Update on Clinical Trials

uniQure Announces First Two Patients Treated in Phase I/II Clinical Trial of AMT130 for the Treatment of Huntington’s Disease ~ Milestone Marks the First-in-Human AAV Gene Therapy Trial for Huntington’s Disease

Lexington, MA and Amsterdam, the Netherlands, June 19, 2020

uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the first two patients in the Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease have been treated. The Phase I/II study is a double-blind, randomized clinical trial being conducted in the United States, with now one patient treated with AMT-130, and one patient who received the imitation surgery.

“For years, uniQure has had an unwavering commitment to advance this first-in-human AAV gene therapy for Huntington’s disease into clinical testing, and this moment marks an important milestone for our company now that we have two AAV gene therapy candidates in clinical development,” said Matt Kapusta, chief executive officer of uniQure. “With the first two patients treated in this trial, we have taken a significant step forward in advancing AMT-130 closer to our goal of developing a therapy that inhibits the production of the mutant huntingtin protein. We are delighted to be working with leading experts in the field to evaluate this promising candidate.”

The Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease will explore the safety, tolerability, and efficacy signals in 26 patients with early manifest Huntington’s disease randomized to treatment with AMT-130 or an imitation (sham) surgery. The five-year, multi-center trial consists of a blinded 18-month core study period followed by unblinded long-term follow-up. Patients will receive a single administration of AMT-130 through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). Additional details are available on www.clinicaltrails.gov (NCT04120493).

The first two patients will be observed for an initial period of 90 days, followed by a meeting of the Data Safety Monitoring Board (DSMB). The DSMB will review the data on the first two patients and make a determination about continued dosing of the next patients.

AMT-130 is uniQure’s first clinical program focusing on the central nervous system (CNS) incorporating its proprietary miQURE™ platform.

“There is an urgent need for disease-modifying options to treat Huntington’s disease, and we’re excited to have an investigational gene therapy now available for HD patients,” stated George Yohrling, chief scientific officer and chief mission officer at Huntington’s Disease Society of America. “Based on the promising preclinical data presented on AMT-130 over the years, we are optimistic about its potential to alter the course of this devastating disease.”

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CARLSBAD, Calif.April 20, 2020 /PRNewswire/ — Ionis Pharmaceuticals, Inc.

NASDAQ: IONS), the leader in RNA-targeted therapeutics, today announced that its partner Roche, also known as Genentech in the United States, has completed enrollment for GENERATION HD1, a global Phase 3 study evaluating the efficacy and safety of tominersen (previously IONIS-HTTRx or RG6042), an investigational antisense therapy for people living with Huntington’s disease (HD).

“Completion of the enrollment of this Phase 3 study is an important landmark for the clinical development of tominersen and for families affected by Huntington’s disease. While there is much work ahead of us, we are now closer to potentially providing a treatment for people living with this devastating disease. We are grateful to Huntington’s disease patients, their families and healthcare providers for their courage and resilience, particularly in the current challenging environment,” said Brett P. Monia, Ph.D., Ionis’ chief executive officer. “At Ionis, knowing that sick people depend on us fuels our passion for discovering and delivering novel antisense medicines like tominersen, the first and only therapy in pivotal trials targeting the underlying cause of HD.”

GENERATION HD1 is evaluating the efficacy and safety of tominersen treatment administered once every two months (eight weeks) or every four months (16 weeks) over a period of 25 months, compared to placebo. The study has completed enrollment with 791 patients across approximately 100 sites around the world.

HD is a devastating, and ultimately fatal, hereditary disease resulting in deterioration in mental abilities and physical control. Currently, there is no approved disease-modifying treatment for HD. There are approximately 3 to 10 per 100,000 people worldwide affected by HD. In the U.S. alone, there are approximately 40,000 people with symptomatic HD and more than 200,000 people at risk of having inherited the gene that causes HD.

About tominersen
Tominersen, previously IONIS-HTTRx or RG6042, is an investigational antisense therapy designed to reduce the production of all forms of the huntingtin protein (HTT), including its mutated variant, mHTT. Tominersen is the first therapy in pivotal trials targeting the underlying cause of HD. In December 2017, Roche licensed the investigational molecule from Ionis.

In the Phase 1/2 study, 46 people with early stage HD were treated with tominersen or placebo for 13 weeks. The data demonstrated significant, dose-dependent reductions in mHTT in the cerebrospinal fluid (CSF) of treated participants with a favorable safety and tolerability profile.

Tominersen is being investigated in a Phase 3 study (GENERATION HD1), an open label extension study in HD patients and a Phase I pharmacokinetics and pharmacodynamics study (GEN-PEAK). These studies, in addition to the non-interventional HD Natural History Study, are important elements of the clinical program to thoroughly evaluate the potential of tominersen to be the first disease-modifying medicine for the treatment of HD. The Phase 3 GENERATION HD1 study is expected to complete in 2022. The timing for this study’s completion remains unchanged.

Additional information about tominersen clinical trials may be found at https://clinicaltrials.gov/ct2/show/NCT03761849.

About Ionis Pharmaceuticals, Inc.
As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world’s first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardiovascular, infectious, and pulmonary diseases.

To learn more about Ionis visit www.ionispharma.com or follow us on twitter @ionispharma.

Ionis’ Forward-looking Statement
This press release includes forward-looking statements regarding Ionis’ alliance with Roche and the development, activity, therapeutic potential, commercial potential and safety of tominersen (IONIS-HTTRx or RG6042). Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are described in additional detail in Ionis’ annual report on Form 10-K for the year ended December 31, 2019, which is on file with the SEC. Copies of this and other documents are available from the Company.