Financial Data and Key Metrics Changes - In Q3 2025, the company's revenue was $1 billion, a 45% year-over-year decline primarily due to lower COVID vaccine demand [3][10] - The net loss for the quarter was $200 million, compared to a net income of $13 million in Q3 2024, resulting in a loss per share of $0.51 [12][13] - Cash and investments at the end of Q3 were $6.6 billion, down from $7.5 billion at the end of Q2 2025 [13] Business Line Data and Key Metrics Changes - Revenue from U.S. markets was $800 million in Q3, with the majority from COVID vaccines, while international revenue was $200 million, with approximately half from Canada [8][9] - Cost of sales decreased by 60% year-over-year to $207 million, driven by lower inventory write-downs and reduced manufacturing capacity [11] - R&D expenses were $801 million, a 30% decrease from the previous year, reflecting lower clinical trial costs [12] Market Data and Key Metrics Changes - The U.S. COVID vaccination market saw a 30% year-over-year decline in cumulative retail vaccinations, with Moderna's market share increasing to 42% [20][21] - The company expects fourth-quarter sales in the U.S. to range from $100 million to $400 million, with full-year U.S. revenue guidance adjusted to $1 billion to $1.3 billion [9][10] Company Strategy and Development Direction - The company is focused on driving the use of its commercial products, advancing its pipeline, and executing with financial discipline [4][6] - Strategic partnerships have been established in Canada, the U.K., and Australia, with local manufacturing facilities and multi-year offtake agreements [4][5] - The company aims to transition from a pandemic-focused business to a diversified portfolio in seasonal vaccines, oncology, and rare diseases [30][31] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the challenges in the COVID vaccine market but expressed confidence in the growth of mNEXSPIKE and the overall pipeline [29][30] - The company is committed to achieving cash break-even by 2028, with ongoing cost reductions and revenue growth strategies [30][56] Other Important Information - The company has discontinued the development of its CMV vaccine after failing to meet primary efficacy endpoints [6][24] - The company has narrowed its revenue guidance for 2025 to $1.6 billion to $2 billion, down from $1.5 billion to $2.2 billion [9][16] Q&A Session Summary Question: Can you help us understand what's being deprioritized to allow for expense management? - The company is driving efficiencies without deprioritizing investments, focusing on reducing unutilized manufacturing capacity and waste [34][35] Question: What is the learning from the CMV vaccine trial? - The pentamer neutralizing antibody response was not sufficient to improve prevention of infection, and further data will be analyzed [44][46] Question: Are you surprised by the slow case accruals in the norovirus program? - The company anticipated the need for a two-season study and remains confident in the commercial opportunity for a highly effective vaccine [50][51] Question: What gives you confidence in the cash break-even target for 2028? - The company sees opportunities for revenue growth through geographic expansion and new product introductions while continuing cost reductions [55][56] Question: How do you expect the split between mNEXSPIKE and Spikevax to evolve? - mNEXSPIKE has become the leading product in the COVID franchise, with expectations for continued growth, while Spikevax will still serve a specific pediatric market [60][61]

ARCT-810 Overview - Arcturus is a commercial mRNA medicines company with a pipeline of multiple therapeutic candidates in advanced clinical trial development[7] - ARCT-810 aims to restore OTC enzyme function, potentially preventing neurological damage and the need for liver transplantation in Ornithine Transcarbamylase (OTC) Deficiency patients[9] - ARCT-810 has received Orphan Drug Designation (FDA), Orphan Medicinal Product Designation (EMA), Fast Track Designation (FDA), and Rare Pediatric Disease Designation (FDA)[14, 15, 16, 17] Clinical Trial Results - European Phase 2 study (N = 8; 6 ARCT-810 / 2 placebo) is completed, and the U S Phase 2 study (N = 3 completed to date) is ongoing[20] - Combined analysis of both Phase 2 studies showed mean glutamine levels decreased significantly (N = 8, p-value = 0 0055)[25] - In the Phase 2 Open-label U S Study, mean glutamine levels decreased significantly (N = 3, p-value = 0 004), with all subjects achieving normal levels after three administrations[28] - Interim Phase 2 data from the U S Open Label Study (N = 3) showed a mean RUF (relative ureagenesis function) increase of +14 7% from baseline to 28 days post-fifth dose, from 29 0% (SD 9 1%) to 43 7% (SD 21 7%), which is statistically significant (p-value = 0 026)[31] Safety and Tolerability - ARCT-810 was generally safe and well-tolerated in Phase 2 studies at all tested dose levels, comprising 40 participants to date, including 20 OTC deficient participants[34, 35] KOL Insights - Glutamine rises earlier than ammonia in OTC deficiency and has lower variability, making it a reliable indicator of urea cycle stress[47] - 15N-Ureagenesis assay directly reflects cycle function, providing a clear readout of therapeutic efficacy[47]