Cancer Nanotechnology: New Opportunities for Targeted Therapies

1. Cancer Nanotechnology: New Opportunities for Targeted Therapies FDA Public Meeting October 10, 2006 Piotr Grodzinski, Ph.D. Director, Nanotechnology for Cancer Programs Office of Technology and Industrial Relations National Cancer Institute

2. Nanotechnology-based Drug Delivery:Key Benefits • Provides multi-functionality: targeting, delivery, reporting • Provides improved therapeutic index • Provides lowered toxic side effects • Delivers multiple drugs directly to tumor site • Enables nucleic acid delivery • Enables non-drug therapies (photothermal, photodynamic) Nanomaterial characterization: Responsible, Systematic, Standardized

3. Multi-Functional Nanoparticle-based Therapies • Multi-functional platforms: • Targeting • Delivery • Reporting, biosensing In one package Free drug formulations do not possess multi-functional characteristics First generation of nano-delivered drugs (no targeting) approved by FDA – Abraxane® M. Ferrari, Nature Reviews 5, 161 (2005)

4. Nanoparticle-based Therapies: Different Approaches Dendrimers: Targeted delivery of methotrexate Nanoshells: Photothermal therapy N. Halas, J. West et al, Ann Biomed Eng. 34, 15 (2006) J. Baker, et al., Cancer Res. 65, 5317 (2005)

5. Uncertainties of Moving Multi-Functional Nanoparticles to the Clinic • Differences exist between the development and regulatory pathway for multi-functional nanoparticles and “traditional” drugs and devices. Need to: • Define the classification (decision tree) in order to determine the characterization process ahead of the submission • Provide interfaces within the regulatory agencies • Establish uniform, publicly available guidelines for the investigators • Determination if therapy is new when it uses an existing drug on a novel delivery platform is a challenge • Gap exists between technology development in an academic setting and further technology maturation through clinical development and regulatory approval

6. NCI Strategy:Alliance for Nanotechnology in Cancer A comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the use of the best capabilities of nanotechnology to cancer applications • Centers of Cancer Nanotechnology Excellence (CCNEs) and Cancer Nanotechnology Platform Partnerships (CNPPs) • To develop novel technologies to deliver drugs more effectively • To develop new, highly sensitive and specific diagnostic techniques • Nanotechnology Characterization Laboratory (NCL) • To develop a standardized assay cascade for preclinical characterization • To identify physical parameters and structure-activity relationships for biocompatibility • Not to address animal efficacy, SAR, PK or PD studies, or manufacturing

7. Nanoparticle Translation Mechanism: From Early Development to the Clinic Opportunities: • Leverage NCL capabilities • Scale up the material manufacturing (GMP) • Provide studies towards IND filing • Initiate Phase 0/Phase I trials Challenges: • High cost • Low interest in academic environment, where most of the innovation resides • Partnerships with the industry needed Next step Nanotechnology Alliance, NCL Adapted from Challenge and Opportunity on the Critical Path to New Medical Products (http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html)

8. Nanotechnology:Environmental and Safety Considerations • Hazard identification • In vitro toxicity • Acute in vivo toxicity • Subchronic/chronic toxicity • Route of exposure • Dose response • External dose • Internal dose • Biologically effective dose • Exposure assessment • Human exposure Nanomaterials production Chronic exposure of the worker Nanomaterials use for biomedical applications Preclinical studies

9. Interagency Collaborations • Standards/Precision Measurement Capabilities • Characterization • Critical path development • Training • Public Interface • Interpret Data on Environment, Health and Safety • Nanobiotechnology Training • Shared Data and Platforms