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]

Financial Data and Key Metrics Changes - Revenue for Q1 2025 was $9.2 million, down from $12.5 million in the prior year quarter, attributed to the timing of revenue recognition under the collaboration agreement with GSK [35] - Research and development expenses increased to $40.6 million from $33.4 million year-over-year, driven by spending on the Inhibin E program and RNA editing programs [35] - General and administrative expenses rose to $18.4 million from $13.5 million, primarily due to share-based compensation and professional fees [35] - Net loss for Q1 2025 was $46.9 million, compared to a net loss of $31.6 million in the prior year quarter [35] - Cash and cash equivalents at the end of Q1 2025 were $243.1 million, down from $302.1 million as of December 31, 2024, expected to fund operations into 2027 [35] Business Line Data and Key Metrics Changes - The company is advancing its clinical pipeline, including obesity, AATD, DMD, and HD programs, with significant progress reported in the last twelve months [6][7] - WVE-007 for obesity is designed to provide sustainable weight loss with infrequent dosing, showing promising preclinical data [8][10] - WVE-006 for AATD is positioned as a first treatment addressing the root cause of the disease, with ongoing clinical trials demonstrating durability of effect [12][13] - WVE-N531 for DMD has shown statistically significant improvements in muscle health and function, with plans for NDA submission in 2026 [15][20] Market Data and Key Metrics Changes - The obesity treatment market is evolving with the introduction of WVE-007, which aims to overcome limitations of current GLP-1 therapies [8][10] - The DMD market has a significant unmet need, with approximately 20,000 new cases annually, and current exon skipping therapies generating about $1.1 billion in sales in 2024 [19] - The Huntington's disease market is also underserved, with no disease-modifying therapies available, affecting over 200,000 people in the US and Europe [21] Company Strategy and Development Direction - The company is focused on unlocking the potential of RNA medicines, with a unique platform enabling a multimodal pipeline and pioneering RNA editing [6][7] - Plans include submitting NDAs for multiple candidates in 2026 and advancing a wholly owned discovery pipeline targeting both hepatic and extrahepatic diseases [14][30] - The company aims to differentiate its therapies through unique mechanisms of action and improved patient outcomes compared to existing treatments [8][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for significant data disclosures throughout 2025 [38] - The company is committed to engaging with regulatory agencies to ensure alignment on accelerated approval pathways for its therapies [45][86] - Management highlighted the importance of comprehensive data to support filings and the potential for transformative impacts on patient health [20][90] Other Important Information - The company is actively engaged in discussions with prospective strategic partners for its Huntington's disease program [23] - Upcoming data releases are expected to provide insights into the efficacy and safety of the company's pipeline candidates [28][34] Q&A Session Summary Question: What triggers data disclosure for the inhibit E program? - The company will look at time points such as one month, three months, and six months for data disclosure, with an internal cutoff for target engagement, weight loss, and biomarkers [41][43] Question: Are all drugs slated for accelerated approval under CDER? - Yes, the company confirmed that all drugs are under CDER, and discussions with the agency have remained consistent regarding the accelerated approval pathway [44][45] Question: What are the major pros and cons of RNA editing versus DNA editing? - RNA editing avoids bystander edits and potential irreversible collateral effects seen in DNA editing, making it a safer option for patients [58][61] Question: Why divide the dataset for AATD into two separate announcements? - The company believes that the 200 mg multidose data will be highly informative and does not plan to hold back data for the 400 mg cohort [71][72] Question: Will monthly dosing data be included in the NDA submission for DMD? - Yes, the plan is to include monthly dosing in the label, with ongoing discussions with the agency to support this [75][84]

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]

Core Insights - Korro Bio, Inc. has appointed Dr. Loïc Vincent as Chief Scientific Officer, bringing over 20 years of drug development experience to the company [2][3] - The company is advancing multiple candidates in its pipeline, including KRRO-110, currently in Phase 1/2a clinical study for Alpha-1 Antitrypsin Deficiency [2] - Korro's RNA-editing platform aims to develop genetic medicines for both rare and prevalent diseases, enhancing precision and long-term tolerability [4] Company Overview - Korro Bio is a clinical-stage biopharmaceutical company focused on RNA editing to create genetic medicines [4] - The company utilizes an oligonucleotide-based approach to expand the reach of genetic therapies, leveraging established regulatory pathways [4] - Korro is headquartered in Cambridge, Massachusetts [4] Leadership Appointments - Dr. GaoZhong Zhu has joined as Senior Vice President of Chemistry, Manufacturing and Controls, with over 25 years of experience in pharmaceutical development [5] - Oliver Dolan has been promoted to Principal Accounting Officer, having served as Senior Vice President of Finance since January 2024 [5]

Financial Data and Key Metrics Changes - Revenue for Q4 2024 was $83.7 million, compared to $29.1 million in Q4 2023, while full-year revenue was $108.3 million versus $113.3 million in 2023, indicating a significant quarter-over-quarter increase primarily due to deferred revenue recognition from the Takeda collaboration [34][35] - R&D expenses increased to $44.6 million in Q4 2024 from $34.1 million in Q4 2023, and for the full year, R&D expenses rose to $159.7 million from $130.0 million in 2023, driven by new program spending [34] - The net income for Q4 2024 was $29 million, a turnaround from a net loss of $16.3 million in the prior year, while the full-year net loss was $96.7 million compared to $57.5 million in 2023 [34][35] - Cash and cash equivalents at year-end 2024 were $302.1 million, up from $200.4 million at the end of 2023, primarily due to financing proceeds and milestone payments [35] Business Line Data and Key Metrics Changes - The company advanced its WVE-007 program for obesity, with initial data expected in the second half of 2025, indicating progress in clinical trials [6][10] - WVE-006 for AATD showed a mean increase of 6.9% micromolar circulating AAT and 10.8% micromolar total AAT two weeks post single dose in the first patient study, demonstrating the potential for effective treatment [11][12] - In DMD, the company is on track to deliver 48-week data from its forward 53 clinical trial, with previous data showing a mean muscle content adjusted dystrophin of 9% [14][16] Market Data and Key Metrics Changes - The obesity treatment market is highlighted as having over 1 billion people globally, with WVE-007 positioned as a potential best-in-class treatment due to its unique mechanism of action [8][9] - The Huntington's disease market impacts over 200,000 people in the US and Europe, with the company emphasizing the importance of early intervention and allele-specific therapies [17][19] Company Strategy and Development Direction - The company is focused on RNA medicines, with a commitment to advancing its pipeline, including WVE-007 for obesity and WVE-006 for AATD, aiming to address significant unmet medical needs [5][6] - The strategy includes leveraging unique mechanisms of action to differentiate from existing therapies, particularly in obesity and genetic diseases [28][29] - The company plans to initiate clinical development of additional RNA editing programs in 2026, expanding its therapeutic reach [13][30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the company's trajectory in 2025, anticipating multiple value-accretive milestones across clinical programs [37] - The management highlighted the importance of addressing the limitations of current obesity treatments and the potential for WVE-007 to provide a sustainable weight loss solution [9][28] - There is a strong focus on regulatory engagement and the potential for accelerated pathways for DMD and Huntington's disease therapies [56][62] Other Important Information - The company has seen increased demand for participation in its clinical studies, particularly for WVE-006, indicating strong interest from both clinicians and patients [12] - The management emphasized the importance of tracking M-protein levels as a key indicator of therapeutic efficacy in AATD treatments [41][45] Q&A Session Summary Question: Can you provide more information on WVE-006's baseline protein levels? - Management indicated that the baseline was below the lower limit of detection, and emphasized tracking M-protein levels as a key metric for therapeutic impact [39][41] Question: How will DEXA scanning be used in the WVE-007 study? - Management confirmed that DEXA scans will be used to assess fat loss versus muscle mass changes, with the goal of demonstrating healthy weight loss [46][47] Question: What are the expectations for the upcoming DMD data readout? - Management confirmed ongoing discussions with regulators regarding the 48-week data and emphasized the importance of understanding dystrophin kinetics over time [51][55] Question: How does the company view the potential for mutant huntingtin lowering as a surrogate endpoint in Huntington's disease? - Management expressed that if the FDA accepts mutant huntingtin lowering as a clinical surrogate, it would be beneficial for the field and the company [60][62] Question: What has changed regarding the prevalence of Huntington's disease? - Management explained that recent research has shown that Huntington's disease begins before symptom onset, leading to a higher estimated prevalence [63][65] Question: How should we think about dosing for RNA editing versus DNA editing? - Management highlighted that dosing should be viewed in terms of efficacy and durability, with ongoing exploration of optimal dosing regimens [91][97]