Alector (ALEC) Status Update summary

Platform Overview and Strategic Vision

• Leadership in immunoneurology, integrating genetics, immunology, and neuroscience to develop therapies for neurodegenerative diseases.

• Proprietary Alector Brain Carrier (ABC) platform enables blood-brain barrier penetration for diverse therapeutic modalities, including antibodies, proteins, enzymes, and nucleic acids.

• ABC platform is modular and tunable, allowing optimization of affinity, valency, and format for specific cargos and disease targets.

• Retains major rights to late-stage immunoneurology candidates and full ownership of novel programs using ABC, with a robust IP portfolio of over 60 patent families and 500+ pending applications.

• Actively exploring partnerships while maintaining the ability to advance programs independently due to strong financial position.

Scientific and Clinical Progress

• ABC technology validated for brain uptake in multiple formats and across species, showing up to 40-fold increases in brain delivery for TFR and over 20-fold for CD98 heavy chain targets.

• Demonstrated that tuning affinity and format of ABC shuttles is critical for optimizing efficacy, safety, and biodistribution, with lower affinity often improving safety profiles.

• Preclinical data show ABC-enabled cargos achieve broad and deep brain biodistribution, with imaging confirming delivery to neuronal layers.

• GCase enzyme replacement therapy for Parkinson’s and Gaucher disease leverages ABC to restore lysosomal function, achieving over 40% increase in brain GCase activity in mice and substrate clearance.

• Safety assessments indicate manageable anemia risk with TFR shuttles, modifiable by adjusting affinity, effector function, and format; CD98 shuttles show favorable hematological and immunological profiles, with no notable safety concerns in NHPs or mice.

Competitive Positioning and Platform Features

• ABC platform offers competitive brain uptake and flexibility compared to other industry BBB technologies, with the main advantage being its pairing with novel immunomodulatory targets.

• Platform is designed to be compatible with a wide range of modalities, including potential future applications with ASOs, RNAi, and small molecules.

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

• ABC toolbox includes multiple formats (scFv, Fab, VHH) and affinity ranges, supporting diverse therapeutic payloads.

• Ongoing efforts to optimize dosing strategies and translate non-human primate PK/safety data to clinical settings, with pharmacodynamic biomarkers guiding clinical development.