Full Press Release Details
ProQR Announces Additional Sepofarsen
Illuminate Trial Analyses and Provides Update on Company Strategy
Netherlands & CAMBRIDGE, Mass., April 13, 2022 -- ProQR Therapeutics N.V. (Nasdaq: PRQR) (the "Company"), a company dedicated
to changing lives through the creation of transformative RNA therapies, today provided an update on its sepofarsen program, following
a comprehensive post-hoc analysis of the data from the Phase 2/3 Illuminate trial in people with CEP290-mediated Leber
congenital amaurosis 10, or LCA10, a severe inherited retinal disease. The Company also announced the completion of an in-depth strategic
review designed to extend the Company's runway and deliver on its commitment to advance RNA therapies for diseases with high unmet
on the outcomes of this strategic review, the Company will prioritize the following strategic objectives:
Company ended 2021 with 187.5 million of cash and cash equivalents on its balance sheet and expects these resources, together with
anticipated expense reductions resulting from a corporate restructuring and the strategic update announced today, will fund currently
planned operations into 2025, and through several milestones, including the potential readout of the modified Phase 2/3 Sirius
trial of ultevursen.
sepofarsen Illuminate analysis
Following the top-line
announcement in February 2022 that Illuminate, ProQR's pivotal Phase 2/3 trial of sepofarsen in CEP290-mediated LCA10,
did not meet the primary endpoint of Best Corrected Visual Acuity (BCVA) at Month 12 compared to a sham procedure control group, comprehensive
post-hoc analyses of the trial were undertaken which revealed:
Overall, the post-hoc
analyses showed that the efficacy signal seen with sepofarsen when comparing active treatment and sham eyes to their corresponding contralateral
eyes across BCVA, FST, and other endpoints, including PROs, was more consistent with the results seen in earlier findings, where the
contralateral eye was used as the control. Based on these results, ProQR will focus on the following core activities related to sepofarsen:
analyses show an encouraging efficacy signal when comparing the active treatment and sham eyes to their corresponding contralateral eyes
across multiple endpoints and are consistent with feedback received from the investigators. In prior interactions, EMA preferred the
use of the contralateral eye as a control, however the protocol was ultimately harmonized globally to use a parallel sham group based
on US regulatory requirements," said Aniz Girach, MD, Chief Medical Officer of ProQR Therapeutics. "While we were disappointed
by the outcome of the primary analysis, we believe that these post-hoc analyses and the observation that approximately a third of the
patients benefited across multiple concordant endpoints in this trial, in combination with the high unmet need in LCA10, warrants a discussion
with the regulators."
Data from the Illuminate
trial will be presented at the upcoming Seventh Annual Retinal Cell and Gene Therapy Innovation Summit, April 29, 2022, and the Association
for Research in Vision and Ophthalmology (ARVO) Annual Meeting, May 1-4, 2022.
The Company will implement
the following portfolio prioritization and restructuring initiatives with the aim to reduce expenses:
These efforts are expected
to extend ProQR's cash runway into 2025.
RNA editing platform technology
The Company will accelerate
the development of its Axiomer RNA editing platform and pipeline activities and expand into areas beyond the eye, including
initially liver and CNS, which have strong alignment with ProQR's oligonucleotide delivery approaches.
In parallel, ProQR will
continue to execute on its partnership with Lilly and selectively enter into additional partnerships designed to advance and capture
the full potential value of the platform. Since the Company discovered its RNA editing technology in 2014, it has established a leading
IP estate in the ADAR editing space, a first industry partnership, and with its broad applicability the platform has significant further
ProQR will present further
non-clinical data for Axiomer and announce its internal development targets in H2 2022.
our strategy on accelerating our Axiomer RNA-base editing platform technology, and a select pipeline of RNA therapies
for inherited retinal diseases as we remain committed to developing RNA therapies for patients with high unmet need" said Daniel
A. de Boer, Founder and CEO of ProQR Therapeutics. "ProQR has a strong cash position with runway into 2025, and we look forward
to continued progress with the business, including providing an update following our discussions in Q3 with the EMA and FDA, and sharing
details of our development plans for Axiomer in the second half of 2022."
De Boer continued, "These
have been extremely difficult decisions to make as we position the business to drive long-term growth and value. I want to thank the
employees separating from ProQR for their significant contributions toward our mission. I also want to acknowledge the disappointment
that many in the eye disease community may feel today, particularly individuals and families living with autosomal dominant retinitis
pigmentosa and Fuchs endothelial corneal dystrophy as we wind down our programs for these indications."
in the promise of RNA therapies, the Company's pioneering efforts in this field, and ProQR employees," said Dinko Valerio,
co-founder and Chairman of ProQR's Supervisory Board. "These are the right steps to take to offer the best opportunity to
create long-term value for all of our stakeholders, including our shareholders whom we thank for their support, and the communities we
Company management will
host a call today, April 13, 2022, at 8:00am EDT to discuss this announcement. The live and archived webcast of the presentation will
be accessible through this webcast link, or through the Events page of the Company's website. The dial-in details for the call
are +1 631-510-7495 (US) and +31 (0) 20 714 3545 (NL), conference ID: 6487386. The archived webcast will be available for approximately
30 days following the presentation date.
About Leber Congenital
Amaurosis 10 (LCA10)
Leber congenital amaurosis
(LCA) is the most common cause of blindness due to genetic disease in children. It consists of a group of diseases of which LCA10 is
the most frequent and one of the most severe forms. LCA10 is caused by mutations in the CEP290 gene, of which the c.2991+1655A>G
(p.Cys998X) mutation has the highest prevalence. 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 that treat the underlying cause of the disease. Approximately 2,000 people
in the Western world have LCA10 because of this mutation.
is an investigational RNA therapy designed to restore vision in Leber congenital amaurosis 10 due to the c.2991+1655A>G mutation (p.Cys998X)
in the CEP290 gene. The mutation leads to aberrant splicing of the mRNA and non-functional CEP290 protein. Sepofarsen is designed
to enable normal splicing, resulting in restoration of normal (wild type) CEP290 mRNA and subsequent production of functional
CEP290 protein. Sepofarsen 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 and rare pediatric disease designation from
the FDA as well as access to the PRIME scheme by the EMA.
About Usher syndrome
type 2a and retinitis pigmentosa
Usher syndrome is the
leading cause of combined deafness and blindness. People with Usher syndrome type 2a are usually born with hearing loss and start to
have progressive vision loss during adulthood. The vision loss can also occur without hearing loss in a disease called non-syndromic
retinitis pigmentosa. Usher syndrome type 2a and non-syndromic retinitis pigmentosa can be caused by mutations in the USH2A gene.
To date, there are no pharmaceutical treatments approved or in clinical development that treat the vision loss associated with mutations
Ultevursen (formerly
QR-421a) is a first-in-class investigational RNA therapy designed to address the underlying cause of vision loss in Usher syndrome type
2a and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. QR-421a is designed to restore
functional usherin protein by using an exon skipping approach with the aim to stop or reverse vision loss in patients. Ultevursen is
intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the US and the
European Union and received fast-track and rare pediatric disease designations from the FDA.
is pioneering a next-generation RNA technology called Axiomer , which could potentially yield a new class of medicines
for genetic diseases. Axiomer "Editing Oligonucleotides", or EONs, mediate single nucleotide changes
to RNA in a highly specific and targeted way using molecular machinery that is present in human cells. The Axiomer EONs
are designed to recruit an endogenously expressed RNA editing system called ADAR, which can direct the change of an Adenosine (A) to
an Inosine (I) in the RNA - an Inosine is translated as a Guanosine (G).
ProQR Therapeutics is
dedicated to changing lives through the creation of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology
called Axiomer , which uses a cell's own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse
a mutation or modulate protein expression and could potentially yield a new class of medicines for genetic diseases. Based on our unique
proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.