Bavituximab:

Targeting Phosphatidylserine, (PS)

an Upstream Immune Checkpoint
to Fight Cancer

Bavituximab

High Levels of PS are Exposed in the Tumor Environment

Cancer leverages this same cellular process to evade
immune detection, allowing tumors to grow unimpeded
by the immune system. High levels of PS are exposed
on the cells in tumors and on small particles shed from
tumor cells known as microvesicles.

Bavituximab is a first-in-class monoclonal antibody that

targets phosphatidylserine (PS) and has demonstrated the
potential to reactivate tumor-fighting immune responses.
In October 2013, data published in the American Association
for Cancer Research (AACR) peer-reviewed journal Cancer
Immunology Research showed that PS-targeting antibodies
mediate multiple immunostimulatory changes in the tumor
environment, including a reduction of tumor-promoting immune cells and an increase in tumor fighting macrophages,
dendritic cells and T-cells 1 .

Bavituximab Targets Phosphatidylserine (PS)

Microvesicle

Tumor cell

Exposed PS in Tumors Induces Multiple Immunosuppressive Effects

PS is engaged by immune cells leading to the
secretion of signaling chemicals that keep immune cells
in a dormant state, preventing them from recognizing
cancer as a foreign invader. Specifically, myeloid
derived suppressor cells (MDSC) and M2 macrophages
accumulate and maintain an immunosuppressive
tumor environment, TGF-beta and IL-10 levels increase,
dendtritic cells fail to mature, T-cells remain naive and
M1 macrophages fail to develop.
Bavituximab Targets Exposed PS in the Tumor Environment

Bavituximab is an investigational cancer treatment

developed by Peregrine Pharmaceuticals that targets
and binds to PS, a molecule that is abundantly exposed
in the tumor environment.

Bavituximab is a chimeric monoclonal antibody that

targets phosphatidylserine (PS), a molecule found on the
inside surface of the membrane of healthy cells.

Phosphatidylserine (PS), (dark purple)

PS Moves to the Exterior on Dying Host Cells

Bavituximab Engages F Receptors on Immune Cells

As a cell naturally dies, PS flips to the outside exposed

surface of the cell.

Bavituximab engages docking molecules on immune

cells and initiates fundamental immunostimulatory
changes in the tumor environment.

[ MDSC, M2 mac, immature DC ]

[ F Receptor ]
[ Bavituximab ]

PS flip during cell death

PS Engages PS Receptors on Immune Cells

Bavituximabs Immunostimulatory Effects

Bavituximab mediates an increase in powerful signaling chemicals that transform immune cells from a state
of tolerating cancer growth, into cells that recognize
and actively fight the tumor. Specifically, this includes
increases in TNF-alpha and IL-12, decreased MDSCs, M2
to M1 macrophage polarization and increases in mature
dendritic cells and tumor-specific cytotoxic T-cells.

PS is a highly immunosuppressive molecule that when

exposed on the surface of a cell is engaged by docking
molecules on immune cells. PS then signals these
immune cells to not attack the cell as normally seen
when fighting a foreign invader.

Routine Disposal of Dying Host Cells

White blood cells are then free to remove aging cells
without the prompting of an immune attack against
the body.

Bavituximab Reactivates Anti-Tumor Immune Responses

Macrophage

Dying host cell

The activated cells of the immune system then work

together to fight cancer by destroying the blood vessels
that feed the tumor, as well as the tumor cells. M1
macrophages destroy cells via antibody dependent
cellular cytotoxicity (ADCC), while mature dendritic cells
present tumor antigens to T-cells facilitating tumorspecific cytotoxic T-cell responses.

[ Bavituximab ]
[ Mature dendritic cell ]
[ Tumor-specific
Cytotoxic T-cell ]

[ M1 macrophage ]

Peregrine Pharmaceuticals, Inc.

14282 Franklin Avenue,
Tustin, CA 92780
Phone: 714-508-6000

Published studies show that the upstream immune

checkpoint blockade mediated by Peregrines PS-targeting
antibodies mobilizes the immune system to fight cancer
by activating both innate and adaptive anti-tumor immune
responses.
1. Yi Yin, Xianming Huang, Kristi D. Lynn, and Philip E.
Thorpe, Phosphatidylserine-Targeting Antibody Induces
M1 Macrophage Polarization and Promotes MyeloidDerived Suppressor Cell Differentiation, Cancer
Immunology Research:October 2013 1:256-268

Bavituximab is being evaluated in second-line non-small

cell lung cancer (NSCLC) as part of the SUNRISE pivotal
Phase III clinical trial. For more information, please visit
www.sunrisetrial.com