FFB-CRI Investing $7.5 Million in Emerging Therapy for USH2A

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The Foundation Fighting Blindness Clinical Research Institute (FFB-CRI) has entered into a partnership with ProQR to develop a retinal therapy for people with Usher syndrome type 2A (USH2A) caused by mutations in exon 13 of the USH2A gene. FFB-CRI will be investing up to $7.5 million in milestone-based funding to advance the treatment, known as QR-421a, toward a Phase 1/2 clinical trial during 2018. ProQR plans to issue the initial data report for the clinical study in 2019.

Mutations in exon 13 of the USH2A gene lead to dysfunctional messenger RNA (mRNA), which are genetic messages that instruct the retinal cells in how to make the USH2A protein. When the mRNA don’t function normally, the USH2A protein isn’t made correctly in the retina, and vision is lost.
QR-421a is an antisense oligonucleotide (AON), which works like a piece of tape to mask the genetic defect. Specifically, QR-421a skips over exon 13, so that functional mRNA is produced.
The goal of the treatment is to stop disease progression and potentially restore some peripheral vision.
ProQR in-licensed the technology underlying QR-421a from Radboud University Medical Center in the Netherlands, where it was invented by lead investigator Dr. Erwin van Wyck. FFB funded earlier lab studies for the development of the AON technology.
“We are excited to team up with the Foundation Fighting Blindness to develop QR-421a for patients that suffer from Usher syndrome 2A due to exon 13 mutations,” says Daniel A. de Boer, CEO of ProQR. “They are the leading private funder of retinal disease research with a very patient centric approach, which is a core pillar of our strategy. Through this partnership with the Foundation, we plan to gain access to important know-how to develop programs in retinal diseases. We expect that the additional funding will allow us to rapidly advance this novel therapy for this orphan disease with a severe unmet need.”
FFB-CRI has also launched a natural history study in 120 people with USH2A mutations. The study — known as RUSH2A (“R” stands for “rate of progression”) — was launched in 2017 and is being conducted at about 20 clinical sites around the world. RUSH2A investigators will use a variety of technologies to monitor changes in vision and retinal structure to document and analyze disease progression. Knowledge and data obtained from this trial are intended to provide a better understanding of how USH2A mutations affect the severity and progression of vision loss and help to inform the development of QR-421a.
QR-421a is the second emerging therapy in ProQR’s growing ophthalmology pipeline scheduled to enter clinical trials. The lead program in the ophthalmology pipeline, QR-110, is currently in a Phase 1/2 safety and efficacy trial in adult and pediatric patients with Leber congenital amaurosis 10 due to the p.Cys998X mutation in the CEP290 gene. This pipeline also contains several other molecules for genetic eye diseases, including QR-411 for Usher syndrome type 2A due to the PE-40 mutation, QRX-1011 for Stargardt disease, and QRX-504 for Fuchs endothelial corneal dystrophy.