- Bavituximab in Combination with Anti-PD-1 in
Breast Cancer Studies Showed a Statistically Significant
Improvement in Overall Survival as Compared to Subjects Receiving
Anti-PD-1 Therapy Alone -
Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a
biopharmaceutical company focused on developing therapeutics to
stimulate the body's immune system to fight cancer, today announced
results from multiple new preclinical studies demonstrating
enhanced anti-tumor activity and immune activation for combinations
of a preclinical bavituximab equivalent and checkpoint inhibitors
such as anti-PD-1 and anti-CTLA-4 in preclinical models of breast
cancer and melanoma. Additionally, the company announced
preliminary results for a new clinical test specifically designed
to illustrate how bavituximab, the company’s investigational
phosphatidylserine (PS)-signaling pathway inhibitor, modulates
immune responses in the tumor microenvironment. Results from
these studies were presented at the 2015 annual meeting of the
Society for Immunotherapy of Cancer (SITC), which was held in
National Harbor, MD, on November 4 - 8, 2015.
“The positive data presented at SITC with regard
to combinations of bavituximab and checkpoint inhibitors further
support our belief that bavituximab has the potential to be a
critical component of innovative combination cancer
immunotherapies,” said Jeff T. Hutchins, vice president preclinical
development of Peregrine. “Particularly exciting is the new
data in animal models of breast cancer which showed that a
significantly greater number of subjects demonstrated anti-tumor
activity when treated with the combination of bavituximab and
anti-PD-1 as compared to treatment with anti-PD-1 alone.
Additionally, combination treatment led to prolonged protection for
animals as evidenced by their lack of new tumor development when
later re-challenged with the same tumors.”
Bavituximab is an investigational immunotherapy
designed to assist the body's immune system by targeting and
modulating the activity of phosphatidylserine (PS), a highly
immune-suppressive signaling molecule expressed broadly on the
surface of cells in the tumor microenvironment. Peregrine’s
PS signaling pathway inhibitor candidates, including bavituximab,
reverse the immunosuppressive environment that many tumors
establish in order to proliferate, while also fighting cancer by
activating immune cells that target and fight cancer.
The preclinical equivalent of bavituximab, ch1N11, is
used in animal model studies as a guide for clinical
development.
Breast Cancer
Researchers from Duke University and Peregrine
evaluated the combination of ch1N11 (preclinical bavituximab
equivalent) and anti-PD-1 therapy versus anti-PD-1 stand-alone
therapy in well-characterized murine breast cancers, including the
triple negative breast cancer (TNBC) model E0771. Study data
showed that the combination therapy significantly enhanced overall
survival (p=0.0016) and was capable of mediating complete tumor
regressions in a greater number of subjects compared to single
agent treatments (60% vs. 20%). Data also demonstrated that
animals receiving combination treatment had significant increases
in tumor associated indicators of immune system activation,
including CD45+, CD8+ and CD3+ T-cells. Importantly, the
combination treatment led to a prolonged anti-tumor immune response
which protected the animals against a re-challenge with the same
tumor. This sustained anti-tumor response suggests the potential of
the combination therapy to trigger immune system memory and support
adaptive immune responses against reemerging disease in breast
cancers. All study animals experienced no signs of adverse effects
following repeated doses of all therapeutic agents.
Melanoma
In follow-on work, researchers from the
University of Texas, Southwestern and Peregrine evaluated
combinations of ch1N11 and checkpoint inhibitors (anti-PD-1 or
anti-CTLA-4) versus each agent as a stand-alone therapy in common
models of melanoma (B16F10 and K1735). Data showed that the
combinations of ch1N11 with either anti-PD-1 or anti-CTLA-4 led to
significantly greater levels of tumor infiltrating CD8+ T cells
than any of the three agents alone. Additionally, findings
demonstrated that the combination therapies were more effective at
shifting the tumor microenvironment from immunosuppressive to
immune active than the single agents, as shown by greater increases
in the ratio of T effector cells to T regulatory cells,
reactivation of tumor infiltrating T cells and restoration of the
effector function of the tumor infiltrating T cells. This
activity was more pronounced for the ch1N11/anti-PD-1 combination
than for the ch1N11/anti-CTLA-4 combination. Based on these
data, study investigators concluded that ch1N11 synergizes with
checkpoint inhibitors to induce strong tumor specific CD8 T cell
immunity.
“There is an extensive and growing collection of
data that demonstrates that phosphatidylserine directly triggers
broad immunosuppression in the tumor microenvironment and
contributes to resistance to checkpoint inhibitor therapy. By
targeting and blocking PS, bavituximab appears able to shift the
tumor environment from immunosuppressive to immune active and, in
turn, enhance the anti-tumor activity of checkpoint inhibitors such
as anti-PD-1 and anti-CTLA4,” said Bruce Freimark, Ph.D., director
of pre-clinical oncology of Peregrine. “This latest data in
well validated models of multiple tumor types further support our
belief that bavituximab may be able to play an essential role in
combination immuno-oncology treatment regimens. With this in
mind, we are committed to evaluating the agent’s potential in
combination with a range of cancer therapies against various cancer
types.”
ImmunoProfiling
Researchers presented preliminary results for a
new custom assay designed to provide detailed profiles of immune
activity in patient tumors. The Opal™ 6-plex quantitative
immunofluorescence (IF) assay is specifically designed to measure
the level and type of lymphocytes, myeloid and dendritic cell
subsets found within the tumor microenvironment. This
information is important as it can be used to correlate immune
response parameters with bavituximab treatment outcome and patient
survival.
Presented results demonstrated that the Opal
assay could reliably detect, measure and phenotype lymphocytes and
monocytes present in tumor tissues from rectal adenocarcinoma,
hepatocellular carcinoma and advanced melanoma patients treated
with bavituximab combination therapies. Importantly, the
findings were able to show changes in key indicators of immune
activation, including CD8+, CD4+ and regulatory T-cells, as well as
myeloid and dendritic cells, in the tumor microenvironment
following bavituximab treatment. The ability of this new
assay to accurately measure specific immune responses is expected
to provide important additional information to assist in
Peregrine’s ongoing development efforts for bavituximab. This
will be particularly valuable as the company works to better
elucidate the connection between the drug candidate’s impact on
immunomodulation and patient response to treatment.
“We are very pleased with the performance of the
Opal assay, particularly its ability to compare the interaction of
up to six phenotypic and functional markers on a single slide of
tissue. The power and prognostic value of such immune
activity assessments in the area of cancer was initially
established by the Immunoscore®, and we believe the Opal assay
represents an important evolution of that work,” said Bernard A.
Fox, Ph.D., Harder Family Endowed Chair for Cancer Research, Member
and Chief, Molecular and Tumor Immunology, Earle A. Chiles Research
Institute, Providence Cancer Center; a world-renowned translational
cancer immunotherapist; a founding member of the Immunoscore
steering committee. “I am looking forward to continued
collaboration with Peregrine to further optimize and validate this
assay to improve our understanding of immune infiltrate in tumors
thereby facilitating the rational design and use of bavituximab in
combination with novel and standard therapies.”
About Bavituximab: A Targeted
Investigational Immunotherapy
Bavituximab is an investigational chimeric
monoclonal antibody that targets phosphatidylserine (PS). Signals
from PS inhibit the ability of immune cells to recognize and fight
tumors. Bavituximab, the lead compound in Peregrine's
immuno-oncology development program, blocks PS to remove this
immunosuppressive signal and sends an alternate immune activating
signal. PS targeting antibodies have been shown to shift the
functions of immune cells in tumors, resulting in robust anti-tumor
immune responses.
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company
with a pipeline of novel drug candidates in clinical trials focused
on the treatment of cancer. The company's lead immunotherapy
candidate, bavituximab, is in Phase III development for the
treatment of second-line non-small lung cancer (the "SUNRISE
trial") along with several investigator-sponsored trials evaluating
other treatment combinations and additional oncology indications.
Peregrine also has in-house cGMP manufacturing capabilities
through its wholly-owned subsidiary Avid Bioservices, Inc.
(www.avidbio.com), which provides development and biomanufacturing
services for both Peregrine and third-party customers. For more
information, please visit www.peregrineinc.com.
Safe Harbor Statement:
Statements in this press release which are not purely historical,
including statements regarding Peregrine Pharmaceuticals'
intentions, hopes, beliefs, expectations, representations,
projections, plans or predictions of the future are forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. The forward-looking statements involve risks
and uncertainties including, but not limited to, the risk that the
data from one or more of the preclinical studies will not be
duplicated in future clinical studies. The company's actual results
could differ materially from those in any such forward-looking
statements. Factors that could cause actual results to differ
materially include, but are not limited to, uncertainties
associated with completing preclinical and clinical trials for our
technologies; the early stage of product development; the
significant costs to develop our products as all of our products
are currently in development, preclinical studies or clinical
trials; obtaining additional financing to support our operations
and the development of our products; obtaining regulatory approval
for our technologies; anticipated timing of regulatory filings and
the potential success in gaining regulatory approval and complying
with governmental regulations applicable to our business. Our
business could be affected by a number of other factors, including
the risk factors listed from time to time in our reports filed with
the Securities and Exchange Commission including, but not limited
to, our annual report on Form 10-K for the fiscal year ended April
30, 2015 as well as any updates to these risk factors filed from
time to time in the company's other filings with the Securities and
Exchange Commission. The company cautions investors not to place
undue reliance on the forward-looking statements contained in this
press release. Peregrine Pharmaceuticals, Inc. disclaims any
obligation, and does not undertake to update or revise any
forward-looking statements in this press release.
Immunoscore® is a registered trademark of Institut National de
la Santé et de la Recherche Médicale (INSERM)
Contacts:
Jay Carlson
Peregrine Pharmaceuticals, Inc.
(800) 987-8256
info@peregrineinc.com
Stephanie Diaz (Investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
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