UniQure N : ESGCT 2021 - Pre-Clinical Proof of Concept of an AAV5-GLA Gene Therapy for Fabry Disease Resulting in Cross-Correction in GLA KO Mice and Non-Human Primates in Target Organs

Pre-clinical proof of concept of an AAV5-GLA gene therapy for Fabry disease resulting in cross-correction in GLA KO mice and non-human primates in target organs

Abstract number OR19

Jolanda Liefhebber - Senior Scientist

Forward Looking Statement and Disclosure

Forward Looking Statement

This presentation contains forward-looking statements. 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. 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. These forward-looking statements include, but are not limited to, statements regarding the development of our gene therapies, the success of our collaborations, and the risk of cessation, delay or lack of success of any of our ongoing or planned clinical studies and/or development of our product candidates. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks associated with the COVID-19 pandemic, collaboration arrangements, our and our collaborators' clinical development activities, regulatory oversight, development of product candidates, product commercialization and intellectual property claims, as well as the risks, uncertainties and other factors described under the heading "Risk Factors" in uniQure's Annual Report on Form 10-K filed on March 1, 2021 and Quarterly Report on Form 10-Q filed July 26, 2021. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.

Disclosure

Employee of uniQure biopharma BV

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Fabry disease:

a lysosomal storage disease

• X-linkedgenetic disorder
• Deficiency of α-galactosidase A (GLA)
• Prevalence: 1:3,700 - 80,000 live births *
• Population: ~15,000 in US and Europe

Symptoms:

• Fatigue and hearing loss
• Neuropathic pain
• Angiokeratomas
• Corneal opacity
• Cardiac disease
• Renal failure
• Stroke risk

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Eyes and

Ears

Heart:

Dysfunction risk

Gastro-

Intestinal

CNS:

Stroke risk

Kidney:

High risk kidney problems; end stage renal disease

Skin and

Sensation

• Spada, et al, Am. J. Hum. Gent. 2006:79, 31-40
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Fabry disease: unmet need with current enzyme replacement therapy (ERT)

• α-galactosidaseA (GLA) degrades:
• • Globotriaosylceramide (Gb3)
  • Lyso-Gb3
• Systemic accumulation of substrate in lysosomes of endothelial cells in the kidney, heart and brain

The standard of care is bi-weekly enzyme replacement therapy (ERT)

• ERT has limited tissue penetration and biodistribution
• Results in poor substrate clearance in the heart and kidney
• Disease progresses despite ERT

Desnick and Schuchman Annu. Rev. Genomics Hum. Gent. 2012; 13:307-35

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Globotriaosylceramide

sugar moiety

fatty acid

sphingosine

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AMT-191:

a one-time treatment for Fabry Disease

AMT-191AAV5-GLA

AAV5 encoding an α-galactosidase A (GLA) transgene

• AAV5-vector	AAV5
capsid

• Low immunogenicity *

• Excellent liver distribution	Expression
	cassette

• Liver specific promoter

• Potent and specific	ITR					ITR
proprietary promoter
				Liver	GLA	polyA
				Promoter

* Majowicz A. et al. Haemophilia 2020; 26:20-20

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