LEIDEN, Netherlands and CAMBRIDGE, Mass., Dec. 17, 2018 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq:PRQR), a company
dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases,
today announced the publication of a peer-reviewed manuscript describing the previously announced interim results of a clinical
trial of QR-110 for the treatment of Leber’s congenital amaurosis 10 (LCA10) in the journal Nature Medicine.
“It was enormously gratifying to see robust improvements in visual acuity and significant augmentations in the patient’s ability
to detect lights, and impressive to observe these effects within the first three months following a single injection,” said
Professor Artur V. Cideciyan, Ph.D., who was one of the co-investigators at the Scheie Eye Institute of the University of
Pennsylvania. “LCA10 is a severe form of childhood blindness and this is a major step forward in the treatment of these previously
incurable conditions,” said Professor Samuel G. Jacobson, M.D., Ph.D, who is the ophthalmologist caring for four of the patients
enrolled in the study and is also a co-investigator at the Scheie Eye Institute.
Published results detail a planned interim analysis of the ongoing PQ-110-001 first-in-human clinical study, evaluating QR-110
in patients with LCA10. The publication focused on a landmark analysis of eight subjects who reached three months of single dose
treatment experience. Results demonstrate a substantive overall improvement in best corrected visual acuity (BCVA) with a mean
improvement of -0.67 LogMAR (SEM 0.32) in the treated eye versus 0.02 LogMAR (SEM 0.05) in the contralateral (control) eye
(p=0.011). The majority of patients showed an increase of at least -0.3 LogMAR in the treated eye, which is generally considered
clinically meaningful, and equivalent to 15 letters, or three lines of improvement for individuals able to read a standard eye
chart. Visual acuity improvements were also associated with concordant improvements in full-field stimulus thresholds to both blue
and red light, improved mobility course navigation and ocular instability measurement.
LCA10 is a severe inherited retinal dystrophy associated with mutations in the CEP290 gene. QR-110 is an RNA-based drug
candidate that has the potential to restore sight or slow down the process of vision loss in patients with LCA10 by correcting the
most common mutation causing LCA10, p.Cys998X.
The ongoing Phase 1/2 PQ-110-001 study of QR-110 will be completed and in parallel a Phase 2/3 "ILLUMINATE" study is expected to
be initiated in the first half of 2019.
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 LCA10 is the most frequent and one of the more severe forms. LCA10 is caused by mutations in the CEP290
gene, of which the p.Cys998X mutation is the most common. LCA10 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 LCA10 because of this mutation.
About QR-110
QR-110 is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of Leber’s
congenital amaurosis 10 due to the p.Cys998X mutation (also known as the c.2991+1655A>G mutation) in the CEP290 gene. The
p.Cys998X mutation is a substitution of one nucleotide in the pre-mRNA that leads to aberrant splicing of the mRNA and
non-functional CEP290 protein. QR-110 is designed to restore normal (wild-type) CEP290 mRNA leading to the production of normal
CEP290 protein by binding to the mutated location in the pre-mRNA causing normal splicing of the pre-mRNA. QR-110 is intended to be
administered through intravitreal injections in the eye and has been granted orphan drug designation in the United States and the
European Union and received fast-track designation by the FDA.
About the PQ-110-001 Phase 1/2 Trial
PQ-110-001 is a first-in-human open-label trial that enrolled 5 children (age 6 - 17 years) and 6 adults (? 18 years) who have
LCA10 due to one or two copies of the p.Cys998X mutation in the CEP290 gene. Patients are receiving four intravitreal injections of
QR-110 into one eye; one injection every three months, with the other eye remaining untreated. Two dose levels are being tested, 80
?g (160 ?g loading dose) and 160 ?g (320 ?g loading dose). The trial is being conducted at three specialized centers with
significant expertise in genetic retinal disease: the University of Iowa, Iowa City, Iowa, U.S., the Scheie Eye Institute at the
University of Pennsylvania, Philadelphia, U.S., and the Ghent University Hospital, Ghent, Belgium.
The primary objectives of the PQ-110-001 trial are safety and tolerability. Secondary objectives include pharmacokinetics, as
well as restoration/improvement of visual function and retinal structure through ophthalmic endpoints, such as visual acuity
(BCVA), mobility course, full field stimulus testing (FST), ocular instability (OCI), optical coherence tomography (OCT), and
pupillary light reflex (PLR). Changes in quality of life in the trial subjects are also being evaluated.
About the Phase 2/3 pivotal “ILLUMINATE” Trial
The Company has agreed with the FDA to submit a protocol to start a Phase 2/3 trial that could serve as the sole registration
trial, to be called "ILLUMINATE". The preliminary design for “ILLUMINATE” is a double-masked, controlled, 12-month study. The trial
is expected to initially enroll 30 patients with LCA10 due to one or two copies of the p.Cys998X mutation and could be adaptively
repowered. The primary endpoints in this trial are expected to include visual acuity and the mobility course. The trial is expected
to be conducted at centers in North America and select European countries. The trial is expected to start in the first half of
2019.
About ProQR
ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of
severe genetic rare diseases such as Leber’s congenital amaurosis 10, dystrophic epidermolysis bullosa and cystic fibrosis. Based
on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.
*Since 2012*
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements. All statements other than statements of historical fact are
forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,”
“goal,” “intend,” “look forward to”, “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar
expressions. Forward-looking statements are based on management’s beliefs and assumptions and on information available to
management only as of the date of this press release. These forward-looking statements include, but are not limited to, statements
regarding QR-110 and its clinical development, including the completion of the ongoing Phase 1/2 clinical trial and commencement of
the planned ILLUMINATE trial, trial design, regulatory pathway and therapeutic potential. Our actual results could differ
materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks
associated with our clinical development activities, including that positive results observed in our prior and ongoing studies may
not be replicated in later trials or guarantee approval of any product candidate by regulatory authorities, regulatory review or
approval process, manufacturing processes and facilities, regulatory oversight, product commercialization, intellectual property
claims, and the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including
certain sections of our annual report filed on Form 20-F. Given these risks, uncertainties and other factors, you should not place
undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if
new information becomes available in the future, except as required by law.
ProQR Therapeutics N.V.
Investor Contact:
Lisa Hayes
Vice President of Investor Relations and Corporate Communications
T: +1 202 360 4855
ir@proqr.com
Media Contact:
Sara Zelkovic
LifeSci Public Relations
T: +1 646 876 4933
Sara@lifescipublicrelations.com
