Dendrimer-based nanotechnology carriers for targeted drug delivery The right drug, to the right place, at the right time

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Dendrimer-based nanotechnology carriers for
targeted drug deliveryThe right drug, to the
right place, at the right time

• Deborah Ladenheim, PhD
• Vice President, Regulatory Affairs
• Avidimer Therapeutics
• www.avidimer.com

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Overview

• Requirements for targeted therapeutics
• Use of AvidimersTM for drug delivery tumor
  detection
• Benefits of targeting with AvidimersTM
• General regulatory considerations

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Challenges Facing Targeted Therapeutics

• Targeted therapeutics must
• Diffuse out of vasculature (lt20 nm)
• Recognize target cells and bind with high avidity
  and specificityto extracellular binding domain
• Internalize and intracellularly traffic to site
  of intended action
• Avoid normal tissue
• Remain intact until reaching its intended site of
  action
• Carrier should be stable andbiologically inert

Vessel
Normal Cell
Targeted therapeutic
Cancer Cell
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Dendrimer platform
Interior Void
Dendrimer dendri (treelike branching) meros (a
part) 5nm
Core
Generation Number
Surface Groups
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Dendrimer Size Comparison
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Making an AvidimerTM
Interior Void
Dendrimer dendri (treelike branching) meros (a
part) 5nm
Core
Generation Number
Surface Groups
AvidimerTM dendrimer ligand drug (and / or
imaging agent)
Drugs
Ligands
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Computer model of a tri-functional AvidimerTM

• Methotrexate
• (ester-linked cytotoxic agent)

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The Value of AvidimersTM for Drug Delivery

• Molecules have a uniform size and shape
• Globular, true nanoscale dendrimer platform (
  5nm diameter)
• Ability to move in and out of vascular pores and
  pass through the filter organs
• Targeted drug delivery
• Ligands on the surface direct the drug to target
  cells
• Attachment of multiple drug molecules allow
  increased drug concentration within the cell
• Improved therapeutic index
• Improved efficacy over traditional therapies
• Lower systemic toxicity to non-targeted cells
• Potential for faster drug development
• Well-known and/or approved drugs
• Well-characterized targeting ligands

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General regulatory considerations for
nanotechnology

• Characterization and heterogeneity
• Polymer/drug/ligand structure
• Size
• Stability
• Environmental impact?
• Develop nanotechnology expertise within the FDA
• Public scrutiny

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