Navidea Biopharmaceuticals Announces 50th Participant Enrolled in the Company’s Phase 3 Trial in Rheumatoid Arthritis

Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) (“Navidea” or the “Company”), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, today announced enrollment of the 50^th participant in the Company’s pivotal NAV3-33 Phase 3 clinical trial titled “Evaluation of Tc 99m Tilmanocept Imaging for the Early Prediction of Anti-TNFα Therapy Response in Patients with Moderate to Severe Active Rheumatoid Arthritis (RA)” (ClinicalTrials.gov Identifier: NCT05246280).

This Phase 3 trial will establish the ability of Tc99m tilmanocept imaging to serve as an early predictor of treatment response in rheumatoid arthritis (“RA”) patients switching to an anti-TNFα therapy, addressing a large unmet medical need. Overall trial size will range from 198-672 patients, with enrollment targeted to achieve a minimum of 100 clinical responders to anti-TNFα therapy and 98 non-responders.

Rheumatoid arthritis is a serious and potentially debilitating disease. The standard practice of treating RA is to monitor patients starting new RA therapies over a course of three to six months and, in those patients for which the new therapies prove to be ineffective, to change their treatments to an alternative therapy. This trial-and-error process of appropriate treatment selection may take several months to more than a year to arrive at an adequate treatment for any RA patient. Imaging with Tc99m tilmanocept, a synthetic molecule with high affinity to CD206 receptors expressed on activated macrophages, offers the potential to provide an early predictor of clinical response by providing an objective, quantifiable readout of changes in macrophage density in the joints of patients undergoing initiation or change of therapy. These macrophage density changes may be observable weeks before disease modification can be detected with standard clinical assessments. Additionally, in patients with a low-macrophage type of RA who have been shown to be less responsive to anti-TNFα therapy, an initial baseline scan alone could point their physicians to another therapy type that has a better chance of success than an anti-TNFα.

The data from the Company’s completed NAV3-31 Phase 2B trial demonstrated that Tc99m tilmanocept can provide robust, quantitative imaging in both healthy controls and in patients with active RA, and that this imaging is reproducible and can define joints with and without RA-involved inflammation. The Phase 2B trial also provided evidence in support of the hypothesis that Tc99m tilmanocept can provide an early prediction of treatment efficacy in patients switching to an anti-TNFα therapy, with an overall accuracy of early treatment response prediction of 90% at 12-week follow up and 86% at 24 weeks.