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]