ImmunoGen Announces Multiple Presentations at AACR Annual Meeting
28 February 2019 - 8:31AM
Business Wire
- Continued Innovation in ADCs
Highlighted in Eleven Posters
- First-in-Class ADAM9-targeting ADC,
IMGC936, Developed in Collaboration with MacroGenics, Demonstrates
Preclinical Activity in Models of Non-Small Cell Lung, Gastric, and
Colorectal Cancers
- Novel DARPin® Drug Conjugate Platform
Evaluated in Collaboration with Molecular Partners AG
ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field
of antibody-drug conjugates (ADCs) for the treatment of cancer,
today announced that 11 posters highlighting continued innovation
in the field of ADCs will be presented at the upcoming American
Association of Cancer Research (AACR) Annual Meeting to be held
March 29 – April 3, 2019 in Atlanta, Georgia.
“ImmunoGen remains at the forefront of ADC innovation and the
data to be presented at AACR further demonstrate the value of our
productive research platform,” said Richard Gregory, Ph.D.,
ImmunoGen’s chief scientific officer.
The schedule of ImmunoGen’s presentations at AACR is as
follows:
IGN Payload Innovation
Title: Antibody-drug conjugates (ADCs) of a new class of
N-10 amino linked DNA alkylating indolino-benzodiazepines (IGNs) –
abstract #224Date: March 31, 2019Time: 1:00-5:00 PM
ET
- In an ongoing effort to further explore
the structure-activity relationship of DNA alkylating effector
molecules for ADCs, a new class of IGNs has been developed that
possesses a self-immolative peptide linker attached at the N-10
amine of the imine-reduced IGN monomer subunit. ADCs with this
class of payload displayed potent, antigen-specific in vitro
activity across a panel of folate receptor α (FRα)-expressing cell
lines.
Title: Antibody-drug conjugates (ADCs) with
indolinobenzodiazepine dimer (IGN) payloads: DNA-binding mechanism
of IGN catabolites in target cancer cells - abstract
#1886Date: March 31, 2019Time: 1:00-5:00 PM ET
- Investigation of the mechanism of
binding of IGN catabolites with DNA in target cancer cells and with
model duplex DNA or hairpin oligonucleotides. Both
mono-and-di-imine IGN molecules remained bound to genomic DNA even
at two days, suggesting a potent interaction with cellular
DNA.
Advancement in Platform Linkers and
Payloads
Title: Optimizing lysosomal activation of antibody-drug
conjugates (ADCs) by incorporation of novel cleavable dipeptide
linkers - abstract #0231Date: March 31, 2019Time:
1:00-5:00 PM ET
- Based on screens of a panel of
dipeptide linkers for efficient lysosomal proteolysis, several
novel, previously unreported peptide linker designs were identified
and incorporated into ADCs bearing a DNA-alkylating IGN payload.
Several dipeptide linker designs were superior in rates of
lysosomal processing compared to a reference standard L-Ala-L-Ala
dipeptide linker.
Title: LC-MS based catabolite identification study of an
ADC with DM21-C, a novel maytansinoid linker-payload - abstract
#538Date: March 31, 2019Time: 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
#3898Date: April 2, 2019Time: 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 #215Date:
March 31, 2019Time: 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
#1439Date: March 31, 2019Time: 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 #5136Date: April 1, 2019Time: 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 #4817Date: April 3, 2019Time: 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 #219Date: March 31, 2019Time: 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 #229Date: March 31,
2019Time: 1:00-5:00 PM ET
- Generation of a cross-reactive model
system that utilized a chimeric anti-murine FRα antibody that binds
both mouse and human FRα and can be conjugated to either
maytansinoid or IGN payloads. This model system was predicted to
have substantial TMDD due to normal tissue expression of FRα. The
results showed that TMDD significantly affected the
pharmacokinetics, biodistribution, and activity of the conjugate
relative to a non-cross-reactive ADC, with lower ADC doses being
more severely impacted than higher doses.
Additional information and full abstracts can be found at
www.aacr.org.
ABOUT IMMUNOGENImmunoGen is developing the next
generation of antibody-drug conjugates (ADCs) to improve outcomes
for cancer patients. By generating targeted therapies with enhanced
anti-tumor activity and favorable tolerability profiles, we aim to
disrupt the progression of cancer and offer our patients more good
days. We call this our commitment to “target a better now.” Our
lead product candidate, mirvetuximab soravtansine, is in a Phase 3
study for folate receptor alpha (FRα)-positive platinum resistant
ovarian cancer, and in Phase 1b/2 testing in combination regimens.
Our novel IGN candidates for hematologic malignancies, IMGN779 and
IMGN632, are in Phase 1 studies.
Learn more about who we are, what we do, and how we do it at
www.immunogen.com.
DARPin® is a registered trademark of Molecular Partners
AG.PROBODY™ is a trademark of CytomX Therapeutics, Inc.
This press release includes forward-looking statements based on
management's current expectations. For these statements, ImmunoGen
claims the protection of the safe harbor for forward-looking
statements provided by the Private Securities Litigation Reform Act
of 1995. Various factors could cause ImmunoGen's actual results to
differ materially from those discussed or implied in the
forward-looking statements, and you are cautioned not to place
undue reliance on these forward-looking statements, which are
current only as of the date of this release. It should be noted
that there are risks and uncertainties related to the development
of novel anticancer products, including risks related to
preclinical and clinical studies, their timings and results, and
the potential that earlier clinical studies may not be predictive
of future results. A review of these risks can be found in
ImmunoGen's Annual Report on Form 10-K for the fiscal year ended
December 31, 2017 and other reports filed with the Securities and
Exchange Commission.
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INVESTOR RELATIONS CONTACTSarah
Kiely781-895-0600sarah.kiely@immunogen.comMEDIA
CONTACTCourtney
O’Konek781-895-0600courtney.okonek@immunogen.comORFTI
ConsultingRobert
Stanislaro212-850-5657robert.stanislaro@fticonsulting.com
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