Positive Toxicology & Production Data on ADCs Generated with SMARTag™ Technology

Over the last decades antibody drug conjugates have received much attention.  This is, in part, due to their huge impact on the development of anticancer drugs. The efficacy of these relatively new compounds is attributed to the unique capabilities of highly targeted precice delivery of cytotoxic payloads to cancer cells.  One of the problems with first generation ADC technology is that it remained difficulty to create conjugates with a uniform drug to antibody ratio (or DAR) and a consistent payload placement on the antibody.  SMARTag™ Technology is changing this.

David Rabuka, Global Head R&D, Chemical Biology, Catalent Pharma Solutions, is scheduled to present new data, highlighting the benefits of SMARTag technology in Antibody Drug Conjugate or ADC development at the upcoming World ADC Summit, to be held at the Maritim Kurhaushotel Bad Homburg, Frankfurt, Germany, on the 23rd – 25th February, 2015.

The proprietary SMARTag site-specific protein modification and cytotoxin-linker technologies, originally developed by Redwood Bioscience Inc, enables the generation of homogenous bioconjugates engineered to enhance potency, safety and stability. The technology employs natural post translational modifications found in human cells to create one or more aldehyde tags at designated sites on protein molecules. These chemical handles are then stably conjugated to cytotoxic payloads to prevent their systemic release.[2][3]

ADC Bio
Lonza
MabPlex
 

The development of Antibody-drug Conjugates using the SMARTag Technology starts with the insertion of a five amino acid sequence (CXPXR) in a target antibody’s DNA. Then cloned antibodies are grown from a specialized Chinese Hamster Ovary (CHO) cell line. Further, the formylglycine-generating enzyme (FGE) recognizes the five-amino acid sequence and converts that site to an aldehyde-bearing amino acid. This aldehyde tag then becomes the site where the linker and cytotoxic load is attached to the antibody.[1][2][3]
The SMARTag platform provides precise payload positioning and defined stoichiometry of payload–protein ratios. The control afforded by the technology enables identification of superior drugs from libraries of differentially designed conjugates.[3]

Site Specific ADC Generation
Rabuka’s presentation, on February 24th at 2.30 p.m., is entitled Site Specific ADC Generation Using SMARTag™ Technology, and will highlight the most recent data in the technology’s development.  The data includes PK and toxicology data from primate studies illustrating how SMARTag technology allows for development of ADCs with favorable stability and safety profiles compared to alternative ADC technologies.

Manufacturing efficiency
Rabuka will also present recent production data, further demonstrating that the SMARTag system can achieve antibody production titers of up to 5 g/L for site specifically modified ADCs, with potentially significant benefits for manufacturing efficiency and cost of goods. The evolution of SMARTag linker technology will also be discussed and the presentation will examine how the choice of linker can alter the efficacy and stability of an ADC in various models.

Rabuka, who is a member of the Advisory Board of this journal, assumed the role of Catalent Pharma Solutions’ Global Head of R&D Chemical Biology in October 2014, following Catalent’s acquisition of Redwood Bioscience Inc., where he previously acted as President and Chief Scientific Officer.