- **Pivotal FTD-GRN Data Imminent**: Phase III INFRONT-3 readout expected mid-Q4 2025, with co-primary endpoints of clinical progression slowing (CDR-NACC-FTLD) and progranulin normalization.
- **Alzheimer's Pipeline Progression**: AL101 Phase II trial completed enrollment, targeting GRN mutation-linked AD pathophysiology.
- **Strong Financial Position**: $307.3M cash runway into 2027, supporting dual late-stage programs and pipeline expansion.
- **FDA Alignment**: Agency认可progranulin as confirmatory endpoint, reinforcing mechanistic rationale.
- **Near-Term Catalysts**: Latozinemab BLA submission anticipated Q2 2026 if data meet pre-specified criteria.

**【CEO Summary Section】**
- Alector is nearing a pivotal inflection point with the mid-Q4 readout of Phase III INFRONT-3 trial for latozinemab in FTD-GRN. 
- Latozinemab is the first progranulin-elevating therapy targeting the root cause of FTD-GRN, with Phase II data showing 2-3x progranulin normalization and 48% slowing of disease progression.
- AL101, a next-gen progranulin antibody, is advancing in Phase II for early Alzheimer's disease, leveraging genetic evidence linking GRN mutations to AD risk.

**【Clinical Overview (Dr. Darby)】**
- FTD-GRN affects ~5-10% of FTD cases (~8,000-17,000 U.S./EU patients), caused by GRN mutations leading to progranulin deficiency.
- Current management is symptomatic; no approved disease-modifying therapies exist.
- Biomarkers like neurofilament light (NfL) and MRI volumetrics enable earlier diagnosis and tracking of neurodegeneration.

**【CMO Financial Commentary】**
- INFRONT-3 Phase III trial: 103 symptomatic/16 presymptomatic GRN mutation carriers, powered to detect 40% slowing of disease progression (CDR-NACC-FTLD sum of boxes).
- FDA-amended statistical plan adds plasma progranulin as co-primary endpoint, reflecting mechanistic importance.
- Trial completion expected Q4 2025; BLA/MAA submissions anticipated Q2 2026.

**【R&D Pipeline Update】**
- Anti-amyloid beta antibody (ADP 037 ABC) engineered for brain penetration, reduced ARIA risk, and subcutaneous delivery.
- GCase replacement therapy (ADP 050 ABC) targets lysosomal dysfunction in Parkinson's and Gaucher disease.
- Additional programs include anti-tau siRNA, reelin modulators, and brain-penetrant enzyme therapies.

**【CFO Financial Update】**
- Q2 2025 cash balance: $307.3M, providing runway into H2 2027.
- 2025 guidance: Collaboration revenue ($13-18M), R&D ($130-140M), G&A ($55-65M).
- Focus on execution across clinical, preclinical, and research pipelines.

**【Q&A Highlights】**
- FDA requested progranulin as co-primary endpoint, reflecting mechanistic validation.
- Trial powered to detect 25% slowing of progression (statistically significant at p<0.05).
- No ARIA events observed; latozinemab safety profile remains clean.
- Open-label extension (Part 2) enrollment strong, providing long-term efficacy data.


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