$1.8 Million Fast-Track NIH SBIR Grant for Manocept™ Immunotherapeutics Evaluation in Kaposi’s Sarcoma Awarded to Navidea

DUBLIN, Ohio–(BUSINESS WIRE)–Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB) announces the receipt
of an initial notice of award for a Fast- track Small Business
Innovation Research (SBIR) grant providing for up to $1.8 million from
the National Institutes of Health’s (NIH) National Cancer Institute
(NCI) to fund evaluation of an investigational Manocept™-based
immunotargeted treatment for Kaposi’s Sarcoma (KS). The novel Manocept
construct is designed to specifically deliver doxorubicin, a chemotoxin,
which can kill KS tumor cells and their tumor-associated macrophages
(TAMs) potentially altering the course of cancer. KS is a serious and
potentially life threatening illness in persons infected with the human
immunodeficiency virus (HIV) and the third leading cause of death in
this population worldwide. The prognosis for patients with KS is poor
with high probabilities for mortality and greatly diminished quality of
life. The development activities of the Manocept immunotherapeutic
platform will be conducted by Navidea and its subsidiary, Macrophage
Therapeutics.
The funds for this Fast-track grant (National Cancer Institute of the
National Institutes of Health under Award Number R44CA206788) will be
released in three parts, which together have the potential to provide up
to $1.8 million in resources over 2.5 years with the goal of completing
an investigational new drug (IND) submission for a Manocept construct
(MT1000 class of compounds) consisting of tilmanocept linked to
doxorubicin for the treatment of KS. The first part of the grant will
provide $232,000 to support analyses including in vitro and cell
culture studies and will be followed by Part 2 and 3 animal testing
studies. If successful, the information from these studies will be
combined with other information in an IND application that will be
submitted to the U.S. Food and Drug Administration (FDA) requesting
permission to begin testing the compound selected in human KS patients.
“We believe that given the data to date from the Manocept platform,
these studies along with a host of other human tumor model studies
ongoing and planned for animal testing will provide a powerful gateway
to a new class of anti-TAM immunotherapies directed at solid tumors. A
drug that selectively kills cells that are highly expressing CD206 is
expected to have an overwhelming, immediate, conspicuous and easily
measured effect on KS tumors,” said Frederick Cope, Ph.D., M.S.,
F.A.C.N., C.N.S., Senior Vice President and Chief Scientific Officer of
Navidea. “This grant will bring us to submission of an IND and the first
time human evaluation for a Manocept immunotherapeutic. We anticipate if
trials are successful, we can bring an effective and life-sparing new
therapy to KS patients who are in desperate need for such a new
treatment.”
“The Manocept platform may offer a unique approach to the treatment of
Kaposi’s sarcoma (KS) and is, we believe, a translational portal to the
therapy of a number of other solid tumors in which macrophages and
tumor-associated macrophages play a key role in tumorigenesis and
metastasis,” said Michael Goldberg, M.D. Chairman of the Board of
Navidea, “We believe that KS serves as model for a development strategy
that can be expanded to other macrophage-dependent solid tumors as well
as a model for therapeutics targeting viruses that incubate in
macrophages. We are encouraged that our therapeutic program has been
recognized by the NIH so soon after we began our therapeutic development
effort. We plan on submitting additional grant requests as soon as we
obtain results from the multiple ongoing studies in various cancer
models, which should read out shortly.”
About the MT1001 Study Efforts in KS
These IND-enabling studies will be conducted in three parts. Part 1
studies require in vitro and cell culture experiments related to
safety and efficacy of an intravenous injection of MT100. In Part 2 and
3, nine preclinical animal studies will build on the Part 1 results and
will further refine safety and efficacy variables including dosing and
drug administration regimens and evaluating the feasibility of the MT
1000-class of molecules, as a novel treatment for KS. Following these
studies, Navidea expects to submit an IND application to the FDA seeking
permission to begin Phase 1/2 clinical evaluation of MT1001 in KS
patients.
About KS
Kaposi sarcoma (KS) is a serious and potentially life threatening
illness in persons infected with the HIV, the causative agent of
acquired immunodeficiency syndrome (AIDS). Tumor associated macrophages
(TAMs) constitute an important tumor component for most types of cancer
(including KS) that contributes to tumor growth and protection from
immune responses. Navidea, through its subsidiary Macrophage
Therapeutics, is developing a receptor targeted drug construct that may
be able to effectively treat KS and could contribute to effective
immunotherapy for a wide variety of cancers.
About the Manocept™ CD206-targeting platform
Navidea Biopharmaceuticals is developing Manocept, a new pharmaceutical
platform technology, targeting cells that express the macrophage mannose
receptor (CD206). A wide variety of immune-targeting applications for
this platform technology are envisioned. Macrophages play important
roles in many disease states and are an emerging target in many
disorders. This flexible and versatile platform acts as an engine for
purpose-built molecules that may enhance diagnostic accuracy, clinical
decision-making, targeted treatments and ultimately patient care. As an
immunodiagnostic tool, the Manocept technology can utilize a breadth of
imaging modalities, including SPECT, PET, intra-operative and/or
optical-fluorescence detection. By linking a therapeutic agent on the
Manocept molecular backbone, there is the potential to develop novel,
targeted immunotherapies specifically designed to selectively deliver an
agent that can kill or alter disease-associated macrophages. MT1000
class of compounds , consisting of a Manocept construct linked to
doxorubicin, is the first in a series of drug delivery constructs that
will utilize Navidea’s Manocept CD206 targeted drug delivery platform.
Navidea’s FDA-approved immunodiagnostic agent, Lymphoseek® (technetium
99m tilmanocept) injection, is representative of the platform’s ability
to successfully exploit this mechanism and offer the potential for
development of new CD206-targeted immunodiagnostic agents and
immunotherapeutics. The development activities of the Manocept
immunotherapeutic platform will be conducted by Navidea‘s subsidiary,
Macrophage Therapeutics.
About Lymphoseek
Lymphoseek^® (technetium Tc 99m tilmanocept) injection is the
first and only FDA-approved receptor-targeted lymphatic mapping agent.
It is a novel, receptor-targeted, small-molecule radiopharmaceutical
used in the evaluation of lymphatic basins that may have cancer
involvement in patients. Lymphoseek is designed for the precise
identification of lymph nodes that drain from a primary tumor, which
have the highest probability of harboring cancer. Lymphoseek is approved
by the U.S. Food and Drug Administration (FDA) for use in solid tumor
cancers where lymphatic mapping is a component of surgical management
and for guiding sentinel lymph node biopsy in patients with clinically
node negative breast cancer, melanoma or squamous cell carcinoma of the
oral cavity. Lymphoseek has also received European approval in imaging
and intraoperative detection of sentinel lymph nodes in patients with
melanoma, breast cancer or localized squamous cell carcinoma of the oral
cavity.
Accurate diagnostic evaluation of cancer is critical, as results guide
therapy decisions and determine patient prognosis and risk of
recurrence. Overall in the U.S., solid tumor cancers may represent up to
1.2 million cases per year. The sentinel node label in the U.S. and
Europe may address approximately 600,000 new cases of breast cancer,
160,000 new cases of melanoma and 100,000 new cases of head and
neck/oral cancer diagnosed annually.
Lymphoseek Indication and Important Safety Information
Lymphoseek is a radioactive diagnostic agent indicated with or without
scintigraphic imaging for:

• Lymphatic mapping using a handheld gamma counter to locate lymph nodes
  draining a primary tumor site in patients with solid tumors for which
  this procedure is a component of intraoperative management.
• Guiding sentinel lymph node biopsy using a handheld gamma counter in
  patients with clinically node negative squamous cell carcinoma of the
  oral cavity, breast cancer or melanoma.

Important Safety Information
In clinical trials with Lymphoseek, no serious hypersensitivity
reactions were reported, however Lymphoseek may pose a risk of such
reactions due to its chemical similarity to dextran. Serious
hypersensitivity reactions have been associated with dextran and
modified forms of dextran (such as iron dextran drugs).
Prior to the administration of Lymphoseek, patients should be asked
about previous hypersensitivity reactions to drugs, in particular
dextran and modified forms of dextran. Resuscitation equipment and
trained personnel should be available at the time of Lymphoseek
administration, and patients observed for signs or symptoms of
hypersensitivity following injection.
Any radiation-emitting product may increase the risk for cancer. Adhere
to dose recommendations and ensure safe handling to minimize the risk
for excessive radiation exposure to patients or health care workers.
In clinical trials, no patients experienced serious adverse reactions
and the most common adverse reactions were injection site irritation
and/or pain (<1%).
FULL LYMPHOSEEK PRESCRIBING INFORMATION CAN BE FOUND AT: WWW.LYMPHOSEEK.COM
About Navidea
Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB) is a biopharmaceutical
company focused on the development and commercialization of precision
immunodiagnostic agents and immunotherapeutics. 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. The development activities of the
Manocept immunotherapeutic platform will be conducted by Navidea in
conjunction with its subsidiary, Macrophage Therapeutics. Navidea’s
strategy is to deliver superior growth and shareholder return by
bringing to market novel products 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 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.
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