Celldex Therapeutics' Rindopepimut Demonstrates Promising Clinical Activity in Patients with EGFRvIII-positive Recurrent

Celldex Therapeutics' Rindopepimut Demonstrates Promising Clinical Activity in
Patients with EGFRvIII-positive Recurrent Glioblastoma at SNO

    Strong interim survival trend (12.0 vs 7.9 months) emerging in ongoing
 bevacizumab naive randomized cohort; 5.6 month median OS (48% > 6 months) in
 bevacizumab refractory single-arm cohort;robust anti-tumorimmune responses
 were generated among heavily pre-treatedpatients with recurrent tumors and
               these responses correlate with improved outcome

   Rindopepimut demonstrates ability to significantly shrink recurrent and
                           refractory glioblastomas

 Long-term survival update also provided for three Phase 2 frontline studies;
EGFRvIII patients continue to exceed expectations with 14% 5-year survival vs
                            0% historical control

HAMPTON, N.J., Nov. 24, 2013 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc.
(Nasdaq:CLDX) today reported interim data from its ongoing, exploratory Phase
2 ReACT study of rindopepimut in recurrent glioblastoma. Rindopepimut is an
immunotherapeutic vaccine that targets the tumor specific oncogene
EGFRvIII(v3). Patients with EGFRvIII-positive glioblastoma typically have a
worse prognosis than the overall glioblastoma population, including poor long
term survival. The ReACT results demonstrate promising signs of clinical
activity in advanced patient populations, including patients both naïve and
refractory to bevacizumab (Avastin^®). An update on long-term survival for the
three completed Phase 2 frontline studies in EGFRvIII-positive glioblastoma
was also presented and results continue to exceed outcomes seen in
contemporary controls. A webcast/conference call will be held at 8:30 am ET on
Monday, November 25^th, to discuss the results (details provided below).

The data were presented in an oral session by David A.Reardon, M.D., Clinical
Director, Center for Neuro-Oncology, Dana-Farber Cancer Center and Associate
Professor of Medicine, Harvard Medical School and the lead investigator of the
ReACT study, at the 4th Quadrennial Meeting of the World Federation of
Neuro-Oncology held in conjunction with the 18th Annual Meeting of the Society
for Neuro-Oncology (SNO).

"Patients who have grown right though Avastin are resistant to all of our
available therapies," said David Reardon, M.D. "The potent immune response
generated by rindopepimut and preliminary signs of anti-tumor activity in the
Avastin refractory patients in the ReACT study are very exciting. The
additional signal of an improved survival outcome in Avastin naïve patients
further supports the potential activity of rindopepimut. I look forward to the
final results of this study and hope they confirm what we have seen so far."

"Expectations for a vaccine to be active in this patient population were very
low," said Thomas Davis, M.D., Senior Vice President and Chief Medical Officer
of Celldex. "If these multiple signals for immunologic and anti-tumor activity
persist in the final data, it may establish a new perspective on the potential
for immunotherapy. These early results have led to the expansion cohort and we
are beginning to plan additional studies of combinations that could further
improve efficacy."

ReACT is a Phase 2 exploratory study designed to determine if adding
rindopepimut to standard of care bevacizumab improves the outcomes for
patients with EGFRvIII-positive recurrent glioblastoma across multiple
measures. As originally designed, the study included 2 groups:

  *Group 1 - bevacizumab naive, n= apx. 70, enrollment ongoing—patients
    randomized to receive either rindopepimut or KLH (administered as a
    control), each along with bevacizumab
  *Group 2 - bevacizumab refractory, n= apx. 25, enrollment
    completed—patients receive rindopepimut plus bevacizumab in a single
    treatment arm

In August 2013, Celldex announced that enrollment had been completed in Group
2 and that, based on early evidence of anti-tumor activity, an expansion
cohort of approximately 75 patients (Group 2C) would be added to better
characterize the potential activity of rindopepimut in this refractory patient
population. As amended, the ReACT study will enroll approximately 170

Clinical Activity Overview 

Group 1- Recurrent GBM; bevacizumab naive

Interim results are available for the first 40 patients enrolled [rindopepimut
+ bevacizumab (n=20); control + bevacizumab n=20)]. 12 patients continue to
receive treatment and 27 continue to be followed for survival. While the data
continue to mature, trends toward both an overall survival (OS) and
progression-free survival (PFS) benefit have been observed on the rindopepimut
arm to date.

Interim ReACT Overall Survival and Progression-free Survival Bevacizumab-Naïve
Recurrent GBM
      Rindo + Bev (n=20)    Control + Bev (n=20)    
OS     12.0 months           7.9 months              HR = .43 (0.13, 1.44) ;
PFS    3.7 months            2.0 months              HR= .74 (0.34, 1.61);

The study suggests that early development of high anti-EGFRvIII titer may be
predictive of improved outcomes in this patient population, as improved
survival was associated with rapid generation of a robust humoral response.
All 8 patients on the rindopepimut arm that developed high titers by day 57
are still alive to date (range of 3.6+ to 17.0+ months). For the remaining 10
patients who did not develop high titers by day 57, 5 remain alive (range of
3.8+ to 12.9+ months).Consistent with the premise that EGFRvIII-positive
patients fare worse than the general glioblastoma population, results to date
suggest that the EGFRvIII-positive patient population had a lower OS in the
Control + Bevacizumab arm than was observed in the bevacizumab registration
study (AVF3708g) in recurrent glioblastoma in all-comers (7.9 months OS, ReACT
vs 9.3 months OS AVF3708g).

14 out of 18 (78%) patients with measurable disease on the rindopepimut arm
experienced any tumor shrinkage versus 9 out of 16 (56%) patients on the
control arm. Assessments of response were conducted by study investigators
according to RANO criteria. Cases with greater than a 25% reduction in area of
measurable disease were also reviewed by an expert panel blinded to treatment

Preliminary Analysis of Objective Response Bevacizumab-Naïve Recurrent GBM
                                       Rindo + Bev        Control + Bev
ORR (confirmed CR/PR)^1,2               3/19 (16%)**       2/16 (13%)**
Any response ( > 50% shrinkage)
including those not sustained at                          
subsequent assessment^1
By Investigator review                 7/19 (37%)         3/16 (19%)
By Expert Panel review                 6/19 (32%)         4/16 (25%)
By Either review                       9/19 (47%)         4/16 (25%)
**Two additional patients in the rindopepimut arm and 1 in the control arm
have experienced greater than 50% shrinkage by either investigator or expert
panel review and are pending follow up for confirmation of response.
^1Response-evaluable patient subset with measurable disease. ^2All concordant
between investigator and expert panel review

70% of patients in the rindopepimut arm had stable disease or better for
greater than 2 months versus 55% in the control arm. Further emphasizing the
benefit in disease control, only 5% of patients treated with rindopepimut
required an increase in steroids versus 35% of patients on the control arm.

Group 2- Recurrent GBM; bevacizumab refractory [defined as having progressed
(grown through) by RANO criteria within two months of prior bevacizumab

Results are available for all 25 patients enrolled in this arm. One patient
continues to receive treatment and 6 continue to be followed for survival.

ReACT Overall Survival and Progression-free Survival Bevacizumab-Refractory
Recurrent GBM
                            Median, months
                             95% CI
OS                           5.6(3.2, 6.7)
PFS                          1.9 months (1.8, 2.8)

PFS results in this refractory population may be more consistent with the
profile of an immunotherapy candidate where PFS does not always correlate
directly with an overall survival benefit. The median OS of 5.6 months is
noteworthy in these heavily pretreated, refractory EGFRvIII-positive patients.
A review of the literature assessing survival in recurrent patients who are
bevacizumab experienced across eight independent studies suggests a
weighted-average survival of 3.6 months (range of 2.6 to 5.8 months) in
all-comers. It is important to note that these eight studies do not
necessarily meet the strict definition of refractory applied in the ReACT
study and that these studies included EGFRvIII-negative patients who tend to
perform better.

Again, results suggest that early development of high anti-EGFRvIII titer may
be predictive for improved outcome in this patient population as improved
survival was associated with rapid generation of a robust humoral response.
For the 13 patients with high titers by day 57, median OS was 6.6 months
versus 3.2 months for the 11 patients who did not develop high titers (HR =
.33 (0.08, 0.67); p=0.009). 69% of patients with high titers were alive at 6
months compared to 18% of patients who did not develop high titers. With no
comparative data available to define expected outcome for EGFRvIII-positive
patients who have failed bevacizumab, an ambitious goal of progression-free
survival of 20% at 6 months was established as the primary endpoint for this
arm; 2 out of 25 (8%) patients are progression-free at six months.

Six out of 24 patients with measurable disease experienced any tumor
shrinkage. Assessments of response were conducted by study investigators
according to RANO criteria. Cases with greater than a 25% reduction in area of
measurable disease were also reviewed by an expert panel blinded to treatment
assignment. Per the investigator review, 4 patients experienced significant
tumor shrinkage; however, two of these were deemed protocol violations because
while the patient had prior bevacizumab exposure, they did not meet the strict
definition of bevacizumab refractory as outlined in the ReACT protocol. 32% of
patients had stable disease or better for greater than 2 months.

Preliminary Analysis of Objective Response Bevacizumab-Refractory Recurrent
Patient         Investigator Assessment              Expert Panel Review
1               PR (79% shrinkage)                   SD*
2               90% shrinkage; not sustained         SD*
Patients with progression > 2 months after discontinuation of bevacizumab:
3               CR (9.3 months duration)             SD*
4               100% shrinkage; not sustained        PR
*Enhancement judged not measureable, but thought to improve on treatment

Immune Response Overview

Remarkably robust humoral responses comparable or exceeding those seen in the
frontline setting (ACT III) were observed despite advanced disease, use of
steroids, prior chemotherapy exposure and the presence of bulky tumor. There
was a four-fold increase in anti-EGFRvIII antibody titers in 84% of
bevacizumab-naïve patients and 79% of bevacizumab-refractory patients. A
high-titer response was noted (range of 1:12,800 to 1:6,553,600) in 50% of
bevacizumab-naïve patients and 67% of bevacizumab-refractory patients and
titers increased with time on study. Importantly, the study suggests that
early development of anti-EGFRvIII titer may be predictive of improved
outcomes in this patient population as improved survival was associated with
rapid generation of humoral response. These results also provide further
support for the rindopepimut/bevacizumab combination approach, as prior
studies have suggested that bevacizumab can enhance immune-mediated anti-tumor
effects in tumor model and may, in turn, optimize EGFRvIII specific immune


Across both Group 1 and Group 2, rindopepimut plus bevacizumab was very well
tolerated (dosing up to 13+ months). There were no unexpected toxicities
associated with concomitant bevacizumab administration and there were no
treatment-related toxicities resulting in discontinuation of study treatment.
Adverse events were consistent with prior studies of rindopepimut.

Phase 2 Frontline Long-term Overall Survival Assessments (ACT III, ACT II and

Celldex also announced today the presentation of four- and five-year survival
data from the Phase 2 rindopepimut clinical program (3 studies; pooled n=105)
in EGFRvIII-positive glioblastoma. Across three Phase 2 studies of
rindopepimut, survival data remains consistent and suggests a substantial and
continuing survival benefit in comparison to independent control datasets (see
chart below) at the median and at all other time points evaluated.

Phase 2 Frontline Long-term Overall Survival Assessments (ACT III, ACT II and
                         Median,      2-year     3-year    4-year    5-year
                        Years        rate       rate      rate      rate
                         (95% CI)
Phase 2 Rindopepimut     2.1 (1.8,    51%        30%       18%       14%
Studies, Pooled (n=105)  2.4)
Matched historical       1.3 (0.9,    6%         6%        0%        0%
control (n=17)*          1.7)
*Patients treated at M.D. Anderson contemporaneously to ACTIVATE, matched for
major eligibility requirements, including EGFRvIII+ GBM, GTR and no PD through

The pooled overall long-term survival results continue to be consistent with
the ACT III Phase 2 study (18% for 4-years and 14% for 5-years). The Phase 3
registration study, ACT IV, is modeled after the ACT III study.

Webcast/Conference Call Information

Celldex management will host a conference call/webcast at 8:30 am ET tomorrow,
Monday, November 25, 2013 to discuss the ReACT study results and the
rindopepimut program. John F. de Groot, M.D., Associate Professor of the
Department of Neuro-Oncology, Director of the Neuro-Oncology Fellowship
Program and Director of Clinical Research in the Department of Neuro-Oncology,
at the University of Texas MD Anderson Cancer Center in Houston, TX will join
the call. Dr. de Groot served on the expert review committee for the ReACT

The conference call and presentation will be webcast live over the Internet
and can be accessed by logging on to the Events & Presentations section under
"Investors and Media" of the Celldex Therapeutics website at www.celldex.com.
The call can also be accessed by dialing (866) 743-9666 (within the United
States) or (760) 298-5103 (outside the United States). The passcode is

A replay of the call will be available forapproximately one week after the
live call concludes through December 2, 2013. To access the replay, dial
855-859-2056 (within the United States) or 404-537-3406 (outside the United
States). The passcode is 10297215.

About Rindopepimut

Rindopepimut is an investigational immunotherapy that targets the tumor
specific oncogene EGFRvIII (v3), a functional and permanently activated
variant of the epidermal growth factor receptor (EGFR), a protein that has
been well validated as a target for cancer therapy. Expression of EGFRvIII
correlates with increased tumorigenicity in mouse models and poor long term
survival in clinical studies of patients with glioblastoma (GBM). In addition,
EGFRvIII-positive cells are believed to stimulate proliferation of
non-EGFRvIII cells through IL-6 cell-to-cell signaling and to release
microvesicles containing EGFRvIII, which can merge with neighboring cells,
transferring tumor-promoting activity. EGFRvIII expression may also be
associated with tumor stem cells that have been identified in GBM. These stem
cells contribute to resistance to cytotoxic therapy and tumor recurrence.
EGFRvIII is expressed in tumors in about 30% of patients with GBM. It has not
been detected at a significant level in normal tissues; therefore, targeting
of this tumor-specific molecule is not likely to impact healthy tissues.

Three Phase 2 trials of rindopepimut—ACTIVATE, ACT II, and ACT III—have been
completed in newly diagnosed EGFRvIII-positive GBM and have shown consistent
improvements in both overall survival and median progression-free survival.
The most common adverse events for rindopepimut include injection site
reactions, fatigue, rash, nausea and pruritus. Rindopepimut is currently being
studied in two clinical trials in EGFRvIII-positive GBM—an international Phase
3 study called ACT IV in newly diagnosed GBM and a Phase 2 study called ReACT
in recurrent GBM.

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.

Avastin is a registered trademark ofGenentech, a member of the Roche Group.

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 (by Celldex and others) of rindopepimut
(CDX-110), Glembatumumab vedotin ("glemba"; CDX-011), CDX-1135, CDX-1401,
CDX-1127, CDX-301, Belinostat and other products. 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 rindopepimut, glemba 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; our
ability to adapt our 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 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.

All forward-looking statements are expressly qualified in their entirety by
this cautionary notice. You are cautioned not to place undue reliance on any
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We have no obligation, and expressly disclaim any obligation, to update,
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of new information, future events or otherwise.

CONTACT: Sarah Cavanaugh
         Vice President of Investor Relations &
         Corp Communications
         Celldex Therapeutics, Inc.
         (781) 433-3161
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