Immune Design Presents Data on the Mechanism of Action of G100 via TLR4 Expressed in B Cell Malignancies at the Inaugural AAC...
June 25 2018 - 8:00AM
- G100 directly targets and modifies TLR4
expressing malignant B cells making them more visible to the
anti-tumor immune response-
Immune Design (Nasdaq:IMDZ), an immunotherapy company focused on
novel therapies in oncology, today announced preclinical and
translational data that support the mechanism of action of G100 in
patients with indolent non-Hodgkin Follicular lymphomas (FL). These
data were presented at the Inaugural AACR International Meeting
Advances in Malignant Lymphoma: Maximizing the Basic-Translational
Interface for Clinical Application 2018 in Boston.
The research presented was designed to
understand why high TLR 4 expression in patient’s samples
correlated with clinical responses to G100 treatment. By analyzing
patient samples, cell lines and mouse lymphoma models the following
was observed:
- Murine and human B-lymphoma cell lines express TLR4 and respond
in vitro to G100 stimulation with upregulation of MHC-II and
co-stimulatory markers CD40 and CD80, typical of the activation of
antigen-presenting function of B-cells;
- In vivo murine tumors of lymphoma models respond to treatment
with G100 in injected tumors as well as distal, untreated tumors
showing local and abscopal tumor control, mediated by systemic
T-cell response;
- Approximately 70% of follicular lymphoma patients in a Phase
1/2 study express TLR4 in >50% of tumor cells in baseline
biopsies. TLR4 expression ranging from 10%-100% of tumor cells was
also detected in biopsies of patients with marginal zone lymphoma,
small lymphocytic lymphoma, diffuse large B-cell lymphoma and
cutaneous T-cell lymphoma; and
- In an ongoing Phase 2 trial of G100 with low dose radiation and
pembrolizumab, almost all patients with an objective tumor response
(³50% tumor shrinkage) showed TLR4 expression in >50% of tumor
cells.
“These data illustrate that in addition to the
known activation by G100 of dendritic cells and macrophages in the
tumor microenvironment, G100 can also act directly on malignant B
cells expressing TLR4. G100 treated malignant B cells may become
more visible to the anti-tumor immune response, which correlates
with clinical responses following intratumoral therapy with G100.”
said Jan ter Meulen, MD, PhD, Chief Scientific Officer at Immune
Design. “In FL patients, a strong correlation was observed between
expression of TLR4 in more than 50% of tumor cells and objective
responses following G100 therapy. This discovery potentially allows
for a TLR4 biomarker-targeted G100 therapy of other tumor types,
independent of histology.”
The full poster presentation can be accessed from the
publications page of the Immune Design website.
About G100
G100 is a product candidate from Immune Design's internal
discovery platforms and contains a potent synthetic small molecule
toll-like receptor-4 (TLR-4) agonist, Glucopyranosyl Lipid A (GLA).
G100 leverages the activation of both innate and adaptive immunity
in the tumor microenvironment to create an immune response against
the tumor's preexisting diverse set of antigens. A growing set of
clinical and preclinical data have demonstrated the ability of G100
to activate tumor-infiltrating lymphocytes, macrophages and
dendritic cells, and promote antigen-presentation and the
recruitment of T cells to the tumor. The ensuing induction of
local and systemic immune responses has been shown to result in
local and abscopal (shrinking of tumors outside the scope of the
localized treatment) tumor control. G100 was evaluated in a Phase 1
study in Merkel cell carcinoma patients and produced a 50% overall
response rate per protocol and a favorable safety profile.
Currently, G100 is being evaluated as both a monotherapy (with
local radiation) and in combination with Merck’s anti-PD-1 agent,
pembrolizumab, pursuant to a clinical collaboration with Merck, in
a randomized Phase 1/2 trial in patients with follicular
non-Hodgkin lymphoma.
About Immune Design
Immune Design is a late-stage immunotherapy company employing
next-generation in vivo approaches to enable the body's immune
system to fight disease. The company's technologies are engineered
to activate the immune system's natural ability to generate and/or
expand antigen-specific cytotoxic immune cells to fight cancer and
other chronic diseases. CMB305 and G100, the leading product
candidates with broad potential in oncology, are based on the
company’s two technology platforms that are potent stimulators of
the immune system – ZVex® and GLAAS® - the fundamental technologies
of which were licensed from the California Institute of Technology
and the Infectious Disease Research Institute (IDRI), respectively.
Both ZVex and GLAAS also have potential applications in infectious
disease and allergy indications, which are being developed through
ongoing pharmaceutical collaborations. Immune Design has
offices in Seattle and South San Francisco. For more information,
please visit www.immunedesign.com.
Cautionary Note on Forward-Looking
Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as "may," "will," "expect," "plan," "anticipate,"
"estimate," "intend" and similar expressions (as well as other
words or expressions referencing future events, conditions or
circumstances) are intended to identify forward-looking statements.
These forward-looking statements are based on Immune
Design's expectations and assumptions as of the date of this
press release. Each of these forward-looking statements involves
risks and uncertainties. Actual results may differ materially from
these forward-looking statements. Forward-looking statements
contained in this press release include, but are not limited to,
statements about the timing of initiation, progress, scope and
outcome of clinical trials for Immune Design's product
candidates and the reporting of clinical data regarding Immune
Design’s product candidates. Many factors may cause differences
between current expectations and actual results including
unexpected safety or efficacy data observed during preclinical or
clinical studies, clinical trial site activation or enrollment
rates that are lower than expected, changes in expected or existing
competition, changes in the regulatory environment, failure
of Immune Design's collaborators to support or advance
collaborations or product candidates and unexpected litigation or
other disputes. Other factors that may cause Immune
Design's actual results to differ from those expressed or
implied in the forward-looking statements in this press release are
discussed in Immune Design's filings with the U.S.
Securities and Exchange Commission, including the "Risk Factors"
sections contained therein. Except as required by law, Immune
Design assumes no obligation to update any forward-looking
statements contained herein to reflect any change in expectations,
even as new information becomes available.
Media ContactJulie
Rathbunjulie.rathbun@immunedesign.com206-769-9219
Investor ContactSylvia
WheelerSylvia.wheeler@immunedesign.com
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