Pharma/Biotech 4R-Tau & PSP Drug Development Programs
Overview
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This page tracks pharmaceutical and biotech companies with active 4R-tau or [Progressive Supranuclear Palsy (PSP)/diseases/progressive-supranuclear-palsy] drug development programs. PSP is a [4R-tauopathy](/mechanisms/tauopathies) characterized by accumulation of 4-repeat (4R) [tau isoforms](/proteins/tau) in the [brain](/brain-regions).
...Pharma/Biotech 4R-Tau & PSP Drug Development Programs
Overview
Mermaid diagram (expand to render)
This page tracks pharmaceutical and biotech companies with active 4R-tau or [Progressive Supranuclear Palsy (PSP)/diseases/progressive-supranuclear-palsy] drug development programs. PSP is a [4R-tauopathy](/mechanisms/tauopathies) characterized by accumulation of 4-repeat (4R) [tau isoforms](/proteins/tau) in the [brain](/brain-regions).
Despite multiple clinical trial failures, several companies continue to pursue therapeutic approaches targeting [tau pathology](/mechanisms/tauopathies) in PSP and related [4R-tauopathies](/mechanisms/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](/proteins/tau) production by targeting [MAPT](/genes/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](/mechanisms/tau-aggregation) 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](/diseases/progressive-supranuclear-palsy) patients. This ASO approach specifically targets the [4R tau isoform](/proteins/tau) 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](/mechanisms/tauopathies) while sparing normal tau function. The company has announced plans for Phase 2 trials in [PSP](/diseases/progressive-supranuclear-palsy)[@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](/brain-regions)
- Oral bioavailability: Easier patient dosing
- [Intracellular targeting](/mechanisms/protein-aggregation): 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](/mechanisms/amyloid-aggregation) + 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)/institutions/university-college-london] - Lead center for PSP clinical trials
- University of Pennsylvania - [Tau biology](/proteins/tau) expertise
- Mayo Clinic - [Neurodegeneration](/diseases/alzheimers-disease) 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 |
References
Unknown, Biogen Pipeline - Tau Programs (n.d.)
Unknown, Oligomerix Pipeline (n.d.)
Unknown, NIO752 PSP Study NCT04539041 (n.d.)
Unknown, Pinteon Therapeutics (n.d.)
[Unknown, Tilavonemab Phase 2 Trial - Lancet Neurology 2021 (2021)](https://pubmed.ncbi.nlm.nih.gov/34118189/)