Cancer Nanotechnology:New Opportunities for

Targeted Therapies

FDA Public MeetingOctober 10, 2006

Piotr Grodzinski, Ph.D.Director, Nanotechnology for Cancer ProgramsOffice of Technology and Industrial Relations

National Cancer Institute

• 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)

Nanotechnology-based Drug Delivery:Key BenefitsNanotechnology-based Drug Delivery:Key Benefits

Nanomaterial characterization: Responsible, Systematic, Standardized

Multi-Functional Nanoparticle-based TherapiesMulti-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)

Nanoshells:Photothermal therapy

N. Halas, J. West et al, Ann Biomed Eng. 34, 15 (2006)

Dendrimers: Targeted delivery of methotrexate

Nanoparticle-based Therapies: Different ApproachesNanoparticle-based Therapies: Different Approaches

J. Baker, et al., Cancer Res. 65, 5317 (2005)

Uncertainties of Moving Multi-Functional Nanoparticles to the Clinic 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

NCI Strategy:Alliance for Nanotechnology in CancerNCI 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

Next step

Adapted from Challenge and Opportunity on the Critical Path to New Medical Products (http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html)

Nanoparticle Translation Mechanism: From Early Development to the ClinicNanoparticle 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

Nanotechnology Alliance, NCL

Nanotechnology:Environmental and Safety ConsiderationsNanotechnology: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

Interagency CollaborationsInteragency Collaborations

• Characterization

• Critical path development

• Training

• Public Interface

• Interpret Data on Environment, Health and Safety

• Shared Data and Platforms

• Standards/Precision Measurement Capabilities

• Nanobiotechnology Training