Update on Clinical Trails

uniQure Announces FDA Clearance of Investigational New Drug Application for AMT-130 in Huntington’s Disease

~ AMT-130 Poised to Become First AAV Gene Therapy to Enter the Clinic for Huntington’s Disease ~

~ Lead Product Candidate from Company’s Proprietary miQURE™ Gene Silencing Platform   ~

LEXINGTON, Mass. and AMSTERDAM, the Netherlands, Jan. 22, 2019 (GLOBE NEWSWIRE) — uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced the U.S. Food and Drug Administration (FDA) has completed its review of the Company’s Investigational New Drug (IND) application for AMT-130, and the IND is now effective allowing uniQure to begin its planned Phase I/II study.  AMT-130 comprises a recombinant AAV5 vector carrying a DNA cassette encoding a microRNA that non-selectively lowers or knocks-down human huntingtin protein in Huntington’s disease patients.

“The FDA’s clearance of our IND for AMT-130 is a significant milestone for Huntington’s disease patients and an important event in the field of gene therapy,” said Matt Kapusta, chief executive officer at uniQure. “We expect that AMT-130 will be the first one-time administered AAV gene therapy to enter clinical testing for the treatment of Huntington’s disease, a devastating neurodegenerative disorder for which there is no approved disease-modifying treatment.

“AMT-130 also represents the first clinical-stage AAV-based therapy specifically designed to silence an abnormal gene in the brain with a single administration, and we believe our proprietary miQURE™ gene silencing platform has the potential to be applied to many other diseases, such as spinocerebellar ataxia type 3 (SCA3),” continued Mr. Kapusta. “This achievement is a major milestone for uniQure’s research organization, who have dedicated years of effort with the hope we can one day offer treatment for the many patients waiting generations for an effective therapy.”

FDA clearance of the IND enables uniQure to initiate its planned dose-escalating, randomized and controlled Phase I/II clinical trial to assess the safety, tolerability and efficacy of a one-time treatment of AMT-130 in patients with Huntington’s disease. uniQure expects to open several clinical sites in the United States and begin dosing patients in the second half of this year.

To read full article, click on link below:

https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=3559434&lang=en-GB&companycode=nl-qure&v=

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28 January 2019

Update on RG6042 Huntington’s disease (HD) programme: First patients enrolled in HD Natural History and Phase III GENERATION HD1 clinical studies

Dear Global Huntington’s Community,

Just over one year ago, we and our partner Ionis Pharmaceuticals announced the results of the first ever study that tested the huntingtin-lowering scientific hypothesis. Today, we are pleased to announce that the first patient has entered into the GENERATION HD1 clinical study – a pivotal, global Phase III study to investigate the efficacy and safety of RG6042 (formerly known as IONIS-HTTRx). If this clinical study is successful, it is our hope that RG6042 will be approved by health authorities and made available for the treatment of manifest Huntington’s disease.

We are grateful to the patients and family members participating in clinical research, as well as everyone supporting them in the broader HD community. Scientific progress is only possible with your collaboration and participation.

Recent updates

• Two global clinical studies have started and first patients are enrolled – an important achievement for the research programme; study status is available on ClinicalTrials.gov

–HD Natural History study (NCT03664804)

This observational study for early manifest HD will run in the USA, Canada, Germany and the UK; planned study sites were announced in late 2018.

Initial sites have opened and the first patients have enrolled; our team continues to work to open recruitment at all study sites as quickly as possible.

–Phase III GENERATION HD1 study (NCT03761849)

We received health authority approvals in the USA and Canada to start this pivotal study for manifest HD. Planned study sites for those countries were announced at the end of 2018 and the first patient has now enrolled.

This study will run in approximately 15 countries; we are diligently working to set up study infrastructure and receive approvals in the remaining countries.

• Ongoing open-label extension of the Phase I/IIa study: sponsorship has been transferred from Ionis to Roche o Patients who completed the Phase I/IIa study have been participating in an openlabel extension study sponsored by Ionis (NCT03342053). Responsibility of this study has now transferred to Roche. Moving forward these patients will roll into a new Roche-sponsored, open-label extension study called GEN-EXTEND. GENEXTEND will allow us to continue to study longer-term effects of RG6042 in those participants who have previously completed a clinical trial for the investigational molecule.

Important to note

• At this time, access to RG6042 is only through clinical studies because the benefits and risks of RG6042 are not yet fully understood. • Additional countries/sites for the Phase III study: Information about additional countries/sites will be announced on a progressive basis, once sites are nearly ready to enrol participants; information will be posted on ClinicalTrials.gov

• Communications about study data: Roche is committed to transparent and timely communications, as well as ensuring the integrity of ongoing clinical trial operations and data collection. In line with our Global Policy on Sharing of Clinical Study Information, we will share overall programme updates and relevant data from completed and ongoing clinical studies with the scientific community via appropriate channels (e.g., scientific meetings, peer-reviewed journals, etc.).

Our team recognises that the need in HD is greater than the capacity of the RG6042 development programme, and that not every person nor every capable HD centre interested in these clinical studies will be able to participate. We can assure you that the studies are designed to provide health authorities with the required data so that the benefit-risk of RG6042 can be determined as quickly as possible. The ultimate goal is that this investigational medicine can be approved by health authorities and made accessible to the broader HD community. Our team continues to engage with health authorities and HD communities around the world on the RG6042 research programme. We look forward to providing you with further updates.

Sincerely, Mai-Lise Nguyen, on behalf of the Roche & Genentech HD team Patient Partnership Director, Rare Diseases Roche Pharma Research & Early Development / Roche Innovation Centre Basel, Switzerland

To read more:  Roche-global-HD-community-letter-Jan-2019.pdf

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December 19, 2018:

RG6042 GENERATION HD1 Study: Expected Sites in USA & Canada Status

The observational HD Natural History study (Clinicaltrials.gov ID: NCT03664804) is open and currently recruiting. The planned sites in Canada, US, Germany and UK were announced in November. Information about the study, including individual site status, is posted on ClinicalTrials.gov.

We are pleased to inform you on progress on the Phase III GENERATION HD1 study (Clinicaltrials.gov ID: NCT03761849). The first countries to open recruitment will be the USA and Canada. Below is a list of planned sites – it is important to note that these sites are not fully activated nor recruiting yet. We hope to complete the final steps as quickly as possible. The GENERATION HD1 study will run in approximately 15 countries; additional countries/sites will be announced on a progressive basis – as we obtain country approvals and when sites are nearly ready to enroll patients. For any clinical study, it is possible that an expected study site does not proceed to enroll participants. This can be for various reasons and we do not want to raise hopes or expectations.

Expected sites for GENERATION HD1 study in the United States of America:

Alabama, Birmingham – University of Alabama Arizona, Phoenix – Barrow Neurological Clinic California, Davis – University of California, Davis California, Palo Alto – Stanford University California, Pasadena – Arcadia Neurology Center California, San Diego – University of California, San Diego Colorado, Englewood – Rocky Mountain Movement Disorders Center District of Columbia, Washington – Georgetown University Florida, Tampa – University of South Florida Illinois, Chicago – Northwestern University Maryland, Baltimore – John Hopkins University Massachusetts, Boston – Beth Israel Deaconess Medical Center Missouri, St Louis – Washington University New York, Amherst – Dent Institute New York, New York – Columbia University Pennsylvania, Pittsburgh – University of Pittsburgh Medical Center Tennessee, Nashville – Vanderbilt University Medical Center Texas, Houston – University of Texas Health Science Center Utah, Salt Lake City – University of Utah Washington, Kirkland – Evergreen Health

Expected sites for GENERATION HD1 study in Canada Alberta, Edmonton – University of Alberta British Columbia, Vancouver – University of British Columbia Ontario, Ottawa – Ottawa Hospital Ontario, Toronto – Centre for Movement Disorders Nova Scotia, Halifax – Queen Elizabeth II Health Sciences Centre Quebec, Montreal – Centre Hospitalier de l’Université de Montréal

Our Clinical Trial Information Support Line for the USA and Canada can be contacted at 1-888-662- 6728. Also, information about the GENERATION HD1 study and sites will soon be posted on ClinicalTrials.gov, including individual site status. Whether your HD clinic or centre is selected for participation or not, this is no reflection on the quality of the many outstanding HD clinics and dedicated care providers around the world. The need in HD is greater than the capacity of our development programme. We have designed the programme to provide the required data to Authorities so that the benefit-risk of RG6042 can be determined as quickly as possible. Our ultimate goal is that this investigational medicine can be approved by Health Authorities, and made accessible to the broader HD community. The decision to join a clinical trial is personal and involves many factors. We encourage anyone interested in participating in any clinical research to discuss with his/her HD specialist about what may be best for his/her situation.

About the Phase III GENERATION HD1 Study The GENERATION HD1 study will evaluate the efficacy and safety of RG6042 treatment given once per month or once every two months (bi-monthly) over a period of 25 months (approx. two years). This global study will enrol up to 660 patients with manifest HD at 80-90 sites in approximately 15 countries around the world. The study will begin at the end of 2018, with patients starting to enrol by early 2019. GENERATION HD1 is designed to determine the effectiveness and safety of RG6042, and therefore includes a comparison to placebo. Participants will be randomized to one of three treatment study arms: RG6042 monthly, RG6042 bi-monthly or placebo monthly. This means for every two participants randomized to RG6042, one will receive placebo. The study is “double-blinded,” meaning neither the participant nor his/her investigator or site staff will know which study arm the participant is assigned. For all patients who complete the GENERATION HD1 study, an open-label extension study with the option of receiving RG6042 (no placebo control) is planned, pending eligibility, approval by Authorities and Ethics Committees/Institutional Review Boards and if data support the continued development of RG6042.

How are the clinical study sites selected? A variety of factors influence site selection, including assessments on experience with HD studies, clinic infrastructure capacity to run the study as well as usual site activities, ability to operationalise the study as quickly and completely as possible, patient population, and geographic location. Whether your HD clinic or centre is selected for participation or not, this is no reflection on the quality of the many outstanding HD clinics and dedicated care providers around the world. The need in HD is greater than the capacity of our development programme. We have designed the programme to provide the required data to Authorities so that the benefit-risk of RG6042 can be determined as quickly as possible. Our ultimate goal is that this investigational medicine can be approved by Health Authorities, and made accessible to the broader HD community