Updated Phase 2 Data of Prophage In Newly Diagnosed GBM Presented at ASCO Show Improvement in Median Progression Free Survival and Overall Survival Independently of Prognostic Markers, Compared with Historical Expectatio

Phase 2 Data of Prophage In Newly Diagnosed GBM Presented at ASCO Show

Improvement in Median Progression Free Survival and Overall Survival

Independently of Prognostic Markers, Compared with Historical

significant improvements seen in patients with less elevated PD-L1

expression in peripheral blood

in overall survival seen independent of MGMT methylation status

LEXINGTON, Mass.--(BUSINESS WIRE)--June 1, 2015--Agenus Inc.

(NASDAQ:AGEN), an immunology company developing innovative treatments

for cancers and other diseases, today announced that patients with newly

diagnosed Glioblastoma Multiforme (GBM) treated with Prophage (AGEN's

individualized heat shock protein (HSP)-based cancer vaccine) plus

Standard of Care (SOC) show substantially longer Progression Free

Survival (PFS) and median Overall Survival (mOS) compared to historical

SOC data, as detailed in an oral presentation at ASCO yesterday by Orin

Bloch, M.D., Khatib Professor of Neurological Surgery and Assistant

Professor of Neurological Surgery and Neurology at Northwestern

University Feinberg School of Medicine.

GBM patients show evidence of tumor-mediated immunosuppression prior to

treatment, measurable in part by greater expression of PD-L1 (Programmed

Death Receptor - Ligand 1) on monocytic white cells in their peripheral

blood. These elevations of peripheral blood monocyte PD-L1 correlate

with elevation of PD-L1 expressing macrophages in their brain tumors,

potentially working against effective immuno-therapy. When outcomes in

this study were analyzed based on the extent of monocyte PD-L1

expression, the 50% of patients with less elevated PD-L1 showed markedly

better PFS and mOS than historical SOC: PFS of 27 months versus

5-9 months and mOS of 45 months versus 15-19 months. Further,

more than a third of these patients remain alive for more than three

years from initial treatment, and more than 80% of these have not

progressed. Prophage plus SOC also gave longer PFS and mOS than

historical SOC data in the 50% of patients with greater monocyte PD-L1

elevation, although the differences were less pronounced. This raises

the possibility of an improved Prophage benefit by combination with

Checkpoint Modulating Antibodies (CPMs) that block PD-1 or PD-L1.

Additionally, the reported data suggest that Prophage added to SOC leads

to longer mPFS and mOS regardless of MGMT methylation status, a known

predictor of response to SOC. When Prophage is added to SOC in MGMT

methylated patients in this study, the mOS was 44.7 months, compared to

~ 23 months reported for comparable MGMT methylated GBM patients on SOC

alone in recent controlled trials (RTOG 0825).

MGMT methylation and PD-L1 expression on monocytes appear to be

independent predictive markers in these patients. Although the apparent

benefit of adding Prophage to SOC was observable in all subgroups of

patients compared to historical SOC outcomes, the prolongations of mPFS

and mOS are especially striking in patients with high MGMT and

less elevated circulating monocyte expression of PD-L1: in this

sub-group more than half the patients live for 4 years from initial

"These data are very promising for a treatment that fits seamlessly with

SOC and has very attractive tolerability and safety," commented

Northwestern's Dr. Bloch, lead investigator of the study. "I am

especially pleased that more than a third of patients with less elevated

monocyte PD-L1 expression are alive for 3 years or more. Using PD-L1

expression on peripheral blood monocytes, we seem to identify about 50%

of patients (those with lower levels of PD-L1 expression) who may derive

the greatest benefit from adding Prophage to SOC. Our data also suggest

that the addition of Checkpoint Modulators of PD-1 or PD-L1 to SOC plus

Prophage in patients with higher monocyte PD-L1 levels may enhance the

benefit of the autologous heat shock protein based vaccine regimen."

"We are very encouraged by these data that suggest that Prophage, our

individualized heat shock protein based vaccine, is beneficial to

patients with GBM regardless of MGMT methylation status," said Robert

Stein, M.D, Ph.D., Chief Scientific Officer of Agenus. "The results in

patients with lower monocyte PD-L1 expression are especially promising.

We believe a well-designed, controlled Phase 3 trial of Prophage plus

SOC is warranted to try to bring this potential treatment advance to

patients afflicted by GBM."

The Phase 2 single-arm trial enrolled forty-six adult patients with

newly diagnosed GBM from eight centers in the U.S. Each patient received

SOC (surgical resection followed by chemoradiation). Within five weeks

of completing radiotherapy, patients received continuing adjuvant

temozolomide as well as weekly Prophage injections for four weeks

followed by monthly Prophage injections until the depletion of vaccine

or tumor progression. The primary endpoints of the trial were PFS and

Agenus is an immunology company developing a series of Checkpoint

Modulators for the treatment of patients with cancer, infectious

diseases, and other immune disorders, heat shock protein (HSP)-based

vaccines, and immune adjuvants. These programs are supported by three

separate technology platforms. Agenus' internal and partnered checkpoint

modulator programs target GITR, OX40, CTLA-4, LAG-3, TIM-3, PD-1 and

other undisclosed programs. The company's proprietary discovery engine

Retrocyte DisplayTM is used to generate fully human and

humanized therapeutic antibody drug candidates. The Retrocyte Display

platform uses a high-throughput approach incorporating IgG format human

antibody libraries expressed in mammalian B-lineage cells. Agenus

recently acquired a powerful yeast antibody display platform termed

SECANT , developed by Celexion, LLC. SECANT allows rapid generation of

soluble, full-length human antibodies. SECANT and Agenus' mammalian

antibody display platform have complementary strengths and further

bolster Agenus' abilities to generate and optimize fully human

monoclonal antibodies. Agenus' heat shock protein-based vaccines have

completed Phase 2 studies in newly diagnosed glioblastoma multiforme,

and in the treatment of herpes simplex viral infection; the heat shock

protein-based vaccine platform can generate personalized as well as off

the shelf products. The company's QS-21 Stimulon adjuvant platform is

extensively partnered with GlaxoSmithKline and with Janssen Sciences

Ireland UC and includes several candidates in Phase 2 trials, as well as

shingles and malaria vaccines which have successfully completed Phase 3

Forward-Looking Statement

This press release contains forward-looking statements that are made

pursuant to the safe harbor provisions of the federal securities laws,