Alector (ALEC) Study Update summary

Pipeline overview and strategy

• Focus on disease-modifying therapies for neurodegenerative diseases using a 3R strategy: remove misfolded proteins, replace deficient proteins, and restore dysfunctional cells.

• Progranulin-elevating antibodies (latozinemab, nivisnebart, and AL101) are late-stage assets, with additional ABC-enabled programs in preclinical development.

• ABC (Alector Brain Carrier) technology enhances delivery of antibodies, enzymes, and siRNA across the blood-brain barrier, supporting multiple modalities.

• Strong financial position with over $300 million in cash, providing operational runway into the second half of 2027.

Progranulin-elevating franchise: FTD-GRN and Alzheimer's disease

• Latozinemab for FTD-GRN has breakthrough, fast track, and orphan drug designations; pivotal phase 3 INFRONT-3 data expected by mid-Q4 2025.

• Nivisnebart (AL101) in Alzheimer's disease is fully enrolled in a phase 2 trial, with interim analysis expected in 1H 2026.

• Both antibodies increase progranulin by blocking sortilin, restoring levels and addressing neurodegenerative mechanisms.

• Phase 2 INFRONT-2 study showed latozinemab increased progranulin 2–3 fold, reduced GFAP, and slowed clinical progression by 48% versus controls.

• INFRONT-3 phase 3 trial is randomized, double-blind, placebo-controlled, with co-primary endpoints of clinical progression (CDR plus NACC FTLD) and plasma progranulin; 103 symptomatic and 16 at-risk participants enrolled.

Clinical and biomarker data

• Latozinemab demonstrated strong plasma-CSF progranulin correlation, supporting plasma as a biomarker.

• GFAP levels declined toward asymptomatic ranges during treatment.

• Clinical progression (CDR plus NACC FTLD) slowed by 48% in treated patients compared to historical controls.

• Phase 3 trial includes secondary endpoints: plasma NfL, GFAP, volumetric MRI.