Carbon Nanotube- Based Cancer Therapeutics Rob Burgess, Ph.D. Founder and President Medical Nanotechnologies Incorporated

MedNanoTech 2 Zyvex Corporation and Zyvex Performance Materials – Carbon Nanotube Functionalization

MedNanoTech 3 Zyvex Performance Materials’ Technical Approach Two distinct functions: Non-damaging binding to the CNT Customizable adhesion to host material (example: polymer such as epoxy) Kentera™ Technology Enables CNTs in 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 Zyvex NanoSolve ® Enhanced Composites

MedNanoTech 4 Kentera-Conjugated Carbon Nanotubes are Soluble in Water Customizable side chains confer solubility

MedNanoTech 5 RF-mediated CNT Thermal Conductivity RF Transmitter RF Receiver RF field Source: Adapted from US Patent Application 2005/ A1 Inventors: Kanzius et al. Target area CNT-introduced regions Source: Gannon et al.

MedNanoTech 6 Source: Chakravarty et al. Carbon nanotubes can be functionalized with antibodies and polar lipids. Source: Marches et al. AFM TEM CNT Functionalization

MedNanoTech 7 Intracellular Accumulation of PEDOT/PSS-Conjugated Carbon Nanotubes 72 hours post-treatment Source: Draper et al. HEK293 Cells CNT Intracellular Delivery

MedNanoTech 8 Carbon nanotube properties make them a unique platform for therapeutic 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

MedNanoTech 9 Kentera and Kentera-conjugated carbon nanotubes are minimally cytotoxic. Source: Draper et al. CNT Cytotoxicity

MedNanoTech 10 Antibody/CNT Cell Surface Binding and Cytotoxicity Source: Chakravarty et al. Antibody/lipid-coated carbon nanotubes are noncytotoxic and bind specifically to cancer cells. Source: Marches et al. Daudi Cells

MedNanoTech 11 Cell Surface Binding Source: Chakravarty et al. Antibody-coated carbon nanotubes bind specifically to cancer cells.

MedNanoTech 12 CNT- Based Cancer Therapeutics Source: Chakravarty et al. Cancer cells are effectively ablated by carbon nanotubes in the presence of NIR light.

MedNanoTech 13 Panc-1 cells containing Kentera-conjugated carbon nanotubes are efficiently ablated upon RF exposure. No SWNTs 11% PI Stained SWNTs 99.7% PI Stained Source: Gannon et al. CNT- Based Cancer Therapeutics

MedNanoTech 14 Kentera/SWNTsKentera H&E TUNEL Intratumoral CNT/Kentera injections demonstrate RF-mediated cellular ablation. Source: Gannon et al.

MedNanoTech 15 Proposed Product Pipeline – Moving Towards Targeting CNTs Monoclonal Antibody Cell SurfaceBreast, Colorectal, Head and Neck Her2, Erbitux Small MoleculeCell Surface, Intracellular LungTarceva, Iressa AptamerCell Surface, Intracellular Renal, LungAS1411 (in dev.) PeptideCell Surface, Intracellular Breast, ThyroidRGD (in dev.) Targeting Agent Mode of Action Cancer Application Known Example(s)

MedNanoTech 16 Criteria for Success: Targeted CNT Cancer Therapeutics 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.

MedNanoTech 17 Acknowledgments UT-Dallas Rocky Draper, Ph.D. Paul Pantano, Ph.D. Inga Musselman, Ph.D. Zyvex Corporation Jim Von Ehr Gareth Hughes, Ph.D. Tanja Kmecko UT-MD Anderson Cancer Center Steve Curley, M.D. UT-SW Medical Center Ellen Vitetta, Ph.D. Radu Marches, Ph.D. Pavitra Chakravarty, Ph.D. Nanoco, LLC Peter Wilk, M.D.

MedNanoTech 18 For Further Information Rob Burgess, Ph.D. President Medical Nanotechnologies, Inc. Phone: