GSK’s MAGE-A3 Cancer Immunotherapeutic Phase 3 Study in Melanoma Misses First Co-Primary Endpoint

  GSK’s MAGE-A3 Cancer Immunotherapeutic Phase 3 Study in Melanoma Misses
  First Co-Primary Endpoint

    In Line with Independent Data Monitoring Committee’s (IDMC) Unanimous
 Recommendation, GSK will Continue Study Until Second Co-primary Endpoint is

Business Wire

LEXINGTON, Mass. -- September 5, 2013

Agenus Inc. (Nasdaq:AGEN) today announced  that GlaxoSmithKline’s (NYSE:GSK)
DERMA^i study, a Phase 3 randomized, blinded, placebo-controlled MAGE-A3
cancer immunotherapeutic^ii (CI) trial, which contains Agenus’QS-21 Stimulon^®
adjuvant^iii, a component of GSK’s novel adjuvant system AS15, did not meet
its first co-primary endpoint. In an independent analysis, the study did not
significantly extend the disease-free survival (DFS)^iv period when compared
to placebo in the overall MAGE-A3 positive trial population.

In line with the Independent Data Monitoring Committee’s (IDMC) unanimous
recommendation, GSK will continue the study until the second co-primary
endpoint is assessed. This co-primary endpoint is based on predefined
criterion that was agreed upon by regulatory authorities. This analysis, which
is based on gene signature, is designed to prospectively identify patients who
may have the capability to be more immunologically responsive and therefore
can potentially benefit from treatment. If further analysis shows that the
predefined gene signature subset data are successful, there is the potential
that a regulatory filing could be considered. GSK anticipates that these data
will be available in 2015. Until then, GSK will remain blinded to all safety
and efficacy data.

The IDMC for the DERMA study indicated that the current review of the safety
information raised no concern for the continuation of the trial.

“We continue to believe that cancer immunotherapeutics have the potential to
deliver significant benefits to patients and we look forward to the analysis
of gene signature data,” said Garo H. Armen, Ph.D., chairman and CEO of Agenus
Inc. “In the near future, we expect to report results of several other QS-21
Stimulon adjuvant containing programs.”

QS-21 Stimulon adjuvant is key component of many vaccines currently in
clinical development. Agenus expects to report Phase 2 data for HerpV,
Agenus’QS-21 Stimulon containing investigational therapeutic vaccine for
genital herpes, during the fourth quarter of 2013. GSK is expected to announce
Phase 3 results from MAGRIT, the MAGE-A3 non-small cell lung cancer (NSCLC)
clinical trial during the first half of 2014. In addition, GSK is expected to
provide an update to the RTS,S program for the prevention of malaria.

About MAGE-A3 and GSK’s Cancer Immunotherapeutics (CIs)

MAGE-A3 is a tumor-specific antigen that is expressed in a large variety of
cancers, including melanoma, NSCLC, head and neck cancer, and bladder cancer,
with no expression in normal cells^v.

GSK's CIs represent a class of novel investigational compounds that are based
on tumor antigens presented to the patient's immune system as recombinant
proteins in combination with a GSK novel adjuvant system. CIs are designed to
trigger a specific immune response against tumor cells expressing these
proteins, rallying antibodies and T-cells to recognize and attack the cancer
cells in a highly specific manner and eventually eliminate them.

This approach primarily aims at reducing the risk of tumor recurrence
following surgery. The highly targeted mode of action of GSK CIs against
specific cancer antigens expressed by tumor cells may allow selection of
patients eligible for the treatment depending on the expression of the tumor
antigens. This may help oncologists to select patient populations most likely
to respond to the treatment.

GSK’s MAGE-A3 CI contains a purified recombinant MAGE-A3 protein combined with
GSK's novel AS15 adjuvant system. It was developed with the goal of inducing
strong and sustained immune responses. AS15 is composed of the QS-21 Stimulon
adjuvant, monophosphoryl lipid A (MPL), and CpG7909, a TLR-9 agonist, in a
liposomal formulation.

Adjuvants are substances, which when used in combination with antigens in
vaccines, enhance the immune response.

About Agenus’ QS-21 Stimulon^® Adjuvant

Agenus’ flagship adjuvant, QS-21 Stimulon adjuvant, is a saponin extracted
from the bark of the Quillaja saponaria tree, also known as the soap bark tree
or Soapbark, an evergreen tree native to warm temperate central Chile. Agenus’
QS-21 Stimulon has become a key component in the development of
investigational preventive vaccine formulations across a wide variety of
infectious diseases, and appears to be essential for several investigational
therapeutic vaccines intended to treat cancer and degenerative disorders.
QS-21 Stimulon has been widely studied and approximately 50,000 patients have
received vaccines containing the adjuvant. QS-21 Stimulon is being studied in
21 vaccine indications, which include GSK’s Phase 3 vaccine programs for RTS,S
for malaria, MAGE-A3 cancer immunotherapeutic for non-small cell lung cancer
and melanoma and HZ/su for shingles. In addition, Janssen’s QS-21 Stimulon
adjuvant-containing vaccine candidate is in Phase 2 trials for the treatment
of Alzheimer’s disease, and Agenus’ HerpV, a therapeutic vaccine for the
treatment of genital herpes, is in a Phase 2 trial with data expected during
the fourth quarter 2013. Agenus is generally entitled to receive milestone
payments as QS-21 Stimulon containing programs advance, as well as royalties
for 10 years after commercial launch, with some exceptions.

About GSK’s DERMA Program

The GSK DERMA study evaluated the efficacy and safety of the MAGE-A3 cancer
immunotherapeutic, when compared to placebo, in MAGE-A3 positive patients
(those whose tumor shows expression of the MAGE-A3 gene) with Stages IIIB/C
surgically resected melanoma. The MAGE-A3 antigen is expressed in
approximately 65% of tumors in Stage III melanoma patients.

The DERMA trial randomized 1,345 patients and is being conducted in 33
countries. In accordance with the study protocol, patients were given up to 13
injections into the muscle of the upper arm or thigh, over a period of 27

For additional information, please visit GSK’s website at

About Melanoma

Melanoma is the most aggressive form of all skin cancers and its incidence is
rising at a rate exceeding all other cancers.^1,2 Worldwide, it is believed
that approximately 160,000 people will be diagnosed with melanoma each year.^3
If detected in its earliest stages and treated properly, melanoma is curable,
however, melanoma is more likely than other skin tumors to spread to other
parts of the body. Patients with stage IIB-C and stage III (locoregional
lymph-node involvement) melanoma have a high risk of relapse following surgery
(60% and 75% risk of recurrence, respectively).^4 There are limited options
for patients with advanced melanoma disease,^5 highlighting that this type of
melanoma represents an area of high unmet medical need.

About Agenus

Agenus Inc. is a biotechnology company working to develop treatments for
cancers and infectious diseases. The company is focused on immunotherapeutic
products based on strong platform technologies with multiple product
candidates advancing through the clinic, including several product candidates
that have advanced into late-stage clinical trials through corporate partners.
For more information, please visit

Notes to editors
      Adjuvant immunotherapy with MAGE-A3 in melanoma GSK 2132231A
i    Antigen-Specific Cancer Immunotherapeutic in patients with resected
      MAGE-A3 cancer immunotherapeutic consists of recombinant MAGE-A3 protein
ii    and a novel immunostimulant AS15 (a combination of QS-21 Stimulon^®
      adjuvant, monophosphoryl lipid A, and CpG7909, a TLR-9 agonist, in a
      liposomal formulation).
iii   QS-21 Stimulon^® adjuvant and the related agreements, and HerpV are
      assets of Antigenics Inc., a wholly owned subsidiary of Agenus Inc.
iv    DFS is defined as the time from randomization to the date of first
      recurrence of the disease or of death, whichever comes first.
v     The exception is testicular cells and placental cells.

         Lens MB, Dawes M Global perspectives of contemporary epidemiological
1.    trends of cutaneous malignant melanoma. Br J Dermatol 2004;
2.       Fitzgerald K. Mechanisms of metastasis. Cellix’s VenaFlux platform
         pursue metastatic movement. Screening 2008; 2: 2-3.
         Ferlay J, Bray F, Pisani P et al. GLOBOCAN 2002 Cancer Incidence,
3.       Mortality and Prevalence Worldwide. IARC CancerBase No. 5, version
         2.0. IARCPress, Lyon, 2004.
         Kirkwood JM, Ibrahim JG, Sondak VK et al. High and low dose
4.       interferon alfa-2b in high-risk melanoma: first analysis of
         intergroup trial E1690 / S9111 / C9190. J Clin Oncol 2000; 18(12):
5.       Tarhini AA, Agarwala SS. Cutaneous melanoma: available therapy for
         metastatic disease. Dermatologic Therapy 2006; 19(1): 19-25.

Stimulon is a registered trademark of Agenus Inc. and its subsidiaries.

Forward-Looking Statement

This press release contains forward-looking statements, including statements
regarding clinical trial activities, the publication of data, and the
potential application of the Company’s technologies and product candidates in
the prevention and treatment of diseases. These forward-looking statements are
subject to risks and uncertainties that could cause actual results to differ
materially. These risks and uncertainties include, among others, the factors
described under the Risk Factors section of our Quarterly Report on Form 10-Q
filed with the Securities and Exchange Commission for the period ended June
30, 2013. Agenus cautions investors not to place considerable reliance on the
forward-looking statements contained in this release. These statements speak
only as of the date of this document, and Agenus undertakes no obligation to
update or revise the statements. All forward-looking statements are expressly
qualified in their entirety by this cautionary statement. Agenus’ business is
subject to substantial risks and uncertainties, including those identified
above. When evaluating Agenus’ business and securities, investors should give
careful consideration to these risks and uncertainties.


Media and Investor:
Agenus Inc.
Jonae R. Barnes, 617-818-2985
Vice President
Investor Relations and Corporate Communications
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