OsteosarcomaNormal Tissues

Human Dog

Companion Animal Cancer Models Large outbred Animals Strong Genetic similarities to Humans

Naturally Occurring cancers Immune competant and syngeneic Relevant Tumor Histology/Genetics Relevant Response Profiles to Conventional Chemotherapy

Tumor Heterogeneity Metastasis Biology Recurrence/Resistance

Cancer IN Companion Animals 65 Million Companion Animals in the US

4 million pet dogs diagnosed with cancer each year

Pet owners seek advanced care for their pets

Comparative Oncology

TO PROVIDE OPPORTUNITIES TO INCLUDE NATURALLY OCCURRING CANCER MODELS IN THE STUDY OF CANCER BIOLOGY AND THERAPY

The CCR - Comparative Oncology Program

•Develop essential reagent kit for the study of comparative models in translational and biology-based research;

•Develop multicenter collaborative network with extramural comparative oncology programs. Within this network design, implement and manage pre-clinical trials involving pet animals that will evaluate novel therapeutic strategies for cancer;

•Increase the awareness of the appropriate use of naturally occurring cancer models within the cancer research community;

Resources and Reagents: opportunities for Layered

Translation

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5000 10000 15000

0102030

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5000 10000 15000

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Human Serum

Canine Serum #1

Canine Serum #2

Canine Serum #3

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Comparative Oncology Trials Consortium (COTC)

Draft Trial Overview

-2-3 Page Summary

- Internal Review

Trial Overview Board

-CCR/CTEP/DTP Members

- Focus on value of dog trial to development path

COTC Consortium Members

-Review Trial Overviews

Solicit Ad Hoc Community Reviews

-Individuals/Groups likely to be involved in clinical development

Re-draft Re-draftRe-draft

Approval Package

Decision Package for CCR Directors

Solicit Ad Hoc Community to Review Full Protocol (JDC)

-Individuals/Groups likely to be involved in clinical development and/or data management

COTC Consortium Members

-Review Full Protocol

Commence Trial

Collaboration Initiated

-Pharma

-NCI CCR-COP

-Academia

Re-draft

Trial Review Process: Effort to ensure integration

Integration of a Comparative Approach

ActivityToxicity

PharmacokineticsPharmacodynamics

DoseRegimenScheduleBiomarkers

Responding HistologiesCombination therapies

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Small AnimalPreclinical Phase III Human

Clinical TrialsQuickTime™ and a

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Tumor-BearingDog Studies

Phase II HumanClinical Trials

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Phase I HumanClinical Trials

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Tumor-BearingDog Studies

Non-Human PrimateBeagle Dog

New Cancer Drug

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Large Pharma

Merck Status: CDA in place, meeting to discuss collaborations has

been scheduled for early January 2006.

Astrazeneca Status: Meeting is planned for mid-November to discuss a trial

in pet dogs.

Small Pharma/Biotech

Genzyme Status: CRADA meeting and presentation completed.

Locus Pharmaceuticals Status: CDA has been completed and a Trial Overview is being

drafted.

Academia/Biotech

SemaCo Status: CDA IN PLACE, in vitro evaluation underway (T Olgios in canine OSA

cell lines)

Colando Pharmaceuticals Status: Currently validating their anti-RRM2 antibody in canine normal and

tumor tissues by Western and Immunohistochemical analysis.

Center for Cancer Research

Radiation Oncology (Jim Mitchel) Tempol Evaluation of intravenous Tempol in pet dogs receiving fractionated

radiation therapy in dogs with head and neck cancer Status - Trial overview in second review

Surgery Branch (Steve Libutti) Phage Delivery of TNF- Evaluation of RGD Targeted Delivery of Phage Expressing TNF- To Tumor

Bearing Dogs Status - Trial approved for initiation

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NewsNature Medicine 11, 1018 (2005) Published online: 28 September 2005; | doi:10.1038/nm1005-1018a

Cancer researchers usher in dog days of medicineGeorge S Mack

Columbia, South Carolina

After thousands of years of friendship, man and dog will soon be working together to advance drug discovery. As part of a new comparative-oncology program at the US National Cancer Institute, researchers are set to begin drug trials in dogs that aim to bridge the gap between preclinical drug studies and effects of the same drug in people.

Two multicenter trials, set to begin in early 2006, will evaluate new therapeutic approaches for cancer in dogs, says program chief Chand Khanna, a veterinary oncologist at the institute's Center for Cancer Research.

"It turns out that many cancers, such as lymphoma, melanoma and osteosarcoma, are well represented in pet dogs," Khanna says. "The dogs will help us prioritize the agents that go into human clinical trials and help make those trials more efficient."

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Wall Street Journal July 7, 2005

Nature Medicine October 2005

The Good News…We have arrived. Now we must deliver

Acknowledgments

Comparative Oncology ProgramCCR, National Cancer Institute Melissa Paoloni

Christina Mazcko

Katherine Hansen

Tumor and Metastasis BiologySection, PEDIATRIC ONCOLOGY BRANCH

CCR, National Cancer Institute Ling Ren

Arnulfo Mendoza

Jessica Cassavaugh

Rachel Blackwood

Sung-Hyeok Hong

Lauren Shapiro

Ben Bruce

Rachel Newman

Gaurav Khanna

AcknowledgmentsMolecular Oncology Section

Pediatric Oncology BranchCCR, National Cancer Institute Xiaolin Wan

Choh Yeung

Lee Helman

Tissue Array Research Project (TARP), CCRStephen HewittKimberly Parker

Biomedical Proteomics Program, CCRLiRoung YuMing ZhouTim Veenstra

Cornell UniversityAnthony Bretscher

Columbia UniversityCharles PowellAlain Borczuk

University of MichiganEvan Keller

University of UmeaGoran Landberg

State University of OhioMark Berryman

LCMB, CCR, National Cancer Institute Yanlin Yu

Glenn Merlino

Cancer Genetics Branch, NHGRIKristin BairdPaul Meltzer

Oncogenomics Section, POB, NCIJaved Khan

Carcinogenesis/Prevention, CCRNancy Colburn