UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 6-K

 

Report of Foreign Private Issuer

Pursuant to Rule 13a-16 or 15d-16 of

the Securities Exchange Act of 1934

 

For the month of July 2020

 

Commission File Number: 001-36622

 

PROQR THERAPEUTICS N.V.

 

Zernikedreef 9

2333 CK Leiden

The Netherlands

Tel: +31 88 166 7000

(Address, Including ZIP Code, and Telephone Number,
Including Area Code, of Registrant’s Principal Executive Offices)

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

 

Form 20-F  x  Form 40-F  o

 

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):  o

 

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):  o

 

 

 


 

On July 20, 2020, ProQR Therapeutics N.V. (the “Company”) presented preliminary data from its Phase 1/2 InSight extension study of Sepofarsen in LCA10 patients using a webcasted conference call. A copy of the presentation is attached hereto as Exhibit 99.1 and is incorporated herein by reference.

 

The Company hereby incorporates by reference the information contained herein into the Company’s registration statement on Form F-3 (File No. 333-228251).

 

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SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

 

 

PROQR THERAPEUTICS N.V.

 

 

 

Date: July 20, 2020

By:

/s/ Smital Shah

 

 

Smital Shah

 

 

Chief Financial Officer

 

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INDEX TO EXHIBITS

 

Number

 

Description

 

 

 

99.1

 

Presentation for webcasted conference call

 

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Exhibit 99.1

EXPERT PERSPECTIVES CALL Sepofarsen – InSight Open Label Extension Study Update July 20, 2020 Exhibit 99.1

 

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, and the clinical development and the 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, 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; 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. P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 2

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>2,000,000 people living with Inherited retinal disease P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 3

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Very few have a treatment >2,000,000 people living with Inherited retinal disease P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 4

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RNA therapies in pipeline >100,000 IRD patients for 50,000 45,000 ~10,000 40,000 35,000 ~7,000 30,000 25,000 ~16,000 20,000 15,000 10,000 5,000 0 Sepofarsen for LCA10 QR-421a for Usher Syndrome QR-1123 for P23H adRP QR-411 for Usher Syndrome QR-1011 for Stargardt’s Disease QRX-461 for Usher Syndrome QRX-136 for LCA10 Other programs for mutations causing IRD’s P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 5 ~500 ~1,000 ~2,000 ~2,000

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ProQR RNA therapy development pipeline REGISTRATIONAL Ophthalmology P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 6 Productive discovery engine leading to steady expansion of the pipeline of molecules targeting Inherited Retinal Diseases Sepofarsen (QR-110) for LCA10 p.Cys998X QR-421a for Usher syndrome 2A exon 13 QR-1123 for P23H adRP - discovered by Ionis QR-504a for FECD3 QR-411 for Usher syndrome 2A PE40 QR-1011 for Stargardt’s disease c.5461-10T>C QRX-461 for Usher syndrome undisclosed mutation QRX-136 for LCA undisclosed mutation DISCOVERY PRECLINICAL DEVELOPMENT PROOF OF CONCEPT TRIALS LATE STAGE/ TRIALS

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Sepofarsen (QR-110) for LCA10 LCA10 Lose sight in first years of life No approved therapy currently available p.Cys998X mutation affects ~2,000 patients in the Western world RNA therapy: sepofarsen Goal: Restore vision/ prevent vision loss in patients with LCA10 Locally adminis-tered in the eye. Routine intra-vitreal procedure Anticipated infrequent dosing of 2 times a year P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 7  Established modality in eye  Orphan drug designation & Rare pediatric  Strong preclinical proof of concept in disease designation human retina in preclinical models  FDA Fast track designation and access to  Top-line Phase 1/2 clinical trial results EMA PRIME program showed rapid, significant and durable •Phase 2/3 Illuminate trial ongoing activity and was well tolerated

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Phase 1/2 + extension trial design Open label, extension trial, LCA10 patients with 1 or 2 copies of p.Cys998X = DSMC review P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 8 001 Study Screening baseline 12 months treatment in worse eye Adult 160/80µg dose Adult 320/160µg dose Pediatric 160/80µg dose Pediatric 320/160µg dose 002 (Extension) Study Extension trial 160/80µg dose Analysis 3-month Data + 2nd eye

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Phase 1/2 showed rapid and sustained benefit Treated Subjects (n=11) BCVA across 2 cohorts Mobility FST 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 -0,7 -0,8 0,2 3,5 Impaired Acuity Less Sensitive Less Impairment 3 0 2,5 -0,2 2 -0,4 * 1,5 -0,6 1 -0,8 0,5 -1 0 -1,2 -0,5 More More Sensitive Improved Acuity Impairment * Visual acuity and FST peaks associated with cataract occurrence. These subjects regained their pre-cataract visual acuity after surgery. 1st eye 2nd eye 1st eye red light 1st eye blue light 2nd eye red light 2nd eye blue light score (n=10) P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 9 Change in BCVA (LogMAR) Change in FST (log cd/m2) Change in Mobility (levels) Eye BCVA – LogMAR (n=11) Red FST – log cd/m2 (n=10) Blue FST – log cd/m2 (n=10) Mobility course – composite Treated (TE) -0.55 (0.26) p<0.05 vs. CE -0.91 (0.18) p<0.01 vs. CE -0.79 (0.23) p<0.02 vs. CE 2.5 (0.99) p=0.1 vs. CE Untreated (CE) -0.12 (0.07) -0.16 (0.16) 0.02 (0.11) 1.75 (0.75)

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Target registration dose – key outcomes Onset of effect at month BCVA 3, sustained out to month 12 FST Mobility 0,2 0,2 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 Impaired Acuity Less Sensitive Less Impairment 0 0 -0,2 -0,2 -0,4 -0,4 -0,6 -0,6 -0,8 -0,8 -1 -1 -1,2 -0,5 More More Sensitive Improved Acuity Impairment 1st eye 2nd eye 1st eye 2nd eye 1st eye red light 1st eye blue light 2nd eye red light 2nd eye blue light score (n=6) P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l 10 Change in BCVA (LogMAR) Change in FST (log cd/m2) Change in Mobility (levels) Eye BCVA – LogMAR (n=6) Red FST – log cd/m2 (n=6) Blue FST – log cd/m2 (n=6) Mobility course – composite Treated (TE) -0.93 (0.43) p=0.13 vs. CE -0.66 (0.14) p<0.05 vs. CE -0.63 (0.31) p=0.09 vs. CE 4.0 (1.27) p=0.06 vs. CE Untreated (CE) -0.22 (0.11) 0.05 (0.17) 0.12 (0.16) 2.7 (1.11)

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InSight open label extension study update Preliminary data P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 11

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InSight study overview • 9 • 7 subjects from the 11 in Phase 1/2 rolled over into the InSight study 2 subjects elected not to roll over for personal reasons subjects have been dosed so far in the extension study, 4 of which have • been dosed in the second eye • • All subjects have been switched over to Phase 2/3 target dose regimen Some redosing visits have been delayed and cross-border travel restrictions due to COVID-19 site limitations • No changes to the overall safety profile P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 12

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Change from baseline to 3 months post dosing -3 -3 -2,5 -2,5 -2 -2 -1,5 -1,5 -1 -1 -0,5 -0,5 0 0 BCVA FST Red FST Blue BCVA FST Red FST Blue BCVA FST Red FST Blue BCVA FST Red FST Blue 1st eye *= 6 month value of 2nd eye as 3 month visit was missed due to COVID-19 P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 13 FST (Log cd/m2) BCVA (LogMAR) Subject P2 Subject P3 Subject P11* (homozygous) Subject P1 X

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Change from baseline to 3 months post dosing Consistent treatment response in both eyes -3 -3 -2,5 -2,5 -2 -2 -1,5 -1,5 -1 -1 -0,5 -0,5 0 0 BCVA FST Red FST Blue BCVA FST Red FST Blue BCVA FST Red FST Blue BCVA FST Red FST Blue 1st eye 2nd eye *= 6 month value of 2nd eye as 3 month visit was missed due to COVID-19 P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 14 FST (Log cd/m2) BCVA (LogMAR) Subject P2 Subject P3 Subject P11* (homozygous) Subject P1 XX

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Subject P2 160 μg 80 μg 80 μg Baseline characteristics 0,5 0 -0,5 -1 -1,5 -2 -2,5 -3 -3,5 2 1,5 1 0,5 0 -0,5 -1 -1,5 1,5 1 0,5 0 -0,5 -1 -1,5 -2 BCVA Change from baseline • • 41yrs, Male, Heterozygous Light Perception, both eyes Treatment response • First eye • Significant and sustained benefit FST red Change from baseline • Lost benefit after not being redosed in first eye for 15 months, as expected Scheduled to be redosed in first eye after COVID-19 • • Second eye FST blue Change from baseline • Responded the same way as first eye • Maximum treatment response -2.74 LogMAR 1st eye 2nd eye Onset of lens opacity Lens replacement IVT injection P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 15 FST (log cd/m2) FST (log cd/m2) BCVA (LogMAR) Direction of improvement Direction of improvement Direction of improvement -2.5 -2.66

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Subject P3 160 μg 80 μg 80 μg 80 μg Baseline characteristics 0,5 0 -0,5 -1 -1,5 -2 -2,5 0,5 BCVA Change from baseline • • 44yrs, Male, Heterozygous 1st eye: 2.4 LogMAR(HM); 2nd eye: 1.66 LogMAR(CF) Treatment response • First eye FST red Change from baseline • Significant and sustained benefit 0 • Developed a cataract in first eye at month 20 leading to reduction in BCVA Lens replacement completed, follow-up measurement pending COVID-19 measures to lift -0,5 -1 • -1,5 0,5 FST blue Change from baseline 0 • Second eye -0,5 • Responded the same way as first eye -1 • Maximum treatment response -1.82 LogMAR -1,5 -2 1st eye 2nd eye Onset of lens opacity Lens replacement IVT injection P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 16 FST (log cd/m2) FST (log cd/m2) BCVA (LogMAR) Direction of improvement Direction of improvement Direction of improvement -0.8 -1.28

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Subject 160 μg P11 Baseline characteristics 0,05 0 -0,05 -0,1 -0,15 -0,2 -0,25 -0,3 -0,35 0,2 0 -0,2 -0,4 -0,6 -0,8 -1 0,2 0 -0,2 -0,4 -0,6 -0,8 -1 BCVA Change from baseline • • 14yrs, Female, Homozygous 1st eye: 0.63 LogMAR(20/80); 2nd eye: 0.48 LogMAR(20/50) Treatment response • First eye FST red Change from baseline • Benefit sustained for 15+ months, likely due to homozygous genotype • Subject will likely get redosed in first eye • Second eye • Responded the same way as first eye FST blue Change from baseline 1st eye 2nd eye IVT injection P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 17 FST (log cd/m2) FST (log cd/m2) BCVA (LogMAR) Direction of improvement Direction of improvement Direction of improvement -0.06 -0.25

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Subject P1 160/80 μg 80 μg 80 μg 80 μg 80 μg 80 μg Baseline characteristics 0,5 0 -0,5 -1 -1,5 -2 -2,5 0,5 0 -0,5 -1 -1,5 -2 -2,5 -3 0,5 0 -0,5 -1 -1,5 -2 -2,5 BCVA Change from baseline • • 19yrs, Male, Heterozygous Light Perception, both eyes Treatment response • First eye • No response on BCVA as started trial at Light perception only Meaningful response on FST Subject perceives meaningful benefit FST red Change from baseline • • • Second eye • Responded the same way as first eye FST blue Change from baseline 1st eye 2nd eye Onset of lens opacity IVT injection P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 18 FST (log cd/m2) FST (log cd/m2) BCVA (LogMAR) Direction of improvement Direction of improvement Direction of improvement

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Summary and next steps • 4 out of 4 second eyes treated have responded consistently with the confirming the benefit seen in Phase 1/2 Safety profile consistent with that observed in the Phase 1/2 results Data supports selection of 160/80 µg target registration dose Additional longitudinal data support 6-month dosing intervals first eye, • • • • Building additional confidence in ongoing Illuminate pivotal Phase 2/3 trial P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 19

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Change from baseline to 3 months post dosing Consistent treatment response in both eyes -3 -3 -2,5 -2,5 -2 -2 -1,5 -1,5 -1 -1 -0,5 -0,5 0 0 BCVA FST Red FST Blue FST Red FST Blue BCVA FST Red FST Blue 1st eye 2nd eye *= 6 month value of 2nd eye as 3 month visit was missed due to COVID-19 P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 20 FST (Log cd/m2) BCVA (LogMAR) Subject P2 Subject P3 Subject P11* (homozygous) Subject P1 XX BCVAFST RedFST Blue BCVA

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Subject P3: Illustration of BCVA improvement • Baseline: 2.4 LogMAR (20/1000) Baseline (2.4 LogMAR) M3 (1.12 LogMAR) M9 (0.58 LogMAR) • 3 months: 1.12 LogMAR (20/125) • Improvement: 1.28 LogMAR* *From being worse than legally blind to navigating freely, watching tv and being able to see family faces. Using “Thru My Eyes” App P r o Q R T h e r a p e u t i c s – E x p e r t P e r s p e c t i v e C a l l P r e l i m i n a r y d a t a 21

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IT’S IN OUR RNA

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