Core Insights - Premarket trading is showing notable activity with significant price movements indicating potential trading opportunities before the market opens [1] Premarket Gainers - Artiva Biotherapeutics, Inc. (ARTV) has increased by 124% to $6.22 [3] - Akanda Corp. (AKAN) is up 39% at $3.10 [3] - Kezar Life Sciences, Inc. (KZR) has risen 38% to $5.80 [3] - Carbon Revolution Public Limited Company (CREV) is also up 38% at $5.15 [3] - Safe & Green Holdings Corp. (SGBX) has increased by 28% to $3.96 [3] - Achieve Life Sciences, Inc. (ACHV) is up 23% at $3.80 [3] - Revolution Medicines, Inc. (RVMD) has risen 8% to $53.90 [3] - Erayak Power Solution Group Inc. (RAYA) is up 8% at $5.76 [3] - ProQR Therapeutics N.V. (PRQR) has increased by 7% to $3.00 [3] - Bio Green Med Solution, Inc. (BGMS) is up 6% at $4.04 [3] Premarket Losers - American Rebel Holdings, Inc. (AREB) has decreased by 41% to $2.09 [4] - Sadot Group Inc. (SDOT) is down 25% at $5.35 [4] - AVITA Medical, Inc. (RCEL) has fallen 24% to $4.04 [4] - Soluna Holdings, Inc. (SLNH) is down 23% at $3.22 [4] - American Battery Technology Company (ABAT) has decreased by 17% to $4.70 [4] - CID HoldCo, Inc. (DAIC) is down 17% at $2.16 [4] - Pinnacle Food Group Limited (PFAI) has fallen 12% to $3.12 [4] - OnKure Therapeutics, Inc. (OKUR) is down 12% at $2.52 [4] - Whitehawk Therapeutics, Inc. (WHWK) has decreased by 12% to $2.29 [4] - Aqua Metals, Inc. (AQMS) is down 7% at $14.50 [4]

Core Insights - ProQR Therapeutics is focused on developing transformative RNA therapies using its proprietary Axiomer™ RNA editing technology platform [1][3] - The company will participate in several upcoming investor conferences, providing opportunities for engagement with investors [1][5] Company Overview - ProQR Therapeutics is dedicated to creating RNA therapies that can address both rare and prevalent diseases with unmet medical needs [3] - The Axiomer technology utilizes the human cell's own ADAR machinery to make precise single nucleotide edits in RNA, potentially reversing mutations or modulating protein expression [2][3] Upcoming Events - ProQR will present at the H.C. Wainwright Genetic Medicines Virtual Conference on October 14-15, 2025, with presentations available on demand starting October 14 [5] - The company will also participate in the H.C. Wainwright Liver Disease Virtual Conference on October 21-22, 2025, and the Chardan's 9th Annual Genetic Medicines Conference on October 21, 2025 [5]

[Unaudited Condensed Consolidated Financial Statements](index=2&type=section&id=Financial%20Statements) [Unaudited Condensed Consolidated Statement of Financial Position](index=2&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Financial%20Position) The statement of financial position provides a snapshot of the company's assets, equity, and liabilities as of June 30, 2025, compared to December 31, 2024, showing a decrease in total assets and equity | Metric | June 30, 2025 (€ thousands) | December 31, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :----------------------- | :------------------------ | :-------------- | :--------- | | Total assets | 137,537 | 167,958 | (30,421) | -18.11% | | Cash and cash equivalents | 119,765 | 149,408 | (29,643) | -19.84% | | Total equity | 66,983 | 88,560 | (21,577) | -24.36% | | Total liabilities | 70,554 | 79,398 | (8,844) | -11.14% | [Unaudited Condensed Consolidated Statement of Profit or Loss and Other Comprehensive Income](index=3&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Profit%20or%20Loss%20and%20Other%20Comprehensive%20Income) The company reported a significant increase in net loss for both the three and six-month periods ended June 30, 2025, primarily driven by higher research and development costs and general and administrative costs, while revenue decreased | Metric | 3 Months Ended June 30, 2025 (€ thousands) | 3 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :------------------------------------ | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | Revenue | 3,817 | 6,305 | (2,488) | -39.46% | | Research and development costs | (11,408) | (7,048) | (4,360) | 61.86% |\ | General and administrative costs | (4,816) | (3,013) | (1,803) | 59.84% | | Operating result | (12,249) | (3,600) | (8,649) | 240.25% | | Result for the period | (12,179) | (2,692) | (9,487) | 352.79% | | Basic loss per share (€) | (0.12) | (0.03) | (0.09) | 300.00% | | Metric | 6 Months Ended June 30, 2025 (€ thousands) | 6 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :------------------------------------ | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | Revenue | 8,336 | 10,755 | (2,419) | -22.49% | | Research and development costs | (23,731) | (16,331) | (7,400) | 45.31% | | General and administrative costs | (8,050) | (6,465) | (1,585) | 24.52% | | Operating result | (23,065) | (11,675) | (11,390) | 97.56% | | Result for the period | (22,258) | (10,350) | (11,908) | 115.05% | | Basic loss per share (€) | (0.21) | (0.13) | (0.08) | 61.54% | - Basic and diluted loss per share are equal due to the anti-dilutive nature of outstanding options while the company is loss-making[5](index=5&type=chunk) [Unaudited Condensed Consolidated Statement of Changes in Equity](index=4&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Changes%20in%20Equity) The statement of changes in equity reflects a decrease in total equity for the six-month period ended June 30, 2025, primarily due to the net loss for the period and negative other comprehensive income, partially offset by share-based payments | Metric | June 30, 2025 (€ thousands) | June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :----------------------- | :----------------------- | :-------------- | :--------- | | Total Equity | 66,983 | 32,854 | 34,129 | 103.88% | | Accumulated Deficit | (447,773) | (410,553) | (37,220) | 9.07% | | Recognition of share-based payments | 1,667 | 1,364 | 303 | 22.21% | - The accumulated deficit increased significantly from **(€410,553,000)** at June 30, 2024, to **(€447,773,000)** at June 30, 2025, reflecting the net loss for the period[7](index=7&type=chunk) [Unaudited Condensed Consolidated Statement of Cash Flows](index=5&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Cash%20Flows) The company experienced a substantial net decrease in cash and cash equivalents for the six-month period ended June 30, 2025, primarily due to cash used in operating activities, which increased significantly compared to the prior year | Metric | 6 Months Ended June 30, 2025 (€ thousands) | 6 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :------------------------------------ | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | Net cash used in operating activities | (27,199) | (21,388) | (5,811) | 27.17% | | Net cash used in investing activities | (325) | (17,999) | 17,674 | -98.20% | | Net cash used in financing activities | (793) | (701) | (92) | 13.12% | | Net decrease in cash and cash equivalents | (28,317) | (40,088) | 11,771 | -29.36% | | Cash and cash equivalents, at end of period | 119,765 | 78,970 | 40,795 | 51.66% | - The decrease in cash used in investing activities was largely due to no significant increase in financial assets in 2025, compared to a **€17,000,000** increase in 2024[8](index=8&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=6&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) [1. General Information](index=6&type=section&id=Note%201.%20General%20Information) ProQR Therapeutics N.V. is a Netherlands-domiciled biotechnology company focused on discovering and developing novel therapeutic medicines, listed on Nasdaq under the ticker PRQR, and operates through several wholly-owned subsidiaries - ProQR Therapeutics N.V. is a biotechnology company focused on the discovery and development of novel therapeutic medicines[9](index=9&type=chunk) - The company's ordinary shares are listed on Nasdaq Capital Market under the ticker symbol PRQR since September 18, 2014[9](index=9&type=chunk) - ProQR Therapeutics N.V. is the ultimate parent company of ten wholly-owned subsidiaries and has full control over Stichting Bewaarneming Aandelen ProQR (ESOP Foundation)[10](index=10&type=chunk)[11](index=11&type=chunk)[12](index=12&type=chunk) [2. Significant Accounting Policies](index=7&type=section&id=Note%202.%20Significant%20Accounting%20Policies) These interim condensed consolidated financial statements are prepared in accordance with IAS 34 and are consistent with the accounting policies from the December 31, 2024 annual statements. Management assesses the company's ability to continue as a going concern for at least one year based on existing funding and projected cash flows - Interim condensed consolidated financial statements are prepared in accordance with IAS 34 Interim Financial Statements[13](index=13&type=chunk) - The accounting policies are consistent with those applied in the annual financial statements for the year ended December 31, 2024[13](index=13&type=chunk) - Management expects the Company to continue as a going concern for at least one year, based on existing funding, current cash position, and projected cash flows[16](index=16&type=chunk) - The Company operates in one reportable segment: the discovery and development of innovative, RNA-based therapeutics[17](index=17&type=chunk) [3. Adoption of New and Revised International Financial Reporting Standards](index=7&type=section&id=Note%203.%20Adoption%20of%20New%20and%20Revised%20International%20Financial%20Reporting%20Standards) New International Financial Reporting Standards and Interpretations that became effective on January 1, 2025, did not have a material impact on the company's condensed consolidated financial statements - New Standards and Interpretations effective January 1, 2025, did not materially impact the condensed consolidated financial statements[18](index=18&type=chunk) [4. Critical Accounting Estimates and Judgements](index=8&type=section&id=Note%204.%20Critical%20Accounting%20Estimates%20and%20Judgements) Management makes significant judgments and estimates, particularly concerning revenue recognition for the Eli Lilly collaboration and the expensing of research and development costs, which are consistent with those described in the 2024 annual financial statements - Significant judgments and estimates are made regarding carrying amounts of assets and liabilities, based on historical experience and other relevant factors[21](index=21&type=chunk) - The significant judgments and key sources of estimation uncertainty are consistent with those described in the Company's annual financial statements for the year ended December 31, 2024[23](index=23&type=chunk) [(i) Revenue recognition for the Eli Lilly and Company research and collaboration agreement](index=8&type=section&id=4.1.%20Revenue%20recognition%20for%20the%20Eli%20Lilly%20and%20Company%20research%20and%20collaboration%20agreement) Revenue recognition for the Eli Lilly collaboration involves significant judgment in identifying a single combined performance obligation (license and R&D services), recognizing revenue over time based on labor hours, and including variable consideration (milestones) when highly probable - The license granted to Lilly is not distinct from associated R&D services, leading to a single combined performance obligation[25](index=25&type=chunk) - Revenue is recognized over time using an input method based on the percentage of labor hours incurred compared to total estimated labor hours[26](index=26&type=chunk) - Equity investments made by Lilly are considered part of the transaction price and initially allocated to deferred revenue[27](index=27&type=chunk) - Variable consideration, such as development milestones, is included in the transaction price when it is highly probable that a significant reversal of cumulative revenue recognized will not occur[28](index=28&type=chunk)[29](index=29&type=chunk) [(ii) Research and development expenditures](index=9&type=section&id=4.2.%20Research%20and%20development%20expenditures) Research and development expenditures are expensed as incurred, as the criteria for capitalization are not met, with estimates made for services performed by vendors - Research and development expenses are reflected in the income statement because capitalization criteria are not met[30](index=30&type=chunk) - Estimates are made for the level of service performed by vendors and associated costs, which may vary from actual incurred amounts[30](index=30&type=chunk)[31](index=31&type=chunk) [5. Cash and Cash Equivalents](index=9&type=section&id=Note%205.%20Cash%20and%20Cash%20Equivalents) Cash and cash equivalents decreased by approximately €29.6 million from December 31, 2024, to June 30, 2025, with balances held at investment-grade banks and including short-term deposits | Metric | June 30, 2025 (€ thousands) | December 31, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :----------------------- | :------------------------ | :-------------- | :--------- | | Cash and cash equivalents | 119,765 | 149,408 | (29,643) | -19.84% | - Cash balances are held at banks with investment grade credit ratings (A-1/P-1/F1 minimum)[32](index=32&type=chunk) - Included in cash and cash equivalents are deposits fixed for at most 3-month periods[32](index=32&type=chunk) [6. Prepayments and Other Receivables](index=9&type=section&id=Note%206.%20Prepayments%20and%20Other%20Receivables) Prepayments and other receivables increased slightly to €3,931,000 at June 30, 2025, primarily consisting of payments for services not yet provided, accrued grant income, and deposits | Metric | June 30, 2025 (€ thousands) | December 31, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :----------------------- | :------------------------ | :-------------- | :--------- | | Prepayments | 2,088 | 2,410 | (322) | -13.36% | | Other receivables | 1,341 | 835 | 506 | 60.60% | | Accrued income from Rett Syndrome Research Trust | 502 | 502 | 0 | 0.00% | | Total | 3,931 | 3,747 | 184 | 4.91% | - All receivables are considered short-term and due within one year[33](index=33&type=chunk) [7. Property, Plant and Equipment](index=10&type=section&id=Note%207.%20Property,%20Plant%20and%20Equipment) Property, plant and equipment primarily consist of buildings, leasehold improvements, laboratory equipment, and a right-of-use asset for the Leiden office, which decreased slightly to €10,903,000 at June 30, 2025 - Property, plant and equipment include buildings and leasehold improvements, laboratory equipment, and other assets[35](index=35&type=chunk) - The right-of-use asset for the Leiden office and laboratory space had a carrying amount of **€10,903,000** at June 30, 2025, down from **€11,433,000** at December 31, 2024[35](index=35&type=chunk) [8. Other Current Liabilities](index=10&type=section&id=Note%208.%20Other%20Current%20Liabilities) Other current liabilities decreased to €7,403,000 at June 30, 2025, mainly comprising accruals for services provided by vendors not yet billed, payroll-related accruals, and other miscellaneous liabilities | Metric | June 30, 2025 (€ thousands) | December 31, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :----------------------- | :------------------------ | :-------------- | :--------- | | Other current liabilities | 7,403 | 8,849 | (1,446) | -16.34% | - These liabilities principally consist of accruals for services provided by vendors not yet billed, payroll related accruals and other miscellaneous liabilities[36](index=36&type=chunk) [9. Borrowings](index=10&type=section&id=Note%209.%20Borrowings) Total borrowings remained stable at €4,727,000 at June 30, 2025, primarily consisting of an Innovation credit for the sepofarsen program, for which a waiver for repayment was extended until December 31, 2025. The company also extinguished debt with Pontifax and Kreos in September 2022 | Metric | June 30, 2025 (€ thousands) | December 31, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :----------------------- | :------------------------ | :-------------- | :--------- | | Innovation credit | 2,899 | 2,899 | 0 | 0.00% | | Accrued interest | 1,828 | 1,683 | 145 | 8.61% | | Total borrowings | 4,727 | 4,582 | 145 | 3.16% | - The waiver for the remaining balance of the Innovation credit, including accrued interest, was extended until December 31, 2025[38](index=38&type=chunk) - Debt with Pontifax and Kreos was extinguished in September 2022, though their warrants remain in place until 2025 and 2026[39](index=39&type=chunk) [10. Lease Liabilities](index=10&type=section&id=Note%2010.%20Lease%20Liabilities) Lease liabilities primarily relate to the company's office and laboratory facilities in Leiden, with the current lease agreement terminating on June 30, 2031. Extension options are not included in the lease term as they are not reasonably certain to be exercised - Lease liabilities primarily consist of the lease for office and laboratory facilities at Zernikedreef in Leiden, Netherlands[40](index=40&type=chunk)[41](index=41&type=chunk) - The current lease agreement for these facilities terminates on June 30, 2031, following a one-year extension in December 2020[41](index=41&type=chunk)[42](index=42&type=chunk) - Subsequent **5**-year extension options are not included in the lease term as the Company is not reasonably certain to exercise them[42](index=42&type=chunk) [11. Deferred Income](index=11&type=section&id=Note%2011.%20Deferred%20Income) Total deferred income decreased to €44,435,000 at June 30, 2025, primarily from payments related to the Eli Lilly and Company collaboration and, to a lesser extent, the Rett Syndrome Research Trust | Source | June 30, 2025 (€ thousands) | December 31, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :------------------------------------ | :----------------------- | :------------------------ | :-------------- | :--------- | | Payments from Eli Lilly and Company (Current) | 17,390 | 21,501 | (4,111) | -19.12% | | Payments from Rett Syndrome Research Trust (Current) | 60 | 441 | (381) | -86.40% | | Payments from Eli Lilly and Company (Non-current) | 26,985 | 29,429 | (2,444) | -8.30% | | Total deferred income | 44,435 | 51,371 | (6,936) | -13.50% | [12. Shareholders' Equity](index=11&type=section&id=Note%2012.%20Shareholders'%20Equity) The company's authorized share capital consists of 170 million ordinary and 170 million preference shares. In October 2024, ProQR completed a public offering and a concurrent private placement with Eli Lilly, raising significant net proceeds. Share-based compensation expenses increased for the six-month period ended June 30, 2025 - Authorized share capital is **€13,600,000**, comprising **170,000,000** ordinary shares and **170,000,000** preference shares, each with a par value of **€0.04**[46](index=46&type=chunk) - In October 2024, the company completed a public offering of **18,000,000** ordinary shares and a partial exercise of underwriters' option, generating net proceeds of approximately **€60,235,000**[48](index=48&type=chunk) - Concurrently, Eli Lilly purchased **3,523,538** ordinary shares in a private placement for gross proceeds of approximately **$12,300,000** (**€11,400,000**)[51](index=51&type=chunk) | Metric | 6 Months Ended June 30, 2025 (€ thousands) | 6 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | Share-based compensation expenses | 1,667 | 1,364 | 303 | 22.21% | [13. Revenue](index=12&type=section&id=Note%2013.%20Revenue) Revenue primarily stems from a global licensing and research collaboration with Eli Lilly, initiated in September 2021 and expanded in December 2022. The company recognizes revenue over time for R&D activities and at a point in time for certain milestones, with $2,000,000 (€1,781,000) in milestones recognized in the first half of 2025 - The company has a global licensing and research collaboration with Eli Lilly and Company, focused on RNA editing platform for genetic disorders[54](index=54&type=chunk) - The collaboration was expanded in December 2022 to include additional targets in the central and peripheral nervous systems[56](index=56&type=chunk) - During the six-month period ended June 30, 2025, the Company reached milestones amounting to **$2,000,000** (**€1,781,000**) under the agreement, which was partially recognized as revenue[58](index=58&type=chunk) - Revenue is initially recognized over time using an input method based on estimated labor hours for R&D services, while variable consideration for development and commercial milestones is recognized at a point in time when achieved and uncertainty is resolved[59](index=59&type=chunk) [14. Other Income](index=14&type=section&id=Note%2014.%20Other%20Income) Other income primarily consists of grant income, totaling €380,000 for the six-month period ended June 30, 2025. This includes an agreement with the Rett Syndrome Research Trust (RSRT) for EONs development, with additional funding secured in December 2024 | Metric | 6 Months Ended June 30, 2025 (€ thousands) | 6 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | Grant income | 380 | 366 | 14 | 3.83% | - In January 2024, the Company entered an agreement with RSRT for EONs development, receiving an initial research grant of up to **€1,015,000**[60](index=60&type=chunk) - In December 2024, the partnership with RSRT expanded to include an additional **$8,150,000** in funding to advance selected candidates into clinical trials, though no amounts have been received or work commenced as of June 30, 2025[60](index=60&type=chunk) [15. Research and Development Costs](index=14&type=section&id=Note%2015.%20Research%20and%20Development%20Costs) Research and development costs increased significantly to €23,731,000 for the six-month period ended June 30, 2025, primarily due to increased outsourced R&D activities and a rise in full-time employee equivalents (FTEs) | Metric | 6 Months Ended June 30, 2025 (€ thousands) | 6 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | Research and development costs | 23,731 | 16,331 | 7,400 | 45.31% | - The increase in R&D costs is mainly due to increased outsourced research and development activities and increased full-time employee equivalents (FTEs) in the first half of 2025[62](index=62&type=chunk) [16. General and Administrative Costs](index=14&type=section&id=Note%2016.%20General%20and%20Administrative%20Costs) General and administrative costs increased to €8,050,000 for the six-month period ended June 30, 2025, compared to the same period in the prior year | Metric | 6 Months Ended June 30, 2025 (€ thousands) | 6 Months Ended June 30, 2024 (€ thousands) | Change (€ thousands) | Change (%) | | :-------------------------- | :------------------------------------ | :------------------------------------ | :-------------- | :--------- | | General and administrative costs | 8,050 | 6,465 | 1,585 | 24.52% | [17. Investments in Financial Assets](index=14&type=section&id=Note%2017.%20Investments%20in%20Financial%20Assets) The company's investments in Phoenicis Therapeutics Inc. and Yarrow Biotechnology Inc. were both valued at €nil as of June 30, 2025, as Phoenicis discontinued operations and Yarrow's fair value was nil - ProQR holds a **3.9%** interest in Phoenicis Therapeutics Inc., which discontinued operations during Q3 2024, resulting in a €nil investment value at June 30, 2025[64](index=64&type=chunk) - ProQR holds a **5.1%** interest in Yarrow Biotechnology Inc., with its financial asset valued at €nil at June 30, 2025[65](index=65&type=chunk) [18. Income Taxes](index=15&type=section&id=Note%2018.%20Income%20Taxes) The company reported no current income tax liability at June 30, 2025, and has not recognized any deferred tax assets due to the uncertainty of future earnings. Tax losses in the Netherlands can be carried forward indefinitely but are subject to annual offset limitations - The current income tax liability is €nil at June 30, 2025[67](index=67&type=chunk) - No deferred tax assets have been recognized due to the uncertainty of future earnings[67](index=67&type=chunk) - Tax losses in the Netherlands may be carried forward indefinitely, but their offset is limited to the first **€1 million** of taxable profit and **50%** of the excess[68](index=68&type=chunk) [19. Related-Party Transactions](index=15&type=section&id=Note%2019.%20Related-Party%20Transactions) The company has no related-party transactions other than compensation paid to its Board members - The Company does not have any transactions with related parties other than compensation to its Board members[69](index=69&type=chunk) [20. Events After Balance Sheet Date](index=15&type=section&id=Note%2020.%20Events%20After%20Balance%20Sheet%20Date) There were no events after the balance sheet date that require disclosure - No events after the balance sheet date were reported[70](index=70&type=chunk)

Core Insights - ProQR Therapeutics is participating in the RNA Editing Summit from July 29-31, 2025, in Boston, MA, showcasing its advancements in RNA therapies using the Axiomer™ RNA editing technology platform [1][2] Company Overview - ProQR Therapeutics is focused on developing transformative RNA therapies, utilizing its proprietary Axiomer™ technology to create a new class of medicines for various diseases, including rare and prevalent conditions [5] - The Axiomer™ technology employs the cell's own ADAR machinery to make precise single nucleotide edits in RNA, potentially reversing mutations or modulating protein expression [4][5] Recent Developments - The company has submitted a Clinical Trial Application (CTA) for AX-0810, aimed at treating cholestatic diseases, and is making progress in central nervous system (CNS) applications of its Axiomer technology [2] - At the RNA Editing Summit, ProQR will present preclinical data related to its CNS programs and the Rett syndrome program targeting MECP2, highlighting the potential of Axiomer in addressing severe neurodevelopmental diseases [2][8] Future Directions - The presentation at the summit will include long-term and multiple dose data from non-human primate (NHP) studies, emphasizing the therapeutic applications of Axiomer in both CNS and liver diseases [8] - ProQR is committed to expanding its pipeline with a focus on unmet medical needs, aiming to advance its lead development programs and clinical trials in the coming years [9]

Core Viewpoint - ProQR Therapeutics has submitted a Clinical Trial Application (CTA) to the European Medicines Agency (EMA) for its lead program AX-0810, which targets NTCP to address cholestatic liver diseases, marking a significant milestone in advancing its Axiomer RNA editing platform into clinical development [1][2][8] Company Overview - ProQR Therapeutics is focused on developing transformative RNA therapies using its proprietary Axiomer™ RNA editing technology platform, which utilizes ADAR-mediated RNA editing to create specific nucleotide changes in RNA [4][5] - The company aims to address unmet medical needs in both rare and prevalent diseases through its innovative RNA repair platform [5] Product Details - AX-0810 is an investigational RNA editing oligonucleotide designed to treat cholestatic liver disease by targeting NTCP, which is involved in bile acid transport [3] - The mechanism of AX-0810 is supported by human genetics data indicating that certain NTCP variants can reduce bile acid reuptake, suggesting potential benefits in improving liver health [3] Clinical Trial Information - The proposed Phase 1 study for AX-0810 will evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adult volunteers, with initial data expected in Q4 2025 [2][8] - The study will also explore biomarkers to assess early signals of target engagement, and is set to commence at a single site in the Netherlands pending regulatory clearance [2]

Core Insights - ProQR Therapeutics is set to present its Axiomer RNA editing technology at two significant scientific conferences in May 2025, showcasing its potential in transforming RNA therapies [1][2] Conference Presentations - ProQR will participate in the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting from May 13-17, 2025, in New Orleans, Louisiana, featuring both oral and poster presentations [3][4] - The company will also present at the TIDES USA 2025: Oligonucleotide and Peptide Therapeutics Conference from May 19-22, 2025, in San Diego, California, with podium presentations [5] Presentation Details - Key presentations include: - "ADAR-Mediated RNA Editing of SLC10A1(NTCP) as a Therapeutic Approach to Reduce Liver Bile Acid Re-Uptake in Cholestatic Diseases" on May 16, 2025 [6] - "ADAR-Mediated RNA Editing-Based Correction of PNPLA3 I148M Functionality to Address Hepatic Steatosis" on May 15, 2025 [6] - "ADAR-Mediated RNA Editing of Premature Termination Codon Results in Functional Correction in MECP2 for Rett Syndrome" on May 15, 2025 [6] - "Advancing Axiomer ADAR RNA Editing Platform - Editing oligonucleotides optimization for therapeutic use" on May 22, 2025 [6] Axiomer Technology Overview - Axiomer™ is a next-generation RNA base editing technology that utilizes ADAR (Adenosine Deaminase Acting on RNA) to make specific single nucleotide edits in RNA, potentially leading to new classes of medicines for various diseases [8][9] - The technology aims to correct disease-causing mutations and modulate protein expression, addressing both rare and prevalent diseases with unmet medical needs [9]

Summary of ProQure Therapeutics Conference Call Company Overview - **Company**: ProQure Therapeutics - **Technology**: Novel RNA editing platform leveraging ADAR to modify individual bases in messenger RNA [5][6] - **CEO**: Daniel DeBoer Core Industry Insights - **RNA Editing vs. DNA Editing**: RNA editing allows for precise modification of individual nucleotides in messenger RNA, which is not achievable with RNA interference (RNAi) [7][8] - **Delivery Mechanism**: Utilizes naked oligonucleotides conjugated to GalNAc sugar for liver delivery, and intrathecal administration for CNS applications [10][11] - **Dosing Frequency**: Anticipated quarterly dosing for liver delivery and every six to nine months for CNS dosing [12] Key Programs and Developments - **Lead Program**: AX810 targeting cholestatic diseases (PSC and biliary atresia) with no approved therapies, focusing on reducing bile acid uptake in the liver [19][20] - **Clinical Trial Application**: Planned submission of a CTA later this quarter, with initial data expected by the end of the year [22] - **Patient Enrollment**: Study to be conducted in healthy volunteers to measure target engagement, primarily through serum bile acid levels [25][26] Additional Programs - **Second Program**: Targets BIVERGALT1 gene associated with reduced cardiovascular disease risk [32] - **Third Program**: Focuses on Rett syndrome, with a $9 million grant from the Rett Syndrome Research Trust [34] - **Fourth Program**: Targets PNPLA3 mutation related to MESH, aiming to restore wild-type protein function [38] Strategic Partnerships - **Partnership with Eli Lilly**: Established in 2021, expanded to 10 targets with $125 million upfront payment and potential $3.75 billion in milestones [44][45] - **Development Structure**: ProQure handles discovery up to hit selection, while Lilly manages development and commercialization [45] Financial Position - **Cash Position**: Approximately EUR 134 million, funding operations into mid-2027 [50] - **Future Plans**: Clinical candidate selection for up to three programs this year, with potential for multiple candidates entering the clinic next year [51] Market Potential and Strategy - **Target Selection**: Focus on targets validated by human genetics, addressing both common and rare diseases [17] - **Commercialization Strategy**: Plans to independently commercialize rare disease products while seeking partnerships for larger indications [42] Conclusion - **Outlook**: ProQure is positioned in a promising field of RNA editing with multiple programs advancing towards clinical trials, supported by strategic partnerships and a solid financial foundation [56]

Unaudited Condensed Consolidated Financial Statements [Unaudited Condensed Consolidated Statement of Financial Position](index=2&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Financial%20Position) As of March 31, 2025, ProQR Therapeutics reported total assets of €151.7 million, a decrease from €168.0 million at year-end 2024, primarily due to a reduction in cash and cash equivalents Consolidated Statement of Financial Position (€ in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Total Assets** | **€151,689** | **€167,958** | | Cash and cash equivalents | €132,414 | €149,408 | | Non-current assets | €13,608 | €14,113 | | **Total Liabilities** | **€72,754** | **€79,398** | | Deferred income (Non-current) | €28,299 | €29,429 | | Deferred income (Current) | €19,250 | €21,942 | | **Total Equity** | **€78,935** | **€88,560** | [Unaudited Condensed Consolidated Statement of Profit or Loss and Other Comprehensive Income](index=3&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Profit%20or%20Loss%20and%20Other%20Comprehensive%20Income) For the three months ended March 31, 2025, the company reported a net loss of €10.1 million, an increase from the €7.7 million loss in the same period of 2024, driven by a significant rise in research and development costs to €12.3 million, while revenue remained relatively stable at €4.5 million Statement of Profit or Loss Highlights (€ in thousands) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Revenue | €4,519 | €4,450 | | Research and development costs | (€12,323) | (€9,283) | | Operating result | (€10,816) | (€8,075) | | Result for the period (Net Loss) | (€10,079) | (€7,658) | | Basic and Diluted loss per share | (€0.10) | (€0.09) | [Unaudited Condensed Consolidated Statement of Changes in Equity](index=4&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Changes%20in%20Equity) Total equity decreased from €88.6 million at the start of 2025 to €78.9 million at March 31, 2025, primarily due to the net loss of €10.1 million for the period, slightly offset by €0.8 million recognized for share-based payments Changes in Equity for Q1 2025 (€ in thousands) | Description | Amount | | :--- | :--- | | Balance at January 1, 2025 | €88,560 | | Result for the period (Net Loss) | (€10,079) | | Other comprehensive income | (€371) | | Recognition of share-based payments | €758 | | Other minor changes | €67 | | **Balance at March 31, 2025** | **€78,935** | [Unaudited Condensed Consolidated Statement of Cash Flows](index=5&type=section&id=Unaudited%20Condensed%20Consolidated%20Statement%20of%20Cash%20Flows) The company experienced a net decrease in cash and cash equivalents of €16.5 million during the first quarter of 2025, driven by €15.8 million used in operating activities, €0.2 million in investing activities, and €0.5 million in financing activities, with cash and cash equivalents at €132.4 million at period-end Cash Flow Summary for Q1 2025 vs Q1 2024 (€ in thousands) | Cash Flow Activity | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | (€15,798) | (€15,132) | | Net cash used in investing activities | (€224) | (€17,732) | | Net cash used in financing activities | (€500) | (€419) | | **Net decrease in cash and cash equivalents** | **(€16,522)** | **(€33,283)** | | **Cash and cash equivalents at end of period** | **€132,414** | **€85,713** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=6&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed explanations of accounting policies, critical judgments, and specific financial items supporting the consolidated statements [Note 1: General Information](index=6&type=section&id=1.%20General%20Information) ProQR Therapeutics N.V. is a Netherlands-based biotechnology company focused on discovering and developing novel therapeutic medicines, with its ordinary shares listed on the Nasdaq Capital Market under the ticker symbol PRQR - The company is a **biotechnology firm** domiciled in Leiden, the Netherlands, focusing on the discovery and development of **novel therapeutic medicines**[9](index=9&type=chunk)[10](index=10&type=chunk) - The company's shares have been listed on Nasdaq since September 18, 2014, and currently trade on the **Nasdaq Capital Market** under the ticker **PRQR**[9](index=9&type=chunk) [Note 2: Significant Accounting Policies](index=7&type=section&id=2.%20Significant%20Accounting%20Policies) The interim financial statements are prepared in accordance with IAS 34 and use accounting policies consistent with the 2024 annual financial statements, with management concluding that the going concern basis is appropriate based on existing funding and business plans - The interim financial statements are prepared according to **IAS 34** and should be read with the annual statements for the year ended December 31, 2024[13](index=13&type=chunk) - Management confirms the adoption of the **going concern basis of accounting**, expecting the company to fund its operations for at least one year from the signing date based on its current cash position and business plan[16](index=16&type=chunk) [Note 3: Adoption of New and Revised International Financial Reporting Standards](index=7&type=section&id=3.%20Adoption%20of%20New%20and%20Revised%20International%20Financial%20Reporting%20Standards) The adoption of new and revised International Financial Reporting Standards effective January 1, 2025, did not have a material impact on the company's condensed consolidated financial statements - New standards and interpretations effective January 1, 2025, had **no material impact** on the financial statements[18](index=18&type=chunk) [Note 4: Critical Accounting Estimates and Judgements](index=8&type=section&id=4.%20Critical%20Accounting%20Estimates%20and%20Judgements) Significant management judgment is applied to revenue recognition for the Eli Lilly collaboration and to research and development expenditures, with the Lilly agreement's license and R&D services treated as a single performance obligation and R&D expenses expensed as incurred - A key judgment in the Eli Lilly collaboration is treating the license and associated R&D services as a **single combined performance obligation**, as the license lacks stand-alone value without ProQR's R&D involvement[24](index=24&type=chunk)[25](index=25&type=chunk) - Revenue from the Lilly agreement is recognized over time using an input method based on the percentage of labor hours incurred versus total estimated hours, with the total deferred revenue balance for this obligation at **€47.3 million** at March 31, 2025[26](index=26&type=chunk) - Research and development expenditures are **expensed in the income statement** as they are incurred because the criteria for capitalization have not been met[30](index=30&type=chunk) [Note 5: Cash and Cash Equivalents](index=9&type=section&id=5.%20Cash%20and%20Cash%20Equivalents) The company's cash and cash equivalents decreased to €132.4 million at March 31, 2025, from €149.4 million at December 31, 2024, with these balances held at banks with investment-grade credit ratings Cash and Cash Equivalents (€ in thousands) | Date | Amount | | :--- | :--- | | March 31, 2025 | €132,414 | | December 31, 2024 | €149,408 | [Note 6: Prepayments and Other Receivables](index=9&type=section&id=6.%20Prepayments%20and%20Other%20Receivables) Prepayments and other receivables increased to €5.1 million as of March 31, 2025, from €3.7 million at the end of 2024, primarily consisting of prepayments for vendor services, accrued grant income, and other receivables Prepayments and Other Receivables Breakdown (€ in thousands) | Category | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Prepayments | 2,910 | 2,410 | | Other receivables | 1,725 | 835 | | Accrued income from RSRT | 502 | 502 | | **Total** | **5,137** | **3,747** | [Note 7: Property, Plant and Equipment](index=10&type=section&id=7.%20Property,%20Plant%20and%20Equipment) Property, plant, and equipment primarily consists of buildings, leasehold improvements, and laboratory equipment, with the right-of-use asset for the leased Leiden office and laboratory space having a carrying amount of €11.1 million at March 31, 2025 - The right-of-use asset for the leased Leiden office and laboratory space had a carrying amount of **€11,122,000** at March 31, 2025, down from €11,433,000 at December 31, 2024[35](index=35&type=chunk) [Note 8: Other Current Liabilities](index=10&type=section&id=8.%20Other%20Current%20Liabilities) Other current liabilities decreased to €7.3 million at March 31, 2025, from €8.8 million at year-end 2024, mainly composed of accruals for services from vendors, payroll-related accruals, and other miscellaneous items - Other current liabilities were **€7,271,000** at March 31, 2025, compared to €8,849,000 at December 31, 2024, consisting mainly of accruals for vendor services and payroll[36](index=36&type=chunk) [Note 9: Borrowings](index=10&type=section&id=9.%20Borrowings) Borrowings relate to an Innovation credit for the sepofarsen program, with a remaining balance of €4.7 million (including accrued interest) classified as current, for which the company received a waiver extended until December 31, 2025, while warrants from previously extinguished debt remain outstanding - The remaining Innovation credit of **€2,899,000** is recognized under current borrowings[37](index=37&type=chunk) - In January 2025, a waiver for the total balance of the Innovation credit, including interest (**€4,582,000**), was extended until December 31, 2025[38](index=38&type=chunk) - Warrants related to extinguished debt with Pontifax and Kreos remain outstanding until 2025 and 2026 and are accounted for as **derivative financial liabilities**[39](index=39&type=chunk) [Note 10: Lease Liabilities](index=10&type=section&id=10.%20Lease%20Liabilities) Lease liabilities primarily relate to the company's headquarters and laboratory facilities in Leiden, the Netherlands, with the current lease agreement for these facilities terminating on June 30, 2031 - The company leases **4,818 square meters** of office and laboratory facilities in Leiden, Netherlands, with the current lease agreement ending on **June 30, 2031**[41](index=41&type=chunk) [Note 11: Deferred Income](index=11&type=section&id=11.%20Deferred%20Income) Total deferred income was €47.5 million at March 31, 2025, down from €51.4 million at year-end 2024, with the vast majority of this balance relating to payments from the Eli Lilly and Company collaboration Deferred Income Breakdown (€ in thousands) | Source | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Payments from Eli Lilly and Company | 47,329 | 50,930 | | Payments from Rett Syndrome Research Trust | 220 | 441 | | **Total Deferred Income** | **47,549** | **51,371** | [Note 12: Shareholders' Equity](index=11&type=section&id=12.%20Shareholders'%20Equity) As of March 31, 2025, the company had 107.7 million ordinary shares issued, having raised approximately $82.1 million in combined gross proceeds from an underwritten public offering and a concurrent private placement with Eli Lilly in late 2024, with share-based compensation expense for Q1 2025 at €758,000 - In October 2024, the company raised gross proceeds of **$69.8 million** (**€64.6 million**) from an underwritten public offering and an additional **$12.3 million** (**€11.4 million**) from a concurrent private placement with Lilly[48](index=48&type=chunk)[51](index=51&type=chunk) - Share-based compensation expense for the three months ended March 31, 2025, was **€758,000**, compared to €736,000 for the same period in 2024[53](index=53&type=chunk) [Note 13: Revenue](index=12&type=section&id=13.%20Revenue) Revenue is generated from the global licensing and research collaboration with Eli Lilly, focused on ProQR's Axiomer® RNA editing platform, with the company achieving milestones worth $1.0 million in Q1 2025, which was added to the transaction price and partially recognized as revenue - The collaboration with Lilly, initiated in September 2021 and expanded in December 2022, utilizes ProQR's **Axiomer® RNA editing platform** for genetic disorders in the liver and nervous system[54](index=54&type=chunk)[56](index=56&type=chunk) - The agreement is accounted for as a **single performance obligation** (license plus R&D), with revenue recognized over time using a labor-hours input method[59](index=59&type=chunk) - In Q1 2025, the company reached milestones of **$1,000,000** (**€918,000**) under the Lilly agreement, which was added to the transaction price[58](index=58&type=chunk) [Note 14: Other Income](index=14&type=section&id=14.%20Other%20Income) Other income for Q1 2025 was €222,000, consisting entirely of grant income from an agreement with the Rett Syndrome Research Trust (RSRT), which focuses on developing editing oligonucleotides (EONs) for MECP2 mutations - Other income of **€222,000** for Q1 2025 (Q1 2024: €210,000) was grant income recognized from the **RSRT agreement**[62](index=62&type=chunk) - The RSRT partnership was expanded in December 2024 to include an additional **$8.15 million** in funding to advance candidates into clinical trials, though no amounts have been received under this expansion as of March 31, 2025[62](index=62&type=chunk) [Note 15: Research and Development Costs](index=14&type=section&id=15.%20Research%20and%20Development%20Costs) Research and development costs increased to €12.3 million for the first quarter of 2025, up from €9.3 million in the same period of 2024, primarily driven by higher outsourced R&D activities and an increase in full-time employee equivalents (FTEs) Research and Development Costs (€ in thousands) | Period | Amount | | :--- | :--- | | Q1 2025 | €12,323 | | Q1 2024 | €9,283 | - The year-over-year increase in R&D costs was mainly due to **increased outsourced research and development activities** and **higher FTE count**[64](index=64&type=chunk) [Note 16: General and Administrative Costs](index=14&type=section&id=16.%20General%20and%20Administrative%20Costs) General and administrative costs were €3.2 million for the three months ended March 31, 2025, a slight decrease from €3.5 million in the corresponding period of 2024 General and Administrative Costs (€ in thousands) | Period | Amount | | :--- | :--- | | Q1 2025 | €3,234 | | Q1 2024 | €3,452 | [Note 17: Investments in Financial Assets](index=14&type=section&id=17.%20Investments%20in%20Financial%20Assets) The company's investments in financial assets, including interests in Phoenicis Therapeutics Inc. and Yarrow Biotechnology Inc., were valued at nil as of March 31, 2025, following Phoenicis' discontinuation of operations in the third quarter of 2024 - The company holds a **3.9% interest in Phoenicis** and a **5.1% interest in Yarrow**, with both investments valued at **€ nil** as of March 31, 2025[66](index=66&type=chunk)[67](index=67&type=chunk) - Phoenicis Therapeutics Inc. discontinued its operations during the quarter ended September 30, 2024[66](index=66&type=chunk) [Note 18: Income Taxes](index=15&type=section&id=18.%20Income%20Taxes) The company had no current income tax liability as of March 31, 2025, and has not recognized any deferred tax assets related to its operating losses due to uncertainty about the timing and amount of future earnings, despite these losses being carried forward indefinitely - **No deferred tax asset** has been recognized for operating losses due to uncertainty of future earnings[69](index=69&type=chunk) - Tax losses can be carried forward indefinitely in the Netherlands, but their offset against future profits is subject to certain limitations[70](index=70&type=chunk) [Note 19: Related-Party Transactions](index=15&type=section&id=19.%20Related-Party%20Transactions) The company's only related-party transactions consist of compensation to its Board members - The company has **no related-party transactions** other than compensation paid to its Board members[71](index=71&type=chunk) [Note 20: Events After Balance Sheet Date](index=15&type=section&id=20.%20Events%20After%20Balance%20Sheet%20Date) There were no significant events that occurred after the balance sheet date of March 31, 2025 - None[72](index=72&type=chunk)

Core Insights - ProQR Therapeutics reported strong financial and operational results for Q1 2025, highlighting a solid balance sheet and a focus on executing its RNA editing programs [2][5][8] Financial Performance - As of March 31, 2025, ProQR held cash and cash equivalents of €132.4 million, down from €149.4 million at the end of 2024 [8] - The net loss for Q1 2025 was €10.1 million, or €0.10 per diluted share, compared to a net loss of €7.7 million, or €0.09 per diluted share, for the same period last year [10][19] - Research and development costs increased to €12.3 million in Q1 2025 from €9.3 million in Q1 2024, while general and administrative costs decreased slightly to €3.2 million from €3.5 million [9] Business Updates - ProQR is on track to submit a Clinical Trial Application (CTA) for its lead RNA editing program, AX-0810, targeting NTCP for cholestatic diseases in Q2 2025, with initial clinical data expected in Q4 2025 [5][6] - The company has strengthened its leadership team with the appointments of Dennis Hom as Chief Financial Officer and Dr. Cristina Lopez Lopez as Chief Medical Officer [6][5] - ProQR achieved a milestone in its collaboration with Eli Lilly, earning $1.0 million (€918,000) during the first quarter [8] Upcoming Milestones - Key upcoming events include the CTA submission for AX-0810 in Q2 2025 and the first clinical data readout in Q4 2025 [5][6] - Other programs in the pipeline include AX-2402 for Rett Syndrome and AX-2911 for MASH, with clinical candidate selections expected in 2025 [6] Research and Development Focus - ProQR's Axiomer RNA editing technology is advancing across liver and CNS programs, with a focus on addressing cholestatic liver diseases and other conditions [5][11] - The company presented at the RNA Editing Gordon Research Conference and plans to showcase multiple abstracts at the upcoming ASGCT Annual Meeting [6]

Company Overview - ProQR Therapeutics NV is focused on developing transformative RNA therapies using its proprietary Axiomer RNA editing technology platform [1][4] - The company aims to create a new class of medicines targeting both rare and prevalent diseases with unmet medical needs [4] Axiomer Technology - Axiomer is a next-generation RNA base editing technology that allows for specific single nucleotide changes in RNA [3][4] - The technology utilizes the human cell's own ADAR (Adenosine Deaminase Acting on RNA) machinery to convert Adenosine (A) to Inosine (I), which is then translated as Guanosine (G), effectively correcting disease-causing mutations [3] Upcoming Events - ProQR management is scheduled to present at the Citizens (JMP) Life Sciences Conference in New York City on May 8, 2025, at 11:30 AM EDT [1] - A live webcast of the presentation will be available on ProQR's website, with a replay accessible for approximately 30 days [2]