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 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.
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[1].
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[2].
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[3].
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[4].
| 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[5].
| 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.
| Attribute | Details |
|---|---|
| Mechanism | Anti-tau monoclonal antibody (mid-region) |
| Phase | Phase 2 |
| Status | Failed in AD and PSP |
Several companies are pursuing small molecule approaches that may offer advantages over antibody-based therapies:
AAV-mediated delivery of tau-modulating genes represents an emerging strategy with potential for sustained therapeutic effect.
Given the failures of monotherapy approaches, companies are exploring:
Key academic centers driving PSP therapeutic research:
| Year | Acquirer | Target | Focus |
|---|---|---|---|
| 2023 | Novartis | Cognitive Therapeutics | Preclinical tau programs |
| 2022 | Bristol-Myers Squibb | - | Ended tau antibody programs |
| 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 |