Consensus Estimate of a loss of $0.44. This compares to loss of $1.53 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of -240.91%. A quarter ago, it was expected that this human gene therapy company would post a loss of $1.12 per share when it actually produced a loss of $0.91, delivering a surprise of 18.75%.Over the last four quarters, the company ...

Financial Performance - The company reported net losses for the years ended December 31, 2024 and 2023, with significant losses in previous years and expects to incur losses in the future[16] - The company reported net losses for the years ended December 31, 2024 and 2023, and anticipates continued losses in the future, indicating a risk of never achieving profitability[16] - The company has incurred significant losses in previous years and will need to raise additional funding to advance product development, which may not be available on acceptable terms[18] Product Development and Clinical Trials - The lead product candidate, AMT-130, is critical for the treatment of Huntington's disease, and any failure in its clinical development could adversely affect the company's business[15] - The company may face delays in clinical trials and challenges in demonstrating the safety and efficacy of its product candidates, which could impact future operations[15] - The company may face delays in clinical trials and challenges in demonstrating safety and efficacy of its product candidates, which could materially harm its business[15] - The company has encountered risks associated with the marketing approval process for gene therapies, which may affect the commercialization of its product candidates[15] Regulatory and Manufacturing Risks - The company has encountered risks related to the manufacturing of gene therapies, which are complex and expensive, potentially leading to delays in development or commercialization[15] - The company is dependent on third-party manufacturers for its product candidates, which may not perform satisfactorily or comply with regulatory requirements[15] - The company relies on third parties for manufacturing its product candidates, which may not perform satisfactorily or comply with regulations[15] - The company plans to leverage specialized regulatory pathways, such as the FDA's accelerated approval pathway, but may struggle to maintain the benefits associated with these designations[15] - The company may leverage specialized regulatory pathways for its product candidates, but there is no guarantee of obtaining or maintaining the associated benefits[15] Market and Competitive Landscape - The market price of the company's ordinary shares has been volatile and may fluctuate substantially in the future[18] - The company faces substantial competition in the industry, which may impact its ability to successfully commercialize its products[18] - The company faces substantial competition and risks that competitors may develop or commercialize competing products more successfully[18] Business Development and Strategic Initiatives - The company’s business development initiatives, including acquisitions and partnerships, may not achieve their intended benefits, posing additional risks[15] - The Lexington Transaction may not yield expected benefits and could introduce additional risks related to manufacturing and supply requirements[15]