AX-0810

LEIDEN, Netherlands & CAMBRIDGE, Mass., Oct. 07, 2024 (GLOBE NEWSWIRE) -- ProQR Therapeutics NV (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through transformative RNA therapies, today announced it will present preclinical data for its proprietary Axiomer™ RNA editing technology platform and its AX-0810 pipeline program for cholestatic diseases targeting NTCP at the 20th Annual Meeting of the Oligonucleotide Therapeutics Society, October 6-9, 2024, in Montreal, QC, Canada. Gerard Platenburg, co-founder and Chief Scientific Officer at ProQR, will present on Tuesday, October 8 at 10:15 am ET (Session IV: DNA/RNA Editing). Oral presentation:“Oligonucleotide guided RNA editing of SLC10A1 (NTCP) as a therapeutic approach to lower bile acid re-uptake in cholestatic diseases” Following OTS, the slide deck will be available via ProQR’s website in the Presentations and Publications section. About Axiomer™ ProQR is pioneering a next-generation RNA base editing technology called Axiomer™, which could potentially yield a new class of medicines for diverse types of 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 called ADAR (Adenosine Deaminase Acting on RNA). Axiomer EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease. About ProQR ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. 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 for ProQR 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 “continue,” "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 our presentation at this conference, our Axiomer™ technology, including the continued development and advancement of our Axiomer platform, the therapeutic potential of our Axiomer RNA editing oligonucleotides and our ability to expand preclinical in vivo and in vitro data, the timing, progress and results of our preclinical studies and other development activities, including the release of data related thereto, and the potential of our technologies and product candidates. 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 most recent 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 shortage and pressure on supply and logistics on the global market; the likelihood of our preclinical and clinical programs being initiated and 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 or suppliers to supply materials for research and development and the risk of supply interruption or delays from suppliers or contract manufacturers; 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, including the collaboration with Eli Lilly and Company; 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; general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties; and risks related to macroeconomic conditions and market volatility resulting from global economic developments, geopolitical instability and conflicts. 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. ProQR Therapeutics N.V. Investor contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorPeter KelleherLifeSci AdvisorsT: +1 617 430 7579 pkelleher@lifesciadvisors.com Media contact:Robert StanislaroFTI ConsultingT: +1 212 850 5657robert.stanislaro@fticonsulting.com

AX-0810 program targeting NTCP for cholestatic diseases and AX-1412 program targeting B4GALT1 for cardiovascular diseases advancing to the clinic in late 2024/early 2025 with translational data and trial design details to be announced in H2 2024$4.5 million in milestones achieved in H1 related to progress in the Lilly partnership€96.2 million cash position as of end of Q2 providing runway into mid-2026, plus additional potential milestones from Lilly partnership LEIDEN, Netherlands & CAMBRIDGE, Mass., Aug. 08, 2024 (GLOBE NEWSWIRE) -- ProQR Therapeutics NV. (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through transformative RNA therapies based on its proprietary Axiomer™ RNA editing technology platform, today reported its financial and operating results for the second quarter ended June 30, 2024, and provided a business update. “In the second quarter, we took important steps toward advancing our first editing oligonucleotide programs to clinical stage, with AX-0810 targeting NTCP for cholestatic diseases and AX-1412 targeting B4GALT1 for cardiovascular diseases on track to enter the clinic in late 2024/early 2025,” said Daniel A. de Boer, Founder and CEO of ProQR. “We were excited to share data at ASGCT in May, demonstrating in vivo proof of target engagement with meaningful changes in disease-relevant biomarkers in non-human primates for our NTCP program. As we progress our CTA/IND-enabling studies, we plan to announce translational data and more about our clinical plans for AX-0810 in the second half of the year, as well as preclinical proof of concept and translational data for AX-1412.” de Boer continued, “Beyond our own pipeline programs, we are pleased with the progress we are making in our partnership with Lilly and highlight the achievement of multiple milestones in the first half of the year. With the benefits of a productive partnership, a differentiated pipeline strategy rooted in human genetics, our leading IP portfolio, and a strong cash balance with runway into mid-2026, we look forward to continued execution as we advance our science and pipeline programs.” Recent Progress and Anticipated Upcoming Events In June, ProQR presented at the RNA Editing Summit in Boston, highlighting its Axiomer technology platform and AX-0810, the Company’s program targeting NTCP for cholestatic diseases. In May at the American Society of Cell and Gene Therapy (ASGCT) Annual Meeting, ProQR presented preclinical proof of concept in vitro and in vivo data for AX-0810 for Cholestatic Diseases targeting NTCP (poster P-705). ProQR scientists showed for the first time in the ADAR RNA editing field in vivo proof of target engagement (RNA editing) with meaningful changes in biomarkers in NHPs using Axiomer RNA Editing Oligonucleotides. At ASGCT, ProQR and partner Eli Lilly presented preclinical data related to Axiomer in poster P-726 titled “Complex Metabolism and Prolonged PK/PD of a GalNAc-Conjugated Editing Oligonucleotide (EON) in Mice”. Anticipated Upcoming Events: AX-0810 targeting NTCP for cholestatic diseases: clinical development candidate translational data to be reported, and design for the clinical trial to be shared in H2 2024 with program to advance to the clinic in late 2024/early 2025.AX-1412 targeting B4GALT1 for cardiovascular diseases: preclinical proof of concept data and translational data to be reported in H2 2024 with program to advance to the clinic in late 2024/early 2025. Potential additional new pipeline target announcements in 2024.Continue to execute on partnership with Eli Lilly and Company (Lilly), with potential additional data updates to come in 2024, along with potential additional milestone income from existing partnership, and potential option to exercise for expansion of deal to 15 targets, which would result in a $50 million opt-in payment to ProQR.ProQR may selectively form new partnerships, which could include multi-target discovery alliances, or product alliances on specific programs. Financial Highlights At June 30, 2024, ProQR held cash and cash equivalents and short term financial assets of €96.2 million, compared to €118.9 million cash and cash equivalents at December 31, 2023. Net cash used in operating activities during the three-month period ended June 30, 2024 was €6.3 million, compared to €10.3 million used for the same period last year. During the first half of 2024, the Company achieved certain milestones in the collaboration agreement with Eli Lilly amounting to $4.5 million (€4.2 million). Milestone income achieved in Q2 was received in July. Research and development (R&D) costs were €7.1 million for the quarter ended June 30, 2024 compared to €5.9 million for the same period last year. General and administrative costs were €3.0 million for the quarter ended June 30, 2024 compared to €4.1 million for the same period last year. Net loss for the three-month period ended June 30, 2024 was €2.7 million, or €0.03 per diluted share, compared to €8.0 million, or €0.10 per diluted share, for the same period last year. For further financial information for the period ended June 30, 2024, please refer to the Q2 financial report filing. About Axiomer™ ProQR is pioneering a next-generation RNA base editing technology called Axiomer™, which could potentially yield a new class of medicines for diverse types of 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 called ADAR (Adenosine Deaminase Acting on RNA). Axiomer™ EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease. About Biliary Atresia (BA) and Primary Sclerosing Cholangitis (PSC) Cholestatic disorders refer to a group of diseases presenting excessive and toxic buildup of bile acids in the liver due to bile ducts dysfunction. This leads to liver damage and a range of debilitating symptoms. Without treatment, liver damage can progress through various stages, ultimately leading to liver failure and elevated risk of liver malignancy, affecting life expectancy. Cholestatic diseases remain leading causes of liver transplantation. There are no approved therapies for primary sclerosing cholangitis (PSC) for adults and biliary atresia (BA) for pediatrics It is estimated that 80,000 and 20,000 individuals have PSC and BA, respectively, in North America and in Europe. About AX-0810 targeting NTCP The majority of the bile acids present in the liver cells originate from the enterohepatic reuptake cycle. The key transporter responsible for hepatic uptake of bile acids from portal circulation is the sodium (Na+)-taurocholate cotransporting polypeptide (NTCP, SLC10A1 gene) expressed in the liver. AX-0810 is designed to introduce a loss of function variant in SLC10A1 RNA that has been found in human genetics to prevent re-uptake of bile acids in liver via NTCP. Based on its mechanism of action, AX-0810 has the potential to become a disease modifying treatment for PSC and BA primarily among other cholestatic diseases. About Cardiovascular Diseases Cardiovascular diseases (CVDs) are a group of health conditions that affect the heart and blood vessels, such as atherosclerosis which can lead to severe problems like heart attacks, heart failure, and stroke. CVDs represent the leading cause of disability and death in the world. Approximately 18 million people die every year from CVDs representing one third of all the global deaths. Despite available lipid lowering therapies and hypertension medications, the risk of CVDs is still projected to increase rapidly over the coming years. About AX-1412 targeting B4GALT1 Gene–based analysis of rare beta-1,4-galactosyltransferase 1 (B4GALT1) missense variant (p.Asn352Ser) is known to lead to B4GALT1 protein loss of function and showed an association with decreased coronary artery disease. These beneficial effects are mediated by hypo-galactosylation of the apolipoprotein B100 and fibrinogen, known – independent – drivers of increased risk of CVDs. AX-1412 introduces a protective variant into B4GALT1 RNA to address the remaining residual risk of developing cardiovascular diseases. ProQR intends to advance AX-1412 targeting B4GALT1 to early clinical proof of concept stage, then would seek to partner this program. About ProQR ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. 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 “continue,” "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 our business, technology, strategy, preclinical model data, our initial pipeline targets and the upcoming strategic priorities and milestones related thereto, our Axiomer™ platform, including the continued development and advancement of our Axiomer platform, the therapeutic potential of our Axiomer RNA editing oligonucleotides and our ability to expand preclinical in vivo and in vitro data, the timing, progress and results of our preclinical studies and other development activities, including the release of data related thereto, our patent estate, including our anticipated strength and our continued investment in it, as well as the timing of our clinical development, the potential of our technologies and product candidates, the collaboration with Lilly and the intended and potential benefits thereof, including the receipt of milestone and royalty payments from commercial product sales, if any, from the products covered by the collaboration, our ability to selectively form new partnerships and enter into future collaborations, 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 expressed or implied by 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 shortage and pressure on supply and logistics on the global market; the likelihood of our preclinical and clinical programs being initiated and 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, including the collaboration with Lilly; 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; general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties; and risks related to macroeconomic conditions and market volatility resulting from global economic developments, geopolitical instability and conflicts. 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. ProQR Therapeutics N.V. Investor contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorPeter KelleherLifeSci AdvisorsT: +1 617 430 7579 pkelleher@lifesciadvisors.com Media contact:Robert StanislaroFTI ConsultingT: +1 212 850 5657robert.stanislaro@fticonsulting.com Financial Tables PROQR THERAPEUTICS N.V.Unaudited Condensed Consolidated Statement of Financial Position June 30, December 31, 2024 2023 €1,000 €1,000 Assets Current assets Cash and cash equivalents 78,970 118,925 Financial asset - current 17,183 — Prepayments and other receivables 5,116 1,538 Other taxes 497 523 Total current assets 101,766 120,986 Property, plant and equipment 16,285 16,897 Investments in financial assets — — Total assets 118,051 137,883 Equity and liabilities Equity Equity attributable to owners of the Company 32,854 41,390 Total equity 32,854 41,390 Current liabilities Borrowings 4,437 — Lease liabilities 1,675 1,614 Derivative financial instruments 184 311 Trade payables 33 1,541 Social securities and other taxes 1,448 1,659 Deferred income 23,827 20,569 Other current liabilities 5,675 8,509 Total current liabilities 37,279 34,203 Borrowings — 4,292 Lease liabilities 13,078 13,828 Deferred income 34,840 44,170 Total liabilities 85,197 96,493 Total equity and liabilities 118,051 137,883 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 Six month period ended June 30, ended June 30, 2024 2023 2024 2023 €1,000 €1,000 €1,000 €1,000 Revenue 6,305 1,205 10,755 1,860 Other income 156 38 366 80 Research and development costs (7,048) (5,909) (16,331) (11,969) General and administrative costs (3,013) (4,145) (6,465) (8,171) Total operating costs (10,061) (10,054) (22,796) (20,140) Operating result (3,600) (8,811) (11,675) (18,200) Finance income and expense 513 470 1,001 (74) Results related to associates and financial assets — — — — Results related to financial liabilities measured at fair value through profit or loss 195 221 127 891 Results on derecognition of financial liabilities — 101 — 509 Result before corporate income taxes (2,892) (8,019) (10,547) (16,874) Income taxes 200 42 197 42 Result for the period (2,692) (7,977) (10,350) (16,832) Other comprehensive income (foreign exchange differences on foreign operation) 85 7 276 (212) Total comprehensive income (2,607) (7,970) (10,074) (17,044) Result attributable to Owners of the Company (2,692) (7,993) (10,350) (16,926) Non-controlling interests — 16 — 94 (2,692) (7,977) (10,350) (16,832) Total comprehensive income attributable to Owners of the Company (2,607) (7,986) (10,074) (17,138) Non-controlling interests — 16 — 94 (2,607) (7,970) (10,074) (17,044) Share information Weighted average number of shares outstanding1 81,665,565 80,939,392 81,618,038 80,913,751 Earnings per share attributable to owners of the Company (Euro per share) Basic loss per share1 (0.03) (0.10) (0.13) (0.21) Diluted loss per share1 (0.03) (0.10) (0.13) (0.21) 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 Attributable to owners of the Company Numberof shares ShareCapital SharePremium Equity settledEmployeeBenefitReserve TranslationReserve AccumulatedDeficit Total Non-controllinginterests TotalEquity €1,000 €1,000 €1,000 €1,000 €1,000 €1,000 €1,000 €1,000 Balance at January 1, 2023 84,246,967 3,370 412,540 29,052 1,212 (379,110) 67,064 (384) 66,680 Result for the period — — — — — (16,926) (16,926) 94 (16,832) Other comprehensive income — — — — (212) — (212) — (212) Recognition of share-based payments — — — 1,860 — — 1,860 — 1,860 Treasury shares transferred (122,584) — — — — — — — — Share options lapsed — — — (3,873) — 3,873 — — — Share options exercised 122,584 — 4 (231) — 231 4 — 4 Balance at June 30, 2023 84,246,967 3,370 412,544 26,808 1,000 (391,932) 51,790 (290) 51,500 Balance at January 1, 2024 84,248,384 3,370 412,894 25,159 817 (400,850) 41,390 — 41,390 Result for the period — — — — — (10,350) (10,350) — (10,350) Other comprehensive income — — — — 276 — 276 — 276 Recognition of share-based payments — — — 1,364 — — 1,364 — 1,364 Treasury shares transferred (326,455) — — — — — — — — Share options lapsed — — — (359) — 359 — — — Share options exercised / RSUs vested 326,455 — 174 (288) — 288 174 — 174 Balance at June 30, 2024 84,248,384 3,370 413,068 25,876 1,093 (410,553) 32,854 — 32,854 PROQR THERAPEUTICS N.V.Unaudited Condensed Consolidated Statement of Cash Flows Three month period Six month period ended June 30, ended June 30, 2024 2023 2024 2023 €1.000 €1.000 €1.000 €1.000 Cash flows from operating activities Net result (2,692) (7,977) (10,350) (16,832) Adjustments for: — Depreciation 711 594 1,402 1,143 — Share-based compensation 628 765 1,364 1,860 — Financial income and expenses (513) (470) (1,001) 74 — Results related to associates and financial assets — — — — — Results related to financial liabilities measured at fair value through profit or loss (195) (221) (127) (891) — Results on derecognition of financial liabilities — (101) — (509) — Income tax expenses (200) — (197) — Changes in working capital (4,614) (3,622) (13,838) 48,668 Cash (used in)/generated from operations (6,875) (11,032) (22,747) 33,513 Corporate income tax received/(paid) 199 — 196 — Interest received 610 685 1,542 865 Interest paid (190) — (379) — Net cash (used in)/generated from operating activities (6,256) (10,347) (21,388) 34,378 Cash flow from investing activities Increase in financial asset - current — — (17,000) — Purchases of property, plant and equipment (267) (294) (999) (430) Sales of property, plant and equipment — — — 47 Net cash used in investing activities (267) (294) (17,999) (383) Cash flow from financing activities Proceeds from exercise of share options 12 4 174 4 Repayment of lease liability (294) (647) (875) (906) Net cash used in financing activities (282) (643) (701) (902) Net (decrease)/increase in cash and cash equivalents (6,805) (11,284) (40,088) 33,093 Currency effect cash and cash equivalents 62 860 133 694 Cash and cash equivalents, at beginning of the period 85,713 138,986 118,925 94,775 Cash and cash equivalents at the end of the period 78,970 128,562 78,970 128,562