ImmunoGen Announces Multiple Presentations at AACR Annual Meeting - Seite 3

Date: April 1, 2019
Time: 8:00 AM-12:00 PM ET

• Under a co-development agreement with MacroGenics, it has been shown that ADAM9 is overexpressed in multiple solid tumor indications and that anti-ADAM9 antibodies are efficiently internalized and degraded by tumor cell lines, making ADAM9 an attractive target for ADC development. IMGC936 is the first ADAM9-targeting ADC to enter preclinical development. In vitro studies have demonstrated targeted cytotoxicity of IMGC936 across a panel of ADAM9-positve tumor cell lines with activity at least 2 logs greater than a non-targeting conjugate. Consistent with the activity observed in vitro, an anti-ADAM9-DM21 conjugate displayed compelling anti-tumor activity in multiple xenograft models representing non-small cell lung, gastric and colorectal cancers.

Title: Preclinical evaluation of a new, non-agonist ADC targeting MET-amplified tumors with a peptide-linked maytansinoid - abstract #4817
Date: April 3, 2019
Time: 8:00 AM-12:00 PM ET

• cMet is an attractive target for ADCs, which may address the unmet treatment need for patients with tumors harboring MET amplification. To assess potential toxicity due to normal tissue expression, binding of our antibody to normal hepatocytes from humans and cynos was measured. Very low expression and binding versus tumor cell lines were found and demonstrated that the cytotoxic activity of disulfide-cleavable maytansinoid ADCs prepared from the hinge-variant cMet antibody was equivalent to the parental form in in vivo models. These data merit further exploration of this ADC as a novel treatment option for patients with MET-amplified tumors.

Optimizing ADC Dosing

Title: The potential benefit of lower drug-antibody ratio (DAR) on antibody-maytansinoid conjugate in vivo efficacy - abstract #219
Date: March 31, 2019
Time: 1:00-5:00 PM

• Describes development of a cross-reactive model system that utilizes a chimeric anti-murine FRα antibody that binds with similar affinity to mouse and human FRα. Using this cross-reactive system, where the target is also expressed in normal tissues, 2.0 DAR conjugates were more efficacious than 3.5 DAR conjugates when dosed at matched payload concentrations in multiple xenograft models, suggesting that lower DAR can be an effective strategy to compensate for target-mediated drug disposition (TMDD).

Title: Utilizing a mouse cross-reactive model system to better understand antibody-drug conjugate pharmacokinetics, biodistribution and efficacy - abstract #229