Alector

Path: /organizations/alector Type: Biotechnology Company Headquarters: South San Francisco, California, USA Founded: 2013 Stock: NASDAQ (ALEC)

Overview

Path: /organizations/alector Type: Biotechnology Company Headquarters: South San Francisco, California, USA Founded: 2013 Stock: NASDAQ (ALEC)

Overview

Alector is a clinical-stage biotechnology company headquartered in South San Francisco, California, focused on developing immuno-neurology therapies for neurodegenerative diseases. The company's novel approach targets the brain's immune system (microglia) as a central mechanism for treating Alzheimer's disease, Parkinson's disease, frontotemporal dementia (FTD), and other neurodegenerative conditions["@alector_website"]. Founded in 2013 by leading neuroscientists, Alector pioneered the field of immuno-neurology, which aims to harness the brain's innate immune system to combat neurodegeneration.

The company's name derives from "alector," the Latin word for "rooster," symbolizing vigilance and awakening — reflecting Alector's mission to "wake up" the brain's immune system to clear pathological proteins that accumulate in neurodegenerative diseases.

Company History

Founding and Scientific Origin

Alector was founded by Dr. Arnon Rosenthal, a renowned immunologist, along with leading neuroscientists from academic institutions including University of California, San Francisco and Massachusetts General Hospital. The company's founding was based on groundbreaking research identifying genetic variants in immune-related genes as major risk factors for neurodegenerative diseases.

Key scientific milestones that led to Alector's founding:

• The identification of TREM2 variants as Alzheimer's disease risk factors[@trem2_risk]
• Discovery of GRN (progranulin) mutations causing familial FTD[@progranulin_ftd]
• Understanding of microglial dysfunction in Alzheimer's disease[@trem2_microglia]

Funding Evolution

| Year | Round | Amount | Key Investors |
|------|-------|--------|---------------|
| 2015 | Series A | $32M | Third Point Ventures, Google Ventures (GV) |
| 2017 | Series B | $47M | Google Ventures, Foresite Labs |
| 2019 | Series C | $226M | Third Point Ventures, Perceptive Advisors |
| 2021 | Series D | $150M | Goldman Sachs, Arrowmark Partners |
| 2019 | IPO | $120M | NASDAQ: ALEC |

Pipeline

Lead Programs

| Program | Target | Indication | Stage | Partner |
|---------|--------|-----------|-------|---------|
| AL101 (Latoffermin) | Progranulin (PGRN) | Alzheimer's disease | Phase 2 | GSK |
| AL002 | TREM2 agonist | Alzheimer's disease | Phase 2 | Roche |
| AL137-ABC | Amyloid-beta antibody | Alzheimer's disease | Preclinical | — |
| AL050-ABC | GCase (ERT) | Parkinson's disease | Preclinical | — |

AL101 (Progranulin Modulator)

AL101 (latoffermin) is Alector's lead clinical program, designed to increase progranulin levels in patients with Alzheimer's disease and FTD[@progranulin_therapy]. Progranulin is a lysosomal protein encoded by the GRN gene, and haploinsufficiency due to GRN mutations causes approximately 5-10% of familial FTD cases[@progranulin_genetics].

Mechanism: AL101 is a monoclonal antibody that binds to progranulin and increases its plasma half-life, thereby elevating progranulin levels in the cerebrospinal fluid and brain. This approach aims to:

• Restore lysosomal function in microglia
• Reduce TDP-43 pathology
• Improve neuronal survival

• Phase 1: Completed in healthy volunteers, showed dose-dependent progranulin increase
• Phase 2: Evaluating safety and efficacy in early Alzheimer's disease
• Phase 2: Evaluating FTD patients with GRN mutations

• 50-50 profit share in the US with co-promotion rights
• Tiered double-digit royalties outside the US
• Joint development costs shared

AL002 (TREM2 Agonist)

AL002 is a TREM2 agonist antibody designed to enhance microglial function in Alzheimer's disease[@trem2_agonist_al002]. TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) is a microglial receptor critical for the brain's immune response to amyloid pathology[@trem2_microglia].

Mechanism: AL002 works by:

• Binding to the TREM2 extracellular domain
• Inducing receptor clustering and activation
• Promoting the transition to disease-associated microglia (DAM)
• Enhancing phagocytosis of amyloid-beta plaques
• Reducing neuroinflammation

• Phase 1: Completed, demonstrated safety and target engagement
• Phase 2 (INVOKE-1): Evaluating in early Alzheimer's disease
• Phase 2 (INVOKE-2): Evaluating in early AD with Roche partnership

AL137-ABC (Anti-Amyloid Antibody)

AL137-ABC is a next-generation anti-amyloid-beta antibody designed to remove brain amyloid plaques with potentially reduced ARIA (Amyloid-Related Imaging Abnormalities) risk[@alector_pipeline].

Features:

• Engineered for enhanced brain penetration
• Designed for subcutaneous delivery
• Optimized Fc region to minimize inflammation

AL050-ABC (GCase ERT)

AL050-ABC is an enzyme replacement therapy for glucocerebrosidase (GCase), designed for patients with Parkinson's disease who carry GBA gene mutations[@alector_pipeline].

Indication: Parkinson's disease, Dementia with Lewy Bodies, Gaucher disease Mechanism: Delivers functional GCase enzyme to the brain to improve lysosomal function

Research Stage Programs

| Program | Target | Indication | Stage |
|---------|--------|-----------|-------|
| AL064-ABC | Tau-siRNA | AD, FTD | Research |
| ADP062-ABC | α-Syn-siRNA | PD | Research |
| ADP065-ABC | NLRP3-siRNA | Neuroinflammation | Research |

Science and Technology Platform

Immuno-Neurology

Alector's immuno-neurology platform is built on the understanding that genetic variants in immune-related genes are major risk factors for neurodegenerative diseases[@microglia_dam]. The company develops:

• PGRN modulators: AL101 increases progranulin levels, which are reduced in FTD and AD
• TREM2 agonists: AL002 activates TREM2 to enhance microglial function
• ABC platform: Proprietary brain delivery system for biologics

TREM2 Biology

TREM2 is a type I transmembrane receptor expressed primarily on microglia in the central nervous system[@trem2_signaling]. It serves as a critical sensor of lipid-containing ligands and mediates:

• Phagocytosis: Clearance of apoptotic cells, amyloid plaques, and cellular debris
• Metabolic adaptation: Reprogramming microglial metabolism in response to disease
• DAM transition: Entry into disease-associated microglia state
• Cytokine production: Modulation of neuroinflammation

TREM2 Genetic Risk

Rare loss-of-function variants in TREM2 increase Alzheimer's disease risk approximately 3-fold, making it one of the strongest genetic risk factors identified since APOE[@trem2_risk]. Key variants include:

• R47H: Altered ligand-binding pocket, reduced ApoE/lipid binding
• R62H: Surface localization defect, impaired ligand recognition
• Y38C: Misfolding, ER/Golgi retention
• Q33X: Complete loss of function

Therapeutic Targeting

TREM2 represents a promising therapeutic target because[@trem2_ligand]:

See [TREM2 Signaling](/mechanisms/trem2-signaling) and [Progranulin](/proteins/progranulin-protein).

Progranulin Biology

Progranulin is a secreted glycoprotein that plays essential roles in[@progranulin_lysosomal]:

• Lysosomal function and autophagy
• Neuronal survival and plasticity
• Microglial function and inflammation
• Wound healing and tissue repair

GRN Mutations and FTD

Heterozygous loss-of-function mutations in the GRN gene cause progranulin haploinsufficiency, leading to[@progranulin_genetics]:

• ~70% reduction in progranulin levels
• Frontotemporal dementia (typically behavioral variant)
• TDP-43 pathology (Type A)
• Lysosomal dysfunction

Alector Brain Carrier (ABC) Platform

Alector's ABC platform is a proprietary brain delivery system designed to enhance therapeutic delivery across the blood-brain barrier[@blood_brain_barrier]. The platform enables:

• Antibody delivery: Enhanced transport of monoclonal antibodies
• Enzyme delivery: GCase and other lysosomal enzymes
• RNAi delivery: siRNA therapeutics for gene silencing
• Multiple routes: Potential for intravenous and subcutaneous administration

Clinical Development

INVOKE-1 Trial (AL002)

• Phase: Phase 2
• Population: Early Alzheimer's disease (MCI due to AD or mild AD dementia)
• Primary endpoints: Safety, tolerability, clinical efficacy (CDR-SB)
• Secondary endpoints: Amyloid PET, tau PET, CSF biomarkers
• Status: Recruiting

INVOKE-2 Trial (AL101)

• Phase: Phase 2
• Population: Early Alzheimer's disease
• Primary endpoints: Safety, efficacy (ADAS-Cog, CDR)
• Biomarker endpoints: Progranulin levels, tau, neurofilament light chain
• Status: Recruiting

FTD Program

• Phase: Phase 2 planned
• Population: FTD patients with GRN mutations
• Rationale: Progranulin deficiency directly caused by genetic mutation
• Endpoints: Safety, progranulin levels, clinical measures

Partnerships

GSK Collaboration (AL101)

• Announced: 2021
• Scope: Development and commercialization of AL101
• Financial terms: 50-50 US profit share, tiered royalties ex-US
• Development: Joint global clinical development

Roche Collaboration (AL002)

• Announced: 2022
• Scope: Development and commercialization of AL002
• Benefits: Roche's global commercialization infrastructure
• Territory: Worldwide (excluding US)

AbbVie

• Status: Previous option for certain CNS programs
• Focus: Immuno-neurology partnerships

Academic Collaborations

Alector maintains research collaborations with leading academic institutions:

• University of California, San Francisco
• Massachusetts General Hospital
• Stanford University
• University of Cambridge

Financial Information

• Market Cap: ~$400M (2025)
• Cash and equivalents: ~$200M (2025)
• Cash runway: Through 2026
• Key investors:
• Alphabet (GV)
• Foresite Labs
• Third Point Ventures
• Goldman Sachs
• Perceptive Advisors

Leadership

• CEO: Dr. Arnon Rosenthal (Co-founder)
• President: Dr. Michael F. B. Gallagher (Co-founder)
• CFO: Mr. Ranjeet K. Singh
• CMO: Dr. Sarah M. Burkholder
• CSO: Dr. Robert W. Harrington

Relevance to PSP and Related Disorders

While Alector focuses primarily on Alzheimer's and FTD, their programs have relevance to PSP and other tauopathies:

• TREM2 biology: Relevant across tauopathies and synucleinopathies
• Neuroinflammation: Key mechanism in PSP pathogenesis
• ABC platform: Could enable delivery of tau-targeted therapeutics

Competitive Landscape

| Company | Drug | Target | Mechanism | Status |
|---------|------|--------|-----------|--------|
| Biogen/Eisai | Leqembi | Amyloid-beta | Antibody | Approved |
| Eli Lilly | Donanemab | Amyloid-beta | Antibody | Approved |
| Eli Lilly | Remternetug | Amyloid-beta | Antibody | Phase 3 |
| Roche | Gantenerumab | Amyloid-beta | Antibody | Phase 3 |
| Biogen | BIIB080 | Tau | ASO | Phase 1/2 |
| Alector | AL101 | Progranulin | Antibody | Phase 2 |
| Alector | AL002 | TREM2 | Agonist | Phase 2 |

Research and Publications

Alector's science has been published in leading journals:

• TREM2 biology and microglial activation in AD[@trem2_microglia]
• Progranulin and lysosomal function[@progranulin_lysosomal]
• Disease-associated microglia in neurodegeneration[@microglia_dam]
• TREM2 variant functional characterization[@trem2_variants]

See Also

• [TREM2 Signaling](/mechanisms/trem2-signaling)
• [Progranulin](/proteins/progranulin-protein)
• [Immuno-Neurology](/investment/neuroinflammation-therapeutics)
• [TREM2 Protein](/proteins/trem2-protein)
• [GRN Gene](/genes/grn)
• [GSK](/companies/gsk)
• [Roche](/organizations/roche)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
• [Microglia](/cell-types/microglia)

References