Progress of the SNM Clinical Trials Network Michael Graham, PhD, MD Clinical Trials Network Co-Chair SNM President 1

2 CTN Organizational Chart

Promote “The Practice of Clinical Trials” through: Accelerated clinical trials for investigational therapeutics Improved availability and performance of imaging biomarkers Increased number of imaging biomarkers available for clinical use Faster, more cost-effective drug development to facilitate patient access Mission 3

Provide an international registry of qualified and certified imaging centers through phantom utilization and ongoing assessment and monitoring Organize a manufacturing registry for production of and access to imaging biomarkers Provide site orientation and training programs to increase adherence to protocols; drive quality Support multisite clinical trials to gather standardized imaging data that will lead to improved efficiency and validity of using imaging biomarkers for therapeutic trials Collect safety and efficacy data of imaging biomarkers through a centralized IND Overall Goals 4

Consistent Growth Network Registries (Dec 09) 5

Pharma companies interested in using imaging technology in drug discovery and development Focus on multicenter clinical trials ~ 1 per year Credentialed academic institutions to conduct studies —Expertise —Technologies/applied standards Site orientation and training programs ―Certified technologists Imaging Biomarker Development Network 6

Registration in the CTN site database: online completion of site-specific information (e.g., equipment, personnel, research experience) Scanner Validation via the CTN Phantom Program Site Qualification: meeting a minimum of pre-determined requirements related to research infrastructure, validated equipment and access to experimental imaging agents. Site Qualification Process 7

FDG FLT FDOPA FAZA FMISO Ga-68 octreotide FES FHDT C-11 acetate No company owns the rights No company will solely benefit No company will sponsor the trials Centralized IND Drugs without parentage 8

Benefits Mechanism of access to radiopharmaceuticals without having to perform pre-clinical studies Access to standardized imaging protocols Decreased cost associated with pharmaceutical IND by not having to file a second tracer IND Shared responsibility for reporting of safety and efficacy data Centralized IND 9

Considerations Community Needs –Therapeutic areas of interest –Current pharmaceutical development Tracer Availability –Location of manufacturers –Agent viability 1.Access to Pre-clinical data Centralized IND Selection 10

Centralized IND Selection 11 Areas of Interest Hypoxia Amyloid Lipid Synthesis Protein Synthesis Dopaminergic Receptors Estrogen Receptors Angiogenesis Apoptosis Testosterone Receptors

First Multicenter IND 3'-deoxy-3'-[ 18 F] fluorothymidine (FLT) 12 F

Why FLT? Community interest Investigational PET imaging biomarker Literature reports of “potential” for demonstrating tumor proliferation Potential as a surrogate marker for evaluating investigational as well as existing oncology therapeutics Broadly applicable to lung, breast, esophageal, GI, brain, lymphoma First Multicenter IND: [F-18] FLT 13

F-MISO Second Multicenter IND 14

Why F-MISO? Community interest Availability Demonstrated ability to image and quantify hypoxia Second Multicenter IND 15

First SNM multicenter IND for an investigational imaging biomarker First three founding members from the pharmaceutical development community on board 200+ members of both the imaging site and manufacturers registries Over 25% participation from outside the U.S. Development and launch of a clinical oncology phantom program Many on-going educational activities to inform about the Network and advance the awareness and understanding of the “Practice of Clinical Trials” within the imaging community –Community Workshop to be held Feb 1-2, 2010 in Albuquerque Accomplishments 16

One new IND per year (next submission expected by mid-2010) Expanded phantom program to include cardiac and brain qualifications Reach beyond PET biomarkers Assist with imaging protocol development, conduct, and integration with imaging CROs Expand multicenter IND capability for imaging biomarkers –Non-proprietary –Proprietary –Individual academic-investigator driven Long-Term Vision 17