GlobeNewswire Inc | Aug 5, 2021 07:00AM EDT

August 05, 2021

-- Top-line data from Phase 2/3 pivotalIlluminatetrial of sepofarsen for CEP290-mediated LCA10 on track for H1 2022 -- QR-421a pivotal Sirius and Celeste Phase 2/3 trials in Usher syndrome and retinitis pigmentosa expected to start by year end 2021 -- Initial clinical data from Phase 1/2 Aurora trial of QR-1123 for autosomal dominant retinitis pigmentosa expected in Q4 2021

LEIDEN, Netherlands & CAMBRIDGE, Mass., Aug. 05, 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 second quarter ended June 30, 2021, and provided a business update.

Across our pipeline, on the partnering front, and with our balance sheet, we have generated significant momentum in the first half of the year as we work to advance our therapies for patients with genetic eye disease, said Daniel A. de Boer, Founder and CEO of ProQR. We completed enrollment in the pivotal trial of sepofarsen, reported positive clinical data for QR-421a, formed a partnership with Yarrow Biotechnology, and strengthened our financial position with a public offering. During the second half of the year, we expect to share the first clinical data for QR-1123 for adRP focusing on safety and tolerability, start our pivotal trials of QR-421a in Usher syndrome and nsRP, and progress enrollment of our fourth pipeline program for a genetic eye disease, QR-504a for Fuchs endothelial corneal dystrophy.

Business Operations and Program Updates

Sepofarsen for Leber congenital amaurosis 10 (LCA10):

-- The Company expects to report top-line results from the pivotal Phase 2/3 Illuminate trial in H1 2022. The Illuminatetrial completed enrollment in January 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 forIlluminateis 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.

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

-- Based on the findings from the Phase 1/2 Stellar trial, the Company plans to advance QR-421a into two pivotal Phase 2/3 trials Sirius in advanced patients, and Celeste in early-moderate patient by year end, pending finalization of the study designs with Regulatory authorities. Each trial could potentially serve as the sole registration trial. -- In Q3, the Company expects to begin 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.

QR-1123 for autosomal dominant retinitis pigmentosa (adRP):

-- The Company has completed enrollment of the fifth single dose cohort of patients in the Phase 1/2 Aurora trial for adRP with initial clinical data (n=11) expected in Q4. Aurora is a first-in-human clinical study, designed to evaluate safety and tolerability. The Company will also be looking for evidence of target engagement and/or disease modification to inform the next steps in development.

QR-504a for Fuchs endothelial corneal dystrophy (FECD):

-- The Fuchs Focus study 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 approximately 10 patients with FECD who are scheduled for corneal transplant with concurrent lens replacement. -- ProQR anticipates reporting initial data from this trial in 2022.

Business updates:

-- In May, Yarrow Biotechnology, Inc., an RTW Investments, LP incubated company, licensed exclusive rights to ProQRs antisense oligonucleotide technology to develop and commercialize potential therapies for an undisclosed non-ophthalmic target. Under the terms of the agreement, ProQR is eligible to receive up to $115 million of upfront and milestone payments, plus single digit percentage royalties on the net sales of any resulting products during the royalty term. ProQR will also have the right to receive an undisclosed percentage of equity in the form of shares of common stock of Yarrow. -- In April, the Company closed an underwritten public offering with gross proceeds totaling approximately $103.5 million.

Financial Highlights

On June 30, 2021, ProQR held cash and cash equivalents of 139.4 million, compared to 75.8 million on December 31, 2020. Net cash used in operating activities during the three-month period ended June 30, 2021 was 10.0 million, compared to 10.5 million for the same period last year.

Research and development costs were 9.7 million for the quarter ended June 30, 2021 compared to 8.6 million for the same period last year.

General and administrative costs were 4.1 million for the quarter ended June 30, 2021 compared to 3.4 million for the quarter ended June 30, 2020.

Net loss for the three-month period ended June 30, 2021 was 15.8 million, or 0.24 per diluted share, compared to 4.1 million, or 0.08 per diluted share, for the same period last year. For further financial information for the period ending June 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 theUSH2Agene. 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 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 www.proqr.com.

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. 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, 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 RTW and Yarrow and the intended benefits thereof, including milestone and royalty payments from commercial product sales, if any, from the products covered by the collaboration and the issuance of equity in Yarrow to ProQR 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 6228skiely@proqr.com or Hans Vitzthum LifeSci Advisors T: +1 617 430 7578hans@lifesciadvisors.com

Media Contact: Cherilyn Cecchini, MD LifeSci Communications T: +1 646 876 5196ccecchini@lifescicomms.com

PROQR THERAPEUTICS N.V. Unaudited Condensed Consolidated Statement of Financial Position

June30, December31, 2021 2020 ?1,000 ?1,000Assets Current assets Cash and cash equivalents 139,442 75,838Prepayments and other receivables 3,761 3,762Social securities and other taxes 381 421 Total current assets 143,584 80,021 Property, plant and equipment 17,928 18,601Investments in associates 224 107Investments in financial assets 621 ? Total assets 162,357 98,729 Equity and liabilities Equity Equity attributable to owners of the Company 118,106 57,091Non-controlling interests (563) (545)Total equity 117,543 56,546 Current liabilities Borrowings 1,562 1,135Lease liabilities 1,383 1,260Derivative financial instruments 1,617 839Trade payables 276 221Current income tax liability ? ?Social securities and other taxes 127 22Pension premiums ? 6Deferred income 1,659 700Other current liabilities 5,750 6,118 Total current liabilities 12,374 10,301 Borrowings 16,972 16,189Lease liabilities 15,468 15,693 Total liabilities 44,814 42,183 Total equity and liabilities 162,357 98,729

PROQR THERAPEUTICS N.V. Unaudited Condensed Consolidated Statement of Profit or Loss and OCI

( in thousands, except share and per share data)

Threemonthperiod Sixmonthperiod endedJune30, endedJune30, 2021 2020 2021 2020 ?1,000 ?1,000 ?1,000 ?1,000Revenue 243 ? 243 ? Other income 411 8,674 552 8,937 Research and development (9,735) (8,587) (18,640) (21,412)costsGeneral and (4,122) (3,446) (7,461) (7,364)administrative costsTotal operating costs (13,857) (12,033) (26,101) (28,776) Operating result (13,203) (3,359) (25,306) (19,839)Finance income and (2,464) (697) (2,757) (161)expenseResults related to ? (52) (107) (186)associatesGain on recognition of ? ? 621 ?financial assetResults related tofinancial liabilities (33) ? (762) ?measured at fair valuethrough profit or loss Result before corporate (15,700) (4,108) (28,311) (20,186)income taxesIncome taxes (53) (11) (60) (11) Result for the period (15,753) (4,119) (28,371) (20,197)Other comprehensiveincome (foreign exchange (141) (135) 255 121differences on foreignoperation) Total comprehensive (15,894) (4,254) (28,116) (20,076)income Result attributable to Owners of the Company (15,746) (4,112) (28,353) (20,167)Non-controlling (7) (7) (18) (30)interests (15,753) (4,119) (28,371) (20,197)Total comprehensive income attributable toOwners of the Company (15,887) (4,247) (28,098) (20,046)Non-controlling (7) (7) (18) (30)interests (15,894) (4,254) (28,116) (20,076) Share information Weighted average number 66,147,153 50,021,194 58,521,508 49,963,614of shares outstanding^1 Earnings per shareattributable to owners of the Company (Euro pershare)Basic loss per share^1 (0.24) (0.08) (0.48) (0.40)Diluted loss per share^1 (0.24) (0.08) (0.48) (0.40)

-- 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.



PROQR THERAPEUTICS N.V. Unaudited Condensed Consolidated Statement of Changes in Equity

AttributabletoownersoftheCompany Equitysettled Option Non- Number Share Share Employee premiumon Translation Accumulated Total controlling Total of shares Capital Premium Benefit convertible Reserve Deficit interests Equity Reserve loan ?1,000 ?1,000 ?1,000 ?1,000 ?1,000 ?1,000 ?1,000 ?1,000 ?1,000Balance atJanuary 1, 53,975,838 2,159 287,214 16,551 ? 151 (211,746) 94,329 (496) 93,8332020Result for ? ? ? ? ? ? (20,167) (20,167) (30) (20,197)the periodOthercomprehensive ? ? ? ? ? 121 ? 121 ? 121incomeRecognitionof ? 2 283 4,542 ? ? ? 4,827 ? 4,827share-basedpaymentsIssuance ofordinary 100,902 2 270 ? ? ? ? 272 ? 272sharesTreasuryshares (296,122) ? ? ? ? ? ? ? ? ?transferredShare options ? ? ? (60) ? ? 60 ? ? ?lapsedShare options 296,122 ? 712 (458) ? ? 458 712 ? 712exercised Balance at 54,076,740 2,163 288,479 20,575 ? 272 (231,395) 80,094 (526) 79,568June30,2020 Balance atJanuary 1, 54,131,553 2,165 288,757 23,825 280 (189) (257,747) 57,091 (545) 56,5462021Result for ? ? ? ? ? ? (28,353) (28,353) (18) (28,371)the periodOthercomprehensive ? ? ? ? ? 255 ? 255 ? 255incomeRecognitionof 112,657 5 382 2,719 ? ? ? 3,106 ? 3,106share-basedpaymentsIssuance ofordinary 16,508,475 660 84,594 ? ? ? ? 85,254 ? 85,254sharesTreasuryshares (127,303) ? ? ? ? ? ? ? ? ?transferredRecognitionof equitycomponent of ? ? ? ? ? ? ? ? ? ?convertibleloanShare options ? ? ? (160) ? ? 160 ? ? ?lapsedShare options 243,189 ? 753 (541) ? ? 541 753 ? 753exercised Balance at 70,868,571 2,830 374,486 25,843 280 66 (285,399) 118,106 (563) 117,543June30,2021



PROQR THERAPEUTICS N.V. Unaudited Condensed Consolidated Statement of Cash Flows

Threemonthperiod Sixmonthperiod ended June30, ended June30, 2021 2020 2021 2020 ?1,000 ?1,000 ?1,000 ?1,000Cash flows from operating activitiesNet result (15,753) (4,119) (28,371) (20,197)Adjustments for: ? Depreciation 602 530 1,233 1,052? Share-based compensation 1,471 1,802 2,719 4,672? Other income ? (8,423) ? (8,423)? Financial income and expenses 2,464 696 2,757 161? Results related to associates ? 52 107 186? Gain on recognition of ? ? (621) ?financial asset? Results related to financialliabilities measured at fair 33 ? 762 ?value through profit or loss? Net foreign exchange gain / (141) (135) 255 121(loss)? Income tax expenses 53 11 60 11 Changes in working capital 1,915 (918) 567 (3,119)Cash used in operations (9,356) (10,504) (20,532) (25,536) Corporate income tax paid (53) (11) (60) (11)Interest received 5 62 5 91Interest paid (575) (34) (1,153) (38) Net cash used in operating (9,979) (10,487) (21,740) (25,494)activities Cash flow from investing activitiesPurchases of property, plant and (52) (344) (84) (542)equipment Net cash used in investing (52) (344) (84) (542)activities Cash flow from financing activitiesProceeds from issuance of 82,601 ? 85,254 ?shares, net of transaction costsProceeds from exercise of share 185 243 753 712optionsProceeds from borrowings 569 289 569 579Proceeds from convertible loans ? 65 ? 65Repayment of lease liability (14) (105) (250) (307) Net cash generated by financing 83,341 492 86,326 1,049activities Net increase (decrease) in cash 73,310 (10,339) 64,502 (24,987)and cash equivalents Currency effect cash and cash (1,746) (583) (898) 178equivalentsCash and cash equivalents, at 67,878 98,063 75,838 111,950beginning of the period Cash and cash equivalents at the 139,442 87,141 139,442 87,141end of the period