A CLINICAL TRIAL FOR PATIENTS WITH HEMOPHILIA B

AMT-061 is an investigational gene therapy being developed by uniQure for the treatment of patients with hemophilia B. AMT-061 is currently being studied in the HOPE-B trial for adults with moderately severe or severe hemophilia B.1

Gene Therapy by uniQureAMT-061

You may have heard about ways scientists

have tried to create a gene therapy to treat hemophilia B.

Read on to learn about AMT-061, an investigational

gene therapy that is now in clinical trials.

GENE THERAPY BY UNIQURE: AMT-061

When infused, gene therapy enters the cells of the liver.

The liver cells produce Factor IX protein.

Studies have shown, the gene persists in the liver with potential for long-term production of Factor IX.4

GENE THERAPY AT WORK IN HEMOPHILIA B2,3

AAV5 vector trafficking Cellular processing Long-term expression

gene cassette

protein shell (capsid)

Factor IX episome

HEALTH OUTCOMES WITH PADUA GENE; EVALUATION IN HEMOPHILIA BAMT-061 is an investigational gene therapy that is now being studied in an important clinical trial called HOPE-B. If successful, the data from this clinical study will be used to seek approval of this new gene therapy for hemophilia B patients.1

This study will test the effects of a single dose of this gene therapy in patients with moderately severe or severe hemophilia B.1

n HOPE-B will evaluate whether AMT-061 can establish enough production of active Factor IX to prevent bleeding episodes.

n HOPE-B will also look at whether the effect of this gene therapy on bleeding episodes is similar to Factor IX prophylaxis.

n Safety of AMT-061 will be assessed throughout the trial by monitoring adverse events, physical examinations, and laboratory measures.

n HOPE-B will be used to investigate whether a single dose of AMT-061 will provide a long-lasting, durable effect.

ABOUT THE HOPE-B TRIAL

AAV5 Capsid: The Shipping Box

• The capsid contains certain “shipping” information, so that it can deliver its contents to where they are needed – the liver.

• The capsid is made from a virus – the adeno-associated virus type 5 (AAV5).

• This type of virus does not cause disease.

Factor IX Gene Cassette: The Instruction Manual!

• The gene cassette is found inside the AAV5 capsid. The capsid delivers the gene cassette to the liver cells.

• The cells in the liver will follow the instructions provided by the gene cassette to make Factor IX.

• This instruction manual stays in the liver cells, allowing them to continue making Factor IX for a long time after a single delivery.

The AMT-061 gene therapy is composed of two pieces: the capsid and the gene cassette. Together, these form the gene therapy vector.

WHO IS ELIGIBLE TO PARTICIPATE IN HOPE-B?

Patients may be able to participate in the study if they are:n Male and at least 18 years old

n Diagnosed with moderately severe or severe congenital hemophilia B (≤2% Factor IX activity)

n Patients with >150 previous exposure days of treatment with Factor IX protein

Patients will not be able to participate in this study if they have:n Developed inhibitors to Factor IX at any time

n Certain abnormal laboratory test results

n A positive test for human immunodeficiency virus, not controlled with antiviral therapy

n An active infection with hepatitis B or C virus

n History of hepatitis B or C exposure and currently receiving antiviral therapy at the last visit prior to dosing

For more information, please visit www.Clinicaltrials.gov or contact uniQure at uniQureHOPE-B@uniqure.com.

WHY SHOULD PATIENTS CONSIDER ENROLLING IN THIS TRIAL?

Clinical trials are essential to the advance of medicine.n Clinical trials are used to find out whether new

treatments and prevention measures are safe and effective for patients.

n The results of clinical trials are used by regulatory agencies to determine whether a new medical therapy can be approved.

Without patients, clinical trials cannot happen.

n Study participants actively contribute to the development of new therapies for other patients in the future.

Participation in HOPE-B may help bring a novel therapy to the hemophilia B community in the future.

Screening1 visit

Lead-In Phase≥6 months

Dosing1 visit

Post-Treatment Follow-Up

1 year

Long-TermFollow-Up

4 years

• Confirm patient eligibility

• Monitor health of study participants

• Collect information on disease management

• Administer a single infusion of AMT-061 to study participants

• Monitor vital signs

• Collect blood samples

• Regular follow-up visits for patient safety and efficacy

• Infrequent follow-up visits for patient safety and efficacy

WHAT WILL HAPPEN DURING THE TRIAL?

There are 5 phases of the HOPE-B trial

For more information, please visit www.Clinicaltrials.gov or contact uniQure at uniQureHOPE-B@uniqure.com.

References

1. uniQure Clinical Trial Protocol. AMT-061 protocol ID CT-AMT-061-02. Version 1.0. February 16, 2018.

2. Warrington KH Jr, Herzog RW. Treatment of human disease by adeno-associated viral gene transfer. Hum Genet. 2006;119(6):571-603.

3. Miesbach W, Meijer K, Coppens M, et al. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 2018;131(9):1022-1031.

4. Niemeyer GP, Herzog RW, Mount J, et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood. 2009;113(4):797-806.