Cancer is a Challenge Cancer is common in humans – a public health problem ~1 of every 3 women will develop cancer ~1 of every 2 men will develop cancer ~1.7 million Americans will be diagnosed with cancer this year >600 thousand Americans will die from cancer this year {9/11 two hundred times each year!}

Cancer – we are having successes Cancer death rates have decreased 25% in past 25 years 80% of children with cancer will be cured of their disease ~67% of adults with cancer will live at least 5 years after a cancer diagnosis ~14 million cancer survivors in the U.S. New therapies are now constantly being developed Targeted tumor-specific therapies Immunotherapies {inducing the patient’s immune system to fight the cancer}

Cancer Remains a Challenge There remains a great need for new cancer therapies – better efficacy, less toxicity The process of developing new cancer therapies is both slow and costly: Average of 13-16 years to bring a new therapeutic from target validation to marketplace <<10% of new drugs developed make it to the marketplace ~$1.8 billion to bring a new drug to market

Cancer Remains a Challenge Many novel drug cancer drug candidates fail in human clinical trials despite evidence of efficacy in traditional pre-clinical mouse tumor models These mouse tumor models lack key characteristics of human cancers Long latency Natural causation Genomic instability Tumor heterogeneity Tumor microenvironment characteristics

The Cancer Challenge and Opportunity Cancer is common in Pets >170 million pets in U.S. (80 million dogs; >90 million cats) ~1 million dogs treated for cancer in U.S. yearly Cancer kills 50% of dogs >10yo (33% of younger dogs) 33% of cats die from cancer Pet owners are highly motivated to enroll in clinical studies

The Cancer Opportunity Many canine tumors share many characteristics with human cancers (e.g. sarcomas, melanoma, lymphoma, glioma, etc.) Histologic appearance Tumor genetics (some genomics information available; need more) Biologic behavior Molecular targets Therapeutic response Acquired resistance Recurrence Metastasis

The Cancer Opportunity Consortium for Canine Comparative Oncology!! A partnership: Collaborate in pre-clinical and clinical research activities Advance understanding of cancer causation Identify cancer susceptibility genes Identify environmental factors involved in cancer Test novel agents Pre-clinical testing Coordinate clinical trials in canines and humans Joint partnerships with Pharma/Biotech PK/PD, biomarkers, dosing/scheduling, combinations

C30 Pilot Projects – 2017-2018 A Phase II Clinical Trial and Pharmacodynamics Study of CP-DOX in Dogs  Ashutosh Chilkoti, PhD and Steven Suter, DVM, PhD, Diplomate ACVIM  A Mouse to Dog to Human (MDH) Drug Discovery Pipeline  William Eward, MD, DVM and Matthew Breen, PhD  Investigating the Dog as a Preclinical Model for Melanoma Therapy Targeting the Long Non-Coding RNA SAMMSON  Shiaowen David Hsu, MD, PhD and Jennifer Luff, VMD, PhD   Comparative Analysis of the Impact of BRAF Mutations in Bladder Cancer – A Marker of Advancing Disease?  Matthew Breen, PhD and Brant Inman, MD  Imaging Cycling Hypoxia in Canine Tumors During Radiotherapy Dosing  Hiroto Yoshikawa, DVM, PhD and Xiaofeng Steve Zhang, PhD