Final Data from Celldex Therapeutic’s CDX-011 Phase 2 Study in Metastatic Breast Cancer Supports Overall Survival Benefit in

  Final Data from Celldex Therapeutic’s CDX-011 Phase 2 Study in Metastatic
  Breast Cancer Supports Overall Survival Benefit in Patients with High GPNMB
  Expression

--Broad activity with greatest benefit in patients with high GPNMB-expressing
                       triple negative breast cancer--

   --Data presented today in a poster session at San Antonio Breast Cancer
                                 Symposium--

Business Wire

NEEDHAM, Mass. -- December 08, 2012

Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced final results from
the Company’s randomized Phase 2b EMERGE study of CDX-011 in patients with
glycoprotein NMB (GPNMB)-expressing, advanced, heavily pretreated breast
cancer. CDX-011 is an antibody-drug conjugate that targets and binds to GPNMB,
a specific protein that is expressed in breast cancer which promotes the
migration, invasion and metastasis of the disease. It is also highly expressed
in triple negative breast cancers where it is associated with increased risk
of recurrence. The results presented today at the 2012 CTRC-AACR San Antonio
Breast Cancer Symposium confirm preliminary findings reported in May and
establish proof of principle with evidence of higher activity in patient
subgroups with high GPNMB expression (expression in ≥25% of tumor cells),
including those with triple negative disease. Progression free and overall
survival benefits were demonstrated in the subgroup of patients with triple
negative disease that also highly expressed GPNMB, and strong trends towards
benefits were seen in all patients with high GPNMB expression. This benefit in
overall survival is seen despite the fact that more than a third of control
patients received CDX-011 as a cross over at the time of disease progression.

While the study was not powered to demonstrate statistical significance
between the arms, beneficial activity in targeted patient populations that
highly expressed GPNMB was consistently observed and, in some cases, was
statistically significant. Treatment of patients with both triple negative
breast cancer and high GPNMB expression showed high overall response rates
(ORR) for the CDX-011 arm (CDX-011 ORR of 33% vs 0% in the Investigator’s
Choice (IC) arm) and an overall survival and progression free survival (PFS)
benefit for CDX-011 that reached statistical significance (CDX-011 median
survival of 10.0 months vs IC of 5.5 months; p=0.003); (CDX-011 median PFS of
3.0 months vs IC of 1.5 months; p=0.008). In patients with high GPNMB
expression, a high response rate was observed in the CDX-011 arm (CDX-011 ORR
of 32% vs IC of 13%) and a trend of improvement in overall survival and PFS
was demonstrated for the CDX-011 arm (CDX-011 median survival of 10.0 months
vs IC of 5.7 months; p=0.18); (CDX-011 median PFS of 2.7 months vs IC of 1.5
months; p=0.14). For the overall study population, response rates, overall
survival and progression free survival after treatment with CDX-011 suggested
anti-tumor activity consistent with the standard of care. Patients receiving
IC alone who crossed over to receive CDX-011 upon disease progression appeared
to represent the better outcomes in the control arm, with a median survival of
12.5 months, as compared to those who did not cross over, with a median of 5.4
months.

“CDX-011 is eliciting impressive response rates in these patients with
heavily-pretreated metastatic disease, where physicians typically have little
expectation of clinical response. Most importantly, these responses appear to
translate into a survival benefit in the patients where we would expect
CDX-011 to work best, the targeted patient populations with high levels of
GPNMB on the tumor cell surface,” said Denise A. Yardley, MD, Senior
Investigator in the Breast Cancer Research Program at the Sarah Cannon
Research Institute and a lead investigator in the EMERGE study. “Based on
these results, it appears that GPNMB is emerging as a potentially important
marker in breast cancer and that CDX-011 holds significant potential as a
possible targeted therapy for triple negative patients, a patient population
that currently has no targeted interventions.”

Thomas Davis, MD, Senior Vice President and Chief Medical Officer of Celldex
Therapeutics, commented, “The mature results presented today confirm the
preliminary results shown previously and support advanced clinical development
of CDX-011, which may play a critical role in treating patients with advanced
breast cancer. We look forward to discussions with the Food and Drug
Administration later this month to design a pivotal study intended to support
approval of CDX-011 for specific patients with breast cancer.”

Final Study Results:

A total of 122 patients were treated on the study, with 81 patients randomized
to the CDX-011 arm and 41 patients to the IC single-agent chemotherapy arm, of
which 15 later crossed over to receive CDX-011. In total, 81 CDX-011 patients
(including cross overs) and 36 IC patients had on-study radiographic
assessments and were evaluable for response. Nearly all patients had Stage IV,
or metastatic, disease. Patients on the CDX-011 arm received a median of six
prior courses of therapy and patients on the IC arm received a median of five
prior courses of therapy. Adverse events prominent with the CDX-011 arm
included rash and peripheral neuropathy, while hematologic toxicity was more
frequent and severe in the IC arm. The Phase 2b EMERGE study required
patients’ tissue to have at least 5% of cells expressing GPNMB at entry and,
based on this low threshold, 99% of screened patients were eligible for entry
allowing for a specific focus on expression pattern subgroups. High GPNMB
expression is defined as ≥25% of tumor epithelial cells expressing GPNMB by
IHC.

Phase 2b EMERGE Final Survival Results: Survival Benefit of CDX-011 is
Greatest in Patients with Triple Negative Disease that Highly Expresses (≥25%)
GPNMB and All Patients with High GPNMB Expression*
                                                               Triple
           All Patients  Triple      High GPNMB  Negative and
                               Negative        Expression   High GPNMB
                                                               Expression
           CDX-011    IC   CDX-011  IC   CDX-011  IC   CDX-011    IC
Median
PFS         2.1        2.0  2.3      1.6  2.7      1.5  3.0        1.5
(months)
           p=0.38      p=0.43    p=0.14    p=0.008
Median OS   7.5        7.4  6.9      6.5  10.0     5.7  10.0       5.5
(months)
           p=0.24      p=0.30    p=0.18    p=0.003

*Analyses include all treated patients. Patients who initially received
Investigator’s Choice (IC) and subsequently crossed over to receive CDX-011
(n=15) are included in the PFS analysis for each treatment. These patients,
with a median OS of 12.5 months (range 4.4 to 21.0 months), are assigned to
the IC arm only for OS analysis.

Phase 2b EMERGE Final Overall Response Results: Activity of CDX-011 is Greatest in
Patients with Triple Negative Disease that Highly Expresses (≥25%) GPNMB and All
Patients with High GPNMB Expression*
                                                                    Triple Negative
           All Patients      Triple Negative  High GPNMB       and
                                                  Expression        High GPNMB
                                                                    Expression
             CDX-011   IC       CDX-011   IC      CDX-011   IC      CDX-011   IC
                                                                    
             (n=81)    (n=36)   (n=27)    (n=9)   (n=25)    (n=8)   (n=12)    (n=4)
% Response                                                  13
(%          16 (10)  14 (8)  19 (7)   0      32 (16)  (13)   33 (8)   0
Confirmed)
% Disease
Control     57       53      67       33     64       38     75       25
Rate

*Responses per RECIST 1.1; IC = Investigator’s Choice; CDX-011 arm includes 15
patients who crossed over to receive CDX-011 treatment after progression on
IC. Analysis of best response excludes patients who discontinued from study
without evaluable post-baseline radiographic imaging (n=16 for CDX-011 arm;
n=5 for IC arm).

About CDX-011:

CDX-011 (glembatumumab vedotin) is an antibody-drug conjugate (ADC) that
consists of a fully-human monoclonal antibody, CR011, linked to a potent
cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology,
comprised of MMAE and a stable linker system for attaching it to CR011, was
licensed fromSeattle Genetics, Inc.The ADC is designed to be stable in the
bloodstream. Following intravenous administration, CDX-011 targets and binds
to GPNMB, a specific protein that is expressed in breast cancer and other
tumor types which promotes the migration, invasion and metastasis of breast
cancer. Upon internalization into the targeted cell, CDX-011 is designed to
release MMAE from CR011 to produce a cell-killing effect. CDX-011 has been
shown to be well tolerated and active, with observed objective responses in
two positive Phase 1/2 trials in metastatic breast cancer and advanced
melanoma. InMay 2010, the U.S. Food and Drug Administration(FDA) granted
Fast Track designation to Celldex’s CDX-011 for the treatment of advanced,
refractory/resistant GPNMB-expressing breast cancer.

About Celldex Therapeutics, Inc.:

Celldex Therapeutics is the first antibody-based combination immunotherapy
company. Celldex has a pipeline of drug candidates in development for the
treatment of cancer and other difficult-to-treat diseases based on its
antibody focused Precision Targeted Immunotherapy (PTI) Platform. The PTI
Platform is a complementary portfolio of monoclonal antibodies,
antibody-targeted vaccines and immunomodulators used in optimal combinations
to create novel disease-specific drug candidates. For more information, please
visit http://www.celldextherapeutics.com.

Safe Harbor Statement Under the Private Securities Litigation Reform Act of
1995: 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 of CDX-011 or any of our other drug
candidates, including rindopepimut (CDX-110), CDX-1135 (formerly TP10),
CDX-1401, CDX-1127, CDX-301, Belinostat and any future action we or the FDA
(or any other regulator) might take with respect to regulatory approvals.
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, future actions that the FDA and other
regulators might take or not take with respect to CDX-011 or any drug
candidate, the market for CDX-011 or any other drug candidate or assay, future
clinical testing which will be necessary before FDA approval could be sought,
our ability to obtain additional capital on acceptable terms, or at all,
including the additional capital which will be necessary to complete the
clinical trials that we initiated in 2012 and plan to initiate in 2013; our
ability to adapt APC Targeting Technology^TM to develop new, safe and
effective vaccines against oncology and infectious disease indications; our
ability to successfully complete product research and further development of
our programs; the uncertainties inherent in clinical testing; our limited
experience in bringing programs through Phase 3 clinical trials; our ability
to manage research and development efforts for multiple products at varying
stages of development; the timing, cost and uncertainty of obtaining
regulatory approvals; the failure of the market for the Company's programs to
continue to develop; our limited cash reserves and our ability to obtain
additional capital on acceptable terms, or at all; 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
risks detailed from time to time in the Company's filings with the Securities
and Exchange Commission, including the Company's Form 10-K for the fiscal year
endedDecember 31, 2011, anditsForms 10-Q and 8-K.

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:

Celldex Therapeutics, Inc.
Sarah Cavanaugh, 781-433-3161
Vice President of IR & Corp Comm
scavanaugh@celldextherapeutics.com
or
For Media:
BMC Communications
Brad Miles, 646-513-3125
bmiles@bmccommunications.com
 
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