As filed with the Securities and Exchange Commission onJune17, 2020February 11, 2022

Registration No. 333-238911333-[_____]

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

AMENDMENT NO.1 TO

​FORM S-1

REGISTRATION STATEMENT

UNDER
THE SECURITIES ACT OF 1933

NAVIDEA BIOPHARMACEUTICALS, INC.

(EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

4995 Bradenton Avenue, Suite 240

Dublin, Ohio 43017
(614) 793-7500
(Address, Including Zip Code, and Telephone Number, Including Area Code, of Registrant’s Principal Executive Offices)

Jed A. LatkinMichael S. Rosol, Ph.D.

Chief Executive Officer, Chief Operating Officer & Chief FinancialMedical Officer

Navidea Biopharmaceuticals, Inc.

4995 Bradenton Avenue, Suite 240

Dublin, Ohio 43017

(614) 793-7500
(Name, Address, Including Zip Code, and Telephone Number, Including Area Code, of Agent for Service)

Copies to:

Martin R. Rosenbaum, Esq.

Faith L. Charles,William M. Mower, Esq.
Thompson HineMaslon LLP
335 Madison Avenue, 12th Floor
New York, New York 10017-4611
(212) 344-5680​90 South 7^th Street, Suite 3300

Minneapolis, MN 55402​

Approximate date of commencement of proposed sale to the public: As soon as practicable after the effective date of this registration statement.

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, as amended (the “Securities Act”), check the following box. ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company in Rule 12b-2 of the Exchange Act. ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

CALCULATION OF REGISTRATION FEE

​

​The Registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment that specifically states that this registration statement shall thereafter become effective in accordance with Section8(a) of the Securities Act of 1933, as amended, or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section8(a), may determine.

The information in this preliminary prospectus is not complete and may be changed.Theselling stockholdermay not sell these securities until the registration statement filed with theU.S.Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and we are not soliciting an offer to buy these securities in any jurisdiction where the offer or sale is not permitted.

PRELIMINARYPROSPECTUSSUBJECT TO COMPLETION, DATED JUNE 17, 2020_______, 2022

4,586,790Subscription Rights to Purchase Up to ●    Shares of

Common Stock

This prospectus relatesWe are distributing to holders of our common stock, $0.001 par value, and to holders of certain of our outstanding warrants, Series D preferred stock and Series E preferred stock, at no charge, non-transferable subscription rights to purchase up to the lesser of $35.0 million or ● shares of our common stock. We refer to the offering that is the subject of this prospectus as the rights offering. In the rights offering, you will receive, on ●, 2022, the record date of the rights offering, ● subscription right for every share of common stock owned or deemed owned as of 4:00 p.m., Eastern Time, on ●, 2022. Shares that are “deemed owned” refer to the shares issuable upon exercise of the outstanding warrants issued to the underwriter in our public offering in 2019 (the “Underwriter Warrants”) and resalethe shares issuable upon conversion of the outstanding Series D preferred stock and Series E preferred stock. The subscription rights will not be tradeable. Each subscription right consists of a basic subscription privilege and an over-subscription privilege. We must receive minimum gross proceeds of $● million from the exercise of the basic subscription privilege and over-subscription privilege in order to complete the offering.

Each basic subscription privilege will entitle you to purchase ● shares of common stock, which we refer to as the basic subscription right, at a subscription price per share of common stock equal to $●. If you exercise your basic subscription privilege in full, and any portion of the shares of common stock remain available under the rights offering which are unsubscribed, you will be entitled to an over-subscription privilege to purchase a portion of the unsubscribed shares of common stock at the subscription price, subject to proration among participants exercising their over-subscription privilege, which we refer to as the over-subscription privilege.

You may only purchase the number of shares of common stock purchasable upon exercise of the number of basic subscription privilege distributed to you in the rights offering, plus the over-subscription privilege, if any. Accordingly, the number of shares of common stock that you may purchase in the rights offering is limited by Keystone Capital Partners, LLC, as selling stockholder,the number of up to 4,586,790 shares of our common stock par value $0.001 per share (the “Shares”), which consists of: (i) 348,389 shares of commonyou owned or were deemed to own under the Underwriter Warrants, Series D preferred stock or Series E preferred stock and (ii) up to 4,238,401 shares of common stock issuable upon conversion of shares of our Series C Redeemable Convertible Preferred Stock, par value $0.001 per share (“Series C Preferred”). The prices at which the selling stockholder may sell the shares will be determined by the prevailing market price for the shares or in negotiated transactions.  We will not receive proceeds from the saleextent to which other participants exercise their basic subscription privileges and over-subscription privileges, which we cannot determine prior to completion of the shares by the selling stockholder.   rights offering.

The selling stockholdersubscription rights will expire if they are not exercised by 5:00 p.m., Eastern time, on ●, 2022, unless the rights offering is an “underwriter” withinextended or earlier terminated by us. If we elect to extend the meaningrights offering, we will issue a press release announcing the extension no later than 9:00 a.m., Eastern time, on the next business day after the most recently announced expiration date of the Securities Actrights offering. We may extend the rights offering for a period not to exceed 30 days in our sole discretion. Once made, all exercises of 1933, as amended (the “Securities Act”).   Wesubscription rights are irrevocable. However, if, on or before the expiration of this rights offering, we do not receive subscriptions or over-subscriptions or a combination thereof for a minimum aggregate of $● , we will paycancel the expensesrights offering and all exercises of registering these shares, butsubscriptions will not be completed and all selling and other expenses incurredfunds advanced in connection with such exercises will be promptly refunded by the selling stockholdersubscription agent. All subscription payments will be paiddeposited into an escrow account maintained by the selling stockholder.subscription agent for the benefit of the holders exercising their subscriptions under the rights offering, and if the rights offering is not completed for any reason all funds will be promptly returned to such subscribers in the amounts advanced in connection with their respective exercises.

This rights offering is being made directly by us. We are not using an underwriter or selling agent. We have engaged ● (“●”), to serve as our subscription and information agent for the rights offering (the “Subscription Agent”). The Subscription Agent will hold in escrow the funds we receive from subscribers until we complete or cancel this rights offering.

We are conducting the rights offering to raise capital that we intend to use for funding the Company’s pivotal Phase 3 trial for Rheumatoid Arthritis (NAV3-33) (as described below), obtaining regulatory approvals, working capital, and for general corporate purposes.

You should carefully consider whether to exercise your subscription rights prior to the expiration of the rights offering. All exercises of subscription rights are irrevocable, even if the rights offering is extended by our board of directors for a period of up to 30 days.

If we amend the rights offering to allow for an extension of the rights offering for a period of more than 30 days or make a fundamental change to the terms of the rights offering set forth in this prospectus, you may cancel your subscription and receive a prompt refund of any money you have advanced. Our board of directors may cancel the rights offering at any time prior to the expiration of the rights offering for any reason. In the event the rights offering is canceled, all subscription payments received by the Subscription Agent will be promptly returned, without interest.

Our board of directors is making no recommendation regarding your exercise of the subscription rights. The subscription rights may not be sold, transferred or assigned and will not be listed for trading on any stock exchange or market. Our common stock is listed on the NYSE American under the symbol “NAVB.” On June 15, 2020,February 11, 2022, the last reported sale price of our common stock on the NYSE American was $3.24$0.95 per share. You are urged to obtain current market quotations for our common stock. The shares of common stock issued in the rights offering will also be traded on the NYSE American under the same symbol.

You should read this prospectus and any prospectus supplement, together with additional information described under the headings “Incorporation of Certain Documents by Reference” and “Where You Can Find More Information,” carefully before you invest in any of our securities.

Investing in our securities involves a high degree of risk. See “Risk Factors”“Risk Factors” on page 1017 of this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.

The date of this prospectus is, 20202022

TABLE OF CONTENTS

You should read this prospectus, including all documents incorporated herein by reference, together with additional information described under “Where You Can Find More Information.”

You may obtain the information incorporated by reference without charge by following the instructions under “Where You Can Find More Information.”

We have not authorized anyone to provide you with information different from that contained or incorporated by reference in this prospectus. The selling stockholder may offer to sell, and seek offers to buy, shares of our common stock only in jurisdictions where offers and sales are permitted. The information contained in this prospectus is accurate only as of the date of this prospectus, regardless of the time of delivery of this prospectus or of any sale of common stock.

In this prospectus, “we,” “us,” “our” and “Navidea” refer to Navidea Biopharmaceuticals, Inc. and its subsidiaries.

ABOUT THIS PROSPECTUS

You should rely only on the information we have provided or incorporated by reference into this prospectus, any applicable prospectus supplement and any related free writing prospectus. We have not authorized anyone to provide you with information different from that contained or incorporated by reference in this prospectus any applicable prospectus supplement or any related free writing prospectus. No dealer, salesperson or other person is authorized to give any information or to represent anything not contained in this prospectus, any applicable prospectus supplement or any related free writing prospectus.connection with the rights offering described herein. You must not rely on any unauthorized information or representation. This prospectus is an offer to sell only the Sharesshares offered hereby, but only under circumstances and in jurisdictions where it is lawful to do so. You should assume that the information in this prospectus, any applicable prospectus supplement or any related free writing prospectus is accurate only as of the date on the front of the document and that any information we have incorporated by reference is accurate only as of the date of the document incorporated by reference,applicable documents, regardless of the time of delivery of this prospectus or any sale of a security. Our business, financial condition, results of operations and prospects may have changed since that date.

The selling stockholder is offering the Shares only in jurisdictions where such issuances are permitted. The distribution of this prospectus and the issuance of the Sharesshares in certain jurisdictions may be restricted by law. Persons outside the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the issuancesale of the Sharesshares and the distribution of this prospectus outside the United States. This prospectus does not constitute, and may not be used in connection with, an offer to sell, or a solicitation of an offer to buy, the Sharesshares offered by this prospectus by any person in any jurisdiction in which it is unlawful for such person to make such an offer or solicitation.

This prospectus is part of a registration statement that we filed with the U.S. Securities and Exchange Commission (the “SEC”), under which the selling stockholder may offer from time to time up to an aggregate of 4,586,790 Shares in one or more offerings. If required, each time the selling stockholder offers Shares, we will provide you with, in addition to this prospectus, a prospectus supplement that will contain specific information about the terms of that offering. We may also authorize one or more free writing prospectuses to be provided to you that may contain material information relating to that offering. We may also use a prospectus supplement and any related free writing prospectus to add, update or change any of the information contained in this prospectus or in documents we have incorporated by reference. This prospectus, together with any applicable prospectus supplements, any related free writing prospectuses and the documents incorporated by reference into this prospectus, includes all material information relating to this offering. To the extent that any statement that we make in a prospectus supplement is inconsistent with statements made in this prospectus, the statements made in this prospectus will be deemed modified or superseded by those made in a prospectus supplement. Please carefully read both this prospectus and any prospectus supplement together with the additional information described below under the section entitled “Incorporation of Certain Information by Reference” before buying any of the securities offered.

This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed, will be filed or will be incorporated by reference as exhibits to the registration statement of which this prospectus is a part, and you may obtain copies of those documents as described below under the section entitled “Where You Can Find More Information.”

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

The Private Securities Litigation Reform Act of 1995 (the “PSLRA”) provides a safe harbor for forward-looking statements made by or on behalf of the Company. Statements in this document which relate to other than strictly historical facts, such as statements about the Company’s plans and strategies, expectations for future financial performance, new and existing products and technologies, anticipated clinical and regulatory pathways, the ability to obtain, and timing of, regulatory approvals of the Company’s products, the timing and anticipated results of commercialization efforts, and anticipated markets for the Company’s products, are forward-looking statements within the meaning of the PSLRA. The words “anticipate,” “believe,” “estimate,” “expect,” “future,” “intend,” “plan,” “project,” and similar expressions identify forward-looking statements that speak only as of the date hereof. Investors are cautioned that such statements involve risks and uncertainties that could cause actual results to differ materially from historical or anticipated results due to many factors including, but not limited to, our history of operating losses and uncertainty of future profitability, accumulated deficit, future capital needs, the outcome of any pending litigation, uncertainty of capital funding, dependence on royalties and grant revenue, limited product line and distribution channels, competition, risks of development of new products, our ability to maintain effective control over financial reporting, our ability to comply with NYSE American continued listing standards, and other risks set forth in our Form 10-K under Item 1A, “Risk Factors” and beginning on page 1017 of this prospectus. Navidea undertakes no obligation to publicly update or revise any forward-looking statements. Forward-looking statements include, but are not limited to, statements about:

You should carefully read this prospectus, the documents that we incorporate by reference into this prospectus and the documents we reference in this prospectus and have filed as exhibits to the registration statement, of which this prospectus is a part, completely and with the understanding that our actual future results may be materially different from what we expect. We qualify all of the forward-looking statements in this prospectus by these cautionary statements.

Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in any forward-looking statements, whether as a result of new information, future events or otherwise.

PROSPECTUS SUMMARY

This summary highlights information contained in other parts of this prospectus or incorporated by reference into this prospectus from our filings with the U.S. Securities and Exchange Commission (the “SEC”“SEC”) listed in the section of the prospectus entitled “Incorporation“Incorporation of Certain Information by Reference.” Because it is only a summary, it does not contain all of the information that should be considerconsidered before purchasing our securities in this offering and it is qualified in its entirety by, and should be read in conjunction with, the more detailed information appearing elsewhere or incorporated by reference into this prospectus. You should read the entire prospectus, the registration statement of which this prospectus is a part, and the information incorporated by reference herein in their entirety, including the “Risk Factors”“Risk Factors” and our financial statements and the related notes incorporated by reference into this prospectus, before purchasing our securities in this offering. Unless the context requires otherwise, references in this prospectus to “the“the Company,” “Navidea,“Navidea,” “we,“we,” “us”“us” and “our”“our” refer to Navidea Biopharmaceuticals, Inc. together with its wholly owned subsidiary,wholly-owned subsidiaries, Navidea Biopharmaceuticals Europe Limited and Navidea Biopharmaceuticals Limited, and ourits majority-owned subsidiary, Macrophage Therapeutics, Inc.

The Company

Navidea Biopharmaceuticals, Inc. (“Navidea,” the “Company,” “we,” “us” or “our”), a Delaware corporation (NYSE American: NAVB), is a biopharmaceutical company focused on the development and commercialization of precision immunodiagnostic agents and immunotherapeutics. Navidea is developing multiple precision-targeted products based on our Manocept™ platform to enhance patient care by identifying the sites and pathways of undetected 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.

In March 2017, the Company completed the sale to Cardinal Health 414, LLC (“Cardinal Health 414”) of its assets related to the Company’s radioactive diagnostic agent Tc99m tilmanocept, marketed under the Lymphoseek^® trademark, used for lymphatic mapping, lymph node biopsy, and the diagnosis of metastatic spread to lymph nodes for staging of cancer, in Canada, Mexico and the United States.

Other than Tc99m tilmanocept, which the Company has a license to distribute outside of Canada, Mexico and the United States, none of the Company’s drug product candidates have been approved for sale in any market.

Our business is focused on two primary types of drug products: (i) diagnostic substances, including Tc99m tilmanocept and other diagnostic applications of our Manocept platform, and NAV4694 (sublicensed in April 2018), and (ii) therapeutic development programs, including therapeutic applications of our Manocept platform. See Note 14 to the consolidated financial statements included in our Annual Report on Form 10-K and our Quarterly Report on Form 10-Q for more information about our business segments.

Technology and Product Candidates

Our primary development efforts over the last several years were focused on diagnostic products, including Lymphoseek,Tc99m tilmanocept, which was soldthe Company has a license to Cardinal Health 414 in March 2017.distribute outside of Canada, Mexico and the United States. Our more recent initiatives have been focused exclusively on diagnostic and therapeutic line extensions based on our Manocept platform.

During the ongoing COVID-19 global pandemic, the Company’s primary focusconcern is the safety of its employees, the employees of its clinical trial sites, and the patients enrolled in its clinical trials. The Company is working hard to mitigate any safety risk along with any long-term impact on its clinical development programs. To date, weWe do not believe there has been any appreciablea significant impact to the Company’s clinical development and regulatory timelines resulting from COVID-19.the ongoing COVID-19 global pandemic. However, the COVID-19 outbreak delayed enrollment in our NAV3-32 clinical study in the United Kingdom due to national COVID-19-related shutdowns. In addition, the regulatory approval process in India has been delayed by the impact of COVID-19 in that country.

As brief overview of recent developments in the Company’s diagnostics area (additional details in following sections), Navidea has enrolled sufficient patients in Arm 3 ofcompleted the Company’s ongoing Phase 2b clinical trial (NAV3-31) evaluating imaging repeatability, reproducibility, and isstability, as well as the capacity of Tc99m tilmanocept imaging to serve as an early predictor of treatment efficacy of anti-tumor necrosis factor alpha (“TNFα”) therapy in patients with moderate to severe Rheumatoid Arthritis (“RA”). In addition, the Company has completed enrollment into a Phase 2b clinical trial (NAV3-35) designed to accrue hand and wrist planar and single photon emission computed tomography/computed tomography (“SPECT/CT”) images from healthy subjects (with SPECT/CT imaging also done on schedule to deliver interim dataa small group of RA patients) so that Navidea can complete a normative database in the timeframe previously communicated.support of its RA imaging commercial product development. The Company’s recently launched pivotal Phase 3 trial for rheumatoid arthritisRA (NAV3-33) also remains on trackis the next step in the development plan for a second-half 2020 launch as previously communicated.indications in RA. The additional Phase 2b trial (NAV3-32) correlating Tc99m tilmanocept uptake in RA-involved joints with CD206 immunohistochemistry findings from synovial biopsies is actively recruiting. In addition, analysisthe investigator-initiated Phase 2 cardiovascular (“CV”) study was completed at Massachusetts General Hospital and a manuscript has been submitted by the investigators. Results of the data from the Company’s cardiovascular Phase 2bthis study remains on schedule. Results provided to Navidea thus fardate have paralleled data in our earlier published article, and these data are supportive of Navidea’s hypothesis that tilmanocept can provide marked signal to background in a host of cardiovascularCV disease applications. Navidea continues to anticipate meeting with the FDA in the coming months to discuss upcoming clinical trial designs.

Manocept Platform - Diagnostics and Therapeutics Background

Navidea’s Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor (CD206) expressed primarily on activated macrophages. This flexible and versatile platform serves as a molecular backbone for purpose-built targeted imaging molecules that may significantly impact patient care by providing enhanced diagnostic accuracy, clinical decision-making, and target-specific treatment. This CD206-targeted drug platform is applicable to a range of diagnostic modalities, including single photon emission computed tomography (“SPECT”),SPECT, positron emission tomography (“PET”), gamma-scanning (both imaging and topical) and intra-operative and/or optical-fluorescence detection, as well as delivery of therapeutic compounds that target macrophages and their role in a variety of immune- and inflammation-involved diseases. The FDA-approvedUnited States Food and Drug Administration (“FDA”)-approved sentinel node/lymphatic mapping agent, Tc99m tilmanocept, is representative of the ability to successfully exploit this mechanism to develop powerful new products and to expand this technology into additional diagnostic and therapeutic applications.

Activated macrophages play important roles in many disease states and are an emerging target in many diseases where diagnostic uncertainty exists. Impairment of the macrophage-driven disease mechanisms is an area of increasing and proven focus in medicine. The number of people affected by all the inflammatory diseases combined is estimated at more than 40 million in the United States and up to 700 million worldwide, making macrophage-mediated diseases an area of remarkable clinical importance. There are many recognized disorders having macrophage involvement, including rheumatoid arthritis (“RA”),RA, atherosclerosis/vulnerable plaque, nonalcoholic steatohepatitis, (“NASH”), inflammatory bowel disease, systemic lupus erythematosus, cancer generally including Kaposi’s sarcoma (“KS”), leishmaniasis, and others that span general clinical areas in oncology,cancer immunology, autoimmunity, infectious diseases, cardiology, CNScentral nervous system diseases, and inflammation. For the near term, we have selected target diseases that may, if successfully developed, benefit from this technology.

The Company has developed processes for producing the first two therapeutic Manocept immuno-construct series, MT-1000the Manocept doxorubicin (“MAN-DOX”) series, which is designed to specifically target and kill or modify activated CD206+ macrophages by delivering doxorubicin, and MT-2000the Manocept dexamethasone (“MAN-DEX”) series, which is designed to inhibit the inflammatory activity of activated CD206+ macrophages by delivering a potent anti-inflammatory agent, dexamethasone. We have contracted with independent facilities to improve chemical syntheses and to produce sufficient quantities of the MT-1000MAN-DOX series and MT-2000MAN-DEX series agents, along with the concomitant analytical standards, to provide material for current and planned preclinical animal studies and future clinical trials. Evaluation of an advanced MAN-DOX construct has been successfully evaluated in both human macrophage cell culture assays and in various syngeneic mouse models of cancer. Similar evaluations of an advanced MAN-DEX construct are currently ongoing.

Manocept Platform – Immuno-Diagnostics Clinical Data

Rheumatoid Arthritis

Two Tc99m tilmanocept dose escalation studies in RA have been completed. The first study was completed and included 18 subjects (nine with active disease and nine healthy subjects) dosed subcutaneously (“SC”) with 50 and 200 µg/2mCi Tc99m tilmanocept (ClinicalTrials.gov NCT02683421). The results of this study were presented at five international meetings, including Biotechnology Innovation Organization, Society of Nuclear Medicine and Molecular Imaging (“SNMMI”), and The American College of Rheumatology (“ACR”). In addition, based on completion of extensive preclinical dosing studies pursuant to our dialog with the FDA, we have completed a Phase 1/2 study involving intravenous (“IV”) dosing of 39 subjects with IV-administered Tc99m tilmanocept (ClinicalTrials.gov NCT02865434). In conjunction with this study, we have completed pharmacokinetic, pharmacodynamics and radiation dosimetry phases in human subjects as well. The majority of the costs of these studies have beenwere supported through a Small Business Innovation Research (“SBIR”) grant (NIH/NIAMSD Grant 1 R44 AR067583-01A1). Results of thisthe Phase 1/2 study were presented at the June 2018 and June 2019 SNMMI meetings, the 2018 European League Against Rheumatism (“EULAR”) meeting and the 2018 ACR meeting. These studies have been combined and submitted for peer review publication and full published results will follow.

In June 2019, the results of the Company’s NAV3-21 clinical study were presented at the SNMMI Annual Meeting in Anaheim, California. The presentation, titled “A Phase 1/2 Study of Intravenously Administered Tc99m Tilmanocept to Determine Safety, Tolerability, Optimal Clinical Dose Selection, and Imaging Timepoint in Patients Clinically Diagnosed with Rheumatoid Arthritis,” was delivered by Arash Kardan, M.D. In addition, an abstract of the presentation was published in the Journal of Nuclear Medicine (2019, Volume 60, Supplement 1). The NAV3-21 study enrolled subjects with active, moderate-to-severe RA, and healthy controls. Results from the completed trial demonstrate that Tc99m tilmanocept is well-tolerated with no serious adverse events, adverse drug reactions, or drug-related adverse events observed. Additionally, static planar images revealed joint-specific Tc99m tilmanocept localization in RA subjects to disease-involved joints of the shoulders, knees, hands, and feet, but no joint-specific localization in healthy control subjects, revealing potentially significant immunodiagnostic information about CD206-expressing synovial macrophage involvement in RA. An optimal imaging time window post-Tc99m tilmanocept IV administration, as well as optimal dosing, were also determined.

In April 2019, the Company received feedback from the FDA regarding the Company’s planned clinical studies that willto evaluate joint disease in patients with RA and monitor patient response to therapy. The Company’s proposed RA studies were discussed with the FDA during an in-person meeting and through follow-up collaborative efforts. The FDA has communicated that the first study, a Phase 2b trial, iswas aligned with expectations for the studies and that they willwould continue to work with Navidea as we progressthe Company progressed into athe second Phase 2b trial correlating Tc99m tilmanocept uptake in RA-involved joints with CD206 immunohistochemistry findings from synovial biopsies and into the planned Phase 3 clinical trial.

In May 2019, we began enrolling patients into the first Phase 2b study, (NAV3-31), entitled “Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (“TUV”) on Tc99m Tilmanocept Planar Imaging” (ClinicalTrials.gov MCT03938636). The NAV3-31 Phase 2bThis study, has three arms: Arm 1 consists of healthy subjects, Arm 2 is comprised of patients with active, moderate-to-severe RA who are on stable therapy, and Arm 3 is a pilot arm of the upcomingsince completed, provided confirmatory support necessary to initiate Navidea’s Phase 3 trial assessing the ability of Tc99m tilmanocept to provide an early indicator of efficacy of anti-tumor necrosis factor (“TNF”) alpha treatment in RA patients.

study program. In October 2019, the Company performed its first interim analysis of this trial, covering subjects enrolling into Arms 1 and 2. The results of this interim analysis were in line with the Company’s hypotheses that Tc99m tilmanocept can provide robust, stable imaging in healthy subjects as well as in patients with active RA, and provide the fundamental information needed to keep moving forward into the Phase 3. A summary of these results was presented at the 2020 EULAR meeting. In May 2020, the Company completedannounced the results of its second interim analysis, which was designed to examine data fromcovering Arm 3 of the studytrial. This Arm mirrored the upcoming Phase 3 in order to evaluatedesign and provided information relevant for sample size calculation for the magnitude of change of Tc99m tilmanocept signal localized to RA-involved joints in patients before and after treatment with an anti-TNF alpha therapyPhase 3 as well as to examine whether this change in localization, if any, can serve as an early, quantifiable predictor of treatment efficacy. The results ofsupport for the second interim analysis support Navidea’s hypotheseshypothesis that Tc99m tilmanocept imaging can provide quantifiablean early indicator of treatment efficacy of anti-TNFα therapeutics. These interim results were presented at the 2020 ACR meeting. In June 2020, the Company announced full enrollment into this trial, with imaging assessmentevents completed in each patient enrolled in Arm 3.

In February 2021, the Company submitted its formal briefing book to the FDA, containing detailed analysis and discussion of RA-involved joints that enables early prediction of clinical responsethe Company’s then-ongoing Phase 2b study (NAV3-31) and prior studies in RA as well as longitudinal monitoringthe design and statistical analysis plan for the proposed Phase 3 for FDA comment. Following the feedback received from the FDA at the end of clinical status.March 2021, the Company continued to work toward completing the analysis of the full NAV3-31 trial dataset and submitted the resultant briefing book containing the results of this analysis in preparation for the standard End-of-Phase 2 Type B meeting, which took place on September 1, 2021. The Company had a constructive meeting with the FDA and, based on the discussion in this meeting and follow-up communication, has made agreed-upon modifications to the trial design for the Phase 3 study (NAV3-33). The Company submitted the modified protocol back to the Agency and initiated the study in December 2021. The pivotal Phase 3 study program will assess joint disease status and monitor patientdetermine Tc99m tilmanocept’s capability to serve as an early predictor of treatment response to therapy.anti-TNFα therapy in patients with RA.

Cardiovascular Disease (“CV”)

In collaboration with researchers at Massachusetts General Hospital, Navidea has completed one and has initiated a secondtwo investigator-initiated clinical studystudies evaluating Tc99m tilmanocept’s ability to enable imaging of atherosclerotic plaques. 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. Non-calcified atherosclerotic plaques include plaques with morphologies indicating a high risk of rupture. Rupture of such plaques causes myocardial infarctions (heart attacks) and a significant portion of ischemic strokes. The studies compared aortic Tc99m tilmanocept uptake imaged by SPECT/CT in clinically asymptomatic subjects with intermediate Framingham Risk Scores (“FRS”) who were infected with Human Immunodeficiency Virus (“HIV”) as compared to healthy, uninfected, FRS and age-matched subjects. Tc99m tilmanocept SPECT/CT images were compared to aortic images of the same subjects obtained by contrast enhanced coronary computed tomography angiography and/or [18F]NaF PET/CT.

A nine-subject study to evaluate diagnostic imaging of emerging atherosclerosis plaque with the Tc99m tilmanocept product dosed subcutaneously is completeSC was performed (ClinicalTrials.gov NCT02542371). The results of this study were presented at two major international meetings (Conference on Retroviruses and Opportunistic Infections (“CROI”) and SNMMI, 2017) and published in early release in the Journal of Infectious Diseases in January 2017 (published in the circulated version, Journal of Infectious Diseases (2017) 215 (8): 1264-1269), confirming that the Tc99m tilmanocept product can both quantitatively and qualitatively target non-calcified plaque in the aortic arch of Acquired Immunodeficiency Syndrome (“AIDS”) patients (supported by NIH/NHLBI Grant 1 R43 HL127846-01). This study was later expanded to include up to 31 participants, and has achieved full enrollment, with a manuscript submitted.

We have also commenced aA second Phase1/Phase 1/2 investigator-initiated study in cooperation with Massachusetts General Hospital in subjects with HIV was initiated that expandsexpanded the original study in both the scope of the drug administration as well as the diagnostic assessment of the subjects. This study will enroll up to 24enrolled both AIDS subjects and healthy controls in imaging non-calcified plaque using IV and SC-administered Tc99m tilmanocept and will expand the initial investigation to the assessment of aortic plaque as well as carotid and coronary arteries. Initial images from this studyanalysis suggested that the SC route of administration led to superior signal-to-background in areas of non-calcified plaque. These results are currently being evaluated.further assessed.

Navidea has also been awarded a $225,000 phase 1 Small Business Technology Transfer grant (1R41HL147640-01A1) entitled Gallium 68 Tilmanocept for PET Imaging of Atherosclerosis Plaques. This grant will supportsupports a research collaboration between Navidea and Dr. Suzanne Lapi of the University of Alabama Birmingham. These efforts will evaluateBirmingham evaluating a mouse model of atherosclerosis. This work has as its aim the evaluation of [68]gallium tilmanocept and various next generation imaging agents for imaging plaques in an animal model of atherosclerosis andvisualizing plaques. Activities began activities in the fourth quarter of 2019. As of January 2022, all images have been acquired with efforts now focused on data analyses.

Kaposi’sKaposi’s Sarcoma

We initiated and completed a study of KS in 2015 (ClinicalTrials.gov NCT022201420) and received additional funding from the National Institutes of Health (“NIH”) in 2016 to continue diagnostic studies in this disease. The new support not only continues the imaging of the cutaneous form of this disease but expands this to imaging of visceral disease via IV administration of Tc99m tilmanocept (NIH/NCI 1 R44 CA192859-01A1; ClinicalTrials.gov NCT03157167). This now-escalated study includes a pathology/biopsy component as well as an imaging component to determine pathology concordance with image assessment. We received Institutional Review Board approval of the clinical protocol and initiated a Phase 1/2 clinical study in KS in 2017. This trial has completed enrollment and imaging. Data and image analysis for this study are ongoing.

Colorectal Cancer (“CRC”) and Synchronous Liver Metastases

During 2017, we initiated an imaging study in subjects with CRC and liver metastases via IV administration of Tc99m tilmanocept. This study was supported through a SBIR grant (NIH/NCI 1 R44 CA1962783-01A1; ClinicalTrials.gov NCT03029988). The trial intended to enroll up to 12 subjects with dose modification. After an interim analysis of the first three completed subjects, a decision was made to not continue with the trial and the study is now closed. An initial presentation took place at SNMMI in June of 2018. An additional report has been submitted to the National Cancer Institute (“NCI”) on the early results of this study. The final study report has been completed and submitted to the FDA.

Nonalcoholic Steatohepatitis

We have concluded a clinical study (ClinicalTrials.gov NCT03332940) that was originally designed to enroll 12 subjects with IV administration of Tc99m tilmanocept and an imaging comparator to identify and quantify the extent of NASH lesions in human patients. A semiquantitative evaluation of the images from the first six subjects indicated that imaging the remaining six subjects planned in the study may not sufficiently further our knowledge of Tc99m tilmanocept imaging in individuals with NASH to justify continuing the study using the current protocol. The study is now complete. Ongoing quantitative analyses of the images from the first six subjects will determine if future studies in subjects with NASH are likely to be productive. Initial results were presented at the NASH Summit in Boston in April 2018, and the results are available on Navidea’s website.

Tuberculosis (“TB”(“TB”)

In April 2019, wethe Company announced that Professor Mike Sathekge, MBChB, M. Med (Nuclear Medicine), PhD, Professor and Head of the Department of Nuclear Medicine in the Faculty of Health Sciences at the University of Pretoria/Steve Biko Academic Hospital, planned to initiate a comparative study evaluating the use of tilmanocept in patients with TB. The purpose of thethis ongoing study is to explore using 68Ga tilmanocept as an aid in TB patient management while contributing to the better understanding of the biology of TB granulomas. The TB granuloma plays multiple roles in tuberculous infection, although much remains unknown about its biology. MacrophagesCD206+ macrophages constitute one of the most abundant cell types in the TB granuloma. Agranulomas. Therefore, a molecular probe such as 68Ga-labeled tilmanocept targeting mannose receptor CD206 expressed on macrophages therefore, holds great promise not only in understanding the behaviorbiology of TB granulomas, but may serve asalso support future development of a tilmanocept-like drug delivery vehicle for delivering therapeutic interventions in the future. Comparing findings on 68Ga tilmanocept PET/CT and FDG PET/CT will contribute to the understanding of the biology of TB granuloma.granulomas. Navidea has provided tilmanocept for use in this study, and several subjects have been injected and imaged to date. Successful completion of this study could lead tosupport an extended claim of 68Ga-tilmanocept.

Biomarker Application and Qualification

In November 2017, the Company commenced the qualification of the biomarker CD206 with the FDA Biomarker Section of The Center for Drug Evaluation and Research (“CDER”). As per FDA protocol, Navidea submitted a draft letter of intent (“LOI”) to CDER prior to the November 2017 meeting. According to the CDER directive, “the Biomarker Qualification Program was established to support the CDER’s work with external stakeholders to develop biomarkers that aid in the drug development process. Through the FDA’s Biomarker Qualification Program, an entity may request regulatory qualification of a biomarker for a particular context of use (“COU”) in drug development.” Following the meeting with the FDA, and because of Navidea’s data sets and the general external publication database, Navidea, in conjunction with FDA, is now reviewing the LOI with the FDA’s recommended consultants. Navidea has revised the LOI draft strategy in order to expedite the application process. In March 2018, Navidea had a follow-up meeting with the FDA’s assigned strategist, during which the potential to further narrow the LOI elements was reviewed. Navidea is continuing the process of finalizing the COU LOI and providing the background data sets for qualification review with the FDA/CDER. Additional meetings have taken place and the pursuit of this qualification is ongoing.

Manocept Platform – In-Vitro and Pre-Clinical Immunotherapeutics Data

The therapeuticCompany has been developing Manocept platform drug delivery model enables the Company to leverage its technology over many potential disease applicationsconstructs that carry various payloads including doxorubicin and dexamethasone. Chemical synthesis techniques have advanced considerably, resulting in more robust and reproducible synthesis protocols that provide products with multiple partners simultaneously without significant capital outlays. To date, the Company has developed two lead families of therapeutic products. The MT-1000 series is designed to deplete activated macrophages via apoptosis and/or alter the phenotype of macrophages. The MT-2000 series is designed to modulate activated macrophages from a classically activated phenotype to the alternatively activated phenotype. Both families have been tested in a number of disease models in rodents.

We have already reported on the peripheral infectious disease aspects of KS, including HIV and HHV8 (CROI, Boston 2016, and KS HHV8 Summit Miami 2015). As noted, we continue this work funded by the NIH/NIAID and NCI. The Company has completed preclinical studies employing both MT 1000-class and 2000-class therapeutic conjugates of Manocept. The positive results from these studies arechemical attributes indicative of Manocept’s specific targeting supported byenhanced in vivo activity. The most advanced drug delivery construct carries a doxorubicin payload and is now in its strong binding affinitythird generation of chemical synthesis protocol design. This third-generation doxorubicin carrying construct has been extensively evaluated in human macrophage cell culture assays and in three experiments using syngeneic mouse cancer models. These experiments show that at treatment doses below what is required to CD206 receptors. This high degreekill macrophages, the doxorubicin-carrying constructs dramatically alters the immunological behavior of specificity is a foundationmacrophages, making them more proinflammatory. In one of the potential forsyngeneic mouse tumor experiments, the MAN-DOX construct significantly synergized the activity of another anticancer therapy producing anti-tumor activity that was greater than either treatment alone. Results from this technologystudy were presented at the New York Academy of Sciences Frontiers in Cancer Immunotherapy 2021 conference on May 14, 2021. Near-term experiments with the Manocept doxorubicin construct include further studies in macrophage cell culture, additional syngeneic mouse tumor models, and a toxicity study in rats. Work involving a second generation Manocept dexamethasone-carrying construct and efforts developing Manocept constructs with different payloads is ongoing. Three new Manocept constructs carrying payloads other than doxorubicin or dexamethasone have progressed to be usefulevaluations in treating diseases linked to the over-activation of macrophages. This includes various cancers as well as autoimmune, infectious, CV, and central nervous system (“CNS”) diseases.macrophage cell culture assays.

Kaposi’sKaposi’s Sarcoma

The novel MT-1000MAN-DOX class constructs are designed to specifically deliver doxorubicin, a chemotoxin, which can kill KS tumor cells and their tumor-associated macrophages, potentially altering the course of cancer. We have received additional funding to continue therapeutic studies in this disease with the goal of completing an investigational new drug (“IND”) submission for a Manocept construct (MT-1000(MAN-DOX class of compounds) consisting of tilmanocept linked to doxorubicin for the treatment of KS. The first part of theEfforts supported by this grant now complete, supported analyses including in vitro and cell culture studies, to be followed by Parts 2 and 3 FDA-required preclinical animal testing studies. The information from these studies will be combined with other information in an IND application that will be submitted to the FDA requesting permission to begin testing the compound in selected KS subjects (supported by NIH/(NIH/NCI 1 R44 CA206788-01). are now complete. The results greatly advanced our knowhow for robustly and reproducibly synthesizing MAN-DOX and related constructs carrying other payloads. The grant-supported efforts were presented at the New York Academy of Sciences Frontiers in Cancer Immunotherapy 2021.

Other Immunotherapeutic Applications

The Company continues to evaluate emerging data in other disease states to define areas of focus, development pathways and partnering options to capitalize on the Manocept platform, including ongoing studies in KS, RA and infectious diseases. The immuno-inflammatory process is remarkably complex and tightly regulated with indicators that initiate, maintain and shut down the process. Macrophages are immune cells that play a critical role in the initiation, maintenance, and resolution of inflammation. They are activated and deactivated in the inflammatory process. Because macrophages may promote dysregulation that accelerates or enhances disease progression, diagnostic and therapeutic interventions that target macrophages may open new avenues for controlling inflammatory diseases. There can be no assurance that further evaluation or development will be successful, that any Manocept platform product candidate will ultimately achieve regulatory approval, or if approved, the extent to which it will achieve market acceptance.

Risks Associated with Our Business and this Offering

Our business and our ability to implement our business strategy are subject to numerous risks, as more fully described in the section of this prospectus entitled “Risk Factors” and under similarly titled headings of the documents incorporated herein by reference. You should read these risks before you invest in our securities. We may be unable, for many reasons, including those that are beyond our control, to implement our business strategy. In particular, risks associated with our business and this offering include:

Corporate Information

Our corporate headquarters are located at 4995 Bradenton Avenue, Suite 240, Dublin, Ohio 43017-3552, and our telephone number is (614) 793-7500. We maintain a website at www.navidea.com, to which we regularly post copies of our press releases as well as additional information about us. The information contained on, or that can be accessed through, our website is not a part of this prospectus. We have included our website address in this prospectus solely as an inactive textual reference.

Our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and all amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”“Exchange Act”), are available free of charge through the investor relations page of our internet website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

SUMMARY OF THE OFFERING

The following summary describes the principal terms of the rights offering, but is not intended to be complete. See the information under the heading “The Rights Offering” in this prospectus for a more detailed description of the terms and conditions of the rights offering.

Securities Offered

We are distributing , at no charge, to holders of our common stock, and to holders of certain of our outstanding warrants, Series D preferred stock and Series E preferred stock, non-transferrable subscription rights to purchase up to an aggregate of ● shares of our common stock. Each of such eligible holders will receive ●  subscription right for each share of common stock owned or deemed to be owned as of 4:00 p.m., New York City time, on ●, 2022; provided, that, the rights may only be exercised for a maximum of the lesser of ● shares or $35.0 million of subscription proceeds.

Participation of Certain Holders of Warrants and Preferred Stock

The holders of the Underwriter Warrants, Series D preferred stock and Series E preferred stock have the right to participate in this rights offering. Each of such eligible holders will receive ● subscription right for each share of common stock that such holder’s Underwriter Warrants are exercisable for and that such holder’s Series D or Series E preferred stock is convertible into. A total of ●  subscription rights will be issued to holders of the Underwriter Warrants, Series D preferred stock and Series E preferred stock.

Basic Subscription Privilege

The basic subscription privilege of each subscription right will entitle you to purchase ● share of our common stock at a subscription price of $● per share.

Over-Subscription Privilege

If you fully exercise your basic subscription privilege and basic subscription rights are exercised for an amount less than $●, you may also exercise an over-subscription right to purchase additional shares of common stock that remain unsubscribed at the expiration of the rights offering, subject to the availability and pro rata allocation of shares among stockholders exercising this over-subscription right.

Minimum Offering Requirement

We will not complete the rights offering unless we receive aggregate subscriptions of at least $● million.

Record Date

●, 2022.

Expiration Date of the Rights Offering

5:00 p.m., Eastern time, on ●, 2022.

Subscription Price

$ ● per share, payable in cash. To be effective, any payment related to the exercise of a right must clear prior to the expiration date of the rights offering.

Use of Proceeds

We are conducting the rights offering for funding the Company’s pivotal Phase 3 trial for RA (NAV3-33), obtaining regulatory approvals, working capital, and for general corporate purposes. See “Use of Proceeds” for a more detailed description of the intended use of proceeds from the rights offering.

Non-Transferability of Rights

The subscription rights granted to you may be exercised only by you, and, therefore, you may not sell, transfer or assign your subscription rights to anyone else.

Material U.S. Federal Income Tax Consequences

Although the authorities governing transactions such as the rights offering are complex and unclear in certain respects, we believe and intend to take the position that the distribution of subscription rights to you with respect to your shares of our common stock should generally be treated, for U.S. federal income tax purposes, as a non-taxable distribution. If you are a U.S. Person (as defined below), see “Material U.S. Federal Income Tax Consequences” beginning on page 28. You should consult your tax advisor as to the particular consequences to you of the rights offering.

TheShares To Be Outstanding After the Rights Offering

As of June 15, 2020, there were 23,525,396January 31, 2022, 30,299,054 shares of our common stock outstanding (16,421,200were issued and outstanding. Assuming no additional shares heldof common stock are issued by non-affiliates) excluding the 4,586,790 shares offered that have been issued or may be issuable to Keystone Capital pursuantus prior to the Purchase Agreement).  If allexpiration of such 4,586,790the rights offering, and assuming ● shares of our common stock offered hereby wereare issued in the rights offering through the exercise of subscription rights, we anticipate that ● shares of our common stock will be issued and outstanding asfollowing the completion of the date hereof, such shares would represent 16.32% of the total common stock outstanding or 21.83% of the non-affiliate shares of common stock outstanding as of the date hereof. rights offering.

The number of shares of our common stock ultimately offered for sale by Keystone Capital is dependent uponoutstanding prior to and immediately after this rights offering, as set forth above, excludes the numberfollowing potentially dilutive securities as of shares acquired by Keystone Capital upon conversion of the Series C Preferred.January 31, 2022:

Risk Factors

Investing in our common stock involves a high degree of risk. You should carefully read and consider the information on page 17 of this prospectus set forth under the headings “Risk Factors” and all other information set forth in this prospectus and the documents incorporated herein by reference before deciding to invest in our common stock.

Dividend Policy

We have never declared or paid any cash dividends to the holders of our common stock and we do not expect to pay cash dividends in the foreseeable future. We currently outstandingintend to retain any earnings for use in connection with the expansion of our business and (ii) 4,238,401for general corporate purposes.

NYSE American Symbol for Common Stock

NAVB

Transfer Agent and Registrar

Continental Stock Transfer & Trust Company, LLC

QUESTIONS AND ANSWERS ABOUT THE RIGHTS OFFERING

The following are examples of what we anticipate may be common questions about the rights offering. The answers are based on selected information included elsewhere in this prospectus. The following questions and answers do not contain all of the information that may be important to you and may not address all of the questions that you may have about the rights offering. This prospectus and the documents incorporated by reference into this prospectus contain more detailed descriptions of the terms and conditions of the rights offering and provide additional information about us and our business, including potential risks related to the rights offering, the shares of common stock issuable upon conversionoffered hereby, and our business. We urge you to read this entire prospectus and the documents incorporated by reference into this prospectus.

Why are we conducting the rights offering?

We are conducting the offering to raise capital that we intend to use for funding the Company’s pivotal Phase 3 trial for Rheumatoid Arthritis (NAV3-33), obtaining regulatory approvals, working capital, and general corporate purposes.

What is the rights offering?

We are distributing to holders of our common stock, and holders of certain of our outstanding warrants, Series D preferred stock and Series E preferred stock, at no charge, non-transferable subscription rights to purchase shares of Series C Preferred. All 4,586,790 Sharescommon stock. On the record date, ●, 2022, you will receive ● subscription right for each whole share of common stock that you owned or were deemed to own as of 4:00 p.m., Eastern Time, on ●, 2022. Each subscription right will entitle the holder to a basic subscription privilege and an over-subscription privilege.

What is the basic subscription privilege?

A basic subscription privilege will entitle you to purchase ● share of common stock at the subscription price. For example, if you owned or were deemed to own100 shares of common stock on the record date, you will receive subscription rights to purchase ● shares of common stock. You may exercise all or a portion of your basic subscription privilege or you may choose not to exercise any basic subscription privilege at all.

If you are being offereda record holder, the number of common shares you may purchase pursuant to your basic subscription privilege is indicated on the subscription rights certificate. If you hold your common stock, Underwriter Warrants, Series D preferred stock or Series E preferred stock in the name of a broker, dealer, bank, or other nominee who uses the services of the Depository Trust Company, or DTC, you will not receive a subscription rights statement. Instead, DTC will issue ● subscription right to your nominee record holder for each share of our common stock that you own or are deemed to own as of the record date. If you are not contacted by your nominee, you should contact your nominee as soon as possible.

See “The Rights Offering — Limitation on the Purchase of Shares of Common Stock” for a description of certain limitations on purchase.

What is the over-subscription privilege?

If you exercise your basic subscription privilege in full, you may also choose to exercise your over- subscription privilege to purchase shares of common stock that the other rights holders do not purchase through the exercise of their basic subscription privilege. You should indicate on your subscription rights certificate, or the form provided by your nominee if your shares are held in the name of a nominee, the aggregate amount you would like to apply to purchase shares of common stock pursuant to your over-subscription privilege.

If sufficient shares of common stock are available, we will seek to honor your over-subscription request in full. If over- subscription requests exceed the number of shares of common stock available, however, we will allocate the available shares of common stock pro-rata among the rights holders exercising the over-subscription privilege in proportion to the number of shares of our common stock each of those rights holders owned on the record date, relative to the number of shares owned on the record date by all rights holders exercising the over-subscription privilege. If this prospectus. pro-rata allocation results in any rights holders receiving a greater number of shares of common stock than the rights holder subscribed for pursuant to the exercise of the over-subscription privilege, then such record holder will be allocated only that number of shares of common stock for which the record holder oversubscribed, and the remaining shares of common stock will be allocated among all other rights holders exercising the over-subscription privilege on the same pro rata basis described above. The proration process will be repeated until all shares of common stock have been allocated. See “The Rights Offering — Limitation on the Purchase of Shares of Common Stock” for a description of certain limitations on purchase.

To properly exercise your over-subscription privilege, you must deliver to the Subscription Agent the subscription payment related to your over-subscription privilege before the rights offering expires. See “The Rights Offering — The Subscription Rights — Over-Subscription Privilege.” To the extent you properly exercise your over-subscription privilege for a number of shares of common stock that exceeds the number of unsubscribed shares of common stock available to you, any excess subscription payments will be returned to you as soon as practicable after the expiration of the rights offering, without interest or penalty.

Our Subscription Agent for the rights offering will determine the over-subscription allocation based on the formula described above.

Will fractional shares be issued upon exercise of subscription rights?

No. We will not issue fractional shares of common stock in the rights offering. Any excess subscription payments received by the Subscription Agent will be returned as soon as practicable after expiration of the rights offering, without interest or penalty.

What effect will the rights offering have on our outstanding common stock?

On January 31, 2022, 30,299,054 shares of our common stock were outstanding. Assuming no additional shares of common stock are issued by us prior to the expiration of the rights offering, assuming this rights offering is fully subscribed for the maximum number of shares of common stock available, approximately ● shares of our common stock will be issued and outstanding. The exact number of shares of common stock that we will issue in this rights offering will depend on subscription price and the number of shares of common stock that are subscribed for in the rights offering.

How was the subscription price formula determined?

Our board of directors determined the subscription price taking into consideration, among other things, the following factors:

In conjunction with the review of these factors, our board of directors reviewed our history and prospects, including our past and present earnings and cash requirements, our prospects for the future, the outlook for our industry and our current financial condition. Our board of directors believes that the subscription price should be designed to provide an incentive to our current stockholders to participate in the rights offering and exercise their basic subscription privilege and their over-subscription privilege.

The subscription price does not necessarily bear any relationship to any established criteria for value. You should not consider the subscription price as an indication of actual value of the Company or our common stock. We cannot assure you that the market price of our common stock will not decline during or after the rights offering. You should obtain a current price quote for our common stock before exercising your subscription rights and make your own assessment of our business and financial condition, our prospects for the future, and the terms of this rights offering. Once made, all exercises of subscription rights are irrevocable.

Am I required to exercise all of the basic subscription privilege I receive in the rights offering?

No. You may exercise any number of your basic subscription rights, or you may choose not to exercise any basic subscription privilege. If you do not exercise any basic subscription privilege, the number of shares of our common stock you own will not change. However, if you choose not to exercise your basic subscription privilege in full, your proportionate ownership interest in the Company will decrease. If you do not exercise your basic subscription privilege in full, you will not be entitled to exercise your over-subscription privilege.

How soon must I act to exercise my subscription rights?

If you received a subscription rights certificate and elect to exercise any or all of your subscription rights, the Subscription Agent must receive your completed and signed subscription rights certificate and payment for both your basic subscription privilege and any over-subscription privilege you elect to exercise before the rights offering expires on ●, 2022, at 5:00 PM Eastern Time. If you hold your common stock, Underwriter Warrants, Series D preferred stock or Series E preferred stock in the name of a broker, dealer, custodian bank, or other nominee, your nominee may establish a deadline before the expiration of the rights offering by which you must provide it with your instructions to exercise your subscription rights, along with the required subscription payment.

May I transfer my subscription rights?

No. The subscription rights may be exercised only by the eligible stockholders or warrant holders to whom they are distributed, and they may not be sold, transferred, assigned or given away to anyone else, other than by operation of law. As a result, a subscription rights certificate may be completed only by the stockholder or warrant holder who receives the statement. The subscription rights will not be listed for trading on any stock exchange or market.

Is there any back-stop or standby purchase commitment in place to purchase rights that are not exercised in the offering?

No, there is not a back-stop or standby purchase commitment in place to purchase rights that are not exercised in the offering.

Does Navidea need to achieve a minimum subscription amount to complete the rights offering?

Yes. We will not complete the rights offering unless we receive aggregate subscriptions of at least $ ● million (or ● shares).] There are no other conditions to completing the rights offering.

If the rights offering is not completed, will my subscription payment be refunded to me?

Yes. The Subscription Agent will hold all funds it receives in escrow until completion of the rights offering. If the rights offering is not completed, the Subscription Agent will return promptly, without interest, all subscription payments. We reserve the right to terminate the offering at any time if, due to market conditions or otherwise, our board of directors deems it advisable not to proceed with the rights offering.

Will our directors and executive officers participate in the rights offering?

To the extent they hold common stock, Series D preferred stock or Series E preferred stock as of the record date, our directors and executive officers will be entitled to participate in the rights offering on the same terms and conditions applicable to other rights holders. None of our directors or executive officers has entered into any binding commitment or agreement to exercise subscription rights received in the rights offering.

John K. Scott, Jr., who is a member of our board of directors, beneficially owns 10,239,947 shares of common stock, representing 31.5% of the outstanding shares, including shares issuable upon the conversion, if any, of Series E preferred stock. If there are sufficient shares that are not purchased pursuant to the basic subscription privilege and Mr. Scott fully or partially exercises his over-subscription privilege, Mr. Scott could become the holder of a majority of the outstanding shares of our common stock. In this event, Mr. Scott could control the election of all members of our board of directors and could control the results of all stockholder votes.

Has the board of directors made a recommendation to stockholders regarding the rights offering?

No. Our board of directors is not making a recommendation regarding your exercise of the subscription rights. You should make your decision based on your assessment of our business and financial condition, our prospects for the future, the terms of the rights offering and the information contained in this prospectus. See “Risk Factors” for discussion of some of the risks involved in investing in our securities.

How do I exercise my subscription rights?

If you hold your common stock, Underwriter Warrants, Series D preferred stock or Series E preferred stock in your name and not through a broker, dealer, bank, or other nominee) on the record date and you wish to participate in the rights offering, you must deliver a properly completed and signed subscription rights certificate, together with payment of the subscription price for both your basic subscription privilege and any over-subscription privilege you elect to exercise, to the Subscription Agent before 5:00 PM Eastern Time, on ●, 2022. If you are exercising your subscription rights through your broker, dealer, bank, or other nominee, you should promptly contact your broker, dealer, bank, or other nominee and submit your subscription documents and payment for the shares of common stock subscribed for in accordance with the instructions and within the time period provided by your broker, dealer, bank or other nominee.

What if my shares are held in “street name”?

If you hold your common stock, Underwriter Warrants, Series D preferred stock or Series E preferred stock in the name of a broker, dealer, bank, or other nominee, then your broker, dealer, bank, or other nominee is the record holder of the shares you own. The record holder must exercise the subscription rights on your behalf. Therefore, you will need to have your record holder act for you.

If you wish to participate in this rights offering and purchase shares of common stock, please promptly contact the record holder of your shares. We will ask the record holder, who may be your broker, dealer, bank, or other nominee, to notify you of this rights offering.

What form of payment is required?

You must timely pay the full subscription price pursuant to the exercise of subscription rights by delivering to the Subscription Agent a cashier’s check, certified check or bank draft drawn on a U.S. bank or a wire transfer of immediately available funds.

When will I receive my new shares of common stock?

The Subscription Agent will arrange for the issuance of the common stock as soon as practicable after the expiration of the rights offering, payment for the shares of common stock subscribed for has cleared, and all prorating calculations and reductions contemplated by the terms of the rights offering have been effected. All shares that you purchase in the rights offering will be issued in book-entry, or uncertificated, form meaning that you will receive a direct registration (DRS) account statement from our transfer agent reflecting ownership of these securities if you are a holder of record of shares. If you hold your shares in the name of a broker, dealer, bank, or other nominee, DTC will credit your account with your nominee with the securities you purchase in the rights offering.

After I send in my payment and subscription rights certificate to the Subscription Agent, may I cancel my exercise of Subscription Rights?

No. Exercises of subscription rights are irrevocable unless the rights offering is terminated, even if you later learn information that you consider to be unfavorable to the exercise of your subscription rights. You should not exercise your subscription rights unless you are certain that you wish to participate in the rights offering.

How much will Navidea receive from the rights offering?

Assuming the rights offering is fully subscribed, including any over-subscription privilege, we estimate that the net proceeds from the rights offering will be approximately $34.8 million, after deducting fees and expenses payable by us.

Are there risks in exercising my subscription rights?

Yes. The exercise of your subscription rights involves risks. Exercising your subscription rights involves the purchase of additional shares of our common stock and you should consider this investment as carefully as you would consider any other investment. We cannot assure you that the market price of our common stock will exceed the subscription price, nor can we assure you that the market price of our common stock will not further decline after the rights offering. We also cannot assure you that you will be able to sell shares of our common stock purchased in the rights offering at a price equal to or greater than the subscription price. In addition, you should carefully consider the risks described under the heading “Risk Factors” for discussion of some of the risks involved in investing in our securities.

Can the board of directors terminate or extend the rights offering?

Yes. Our board of directors may decide to terminate the rights offering at any time and for any reason before the expiration of the rights offering. We also have the right to extend the rights offering for period not to exceed 30 days. We do not presently intend to extend the rights offering. We will notify rights holders if the rights offering is terminated or extended by issuing a press release.

If the rights offering is not completed or is terminated, will my subscription payment be refunded to me?

Yes. The Subscription Agent will hold all funds it receives in a segregated bank account until completion of the rights offering. If we cancel the offering, you will receive a refund of the money you have advanced, without interest. If you own stock or warrants in “street name,” it may take longer for you to receive your subscription payment because the Subscription Agent will return payments through the record holder of your stock or warrants.

How do I exercise my subscription rights if I live outside the United States?

The Subscription Agent will hold subscription rights certificates for stockholders having addresses outside the United States. To exercise subscription rights, foreign stockholders must notify the subscription agent and timely follow other procedures described in the section entitled “The Rights Offering — Foreign Stockholders”.

What fees or charges apply if I purchase shares of our common stock?

We are not charging any fee or sales commission to issue subscription rights to you or to issue shares to you if you exercise your subscription rights. If you exercise your subscription rights through the record holder of your shares, you are responsible for paying any fees your record holder may charge you.

What are the U.S. federal income tax consequences of exercising subscription rights?

The U.S. federal income tax consequences of the rights offering will depend on whether the rights offering is part of a “disproportionate distribution.” We intend to take the reporting position that the subscription rights issued to common shareholders pursuant to the rights offering (a) are not part of a “disproportionate distribution” and (b) will not be a taxable distribution with respect to your existing securities. The disproportionate distribution rules are complicated, however, and their application is uncertain, and thus we are unable to obtain a definitive tax counsel opinion regarding the application of such rules. The position we are taking is not binding on the Internal Revenue Service (“IRS”) or the courts and it is possible that the IRS could successfully challenge our reporting position and assert that the rights offering is a taxable distribution. You should consult your tax advisor as to the tax consequences of the rights offering in light of your particular circumstances. For a more detailed discussion, see “Certain U.S. Federal Income Tax Consequences” on page 28.

To whom should I send my forms and payment?

If your shares are held in the name of a broker, dealer or other nominee, then you should send your subscription documents, rights certificate, notices of guaranteed delivery and subscription payment to that record holder. If you are the record holder, then you should send your subscription documents, rights certificate, notices of guaranteed delivery and subscription payment by registered mail, return receipt requested or courier service to:

[Subscription Agent Name]

[Mailing Address]

You are solely responsible for completing delivery to the Subscription Agent of your subscription documents, rights certificate and payment. We urge you to allow sufficient time for delivery of your subscription materials to the Subscription Agent.

Whom should I contact if I have other questions?

If you have any questions about the rights offering, including questions about subscription procedures and requests for additional copies of this prospectus or other documents, please contact the information agent,                     , at or by email at .

RISK FACTORS

Investing in our securities involves a high degree of risk. Prior to making a decision about investing in our securities, you should carefully consider the specific risk factors discussedset forth below, the other information contained in this prospectus and any other risks described in our filings with the sectionsSEC, including but not limited to under the section entitled “Risk Factors”“Risk Factors” contained in our annual report onForm 10-K for the fiscal year ended December 31, 2019 under the heading “Item 1A. Risk Factors,” and2020, as describedamended or may be described in any subsequentsupplemented by subsequently filed quarterly reportreports on Form 10-Q underand Current Reports on Form 8-K. Any of these risks could materially and adversely affect our business, financial condition, results of operations, liquidity and cash flows. In such a case, you may lose all or part of your investment. The risks described below and referenced above are not the heading “Item 1A. Risk Factors,” as well as in any applicable prospectus supplementonly risks facing us. Additional risks and containeduncertainties not currently known to us or those we currently view to be contained inimmaterial may also materially adversely affect our filings with the SECbusiness, financial condition, results of operations, liquidity and incorporated by reference in this prospectus, together with all of the other information contained in this prospectus, or any applicable prospectus supplement. For a description of these reports and documents, and information about where you can find them, see “Where You Can Find More Information” and “Incorporation of Certain Information by Reference.”cash flows. If any of the risks or uncertainties described in this prospectus or our SEC filings or any prospectus supplement or anysuch additional risks and uncertainties actually occur, our business, financial condition andor results of operations could be materially and adversely affected.affected, which could cause our actual operating results to differ materially from those indicated or suggested by forward-looking statements made in this prospectus or our SEC filings or presented elsewhere by management from time to time. In that case, the trading price of our securitiescommon stock could decline and you mightcould lose all or part of your investment. Please also see “Special Note Regarding Forward-Looking Statements” beginning on page 2.

Risks Related to this Rights Offering and Our CommonStock

Our failure to maintain continued compliance with the listing requirements of the NYSE American exchange could result in the delisting of our common stock.

Our common stock has been listed on the NYSE American since February 2011. The rules of NYSE American provide that shares be delisted from trading in the event the financial condition and/or operating results of the Company appear to be unsatisfactory, the extent of public distribution or the aggregate market value of the Common Stock has become so reduced as to make further dealings on the NYSE American inadvisable, the Company has sold or otherwise disposed of its principal operating assets, or has ceased to be an operating company, or the Company has failed to comply with its listing agreements with the NYSE American. For example, the NYSE American may consider suspending trading in, or removing the listing of, securities of an issuer that has stockholders’ equity of less than (i) $2.0 million if such issuer has sustained losses from continuing operations and/or net losses in two of its three most recent fiscal years, (ii) $4.0 million if such issuer has sustained losses from continuing operations and/or net losses in three of its four most recent fiscal years, and (iii) $6.0 million if such issuer has sustained losses from continuing operations and/or net losses in its five most recent fiscal years.

On January 28, 2022, we received a deficiency letter from the NYSE American stating that we were not in compliance with Section 1003(a)(iii) of the NYSE American Company Guide. The deficiency letter noted that we had stockholders’ equity of $4.1 million as of September 30, 2021, and had reported net losses from continuing operations in our five most recent fiscal years ended December 31, 2020.

We are required to submit a plan to the NYSE American by February 28, 2022 advising of actions we have taken or will take to regain compliance with the continued listing standards by July 28, 2023. We intend to submit a plan by the deadline. If we fail to submit a plan or if our plan is not accepted, or if we do not make progress consistent with the plan, or if we fail to regain compliance by the deadline, the NYSE American may commence delisting procedures.

Our common stock will continue to be listed on the NYSE American while we attempt to regain compliance with the listing standard noted, subject to our compliance with other continued listing requirements. Our common stock will continue to trade under the symbol “NAVB,” but will have an added designation of “.BC” to indicate that we are not in compliance with the NYSE American’s listing standards. The NYSE American notification does not affect our business operations or our SEC reporting requirements and does not conflict with or cause an event of default under any of our material agreements.

The delisting of our common stock from the NYSE American likely would reduce the trading volume and liquidity in our common stock and may lead to decreases in the trading price of our common stock. The delisting of our common stock may also materially impair our stockholders’ ability to buy and sell shares of our common stock. In addition, the delisting of our common stock could significantly impair our ability to raise capital.

As a result of the rights offering, a major stockholder may become the majority holder of our common stock and may have the ability to control the election of directors and all other stockholder votes.

John K. Scott, Jr., who is a member of our Board of Directors, beneficially owns 10,239,947 shares of common stock, representing 31.5% of the outstanding shares. If there are sufficient shares that are not purchased pursuant to the basic subscription privilege and Mr. Scott fully or partially exercises his over-subscription privilege, Mr. Scott could become the holder of a majority of the outstanding shares of our common stock. In this event, Mr. Scott could control the election of all members of our Board of Directors and could control the results of all stockholder votes.

The subscription price determined for this rights offering is not necessarily an indication of the value of your investment.our common stock.

The issuancesubscription price is not necessarily related to our book value, results of operations, cash flows, financial condition or the future market value of our common stock. We cannot assure you that you will be able to sell shares purchased in this rights offering at a price equal to or greater than the subscription price. We do not intend to change the subscription price in response to changes in the market price of our common stock prior to Keystone Capital may cause substantial dilution to our existing stockholders and the saleclosing of the rights offering.

such Shares acquired by Keystone Capital couldThe rights offering may cause the price of our common stock to decline.

We are registering for sale (i) 348,389 shares of common stock and (ii) up to 4,238,401 shares of common stock issuable upon conversion of shares of our Series C Preferred. The number of Shares ultimately offered for sale by Keystone Capital under this prospectus is dependent upon the number of Shares issued to Keystone Capital upon conversion of the Series C Preferred. Depending on a variety of factors, including market liquidity of our common stock, the issuance of Shares to Keystone Capital may cause the trading price of our common stock to decline.

Keystone Capital is irrevocably bound to purchase all of the Series C Preferred and, following receipt of Shares upon the conversion thereof, may sell all, some or none of such Shares. The sale of a substantial number of Shares of our common stock by Keystone Capital in this offering, or anticipation of such sales, could cause the trading price of our common stock to decline or make it more difficult for us to sell equity or equity-related securities in the future at a time and at a price that we might otherwise desire.

Because we do not expect to pay dividends on our common stock in the foreseeable future, stockholders will only benefit from owning common stock if it appreciates.

We have paid no cash dividends on any of our common stock to date, and we currently intend to retain our future earnings, if any, to fund the development and growth of our business. As a result, with respect to our common stock, we do not expect to pay any cash dividends in the foreseeable future, and payment of cash dividends, if any, will also depend on our financial condition, results of operations, capital requirements and other factors and will be at the discretion of our Board of Directors. Furthermore, we are subject to various laws and regulations that may restrict our ability to pay dividends and we may in the future become subject to contractual restrictions on, or prohibitions against, the payment of dividends. Due to our intent to retain any future earnings rather than pay cash dividends on our common stock and applicable laws, regulations and contractual obligations that may restrict our ability to pay dividends on our common stock , the success of your investment in our common stock will likely depend entirely upon any future appreciation and there is no guarantee that our common stock will appreciate in value.

The KEYSTONE Capital Transaction

General

On May 6, 2020, Navidea entered into the Purchase Agreement with Keystone Capital, pursuant to which Navidea agreed to issue to Keystone Capital 420,000 shares of newly-designated Series C Preferred stock for an aggregate purchase price of $4.2 million. Of the $4.2 million aggregate gross proceeds, as of the date of this registration statement, we have received $500,000 as payment for Series C Preferred shares, which were subsequently converted into 348,389 Shares of common stock.

The Series C Preferred have the rights set forth in the Series C Preferred Certificate (as defined below). The sale of Series C Preferred to Keystone Capital is being conducted in reliance on the exemption from registration afforded by Section 4(a)(2) of the Securities Act and Rule 506 of Regulation D promulgated under the Securities Act and corresponding provisions of state securities or “blue sky” laws.

Pursuant to the Purchase Agreement, Keystone Capital is irrevocably bound to purchase the Series C Preferred in amounts to be determined by it in one or more closings (each, a “Call Closing”) on or before November 6, 2020 (the “Purchase Period”), provided that all of the shares of Series C Preferred under the Purchase Agreement must be purchased by Keystone Capital on or prior to such date.

Under the Purchase Agreement, Navidea also agreed to use its commercially reasonable best efforts to register under the Securities Act the resale of the Shares that may be issued to Keystone Capital upon conversion of the Series C Preferred, and to maintain the effectiveness of such registration statement until the earlier of when such Shares are sold or until all of the Shares may be sold without restriction under Rule 144 under the Securities Act.

As of June 15, 2020, there were 23,525,396 shares of our common stock outstanding (16,421,200 shares held by non-affiliates) excluding the 4,586,790 Shares that have been issued or may be issuable to Keystone Capital pursuant to the Purchase Agreement.  If all of such 4,586,790 Shares offered hereby were issued and outstanding as of the date hereof, such shares would represent 16.32% of the total common stock outstanding or 21.83% of the non-affiliate shares of common stock outstanding as of the date hereof.

Pursuant to the Purchase Agreement, we are registering 4,238,401 Shares under the Securities Act, which includes shares of common stock that may be issuable to Keystone Capital after this registration statement is declared effective under the Securities Act upon conversion of Series C Preferred, as well as 348,389 Shares that have already been issued to Keystone Capital upon its conversion of 50,000 shares of Series C Preferred prior to the date of this registration statement. All 4,586,790 Shares are being offered pursuant to this prospectus.

Description of Series C Preferred

For a description of the Series C Preferred, see “Description of Securities—Description of Series C Preferred.”

No Short-Selling or Hedging by Keystone Capital

Keystone Capital has agreed that neither it nor any of its affiliates acting on its behalf or pursuant to any understanding with it, will execute any “short sales” of Navidea’s common stock as defined in Rule 200 of Regulation SHO under the Exchange Act during the Purchase Period.

Effect of Performance of the Purchase Agreement on Our Stockholders

The Purchase Agreement does not limit the ability of Keystone Capital to convert the Series C Preferred or to sell any or all of the 4,586,790 Shares registered in this offering. The sale by Keystone Capital of a significant number of Shares registered in this offering at any given time could causeDepending upon the market price of our common stock to decline and/or to be highly volatile.  Keystone Capital may ultimately acquire all, some or noneat the time of our announcement of the 4,238,401 sharesrights offering and its terms, including the subscription price, together with the number of Shares not yet issued but registered for resale in this offering.  After it has acquired such Shares, it may sell all, some or none of such Shares. Therefore, sales of Series C Preferred, and the issuance of the underlying shares of common stock we could issue if the rights offering is completed, may result in a decrease in the market price of our common stock. This decrease may continue after the completion of the rights offering. If that occurs, your purchase of shares of our common stock in the rights offering may be at a price greater than the prevailing market price.

Because you may not revoke or change your exercise of the subscription rights, you could be committed to Keystone Capital by usbuying shares above the prevailing market price at the time the rights offering is completed.

Once you exercise your subscription rights, you may not revoke or change the exercise. The market price of our common stock may decline before the subscription rights expire. If you exercise your subscription rights, and, afterwards, the market price of our common stock decreases below the subscription price, you will have committed to buying shares of our common stock at a price above the prevailing market price and could have an immediate unrealized loss.

Our common stock is traded on the NYSE American Exchange under the symbol “NAVB,” and the closing sale price of our common stock on February 10, 2022 was $0.91 per share. There can be no assurances that the market price of our common stock will equal or exceed the subscription price at the time of exercise or at the expiration of the subscription rights offering period.

You may not be able to resell any shares of our common stock that you purchase pursuant to the Purchase Agreement alsoexercise of subscription rights immediately upon expiration of the subscription rights offering period or be able to sell your shares at a price equal to or greater than the subscription price.

If you exercise subscription rights, you may resultnot be able to resell the common stock purchased by exercising your subscription rights until you, or your broker, custodian bank or other nominee, if applicable, have received those shares. Moreover, you will have no rights as a shareholder of the shares you purchased in substantial dilutionthe rights offering until we issue the shares to you. Although we will endeavor to issue the interestsshares as soon as practicable after completion of other holdersthe rights offering, including the guaranteed delivery period and after all necessary calculations have been completed, there may be a delay between the expiration date of the rights offering and the time that the shares are issued. In addition, we cannot assure you that, following the exercise of your subscription rights, you will be able to sell your common stock at a price equal to or greater than the subscription price.

If you do not exercise your subscription rights in full, your percentage ownership and voting rights in Navidea will experience dilution.

If you choose not to exercise your subscription rights, you will retain your current number of shares of our common stock. If other stockholders fully exercise their subscription rights or exercise a greater proportion of their subscription rights than you exercise, the percentage of our common stock owned by these other stockholders will increase relative to your ownership percentage and your voting and other rights in Navidea will likewise be diluted.

We may cancel the rights offering at any time prior to the expiration of the rights offering period, and neither we nor the Subscription Agent will have any obligation to you except to return your subscription payment.

We may at our sole discretion cancel the rights offering at any time prior to the expiration of the rights offering period. If we elect to cancel the rights offering, neither we nor the Subscription Agent will have any obligation with respect to the subscription rights except to return to you, without interest or penalty, as soon as practicable any subscription payments.

PercentageIf you do not act promptly and follow the subscription instructions, your exercise of Outstanding Shares of Common Stock After Giving Effect to the Purchased Shares Issued to Keystone Capitalsubscription rights will be rejected.

PursuantRights holders that desire to purchase shares in the rights offering must act promptly to ensure that all required forms and payments are actually received by the Subscription Agent prior to the termsexpiration date of the Purchase Agreement, we will issue to Keystone Capital 420,000 sharesrights offering. If you are a beneficial owner of our Series C Preferred, which will be convertible into a number of fully paid and nonassessable shares of common stock, equalSeries D preferred stock or Series E preferred stock, you must act promptly to $10.00 dividedensure that your broker, dealer, custodian bank or other nominee acts for you and that all required forms and payments are actually received by 90%the Subscription Agent prior to the expiration of the then-current fair market value of common stock (subjectrights offering period. We are not responsible if your broker, dealer, custodian bank or nominee fails to ensure that all required forms and payments are actually received by the Subscription Agent prior to the adjustments set forthexpiration of the rights offering period. If you fail to complete and sign the required subscription forms, send an incorrect payment amount or otherwise fail to follow the subscription procedures that apply to your exercise in the Purchase Agreement,rights offering prior to the “expiration of the rights offering period, the Subscription Agent may, depending on the circumstances, reject your subscription or accept it only to the extent of the payment received. Neither we nor the Subscription Agent undertakes to contact you concerning, or attempt to correct, an incomplete or incorrect subscription form. We have the sole discretion to determine whether the exercise of your subscription rights properly and timely follows the subscription procedures.

Conversion RateIf you make payment of the subscription price by uncertified personal check, your check may not clear in sufficient time to enable you to purchase shares in the rights offering.”). 

Any uncertified personal check used to pay the subscription price in the rights offering must clear prior to the expiration date of the rights offering, and the clearing process may require five or more business days. As a result, if you choose to use an uncertified personal check to pay the subscription price, it may not clear prior to the expiration date, in which event you would not be eligible to exercise your subscription rights. You may eliminate this risk by paying the subscription price by cashier’s check, certified check or bank draft drawn on a U.S. bank.

The receipt of subscription rights may be treated as a taxable dividend to you.

The numberU.S. federal income tax consequences of shares ultimately offered for sale by Keystone Capital in thisthe rights offering to shareholders will depend on whether the rights offering is dependent upon, among other things,part of a “disproportionate distribution.” We intend to take the numberreporting position that the subscription rights issued to common shareholders pursuant to the rights offering (a) are not part of Shares received by Keystone Capital upon exercisea “disproportionate distribution” and (b) will not be a taxable distribution with respect to your existing securities. The disproportionate distribution rules are complicated, however, and their application is uncertain, and thus we are not obtaining a definitive opinion from tax counsel regarding the application of such rules. Accordingly, it is possible that the IRS could successfully challenge our reporting position and assert that the rights offering is a taxable distribution. For a discussion of the Series C Preferred. tax consequences if this distribution is non-taxable and the tax consequences if it is taxable, see the discussion in “Material U.S. Federal Income Tax Consequences.”

The following table sets forthsubscription rights are non-transferable and thus there will be nomarket for them.

You may not sell, transfer or assign your subscription rights to anyone else. We do not intend to list the maximum numbersubscription rights on any securities exchange or any other trading market. Because the subscription rights are non-transferable, there is no market or other means for you to directly realize any value associated with the subscription rights.

We will have considerable discretion over the use of the proceeds of the rights offering. Because our management will have broad discretion over the use of the net proceeds, you may not agree with how we use the proceeds, and percentagewe may not invest the proceeds successfully.

We have not determined the amount of outstanding common stocknet proceeds that we will apply to various corporate purposes. Our board of directors and management will have considerable discretion in the application of the net proceeds from this rights offering, and it is possible that we may allocate the proceeds differently than investors in the rights offering may desire or that we may fail to maximize the return on these proceeds. Accordingly, you will be held by Keystone Capital after giving effectrelying on the judgment of our management with regard to the saleuse of Series C Preferredthe proceeds from the rights offering, and you will not have the issuanceopportunity, as part of shares of common stock issuableyour investment decision, to Keystone Capital upon conversion thereof, based on varying average trading prices:assess whether the proceeds are being used appropriately. It is possible that the proceeds will be invested in a way that does not yield a favorable, or any, return for the Company.