Mersana Therapeutics Presents Preclinical Data Further Demonstrating Differentiating Aspects of Its ADC Platform Technology a...
April 17 2018 - 1:01PM
Detailed Characterization of Unique DolaLock
Technology Enhancements to Drug Efficacy and Tolerability
Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage
biopharmaceutical company focused on discovering and developing a
pipeline of antibody drug conjugates (ADCs) based on its Dolaflexin
and other proprietary platforms, today announced new data on
Mersana’s lead ADC platform, Dolaflexin, and on the HER2 targeted
ADC XMT-1522, presented as part of the 2018 American Association
for Cancer Research (AACR) Annual Meeting being held April 14-18 in
Chicago, IL.
“The data presented in these posters demonstrate the benefits of
our differentiated approach to ADCs,” said Timothy B. Lowinger,
Chief Scientific Officer, Mersana Therapeutics. “The DolaLock
controlled bystander effect represents a unique approach to enhance
both efficacy and tolerability. In addition, we are excited about
the potential of XMT-1522 to be combined with checkpoint inhibitors
to provide significant additional clinical benefit to patients in
need.”
In a poster presented on Sunday, April 15,
“Unique Pharmacologic Properties of Dolaflexin-based ADCs – a
Controlled Bystander Effect,” Mersana demonstrated the ability of
the DolaLock controlled bystander effect to improve the efficacy
and tolerability of ADC therapies. Mersana investigators
demonstrated the release and intracellular conversion of auristatin
F-hydroxypropylamide (AF-HPA) to auristatin F (AF), as well as
biodistribution and tumor retention in vivo. AF-HPA is the initial
drug release product, which is freely cell permeable. Intra-tumor
metabolism helps convert the AF-HPA to AF, which is non-cell
permeable and highly potent. Conversion of AF-HPA to AF was
observed within tumor cells, and co-culture assays with
HER2-positive and HER2-negative cells confirmed the cell
permeability and bystander-killing capabilities of AF-HPA.
Biodistribution studies revealed time-dependent concentrations of
AF-HPA and AF as well as significant accumulation of AF in
xenograft tumor models.
A second poster presented on Tuesday, April 17,
“Synergy of an anti-HER2 ADC TAK-522 (XMT-1522) in
combination with anti-PD1 monoclonal antibody (mAb) in a syngeneic
breast cancer model expressing human HER2” co-authored by Takeda
and Mersana, characterized the ability of both the free payload
AF-HPA and the ADC XMT-1522 to induce immunogenic cell death (ICD)
in cells. In addition, a novel syngeneic breast cancer (4T1) model
expressing human HER2 at a relatively low antigen density was
developed. XMT-1522 showed significant inhibition of tumor growth
in this poorly immunogenic tumor model. A combination of XMT-1522
and a checkpoint inhibitor further enhanced the anti-tumor
efficacy, resulting in complete responses.
About XMT-1522 XMT-1522 is a
Dolaflexin ADC targeting HER2-expressing tumors. XMT-1522 comprises
a proprietary HER2 antibody which is conjugated with Mersana’s
Dolaflexin platform – a Fleximer polymer linked with a
proprietary auristatin payload. XMT-1522 provides a drug load of
approximately 12 molecules per antibody, specifically designed to
improve potency while simultaneously increasing tolerability.
XMT-1522 has the potential to extend HER2-targeted therapy beyond
the current “HER2-positive” populations into patients with lower
levels of HER2 expression. The Phase 1 protocol will evaluate
XMT-1522 in patients with advanced HER2-positive breast and gastric
cancer, as well as advanced breast cancer with low HER2 expression
and non-small cell lung cancer. More information on the ongoing
Phase 1 clinical study can be found at clinicaltrials.gov.
About Dolaflexin The Dolaflexin
platform is designed to increase the efficacy, safety and
tolerability of ADCs by overcoming key limitations of existing
technologies based on direct conjugation of a payload molecule to
an antibody. Dolaflexin consists of Fleximer, a biodegradable,
highly biocompatible, water soluble polymer, to which are attached
multiple molecules of our proprietary auristatin drug payload,
using a linker specifically optimized for use with our polymer. The
high-water solubility of the Fleximer polymer compensates for the
low solubility of the payload, surrounding the payload and
protecting it from aggregation and maintaining stability in
circulation. Multiple molecules of this Dolaflexin polymer-drug
conjugate can then be attached to an antibody of choice, which
significantly increases the payload capacity of the resulting ADC.
This approach differs from most other ADC technologies that
conjugate the payload directly conjugated to the antibody via a
linker. Using its Dolaflexin platform, Mersana has been able to
generate ADCs with a very high Drug-to-Antibody Ratio (DAR),
between 12 to 15, while maintaining acceptable pharmacokinetics and
drug-like properties in animal models. This represents a three to
four-fold increase in DAR relative to traditional ADC
approaches.
About Mersana Therapeutics
Mersana Therapeutics is a clinical-stage biopharmaceutical company
using its differentiated and proprietary ADC platforms to develop
highly targeted drugs with increased tolerability and expanded
opportunities to deliver meaningful clinical benefit to
patients. Mersana’s product candidate XMT-1522 is in Phase 1
clinical trials in patients with advanced tumors expressing HER2,
including breast cancer, non-small-cell-lung-cancer (NSCLC) and
gastric cancer patients. The Company’s second product
candidate, XMT-1536, is in Phase 1 clinical trials in patients with
tumors expressing NaPi2b, including ovarian cancer, NSCLC and other
cancers. In addition, multiple partners are using Mersana’s
platform to advance their ADC pipelines.
Media Contact
Paul Kidwell paulkidwell@comcast.net 617-680-1088
Investor ContactStern Investor Relations,
Inc.Christina Tartagliachristina@sternir.com(212) 362-1200
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