Biliary Atresia

Kayfanda® (odevixibat) approved as new treatment choice for cholestatic pruritus in children from six months with the rare liver condition, Alagille Syndrome E.U. marketing authorization for Kayfanda based on data from ASSERT the only Phase III trial completed in patients with Alagille SyndromeKayfanda approval for use in the E.U. further expands Ipsen’s rare cholestatic liver disease portfolio PARIS, FRANCE, xx September, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the European Commission has approved Kayfanda® (odevixibat) under exceptional circumstances for the treatment of cholestatic pruritus in Alagille Syndrome (ALGS) in patients aged 6 months or older. Kayfanda is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor. Odevixibat, the active substance in Kayfanda, blocks the ileal bile acid transporter (IBAT), which ultimately results in a decrease in serum bile acids that can form in the liver. ”Patients living with Alagille syndrome often endure a very poor quality of life as a result of the intolerable itch, which is one of the most significant symptoms of this condition,” said Christelle Huguet, Executive Vice President and Head of Research and Development, Ipsen. “Today’s decision is therefore very welcome. We will now continue in our ongoing efforts to make this new treatment option available for use with patients living in the E.U.” Approval of Kayfanda, known in ALGS as Bylvay® outside of the E.U., was based on the ASSERT Phase III clinical trial data.1 ASSERT is the world’s first and only Phase III trial completed in patients with ALGS. These data demonstrated statistically significant and clinically meaningful improvements from baseline to month 6 in scratching severity for patients on Kayfanda versus placebo. This was observed rapidly and maintained over the period of the study. A statistically significant reduction in serum bile acid concentration at the end of treatment was also demonstrated for patients on Kayfanda versus placebo, with improvements in multiple observer-reported sleep parameters. The overall incidence of treatment emergent adverse events with Kayfanda was similar to placebo, with a low drug-related diarrhea rate in patients with ALGS. “ALGS is a distressing condition, which often presents in the first few months of life. One of the most common symptoms reported, as a result of the condition, is severe pruritus, with children scratching to the point of bleeding and the itch causing sleep disturbances for the child and their carers,” said Professor Henkjan Verkade, Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital and University Medical Center Groningen, Netherlands. “To have a new treatment option that has been shown to reduce the itch and improve sleep is a very positive development for the ALGS community.” ALGS is an inherited rare, genetic disorder that can affect multiple organs including the liver, heart, skeleton, eyes and kidneys. Liver damage may result from having fewer than normal, narrowed or malformed bile ducts, which leads to a build-up of toxic bile acid, known as cholestasis and this in turn can cause fibrosis and progressive liver disease. Approximately 95% of patients with the condition present with chronic cholestasis, usually within the first few months of life and as many as 88% also present with severe, intractable pruritus. The estimated global incidence of ALGS is 3 in 100,000 live births. Ipsen has also received E.U. approval for Iqirvo® (elafibranor) for Primary Biliary Cholangitis, another important treatment in the company’s leading rare cholestatic liver disease portfolio. Kayfanda is known in ALGS as Bylvay® outside of the European Union (E.U.). Under the brand name of Bylvay it was approved in the E.U. as the first drug treatment option for all types of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older. The medicine is also currently being studied in a Phase III trial, BOLD, in Biliary Atresia with data anticipated in 2026. ENDS About Kayfanda® (odevixibat)Kaydanda® (odevixibat) is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor approved under exceptional circumstances in the E.U. for the treatment of cholestatic pruritus in Alagille syndrome (ALGS) in patients aged 6 months or older. Odevixibat was approved in June 2021 in the E.U. under the brand name Bylvay®, as the first drug treatment option for all types of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older, and in the U.S. under the brand name Bylvay®, as the first drug treatment option for patients 3 months of age and older living with cholestatic pruritus due to PFIC. Bylvay has received orphan exclusivity for the treatment of PFIC in the E.U. and in the U.S. In June 2023 Bylvay was approved in the U.S. for the treatment of cholestatic pruritus in patients from 12 months of age with ALGS and received orphan exclusivity for ALGS. About ASSERTASSERT is a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and efficacy of 120 µg /kg/day odevixibat for 24 weeks in relieving pruritus in patients with ALGS with 32 sites across North America, Europe, Middle East, and Asia Pacific. The trial enrolled patients aged 0 to 17 years of age with a genetically confirmed diagnosis of ALGS. In the primary analysis, the study met the primary endpoint showing highly statistically significant improvement in pruritus as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale), from baseline at month 6 (weeks 21 to 24), compared to the placebo arm (p=0.002). More than 90% of patients were pruritus responders (≥ 1 point change at any time during 24 weeks). The study also met the key secondary endpoint showing a highly statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24 (compared to the placebo arm p=0.001). Statistically significant improvements in multiple sleep parameters were observed as early as weeks 1-4 compared to patients on placebo with continued improvement through week 24. In the study, there were no patient discontinuations and 96% of patients rolled over into the open-label extension study. Odevixibat had an overall adverse event incidence similar to placebo and a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo). 1 Full results of the ASSERT study have been published in the Lancet, Gastroenterology & Hepatology in April 2024, Important safety information and recommendations for the use of Kayfanda will be detailed in the Summary of Product Characteristics (SmPC), published in the European public assessment report (EPAR) and available in all official EU languages. The full SmPC will be found at: http://www.ema.europa.eu About Ipsen We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fuelled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries. Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com. Ipsen contacts Investors Craig Marks | + 44 (0)7584 34 91 93 | craig.marks@ipsen.comNicolas Bogler | + 33 6 52 19 98 92 | nicolas.bogler@ipsen.com Media Anna Gibbins | + 44 7717 80 19 00| anna.gibbins@ipsen.com Disclaimers and/or Forward-Looking Statements IpsenThe forward-looking statements, objectives and targets contained herein are based on Ipsen’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com. References Ovchinsky N., et al. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSRT); a phase 3, double-blind, randomized, placebo-controlled trial. Lancet Gastroenterol / Hepatol. 2024 doi.org/10.1016/S2468-1253(24)00074-8 Attachment Ipsen PR_Kayfanda ALGS EC decision_230924

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

Innovative mixed reality technology enhances pre-surgical planning at NUH's specialised paediatric organ transplant centre in Singapore SINGAPORE, June 5, 2024 /PRNewswire/ -- For the last three decades, the transplant team at the National University Hospital (NUH)'s Department of Paediatric Surgery in the Khoo Teck Puat – National University Children's Medical Institute (KTP-NUCMI) and the National University Centre for Organ Transplantation (NUCOT) has journeyed with countless paediatric warriors who have bravely overcome various challenges on their road to recovery. One remarkable child is little Avira, who at two years old, has already undergone two major life-saving surgeries. Continue Reading Avira Han (left) with her family and her team of doctors from the National University Hospital. (Credit: National University Health System) Diagnosed with a rare illness known as biliary atresia when she was less than a month old, bile was trapped inside Avira's liver, which led to liver damage and scarring. If left untreated, her liver would eventually fail. Biliary atresia occurs in approximately one in every 20,000 live births, with a slightly higher prevalence in females. Overcoming the first hurdle with primary treatment Liver transplantation has proven highly successful in the long-term treatment of children with biliary atresia, with an overall survival of more than 90 per cent. However, the initial treatment is to perform a Kasai procedure because 50 to 60 per cent of children experience significant improvement and may survive well with their own liver until much older. Hence, Avira first underwent the Kasai procedure at two months old, where her surgeon Adjunct Associate Professor Vidyadhar Mali, a Senior Consultant in the Department of Paediatric Surgery at KTP-NUCMI, NUH, and the Surgical Director of the Paediatric Kidney and Liver Transplantation Programmes at NUCOT, removed the obstructed bile ducts outside the liver and attached a loop of the small intestine directly to the liver, restoring bile flow. Nonetheless, three in five children may still face progressive liver-related complications following a Kasai procedure. For Avira, a post-operative follow-up two months later revealed progressive deterioration of her liver function and a liver transplant was deemed necessary. Her mother, Mrs Han, stepped forward as a donor. Preparing for a complex, high-risk surgery with hybrid mixed reality technology Preparing Avira for her transplant required overcoming significant challenges. Liver transplants in a small child (weighing less than 10kg) is relatively rare and considered highly challenging. These cases require specialised surgical expertise and careful planning due to the complexities involved in such small patients. Factors such as the child's small size, the need for appropriately sized liver donor grafts, and the delicate nature of paediatric patients add significant risks and technical difficulty to the procedure. Being extremely small, Avira needed to be on a feeding tube to gain weight in two months. Furthermore, her small size meant that her surgeons would have to split her mother's donated liver (known as graft reduction) to ensure that the organ would be a right fit for Avira. Unlike adults, small children being transplanted with grafts too large or too small for them may present issues following liver transplantation and as the child grows older. Studies have found that different approaches and graft-size matching strategies that are age- and body weight-appropriate are crucial for better outcomes in paediatric living donor liver transplantations. In addition to reducing the graft size of the donor liver, the surgical team needed to determine the exact size of the liver graft needed. Incorrectly estimating the size of the graft could lead to a longer time on the operating table for Avira, and could also increase the risk of graft damage. To ensure the right size of the graft for Avira, the surgical team, led by Adj A/Prof Mali, employed a hybrid technique of utilising mixed reality imaging ("holomedicine") to compare the child's CT scan and the CT scan of the donor liver. This played an important role in accurate pre-operative estimation of the mother's liver size into Avira's body. "Holomedicine leverages mixed reality to interact with virtual objects superimposed onto the real world, allowing for unparalleled accuracy in pre-surgical planning," explained Dr Gao Yujia, Consultant, Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, NUH, and the Assistant Group Chief Technology Officer leading the holomedicine programme at the National University Health System (NUHS). "This hybrid technique enhances surgical planning, giving us a solid road map with the potential of greater precision so that patient care and safety can be improved during the surgery itself," said Adj A/Prof Mali. Little Avira's transplant surgery – which took place in July 2022 – was a success, with both mother and child making a full recovery. Today, Avira is much like other children her age, a playful and energetic toddler, with a bright future ahead. NUCOT is the only specialist centre in Singapore which has both adult and paediatric liver and kidney transplantation services under one roof, bringing together a comprehensive multidisciplinary suite of medical specialty services required throughout our patients' transplantation journeys. As we celebrate World Transplant Day, we honour the courage of all transplanted children and their families. Through continuous innovation and compassionate care, NUCOT remains committed to transforming lives and offering hope to families navigating the complexities of organ transplantation. SOURCE National University Hospital