Key Updates

• The first patient has received the first dose of QR-110 in the Phase 1/2 safety & efficacy clinical trial (PQ-110-001: NCT03140969) in children and adults with Leber’s congenital amaurosis 10 (LCA 10).
• LCA 10 is one of the most prevalent forms of gene-related blindness in children worldwide and currently there are no therapies commercially available or in clinical development for this disease.
• QR-110 has received fast track designation by the U.S. Food and Drug Administration (FDA) and has been granted orphan drug designation in the United States and European Union.
• Interim safety and efficacy trial results from the majority of patients after 6 months of treatment are expected in 2018, full 12 month treatment data from all patients are expected in 2019.

LEIDEN, the Netherlands (GLOBE NEWSWIRE) — ProQR Therapeutics N.V. (Nasdaq:PRQR) today announced that the first patient has been dosed in the Phase 1/2 open-label trial assessing the safety, tolerability, pharmacokinetics and efficacy of QR-110. The trial will enroll approximately six adults and six children who have Leber’s congenital amaurosis 10 (LCA 10) due to the p.Cys998X mutation in the CEP290 gene. Subjects will receive a dose of QR-110 every three months for a total of four doses in one eye. The trial is planned to be conducted at three specialized centers: the University of Iowa, Iowa City, IA, US, the Scheie Eye Institute at the University of Pennsylvania, Philadelphia, PA, US and the Ghent University Hospital, Ghent, Belgium.

Benjamin Yerxa, PhD., Chief Executive Officer at Foundation Fighting Blindness, stated, “We are delighted with the launch of ProQR’s clinical trial for its treatment for people with devastating vision loss caused by the p.Cys998X mutation in CEP290. There are no other options for these patients, and furthermore, we believe most emerging gene replacement technologies do not have the capacity to deliver the large CEP290 gene to the retina.”

QR-110 is ProQR’s lead program in the ophthalmology pipeline that also includes two programs for Usher syndrome, a program for Fuchs endothelial corneal dystrophy and a program for Stargardt’s disease. QR-110 is ProQR’s second program to enter clinical development, following QR-010, which is being developed for the most common mutation causing cystic fibrosis.

“This announcement recognizes an important next step towards achieving our goal of developing precision medicines based on molecular diagnostics and our RNA therapeutic platform,” said David M. Rodman, MD, Chief Development Strategy Officer of ProQR. “The QR-110 program is the first in a planned series of ophthalmology trials utilizing our RNA therapy platform to target the underlying cause of blindness in patients with inherited forms of retinal dystrophy. We expect this trial will give us fundamental information regarding the safety, efficacy and developability of QR-110 in adults and children with LCA 10.”

Key facts on QR-110

• QR-110 aims to delay the progression of the disease or restore vision in people with LCA 10 due to the p.Cys998X mutation in the CEP290 gene.
• QR-110 is a single stranded RNA oligonucleotide designed to restore wild-type or normal CEP290 mRNA.
• In pre-clinical studies of QR-110, it was shown to convert close to 100% of the mutant mRNA to wild-type in a homozygous optic cup organoid model.
• A long half-life in the eye allowing for infrequent dosing.
• Administered through intravitreal administration, which is considered a routine procedure.
• A ProQR sponsored pre-evaluation/retrospective natural history study collecting data of 22 LCA 10 patients over a period of 16 years was completed in 2017 (Samuel G. Jacobson et al; Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the Intronic Mutation in the CEP290 Gene. Invest. Ophthalmol. Vis. Sci. 2017;58(5):2609-2622.)

About Leber’s Congenital Amaurosis 10

Leber’s congenital amaurosis (LCA) is the most common cause of blindness due to genetic disease in children and consists of a group of diseases of which LCA 10 is the more severe forms. LCA 10 is caused by mutations in the CEP290 gene of which the p.Cys998X mutation is the most common. LCA 10 leads to early loss of vision causing most people to lose their sight in the first few years of life. To date, there are no treatments approved or other products in clinical development that treat the underlying cause of the disease. Approximately 2,000 people in the Western world have LCA 10 because of this mutation.