Attralus Inc
Non-clinical Development
Dr. Suganya Selvarajah is a Neurobiology professional with experience in drug discovery and preclinical development of therapeutics with focus on antibodies, peptides, and small molecules. Academic experience includes a Ph.D in Immunology and Virology at the University of Edinburgh, post-doctoral experience at the Scripps Research Institute, La Jolla working with Prof. Dennis Burton. Subsequently worked as a principal investigator and staff scientist at the University of California San Francisco (UCSF). She has ten years of biotechnology industry experience which includes being Head of Neurobiology at Prosetta Biosciences, San Francisco. Her current role is Director of Biology at Attralus Inc, San Francisco. Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to amyloidosis.

Presenter of 1 Presentation

DEVELOPMENT OF BRAIN SHUTTLE ENABLED AT-04, A NOVEL PEPTIBODY THAT BINDS NEUROPATHOLOGIC FIBRILLAR AGGREGATES

Session Type
SYMPOSIUM
Date
Sat, 01.04.2023
Session Time
08:40 - 10:40
Room
ONSITE - HALL F1+F2+F3
Lecture Time
09:25 - 09:40

Abstract

Aims

Aβ amyloid deposits and aggregates of phosphorylated tau occur together in the brains of AD patients. Simultaneous removal of these aggregates from the brain would likely achieve the greatest therapeutic benefit. Thus, we have generated AT-04, a genetic fusion of human IgG1 Fc domain and pan-amyloid-reactive p5R peptide which binds amyloid deposits, and amyloid fibrils. To maximize brain delivery, AT-04 was genetically fused to brain shuttles derived from VNAR single domain antibodies to transferrin receptor 1 (TfR1).

Methods

The binding of AT-04 alone and fused to the surrogate mouse (TXB2) or primate (TXP1) brain shuttle to Aβ fibrils, tau aggregates or TfR1 will be measured by ELISA. Binding to Fc-gamma receptors will be measured using surface plasmon resonance and phagocytosis of Aβ(1-40) amyloid-fibrils using a fluorescence uptake assay. Binding of the AT-04/TXP1 fusion to Aβ plaques in brain tissue sections from AD patients will be assessed by immunohistochemistry. Brain and plasma concentrations of AT-04/TXB2 fusion in mice will be assessed after IV administration.

Results

In contrast to an Aducanumab homolog, AT-04 bound to synthetic phosphorylated tau aggregates in addition to Aβ(1-40) synthetic fibrils. AT-04 also bound Fc-gamma receptors like full length human IgG1 and activated phagocytosis of Aβ(1-40) amyloid fibrils. Additionally, AT-04 colocalized with Aβ plaques in brain tissue sections from patients with AD. The effect of the VNAR brain shuttles fused to AT-04 on binding Aβ(1-40) fibrils, Fc-gamma receptors, phagocytic activity and colocalization with amyloid plaques in AD brain will be compared to that of AT-04 alone.

Conclusions

Conjugation of AT-04 to a VNAR-derived brain shuttle to enhance brain penetration has the potential to effectively clear neuropathic fibrillar deposits and offer a novel immunotherapeutic for patients with AD.

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