Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) (“Navidea” or the “Company”), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, today announced acceptance of its abstract titled, “CD206 Targeted Delivery of Bisphosphonate Payloads Alter Human Macrophage Phenotypes Towards M1-like” for presentation of a poster at this year’s Tumor Myeloid-Directed Therapies Summit.

The 2nd annual Tumor Myeloid-Directed Therapies Summit meeting will be held June 14-16, 2022 in Boston, MA. The presentation will take place Tuesday, June 14. Meeting information can be found on the conference website (https://tumor-myeloid-therapeutics.com).

The poster will present information related to the synthesis of two novel bisphosphonate drugs that have been attached to Navidea’s CD206-targeted drug delivery platform molecule, Manocept. These constructs use a novel degradable linker to release the therapy only once they have been internalized into a CD206-expressing cell, such as a tumor associated macrophage. The new therapeutic constructs were evaluated in human macrophage cell culture assays to compare the ability of the new constructs with unbound free therapy to shift the phenotype of macrophages toward a proinflammatory gene expression pattern. The new drug delivery constructs successfully shifted the phenotypes of human macrophages towards a proinflammatory state and compared favorably to the unbound free therapy. The new drug constructs also induced a highly significant reduction in macrophage expression of signal regulatory protein alpha (“SIRPα”), the receptor for the “don’t eat me” signal that, when activated, suppresses the ability of macrophages to attack and phagocytize disease associated cells such as cancer cells. The ability to induce this type of phenotypic change in macrophages could have far-reaching applications in cancer immunotherapy.

Dr. Michael Rosol, Chief Medical Officer for Navidea, said, “These new therapeutic constructs demonstrate the power of our adaptable platform technology to deliver a wide array of small molecule payloads in a targeted fashion to macrophages involved in the propagation of a variety of severe illnesses including cancer.”

About Navidea

Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) is a biopharmaceutical company focused on the development of precision immunodiagnostic agents and immunotherapeutics. Navidea is developing multiple precision-targeted products based on its Manocept™ platform to enhance patient care by identifying the sites and pathways of disease and enable better diagnostic accuracy, clinical decision-making, and targeted treatment. Navidea’s Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor expressed on activated macrophages. The Manocept platform serves as the molecular backbone of Tc99m tilmanocept, the first product developed and commercialized by Navidea based on the platform. 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.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends affecting the financial condition of our business. Forward-looking statements include our expectations regarding pending litigation and other matters. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: our history of operating losses and ability to obtain additional financing; our ability to continue as a going concern; the final outcome of any pending litigation; our ability to successfully complete research and further development of our drug candidates; the timing, cost and uncertainty of obtaining regulatory approvals of our drug candidates; our ability to successfully commercialize our drug candidates; dependence on royalties and grant revenue; our ability to implement our growth strategy; anticipated trends in our business; our limited product line and distribution channels; advances in technologies and development of new competitive products; our ability to comply with the NYSE American continued listing standards; our ability to maintain effective internal control over financial reporting; the impact of the current coronavirus pandemic; and other risk factors detailed in our most recent Annual Report on Form 10-K and other SEC filings. You are urged to carefully review and consider the disclosures found in our SEC filings, which are available at http://www.sec.gov or at http://ir.navidea.com.

Investors are urged to consider statements that include the words “will,” “may,” “could,” “should,” “plan,” “continue,” “designed,” “goal,” “forecast,” “future,” “believe,” “intend,” “expect,” “anticipate,” “estimate,” “project,” and similar expressions, as well as the negatives of those words or other comparable words, to be uncertain forward-looking statements.

You are cautioned not to place undue reliance on any forward-looking statements, any of which could turn out to be incorrect. We undertake no obligation to update publicly or revise any forward-looking statements, whether as a result of new information, future events or otherwise after the date of this report. In light of these risks and uncertainties, the forward-looking events and circumstances discussed in this report may not occur and actual results could differ materially from those anticipated or implied in the forward-looking statements.

Investor Relations Contact Navidea Biopharmaceuticals, Inc. Jeffrey Smith Vice President of Operations 614-822-2365 jsmith@navidea.com

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