UniQure N : December 2023 Huntington's Disease Program Update AMT-130

Huntington's

Disease Program Update AMT-130

December 19, 2023

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," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions and the negatives of those terms. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this presentation. Examples of these forward-looking statements include, but are not limited to, statements concerning: the potential clinical and functional effects of AMT-130, including as an effective treatment option for patients with Huntington's disease; the utility of CSF mHTT or NfL as an effective biomarkers of target engagement with respect to AMT-130; the design and engineering of AMT-130 to maximize clinical and functional benefit; the potential that volumetric data yielded from the AMT-130 clinical trial will be clinically significant; our use of a natural history cohort as a basis for comparison with respect to the efficacy of AMT-130; the initiation of the third cohort in our ongoing Phase I/II clinical trial of AMT-130 and the timing and release of additional clinical data; and our plans to request regulatory interactions with the relevant authorities in the U.S. and Europe and the potential for accelerated regulatory pathways. Because these statements are subject to risks and uncertainties, our actual results could differ materially from those expressed in these forward-looking statements. These risks and uncertainties include, among others: risks related to our ongoing Phase I/ll clinical trial of AMT-130, including the risk that such trial will be unable to demonstrate efficacy data sufficient to support further clinical development and the risk that interim data from the trial may not be predictive of later data readouts; risks related to our financial position and share price, including our ability to raise sufficient capital to support further development of our clinical programs, as needed and on acceptable terms; risks related to our reliance on third parties to conduct, supervise, and monitor our preclinical studies and clinical trials and to manufacture components of our drug product, including the clinical trial for AMT-130; and our ability to obtain, maintain and protect our intellectual property. These and other risks and uncertainties are described more fully under the heading "Risk Factors" in our periodic filings with the U.S. Securities and Exchange Commission ("SEC"), including in our Annual Report on Form 10-K filed with the SEC on February 27, 2023, our Quarterly Reports on Form 10-Q filed with the SEC on May 9, 2023, August 1, 2023 and November 7, 2023, and other filings that we make with the SEC from time to time.

Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements and, except as required by law, we assume no obligation to update these forward-looking statements to reflect events that occur or circumstances that exist after the date on which they were made.

Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third -party sources. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.

AMT-130: ongoing encouraging trends in treated patients

• AMT-130continues to be generally well-tolerated, with a manageable safety profile across both doses
• Patients treated with AMT-130 show evidence of preserved neurologic function relative to baseline, and potential dose-dependent clinical benefit relative to a non-concurrent criteria- matched natural history
• Continued favorable trends in CSF NfL were observed across both doses, with low-dose patients below baseline at 30 months and high-dose patients near baseline at 18 months
• CSF mHTT values are close to the lower-limit of detection, and may not be an effective measure of target engagement for a striatally-administeredHTT-lowering therapy

AMT-130 Clinical Trial Overview

Walid Abi-Saab, M.D. Chief Medical Officer

Huntington's disease (HD): significant unmet medical need

• Autosomal dominant inherited disorder (50% risk if a parent has HD)
• The disease progresses from premanifest to early motor diagnosis to advanced disease over 10-15 years1
• Patients enrolled in the HD-GeneTRX studies are at an early to moderate stage of disease progression

1. Ross, C. A. et al. Nat. Rev. Neurol. 10, 204-216 (2014)

HD-GeneTRX1 - A Phase 1/2, Randomized, Double-Blind,Sham-Control Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-AdministeredrAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington's Disease; HD-GeneTRX2 - Phase Ib/II Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-Administered rAAV5- miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington Disease

Huntington's disease (HD): manifestation

AMT-130: mechanism of action in Huntington's disease

AMT-130 is a modified AAV5 viral vector containing an HTT exon1 targeting miRNA