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

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

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

Delaware Health Sciences Alliance

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

Colorectal Cancer and Women

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

The One-Two Punch: Finding and Eradicating Occult Metastases

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

The First Punch: Identifying Patients with Occult Metastases

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

The Second Punch: Eliminating Occult Metastases

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

Control GCC p<0.001 Days Percent Survival ControlGCC *** Immunization Tumor Number GCC Vaccine Protects Against Metastatic Colon Cancer in Mice

Individualizing Cancer Immunotherapy Control GCC p<0.001 Days Percent Survival

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.