Navidea Biopharmaceuticals, Inc. (NAVB) is a biopharmaceutical company focused on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. The company's primary focus is on its Manocept platform, which serves as the molecular backbone for its lead product, Tc99m tilmanocept, and a pipeline of diagnostic and therapeutic candidates.

Business Overview

Navidea's Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor expressed on activated macrophages. This versatile platform enables the development of purpose-built targeted imaging molecules that can significantly impact patient care by providing enhanced diagnostic accuracy, clinical decision-making, and target-specific treatment. The Manocept platform is applicable to a range of diagnostic modalities, including SPECT, PET, gamma-scanning, and intra-operative/optical-fluorescence detection, as well as the delivery of therapeutic compounds.

The company's lead product, Tc99m tilmanocept, is an FDA-approved sentinel node/lymphatic mapping agent. Navidea has a license to distribute Tc99m tilmanocept outside of Canada, Mexico, and the United States. The company is also developing additional imaging product candidates based on the Manocept platform, targeting indications such as rheumatoid arthritis (RA), cardiovascular disease, and Kaposi's sarcoma.

In addition to its diagnostic efforts, Navidea is advancing therapeutic applications of the Manocept platform, including the MAN-DOX, MAN-PAC, MAN-BIS, and MAN-DEX series, which are designed to target and modulate activated CD206-positive macrophages in various disease states.

Financials

For the full year 2022, Navidea reported annual revenue of $65,652, annual net loss of $17,215,039, annual operating cash flow of -$8,986,570, and annual free cash flow of -$9,376,919. The company's financial performance has been impacted by its ongoing research and development efforts, as well as legal and regulatory challenges.

In the third quarter of 2023, Navidea reported no sales revenue, compared to $7,516 in the same period of 2022. Research and development expenses decreased 30% to $830,000, while selling, general, and administrative expenses decreased 64% to $1.3 million. The company's net loss for the third quarter of 2023 was $2,255,339, compared to a net loss of $5,707,825 in the same period of 2022.

For the first nine months of 2023, Navidea reported no sales revenue, compared to $14,035 in the same period of 2022. Research and development expenses decreased 21% to $3.2 million, while selling, general, and administrative expenses decreased 44% to $3.8 million. The company's net loss for the first nine months of 2023 was $5,124,853, compared to a net loss of $11,694,528 in the same period of 2022.

Manocept Platform: Diagnostics

Navidea's primary focus in the diagnostic space has been on the development of Tc99m tilmanocept and other Manocept-based imaging agents. The company has completed several clinical trials evaluating Tc99m tilmanocept's potential in various indications, including rheumatoid arthritis, cardiovascular disease, and Kaposi's sarcoma.

In rheumatoid arthritis, Navidea has completed a Phase 2b clinical trial (NAV3-31) evaluating the imaging repeatability, reproducibility, and stability of Tc99m tilmanocept, as well as its potential to serve as an early predictor of treatment efficacy of anti-TNFα therapy. The company has also completed enrollment into a Phase 2b clinical trial (NAV3-35) designed to establish a normative database to support its RA imaging commercial product development. Navidea's ongoing pivotal Phase 3 trial for RA (NAV3-33) is the next step in the development plan for this indication.

In the cardiovascular disease space, Navidea has completed two investigator-initiated clinical studies evaluating Tc99m tilmanocept's ability to enable imaging of atherosclerotic plaques. The results of these studies provide strong preliminary evidence of the potential of Tc99m tilmanocept to accumulate specifically in and enable imaging of non-calcified atherosclerotic plaques, which are associated with a high risk of rupture and can cause myocardial infarctions and ischemic strokes.

Manocept Platform: Therapeutics

Navidea has also been developing therapeutic applications of its Manocept platform, including the MAN-DOX, MAN-PAC, MAN-BIS, and MAN-DEX series. These constructs are designed to target and modulate activated CD206-positive macrophages in various disease states, such as Kaposi's sarcoma and leishmaniasis.

Experiments utilizing human macrophage assays have shown that at treatment doses below what is required to kill macrophages, all three construct series (MAN-DOX, MAN-PAC, and MAN-BIS) dramatically alter the immunological behavior of macrophages, making them more proinflammatory. In syngeneic mouse tumor experiments, the MAN-DOX and MAN-PAC constructs have significantly synergized the activity of another anticancer therapy, producing anti-tumor activity greater than either treatment alone.

Risks and Challenges

Navidea faces several risks and challenges in the development and commercialization of its Manocept platform products. These include the ability to successfully complete clinical trials, obtain regulatory approvals, and secure the necessary funding to support its development programs. The company is also engaged in ongoing litigation with CRG and its former President and Chief Executive Officer, Dr. Michael Goldberg, which could have a material impact on its financial position and operations.

Additionally, the current conflict between Ukraine and Russia has created volatility in the global capital markets, which could make it more difficult for Navidea to obtain debt or equity financing. The company's operations and those of its suppliers, distributors, and other business partners may also be disrupted by the ongoing geopolitical tensions and their economic consequences.

Outlook

Navidea expects its total research and development expenses, including both out-of-pocket charges and internal headcount and support costs, to be lower in 2023 than in 2022. The company will continue to focus on the advancement of its efforts with the Manocept platform, including the ongoing development of its diagnostic and therapeutic candidates.

However, based on the company's current working capital and projected cash burn, management believes that there is substantial doubt about Navidea's ability to continue as a going concern for a period of one year from the filing of its latest Quarterly Report on Form 10-Q. The company will continue to evaluate potential funding and other resources required for the continued development, regulatory approval, and commercialization of its Manocept platform product candidates, as well as potential options for advancing development.

Conclusion

Navidea Biopharmaceuticals is a biopharmaceutical company with a focus on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics based on its Manocept platform. The company has made progress in advancing its diagnostic and therapeutic candidates, but faces significant challenges, including ongoing litigation, volatility in the global capital markets, and substantial doubt about its ability to continue as a going concern.

Despite these challenges, Navidea's Manocept platform holds promise in addressing a range of diseases where macrophages play a critical role. The company's continued efforts to develop and commercialize its Manocept-based products will be crucial in determining its long-term success and the potential impact of its technology on patient care.