Rob Burgess, Ph.D. President Medical Nanotechnologies, Inc.

Nanomedical Functionality - Carbon Nanotube Cancer Therapeutics Rob Burgess, Ph.D. President Medical Nanotechnologies Incorporated

MedNanoTech 3 Zyvex Corporation and Zyvex Performance Materials – Carbon Nanotube Functionalization

MedNanoTech 4 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 5 Kentera-Conjugated Carbon Nanotubes are Soluble in Water Customizable side chains confer solubility

MedNanoTech 6 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

MedNanoTech 7 RF-Dependent Kentera-Solubilized Carbon Nanotube Thermal Conductivity Source: Curley et al.

MedNanoTech 8 CNT-Based Cancer Therapeutics Market Cancer therapeutics is the world’s 3 rd largest therapeutics market, worth $35B in 2003 and projected to be $60B in 2010 with a 8% CAGR (Pharmaceutical Business Review). Main Technical Barriers to Entry The key to the cancer therapeutic market penetrance is more potent therapy and less discomfort. MedNanoTech’s Technological Advantages Initial studies suggest Kentera CNT functionalization technology combined with external electromagnetic excitation could address efficacy and side effects for a number of types of cancers. Cancer therapeutics is transitioning from nonspecific shotgun approaches to targeted methodologies with higher efficacy and fewer side effects.

MedNanoTech 9 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 10 Many Types of Cancer May be Treatable by RF or Near IR CNT Therapies Bone Brain *Breast Cervical *Colorectal Head and Neck  Liver *Lung Melanoma Ovarian  Pancreatic *Prostate Testicular * Denotes top four with respect to incidence.

MedNanoTech 11 Kentera and Kentera-conjugated carbon nanotubes are minimally cytotoxic. Source: Draper et al.

MedNanoTech 12 Optical microscopy image of polypyrrole/MWNT nanocomposite coated onto gold wire in normal rat kidney cell culture – no cytotoxicity observed. Carbon nanotubes wrapped in polypyrrole exhibit no toxicity. Source: Draper et al.

MedNanoTech 13 Intracellular Accumulation of PEDOT/PSS-Conjugated Carbon Nanotubes 72 hours post-treatment Source: Draper et al. HEK293 Cells Arrows indicate dynamic movement of CNTs within the cytoplasm.

MedNanoTech 14 Cells containing Kentera-conjugated carbon nanotubes are efficiently ablated upon RF exposure. No SWNTs 11% PI Stained SWNTs 99.7% PI Stained Source: Curley et al.

MedNanoTech 15 Kentera/SWNTsKentera H&E TUNEL Intratumoral CNT/Kentera injections demonstrate RF-mediated cellular ablation. Source: Curley et al.

MedNanoTech 16 CNT/Conjugated-polymer Technological Advantages Mechanism of action well established Efficient conjugation of CNTs to virtually any targeting agent or drug Effective dispersion of CNTs in an aqueous environment Extracellular and intracellular CNT localization Adjuvant and combination therapies can be developed with precision Therapeutics manufacture is controllable Conjugated polymer properties well established Conjugated polymer allows for efficient attachment of targeting molecules to CNTs

MedNanoTech 17 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 18 Criteria for Success: Targeted CNT Cancer Therapeutics Functionality Dispersion - Effective aqueous dispersion must be demonstrated. Preliminary results are encouraging. (internal research) Efficacy – CNT’s must aggressively ablate targeted tissue. Preliminary results are encouraging. Toxicity – CNT’s and polymer functionalization must be demonstrated as nontoxic. Preliminary results are encouraging Specificity – CNT’s must be successfully targeted to tumorigenic tissue and away from healthy tissue. Collaborators gearing up to test this.

MedNanoTech 19 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. Nanoco, LLC Peter Wilk, M.D

MedNanoTech 20 For Further Information Rob Burgess, Ph.D. President Medical Nanotechnologies, Inc. Phone: