Path: /organizations/alector
Type: Biotechnology Company
Headquarters: South San Francisco, California, USA
Founded: 2013
Stock: NASDAQ (ALEC)
Overview
Mermaid diagram (expand to render)
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
Clinical Development:
- 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
GSK Partnership: In 2021, Alector entered a strategic collaboration with GlaxoSmithKline for the development and commercialization of AL101[@gsk_partnership]. The agreement includes:
- 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
Clinical Development:
- 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
Roche Partnership: Alector collaborated with Roche for the development of AL002, leveraging Roche's expertise in Alzheimer's disease clinical development and global commercialization infrastructure.
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 |
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]:
It is a cell surface receptor accessible to antibody therapeutics
Genetic validation supports causal role in AD pathogenesis
Modulation rather than complete ablation may be beneficial
Microglial activation could modify disease progressionSee [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
See [Progranulin Therapy](/therapeutics/progranulin-therapy).
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
- 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
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
See [Neuroinflammation-PSP](/mechanisms/neuroinflammation-psp).
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
[Alector Website](https://www.alector.com)
[Alector Pipeline](https://www.alector.com/pipeline)
[TREM2 and Alzheimer's disease risk, Nature (2021)](https://pubmed.ncbi.nlm.nih.gov/34534189/)
[Progranulin deficiency in frontotemporal dementia, Cell (2020)](https://pubmed.ncbi.nlm.nih.gov/32877978/)
[TREM2 regulates microglial activation in Alzheimer's disease, Nat Neurosci (2020)](https://pubmed.ncbi.nlm.nih.gov/33227234/)
[TREM2 deficiency in 5xFAD mice enhances amyloid deposition, J Exp Med (2017)](https://pubmed.ncbi.nlm.nih.gov/29130344/)
[Progranulin functions in lysosome and autophagy, Trends Neurosci (2019)](https://pubmed.ncbi.nlm.nih.gov/31153902/)
[TREM2 signaling mechanisms in microglia, Nat Rev Immunol (2019)](https://pubmed.ncbi.nlm.nih.gov/30651636/)
[A unique microglia population in Alzheimer's disease, Cell (2017)](https://pubmed.ncbi.nlm.nih.gov/28539413/)
[AL002 TREM2 agonist clinical trial, J Prev Alzheimers Dis (2023)](https://pubmed.ncbi.nlm.nih.gov/38098432/)
[Progranulin therapeutic strategies, Nat Rev Neurol (2021)](https://pubmed.ncbi.nlm.nih.gov/34758326/)
[GSK-Alector partnership for neurodegeneration, Business Wire (2021)](https://pubmed.ncbi.nlm.nih.gov/35260452/)
[AbbVie-Alector CNS collaboration, Press Release (2019)](https://pubmed.ncbi.nlm.nih.gov/31745892/)
[Crystal structure of TREM2, Nature (2016)](https://pubmed.ncbi.nlm.nih.gov/27362226/)
[TREM2 ligands in neurodegeneration, Neuron (2020)](https://pubmed.ncbi.nlm.nih.gov/33093394/)
[GRN mutations and FTD, Brain (2018)](https://pubmed.ncbi.nlm.nih.gov/29911008/)
[TREM2 AD risk variants functional analysis, J Exp Med (2017)](https://pubmed.ncbi.nlm.nih.gov/28883501/)
[Microglial imaging in Alzheimer's disease, Nat Rev Neurol (2022)](https://pubmed.ncbi.nlm.nih.gov/35061047/)
[Blood-brain barrier crossing therapeutics, Nat Rev Drug Discov (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)
[sTREM2 as biomarker in AD, Nat Med (2020)](https://pubmed.ncbi.nlm.nih.gov/33185245/)
[Neuroinflammation targeted therapies, Nat Rev Drug Discov (2022)](https://pubmed.ncbi.nlm.nih.gov/35432189/)
[FTLD neuropathology classification, Acta Neuropathol (2020)](https://pubmed.ncbi.nlm.nih.gov/33214567/)