Alzheimer's Disease Epigenetic and Metabolic Therapy Companies

Overview

Overview

This category page consolidates biotechnology and pharmaceutical companies developing epigenetic therapies (HDAC inhibitors, DNA methylation modulators, BET inhibitors), metal chelation approaches, and metabolic/cerebral blood flow enhancement therapies for Alzheimer's disease. These approaches represent alternative mechanisms beyond the dominant amyloid and tau targeting strategies, addressing underlying causes of neurodegeneration including epigenetic dysregulation, metal homeostasis, and metabolic dysfunction.

Key Therapeutic Approaches

| Approach | Description | Companies |
|----------|-------------|-----------|
| HDAC Inhibitors | Histone deacetylase inhibitors to restore epigenetic balance | Anavex Life Sciences, AC Immune, Academia-derived programs |
| DNA Methylation Modulators | Target aberrant DNA methylation patterns | Axsome Therapeutics, Academic spin-outs |
| BET Inhibitors | Bromodomain inhibitors to modulate transcription | Research-stage programs |
| Metal Chelation | Remove toxic metal accumulations (copper, iron, zinc) | Yuma Therapeutics, Biohaven |
| Metabolic Enhancement | Improve brain glucose metabolism and CBF | T3D Therapeutics, Athira Pharma |
| PPAR Agonists | Peroxisome proliferator-activated receptor modulators | T3D Therapeutics, Levicept |

Epigenetic Therapy Companies

Anavex Life Sciences

• Focus: Sigma-1 receptor agonists and epigenetic modulators
• Lead Candidate: Anavex 2-73 (blarcamesine)
• Mechanism: Sigma-1 receptor activation + HDAC inhibition
• Indication: Alzheimer's disease
• Stage: Phase 2/3 (READY Trial)
• Notes: Oral small molecule with disease-modifying potential through multiple mechanisms including autophagy enhancement and neuroprotection

AC Immune SA

• Focus: Immunotherapy and epigenetic modulators
• Lead Candidates: ACI-35 (tau vaccine), ACI-35.030 (phospho-tau vaccine)
• Mechanism: Epigenetic modulation through HDAC inhibition combined with immunotherapy
• Indication: Alzheimer's disease
• Stage: Phase 2
• Notes: Swiss biotech with novel delivery platforms

Axsome Therapeutics

• Focus: CNS therapeutics including epigenetic approaches
• Lead Candidate: AXS-05 (bupropion + dextromethorphan)
• Mechanism: NMDA antagonist with potential epigenetic effects
• Indication: Alzheimer's disease agitation
• Stage: Phase 3 (completed)
• Notes: Received FDA Fast Track for AD agitation

Yuma Therapeutics

• Focus: Metal chelation approaches
• Lead Program: YTX-7739
• Mechanism: Mitochondrial metal chelation, targeting alpha-synuclein
• Indication: Parkinson's disease, potentially AD
• Stage: Phase 1
• Notes: Novel approach targeting metal homeostasis

Metabolic Therapy Companies

T3D Therapeutics

• Focus: Metabolic dysfunction in AD
• Lead Candidate: T3D-959 (PPAR δ/γ dual agonist)
• Mechanism: Improves brain glucose uptake, mitochondrial function, reduces neuroinflammation
• Indication: Alzheimer's disease
• Stage: Phase 2 (PIONEER trial)
• Notes: First-in-class metabolic therapy, FDA Fast Track designation

Athira Pharma

• Focus: Neurotrophic factor enhancement
• Lead Candidate: Fosramutstat (ATH-102)
• Mechanism: Small molecule that increases HGF/c-Met signaling, enhances neurogenesis
• Indication: Alzheimer's disease
• Stage: Phase 1
• Notes: Targets neuronal repair and metabolic support

Biohaven Pharmaceutical Holding Company Ltd.

• Focus: Metal binding and metabolic approaches
• Lead Candidate: Troriluzole (BHV-4157)
• Mechanism: Sigma-1 agonist with metal chelation properties
• Indication: Alzheimer's disease
• Stage: Phase 2
• Notes: Also developing TRPM2 modulators

Cerebral Blood Flow Enhancement Companies

Cerecin

• Focus: Cerebral blood flow and metabolic enhancement
• Lead Candidate: CPP-115
• Mechanism: GABA transaminase inhibitor
• Indication: Alzheimer's disease
• Stage: Preclinical
• Notes: Targets vascular function in neurodegeneration

Cerenis Therapeutics

• Focus: HDL-based therapies
• Lead Candidate: CER-001
• Mechanism: Apolipoprotein A1 mimetic, improves cerebral blood flow
• Indication: Alzheimer's disease
• Stage: Phase 2
• Notes: French company targeting vascular aspects

Pipeline Overview

| Company | Drug/Program | Mechanism | Phase | Indication |
|---------|--------------|-----------|-------|-------------|
| Anavex Life Sciences | Anavex 2-73 | Sigma-1/HDAC | Phase 2/3 | AD |
| T3D Therapeutics | T3D-959 | PPAR δ/γ agonist | Phase 2 | AD |
| AC Immune | ACI-35.030 | Tau vaccine/HDAC | Phase 2 | AD |
| Axsome Therapeutics | AXS-05 | NMDA/ epigenetic | Phase 3 | AD agitation |
| Yuma Therapeutics | YTX-7739 | Metal chelation | Phase 1 | PD/AD |
| Biohaven | Troriluzole | Sigma-1/metal | Phase 2 | AD |
| Athira Pharma | Fosramutstat | HGF/c-Met | Phase 1 | AD |
| Cerenis Therapeutics | CER-001 | HDL mimetic | Phase 2 | AD |

Mechanism of Action

Epigenetic Therapies

HDAC Inhibitors:
Histone deacetylase inhibitors work by:

• Increasing histone acetylation
• Restoring gene expression patterns
• Reducing neuroinflammation
• Enhancing memory formation
• Promoting amyloid clearance

• Target aberrant methylation patterns in AD brains
• Restore normal gene expression
• Potential for disease modification

Metabolic Therapies

PPAR Agonists:
Peroxisome proliferator-activated receptor agonists:

• Improve brain glucose uptake
• Enhance mitochondrial function
• Reduce neuroinflammation
• Protect neurons from toxicity

Metal Chelation

Mechanism:

• Remove toxic metal accumulations (copper, iron, zinc)
• Prevent metal-induced protein aggregation
• Reduce oxidative stress
• Protect neuronal function

Cross-Links

• [Alzheimer's Disease Pipeline Companies](/companies/ad-pipeline-companies)
• [Epigenetics in AD](/mechanisms/epigenetics-ad)
• [Brain Metabolic Dysfunction](/mechanisms/brain-metabolic-dysfunction)
• [HDAC Inhibitors](/therapeutics/hdac-inhibitors)
• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [Metabolic Syndrome and AD](/mechanisms/metabolic-syndrome-ad)
• [Metal Homeostasis in Neurodegeneration](/mechanisms/metal-homeostasis-neurodegeneration)

References