Celldex Presents Varlilumab Mechanism Data at SITC Annual Meeting 2015
06 November 2015 - 11:00PM
-- Preclinical data suggest cancers vary in
sensitivity to mechanisms of CD27 immune modulation --
-- Clinical experience with varlilumab is
consistent with immune co-stimulation and regulatory T cell
depletion mechanisms, a potential unique benefit for varlilumab
--
-- Multiple Phase 1/2 varlilumab combination
studies currently ongoing --
Celldex Therapeutics, Inc. (NASDAQ:CLDX) today presented new
preclinical data on varlilumab, a fully human monoclonal agonist
antibody that binds and activates CD27, a critical co-stimulatory
molecule in the immune activation cascade. Results suggest that
cancers may respond to CD27 immune modulation by independent
mechanisms, such as immune co-stimulation and regulatory T cell
(Treg) depletion. Varlilumab has the unique ability to act through
both of these mechanisms. The new data were presented in a poster
entitled "The mechanism of anti-tumor immunity induced by
varlilumab, a CD27 agonist mAb, is model dependent" at the Society
for the Immunotherapy of Cancer (SITC) Annual Meeting.
"Our data show that CD27 modulation through varlilumab results
in immune activation and suppression of Treg activity, either of
which can be independently responsible for a therapeutic effect,
depending on the cancer model," said Tibor Keler, Ph.D., Executive
Vice President and Chief Scientific Officer of Celldex
Therapeutics. "Because individual human cancers are also likely to
have different sensitivities to these anti-tumor activities,
varlilumab's ability to act through both mechanisms provides the
broadest potential for therapeutic benefit. Our collection of
preclinical and clinical results to date support Celldex's broad
clinical development program across tumor types and in combinations
with other anti-tumor agents."
To better understand each mechanism separately, scientists
engineered varlilumab to possess either strong co-stimulatory
activity (varli-mG1) or strong Treg suppression activity
(varli-mG2a) and analyzed their efficacy in several preclinical
tumor models. The data indicated that potent co-stimulation
activity was required for therapeutic activity in a BCL1 lymphoma
model, whereas control of Tregs was required for activity in
several other models, such as E.G7 thymoma, CT26 colorectal and
colon 26. Importantly, varlilumab has a combination of immune
co-stimulation and Treg depleting activity and demonstrated potent
anti-tumor activity in all the models.
The immune stimulating and Treg depleting effects of varlilumab
were also observed in Celldex's Phase 1, single-agent clinical
trial of varlilumab in patients with refractory, advanced cancers.
Specifically, varlilumab administration was associated with a rapid
and transient induction of pro-inflammatory cytokines, activation
of T cells as assessed by increased HLA-DR expression and a
significant decrease in circulating Tregs. The study also
demonstrated promising clinical activity. Two patients experienced
durable objective responses including a complete response in
Hodgkin lymphoma (18.9+ months) and a partial response in renal
cell carcinoma (13.6+ months). Thirteen patients experienced stable
disease (3-36.2+ months). Varlilumab was very well tolerated and
demonstrated minimal toxicity, even in elderly patients. There was
no indication of immune-mediated adverse events often seen with
other immunotherapies. Varlilumab is currently being studied in
multiple ongoing Phase 1/2 clinical trials with several anti-tumor
agents, including nivolumab (Opdivo®), ipilimumab (Yervoy®) and
sunitinib (Sutent®) in advanced-stage cancers. Efforts are underway
for additional Phase 2 studies with varlilumab, including a
combination with atezolizumab (Roche's anti-PDL1 antibody), and the
Company will provide updates on these studies as they are
initiated.
About Varlilumab
Varlilumab is a fully human monoclonal agonist antibody that
binds and activates CD27, a critical co-stimulatory molecule in the
immune activation cascade. CD27 can be effectively manipulated with
activating antibodies to induce potent anti-tumor responses and may
result in fewer toxicities due to its restricted expression and
regulation. Varlilumab is a potent anti-CD27 agonist that induces
activation and proliferation of human T cells when combined with T
cell receptor stimulation. In lymphoid malignancies that express
CD27 at high levels, varlilumab may have an additional mechanism of
action through a direct anti-tumor effect. Data from a Phase 1
dose-escalation study of varlilumab demonstrated potent immunologic
activity consistent with its mechanism of action and anti-tumor
activity in patients with advanced, refractory disease. No maximum
tolerated dose was reached and minimal toxicities were observed.
Celldex has initiated a broad development program for varlilumab to
explore its role as an immune activator in combination with a
number of complementary investigational and approved oncology
drugs.
Opdivo® and Yervoy® are registered trademarks of Bristol-Myers
Squibb Co. Sutent® is a registered trademark of Pfizer, Inc.
About Celldex Therapeutics, Inc.
Celldex is developing targeted therapeutics to address
devastating diseases for which available treatments are inadequate.
Our pipeline is built from a proprietary portfolio of antibodies
and immunomodulators used alone and in strategic combinations to
create novel, disease-specific therapies that induce, enhance or
suppress the body's immune response. Visit www.celldex.com.
Forward Looking Statement
This release contains "forward-looking statements" made pursuant
to the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995, including those related to the Company's
strategic focus and the future development and commercialization
(by Celldex and others) of RINTEGA® ("rindopepimut"; "rindo";
CDX-110), glembatumumab vedotin ("glemba"; CDX-011), varlilumab
("varli"; CDX-1127), CDX-1401, CDX-301 and other products and our
goals for 2015. Forward-looking statements reflect management's
current knowledge, assumptions, judgment and expectations regarding
future performance or events. Although management believes that the
expectations reflected in such statements are reasonable, they give
no assurance that such expectations will prove to be correct and
you should be aware that actual results could differ materially
from those contained in the forward-looking statements.
Forward-looking statements are subject to a number of risks and
uncertainties, including, but not limited to, our ability to
successfully complete research and further development and
commercialization of RINTEGA, glembatumumab vedotin and other drug
candidates; our ability to obtain additional capital to meet our
long-term liquidity needs on acceptable terms, or at all, including
the additional capital which will be necessary to complete the
clinical trials that we have initiated or plan to initiate; the
uncertainties inherent in clinical testing and accruing patients
for clinical trials; our limited experience in bringing programs
through Phase 3 clinical trials; our ability to manage and
successfully complete multiple clinical trials and the research and
development efforts for our multiple products at varying stages of
development; the availability, cost, delivery and quality of
clinical and commercial grade materials produced by our own
manufacturing facility or supplied by contract manufacturers, who
may be our sole source of supply; the timing, cost and uncertainty
of obtaining regulatory approvals; our ability to maintain and
derive benefit from the Breakthrough Therapy Designation for
RINTEGA, which does not change the standards for regulatory
approval or guarantee regulatory approval on an expedited basis, or
at all; the failure of the market for the Company's programs to
continue to develop; our ability to protect the Company's
intellectual property; the loss of any executive officers or key
personnel or consultants; competition; changes in the regulatory
landscape or the imposition of regulations that affect the
Company's products; and other factors listed under "Risk Factors"
in our annual report on Form 10-K and quarterly reports on Form
10-Q.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only
as of the date of this release. We have no obligation, and
expressly disclaim any obligation, to update, revise or correct any
of the forward-looking statements, whether as a result of new
information, future events or otherwise.
CONTACT: Company Contact:
Sarah Cavanaugh
Vice President of Investor Relations &
Corp Communications
Celldex Therapeutics, Inc.
(781) 433-3161
scavanaugh@celldex.com
Media Inquiries:
Dan Budwick
Pure Communications, Inc.
(973) 271-6085
dan@purecommunicationsinc.com
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