ProQR Announces Third Quarter 2021 Operating and Financial Results

  • Top-line data from pivotal Phase 2/3 Illuminate trial of sepofarsen for CEP290-mediated LCA10 anticipated late Q1/early Q2 2022
  • Five-target collaboration with Lilly highlights significant potential of ProQR’s Axiomer® RNA base-editing platform and strengthens financial position with $50 million in upfront and equity and up to $1.25 billion in milestones
  • QR-421a Phase 2/3 Sirius and Celeste trials in Usher syndrome and retinitis pigmentosa on track to start by year end 2021
  • Company to host an “Analyst Event” on November 18, 2021 to highlight clinical stage pipeline programs and Axiomer® RNA editing platform

 LEIDEN, Netherlands & CAMBRIDGE, Mass., Nov. 04, 2021 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq: PRQR) (the “Company”), a company dedicated to changing lives through the creation of transformative RNA therapies for genetic eye diseases, today reported its financial and operating results for the third quarter ended September 30, 2021, and provided a business update.

“In the third quarter we made significant progress across our pipeline and platform to develop medicines for patients in need. We continue to be on track for the readout of the sepofarsen Illuminate trial in the first half of next year and are narrowing our guidance for this to a late Q1/early Q2 timeframe. Other significant milestones achieved in Q3, include the partnership we entered into with Lilly around our Axiomer RNA base-editing platform and the appointment of Theresa Heggie as our Chief Commercial Officer,” said Daniel A. de Boer, Founder and CEO of ProQR. “Theresa is a seasoned leader with deep rare disease experience, including the launch of multiple products. Her expertise further strengthens our team and supports our commitment to bringing our pipeline of therapies to patients with genetic eye diseases.”

De Boer continued, “More broadly, our pipeline programs are progressing as anticipated. We expect to start two Phase 2/3 trials of QR-421a in Usher syndrome and nsRP before the end of the year. In Q4 we will share an update from our QR-1123 program in adRP and our QR-504a Fuchs Focus trial is open for enrollment, representing our first corneal program.”

Business Operations and Program Updates

Sepofarsen for CEP290-mediated Leber congenital amaurosis 10 (LCA10):

  • The Company expects to report top-line results from the Phase 2/3 Illuminate trial in late Q1/early Q2 2022.  The Illuminate trial completed enrollment in January 2021 following randomization of 36 patients aged 8 years or older to receive either sepofarsen at the target registration dose, a low dose, or sham treatment. The primary endpoint for Illuminate is mean change from baseline in best-corrected visual acuity (BCVA) at Month 12.
  • Enrollment is ongoing in the Phase 2/3 Brighten trial of sepofarsen in LCA10. The primary objective of this study is to evaluate safety and tolerability of sepofarsen in patients under 8 years of age.
  • The Company will share updated data from the Phase 1/2 InSight extension study later this month at the Analyst Event scheduled for November 18.

QR-421a for Usher syndrome and non-syndromic retinitis pigmentosa (nsRP):         

  • Based on the findings from the Phase 1/2 Stellar trial, the Company is advancing QR-421a into two pivotal Phase 2/3 trials – Sirius in advanced patients, and Celeste in early-moderate patients – by year end. Each trial could potentially serve as the sole registration trial.
  • The Company has begun enrolling eligible patients from the Phase 1/2 Stellar trial in the open-label extension study Helia, which will include multiple dose treatments for both eyes.
  • In September, findings from the Phase 1/2 Stellar trial were presented in an oral presentation at the European Society of Retina Specialists (EURETINA) virtual congress.

Earlier-stage clinical pipeline:

  • The Company anticipates sharing initial findings from the Phase 1 Aurora trial of QR-1123 for autosomal dominant retinitis pigmentosa (adRP) in Q4. Aurora is a first-in-human clinical study, designed to evaluate safety and tolerability. The Company will be looking for evidence of target engagement and/or disease modification to inform the next steps in development.
  • The Fuchs Focus study of QR-504a for Fuchs Endothelial Corneal Dystrophy (FECD) is currently open for enrollment. This study is evaluating safety, tolerability, and molecular biomarker(s), i.e., target engagement, in the corneal endothelium following a single intravitreal injection of QR-504a in patients with FECD who are scheduled for corneal transplant with concurrent lens replacement.

Business updates:

  • In September, Eli Lilly and Company (Lilly) and ProQR entered into a licensing and research collaboration related to ProQR’s proprietary Axiomer RNA base-editing platform. Under the terms of the agreement, ProQR will receive $50 million consisting of an upfront payment of $20 million, as well as an equity investment in its ordinary shares of $30 million. ProQR is eligible to receive up to approximately $1.25 billion in milestones, plus royalties.
  • In October, Theresa Heggie was appointed Chief Commercial Officer (CCO). As CCO, Ms. Heggie is responsible for overseeing the Company’s commercial strategy and global commercial operations. She brings extensive global rare disease commercialization experience having previously served in senior commercial and operating roles at both Alnylam Pharmaceuticals and Shire.

Upcoming Analyst Event:

  • ProQR will host an Analyst Event for the investment community via webcast on Thursday, November 18, from 12-2pm ET. ProQR leadership will highlight key advancements from its clinical-stage pipeline, including data from the Phase 1/2 Insight extension study of sepofarsen. The Company will also highlight the sepofarsen program more broadly, recapping data from the program to date, sharing the perspective of a patient from the Phase 1/2 trial, and reviewing the Phase 2/3 Illuminate trial design and assumptions. The QR-421a, QR-1123, QR-504a, and RNA editing programs will also be featured. The live and archived webcast will be accessible through this webcast link, or through the Events page of the Company’s website.

Financial Highlights

At September 30, 2021, ProQR held cash and cash equivalents of €156.1 million, compared to €75.8 million at December 31, 2020. Net cash used in operating activities during the three-month period ended September 30, 2021 was €8.1 million, compared to €9.8 million for the same period last year. After September 30, 2021, ProQR received an upfront payment of $20 million from Lilly related to the Axiomer licensing and research collaboration.

Research and development costs were €11.1 million for the quarter ended September 30, 2021, compared to €8.3 million for the same period last year.

General and administrative costs were €4.6 million for the quarter ended September 30, 2021 compared to €2.8 million for the same period last year.

Net loss for the three-month period ended September 30, 2021 was €15.1 million or €0.22 per share, compared to a €13.2 million loss or €0.26 per share for the same period last year.

For further financial information for the period ended September 30, 2021, please refer to the financial statements appearing at the end of this release.

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 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.

About Sepofarsen

Sepofarsen (QR-110) is being evaluated in the pivotal Phase 2/3 Illuminate trial and is a first-in-class investigational RNA therapy designed to address the underlying cause of Leber 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 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 Non-Syndromic Retinitis Pigmentosa (nsRP)

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 in USH2A.

About QR-421a

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. QR-421a 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.

About Autosomal Dominant Retinitis Pigmentosa (adRP)

Autosomal dominant retinitis pigmentosa, or adRP, is a severe and rare genetic disease that causes progressive problems in night vision during childhood, leading to visual field loss and frequently resulting in blindness in mid adulthood. In the United States, the most prevalent mutation associated with adRP is the P23H point mutation (also known as the c.68C>A mutation) in the rhodopsin (RHO) gene and affects approximately 2,500 people. This mutation causes misfolding of the rhodopsin protein that becomes toxic to the photoreceptor cells and at the same time diminishes the function of the wild type allele. Over time this results in cell death and progressive vision loss. There are currently no therapies approved or in clinical development for P23H adRP. A natural history study in patients with P23H adRP has been conducted.

About QR-1123

QR-1123 is being evaluated in the Phase 1/2 Aurora trial and is a first-in-class investigational RNA therapy designed to treat adRP due to the P23H mutation in the RHO gene. QR-1123 was discovered and developed by Ionis Pharmaceuticals using Ionis’ proprietary antisense technology. The therapy aims to inhibit the formation of the mutated toxic version of the rhodopsin protein by specifically binding the mutated RHO mRNA. Binding of QR-1123 causes allele specific knockdown of the mutant mRNA by a mechanism called RNase H mediated cleavage without affecting the normal RHO mRNA. QR-1123 is intended to be administered through intravitreal injections in the eye. QR-1123 has been granted Orphan Drug designation in the United States and received Fast Track designation from the FDA.

About Fuchs Endothelial Corneal Dystrophy (FECD)

Fuchs endothelial corneal dystrophy (FECD) type 3 is a common genetic disease that leads to progressive degeneration of the corneal endothelium resulting in corneal edema, scarring and vision loss. Blisters on the cornea are a major cause of pain in patients with advanced FECD. Currently there are no treatment options available to stop or slow down FECD and disease management is aimed to reduce symptoms. The only effective therapy for late-stage FECD is corneal transplantation. The availability of donors, risk of rejection, and the inherent risk of such surgeries are some of the limitations of this option. FECD is a common disorder affecting more than 4% of people over the age of 40 in the United States, with similar numbers reported for other parts of the World. Trinucleotide repeat (TNR) expansion mutations in the TCF4 gene are a common cause of FECD. In people of European descent, around 75% of FECD patients have TNR expansions in TCF4.

About QR-504a

QR-504a is a first-in-class investigational RNA therapy designed to address the underlying cause of Fuchs endothelial corneal dystrophy (FECD) due to trinucleotide repeat (TNR) expansion mutations in the TCF4 gene. The TNR expansions cause the TCF4 RNA to aggregate in the corneal endothelial cells forming the characteristic nuclear RNA foci and eventually resulting in FECD. QR-504a is designed to target the TNRs in the TCF4 RNA. The aim is to reduce aggregation and the formation of RNA foci to prevent or stop corneal degeneration in patients with FECD. QR-504a is intended to be administered through intravitreal injections in the eye.

About Axiomer and Trident

ProQR 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).

Our TRIDENT™ RNA pseudouridylation platform enables the suppression of nonsense mutations and premature stop codons (PTC) that cause human genetic diseases. Since all premature stop codons contain uridine, pseudouridylation of that uridine converts those nonsense codons into sense codons. TRIDENT technology harnesses endogenously expressed pseudouridylation machinery to guide RNAs to inhibit nonsense mRNA-mediated decay (NMD) in a sequence-specific manner and promote PTC readthrough. The TRIDENT technology has the potential to be applied in approximately 11% of all genetic mutations.

About ProQR

ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies for the treatment of severe genetic rare diseases such as Leber congenital amaurosis 10, Usher syndrome and retinitis pigmentosa. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.

Learn more about ProQR at


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. Such forward-looking statements include, but are not limited to, statements regarding sepofarsen (QR-110) and the clinical development and the therapeutic potential thereof, statements regarding QR-421a and the clinical development and the therapeutic potential thereof, statements regarding QR-1123 and the clinical development and therapeutic potential thereof, statements regarding the QR-504a and the clinical development and therapeutic potential thereof, statements regarding our pipeline of programs targeting inherited retinal dystrophies, including timing of commencing clinical trials and enrollment of patients therein, our other programs and business operations (including Axiomer and Trident), the expected impact of the COVID-19 on our business operations, including our research and development plans and timelines and the supply chain for our clinical and development programs, statements regarding the collaboration with Lilly and the intended benefits thereof, including the upfront payment, equity investment, and milestone and royalty payments from commercial product sales, if any, from the products covered by the collaboration, statements regarding information in the upcoming analyst event and our financial position and cash runway. 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. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, 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. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted by the COVID-19 pandemic; the likelihood of our clinical programs being executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers to supply materials for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in research and development; our ability to maintain and service our loan facility with Pontifax and Kreos; general business, operational, financial and accounting risks; and risks related to litigation and disputes with third parties. 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.

Cautionary Note on Future Updates

The statements contained in this press release reflect our current views with respect to future events, which may change significantly as the global consequences of the COVID-19 pandemic rapidly develop. Accordingly, we do not undertake and specifically disclaim any obligation to update any forward-looking statements.

ProQR Therapeutics N.V.

Investor Contact:
Sarah Kiely
ProQR Therapeutics N.V.
T: +1 617 599 6228
Hans Vitzthum
LifeSci Advisors
T: +1 617 430 7578

Media Contact:
Cherilyn Cecchini, MD
LifeSci Communications
T: +1 646 876 5196

Unaudited Condensed Consolidated Statement of Financial Position

    September 30,    December 31, 
    2021   2020
    € 1,000   € 1,000
Current assets          
Cash and cash equivalents   156,141   75,838
Prepayments and other receivables   20,407   3,762
Social securities and other taxes   511   421
Total current assets   177,059   80,021
Property, plant and equipment   17,559   18,601
Investments in associates   92   107
Investments in financial assets   621  
Total assets   195,331   98,729
Equity and liabilities          
Equity attributable to owners of the Company   128,606   57,091
Non-controlling interests   (585)   (545)
Total equity   128,021   56,546
Current liabilities          
Borrowings   1,791   1,135
Lease liabilities   1,395   1,260
Derivative financial instruments   2,263   839
Trade payables   894   221
Current income tax liability    
Social securities and other taxes   546   22
Pension premiums     6
Deferred income   19,987   700
Other current liabilities   7,812   6,118
Total current liabilities   34,688   10,301
Borrowings   17,513   16,189
Lease liabilities   15,109   15,693
Total liabilities   67,310   42,183
Total equity and liabilities   195,331   98,729

Unaudited Condensed Consolidated Statement of Profit or Loss and OCI
(€ in thousands, except share and per share data)

    Three month period   Nine month period
    ended September 30,    ended September 30, 
       2021   2020   2021   2020
    € 1,000   € 1,000   € 1,000   € 1,000
Revenue   872     1,115  
Other income   286   251   838   9,188
Research and development costs   (11,124)   (8,304)   (29,764)   (29,716)
General and administrative costs   (4,591)   (2,809)   (12,052)   (10,173)
Total operating costs   (15,715)   (11,113)   (41,816)   (39,889)
Operating result   (14,557)   (10,862)   (39,863)   (30,701)
Finance income and expense   266   (1,863)   (2,491)   (2,024)
Results related to associates   (132)   (84)   (239)   (270)
Gain on recognition of financial asset       621  
Results related to financial liabilities measured at fair value through profit or loss   (611)   (305)   (1,373)   (305)
Result before corporate income taxes   (15,034)   (13,114)   (43,345)   (33,300)
Income taxes   (35)   (75)   (95)   (86)
Result for the period   (15,069)   (13,189)   (43,440)   (33,386)
Other comprehensive income (foreign exchange differences on foreign operation)   206   (255)   461   (134)
Total comprehensive income   (14,863)   (13,444)   (42,979)   (33,520)
Result attributable to                    
Owners of the Company   (15,047)   (13,181)   (43,400)   (33,348)
Non-controlling interests   (22)   (8)   (40)   (38)
    (15,069)   (13,189)   (43,440)   (33,386)
Total comprehensive income attributable to                
Owners of the Company   (14,841)   (13,436)   (42,939)   (33,482)
Non-controlling interests   (22)   (8)   (40)   (38)
    (14,863)   (13,444)   (42,979)   (33,520)
Share information                    
Weighted average number of shares outstanding1   68,263,034   50,143,262   61,804,367   50,017,990
Earnings per share attributable to owners of the Company (Euro per share)                
Basic loss per share1   (0.22)   (0.26)   (0.70)   (0.67)
Diluted loss per share1   (0.22)   (0.26)   (0.70)   (0.67)
  1. For these periods the potential exercise of share options is not included in the diluted earnings per share as the Company was loss-making. Due to the anti-dilutive nature of the outstanding options, basic and diluted earnings per share are equal.

Unaudited Condensed Consolidated Statement of Changes in Equity

    Attributable to owners of the Company        
of shares
   Equity settled
premium on
   Total    Non-
         € 1,000   € 1,000   € 1,000   € 1,000   € 1,000   € 1,000   € 1,000   € 1,000   € 1,000
Balance at January 1, 2020   53,975,838   2,159   287,214   16,551     151   (211,746)   94,329   (496)   93,833
Result for the period               (33,348)   (33,348)   (38)   (33,386)
Other comprehensive income             (134)     (134)     (134)
Recognition of share-based payments     2   283   6,218         6,503     6,503
Issuance of ordinary shares   100,902   2   270           272     272
Treasury shares transferred   (299,615)                  
Recognition of equity component of convertible loan           280       280     280
Share options lapsed         (63)       63      
Share options exercised   299,615     724   (466)       466   724     724
Balance at September 30, 2020   54,076,740   2,163   288,491   22,240   280   17   (244,565)   68,626   (534)   68,092
Balance at January 1, 2021   54,131,553   2,165   288,757   23,825   280   (189)   (257,747)   57,091   (545)   56,546
Result for the period               (43,400)   (43,400)   (40)   (43,440)
Other comprehensive income             461     461     461
Recognition of share-based payments   112,657   5   382   4,435         4,822     4,822
Issuance of ordinary shares   20,498,451   820   107,657           108,477     108,477
Treasury shares transferred   (217,933)                  
Share options lapsed         (391)       391      
Share options exercised   338,653   5   1,150   (821)       821   1,155     1,155
Balance at September 30, 2021   74,863,381   2,995   397,946   27,048   280   272   (299,935)   128,606   (585)   128,021

Unaudited Condensed Consolidated Statement of Cash Flows

    Three month period    Nine month period
    ended September 30,    ended September 30, 
       2021   2020   2021   2020
    € 1,000   € 1,000   € 1,000   € 1,000
Cash flows from operating activities                    
Net result   (15,069)   (13,189)   (43,440)   (33,386)
Adjustments for:                
— Depreciation   544   651   1,777   1,703
— Share-based compensation   1,716   1,676   4,435   6,348
— Other income         (8,423)
— Financial income and expenses   (266)   1,863   2,491   2,024
— Results related to associates   132   84   239   270
— Gain on recognition of financial asset       (621)  
— Results related to financial liabilities measured at fair value through profit or loss   611   305   1,373   305
— Net foreign exchange gain / (loss)   206   (255)   461   (134)
— Income tax expenses   35   75   95   86
Changes in working capital   4,630   (321)   5,197   (3,440)
Cash used in operations   (7,461)   (9,111)   (27,993)   (34,647)
Corporate income tax paid   (35)   (157)   (95)   (168)
Interest received     27   5   118
Interest paid   (561)   (569)   (1,714)   (607)
Net cash used in operating activities   (8,057)   (9,810)   (29,797)   (35,304)
Cash flow from investing activities                
Purchases of property, plant and equipment   (175)   (264)   (259)   (806)
Net cash used in investing activities   (175)   (264)   (259)   (806)
Cash flow from financing activities                    
Proceeds from issuance of shares, net of transaction costs   23,223     108,477  
Proceeds from exercise of share options   402   12   1,155   724
Proceeds from borrowings   284     853   579
Proceeds from convertible loans     13,477     13,542
Repayment of lease liability   (347)   (235)   (597)   (542)
Net cash generated by financing activities   23,562   13,254   109,888   14,303
Net decrease in cash and cash equivalents   15,330   3,180   79,832   (21,807)
Currency effect cash and cash equivalents   1,369   (1,474)   471   (1,296)
Cash and cash equivalents, at beginning of the period   139,442   87,141   75,838   111,950
Cash and cash equivalents at the end of the period   156,141   88,847   156,141   88,847



You might like this