- Substantial progress in 2019 with final data from Phase 1/2 trial of sepofarsen for Leber’s congenital amaurosis 10 showing rapid, significant and durable improvements in vision; Phase 2/3 pivotal trial Illuminate initiated with data expected in H1 2021
- Phase 1/2 Stellar trial initiated for QR-421a for Usher syndrome type 2A exon 13; on track to report first clinical data for QR-421a in late Q1 2020
- Initiated a first-in-human trial for the third inherited retinal disease program, QR-1123 for autosomal dominant retinitis pigmentosa
- €48.6 million net proceeds from public offering in 2019 extended cash runway into 2022
“We made significant progress in 2019 as we advanced our portfolio of investigational RNA therapies for patients that suffer from inherited retinal diseases and are in a strong position as we enter 2020,” said
Corporate Highlights and Business Update
Sepofarsen (QR-110) for Leber’s congenital amaurosis 10 (LCA10)
- Reported positive top-line results from the Phase 1/2 clinical trial. In the trial, sepofarsen was observed to be well tolerated with rapid, significant and durable improvements in vision maintained at month twelve. The target registration dose for the ongoing Phase 2/3 Illuminate trial showed a favorable benefit/risk profile in the Phase 1/2 trial.
- The findings from the Phase 1/2 trial support the design of the ongoing Phase 2/3 Illuminate trial that could be the sole registration trial for the program. Top-line data from Illuminate are expected during H1 2021.
- Received Rare Pediatric Disease designation from the
Food and Drug Administration(FDA).
- Granted access to the PRIority MEdicines (PRIME) program by the
European Medicines Agency(EMA).
- The Company expects to report updated data from the InSight extension study H2 2020, including data from contralateral eye treatment.
QR-421a for Usher syndrome type 2
- The Phase 1/2 Stellar trial of QR-421a in patients with Usher syndrome type 2 is ongoing and on track to deliver interim data in late Q1 2020.
- Received Rare Pediatric Disease designation and Fast Track designation from the FDA.
QR-1123 for autosomal dominant retinitis pigmentosa (adRP)
- The ongoing Phase 1/2 Aurora trial of QR-1123 in patients with adRP began enrolling patients in
December 2019and initial data from the study are expected in 2021.
- Received Orphan Drug designation and Fast Track designation from the FDA.
QR-504a for Fuchs Endothelial Corneal Dystrophy (FECD)
- The Company expects to advance QR-504a for FECD to clinical development in 2020. The most common genetic cause for FECD occurs in the TCF4 gene causing FECD type 3 (FECD3). The Phase 1 trial is planned to be an open label, single-dose, dose escalation, exploratory study to evaluate safety, tolerability, and molecular biomarker(s) in corneal endothelium following a single intravitreal injection in patients with FECD3 scheduled for corneal transplant.
- Earlier this month, ProQR announced its participation in the
Foundation Fighting Blindness“My Retina Tracker Program”, a collaborative, open access program providing no-cost genetic testing and genetic counseling for individuals in the U.S.with a clinical diagnosis of an IRD such as LCA and Usher syndrome.
October 2019, the Company closed an underwritten public offering of 9,090,909 ordinary shares at a price of $5.50per share, excluding full exercise of underwriters’ option to purchase 1,363,636 additional ordinary shares for total gross proceeds of $57.5 million. Net proceeds totaled approximately €48.6 million. With the addition of this capital ProQR’s operations are expected to be funded into 2022.
April 2019, the Company appointed to the Supervisory Board Bart Filius, Chief Operating Officer and Chief Financial Officer at Galapagos NV and Theresa Heggie, Senior Vice President, Head of Canada, Europe, Middle East and Africa at Alnylam Pharmaceuticals.
At December 31, 2019, ProQR held cash and cash equivalents of €112.0 million, compared to €105.6 million at December 31, 2018. The increase in cash was primarily from a public offering in October of which the net proceeds totaled €48.6 million. Net cash used in operating activities during the three month period and full year ended December 31, 2019 was €12.0 million and €44.0 million respectively, compared to €9.1 million and €28.5 million for the same period last year.
Research and development costs increased to €13.9 million for the quarter ended December 31, 2019 from €9.5 million for the same period in 2018. Research and development costs for the year ended December 31, 2019 were €46.5 million, compared to €29.5 million for the same period in 2018.
General and administrative costs decreased to €3.9 million for the quarter ended December 31, 2019 from €4.6 million for the same period in 2018. General and administrative costs for the year ended December 31, 2019 were €12.9 million, compared to €12.5 million for the same period in 2018.
Net loss for the three month period ended December 31, 2019 was €18.6 million or €0.39 per diluted share, compared to a €13.0 million loss or €0.33 per diluted share for the same period in 2018. Net loss for the year ended December 31, 2019 was €56.7 million or €1.38 per diluted share, compared to €37.1 million, or €1.08 per diluted share for the same period ended December 31, 2018. For further financial information for the period ended December 31, 2019, please refer to the financial statements at the end of this release.
2019 Annual Reports
The consolidated statement of financial position of ProQR Therapeutics N.V. as of December 31, 2019 and December 31, 2018, the consolidated statements of comprehensive loss for the years and the three month periods ended December 31, 2019 and 2018, the related consolidated statement of changes in equity for the years ended December 31, 2019 and 2018 and the consolidated statements of cash flows for years and three months periods ended December 31, 2019 and 2018 as presented in this press release are unaudited. ProQR Therapeutics N.V. will publish its 2019 Annual Report on Form 20-F and Statutory Annual Report later in Q1 2020. The reports will be published on our website at www.proqr.com.
About Leber’s Congenital Amaurosis 10 (LCA10)
Leber’s 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 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.
Sepofarsen (QR-110) is being evaluated in the pivotal Phase 2/3 Illuminate trial and 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 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
About Usher Syndrome Type 2
Usher syndrome is the leading cause of combined deafness and blindness. Patients with this syndrome generally progress to a stage in which they have very limited central vision and moderate to severe deafness. Usher syndrome type 2 is one of the most common forms of Usher syndrome and 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 Usher syndrome type 2.
QR-421a is being evaluated in the Phase 1/2 Stellar trial and is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of vision loss in Usher syndrome type 2 and non-syndromic retinitis pigmentosa (RP) 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
QR-1123 is being evaluated in the Phase 1/2 Aurora trial and is a first-in-class investigational RNA-based oligonucleotide 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 was in-licensed from Ionis Pharmaceuticals in 2018. 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) is a common inherited condition characterized by the dysfunction and degeneration of the corneal endothelium, a single cell layer of cells on the inside of the cornea. FECD is a common disorder; it is estimated that FECD affects more than 4% of individuals over the age of 40 in the
We are developing QR-504a as an RNA therapy for the treatment of FECD3. We plan to advance the QR-504a program into a first clinical trial in late-stage disease patients in 2020. QR-504a is designed to target the intronic TNRs in the TCF4 RNA. The aim is to reduce aggregation and the formation of RNA foci in order to normalize the RNA splicing patterns, and prevent or halt corneal degeneration in patients with FECD3.
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).
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 our pipeline of programs targeting inherited retinal dystrophies, 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 QR-504a and the clinical development and therapeutic potential thereof, statements regarding the timing of expected results from clinical trials and plans for seeking marketing approvals for our product candidates, 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
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Unaudited Condensed Consolidated Statement of Financial Position
|€ 1,000||€ 1,000|
|Cash and cash equivalents||111,950||105,580|
|Prepayments and other receivables||1,866||1,544|
|Social securities and other taxes||850||1,243|
|Total current assets||114,666||108,367|
|Property, plant and equipment||2,440||1,864|
|Investments in associates||429||—|
|Equity and liabilities|
|Equity attributable to owners of the Company||94,329||92,915|
|Current income tax liability||64||—|
|Social securities and other taxes||108||—|
|Other current liabilities||8,812||7,473|
|Total current liabilities||10,993||8,160|
|Total equity and liabilities||117,535||110,231|
Unaudited Condensed Consolidated Statement of Profit or Loss and OCI
(€ in thousands, except share and per share data)
|Three month period||Year|
|ended December 31,||ended December 31,|
|€ 1,000||€ 1,000||€ 1,000||€ 1,000|
|Research and development costs||(13,931)||(9,542)||(46,491)||(29,514)|
|General and administrative costs||(3,917)||(4,640)||(12,887)||(12,540)|
|Total operating costs||(17,848)||(14,182)||(59,378)||(42,054)|
|Finance income and expense||(937)||(128)||402||(792)|
|Results related to associates||(150)||—||429||—|
|Result before corporate income taxes||(18,511)||(12,977)||(56,614)||(37,085)|
|Result for the period||(18,579)||(12,977)||(56,746)||(37,086)|
|Other comprehensive income||(78)||(13)||43||(28)|
|Total comprehensive income (attributable to owners of the Company)||(18,657)||(12,990)||(56,703)||(37,114)|
|Result attributable to|
|Owners of the Company||(18,534)||(12,944)||(56,480)||(36,894)|
|Weighted average number of shares outstanding1||47,372,744||38,809,784||41,037,244||34,052,520|
|Earnings per share attributable to the equity holders of the Company (expressed in Euro per share)|
|Basic loss per share1||(0.39)||(0.33)||(1.38)||(1.08)|
|Diluted loss per share1||(0.39)||(0.33)||(1.38)||(1.08)|
- 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
|Attributable to owners of the Company|
|€ 1,000||€ 1,000||€ 1,000||€ 1,000||€ 1,000||€ 1,000||€ 1,000||€ 1,000|
| Balance at
|Result for the period||—||—||—||—||—||(36,894)||(36,894)||(192)||(37,086)|
|Other comprehensive income||—||—||—||—||(28)||—||(28)||—||(28)|
|Recognition of share-based payments||112,473||4||2,185||3,224||—||—||5,413||—||5,413|
|Issuance of ordinary shares||6,612,500||265||83,926||—||—||—||84,191||—||84,191|
|Share options lapsed||—||—||—||(97)||—||97||—||—||—|
|Share options exercised||226,098||—||870||(724)||—||724||870||—||870|
| Balance at
| Balance at
|Result for the period||—||—||—||—||—||(56,480)||(56,480)||(266)||(56,746)|
|Other comprehensive income||—||—||—||—||43||—||43||—||43|
|Recognition of share-based payments||371,306||15||3,145||5,948||—||—||9,108||—||9,108|
|Issuance of ordinary shares||10,454,545||418||48,132||—||—||—||48,550||—||48,550|
|Share options lapsed||—||—||—||(44)||—||44||—||—||—|
|Share options exercised||46,900||—||193||(133)||—||133||193||—||193|
| Balance at
Unaudited Condensed Consolidated Statement of Cash Flows
|Three month period||Year|
|€ 1,000||€ 1,000||€ 1,000||€ 1,000|
|Cash flows from operating activities|
|— Share-based compensation||4,494||3,168||9,108||5,413|
|— Financial income and expenses||937||128||(402)||792|
|— Results related to associates||150||—||(429)||—|
|— Net foreign exchange gain / (loss)||(79)||(13)||43||(28)|
|Changes in working capital||39||220||1,783||1,295|
|Cash used in operations||(12,529)||(9,208)||(44,591)||(28,622)|
|Corporate income tax paid||—||—||(64)||(1)|
|Net cash used in operating activities||(11,956)||(9,103)||(43,970)||(28,493)|
|Cash flow from investing activities|
|Purchases of property, plant and equipment||(239)||(27)||(580)||(312)|
|Net cash used in investing activities||(239)||(27)||(580)||(312)|
|Cash flow from financing activities|
|Proceeds from issuance of shares, net of transaction costs||48,550||(104)||48,550||84,191|
|Proceeds from exercise of share options||27||210||193||870|
|Proceeds from borrowings||2,027||163||2,027||264|
|Proceeds from convertible loans||—||702||690||1,132|
|Repayment of lease liability||(400)||—||(1,261)||—|
|Net cash (used in)/generated by financing activities||50,204||971||50,199||86,457|
|Net increase/(decrease) in cash and cash equivalents||38,009||(8,159)||5,649||57,652|
|Currency effect cash and cash equivalents||(851)||23||721||(171)|
|Cash and cash equivalents, at beginning of the period||74,792||113,716||105,580||48,099|
|Cash and cash equivalents at the end of the period||111,950||105,580||111,950||105,580|
Source: ProQR Therapeutics N.V.