ProQR Announces Third Quarter 2020 Operating and Financial Results

• Illuminate Phase 2/3 trial of sepofarsen expected to complete enrollment in Q1 2021; additional data from Phase 1/2 InSight extension study to be reported in H2 2021

• Enrollment completed for QR-421a dosing cohorts and data from next Phase 1/2 interim analysis expected in H1 2021

• Initial data from Phase 1/2 trial of QR-1123 expected in 2021

• QR-504a clinical study in Fuchs expected to start in H1 2021

• Cash runway into 2023

LEIDEN, Netherlands & CAMBRIDGE, Mass., Nov. 16, 2020 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq: PRQR) (the “Company”), a company dedicated to changing lives through the creation of transformative RNA therapies for inherited retinal diseases (IRDs), today reported its financial and operating results for the third quarter ended September 30, 2020 and provided a business update, including updated timeline guidance for the Company’s clinical stage programs.

“We’re pleased to report that our clinical trials are back on track after the COVID-19 disruption, with all ongoing trials either already completed or expected to complete enrollment in the near term. With this progress we are well positioned heading into 2021 and beyond to make meaningful advancements across our portfolio,” said Daniel A. de Boer, Chief Executive Officer of ProQR. “We will enter 2021 with the Illuminate trial of sepofarsen expected to complete enrollment in the first quarter and we anticipate reporting data across our clinical pipeline during the year ahead, which represents the opportunity for multiple potential value inflection points. This will include the next interim analysis for QR-421a and initial data for QR-1123. We also plan to share updated data from the Phase 1/2 extension study of sepofarsen and to start dosing patients with QR-504a.”

De Boer continued, “As we continue to build a robust IRD translational platform, we are pleased to have appointed Naveed Shams, MD, PhD, as our Chief Scientific Officer. Naveed is a proven leader with deep ophthalmology experience, including multiple product approvals globally. This expertise further strengthens our focus as an ophthalmology company and supports our commitment to bringing therapies to patients with inherited retinal diseases.”

Business Operations and Program Updates

Sepofarsen, lead clinical candidate for Leber congenital amaurosis 10 (LCA10) in the Phase 2/3 Illuminate trial:

• In July, the Company presented positive data from the ongoing InSight extension study of sepofarsen for LCA10, in which patients from the completed Phase 1/2 study were offered treatment in their second eye. These data showed that in 4 out of 4 second eyes treated, the treatment response was consistent with the first eye treated including a significant and sustained benefit, building further confidence in the Phase 2/3 Illuminate trial.

  • In October and November, the following data was presented at Euretina and the American Academy of Ophthalmology (AAO) virtual annual meetings, and both presentations were selected as “Best Poster” at AAO:

    • Phase 1b/2 trial results of the intravitreal sepofarsen RNA therapy in LCA10 (encore presentations)

    • Full-field stimulus testing (FST) to assess sepofarsen patient response in LCA10

• The Company has activated sites in North America, Europe, and South America to enable rapid completion of the Illuminate trial enrollment. All of the remaining patients to be enrolled in the trial have been pre-screened and identified.

• Upcoming sepofarsen anticipated events:

  • The Company expects to complete enrollment in the Phase 2/3 pivotal Illuminate trial in Q1 2021, assuming sites are able to continue operations with respect to the COVID-19 public health emergency. The primary endpoint for Illuminate is mean change from baseline in BCVA at 12 months.

  • Start a pediatric trial of sepofarsen in patients under 8 years of age in 2021. The primary objectives of this study are safety and tolerability,

  • Report updated data from the next interim analysis of the Phase 1/2 InSight extension study in H2 2021.

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

• Enrollment of the Phase 1/2 Stellar trial dose expansion (100 µg homozygous) and dose escalation (200 µg) cohorts is complete.

• The Company anticipates reporting data from the next planned interim analysis of the Phase 1/2 Stellar trial in H1 2021.

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

• The Phase 1/2 Aurora trial is ongoing with 4 of the 5 planned single dose cohorts having completed enrollment.

• ProQR anticipates reporting initial data from the single dose cohorts of this program in 2021.

QR-504a for Fuchs Endothelial Corneal Dystrophy (FECD):

• All preparations for the start of a Proof of Mechanism trial of QR-504a in patients with FECD are completed and, pending the lifting of COVID-19 restrictions, the Company plans to start enrolling patients with FECD type 3 in H1 of 2021.

• Report initial data in H1 2022.

Business updates:

• In July, to support funding of the Company’s pipeline, ProQR entered into a strategic convertible debt financing agreement with Pontifax Ventures where the Company will have access to up to $30 million in three tranches of $10 million with the first tranche drawn by the Company at closing. Subsequent to the closing with Pontifax, in August the loan facility was expanded by an additional €15 million (in three tranches of €5 million) with Kreos Capital, with €5 million drawn by the Company at closing. If fully drawn down, the capital from these facilities extends ProQR’s runway into 2023.

• In October, Naveed Shams, MD, PhD, was appointed Chief Scientific Officer (CSO). As CSO, Dr. Shams provides strategic direction, oversight, and execution for ProQR’s research and early development efforts. He joined ProQR from Santen, a global company focused on ophthalmology, where he most recently served as Senior Corporate Officer, Head of Global Research and Development and Chief Scientific Officer.

Financial Highlights

At September 30, 2020, ProQR held cash and cash equivalents of €88.8 million, compared to €112.0 million at December 31, 2019. Net cash used in operating activities during the three-month period ended September 30, 2020 was €9.8 million, compared to €8.8 million for the same period last year.

Research and development costs were €8.3 million for the quarter ended September 30, 2020, compared to €11.1 million for the same period last year.

General and administrative costs were €2.8 million for the quarter ended September 30, 2020 compared to €2.9 million for the same period last year.

Net loss for the three-month period ended September 30, 2020 was €13.2 million or €0.26 per share, compared to a €12.2 million loss or €0.31 per share for the same period last year.

For further financial information for the period ended September 30, 2020, 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 2 and Non-Syndromic Retinitis Pigmentosa

Usher syndrome is the leading cause of combined deafness and blindness. People with Usher syndrome type 2 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 2 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 being evaluated in the Phase 1/2 Stellar trial and 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 (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 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 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 U.S., and similar prevalence is noted for other global regions. There are different types of this disease and we focus on age-related FECD Type 3 (FECD3). Some patients with age-related FECD develop advanced disease with corneal edema and corneal clouding. These symptoms can lead to complete vision loss and the need for surgery such as a corneal transplant.

About QR-504a

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-in-human clinical trial in late-stage disease patients in 2021. 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.

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.

*Since 2012*

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 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, our other programs and business operations, including timing of commencing clinical trials and enrollment of patients therein, 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, our loan facility with Pontifax 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 general business, financial and accounting risks and litigation. 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
skiely@proqr.com
or
Hans Vitzthum
LifeSci Advisors
T: +1 617 535 7743
hans@lifesciadvisors.com

Media Contact:
Alison Chen
LifeSci Communications
T: +1 646 876 4932
achen@lifescicomms.com

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

		September 30,		December 31,
		2020		2019
		€ 1,000		€ 1,000
Assets
Current assets
Cash and cash equivalents		88,847		111,950
Prepayments and other receivables		2,759		1,866
Social securities and other taxes		552		850
Total current assets		92,158		114,666
Property, plant and equipment		17,875		2,440
Investments in associates		159		429
Total assets		110,192		117,535
Equity and liabilities
Equity
Equity attributable to owners of the Company		68,626		94,329
Non-controlling interests		(534)		(496)
Total equity		68,092		93,833
Current liabilities
Borrowings		949		343
Lease liabilities		1,308		508
Derivative financial instruments		1,092		—
Trade payables		291		445
Current income tax liability		—		64
Social securities and other taxes		155		108
Pension premiums		—		2
Deferred income		863		711
Other current liabilities		6,159		8,812
Total current liabilities		10,817		10,993
Borrowings		16,577		12,709
Lease liabilities		14,706		-
Total liabilities		42,100		23,702
Total equity and liabilities		110,192		117,535

PROQR THERAPEUTICS N.V.
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,
		2020		2019		2020		2019
		€ 1,000		€ 1,000		€ 1,000		€ 1,000
Other income		251		530		9,188		1,509
Research and development costs		(8,304)		(11,074)		(29,716)		(32,560)
General and administrative costs		(2,809)		(2,903)		(10,173)		(8,970)
Total operating costs		(11,113)		(13,977)		(39,889)		(41,530)
Operating result		(10,862)		(13,447)		(30,701)		(40,021)
Finance income and expense		(1,863)		1,375		(2,024)		1,339
Results related to financial liabilities measured at fair value through profit or loss		(305)		—		(305)		—
Results related to associates		(84)		(119)		(270)		579
Result before corporate income taxes		(13,114)		(12,191)		(33,300)		(38,103)
Income taxes		(75)		—		(86)		(64)
Result for the period		(13,189)		(12,191)		(33,386)		(38,167)
Other comprehensive income		(255)		147		(134)		121
Total comprehensive income (attributable to owners of the Company)		(13,444)		(12,044)		(33,520)		(38,046)
Result attributable to
Owners of the Company		(13,181)		(12,139)		(33,348)		(37,945)
Non-controlling interests		(8)		(52)		(38)		(222)
		(13,189)		(12,191)		(33,386)		(38,167)
Share information
Weighted average number of shares outstanding1		50,143,262		38,912,701		50,017,990		38,902,203
Earnings per share attributable to the equity holders of the Company (expressed in Euro per share)
Basic loss per share1		(0.26)		(0.31)		(0.67)		(0.98)
Diluted loss per share1		(0.26)		(0.31)		(0.67)		(0.98)

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.

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

		Attributable to owners of the Company
								Equity settled		Option
								Employee		premium on								Non-
		Number of		Share		Share		Benefit		convertible		Translation		Accumulated				controlling		Total
		shares		Capital		Premium		Reserve		loan		Reserve		Deficit		Total		interests		Equity
				€ 1,000		€ 1,000		€ 1,000		€ 1,000		€ 1,000		€ 1,000		€ 1,000		€ 1,000		€ 1,000
Balance at January 1, 2019		43,149,987		1,726		235,744		10,780		—		108		(155,443)		92,915		(230)		92,685
Result for the period		—		—		—		—		—		—		(37,945)		(37,945)		(222)		(38,167)
Other comprehensive income		—		—		—		—		—		121		—		121		—		121
Recognition of share-based payments		—		—		—		4,614		—		—		—		4,614		—		4,614
Issuance of ordinary shares		—		—		—		—		—		—		—		—		—		—
Treasury shares transferred		(40,259)		—		—		—		—		—		—		—		—		—
Share options lapsed		—		—		—		(33)		—		—		33		—		—		—
Share options exercised		40,259		—		166		(115)		—		—		115		166		—		166
Balance at September 30, 2019		43,149,987		1,726		235,910		15,246		—		229		(193,240)		59,871		(452)		59,419
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

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

		Three month period				Nine month period
		ended September 30,				ended September 30,
		2020		2019		2020		2019
		€ 1,000		€ 1,000		€ 1,000		€ 1,000
Cash flows from operating activities
Net result		(13,189)		(12,191)		(33,386)		(38,167)
Adjustments for:
— Depreciation		651		506		1,703		1,543
— Share-based compensation		1,676		1,226		6,348		4,614
— Other income		—		—		(8,423)		—
— Financial income and expenses		1,863		(1,375)		2,024		(1,339)
— Results related to associates		84		119		270		(579)
— Results related to financial liabilities measured at fair value through profit or loss		305		—		305		—
— Net foreign exchange gain / (loss)		(255)		148		(134)		122
Changes in working capital		(246)		2,718		(3,354)		1,744
Cash used in operations		(9,111)		(8,849)		(34,647)		(32,062)
Corporate income tax paid		(157)		—		(168)		(64)
Interest received		27		90		118		176
Interest paid		(569)		(13)		(607)		(64)
Net cash used in operating activities		(9,810)		(8,772)		(35,304)		(32,014)
Cash flow from investing activities
Purchases of property, plant and equipment		(264)		(32)		(806)		(341)
Net cash used in investing activities		(264)		(32)		(806)		(341)
Cash flow from financing activities
Proceeds from issuance of shares, net of transaction costs		—		—		—		—
Proceeds from exercise of share options		12		2		724		166
Proceeds from borrowings		—		—		579		—
Proceeds from convertible loans		13,477		—		13,542		690
Repayment of lease liability		(235)		(290)		(542)		(861)
Net cash generated by (used in) financing activities		13,254		(288)		14,303		(5)
Net increase/(decrease) in cash and cash equivalents		3,180		(9,092)		(21,807)		(32,360)
Currency effect cash and cash equivalents		(1,474)		1,420		(1,296)		1,572
Cash and cash equivalents, at beginning of the period		87,141		82,464		111,950		105,580
Cash and cash equivalents at the end of the period		88,847		74,792		88,847		74,792