4R-Tau & PSP Therapeutics Pipeline

Pharma/Biotech 4R-Tau & PSP Drug Development Programs

Overview

This page tracks pharmaceutical and biotech companies with active 4R-tau or Progressive Supranuclear Palsy (PSP) drug development programs. PSP is a 4R-tauopathy characterized by accumulation of 4-repeat (4R) tau isoforms in the brain.

Despite multiple clinical trial failures, several companies continue to pursue therapeutic approaches targeting tau pathology in PSP and related 4R-tauopathies.

Companies with Active PSP Programs

Biogen

Lead Program: BIIB080 (MAPTRx)

Pharma/Biotech 4R-Tau & PSP Drug Development Programs

Overview

This page tracks pharmaceutical and biotech companies with active 4R-tau or Progressive Supranuclear Palsy (PSP) drug development programs. PSP is a 4R-tauopathy characterized by accumulation of 4-repeat (4R) tau isoforms in the brain.

Despite multiple clinical trial failures, several companies continue to pursue therapeutic approaches targeting tau pathology in PSP and related 4R-tauopathies.

Companies with Active PSP Programs

Biogen

Lead Program: BIIB080 (MAPTRx)

| Attribute | Details |
|-----------|---------|
| Mechanism | Antisense oligonucleotide (ASO) targeting MAPT gene |
| Target | Tau protein reduction |
| Indication | Alzheimer's disease, PSP |
| Phase | Phase 1/2 |
| Status | Active |

BIIB080 is an antisense oligonucleotide that reduces tau protein production by targeting MAPT mRNA. The drug works by lowering all tau isoforms, including the 4R tau variant. Biogen also has gosuranemab (BIIB092), though that trial failed in PSP[@biogen].

Oligomerix

Lead Program: OLX-07010

| Attribute | Details |
|-----------|---------|
| Mechanism | Tau self-association inhibitor (small molecule) |
| Target | Tau oligomers |
| Indication | Alzheimer's disease, PSP |
| Phase | Phase 1a (AD), Preclinical (PSP) |
| Status | Active |

OLX-07010 is a first-in-class small molecule that inhibits tau oligomer formation. This approach targets intracellular tau oligomers, addressing the toxic species believed to drive neurodegeneration. The company is based on NYU research[@oligomerix].

Novartis/Ionis

Lead Program: NIO752

| Attribute | Details |
|-----------|---------|
| Mechanism | Antisense oligonucleotide (ASO) |
| Target | MAPT mRNA, specifically reduces 4R tau isoform |
| Indication | PSP |
| Phase | Phase 1 (Completed) |
| Status | Completed |

NIO752 demonstrated target engagement with reduced CSF tau in PSP patients. This ASO approach specifically targets the 4R tau isoform prevalent in PSP[@nio].

Pinteon Therapeutics

Lead Program: PNT001

| Attribute | Details |
|-----------|---------|
| Mechanism | Conformant monoclonal antibody |
| Target | Pathological tau conformations |
| Indication | Alzheimer's disease, CTE, PSP |
| Phase | Phase 1 (Completed) |
| Status | Planning Phase 2 for PSP |

PNT001 uses a proprietary conformant antibody technology that selectively binds to pathological tau conformations while sparing normal tau function. The company has announced plans for Phase 2 trials in PSP[@pinteon].

Companies with Failed PSP Programs

AbbVie - Tilavonemab (ABBV-8E12)

| Attribute | Details |
|-----------|---------|
| Mechanism | Anti-tau monoclonal antibody (N-terminal epitope) |
| Phase | Phase 2 |
| Status | Failed |

Tilavonemab was evaluated in a Phase 2 randomized placebo-controlled trial in PSP. The trial failed to meet its primary efficacy endpoint despite achieving biomarker reductions in CSF tau. This failure highlighted the challenge of targeting extracellular tau in PSP and the importance of epitope selection[@tilavonemab2021].

Biogen - Gosuranemab (BIIB092)

| Attribute | Details |
|-----------|---------|
| Mechanism | Anti-tau monoclonal antibody |
| Phase | Phase 2 |
| Status | Terminated |

Gosuranemab was terminated early after interim analysis showed the primary endpoint was unlikely to be met.

Roche - Semorinemab (RG6100)

| Attribute | Details |
|-----------|---------|
| Mechanism | Anti-tau monoclonal antibody (mid-region) |
| Phase | Phase 2 |
| Status | Failed in AD and PSP |

Emerging Approaches

Small Molecule Tau Aggregation Inhibitors

Several companies are pursuing small molecule approaches that may offer advantages over antibody-based therapies:

• Blood-brain barrier penetration: Small molecules can more readily access the CNS
• Oral bioavailability: Easier patient dosing
• intracellular targeting: Can reach intracellular tau oligomers

Gene Therapy Approaches

AAV-mediated delivery of tau-modulating genes represents an emerging strategy with potential for sustained therapeutic effect.

Combination Approaches

Given the failures of monotherapy approaches, companies are exploring:

• Amyloid + tau targeting combinations
• Neuroprotective + disease-modifying approaches
• Biomarker-driven patient selection

Academic-Industry Collaborations

Key academic centers driving PSP therapeutic research:

• University College London (UCL) - Lead center for PSP clinical trials
• University of Pennsylvania - Tau biology expertise
• Mayo Clinic - Neurodegeneration research
• CurePSP Foundation - Funding and patient advocacy

Recent M&A Activity

| Year | Acquirer | Target | Focus |
|------|----------|--------|-------|
| 2023 | Novartis | Cognitive Therapeutics | Preclinical tau programs |
| 2022 | Bristol-Myers Squibb | - | Ended tau antibody programs |

Pipeline Summary

| Company | Drug | Mechanism | Phase | Indication |
|---------|------|-----------|-------|------------|
| Biogen | BIIB080 | Tau ASO | Phase 1/2 | AD, PSP |
| Oligomerix | OLX-07010 | Tau oligomer inhibitor | Phase 1a | AD, PSP |
| Novartis/Ionis | NIO752 | Tau ASO | Phase 1 | PSP (completed) |
| Pinteon | PNT001 | Conformant mAb | Phase 1 | AD, PSP |
| AbbVie | Tilavonemab | Anti-tau mAb | Phase 2 | Failed |

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References