Financial Data and Key Metrics Changes - Revenue for Q2 2025 was $28 million, a decrease of $22 million compared to Q2 2024, while revenue for the first half of 2025 was $58 million, down $30 million year-over-year [19] - Total operating expenses for Q2 2025 were $40 million, down from $71 million in Q2 2024, and for the first half of 2025, operating expenses were $86 million compared to $139 million in the prior year [19][20] - The net loss for Q2 2025 was approximately $9.2 million or $0.34 per diluted share, compared to a net loss of $17.2 million or $0.64 per diluted share in Q2 2024 [22] Business Line Data and Key Metrics Changes - The ARCT032 program for cystic fibrosis is advancing with enrollment in a Phase 2 trial, focusing on participants who do not benefit from existing CFTR modulator therapies [6][8] - The ARCT810 program for ornithine transcarbamylase deficiency showed positive interim data, with decreases in glutamine levels observed in participants [9][10] - The company is preparing for regulatory meetings regarding its partnered COVID-19 vaccine, with applications filed in multiple regions [12][13] Market Data and Key Metrics Changes - The company has streamlined its operations to focus on the OTC and cystic fibrosis programs, extending its financial runway into 2028 [18] - Cash, cash equivalents, and restricted cash were reported at $253.4 million as of June 30, 2025, down from $293.9 million at the end of 2024 [22] Company Strategy and Development Direction - The company is focusing on its mRNA therapeutics and vaccines pipeline, with plans to provide interim data from the Phase 2 CF study in September 2025 [23] - The company aims to engage with the FDA regarding pivotal trial designs and biomarker strategies for its therapeutic programs [39][40] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the safety and tolerability of its inhaled mRNA therapeutics, addressing historical challenges in the field [36] - The company anticipates that achieving safety and a positive measurable FEV will allow for further development of its cystic fibrosis program [28][46] Other Important Information - The company appointed Dr. Monsef Slawi as Chairman of the Board effective July 1, 2025 [17] - The restructuring plan is nearing completion, consolidating operations to enhance focus on key therapeutic areas [18] Q&A Session Summary Question: Can you provide a refresher on the success criteria for the CF program? - Management indicated that a 3% threshold for FEV improvement is expected to advance the program, with a focus on safety and tolerability [27][30] Question: What safety or efficacy data do you have on a blinded basis? - Management discussed the importance of addressing toxicology and tolerability issues in inhaled RNA therapeutics, emphasizing their advancements in delivery systems [36][38] Question: Will you proceed to a higher dose cohort for CF? - The current plan includes a 12-subject trial with three doses, and management confirmed flexibility in the dosing strategy [59] Question: What is the timing for the end of Phase II meeting with the FDA? - Management expects to complete Phase II enrollment this year and engage with the FDA shortly thereafter, aiming for a Phase III initiation in 2026 [78] Question: How will you discern treatment effects without a placebo arm? - Management noted that a placebo strategy could be implemented in Phase III, leveraging historical FEV data for self-control [88] Question: What are the expectations for the OTC program? - Management indicated that decisions regarding the higher dose cohort will influence the timeline for data release, with ongoing discussions with regulatory agencies [104]

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]