Alector (ALEC) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Scientific and strategic overview

• Focuses on recruiting the brain's immune system to address multiple neurodegenerative pathologies, leveraging human genetics for drug validation.

• Approach differs from traditional therapies by targeting immune checkpoints and stimulatory molecules rather than misfolded proteins alone.

• Recent advances in Alzheimer's and other neurodegenerative diseases show the field is now tractable, with improved clinical trial tools and imaging.

• Pipeline is differentiated by targeting microglia health, aiming for broader efficacy across multiple brain pathologies.

• Belief that microglia-modulating drugs will yield superior clinical outcomes due to their broad mechanism.

AL002 (TREM2 program) and INVOKE-2 trial

• Phase II INVOKE-2 study in Alzheimer's is on track for data in Q4, measuring disease progression over 48–96 weeks with three dose arms and placebo.

• Primary endpoint is slowing disease progression (CDR Sum of Boxes), with additional biomarker analysis for amyloid, tau, and microglial health.

• ARIA events observed are similar to those seen with anti-Aβ antibodies, mostly mild and manageable with slow dose escalation.

• Patient population is early-stage Alzheimer's, confirmed by PET imaging and consistent with intended treatment group.

• Efficacy is expected even with modest amyloid reduction, not requiring complete amyloid clearance as with anti-Aβ drugs.

TREM2 mechanism and competitive landscape

• Drug is designed to activate membrane-bound TREM2 on microglia, enhancing their protective functions.

• Soluble TREM2 is considered a regulatory by-product, with the drug focused on the membrane receptor for efficacy.