Alector (ALEC) Status Update summary

Strategic leadership and pipeline progress

• Positioned to be first with TREM2 activating drug data in Alzheimer's by year-end and first with Phase III progranulin-elevating drug data in frontotemporal dementia by end of next year.

• Ongoing clinical programs include Phase 2 studies in Alzheimer's disease and a pivotal Phase 3 study in frontotemporal dementia.

• The proprietary Alector Brain Carrier (ABC) platform is central to expanding the pipeline for brain-penetrant therapies.

• Exploring partnerships to expand technology applications and accelerate development.

• Retains major rights to late-stage programs and full ownership of novel ABC-enabled assets, with a robust IP portfolio.

Technology platform and scientific innovation

• ABC leverages receptor-mediated transcytosis via transferrin receptor (TfR) and CD98 heavy chain to shuttle diverse cargos across the BBB.

• Platform is modular and tunable, allowing optimization of affinity, valency, and format for different therapeutic needs.

• Demonstrated significant increases in brain uptake (up to 40x in NHPs for TfR-ABC, >20x in mice for CD98hc-ABC) for antibody and protein cargos in preclinical models.

• Manufacturability supports high concentration stability and potential for subcutaneous administration.

• Safety risks such as anemia with TFR shuttles are being addressed through affinity and effector function tuning.

Pipeline and therapeutic applications

• Lead programs include latozinemab and AL101 (progranulin elevation) and AL002 (TREM2 activation), with late-stage trials in Alzheimer's and frontotemporal dementia.

• ABC platform enables development of enzyme replacement therapies, such as brain-penetrant GCase for Parkinson's disease, Lewy body dementia, and Gaucher disease.

• GCase ABC demonstrated restoration of enzyme activity in GBA1 knockout models and over 40% increase in brain GCase activity in vivo, with substrate clearance.

• Focused on Parkinson's and LBD for GCase program due to greater relevance for CNS pathology compared to Gaucher disease.

• ABC platform underpins a broad pipeline targeting AD, FTD, PD, LBD, ALS, and Gaucher disease.