Summary of Arcturus Therapeutics KOL Presentation on ARCT-810 Phase II Interim Data for OTC Deficiency Company Overview - **Company**: Arcturus Therapeutics - **Headquarters**: San Diego - **Focus**: mRNA medicines, specifically targeting rare liver diseases like ornithine transcarbamylase (OTC) deficiency [5][6] Industry Context - **Industry**: Biotechnology, specifically in the development of mRNA therapeutics for rare diseases - **Condition**: OTC deficiency is the most common urea cycle disorder with significant unmet medical needs [6][7] Key Points from the Presentation 1. **ARCT-810 Overview**: - ARCT-810 is an mRNA therapeutic designed to replace dysfunctional OTC enzymes, improving urea cycle activity, detoxifying ammonia, and potentially eliminating the need for liver transplants [6][7][8] - It utilizes Arcturus' proprietary lunar delivery platform for effective delivery to hepatocytes [7] 2. **Regulatory Designations**: - ARCT-810 has received multiple designations: orphan drug designation, orphan medicinal product designation, fast track designation, and rare pediatric disease designation [8] 3. **Phase II Study Design**: - Two Phase II studies were conducted: one in the US and one in Europe, focusing on safety, tolerability, and biomarker assessments [11][12] - The US study enrolled patients with more severe disease, while the European study included patients with stable disease [12] 4. **Biomarker Results**: - **Plasma Glutamine**: - In the European study, mean glutamine levels decreased from high to normal during treatment and began to rise again after four weeks post-treatment [13][14] - In the US study, glutamine levels normalized after three doses and remained normal for approximately twenty days [14] - **Ureagenesis Function**: - The new N15 assay showed significant increases in relative ureagenesis function (RUF) post-treatment, with a mean increase of 14.7% [16][17] - Two subjects achieved RUF levels above 50%, indicating clinically meaningful improvements [17] - **Ammonia Levels**: - Ammonia levels remained stable and within normal ranges after treatment, supporting the favorable glutamine and ureagenesis data [18] 5. **Safety Profile**: - The safety database included 40 participants, indicating that ARCT-810 was generally safe and well-tolerated [19] - No serious infusion-related reactions were reported, and adverse events were manageable [19][20] 6. **Next Steps**: - Arcturus plans to complete the ongoing Phase II US study and engage with regulatory agencies for a multi-biomarker driven pivotal trial [68][69] Additional Insights - **Clinical Implications**: - The KOLs emphasized the importance of normalizing diet and reducing the need for ammonia scavengers as key success metrics for OTC therapies [78][80] - mRNA therapies are viewed as a potential alternative to liver transplants, especially for severe cases [100][101] - **Comparison with Other Therapies**: - ARCT-810 is positioned as a more effective solution compared to existing ammonia scavengers, which do not restore urea cycle function [87][88] Conclusion - The interim data for ARCT-810 demonstrates promising results in reducing glutamine levels and improving urea cycle function, with a favorable safety profile. The company is poised to advance its clinical development and regulatory strategy to address the significant unmet needs in OTC deficiency treatment [67][68]

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Core Insights - Avidity Biosciences announced positive topline data from the Phase 1/2 FORTITUDE™ program for delpacibart braxlosiran (del-brax) in treating Facioscapulohumeral Muscular Dystrophy (FSHD), showing improvements in function, strength, and patient-reported outcomes compared to placebo [1][3][6] - The company plans to submit a Biologics License Application (BLA) for accelerated approval in the second half of 2026 [1][3] - Del-brax is the first investigational therapy targeting the underlying cause of FSHD by directly addressing the DUX4 gene, with no approved therapies currently available for this condition [2][13] Group 1: Clinical Data and Results - The FORTITUDE™ trial included a randomized, placebo-controlled, double-blind study evaluating 39 participants on doses of 2 mg/kg or 4 mg/kg of del-brax over 12 months [5][10] - Results indicated consistent improvements in functional mobility and muscle strength, as measured by the 10-Meter Walk-Run test, Timed Up and Go, and quantitative muscle testing [6][9] - Significant reductions in biomarkers such as KHDC1L and creatine kinase were observed, indicating muscle damage [6][7] Group 2: Safety and Regulatory Pathway - Del-brax demonstrated favorable long-term safety and tolerability, with most adverse events being mild or moderate, and no serious adverse events reported [7][9] - The U.S. FDA has opened the accelerated approval regulatory pathway for del-brax, and a global Phase 3 FORWARD™ study has been initiated [3][4] Group 3: Future Developments - The ongoing biomarker cohort of the FORTITUDE trial aims to assess the impact of del-brax on KHDC1L levels, with topline data expected in Q2 2026 [7][11] - Avidity is advancing its clinical development pipeline, focusing on RNA therapeutics through its proprietary Antibody Oligonucleotide Conjugates (AOCs™) platform [16]

Dr. Wright brings deep experience across a wide breadth of therapeutic areas and modalities and will guide clinical development of Wave's robust RNA medicines pipeline CAMBRIDGE, Mass., May 28, 2025 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced the appointment of Christopher Wright, MD, PhD, as Chief Medical Officer. Dr. Wright will join Wave's executive te ...

"We are honored to welcome Dr. Zamore to our Science Advisory Board," said Dr. Zdravka Medarova, Chief Scientific Officer and co-founder of TransCode Therapeutics. "His deep expertise in RNA biology and his track record of translating scientific discoveries into therapeutic innovations will be invaluable as we advance our pipeline of RNA-targeted cancer therapies." RNA pioneer and biotechnology innovator joins TransCode Therapeutics Science Advisory Board to advance RNA oncology Dr. Zamore co-founded Alnyla ...

Financial Data and Key Metrics Changes - For Q1 2025, revenues were $29.4 million, down from $38 million in Q1 2024, primarily due to lower development milestone revenues from the CSL collaboration as the COVID vaccine transitions to commercialization [19][20] - Research and development expenses decreased to $34.9 million from $53.6 million year-over-year, driven by lower manufacturing costs, with expectations for further declines in the second half of fiscal year 2025 [20][21] - General and administrative expenses were $11.3 million, down from $14.9 million in the same period last year, attributed to reduced share-based compensation costs [21] - The net loss for Q1 2025 was approximately $14.1 million, or $0.52 per diluted share, compared to a net loss of $3 million, or $1 per diluted share, in Q1 2024 [21] Business Line Data and Key Metrics Changes - The mRNA therapeutics pipeline is being prioritized, with significant focus on the CF and OTC programs, while the COVID vaccine program is transitioning to commercialization [11][18] - The ARCT032 program for cystic fibrosis is in Phase II, with enrollment expected to complete by the end of 2025, and interim data anticipated in mid-2025 [7][10] - The ARCT810 program for OTC deficiency is also in Phase II, with interim data expected in Q2 2025 [8][10] Market Data and Key Metrics Changes - The company received an initial milestone payment from CSL related to the EU approval of the COVID vaccine, with further payments anticipated as the program progresses [11][19] - The company is preparing for a Marketing Authorization Application in the UK in Q2 2025 and a BLA filing in the US in Q3 2025 [12] Company Strategy and Development Direction - The company has made a strategic decision to focus resources on mRNA therapeutics, particularly CF and OTC programs, due to current market conditions and regulatory uncertainties [18][19] - The STAR self-amplifying mRNA platform continues to receive positive feedback from publications, enhancing the company's position in the market [12][14] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming clinical data from the CF and OTC programs, highlighting the potential for significant advancements in treatment options [22][23] - The company remains committed to maintaining a strong financial position, with a cash runway extended into 2028, allowing for the achievement of near-term milestones [21][22] Other Important Information - The company is utilizing a newly developed 15N ureogenesis assay to monitor the effects of ARCT810 in clinical development, which is expected to provide valuable data [10][18] - Long-term data from the COVID vaccine trial suggests a favorable safety profile, with no reports of myocarditis or pericarditis [14] Q&A Session Summary Question: Can you provide more details on the changes made to extend the cash runway and potential incoming cash flows? - Management indicated that tough decisions were made regarding cost reductions and focusing on critical programs, which contributed to extending the cash runway [27][28] Question: What milestones should we expect related to the UK and US approvals for the COVID vaccine? - There are no milestones associated with the UK or US approvals; however, a milestone is anticipated with the first US revenues from the COVID vaccine, expected in 2028 [30][31] Question: What is the expected size of the initial interim cohort for ARCT032 and the bar for success? - The interim data set is expected to include 6 to 9 subjects, with a bar for success set at a 3% improvement in lung function [35][36] Question: How does ARCT032 differ from competitor programs in terms of tolerability? - The company highlighted its exclusive LUNAR lipid nanoparticle delivery technology and the high purity of its mRNA constructs as key differentiators [42][43] Question: What are the expected biomarkers for the OTC program? - Management confirmed that glutamine, orotic acid, and other biomarkers will be measured to assess the effectiveness of the treatment [86][87]

Financial Data and Key Metrics Changes - For Q1 2025, revenues were $29.4 million, down from $38 million in Q1 2024, primarily due to lower development milestone revenues from the CSL collaboration as the COVID vaccine transitions to commercialization [17][18] - Research and development expenses decreased to $34.9 million from $53.6 million year-over-year, driven by lower manufacturing costs, partially offset by increased costs for CF and OTC programs [18][19] - General and administrative expenses were $11.3 million, down from $14.9 million in the same period last year, mainly due to reduced share-based compensation costs [19][20] - The net loss for Q1 2025 was approximately $14.1 million, or $0.52 per diluted share, compared to a net loss of $3 million, or $1 per diluted share, in Q1 2024 [20] Business Line Data and Key Metrics Changes - The mRNA therapeutics pipeline is being prioritized, with significant focus on CF and OTC programs, while the COVID vaccine program is transitioning to commercialization [10][16] - The company expects to complete Phase II enrollment for ARCT032 by the end of 2025 and provide interim data for the first two cohorts in mid-2025 [6][9] - The ARCT-810 program for OTC deficiency is also progressing, with interim data expected in Q2 2025 [7][9] Market Data and Key Metrics Changes - The company received an initial milestone payment from CSL related to the EU approval of the COVID vaccine, Costave, and anticipates further milestone payments as the program progresses [10][17] - The company is preparing for a Marketing Authorization Application (MAA) filing in the UK in Q2 2025 and a U.S. BLA filing in Q3 2025 [11] Company Strategy and Development Direction - The company has made a strategic decision to focus resources on mRNA therapeutics, particularly CF and OTC programs, due to current market conditions and regulatory uncertainties [10][16] - The STAR self-amplifying mRNA platform continues to receive positive feedback from publications, enhancing the company's position in the market [11][13] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming clinical data from CF and OTC programs, indicating a strong cash runway extending into 2028 [21] - The company remains committed to advancing its therapeutic programs and believes that the science will support its regulatory interactions [100] Other Important Information - The company has received FDA Fast Track designation for ARCT2304, its mRNA vaccine candidate for pandemic influenza A [14] - The 15N Ureogenesis Assay is expected to provide important data for monitoring the effect of ARCT-810 in clinical development [9][108] Q&A Session Summary Question: Can you provide more details on extending the cash runway and potential cash flows? - Management indicated that focusing on critical programs and making cost reductions contributed to extending the cash runway, with a conservative approach to cash burn forecasts [26][27] Question: What milestones should we expect related to UK and U.S. approvals for the COVID vaccine? - There are no milestones associated with UK or U.S. approvals; however, a milestone is anticipated with the first U.S. revenues from Costave, expected in 2028 [31][60] Question: What is the expected size of the interim cohort for ARCT032? - The interim data set is expected to include 6 to 9 subjects, with a bar for success set at a 3% improvement in lung function [36][37] Question: How does ARCT032 differ from competitor programs? - The key differentiators include the exclusive LUNAR lipid nanoparticle delivery technology and the high purity of the mRNA construct, which may enhance safety and tolerability [44][45] Question: What are the thresholds for FEV1 improvement in the CF program? - A 3% improvement in FEV1 is considered a significant threshold, with higher improvements potentially allowing for smaller Phase III trial sizes [86][87] Question: Will other biomarkers be measured in the OTC program? - In addition to glutamine, orotic acid and other amino acids will also be measured as part of the biomarker strategy [88][89]

15 patients treated across four escalating dose levels of TTX-MC138 No significant safety or dose limiting toxicities reported 10 patients remain on study with no evidence of disease progression PD analysis at 24 hours post-dosing provides evidence of miR-10b target engagementBOSTON, May 8, 2025 /PRNewswire/ -- TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, today announced that the third patient in Cohort 4 of its ...

A total of 13 patients treated with four escalating doses of TTX-MC138 No significant safety or dose limiting toxicities reported Two patients have so far maintained stable disease on treatment for at least seven months PD analysis at 24 hours post-dosing provides evidence of miR-10b target engagementBOSTON, May 1, 2025 /PRNewswire/ -- TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, today announced further progress ...

Financial Data and Key Metrics Changes - Total operating loss from continuing operations increased from $6.6 million in 2023 to $6.9 million in 2024 [22] - Research and development expenses rose to $3.7 million in 2024 from $3.4 million in 2023 [22] - General and administrative expenses decreased from $3.5 million in 2023 to $3.2 million in 2024 [22] - Net loss for 2024 was $8.5 million compared to $4.3 million in the previous year [23] - Cash and cash equivalents at year-end 2024 increased to $1 million from $700,000 at the end of 2023 [25] Business Line Data and Key Metrics Changes - The RNA delivery business showed progress with new partnerships and improved manufacturing processes [6] - The company aims to advance at least one flagship program to an investigational new drug IND filing with the FDA in 2026 [14] - The legacy assets, including the nasal spray products, are expected to see significant commercial opportunities with ongoing discussions for partnerships [20] Market Data and Key Metrics Changes - The global radiopharmaceutical market reached $8.4 billion in size in 2024 and is expected to grow to $17.1 billion by 2033 [13] - The company received marketing approval for its nasal spray in Mainland China, indicating a major commercial opportunity [17] Company Strategy and Development Direction - The company plans to spin off a majority of its RNA delivery subsidiary, Altamira Therapeutics AG, to better capitalize on growth opportunities [8] - The strategy includes licensing the RNA delivery platform technology to partners in the biotech and pharma industry [12] - The company is transitioning to a holding company model, focusing on managing and monetizing its participations and assets [25] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the challenges posed by the NASDAQ delisting but expressed optimism about the planned spin-off and private equity involvement [28] - The company is focused on building its RNA delivery business and addressing the potential for RNA therapeutics [28] Other Important Information - The financial statements for 2024 were presented in U.S. dollars for the first time, reflecting a shift in reporting [20] - The company has filed several patent applications to protect its proprietary programs [14] Q&A Session Summary Question: What are the expectations for the RNA delivery business? - Management highlighted the growing momentum in the RNA delivery business and the importance of appropriate funding to continue progress [27] Question: How does the company plan to address the NASDAQ delisting? - Management discussed the painful experience of the delisting but emphasized the planned spin-off and private equity involvement as beneficial alternatives [28]