- Results demonstrated programmed cell death in
KS tumor cells and anti-HIV activity -
- Reinforces therapeutic potential of targeting
activated macrophages via the CD206 receptor -
Macrophage Therapeutics, Inc., a subsidiary of Navidea
Biopharmaceuticals, Inc. (NYSE MKT: NAVB), today announced that
preclinical results in Kaposi’s Sarcoma (KS) demonstrated that a
cytotoxic drug, doxorubicin, linked to Manocept™ was targeted to
and dose-dependently taken up in CD206+ KS tumor cells and tumor
associated macrophages (TAMs) and caused apoptotic death of the KS
tumor cells and TAMs. The results are being presented at the 18th
International Workshop on Kaposi's Sarcoma Herpesvirus
(KSHV) and Related Agents in Hollywood, Florida by Michael S.
McGrath, M.D., Ph.D., Professor, Departments of Laboratory
Medicine, Pathology, and Medicine at the University of California,
San Francisco (UCSF). The study also shows that Cy3-Manocept and a
Cy3-Manocept-doxorubicin conjugate quantitatively permitted the
evaluation of tumor burden, tissue uptake of Manocept and tumor
response to therapy in vitro and ex vivo, supporting the potential
for the Manocept platform to be used not only diagnostically but as
a precision targeted molecule to deliver payloads to tumor sites
throughout the body.
“Advances in the treatment of cancer such as the recently
approved PD1 and PDL1 inhibitors demonstrate the benefit of
disrupting the communication signals between tumors and immune
cells,” said Frederick O. Cope, Ph.D., FACN, Chief Scientific
Officer of Macrophage Therapeutics. “Based on the role tumor
associated macrophages are thought to play in the progression of
cancer, there exists a strong rationale that targeting CD206
represents a therapeutic pathway that is highly likely to exist
across tumor types, and which reverses the immunosuppressive
effects of cancer cells.”
“In my experience, the impressive loss of TAMs demonstrated in
these Manocept studies is unique and potentially extremely relevant
clinically,” said Dr. McGrath. “The results from data in primary
human KS tissue, which provides the closest experimental model to
human patients, showed not only selective killing of only CD206+ KS
tumor cells and macrophages, but demonstrated through a biomarker
that the Manocept conjugate induced programmed cell death in tumor
cells and exhibited unprecedented anti-HIV activity which could
eventually address a broad unmet need for patients with Kaposi’s
sarcoma and other tumor types.”
The preclinical studies included use of Human peripheral blood
mononuclear cells (PBMCs) to measure the time course of Manocept
uptake in CD206+ macrophages. Flow cytometry studies identifying
CD206+ cells allowed quantitation of the amount of Cy3-Manocept
bound to and internalized into the CD206+ cells and also verified
Cy3-Manocept-doxorubicin internalization. Confocal microscopy was
used with KS biopsies that were cultured overnight with
Cy3-Manocept or Cy3-Manocept-doxorubicin and showed that all cells
within the KS tissue including macrophages and spindle cells were
CD206+ and incorporated the Cy3-Manocept with and without
doxorubicin. In KS organ cultures, immunofluorescence assays for
the detection of antibodies against latent nuclear antigen
(IFA-LANA) and Annexin V were performed. Inhibition studies showed
Cy3-Manocept-doxorubicin exhibited anti-HIV activity in HIV
infected macrophage culture. In summary, the data presented include
evidence that:
- KS tissue based cells take up
Cy3-Manocept or Cy3-Manocept-doxorubicin into both KS tumor cells
and TAMs.
- Manocept conjugate uptake is dose and
time dependent in CD206+ macrophages
- Cy3-Manocept and
Cy3-Manocept-doxorubicin bind to CD206 positive macrophages
equivalently indicating that the linkage of a drug conjugate did
not lessen the CD206 binding ability
- Manocept-doxorubicin killed CD206
expressing macrophages. After 24 hours, Cy3-Manocept-doxorubicin
killed 70% of CD206 positive macrophages in tissue cultures.
Doxorubicin alone showed no toxicity.
- KS organ culture treated with
Manocept-doxorubicin resulted in the loss of macrophages and
induced programmed tumor cell death and apoptosis in KS HHV8+
spindle cells, and showed anti-HIV activity in HIV infected
macrophage cultures.
“We are very encouraged that our Manocept platform, with its
unique ability to seek out activated macrophages, may selectively
deliver a therapeutic that can kill tumor cells, tumor support
cells and virus contained in the macrophage. This activity was seen
with a therapeutic that without our delivery system would not be
effective on the tumor, the TAM’s or either of the viruses. This
data suggests that targeting the activated macrophage is a viable
strategy for attacking cancers that have TAM’s. It is well
established that depleting TAM’s makes the tumor more susceptible
to chemotherapy, radiation therapy and many of the new and emerging
immune therapy drugs. In addition the effect of this agent with no
known anti-viral properties on killing both HIV and HHV8 suggests a
novel anti-viral strategy that will not require development of
specific tailored drugs to a given virus,” said Michael M.
Goldberg, M.D., CEO of Macrophage Therapeutics and Director of
Navidea. “We look forward to advancing development of our broad
therapeutic platform through animal testing this summer in a number
of solid tumor models as well as explore the potential of our
technology in CNS diseases, viral diseases and animal models of
auto-immune disease. Our goal is to seek strategic collaborations
with industry leaders to enable rapid development. Finally, we will
host an investor day at the end of the summer where we will review
the accumulated data being generated.”
Navidea and Macrophage Therapeutics plan a webcast to provide
investors with a complete look at the data being presented at the
International Workshop on Kaposi's Sarcoma Herpesvirus
(KSHV) and Related Agents conference on July 7, 2015 at 1:00
pm EDT. Webcast details will be available on the Navidea
website.
About Manocept CD206 Targeting Platform for Therapeutics
Development
Manocept™ CD206 Targeting Platform is a proprietary
mannose-containing, receptor-directed technology platform designed
to engineer novel, synthetic receptor targeted imaging agents and
therapeutics for cancer and other diseases. Manocept’s unique
structural and molecular properties enable the design of novel
immuno-constructs that selectively target and bind to CD206
(mannose receptor) and other C-type Lectins found on activated,
disease-associated macrophages and tumor associated macrophages
(TAMs). The Manocept CD206 Targeting Platform provides a novel and
valuable approach to the design of drug molecules targeting CD206
disease-associated macrophages for therapeutic purposes.
About Kaposi’s Sarcoma
Kaposi sarcoma (KS) is a cancer that develops from the cells
that line lymph nodes or blood vessels. It usually appears as
tumors on the skin or on mucosal surfaces such as inside the mouth,
but tumors can also develop in other parts of the body, such as in
the lymph nodes (bean-sized collections of immune cells throughout
the body), the lungs, or digestive tract. The abnormal cells of KS
form purple, red, or brown blotches or tumors on the skin. These
affected areas are called lesions. The skin lesions of KS most
often appear on the extremities, trunk and face. AIDS-related KS is
the most common type of KS in the United States which develops in
people who are infected with HIV, the virus that causes AIDS. KS
can also develop in people whose immune systems have been
suppressed after an organ transplant and is called
transplant-related KS.1
About Navidea
Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB) is a
biopharmaceutical company focused on the development and
commercialization of precision diagnostics, therapeutics and
radiopharmaceutical agents. Navidea is developing multiple
precision-targeted products and platforms including Manocept™ and
NAV4694 to help identify the sites and pathways of undetected
disease and enable better diagnostic accuracy, clinical
decision-making, targeted treatment and, ultimately, patient care.
Lymphoseek® (technetium Tc 99m tilmanocept) injection, Navidea’s
first commercial product from the Manocept platform, was approved
by the FDA in March 2013 and in Europe in November 2014. Navidea’s
strategy is to deliver superior growth and shareholder return by
bringing to market novel radiopharmaceutical agents and
therapeutics, and advancing the Company’s pipeline through global
partnering and commercialization efforts. For more information,
please visit www.navidea.com.
About Macrophage Therapeutics
Macrophage Therapeutics, Inc., a newly created subsidiary of
Navidea Biopharmaceuticals, Inc. (NAVB), is developing therapeutics
using the patented Manocept immunotherapy platform licensed from
Navidea to target over-active macrophages implicated in cancer,
cardiovascular, central nervous system, autoimmune, antiviral, and
skin diseases. Manocept specifically targets CD206, or the mannose
receptor prevalent on over-active macrophages. The technology
enables highly specific targeted delivery of active (either
existing or yet to be developed) agents that can modulate the
activity of over-active macrophages that have been implicated in
many diseases. Targeted delivery should significantly enhance a
given compound’s efficacy and safety.
The Private Securities Litigation Reform Act of 1995 (the Act)
provides a safe harbor for forward-looking statements made by or on
behalf of the Company. Statements in this news release, which
relate to other than strictly historical facts, such as statements
about the Company’s plans and strategies, expectations for future
financial performance, new and existing products and technologies,
anticipated clinical and regulatory pathways, and markets for the
Company’s products are forward-looking statements within the
meaning of the Act. The words “believe,” “expect,” “anticipate,”
“estimate,” “project,” and similar expressions identify
forward-looking statements that speak only as of the date hereof.
Investors are cautioned that such statements involve risks and
uncertainties that could cause actual results to differ materially
from historical or anticipated results due to many factors
including, but not limited to, the Company’s continuing operating
losses, uncertainty of market acceptance of its products, reliance
on third party manufacturers, accumulated deficit, future capital
needs, uncertainty of capital funding, dependence on limited
product line and distribution channels, competition, limited
marketing and manufacturing experience, risks of development of new
products, regulatory risks and other risks detailed in the
Company’s most recent Annual Report on Form 10-K and other
Securities and Exchange Commission filings. The Company undertakes
no obligation to publicly update or revise any forward-looking
statements.
1 American Cancer Society web accessed 22May2015.
http://www.cancer.org/cancer/kaposisarcoma/detailedguide/kaposi-sarcoma-what-is-kaposi-sarcoma
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Macrophage TherapeuticsJames Goldschmidt, Ph.D.,
484-225-0341jgoldschmidt@macrophagetx.comorNavidea
BiopharmaceuticalsInvestorsTom
Baker, 617-532-0624tbaker@navidea.comorMediaSharon Correia, 978-655-2686Associate
Director, Corporate Communications
Navidea Biopharmaceuticals (AMEX:NAVB)
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