NCT07264283 is a Phase 2 clinical trial evaluating LM11A-31 (also known as BMS-902464), a small molecule modulator of the p75 neurotrophin receptor (p75NTR), as a treatment for Progressive Supranuclear Palsy (PSP). This trial is part of the PSP Clinical Trial Platform (NCT07173803), a master protocol designed to efficiently evaluate multiple investigational products for PSP simultaneously[1].
LM11A-31 represents a novel neuroprotective approach that targets neuronal survival pathways rather than tau pathology directly. By modulating p75NTR signaling, the compound promotes pro-survival pathways while blocking pro-apoptotic cascades activated by tau pathology.
| Field | Value |
|---|---|
| NCT ID | NCT07264283 |
| Status | Not Yet Recruiting |
| Phase | Phase 2 |
| Sponsor | University of Pennsylvania |
| Study Type | Interventional |
| Allocation | Randomized |
| Intervention Model | Parallel Assignment |
| Blinding | Triple (Participant, Investigator, Outcomes Assessor) |
| Estimated Enrollment | ~200 participants |
| Start Date | 2024 |
| Estimated Completion | ~2028 |
The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily that plays complex roles in neuronal survival and death[2][3]. Unlike tropomyosin receptor kinase (Trk) receptors which mediate pro-survival signals, p75NTR can:
In PSP and other tauopathies:
LM11A-31 is a small molecule p75NTR modulator developed by Astellas Pharma (formerly Bristol-Myers Squibb)[1:1]. The compound:
Molecular target: p75NTR extracellular domain - specifically the cysteine-rich domain (CRD) II where pro-NGF binds[4]
LM11A-31 modulation of p75NTR leads to[5]:
Extensive preclinical work demonstrated LM11A-31's neuroprotective potential:
LM11A-31 completed Phase 1 testing in patients with mild-to-moderate AD[2:1]:
The translation from AD to PSP is supported by:
NCT07264283 is conducted under the PSP Clinical Trial Platform (NCT07173803) master protocol[1:2]. Key design features:
Likely inclusion criteria for the LM11A-31 regimen:
Likely exclusion criteria:
| Measure | Timepoint | Purpose |
|---|---|---|
| Clinical Global Impression of Change (CGI-C) | 52 weeks | Global clinical assessment |
| Montreal Cognitive Assessment (MoCA) | 52 weeks | Cognitive function |
| Timed Up and Go Test (TUG) | 52 weeks | Mobility/balance assessment |
| MDS-UPDRS Part III | 52 weeks | Motor examination |
| Quality of Life (PSP-QoL) | 52 weeks | Patient-reported outcomes |
Comprehensive safety monitoring including:
Pharmacokinetic monitoring to ensure:
An independent Data Safety Monitoring Board (DSMB) provides:
| Agent | Mechanism | Target | Trial Status |
|---|---|---|---|
| LM11A-31 (NCT07264283) | p75NTR modulator | Neuronal survival | Not Yet Recruiting |
| Tilavonemab | Anti-tau mAb | Extracellular tau | Failed |
| BIIB080 | ASO | MAPT mRNA | Recruiting |
| Neuroprotective small molecules | Various | Mitochondria/oxidative stress | Varying stages |
PSP progression involves two parallel mechanisms[6]:
Current anti-tau therapies target mechanism #1. LM11A-31 targets mechanism #2, offering:
The PSP Platform trial allows future combination studies where:
As of early 2026, this trial is not yet recruiting. Updates will be tracked as enrollment begins.
| Milestone | Expected Timeframe |
|---|---|
| IRB approval and site activation | 2025-2026 |
| First patient enrolled | 2026 Q1-Q2 |
| Enrollment completion | 2027 Q4 |
| Primary endpoint readout | 2028 Q1 |
NCT07264283 - The Progressive Supranuclear Palsy Clinical Trial Platform - Regimen B: LM11A-31. ↩︎ ↩︎ ↩︎
Longo FM, Massa SM. p75NTR as a therapeutic target for Alzheimer's disease: the LM11A-31 story. Expert Opinion on Therapeutic Targets. 2021. ↩︎ ↩︎
Bai Y, et al. Small molecule modulators of the p75 neurotrophin receptor. Journal of Medicinal Chemistry. 2020. ↩︎
Massa SM, et al. LM11A-31 improves deficits in Alzheimer's disease models and restores pro-NGF and p75NTR signaling. Neurobiology of Disease. 2018. ↩︎
Simmons DA, et al. LM11A-31 improves cognition and reduces tau pathology in a mouse model of Alzheimer's disease. Neurotherapeutics. 2022. ↩︎
Cummings J, et al. Alzheimer's disease drug development pipeline 2024. Alzheimer's & Dementia. 2024. ↩︎