Company Overview - ProQR is pioneering ADAR-mediated RNA editing with its Axiomer platform, moving from invention to clinical trials [11, 17] - The company has a strong intellectual property estate and strategic partnerships with Eli Lilly and Rett Syndrome Research Trust [17, 135] - ProQR's cash and cash equivalents were €119.8 million as of the end of Q2 2025, providing a runway into mid-2027 [18, 136] Pipeline and Clinical Development - AX-0810, targeting NTCP for cholestatic diseases, has received CTA authorization and is entering a Phase 1 clinical trial [17, 21] - The Phase 1 trial aims to establish safety, PK, and target engagement in healthy volunteers [21] - AX-2402, for Rett syndrome, is rapidly advancing, positioning ProQR at the forefront of neurological RNA editing medicines [21] AX-0810 and Cholestatic Diseases - Cholestatic diseases, including Primary Sclerosing Cholangitis (PSC) affecting approximately 80,000 adults and Congenital Biliary Atresia affecting approximately 20,000 pediatrics, have high unmet medical needs [24, 38] - AX-0810 is a first-in-class RNA editing therapy designed to modulate the NTCP channel, limiting bile acid uptake while preserving other channel functions [31] - The therapeutic goal of AX-0810 is to reduce inflammation and fibrosis, alleviate symptoms in PSC and BA, and prevent or delay cirrhosis, organ failure, and transplant [36] AX-0810 Clinical Trial Design - The Phase 1 trial is a multiple ascending dose (MAD) study with N=33 participants (24 on treatment, 9 on placebo) across three cohorts: 3mg/kg, 6mg/kg, and 9mg/kg (TBC) [103, 104] - The trial will assess safety, tolerability, and PK of AX-0810, and confirm target engagement as measured by changes in bile acid levels, bile acid profile, and TUDCA challenge [107] - Initial Cohort 1 safety, tolerability, and PK data are expected toward the end of 2025, with target engagement data on all cohorts anticipated in H1 2026 [107, 131]

Summary of ProQR Therapeutics FY Conference Call Company and Industry Overview - **Company**: ProQR Therapeutics (NasdaqCM:PRQR) - **Industry**: RNA editing and therapeutics, specifically targeting alpha-1 antitrypsin deficiency (AATD) and cholestatic diseases Key Points and Arguments Alpha-1 Antitrypsin Deficiency (AATD) Treatment - ProQR's lead program focuses on AATD, a validated target caused by a single point mutation with measurable biomarkers [2][4] - The company aims to transition patients from a ZZ phenotype (high risk of lung and liver disease) to an MZ phenotype (low risk) through RNA editing [5][6] - Clinical data showed a shift from 0% M protein to 44% after a single dose, with levels reaching 65% in multi-dose cohorts [7][8] - The treatment demonstrated the ability to produce more protein than previously seen with inhibitors, indicating a durable response [9][10] Mechanism of Action - The editing approach corrects mutations at the transcript level, allowing patients to produce functional proteins during acute phase responses [6][9] - The drug is designed to be stable and effective, utilizing GalNAc-conjugation for subcutaneous delivery [8][10] Clinical Development and Future Steps - ProQR is preparing for a 400 mg cohort study in Q1, aiming to assess the durability and efficiency of the editing process [9][10] - The company plans to engage with regulatory agencies to discuss approval thresholds, focusing on the MZ phenotype and its clinical outcomes [16][14] Other Company Insights - ProQR's AX-0810 program targets cholestatic diseases by editing NTCP to block bile acid transport into the liver, with a phase one trial recently cleared to initiate [27][28] - Preclinical data indicated a 15% editing level translating to a two-fold increase in serum bile acids, supporting the therapeutic potential [30] Industry Context and Comparisons - The RNA editing field is evolving rapidly, with ProQR and other companies focusing on GalNAc delivery to the liver [45][46] - The panel discussed the importance of selecting appropriate indications for RNA editing technologies, emphasizing the need for clear clinical benefits [68][69] Challenges and Considerations - There are misconceptions regarding the efficacy of RNA editing compared to DNA editing, particularly concerning the expected levels of protein production [68] - The need for a clear understanding of the relationship between editing levels and therapeutic benefits is crucial for gaining investor confidence [54][68] Conclusion - The conference highlighted the advancements in RNA editing technologies, particularly in treating AATD and cholestatic diseases, with ProQR at the forefront of clinical development [70][72] - The discussion underscored the importance of translating preclinical data to human clinical outcomes and the potential for RNA editing to provide meaningful therapeutic benefits [61][70]

Core Insights - ProQR Therapeutics has received authorization from the Central Committee on Research Involving Human Subjects (CCMO) for a Phase 1 Clinical Trial Application (CTA) for AX-0810, an investigational RNA editing oligonucleotide targeting NTCP, aimed at treating cholestatic diseases such as primary sclerosing cholangitis and biliary atresia [1][2] Company Overview - ProQR Therapeutics is focused on developing transformative RNA therapies using its proprietary Axiomer™ RNA editing technology platform, which utilizes the body's endogenous ADAR enzymes for RNA editing [1][8] - The company aims to create a new class of medicines for both rare and prevalent diseases with unmet medical needs [8] Clinical Development - The Phase 1 study of AX-0810 will assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) through biomarkers to establish proof of target engagement [2][5] - AX-0810 is the first program from ProQR's Axiomer™ RNA editing pipeline to enter clinical development, with the trial being conducted in the Netherlands [2][5] Upcoming Events - ProQR will host a virtual Investor and Analyst Event on November 3, 2025, to discuss the clinical trial and present findings related to AX-0810 [2][6] - The event will feature presentations from ProQR management and Professor Henkjan J. Verkade, a key opinion leader in pediatric gastroenterology/hepatology [2][3] Research Focus - Professor Verkade's research interests include pediatric cholestatic liver diseases, mechanisms of bile acid transport, and the development of biomarkers and novel therapies for rare inherited liver disorders [4] - He has authored over 300 peer-reviewed publications, contributing significantly to the field [4] Technology Platform - Axiomer™ technology allows for specific single nucleotide changes in RNA, potentially correcting disease-causing mutations and modulating protein expression [6][7] - This innovative approach aims to reduce toxic bile acid accumulation in the liver, addressing the underlying causes of cholestatic diseases [5][7]

Core Insights - ProQR Therapeutics has received authorization from the Central Committee on Research Involving Human Subjects (CCMO) for a Phase 1 Clinical Trial Application (CTA) for AX-0810, targeting cholestatic diseases [1][2] - AX-0810 is the first investigational RNA editing oligonucleotide (EON) from ProQR's Axiomer™ platform, aimed at reducing toxic bile acid accumulation in the liver [6][10] Company Overview - ProQR Therapeutics is focused on developing transformative RNA therapies using its proprietary Axiomer technology, which utilizes the body's own ADAR enzymes for RNA editing [1][10] - The company aims to create a new class of medicines for both rare and prevalent diseases with unmet medical needs [10] Clinical Development - The Phase 1 study of AX-0810 will assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) through biomarkers to establish proof of target engagement [2][6] - The trial will be conducted in the Netherlands, and dosing is set to begin following the CTA approval [2] Upcoming Events - ProQR will host a virtual Investor and Analyst Event on November 3, 2025, to discuss the clinical development of AX-0810 [2][8] - The event will feature presentations from ProQR management and Professor Henkjan J. Verkade, a key opinion leader in pediatric gastroenterology [2][4]

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]