Results of Lymphoseek® Phase 3 Clinical Trials in Breast Cancer Published in Annals of Surgical Oncology

  Results of Lymphoseek® Phase 3 Clinical Trials in Breast Cancer Published in
  Annals of Surgical Oncology

   - Lymphoseek Meets Primary Efficacy Endpoint in Assessment of Lymphatic
             Mapping Performance in Patients with Breast Cancer -

Business Wire

DUBLIN, Ohio -- March 21, 2013

Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB), a biopharmaceutical company
focused on the development and commercialization of precision diagnostic
radiopharmaceuticals, today announced the peer-reviewed publication of results
from two Phase 3 clinical trials of Lymphoseek^® (technetium 99m tilmanocept)
Injection in patients with breast cancer. The trials assessed the performance
of Lymphoseek against the standard of care, vital blue dye (VBD), in lymphatic
mapping. Results demonstrated that Lymphoseek met its primary efficacy
endpoint of rate of agreement, or concordance, with VBD. The study,
“Comparative Evaluation of [^99mTc]Tilmanocept for Sentinel Lymph Node Mapping
in Breast Cancer Patients: Results of Two Phase 3 Trials,” was published in
the current online edition of the journal Annals of Surgical Oncology [DOI

Lymphoseek is a receptor-targeted radiopharmaceutical recently approved by the
U.S. Food and Drug Administration and indicated for use in lymphatic mapping
for breast cancer and melanoma. In this procedure key lymph nodes adjacent to
a primary tumor, that may contain tumor metastases, are identified and
biopsied to determine if cancer has spread to these lymph nodes.

“Lymphoseek was specifically designed to provide clinicians who perform
lymphatic mapping procedures with actionable information, and we believe that
the data reported in this publication demonstrate its utility and safety in
identifying tumor-draining lymph nodes,” said Frederick Cope, Ph.D., Senior
Vice President, Pharmaceutical Research and Clinical Development of Navidea.
“These data from breast cancer patients, in conjunction with previously
published data from our Phase 3 clinical trials in melanoma, comprise part of
our NDA registration package for Lymphoseek with the FDA. We are confident
that Lymphoseek may hold significant improvement for patients who undergo
lymphatic mapping procedures.”

“Tilmanocept was originally developed at UCSD as a targeted molecular approach
to help stage breast cancer and melanoma patients, and we advanced the agent
through Phase 1 clinical trials with funding provided by Susan G. Komen Breast
Cancer Foundation and the American Cancer Society," said Anne Wallace, M.D.,
Chief, Division of Plastic Surgery; Professor of Surgery, UC San Diego School
of Medicine; Director of the Breast Care Unit; UC San Diego Moores Cancer
Center; and a Principal Investigator in the Lymphoseek Phase 3 clinical
trials. “The results from these Phase 3 clinical trials in breast cancer
demonstrate the potential that specifically-designed imaging agents may have
an important role in reliably localizing tumor-draining lymph nodes and in
optimizing patient management post-surgery. Appropriate lymphatic mapping and
sentinel node biopsy can benefit certain patients by sparing them removal of
unnecessary lymphoid tissue and preventing side effects such as lymphedema or
swelling, pain and sensory changes, scarring or disfigurement, and extended
recovery times.”

Completed Lymphoseek Phase 3 Clinical Trials in Breast Cancer

Two Phase 3 non-randomized trials were conducted in patients with breast
cancer undergoing lymphatic mapping. The primary endpoint was the rate of
agreement (concordance) between [^99mTc]tilmanocept and vital blue dye, which
was defined as the proportion of lymph nodes identified by VBD that were also
identified by Lymphoseek. A pre-specified minimum rate of agreement of 90% had
been established in the trials’ statistical plan. In the trials, a total of
148 patients with breast cancer from 13 centers received [^99mTc]tilmanocept
followed by vital blue dye and then underwent sentinel lymph node mapping.
Lymph nodes that demonstrated [^99mTc]tilmanocept uptake and/or the presence
of blue dye were removed and examined for the presence of tumor. Of the 209
blue-dyed lymph nodes removed from the patients, 207 (99.04%) demonstrated
[^99mTc]tilmanocept uptake (p<0.0001).

In assessing reverse concordance (the proportion of blue-dyed nodes relative
to all nodes with [^99mTc]tilmanocept uptake) according to the protocol,
Lymphoseek detected 320 lymph nodes. Of these nodes, VBD detected 207

Lymph node identification

The performance of [^99mTc]tilmanocept in intraoperative lymph node
identification was also assessed. Of the patients injected with both
[^99mTc]tilmanocept and vital blue dye who underwent surgical removal of the
lymph nodes, 146 patients had at least one radioactive node, due to
[^99mTc]tilmanocept uptake, and 131 patients had at least one blue node. This
difference was statistically significant (p<0.0001).


Of 33 pathology-positive lymph nodes (18.2% patient pathology rate),
[^99mTc]tilmanocept detected 31 of 33 positive lymph nodes found in the
patients. Blue dye detected 25 of the 33 positive lymph nodes, but no positive
lymph nodes were detected exclusively by vital blue dye.


[^99mTc]tilmanocept was well tolerated in the trials, with no serious adverse
reactions ascribed to the radiopharmaceutical.

About Lymphoseek^®

Indication and Important Safety Information About Lymphoseek


Lymphoseek (technetium Tc 99m tilmanocept) Injection is indicated for
lymphatic mapping with a hand-held gamma counter to assist in the localization
of lymph nodes draining a primary tumor site in patients with breast cancer or

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

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.

The most common adverse reactions are injection site irritation and/or pain


Lymphoseek^® (technetium Tc 99m tilmanocept) Injection is a novel,
receptor-targeted, small-molecule radiopharmaceutical used in lymphatic
mapping procedures that are performed to help stage breast cancer and
melanoma. Lymphoseek is designed to identify the lymph nodes that drain from a
primary tumor, which have the highest probability of harboring cancer, in
patients with breast cancer or melanoma. Lymphoseek was approved for use by
the U.S. Food and Drug Administration in March, 2013.

Lymphatic mapping is a procedure in which lymph nodes that may contain tumor
metastases are identified and biopsied to determine if cancer has spread
beyond the primary tumor. Accurate staging of cancer is critical, as it guides
therapy decisions and determines patient prognosis and risk of recurrence.
According to the American Cancer Society, approximately 232,000 new cases of
breast cancer and 77,000 new cases of melanoma are expected to be diagnosed in
the United States in 2013.^1

About Lymphatic Mapping

Lymphatic mapping is a procedure designed to guide lymph node dissection and
biopsy procedures. It consists of Intraoperative Lymphatic Mapping (ILM) often
accompanied by lymphoscintigraphy. Lymphoscintigraphy is an imaging procedure
routinely performed pre-operatively to provide guidance on the location of
lymph nodes to be biopsied. ILM is a surgical procedure in which lymph nodes
draining the area around a tumor are identified and biopsied to determine if
cancer has spread to the lymph nodes. These nodes, medically referred to as
“Sentinel Lymph Nodes,” are removed and analyzed for the presence of malignant
cells. Lymphatic Mapping provides an accurate staging procedure that can help
ensure optimal surgical and therapeutic choices, including the avoidance of
the morbidity of a complete lymph node dissection for patients in whom the
Sentinel Lymph Nodes were found to be free of cancer.

About Navidea Biopharmaceuticals, Inc.

Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB) is a biopharmaceutical
company focused on the development and commercialization of precision
diagnostics and radiopharmaceutical agents. Navidea is actively developing
four radiopharmaceutical agent platforms – Lymphoseek^®, NAV4694, NAV5001 and
RIGScan^TM – to help identify the sites and pathways of undetected disease and
enable better diagnostic accuracy, clinical decision-making and, ultimately,
patient care. Navidea’s strategy is to deliver superior growth and shareholder
return by bringing to market novel radiopharmaceutical agents and advancing
the Company’s pipeline through selective acquisitions, global partnering and
commercialization efforts. For more information, please visit

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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

^1 Source: ACS Cancer Facts & Figures, 2013


Navidea Biopharmaceuticals
Brent Larson, 614-822-2330
Sr. VP & CFO
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