ImmunoGen Announces Multiple Presentations at AACR Annual Meeting - Seite 2

Date: March 31, 2019
Time: 1:00-5:00 PM ET

• ImmunoGen’s newest ADC design uses the novel maytansinoid linker-payload, DM21-C that bears a peptidase/protease-cleavable linker. The goal of this study was to identify the catabolites generated upon incubation in antigen-positive cancer cells (both cell pellet and media), in mouse plasma, as well as in in vitro catabolic systems. DM51 (the thiol- resulting from self-immolation of the cleaved linker-payload) was identified as a major catabolite of the DM21-C ADC.

Title: Preclinical evaluation of DM21, a next‐generation maytansinoid payload with a stable peptide linker - abstract #3898
Date: April 2, 2019
Time: 1:00-5:00 PM ET

• To evaluate the toxicity of DM21 as an ADC, it was conjugated to the non‐targeting, chimeric anti‐soybean trypsin inhibitor antibody (chKTI), and administered to cynomolgus monkeys in two groups with separate dose levels. chKTI‐DM21 was well-tolerated at both doses.

Novel Approaches to ADC Development

Title: Generation of site-specific DARPin drug conjugates using EGFR as a model system - abstract #215
Date: March 31, 2019
Time: 1:00-5:00 PM ET

• DARPin molecules are small engineered proteins, derived from natural ankyrin repeat proteins that are selected to bind to specific targets with high affinity. DARPin drug conjugates (DDCs) were developed using a model EGFR multi-specific DARPin molecule, consisting of four DARPin domains linked together. Biophysical characterization showed the DDCs to be well behaved in stability and solubility assays.

Title: Development of a Probody-Drug Conjugate (PDC) targeting EpCAM for the treatment of solid tumors - abstract #1439
Date: March 31, 2019
Time: 1:00-5:00 PM ET

• EpCAM is an attractive target for ADC development due to its overexpression on a variety of tumors of epithelial origin; however, EpCAM is also expressed on a variety of normal epithelia, thus limiting its utility as an ADC target due to potential toxicity. We aim to overcome this limitation by developing an EpCAM-targeting Probody drug conjugate (PDC). EpCAM-targeting PDCs were better tolerated than the corresponding EpCAM-targeting ADC even at higher dose levels and displayed longer half-lives and greater exposure.

Title: IMGC936, a first-in-class ADAM9-targeting antibody-drug conjugate, demonstrates promising anti-tumor activity - abstract #5136