OREANDA-NEWS. ProQR Therapeutics N.V. (Nasdaq:PRQR), a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe orphan diseases such as cystic fibrosis (CF) and Leber's congenital amaurosis Type 10 (LCA10), today announced results for the second quarter of 2016.

“We continue to make good progress with our three different development programs, all RNA oligonucleotides for serious genetic diseases. For QR-010 for patients with CF due to the ?F508 mutation, we will present top-level results from clinical proof-of-concept study, PQ-010-002 later this year during the North American Cystic Fibrosis Conference (NACFC)", said Daniel de Boer, Chief Executive Officer of ProQR. “For QR-110 for patients with LCA10, we presented strong pre-clinical proof-of-concept data at the Association for Research in Vision and Ophthalmology (ARVO) conference. We plan to move this program towards the clinic this year. For QR-313 for dystrophic epidermolysis bullosa (DEB) patients due to mutations in Exon 73, we continue to strengthen the pre-clinical proof-of-concept in important clinically relevant models. In addition to our three molecules in development, we are strengthening our pipeline of RNA oligonucleotides for severe genetic diseases through our innovation unit.”

Financial Highlights

At June 30, 2016, ProQR held cash and cash equivalents of €76.3 million, compared to €85.5 million at March 31, 2016. Net cash used in operating activities during the three month period ended June 30, 2016 was €8.3 million, compared to €5.9 million for the same period last year.

Research and development costs increased to €8.6 million for the quarter ended June 30, 2016 from €5.4 million for the same period last year and comprised of allocated employee costs including share-based payments, the costs of materials and laboratory consumables, outsourced activities, license and intellectual property costs and other allocated costs. The increase in expenses was primarily due to the advancement of our pipeline, which included clinical development of QR-010, preclinical development of QR-110 and progress of our innovation programs such as QR-313 for epidermolysis bullosa, which moved into pre-clinical development this quarter and other pipeline programs.

General and administrative costs increased to €2.6 million for the quarter ended June 30, 2016 from €1.8 million for the same period last year, in line with the growth of our organization.

Net result for the three month period ended June 30, 2016 was a €10.0 million loss or €0.43 per share, compared to a €8.6 million loss or €0.37 per share for the same period last year. For further financial information for the period ending June 30, 2016, please refer to the financial statements appearing at the end of this release.

Corporate Highlights

  • QR-010 for patients with CF due to the ?F508 mutation is being studied in two global clinical trials. PQ-010-002 is a proof-of-concept study evaluating the effect of QR-010 on an important measurement of CFTR function, the nasal potential difference (NPD). PQ-010-002 is an open label 28-day study of topical exposure of QR-010 in 16 CF patients, 8 homozygous (carrying two copies) for the ?F508 mutation and 8 compound heterozygous (one copy of the ?F508 plus one other CF disease causing mutation) with the option to enroll an additional 16. Top-line data from the first 16 patients is expected to be presented during the NACFC, Orlando, Florida, October 27 - 29, 2016. The other study, PQ-010-001 is a Phase 1b randomized, double-blind, placebo-controlled, dose-escalation 28-day study. The safety, tolerability and pharmacokinetics of single and multiple ascending doses of inhaled QR-010 will be evaluated in 64 CF patients carrying two copies (homozygotes) of the ?F508 mutation. In addition, exploratory efficacy endpoints in this study include sweat chloride, weight gain, CFQ-R Respiratory Symptom Score and lung function, measured by FEV1. This study is not powered for statistical significance on any of these exploratory endpoints. The company expects to present preliminary safety data from the single ascending dose cohorts at the same time as results for study PQ-010-002.
  • At the 2016 European Cystic Fibrosis Conference (ECFS, June 10 2016) the company presented additional pre-clinical data for QR-010 in a presentation titled “QR-010 penetrates the CF-like mucus barrier in vitro and in vivo.” QR-010 was shown to diffuse rapidly through CF-like mucus layers in in vitro and in vivo models. QR-010 was also shown to be stable in CF sputum, in the presence of CF lung bacteria and in the presence of clinically relevant levels of CF standard-of-care.
  • QR-110, for patients with LCA10 due to the p.Cys998X mutation received orphan drug designation (ODD) from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). ODD in the U.S. and the European Union confers a special status for investigational drugs that are being developed for rare diseases.
  • ProQR strengthened its Supervisory Board with the appointment of James Shannon, MD in June 2016. James was the former Chief Medical Officer at GlaxoSmithKline and Global Head of Pharma Development at Novartis. We believe that James’ broad knowledge and expertise in drug development and pharma will be of significant value to the Supervisory Board.
  • The company moved headquarters to Zernikedreef 9, 2333 CK Leiden, the Netherlands.

Subsequent events

  • The company has moved its product candidate for the third program, QR-313 (previously named QRX-313) into pre-clinical development for the treatment of dystrophic epidermolysis bullosa (DEB). QR-313 is an RNA oligonucleotide designed to induce the exclusion of a part of the RNA (exon skipping) that contains a disease causing mutation with the aim to restore functional COL7a1 protein and with that the anchoring fibrils that bind the layers of skin together. QR-313 is the second program to be added to the pipeline behind the CF and LCA10 programs from ProQR’s internal innovation (discovery) unit.
  • QR-010 received a Fast Track designation by the US Food and Drug Administration (FDA). Drugs that are under development for serious conditions and have the potential to fulfill an unmet medical need can receive this designation. It was established with the intention to bring promising drugs to patients sooner by facilitating the development with more frequent FDA interactions and expediting the review process.

About ProQR

ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe orphan diseases such as cystic fibrosis and Leber’s congenital amaurosis. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind. Since 2012.

About QR-010

QR-010 is a first-in-class RNA-based oligonucleotide designed to address the underlying cause of the disease by repairing the mRNA in CF patients that have the DF508 mutation. The DF508 mutation is a deletion of three of the coding base pairs, or nucleotides, in the CFTR gene, which results in the production of a misfolded CFTR protein that does not function normally. QR-010 is designed to bind to the defective CFTR mRNA and restore CFTR function. QR-010 is designed to be self-administered via an optimized eFlow® Nebulizer (PARI Pharma GmbH). eFlow® is a small, handheld aerosol delivery device which nebulizes QR-010 into a mist inhaled directly into the lungs. We believe this route of administration could allow maximum exposure of QR-010 to the primary target organ, the lung, as well as significant exposure to other affected organs through systemic absorption into the blood. QR-010 has been granted orphan drug designation in the United States and the European Union. The QR-010 project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633545.

About QR-110

QR-110 is a first-in-class RNA-based oligonucleotide designed to address the underlying cause of Leber’s congenital amaurosis Type 10 due to the p.Cys998X 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 wild-type CEP290 mRNA leading to the production of wild-type 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.

About QR-313

QR-313 is a first-in-class RNA-based oligonucleotide designed to address the underlying cause of dystrophic epidermolysis bullosa (DEB) due to mutations in exon 73 of the COL7A1 gene. Mutations in this exon can cause loss of functional collagen type VII (C7) protein. Absence of C7 results in the loss of anchoring fibrils that normally link the dermal and epidermal layers of the skin together. QR-313 is designed to exclude exon 73 from the mRNA (exon skipping) and produce truncated but functional C7 protein and thereby restores functionality of the anchoring fibrils.


Unaudited Condensed Consolidated Statement of Financial Position
    June 30,    December 31, 
    2016   2015
    € 1,000   € 1,000
Current assets        
Cash and cash equivalents   76,311   94,865
Prepayments and other receivables   3,185   1,948
Social securities and other taxes   651   956
Total current assets   80,147   97,769
Property, plant and equipment   3,670   2,199
Intangible assets   116   141
Total assets   83,933   100,109
Liabilities and shareholders' equity        
Current liabilities        
Finance lease liabilities   --   15
Trade payables   1,038   885
Social securities and other taxes   303   235
Pension premiums   43   16
Deferred income   --   144
Other current liabilities   6,349   4,191
Total current liabilities   7,733   5,486
Borrowings   5,267   4,824
Total liabilities   13,000   10,310
Shareholders' equity        
Shareholders' equity   70,933   89,799
Total liabilities and shareholders' equity   83,933   100,109
Unaudited Condensed Consolidated Statement of Profit or Loss and OCI
(€ in thousands, except share and per share data)
      Three month period       Six month period  
      ended June 30,       ended June 30,  
      2016       2015       2016       2015  
      € 1,000       € 1,000       € 1,000       € 1,000  
Other income     589       748       1,278       1,086  
Research and development costs     (8,606 )     (5,427 )     (15,504 )     (10,907 )
General and administrative costs     (2,615 )     (1,777 )     (5,217 )     (3,380 )
Total operating costs       (11,221 )       (7,204 )       (20,721 )       (14,287 )
Operating result       (10,632 )       (6,456 )       (19,443 )       (13,201 )
Finance income and expense       673         (2,168 )     (714 )     4,812  
Result before corporate income taxes       (9,959 )       (8,624 )       (20,157 )       (8,389 )
Income taxes     --       --       --       --  
Net loss attributable to equity holders of the Company       (9,959 )       (8,624 )       (20,157 )       (8,389 )
Other comprehensive income     (5 )     --       0       --  
Total comprehensive loss (attributable to equity holders of the Company)       (9,964 )       (8,624 )       (20,157 )       (8,389 )
Share information                
Weighted average number of shares outstanding1     23,346,340       23,343,253       23,346,153       23,340,971  
Earnings per share attributable to the equity holders of the Company (expressed in Euro per share)                
Basic loss per share1       (0.43 )       (0.37 )     (0.86 )     (0.36 )
Diluted loss per share1       (0.43 )       (0.37 )     (0.86 )     (0.36 )
1.  For this period presented in these financial statements, the potential exercise of share options is not included in the diluted earnings per share calculation as the Company was loss-making in all periods. Due to the anti-dilutive nature of the outstanding options, basic and diluted earnings per share are equal in this period.
Unaudited Condensed Consolidated Statement of Changes in Equity
    Number of
        € 1,000   € 1,000   € 1,000   € 1,000     € 1,000       € 1,000  
Balance at January 1, 2015   23,338,154   934   123,581   687   --       (15,798 )     109,404  
Net loss   --   --   --   --   --     (8,389 )     (8,389 )
Recognition of share-based payments   --   --   --   619   --   --     619  
Share options exercised   5,217   0   6   --   --   --     6  
Balance at June 30, 2015   23,343,371   934   123,587   1,306   --       (24,187 )     101,640  
Balance at January 1, 2016   23,345,965   934   123,595   1,899   1       (36,630 )       89,799  
Net loss   --   --   --   --   --     (20,157 )     (20,157 )
Other comprehensive income   --   --   --   --   0   --     0  
Recognition of share-based payments   --   --   --   1,289   --   --     1,289  
Share options exercised   891   0   2   --   --   --     2  
Balance at June 30, 2016   23,346,856   934   123,597   3,188   1       (56,787 )       70,933