Carbon NanotubeBased Cancer Therapeutics Medical Nanotechnologies Incorporated Rob Burgess, Ph.D. Founder and President www.nanomedinc.com Zyvex Corporation and Zyvex Performance Materials – Carbon Nanotube MedNanoTech Functionalization 2 Zyvex Performance Materials’ Technical Approach MedNanoTech Zyvex NanoSolve® Enhanced Composites • • • • • • Sizing agent or tailored coupling agent Exfoliation of CNT Uniform dispersion Adhesion to polymer Not a surfactant Other advanced capabilities — Process knowledge — Custom formulations Two distinct functions: • Non-damaging binding to the CNT • Kentera™ Technology 3 Customizable adhesion to host material (example: polymer such as epoxy) Enables CNTs in Composites Kentera-Conjugated Carbon Nanotubes are Soluble in Water •Customizable side chains confer solubility 4 MedNanoTech RF-mediated CNT Thermal Conductivity MedNanoTech RF field RF Transmitter RF Receiver Target area Source: Adapted from US Patent Application 2005/0251234 A1 Inventors: Kanzius et al. CNT-introduced regions Source: Gannon et al. 5 CNT Functionalization MedNanoTech Carbon nanotubes can be functionalized with antibodies and polar lipids. AFM TEM Source: Chakravarty et al. AFM Source: Marches et al. 6 CNT Intracellular Delivery MedNanoTech Intracellular Accumulation of PEDOT/PSS-Conjugated Carbon Nanotubes HEK293 Cells 72 hours post-treatment 7 Source: Draper et al. Carbon nanotube properties make them a unique platform for therapeutic MedNanoTech applications. • Organized Structure • Mechanism of Action Known • RF and Near IR Sensitive • Electrically and Thermally Conductive • Can be Functionalized with a Variety of Molecules • Can Penetrate Cells 8 CNT Cytotoxicity MedNanoTech Kentera and Kentera-conjugated carbon nanotubes are minimally cytotoxic. 9 Source: Draper et al. Antibody/CNT Cell Surface Binding and Cytotoxicity Antibody/lipid-coated carbon nanotubes are noncytotoxic and bind specifically to cancer cells. Daudi Cells Source: Chakravarty et al. Source: Marches et al. 10 MedNanoTech Cell Surface Binding MedNanoTech Antibody-coated carbon nanotubes bind specifically to cancer cells. 11 Source: Chakravarty et al. CNT- Based Cancer Therapeutics MedNanoTech Cancer cells are effectively ablated by carbon nanotubes in the presence of NIR light. 12 Source: Chakravarty et al. CNT- Based Cancer Therapeutics MedNanoTech Panc-1 cells containing Kentera-conjugated carbon nanotubes are efficiently ablated upon RF exposure. No SWNTs 11% PI Stained 13 SWNTs 99.7% PI Stained Source: Gannon et al. Intratumoral CNT/Kentera injections demonstrate RF-mediated cellular MedNanoTech ablation. Kentera/SWNTs Kentera H&E TUNEL 14 Source: Gannon et al. Proposed Product Pipeline – Moving Towards Targeting CNTs Monoclonal Antibody Cell Surface Breast, Colorectal, Head and Neck MedNanoTech Her2, Erbitux Small Molecule Cell Surface, Intracellular Lung Tarceva, Iressa Aptamer Cell Surface, Intracellular Renal, Lung AS1411 (in dev.) Peptide Cell Surface, Intracellular Breast, Thyroid RGD (in dev.) Targeting Agent Mode of Action Cancer Application Known Example(s) 15 Criteria for Success: Targeted CNT Cancer Therapeutics MedNanoTech Functionality Dispersion - Effective aqueous dispersion must be demonstrated. Efficacy – CNT’s must aggressively ablate targeted tissue. • Toxicity – CNT’s and polymer functionalization must be demonstrated as nontoxic. • Specificity – CNT’s must be successfully targeted to tumorigenic tissue and away from healthy tissue. 16 Acknowledgments MedNanoTech Zyvex Corporation Jim Von Ehr Gareth Hughes, Ph.D. Tanja Kmecko UT-Dallas Rocky Draper, Ph.D. Paul Pantano, Ph.D. Inga Musselman, Ph.D. UT-SW Medical Center Ellen Vitetta, Ph.D. Radu Marches, Ph.D. Pavitra Chakravarty, Ph.D. UT-MD Anderson Cancer Center Steve Curley, M.D. Nanoco, LLC Peter Wilk, M.D. 17 For Further Information MedNanoTech Rob Burgess, Ph.D. President Medical Nanotechnologies, Inc. Email: rob.burgess@nanomedinc.com Phone: 214-440-2311 www.nanomedinc.com 18