Tiziana Life Sciences Initiates Phase 2 Trial Testing Intranasal Foralumab for Alzheimer's Disease Neuroinflammation
Key Insights
Tiziana Life Sciences has begun enrollment in a Phase 2 randomized, placebo-controlled trial evaluating intranasal foralumab as both monotherapy and in combination with FDA-approved anti-amyloid therapies for early Alzheimer's disease.
New TSPO-PET imaging evidence demonstrates persistent and widespread microglial activation in an Alzheimer's patient despite treatment with lecanemab, confirming that neuroinflammation remains present even after amyloid plaque reduction.
The trial will test whether intranasal foralumab, a fully human anti-CD3 (search) monoclonal antibody, can reduce microglial activation and slow cognitive decline by targeting the inflammatory component of Alzheimer's disease.
Tiziana Life Sciences has commenced enrollment in a Phase 2 randomized, placebo-controlled clinical trial evaluating intranasal foralumab for early Alzheimer's disease, with the first patient expected to be dosed next week. The biotechnology company's lead development candidate represents a novel approach targeting neuroinflammation that persists even after amyloid plaque reduction with current FDA-approved therapies.
Novel Approach Targets Persistent Neuroinflammation
The Phase 2 clinical trial will evaluate intranasal foralumab both as monotherapy and in combination with FDA-approved anti-amyloid therapies lecanemab or donanemab in patients with early Alzheimer's disease. Baseline clinical assessments, cognitive testing, TSPO-PET imaging, and fluid biomarkers have been completed in the first participants screened in the trial.
The clinical trial launch is supported by new TSPO-PET imaging evidence demonstrating persistent and widespread microglial activation in an Alzheimer's patient despite treatment with lecanemab. Lecanemab, marketed by Eisai and Biogen as Leqembi, is one of the two FDA-approved anti-amyloid therapies for treating early Alzheimer's and is proven to reduce beta-amyloid plaques.
Dr. Howard Weiner, Chairman of Tiziana's Scientific Advisory Board and co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women's Hospital, stated, "This PET finding is a critical insight: clearing amyloid does not turn off the brain's inflammatory response. We believe intranasal foralumab directly addresses this residual neuroinflammation by inducing regulatory T cells to migrate to the brain and calm activated microglia — a mechanism we have already shown reduces microglial activation in secondary progressive multiple sclerosis."
Dual-Target Strategy for Disease Modification
The study will evaluate whether intranasal foralumab as a monotherapy reduces microglial activation and slows cognitive decline by suppressing neuroinflammation. Additionally, the trial will assess whether combination therapy with lecanemab or donanemab provides additive or synergistic benefit by simultaneously targeting amyloid pathology and persistent microglial inflammation.
"With enrolment now underway and baseline neuroimaging and biomarkers secured, we are on the verge of testing a fundamentally new approach to Alzheimer's — one that treats the chronic brain inflammation that is associated with ongoing neurodegeneration," said Ivor Elrifi, Chief Executive Officer of Tiziana Life Sciences. "This milestone marks an important step toward testing whether immune modulation alone, or in combination with amyloid removal, can achieve disease modification."
Promising Multiple Sclerosis Data Supports Approach
Intranasal foralumab is a fully human anti-CD3 (search) monoclonal antibody designed to induce regulatory T cells and suppress pathological neuroinflammation. The therapy has demonstrated efficacy in neuroinflammatory conditions, with TSPO-PET scans from intranasal foralumab-treated multiple sclerosis patients showing marked reduction in microglial activation over a 6-month treatment period.
Currently, 14 patients with non-active secondary progressive multiple sclerosis have been dosed in an open-label intermediate sized Expanded Access Program, with either improvement or stability of disease seen within 6 months in all patients. The drug is also being studied in a Phase 2a, randomized, double-blind, placebo-controlled, multicenter, dose-ranging trial in patients with non-active secondary progressive multiple sclerosis.
Trial Design and Endpoints
The Phase 2 study is designed to evaluate the safety, tolerability, and efficacy of intranasal foralumab as both a monotherapy and in combination with lecanemab or donanemab in early/mild Alzheimer's disease. Key endpoints will include measures of neuroinflammation via TSPO-PET imaging, cognitive function, and biomarker changes related to amyloid and tau pathology.
Foralumab is positioned as a potential first-in-class therapy to address the inflammatory component of Alzheimer's disease that remains active even after amyloid clearance. The drug is the only fully human anti-CD3 (search) monoclonal antibody currently in clinical development, representing a novel avenue for treating neuroinflammatory and neurodegenerative diseases through immunomodulation.