Monoclonal antibodies (mAbs) have demonstrated considerable utility in cancer treatment. There are a number of unmodified mAbs currently available for patient treatment. However, in order to improve the therapeutic value of mAbs considerable effort is being focused on enhancing their activity by attaching cytotoxic drugs to the biomolecules. This combination of small molecule drugs and antigen specific biomolecules results in a targeted system for drug delivery, an antibody-drug conjugate (ADC). However, many ADCs in development have had issues with variable potency as well as toxicity. A significant obstacle to the creation of a successful modified ADC therapeutic is the need to produce the conjugated product in a homogenous form with a defined and controlled toxic payload. However, the existing methods for chemical protein modification result in mixtures of product, with varying amounts of toxin conjugated to the antibody in numerous locations. We have developed a technology platform that enables the chemical modification of proteins in a controlled, site-specific manner. Using this technology we can generate a panel of modified recombinant IgGs that have homogenous attachment sites and are easy to chemically elaborate with a toxic payload. The resulting homogenous ADCs are loaded with a defined amount of drug placed at a defined position on the protein. If successful, we believe this work will change the utility of ADC therapeutics and will result in a robust pipeline of best in class drugs. Our first proposed ADC product is an anti-CD22 IgG site-specifically conjugated with maytansine to be used for the treatment of B-cell leukemia and lymphomas. We will generate a panel of anti-CD22 ADCs and select a lead candidate to be developed as a potential biotherapeutic for clinical studies.

Public Health Relevance

The combination of small molecule drugs and antigen specific biomolecules results in a targeted system for drug delivery, an antibody-drug conjugate (ADC). Redwood Bioscience's aldehyde-tagged technology can generate novel, best-in-class ADCs. The first ADC therapeutic will be for the treatment B-cell leukemia and lymphomas.

Agency
National Institute of Health (NIH)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44GM096494-03
Application #
8655167
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Marino, Pamela
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Redwood Bioscience, Inc.
Department
Type
DUNS #
City
Burlingame
State
CA
Country
United States
Zip Code
94010