Alector, Inc. · NASDAQ:ALEC
Alector — The 7th CNS Drug Delivery Summit (December 2025)
24 slides from Alector's conference presentation, Dec 11, 2025
Slide 1: Enhancing Alector's pipeline with Alector Brain Carrier (ABC) Platform
Enhancing Alector's pipeline with Alector Brain Carrier (ABC) Platform Toey Nivitchanyong Sr Staff Scientist, Alector The 7th CNS Drug Delivery Summit 12/11/2025
Slide 2: Alector Brain Carrier (ABC) is Designed for Effective Brain Delivery
Alector Brain Carrier (ABC) is Designed for Effective Brain Delivery Alector Brain Carrier (ABC) Receptor-Mediated Transcytosis • BBB technology that enables non-invasive peripheral delivery of therapeutics to the brain • Versatile and tunable design seeks to optimize efficacy and safety • Validated
Slide 3: Alector's Versatile Drug Configurations are Tailored to the Cargo
Alector’s Versatile Drug Configurations are Tailored to the Cargo Antibody Cargo Enzyme Cargo Nucleic Acid Cargo Therapeutic arm Therapeutic arm Nucleic Acid Cargo Enzyme cargo ABC Adaptable Adaptable Adaptable Adaptable Adaptable Fc Adaptable linker Fc linker Fc linker ABC ABC Versatile Configurati
Slide 4: Adaptable TfR Binding Affinities for a Variety of Cargos
Adaptable TfR Binding Affinities for a Variety of Cargos 1000-Fold Affinity Range Tailored to ABC Displays Affinity-Dependent TfR Affinity-Dependent Entry to the Antibodies, Enzymes, and siRNA Internalization into Human Brain Frontal Cortex of NHP Endothelial Cells TfR Binder KD (nM) 500nM 100nM 500
Slide 5: ABC Epitope is Associated with Reduced ADCC and Lower Reticulocyte Loss
ABC Epitope is Associated with Reduced ADCC and Lower Reticulocyte Loss For antibody cargo that requires Fc effector function Structure of the Human Transferrin TfR Dependent ADCC is Determined Alector’s TfR ABC Epitope is Associated Receptor Bound to TfR and Binding by the TfR Binding Epitope with
Slide 6: ABC Applied Toward Multiple Drug Modalities to Enhance Alector's Pipeline
ABC Applied Toward Multiple Drug Modalities to Enhance Alector's Pipeline Antibodies + ABC Removing Aβ Removing Tau Enzymes + ABC Replacing GCase siRNAs + ABC Removing Tau Removing α-Synuclein Removing NLRP3 Property of Alector 66
Slide 7: AL137: ABC-Enabled Anti-Aβ Antibody for Alzheimer's Disease
AL137: Alector Brain Carrier (ABC)— Enabled Anti-Aβ Antibody for Alzheimer's Disease Property of Alector 7
Slide 8: Design of AL137: ABC-Enabled Anti-Aβ Antibody with Distinct Safety and Efficacy Features
Design of AL137: ABC-Enabled Anti-Aβ Antibody with Distinct Safety and Efficacy Features Engineered 1 Anti-PyroGlu3 Aβ Binding Epitope Fully Active Constant Region 2 4 Optimized Linker 3 Optimized TfR-Binding Epitope and Affinity to Maximize Brain Penetration and Reduce Hematologic Adverse Effects P
Slide 9: Anti-A-ABC Facilitates Phagocytosis of PyroGlu3 Aβ by Human Microglia
Anti-A-ABC Facilitates Phagocytosis of PyroGlu3 Aβ by Human Microglia Fluorescent Imaging (red) of PyroGlu3 Anti-pE3-ADependent Phagocytosis of PyroGlu3 Aβ Phagocytosed by Microglia in 24h Aβ by Human IPSC Microglia in Culture PyroGlu3 Aβ only +huIgG iMicroglia Aβ A only Isotype Anti-pE3-Abeta A
Slide 10: AL137 Binds to Amyloid Plaque in Human and Mouse AD Brains
AL137 Binds to Amyloid Plaque in Human and Mouse AD Brains AL137-mTfR Colocalizes with A Plaques in the 5XFAD AD Mouse Reduction in Brain Aβ42 Iso mTfR AL137-mTfR AL137-mTfR in AL137 mTfR-Dosed Mice Iso Control p=0.035 50 mg/kg 5 mg/kg 5 mg/kg 3D Reconstruction AL137 Colocalizes with A Plaques on
Slide 11: AL137 Demonstrates Enhanced CSF Uptake Over Time
AL137 Demonstrates Enhanced CSF Uptake Over Time CSF Concentration Following 1st and 2nd Administration CSF AL137 naked vs AL137 3mg/kg 12.5x 6.5x 4.5x Three monkeys per group were injected on days 1 and 9 (red arrows). Property of Alector 11
Slide 12: ABC Enhances Brain Uptake of AL137: Anti-Aβ Antibody Lead
ABC Enhances Brain Uptake of AL137: Anti-Aβ Antibody Lead Frontal Cortex Hippocampus 15x 8x 29x 32x AL137-Naked AL137 AL137-Naked AL137 AL137-Naked AL137 AL137-Naked AL137 3 mg/kg 3 mg/kg 30 mg/kg 30 mg/kg 3 mg/kg 3 mg/kg 30mg/kg 30mg/kg Three monkeys per group were i.v. dosed on days 1 and
Slide 13: AL050: ABC-Enabled GCase ERT for Parkinson's Disease
AL050: Alector Brain Carrier (ABC)—Enabled GCase ERT for Parkinson's Disease Property of Alector 13
Slide 14: GBA1 Gene Mutations are a Major Risk Factor for Neurodegenerative Diseases
GBA1 Gene Mutations are a Major Risk Factor for Neurodegenerative Diseases GBA1 mutations lead to reduced GCase enzyme activity and toxic substrate accumulation (GlcCer and GlcSph) in the brain No therapy has effectively restored GCase activity in the brain: Current GCase enzyme replacement therapy
Slide 15: Optimized Design of AL050: ABC-Enabled GCase Enzyme Replacement Therapy (ERT)
Optimized Design of AL050: ABC-Enabled GCase Enzyme Replacement Therapy (ERT) Engineered GCase Optimal TfR with Improved Epitope and Activity and Stability 1 Binding Affinity 3 Optimal 4 Drug Format Silenced 2 Constant Region Property of Alector 15
Slide 16: AL050 Affinity Was Optimized for Cell Rescue and Lysosomal Uptake
AL050 Affinity Was Optimized for Cell Rescue and Lysosomal Uptake GCase-ABC Is Delivered to the Lysosomes Ability of AL050 to Rescue GCase Activity in GBA1- / - of GBA1- / - Neuroblastoma Cells Neuroblastoma Cells Is TfR-Affinity-Dependent Overlay GCase-ABC TfR Affinity Isotype Low EEA-1 LAMP-1 High
Slide 17: AL050 Displays ~40 Fold Longer Enzymatic Activity in NHP Plasma
AL050 Displays ~40 Fold Longer Enzymatic Activity in NHP Plasma Compared to Current GCase ERTs AL050 Displays GCase Enzymatic Activity Current GCase ERTs Display Enzymatic Activity Half-Life of ~6.6 hours in NHP Plasma Half-Life of 4 to 10 Minutes in Plasma Imiglucerase: T½ Enzymatic Activity 3.6 –
Slide 18: AL050 Did Not Negatively Impact Reticulocytes, RBC Count or Hemoglobin Levels
AL050 Did Not Negatively Impact Reticulocytes, RBC Count or Hemoglobin Levels Reticulocyte Counts in Red Blood Cell Counts Were Not Hemoglobin Levels Were Not Normal Range Affected Affected Three NHP per group were injected on days 1 and 8 (vertical lines). Property of Alector 18
Slide 19: ABC Enhances Brain Delivery and Activity of Engineered GCase
ABC Enhances Brain Delivery and Activity of Engineered GCase Brain Delivery Brain Activity Substantia Nigra Putamen Substantia Nigra Putamen X6 X19 63% Increase 124% Increase Three NHP per group were injected on days 1 and 8. Brain tissues were collected 24 hours after the second injection and drug
Slide 20: AL050 Surrogate Rescues Brain GCase Activity and Reduces Toxic Substrate Accumulation
AL050 Surrogate Rescues Brain GCase Activity and Reduces Toxic Substrate Accumulation in the Brain of Gba1-Mutant Mice GCase-ABC Increases Brain GCase GCase-ABC Reduces GlcSph Durable (28d) Reduction in Brain GlcSph +95% - 78% 8dpi -70% -40% Wild-type or Gba1-mutant mice were injected once (left, ri
Slide 21: Alector Brain Carrier (ABC)-Enabled siRNA Programs
Alector Brain Carrier (ABC)—Enabled siRNA Programs Property of Alector 21
Slide 22: siRNA-ABC: Support Effective Brain Distribution with Peripheral Delivery
siRNA-ABC: Support Effective Brain Distribution with Peripheral Delivery HI GH BRAIN PHARMACOKINETICS PA R A M E T E R S T E S T E D P E N E T R AT I O N ABC enables high brain Long plasma half-life ~1,000-fold range of TfR penetration with compared to chemically affinities peripheral delivery stabi
Slide 23: Peripheral Delivery of Sod1 siRNA-ABC matches or is Better Than ICV Delivery
Peripheral Delivery of Sod1 siRNA-ABC matches or is Better Than ICV Delivery: 50-89% Knockdown Across Multiple Rodent Brain Structures Cerebellum Spinal Cord Striatum Study Design 4 IV or 1 ICV (5 mg/kg siRNA equivalent dose) Day 0 1 8 15 22 25 Thalamus Cortex Hippocampus Brain Stem Property of Alec
Slide 24: Thank You
Wi Thank You
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