The Science Behind Taxus

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The Science Behind Taxus

• Advanced Angioplasty 2004

Christian Vander Velde, Boston Scientific Europe,
Marketing
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TAXUS Technology
Polymer
Paclitaxel
Platform

• Express Stent
• Tandem Architecture
• Flexibility
• Maverick Balloon
• Deliverability

• Binds tubulin
• Microtubular dynamics
• Multifunctional

• Uniformity
• Durability
• Biphasic Controlled Release Kinetics

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TAXUS Technology - Paclitaxel
Table adapted from the experimental models by
Ferns et al.
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TAXUS Technology - Paclitaxel
Paclitaxel selectively impacts smooth muscle
cells, platelets, and white blood cell activity
without affecting endothelial cells

• Paclitaxel is a multi-functional drug which
  effectively
• Inhibits proliferation
• Inhibits migration
• Inhibits inflammation
• Inhibits secretion

Restenosis
Prevents

• Paclitaxel enables healing by selectively
  impacting the cells that cause restenosis while
  allowing healthy healing of endothelial cells
• TAXUS shows similar healing between control bare
  metal stent and paclitaxel

Endothelialization
Promotes
Axel et al, AHA 1997, Karsch et al, SIC 1998
Endothelialization of a paclitaxel-eluting stent
in a porcine coronary artery
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Polymer Carrier Considerations Chemical/Physical
and Biological
Biocompatible
Formulate/ process
Coating Integrity
Sterilization
Drug Loading Drug release
Vascular compatible
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Coating Integrity BSC Carrier- TransluteTM
Coated, Loaded, Sterilized, Expanded
40x
200x

• Smooth, Uniform Coverage
• No Cracking, Flaking or Delaminating

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Uniform PTx Content Along Stents of Different
Lengths
(15, 24, 32 mm stents -- 1ug/mm2)
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Uniform PTx Release From ExpressTM Stents of
Different Lengths
1.0 ug/mm2, Slow release 16 mm
1.0 ug/mm2, Slow Release 24 mm
1.0 ug/mm2, Slow Release 32 mm
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Polymer-based Clinical Data

• TRIAL DOSE OF PTx LATE LOSS mm
• TAXUS I 1.0ug/mm2 SR
  0.36 /- 0.48
• TAXUS II 1.0ug/mm2 SR
  0.31 /- 0.39
• TAXUS II 1.0ug/mm2 MR
  0.30 /- 0.39
• TAXUS IV 1.0ug/mm2 SR 0.39 /-
  0.50
• Confirmed by IVUS analysis (TAXUS II -
  Circulation January 20, 2004)

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In Vivo Considerations for Polymers and Drugs

• Animal Model
• Rat
• Rabbit
• Swine
• Canine
• Implant Time
• Implant Location
• Sub Q
• IM
• Iliac
• Coronary
• Other

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Polymer CarriersVascular Compatibility
Failed candidates (normal porcine coronary model)
Polyurethane-coated Stent (2 months)
Bare Stent
Sub-optimal drug carriers can cause severe
inflammatory response
In Collaboration w/Drs. Rogers and Edelman,MIT
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Effect of Animal Model and Implant SiteRat
Subcutaneous Implant Model
28 day Implant - HE Staining
Polyurethane-coated Stent
Bare Stent
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Effect of Animal Model and Implant Site
Porcine Coronary 28 day
Bare Stent
Polyurethane-coated Stent
In Collaboration w/Drs. Rogers and Edelman,MIT
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Effect of Animal Model and Implant Site
Rabbit Iliac Artery
28 day PLA/PCL coated stent
56 day PLA/PCL coated stent
In Collaboration w/Drs. Rogers and Edelman, MIT
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Effect of Animal Model and Implant Site
Porcine Coronary Artery
35 day PLA/PCL
In Collaboration w/Drs. Rogers and Edelman, MIT
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Vascular CompatibilityTransluteTM
180D Bare control
90D Bare control
90D polymer coated
180D polymer coated
In collaboration with Dr. Rob Schwartz Mayo
Clinic and Dr. Greg Wilson Sick
Childrens-Toronto
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Translute Polymer Long term (180 days) vascular
compatibility
180 day

• Good safety profile
• Polymer similar to control
• Reproduced from lot to lot

Translute only Express stent
In collaboration with Dr. Rob Schwartz Mayo
Clinic and Dr. Greg Wilson Sick
Childrens-Toronto
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Vascular Compatibility TransluteTM
Endothelial coverage (PECAM 1, 0-5)
Luminal Stenosis
Inflammation (CD45, 0-4)
No significant differences
In Collaboration w/Drs. Rogers and Edelman,MIT
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TAXUS Technology - Translute Polymer

• Polymer-based matrices provide
• ease of handling
• uniform dose along stent and dosing in a
  controlled manner consistency
• a matrix by which drug release can be manipulated
  to achieve a desired biological response

With greater opportunities come greater challenges
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TransluteTM Polymer stability

• TransluteTM coating integrity was maintained in
  10-year equivalency tests
• The TransluteTM polymer has shown remarkable
  stability out to two years in an animal model
• Harsh conditions (alcohol storage, mild heat,
  agitation) fail to degrade the polymer
• Tests have shown that following physical abrasion
  of the polymer, the release is not markedly
  increased

data on file
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Thank You !