Anti Tau Therapeutics is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Anti-Tau Therapeutics | |
|---|---|
| Category | Disease-Modifying Therapy |
| Target Diseases | Alzheimer's Disease, Progressive Supranuclear Palsy, Corticobasal Degeneration, Primary Tauopathies |
| Mechanism | Reduce tau phosphorylation, aggregation, and propagation |
| Approaches | Kinase inhibitors, aggregation inhibitors, immunotherapy, microtubule stabilizers |
Anti-tau therapeutics aim to modify the course of tauopathies by targeting the pathological accumulation and spread of hyperphosphorylated tau protein. Tau normally stabilizes microtubules, but in disease states it becomes hyperphosphorylated, dissociates from microtubules, aggregates into neurofibrillary tangles (NFTs), and spreads between neurons in a prion-like manner. These therapies represent the most advanced disease-modifying approaches for Alzheimer's disease and primary tauopathies[1].
GSK-3β is the primary kinase responsible for pathological tau phosphorylation.
Critical for normal tau phosphorylation; hyperactivation contributes to pathology.
Tau loss-of-function leads to microtubule destabilization.
AADvac1 (Axon Neuroscience)
ACI-35 (AC Immune)
Lecanemab (BAN2401) (Eisai/Biogen)
Donanemab (LY3002813) (Eli Lilly)
Anti-tau antibodies in development:
| Rank | Drug | Company | Mechanism | Target Epitope | Phase | NCT ID | Key Results | IgG Subclass | Status |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Etalanetug (E2814) | Eisai | Anti-tau mAb | MTBR (p-tau396/404) | Phase III | NCT05355493 | MTBR-tau-243 ↓30-70%, pTau217 ↓50% | IgG1 | Active |
| 2 | BIIB080 (MAPTRx) | Biogen/Ionis | ASO | MAPT mRNA | Phase II | NCT05399888 | 50-60% CSF tau reduction | N/A | Active |
| 3 | Bepranemab | UCB | Anti-tau mAb | aa 235-250 (MTBR) | Phase II | NCT05462106 | 58% tau-PET reduction, subgroup benefit | IgG4 | Active |
| 4 | JNJ-63733657 | Janssen | Anti-tau mAb | p-tau217 | Phase II | NCT04619420 | CSF p-tau217 reduction | IgG1 | Active |
| 5 | LY3372689 (Oglemilide) | Eli Lilly | OGA Inhibitor | O-GlcNAcylation | Phase II | NCT05063552 | Target engagement demonstrated | N/A | Active |
| 6 | PRX005 | Prothena/BMS | Anti-tau mAb | MTBR | Phase I | NCT05394125 | Ongoing | IgG1 | Active |
| 7 | Posdinemab (BMS-986446) | BMS | Anti-tau mAb | Mid-domain | Phase II | NCT05514899 | Ongoing | IgG1 | Active |
| 8 | MK-2214 | Merck | Anti-tau mAb | p-tau413 | Phase I | NCT05828832 | Ongoing | IgG1 | Active |
| 9 | Semorinemab | Roche | Anti-tau mAb | N-terminus | Phase II | NCT04382253 | TAURIEL failed, LAURIET mixed | IgG4 | Active |
| 10 | LU-AF87908 | Lundbeck | Anti-tau mAb | p-tau396/404 | Phase I | NCT06310149 | Phase I ongoing | IgG1 | Active |
| 11 | APNMAB005 | Alector | Anti-tau mAb | Synaptic oligomeric tau | Phase I | NCT05693922 | First-in-human ongoing | IgG1 | Active |
| 12 | NIO752 | Roche | ASO | MAPT mRNA | Phase I | NCT05838953 | Dose-escalation ongoing | N/A | Active |
| 13 | ASN90 | Asceneuron | OGA Inhibitor | O-GlcNAcylation | Phase I/II | NCT05239017 | Phase I complete, Phase II planned | N/A | Active |
| 14 | AADvac1 | Axon Neuroscience | Vaccine | p-tau | Phase II | NCT02579252 | Did not meet primary endpoint | N/A | Active |
| 15 | ACI-35 | AC Immune | Vaccine | p-tau396/404 | Phase Ib/IIa | NCT04445831 | Strong immune response | N/A | Active |
| 16 | LMTX (HMTM) | TauRx | Aggregation Inhibitor | Tau aggregates | Phase III | NCT03446001 | Controversial, not approved | N/A | Discontinued |
| 17 | Gosuranemab | Biogen | Anti-tau mAb | N-terminal | Phase II | NCT02460094 | Failed: no clinical benefit | IgG1 | Discontinued |
| 18 | Tilavonemab | AbbVie | Anti-tau mAb | N-terminal | Phase II | NCT02880991 | Failed in PSP | IgG1 | Discontinued |
| 19 | Zagotenemab | Eli Lilly | Anti-tau mAb | MC1 epitope | Phase II | NCT03518028 | Failed: no clinical benefit | IgG1 | Discontinued |
MTBR-Targeting (Showing Promise):
p-tau217 Targeting:
Mid-Domain Targeting:
p-tau413 Targeting:
p-tau396/404 Targeting:
Synaptic Oligomeric Tau:
N-Terminal Targeting (FAILED):
| Drug | Company | Mechanism | Phase | Indication |
|---|---|---|---|---|
| Lecanemab | Eisai/Biogen | mAb (Aβ/tau) | III/Approved | Early AD |
| Donanemab | Eli Lilly | mAb (N-tau) | III/Approved | Early AD |
| AADvac1 | Axon | Vaccine | II | AD/PSP |
This section provides comprehensive clinical trial data for the three lead anti-tau therapeutics: E2814, BIIB080, and bepranemab.
DIAN-TU Study (NCT05355493)
| Parameter | Details |
|---|---|
| Sponsor | Eisai |
| Phase | Phase III |
| Population | Autosomal dominant AD (PSEN1, PSEN2, APP mutations) |
| Enrollment | ~200 participants |
| Design | Randomized, placebo-controlled |
| Primary Endpoints | Cognitive decline (DIAN-MCI), tau PET |
| Key Results | MTBR-tau-243 reduced 30-70%; CSF pTau217 reduced 50% at 2 years |
| Status | Active, enrolling |
⚠️ 4R-Tauopathy Trial (NCT05615614) — DOES NOT EXIST IN CLINICALTRIALS.GOV
| Parameter | Details |
|---|---|
| NCT ID | NCT05615614 — DOES NOT EXIST |
| Status | No active 4R-tauopathy (PSP/CBS) trial for E2814 |
Current E2814 trials:
Phase II Dose-Finding with Lecanemab (NCT06602258)
| Parameter | Details |
|---|---|
| NCT ID | NCT06602258 |
| Population | MCI due to AD (n=105, target 90) |
| Design | E2814 + lecanemab combination |
| Duration | 18 months |
| Sites | 34 sites in U.S. and Japan |
| Primary Endpoint | Change in CSF MTBR-tau-243 at 6 months |
| Expected Completion | August 2027 |
Phase I Study (NCT03119818)
| Parameter | Details |
|---|---|
| Population | Healthy volunteers, mild AD |
| Key Results | Dose-dependent CSF tau reduction up to 50-60% |
| Publication | Nature Medicine (2022) |
| Status | Completed |
Phase I/II Study (NCT04784160)
| Parameter | Details |
|---|---|
| Population | Mild Alzheimer's disease |
| Key Results | Sustained dose-dependent CSF tau reductions |
| Publication | JAMA Neurology (2023) |
| Status | Completed |
Phase II Study (NCT05399888)
| Parameter | Details |
|---|---|
| NCT ID | NCT05399888 |
| Population | Early Alzheimer's disease |
| Phase | Phase II |
| Enrollment | ~300 participants |
| Primary Endpoints | Safety, tolerability, cognitive endpoints |
| Secondary Endpoints | CSF tau reduction, tau PET |
| Design | Randomized, placebo-controlled |
| Status | Active/recruiting (2026) |
| Designation | FDA Fast Track |
Phase II Alzheimer's Disease (NCT04867616)
| Parameter | Details |
|---|---|
| NCT ID | NCT04867616 |
| Population | 466 participants with MCI or mild AD dementia |
| Primary Endpoint | CDR-SB change from baseline |
| Status | Completed (primary endpoint not met) |
| Key Results | Primary not met; 58% tau-PET reduction; 33% slower decline in low-tau, non-ApoE4 carriers |
| Safety | No ARIA observed |
Phase I PSP Study
| Parameter | Details |
|---|---|
| Population | 25 PSP patients |
| Duration | December 2019 – November 2021 |
| Status | Completed |
| Results | Safe, no concerns |
| Extension | Open-label extension (n=19, expected March 2027) |
Phase II PSP Trial
| Parameter | Details |
|---|---|
| NCT ID | NCT05318985 |
| Target | pSer208 epitope (abundant in PSP) |
| Status | Active development |
| Rationale | 4R tauopathy with prominent brainstem pathology |
| Drug | Phase | NCT ID | Primary Endpoint | Key Efficacy Finding |
|---|---|---|---|---|
| E2814 | III | NCT05355493 | Cognitive, tau PET | MTBR-tau-243 ↓30-70%, pTau217 ↓50% |
| BIIB080 | II | NCT05399888 | Safety, CSF tau | 50-60% CSF tau reduction |
| Bepranemab | II | NCT04867616 | CDR-SB | Not met; 58% tau-PET reduction |
The study of Anti Tau Therapeutics has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
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