Alectos Therapeutics Inc

Alectos Therapeutics Inc

Headquarters: Vancouver, British Columbia, Canada Founded: ~2015 Ticker: Private Website: [alectos.com](https://www.alectos.com)

Overview

Alectos Therapeutics Inc

Headquarters: Vancouver, British Columbia, Canada Founded: ~2015 Ticker: Private Website: [alectos.com](https://www.alectos.com)

Overview

Alectos Therapeutics is a Canadian biotechnology company pioneering small-molecule therapeutics targeting enzymes involved in neurodegenerative disease pathology. The company is advancing two major programs: O-GlcNAcase (OGA) inhibitors for Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury; and GBA2 inhibitors for Parkinson's disease and lysosomal storage disorders, including a partnered program with [Biogen](/organizations/biogen)[@biogenDeal2022].

The company has established strategic partnerships with major pharmaceutical companies, including a 2022 license agreement with [Biogen](/organizations/biogen) valued at $15M upfront plus milestones for the GBA2 inhibitor AL01811, and a prior partnership with [Merck](/organizations/merck) for early OGA inhibitor clinical development["@alecosWebsite2026"].

Technology Platform

Alectos builds its pipeline on deep expertise in glycosidase biology and the role of protein post-translational modifications in neurodegeneration:

• O-GlcNAcase Inhibition: OGA removes O-GlcNAc from serine/threonine residues. Inhibiting OGA increases O-GlcNAcylation of proteins including [tau](/proteins/tau-protein), which competes with phosphorylation at the same sites[@ogaRationale2018]. Hyperphosphorylated tau is a hallmark of Alzheimer's disease and related tauopathies.
• GBA2 Inhibition: Glucosylceramidase 2 (GBA2) is a non-lysosomal glucosylceramidase involved in lipid metabolism. GBA2 inhibition increases glucosylceramide levels, which may support lysosomal function relevant to Parkinson's disease[@gba2Review2021].
• Blood-Brain Barrier Penetrant Small Molecules: Alectos focuses on small molecules with proven CNS penetration — a key differentiator from many biologic approaches to neurodegeneration.

Pipeline

OGA Inhibitor Program

| Attribute | Details |
|-----------|--------|
| Mechanism | O-GlcNAcase (OGA) inhibition |
| Goal | Increase tau O-GlcNAcylation to reduce pathological tau phosphorylation |
| Indication | Alzheimer's disease, Parkinson's disease, acute ischemic stroke, traumatic brain injury |
| Stage | Preclinical / IND-enabling |
| Status | Active development |

Scientific Rationale[@ogaTau2020][@ogaCrystalStructure2019]:

O-GlcNAcylation is a reversible post-translational modification wherein O-linked N-acetylglucosamine (GlcNAc) is added to serine and threonine residues by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). [Tau](/proteins/tau-protein) is extensively O-GlcNAcylated under normal conditions, and this modification competes sterically with phosphorylation at overlapping sites (Ser/Thr-Pro motifs). In Alzheimer's disease, tau O-GlcNAcylation decreases while phosphorylation increases, shifting the balance toward pathological aggregation.

Inhibiting OGA reverses this imbalance:

Alectos repatriated its OGA inhibitor program from [Merck](/organizations/merck) after Merck discontinued its Phase 1 OGA inhibitor (MK-8719)[@ogaTherapeuticPotential2020]. The company is developing next-generation OGA inhibitors with improved selectivity, CNS penetration, and pharmacokinetic properties.

GBA2 Inhibitor Program — Licensed to Biogen

| Attribute | Details |
|-----------|--------|
| Compound | AL01811 |
| Mechanism | GBA2 (non-lysosomal glucosylceramidase) inhibition |
| Indication | Parkinson's disease, lysosomal storage disorders |
| Stage | Preclinical (licensed to Biogen) |
| Status | Biogen partnership — $15M upfront, milestones |

Deal Details[@biogenDeal2022]:

In June 2022, Alectos entered a license and collaboration agreement with [Biogen](/organizations/biogen) for AL01811, a GBA2 inhibitor. Under the agreement:

• Alectos received $15M upfront
• Alectos is eligible for potential future development and commercial milestone payments
• Biogen obtained exclusive worldwide rights to develop and commercialize AL01811

Historical Partnership: Merck on OGA

Alectos previously partnered with [Merck](/organizations/merck) to pioneer the first clinical OGA inhibitor, which progressed through Phase 1 trials. Following Merck's discontinuation of the program (MK-8719), Alectos repatriated the OGA rights and is advancing its own next-generation inhibitor program with improved drug-like properties.

Competitive Landscape

Alectos competes with larger pharmaceutical companies in the OGA inhibitor space:

| Company | Compound | Mechanism | Stage | Indication |
|---------|----------|-----------|-------|------------|
| [Ferrer Internacional](/organizations/ferrer-internacional) | FNP-223 | OGA inhibitor | Phase 2 | PSP |
| [Eli Lilly](/organizations/eli-lilly) | LY-3372689 | OGA inhibitor | Phase 2 | AD, PSP |
| Roche / AC Immune | RG6289 | OGA inhibitor | Phase 1 | AD |
| Merck | MK-8719 | OGA inhibitor | Discontinued | AD |
| Alectos | OGA program | OGA inhibitor | Preclinical | AD, PD, stroke, TBI |
| Alectos / Biogen | AL01811 | GBA2 inhibitor | Preclinical (Biogen) | PD, LSD |

Competitive Differentiators:

• Small molecule vs. biologics: OGA inhibitors are small molecules that can achieve CNS exposure more readily than antibodies
• Novel chemical matter: Next-generation selectivity and pharmacokinetics vs. first-generation OGA inhibitors
• Dual mechanism potential: OGA inhibitors may address both tau pathology and synaptic dysfunction

Research and Development

OGA Biology

O-GlcNAcylation is increasingly recognized as a critical regulator of neuronal protein function[@ogaRationale2018]. Key research findings:

• Tau regulation: [Tau](/proteins/tau-protein) O-GlcNAcylation peaks during early development and declines with age and in AD
• Synaptic proteins: NMDA receptors, AMPA receptors, and scaffolding proteins are O-GlcNAcylated — modification supports synaptic stability
• APP processing: O-GlcNAcylation of [APP](/proteins/app-protein) influences amyloid-beta production
• Neuroprotection: OGA inhibition reduces excitotoxicity, oxidative stress, and ER stress in model systems

GBA2 Biology

GBA2 (also known as GANC) is a membrane-associated glucosylceramidase distinct from the lysosomal enzyme GBA (acid beta-glucosidase)[@gba2Review2021]:

• Substrate: Glucosylceramide (GlcCer) to glucose + ceramide
• Location: Endoplasmic reticulum, plasma membrane, lipid rafts
• Function: Regulates cellular glucosylceramide levels; involved in autophagy and membrane trafficking
• PD relevance: GBA2 inhibition increases GlcCer, which may compensate for reduced GBA activity in GBA-associated PD

Corporate History

| Year | Event |
|------|-------|
| ~2015 | Company founded in Vancouver, BC |
| 2018 | Partnership with Merck for OGA inhibitor program |
| 2022 | License agreement with Biogen for GBA2 inhibitor AL01811 — $15M upfront |
| 2023 | Merck discontinues MK-8719 OGA inhibitor; Alectos repatriates OGA rights |
| 2024 | Advancing next-generation OGA inhibitor program |

Cross-References

• [OGA Inhibitor Landscape](/therapeutics/oga-inhibitor-landscape)
• [Tau Phosphorylation Pathway](/mechanisms/tau-phosphorylation-pathway)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Biogen Company Profile](/organizations/biogen)
• [Lysosomal Dysfunction in PD](/mechanisms/lysosomal-dysfunction-parkinson)
• [Tauopathy Therapeutic Targets](/therapeutics/tauopathy-therapeutic-targets)

References