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

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 melanoma of the skin. 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. Lymphoseek is a receptor-targeted radiopharmaceutical under development for use in lymphatic mapping, a procedure in which 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. The study, was published in the current online edition of the journal [DOI 10.1245/s10434-012-2612-z].

“Both the incidence rate and the death rate for melanoma continue to increase, in the United States and in many other parts of the world," said Vernon K. Sondak, M.D., Chair, Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa Fla., and Principal Investigator for melanoma in the Lymphoseek Phase 3 clinical trials. "Most patients present with clinically localized disease, but microscopic metastases to the regional lymph nodes are common and are the major prognostic factor for these patients. Over the past 20 years, surgical staging of the regional nodes with intraoperative lymphatic mapping and sentinel node biopsy has emerged as the worldwide standard of care for patients with clinically node-negative intermediate and thick melanomas, and for selected patients with higher-risk thin primaries as well. New technologies offer the promise of improving intraoperative lymphatic mapping, potentially allowing procedures to be done rapidly and with less risk of misclassifying patients as node-negative when, in fact, their cancer has already spread to the regional nodes.”

“Lymphoseek was specifically designed to provide actionable information for clinicians who perform lymphatic mapping procedures, and we believe that the data reported in this publication demonstrate its utility and safety in identifying tumor-draining lymph nodes,” said Mark Pykett, Ph.D., President and CEO of Navidea. “These data from melanoma patients, as well as data from our Phase 3 trials in breast cancer, comprise part of our NDA registration package for Lymphoseek with the FDA, and we are confident that Lymphoseek may hold significant promise for patients undergoing lymphatic mapping procedures.”

Two Phase 3 non-randomized trials (NE03-05, NE03-09) were conducted in patients with cutaneous melanoma undergoing lymphatic mapping. The primary endpoint was the rate of agreement (concordance) between Lymphoseek and VBD, 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 154 patients with melanoma from 15 centers received Lymphoseek followed by VBD and then underwent sentinel lymph node mapping. Lymph nodes that demonstrated Lymphoseek uptake and/or the presence of blue dye were removed and examined for the presence of tumor. Of the 235 blue-dyed lymph nodes removed from the 154 patients, 232 (98.7%) demonstrated Lymphoseek uptake (p<0.001).

In assessing reverse concordance (the proportion of blue-dyed nodes relative to all nodes with Lymphoseek uptake) according to the protocol, Lymphoseek detected 364 lymph nodes. Of these nodes, VBD detected 232 (63.7%).

The performance of Lymphoseek in intraoperative lymph node identification was also assessed. Of the 154 patients injected with both Lymphoseek and VBD who underwent surgical removal of the lymph nodes, 150 patients (97.4%) had at least one radioactive node, due to Lymphoseek uptake, and 138 patients (89.6%) had at least one blue node. This difference was statistically significant (p<0.002).

Melanoma-containing lymph nodes were detected in 34 (22.1%) patients; Lymphoseek identified all 45 melanoma-positive lymph nodes found in the 34 patients. Four of these 34 node-positive patients were detected exclusively by Lymphoseek. Blue dye detected 36 of the 45 melanoma-positive lymph nodes, but no melanoma-positive lymph nodes were detected exclusively by VBD.

Lymphoseek was well tolerated in the trials, with no serious adverse reactions ascribed to the radiopharmaceutical.

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.

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 229,000 new cases of breast cancer and 76,000 new cases of melanoma are expected to be diagnosed in the United States in 2012.

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, commonly 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.

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, CFT and RIGScan – 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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