Financial Data and Key Metrics Changes - The company closed the quarter with $307.3 million in cash, which is expected to provide runway into 2027 [38] - Updated financial guidance for 2025 includes collaboration revenue anticipated between $13 million and $18 million, total research and development guidance between $130 million and $140 million, and total general and administrative guidance between $55 million and $65 million [38] Business Line Data and Key Metrics Changes - The pivotal Phase III INFROM3 trial of Latozinimab is expected to provide top-line data by mid Q4 2025, focusing on frontotemporal dementia due to the GRN gene mutation [5][6] - The Phase II trial of AL-101, targeting early Alzheimer's disease, completed enrollment in April 2025, with trial completion expected in 2026 [7][30] Market Data and Key Metrics Changes - FTD GRN accounts for approximately 5% to 10% of all FTD cases, representing about 8,000 to 17,000 cases in the US and EU [22] - The incidence of FTD in the US is estimated to be 15 to 22 cases per 100,000 person-years, resulting in a prevalence of about 50,000 to 60,000 concurrent cases [15] Company Strategy and Development Direction - The company aims to deliver therapies that eradicate neurodegeneration and improve patient outcomes, focusing on building a durable biotechnology company [9] - The proprietary Electric Brain Carrier technology platform is designed to enable effective delivery of therapies across the blood-brain barrier [8][33] Management's Comments on Operating Environment and Future Outlook - Management emphasized the urgent unmet need in treating frontotemporal dementia and the importance of their clinical programs [10][22] - The company is preparing for potential BLA and MAA submissions in 2026 based on the strength of their trial design and clinical data [29] Other Important Information - The INFROM3 trial is a 96-week randomized, double-blind, placebo-controlled global trial evaluating Latozinimab in symptomatic and at-risk individuals with confirmed GRN mutations [25] - The company has received breakthrough therapy and fast track designations from the FDA for Latozinimab [28] Q&A Session Summary Question: Clarification on the statistical analysis plan changes - The change to include progranulin as a co-primary endpoint was made at the request of the FDA, recognizing its mechanistic role [42] Question: Concerns about plasma progranulin levels - The FDA did not specify a threshold for progranulin levels but emphasized its importance as a biologically meaningful marker [51] Question: Thoughts on the potential for a 25% slowing of cognitive decline - A 25% reduction would be meaningful in a disease with no other therapeutic options, and the safety profile appears favorable compared to anti-amyloid therapies [56][58] Question: Discussion on the open-label extension of the INFROM study - The company is satisfied with the number of subjects opting into the open-label extension, which will provide meaningful data on treatment persistence [108]