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]

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]

Company Overview - ProQR Therapeutics N.V. 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 will hold its Annual General Meeting (AGM) on June 3, 2025, at 15:30 CEST in Amsterdam, Netherlands [1] - Relevant documents for the AGM will be available on ProQR's website and the SEC's website [2]

Core Insights - ProQR Therapeutics has appointed Dennis Hom as Chief Financial Officer and Dr. Cristina Lopez Lopez as Chief Medical Officer to advance its Axiomer platform and RNA editing programs into clinical stages [1][2][3] Leadership Appointments - Dennis Hom brings over 25 years of financial leadership experience, having raised more than $4.5 billion in capital and executed transactions totaling over $57 billion in disclosed value [2] - Dr. Cristina Lopez Lopez has over 20 years of experience in translational R&D, previously serving as Global Head of Neurodegeneration at Johnson & Johnson and holding senior roles at Roche and Novartis [3] Transition of Current Executives - Current CFO Jurriaan Dekkers and Chief Corporate Development Officer René Beukema will step down but remain during a transitional period to ensure continuity [4][5] Axiomer Technology Overview - ProQR is pioneering Axiomer™, a next-generation RNA base editing technology that allows specific single nucleotide edits in RNA, potentially leading to new medicines for various diseases [5][7] - Axiomer™ Editing Oligonucleotides (EONs) utilize the human cell's ADAR machinery to correct disease-causing mutations in RNA, modulating protein expression or altering protein functions [5]

Core Viewpoint - ProQR reported a quarterly loss of $0.10 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.07, marking an earnings surprise of -42.86% [1] Financial Performance - The company posted revenues of $4.6 million for the quarter ended December 2024, missing the Zacks Consensus Estimate by 51.53%, compared to revenues of $3.54 million a year ago [2] - Over the last four quarters, ProQR has surpassed consensus EPS estimates three times and topped consensus revenue estimates two times [2] Stock Performance - ProQR shares have declined approximately 30.2% since the beginning of the year, contrasting with the S&P 500's decline of -4.8% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.09 on revenues of $11.57 million, and for the current fiscal year, it is -$0.36 on revenues of $28.29 million [7] Industry Outlook - The Medical - Biomedical and Genetics industry, to which ProQR belongs, is currently in the top 26% of over 250 Zacks industries, indicating a favorable outlook [8] - Empirical research suggests a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact ProQR's stock performance [5]

Financial Reporting and Compliance - The financial statements have been prepared in accordance with IFRS, requiring estimates and assumptions that may differ from actual results[538] - There have been no material adjustments to prior period estimates for any of the periods included in the Annual Report[538] - The Company uses non-GAAP financial measures alongside IFRS measures to present its financial position and operating results[24] - The Company maintains its books and records in euro, presenting financial statements in this currency as its functional currency[25] Risks and Uncertainties - Forward-looking statements involve risks and uncertainties that may cause actual results to differ materially from expectations[32] - The Company faces risks related to geopolitical developments, including economic sanctions and trade barriers that could impact operations[37] - The impact of health epidemics and global supply chain pressures may slow or halt operations and activities[37] - The Company has not made any updates to forward-looking statements after the date of the Annual Report[36] Clinical Trials and Collaborations - The Company relies on contract research organizations (CROs) for timely enrollment in clinical trials, which may affect execution timelines[33] - The collaboration with Eli Lilly and Company includes potential milestone and royalty payments from commercial product sales[33]

[ProQR Year End 2024 Operating and Financial Results](index=1&type=section&id=ProQR%20Announces%20Year%20End%202024%20Operating%20and%20Financial%20Results) [Business Update & Recent Progress](index=1&type=section&id=Business%20Update%20%26%20Recent%20Progress) ProQR advances its Axiomer RNA editing platform, anticipating multiple clinical data readouts by 2026, supported by financing - The company is entering a pivotal growth phase, expecting up to **four clinical trial data readouts in 2025 and 2026**, with the first topline data for its NTCP program (AX-0810) anticipated in **Q4 2025**[3](index=3&type=chunk)[5](index=5&type=chunk) - In October 2024, ProQR raised approximately **$82.1 million** in gross proceeds through a public offering and a concurrent private placement with Eli Lilly, extending its cash runway into **mid-2027**[3](index=3&type=chunk)[8](index=8&type=chunk) - Strategic partnerships are a key focus, highlighted by a **$3.9 billion collaboration with Eli Lilly** and an expanded collaboration with the Rett Syndrome Research Trust, which secured up to **$9.2 million in total funding**[3](index=3&type=chunk)[8](index=8&type=chunk) - In December 2024, Dr. Peter A. Beal, a leading expert in ADAR and RNA biology, was appointed as Chief ADAR Scientist to drive the development of the Axiomer platform[8](index=8&type=chunk) [Anticipated Upcoming Events & Pipeline Milestones](index=2&type=section&id=Anticipated%20Upcoming%20Events%20%26%20Pipeline%20Milestones) ProQR outlines key pipeline milestones, with lead candidate AX-0810 targeting initial clinical data in Q4 2025 Pipeline Development Milestones | Program | Target Indication | Anticipated Milestone | | :--- | :--- | :--- | | **AX-0810** | NTCP for Cholestatic diseases | Q2 2025: CTA submission<br>Q4 2025: First clinical data | | **AX-2402** | MECP2 (R270X) for Rett Syndrome | 2025: Clinical candidate selection<br>2026: Clinical trial initiation & topline data | | **AX-2911** | PNPLA3 for MASH | 2025: Clinical candidate selection<br>2026: Clinical trial initiation & topline data | | **AX-1412** | B4GALT1 for Cardiovascular diseases | mid-2025: Update on optimization for GalNAc delivery | - The partnership with Lilly may be expanded to a total of **15 targets**, which would trigger a **$50 million opt-in payment** to ProQR[8](index=8&type=chunk) [Year End 2024 Financial Highlights](index=2&type=section&id=Year%20End%202024%20Financial%20Highlights) ProQR ended 2024 with a strong cash position of **€149.4 million**, extending its financial runway into mid-2027 Key Financial Metrics (Year Ended Dec 31) | Financial Metric | 2024 (€ million) | 2023 (€ million) | Change (€ million) | | :--- | :--- | :--- | :--- | | Cash and cash equivalents | €149.4 | €118.9 | +€30.5 | | Net cash (used in)/generated by operating activities | (€36.4) | €21.5 | -€57.9 | | Research and development costs | €36.4 | €25.1 | +€11.3 | | General and administrative costs | €13.7 | €16.2 | -€2.5 | | Net loss | €27.8 | €27.7 | +€0.1 | | Net loss per diluted share | €0.32 | €0.35 | -€0.03 | - The net positive cash flow from operations in 2023 was primarily due to the receipt of a **$60 million upfront payment** from Eli Lilly[7](index=7&type=chunk) - The increase in R&D costs in 2024 was driven by increased investments in the Axiomer platform and advancing pipeline programs[9](index=9&type=chunk) [Company & Technology Overview](index=3&type=section&id=About%20Axiomer) ProQR focuses on its proprietary Axiomer RNA editing technology, utilizing the cell's own ADAR machinery for precise RNA edits - ProQR's core technology is **Axiomer**, a next-generation RNA base editing platform[11](index=11&type=chunk)[12](index=12&type=chunk) - The technology utilizes a patient's own cellular machinery, specifically **ADAR (Adenosine Deaminase Acting on RNA) enzymes**, to edit RNA[11](index=11&type=chunk) - The mechanism involves using **Editing Oligonucleotides (EONs)** to direct ADAR to convert a specific Adenosine (A) to an Inosine (I), which the cell translates as a Guanosine (G), thereby correcting mutations or modulating protein function[11](index=11&type=chunk) [Forward Looking Statements](index=4&type=section&id=Forward%20Looking%20Statements) This section serves as a legal disclaimer, cautioning that the report contains forward-looking statements subject to significant risks - The press release includes forward-looking statements regarding clinical trial timelines, data readouts, CTA filings, the potential of the Axiomer platform, and financial position[14](index=14&type=chunk) - Key risks that could affect results include the timing and cost of clinical trials, reliance on contract research organizations and manufacturers, unpredictability of regulatory review, and general economic and geopolitical instability[14](index=14&type=chunk) - The company advises against placing undue reliance on these forward-looking statements and assumes no obligation to update them[14](index=14&type=chunk)