1. Clinical & Translational Science: Individualizing Cancer Immunotherapy Scott A. Waldman, MD, PhD, FCP Thomas Jefferson University

2. Clinical & Translational Science: Individualizing Cancer Immunotherapy Scott A. Waldman, MD, PhD, FCP Director, Delaware Valley Institute for Clinical and Translational Science Chair, Department of Pharmacology and Experimental Therapeutics Director, GI Malignancies Program, Kimmel Cancer Center Thomas Jefferson University Philadelphia, Pennsylvania

3. Disclosures I am the Chair of the Scientific Advisory Board of Targeted Diagnostics & Therapeutics, Inc. (TDT; uncompensated) TDT provides research support to my laboratory TDT licenses patents which are the subject of this presentation This technology has been sublicensed to DiagnoCure, which does not provide support for this work I am entitled to a share of royalties collected by Thomas Jefferson University upon the sale of products resulting from patents on which I am an inventor

4. Delaware Health Sciences Alliance

5. Delaware Valley Institute for Clinical and Translational Science (DVICTS) Translational Investigators

6. Colorectal Cancer and Women

7. Stage, Prognosis and Prediction % of cases at presentation Stage IStage IIStage IIIStage IV % 5 year survival 14 8964383 283721 Stage Recurrence (%) 2040 Caucasian African American

8. The One-Two Punch: Finding and Eradicating Occult Metastases

9. Guanylyl Cyclase C (GCC) as a Marker and Target in Colon Cancer N T F Y C C E L C C N P A C A G C Y

10. The First Punch: Identifying Patients with Occult Metastases

11. Identifying Patients With Occult Metastases Using Molecular Detection Low Risk (<5%) High Risk (>80%) Hazard Ratio=65

12. The Second Punch: Eliminating Occult Metastases

13. Novel Vaccine Approaches to Colon Cancer: Cancer Mucosal Antigens 1 2 T cell AP C Cancer Mucosa Antigens 5 X CRC Metastase s Effecto r T cells 4 3

14. 203040 0 20 40 60 80 100 Control GCC p<0.001 Days Percent Survival ControlGCC 0 100 200 300 400 *** Immunization Tumor Number GCC Vaccine Protects Against Metastatic Colon Cancer in Mice

15. Individualizing Cancer Immunotherapy 203040 0 20 40 60 80 100 Control GCC p<0.001 Days Percent Survival

16. Acknowledgements Thomas Jefferson University and Kimmel Cancer Center  Pharmacology  Stephanie Schulz  Peng Li  Janis Haaf  Chris Bonaccorso  Egeria Lin  Ahmara Gibbon  Michael Valentino  David Zuzga  Adam Snook  Alex Meija Medical Oncology  Edith Mitchell Pathology  Juan Palazzo  Biostatistics  Terry Hyslop  Surgery  Scott Goldstein  Gerald Isenberg Christiana Care  Bruce Boman  Nicholas Petrelli Funding  NIH  PA Department of Health  TDT, Inc.