On March 30, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its collaboration partner for daratumumab, Janssen Biotech, Inc., has decided not to initiate stage 2 of the Phase II study (CARINA, LYM2001) of daratumumab in three types of relapsed or refractory non-Hodgkin’s lymphoma (NHL) (Press release, Genmab, MAR 30, 2017, View Source [SID1234518322]). The study will not proceed to stage 2 as a data review showed that two cohorts of the study, investigating the use of daratumumab monotherapy in relapsed or refractory patients with follicular lymphoma (FL), and with diffuse large B-cell lymphoma (DLBCL) did not reach the predefined futility thresholds of overall response rates (ORR) of 50%, and 30%, respectively. In the third cohort in the study, patients with mantle cell lymphoma (MCL), ORR was not evaluable due to slow recruitment, driven by the aggressive nature of the disease in its final stages. This has no impact on other ongoing or planned studies with daratumumab.

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"While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue. Daratumumab is still being investigated in a number of indications including multiple myeloma and other hematological cancers such as NK/T-cell lymphoma and myelodysplastic syndrome as well as in solid tumors," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CARINA LYM2001 study
The Phase II study (NCT02413489) is a three arm (DLBCL, FL, MCL), open-label multicenter study, which planned to enroll up to 210 patients in 2 stages with relapsed or refractory non-Hodgkin’s lymphoma. Stage 1 of the study was designed to provide a preliminary assessment of monotherapy activity, with stage 2 designed to further evaluate safety and efficacy of daratumumab monotherapy. Stage 2 will now not proceed. The primary endpoint of the study was overall response rate. The safety profile of daratumumab in these diseases was also assessed.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, NK/T-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapiesa

On March 30, 2017 RXi Pharmaceuticals Corporation (NASDAQ: RXII), a clinical-stage RNAi company developing innovative therapeutics that address significant unmet medical needs, reported its financial results for the fourth quarter and year ended December 31, 2016, and provided a business update (Filing, Q4/Annual, RXi Pharmaceuticals, 2016, MAR 30, 2017, View Source [SID1234518411]).

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"We believe RXi is well positioned for a strong business and development performance in 2017 due to the acquisition of MirImmune Inc. and the strengthening of our balance sheet through a financing at the end of 2016. As a result, the Company has already initiated programs in the immuno-oncology and cell therapy space, an exciting therapeutic area in health care today," said Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. He further added that, "The capital that we received from our shareholders allows us to put a strong focus on these immuno-oncology programs while completing and reporting our ongoing clinical trials in dermatology and ophthalmology in the second half of 2017."

The Company will host a conference call today at 4:30 p.m. EDT to discuss financial results and provide an update on the Company. The webcast link will be available under the "Investors – Event Calendar" section of the Company’s website, www.rxipharma.com. The event may also be accessed by dialing toll-free in the United States and Canada: +1 888-669-0684. International participants may access the event by dialing: +1 862-225-5361. An archive of the webcast will be available on the Company’s website approximately two hours after the presentation.

Select Fourth Quarter and Fiscal 2016 Financial Highlights
Cash Position
On December 21, 2016, the Company closed an underwritten public offering of (i) 2,131,111 Class A Units, at a public offering price of $0.90 per unit, consisting of one share of the Company’s common stock, and a five-year warrant to purchase one share of common stock at an exercise price of $0.90 per share and (ii) 8,082 Class B Units, at a public offering price of $1,000 per unit, consisting of one share of Series B convertible preferred stock, which is
convertible into 1,111.11 shares of common stock, and 1,111.11 warrants. The offering included an over-allotment option for the underwriters to purchase an additional 1,666,666 Class A Units, which the underwriters fully exercised. The total net proceeds of the offering, including the exercise of the over-allotment option, was $10.1 million after deducting underwriting discounts and commissions and offering expenses paid by the Company.
At December 31, 2016, the Company had cash of $12.9 million, compared with cash, cash equivalents and short-term investments of $10.6 million at December 31, 2015. The Company believes that its existing cash should be sufficient to fund operations for at least the next twelve months.
Research and Development Expenses
Research and development expense for the quarter ended December 31, 2016 was $1.3 million, which included less than $0.1 million of non-cash stock-based compensation expense, as compared with $1.7 million for the quarter ended December 31, 2015, which included $0.1 million of non-cash stock-based compensation expense.
Research and development expense for the year ended December 31, 2016 was $5.4 million, which included $0.2 million of non-cash stock-based compensation expense, as compared with $6.9 million for the year ended December 31, 2015, which included $0.6 million of non-cash stock-based compensation expense.
The decrease in research and development expense quarter over quarter and year over year was primarily due to cash and equity fees payable to Hapten Pharmaceuticals, LLC upon the close of the Samcyprone licensing agreement and manufacturing expenses for the RXI-109 drug product, both of which occurred in 2015. Additionally, the Company saw a decrease in stock-based compensation expense due to the full vesting of stock options in 2016 from stock options that had been granted in 2012.
General and Administrative Expenses
General and administrative expense for the quarter ended December 31, 2016 was $1.0 million, which included $0.1 million of non-cash stock-based compensation expense, as compared with $0.9 million for the quarter ended December 31, 2015, which included $0.2 million of non-cash stock-based compensation expense.
General and administrative expense for the year ended December 31, 2016 was $3.6 million, which included $0.5 million of non-cash stock-based compensation expense, as compared with $3.3 million for the year ended December 31, 2015, which included $0.9 million of non-cash stock-based compensation expense.
The increase in general and administrative expense quarter over quarter and year over year was primarily due to the Company’s focus on business development activities and an increase in legal expenses due to the Company’s acquisition of MirImmune Inc. These increases in general and administrative expense were offset by a decrease in stock-based compensation expense due to the full vesting of stock options in 2016 from stock options that had been granted in 2012.
Convertible Preferred Stock
Accretion of convertible preferred stock and dividends were $2.1 million for the quarter ended December 31, 2016. There was no such expense for the quarter ended December 31, 2015.
Accretion of convertible preferred stock and dividends were $2.1 million for the year ended December 31, 2016, compared with $0.2 million for the year ended December 31, 2015.
The increase quarter over quarter and year over year was due to the one-time charge related to the beneficial conversion feature of the Series B convertible preferred stock issued in connection with the completion of the Company’s December 2016 underwritten public offering offset by a decrease related to the fair value of dividends on the Company’s Series A and Series A-1 convertible preferred stock. The Company no longer had any Series A or Series A-1 convertible preferred stock authorized, issued or outstanding as of December 31, 2016 and 2015.
Net Loss Applicable to Common Stockholders
Net loss applicable to common stockholders for the quarter ended December 31, 2016 was $4.4 million, compared with $2.6 million for the quarter ended December 31, 2015.
Net loss applicable to common stockholders for the year ended December 31, 2016 was $11.1 million, compared with $10.4 million for the year ended December 31, 2015.
The increase in net loss applicable to common stockholders for the quarter and year ended December 31, 2016 as compared to the same prior year periods was due to the one-time charge related to the beneficial conversion feature of the Company’s Series B convertible preferred stock offset by a decrease in operating expenses, as described above.
Select Fourth Quarter 2016 and Recent Corporate Highlights
Select Business and Corporate Highlights
Building on the pioneering discovery of RNAi by RXi founder and Nobel Laureate, Dr. Craig Mello, scientists at RXi have harnessed the naturally occurring RNAi process which has the ability to "silence" or down-regulate the expression of a specific gene that may be overexpressed in a disease condition. RXi developed a robust RNAi therapeutic platform, including self-delivering RNA (sd-rxRNA) compounds, that have the ability to highly selectively block the expression of any target in the genome, thus providing applicability to many therapeutic areas.
Immuno-Oncology
In March 2015, MirImmune Inc., a privately-held company focused on the development of next generation immunotherapies for the treatment of cancer, entered into an exclusive license agreement for use of RXi’s sd-rxRNA technology in developing innovative cell-based cancer immunotherapies. MirImmune’s progress in cell therapy using RXi’s technology formed a strong foundation for therapeutic development in the immuno-oncology space. As a result, RXi entered into an agreement to acquire MirImmune which was completed earlier this year. The Company’s goal, through internal research and external partnerships, is to develop more effective treatments resulting in better quality of life and extended survival for patients.
The Company has initiated a program developing cell-based immunotherapies to treat cancer based on its proprietary sd-rxRNA therapeutic compounds. To date, the unique applicability of sd-rxRNA for immune checkpoint modulation in cellular immuno-oncology therapies has been demonstrated, including:

• Selection of lead sd-rxRNA compounds against six different extracellular and intracellular immune check points

• Demonstrated silencing of all tested checkpoint targets in vitro, singly and in combinations

• Efficient and long-lasting silencing of immune checkpoints in vivo

• Applicability of sd-rxRNA transfection in cell therapy to solid tumors

• Filing of intellectual property that covers the use of RNAi compounds for use in cell therapy
To support this ongoing initiative, Alexey Eliseev, PhD has been appointed as RXi’s Chief Business Officer. Dr. Eliseev is a highly accomplished leader with over 20 years of experience in academia, biotechnology industry and venture capital and most recently was the founder and CEO of MirImmune Inc. In addition, RXi has appointed two leading oncology experts to its Scientific Advisory Board. RXi’s new SAB members are Dr. Rolf Kiessling, Professor in Experimental Oncology at Karolinska Institutet and Senior Chief Physician of Radiumhemmet at Karolinska Hospital as well as medical oncology expert Dr. James D. Griffin, Chairman, Department of Medical Oncology, Dana-Farber Cancer Institute. Dr. Griffin also serves as Professor, Medicine, Harvard Medical School and Director, Medical Oncology, Brigham and Women’s Hospital.
Dermatology
The Company’s ongoing Phase 2 clinical trial, RXI-109-1402, is being conducted to evaluate its first clinical candidate RXI-109, an sd-rxRNA compound targeting connective tissue growth factor (CTGF) to reduce scar formation in the skin following scar revision surgery. This study is now fully enrolled and the Company will provide full read-out, for Cohorts 3 and 4, H2-2017.
Samcyprone, the Company’s second clinical candidate, is a topical immunotherapy currently being evaluated in a Phase 2a clinical trial. RXI-SCP-1502 is a multi-center, multi-dose trial conducted in subjects with at least one cutaneous, plantar or periungual wart. The Company expects to share early read-outs H2 2017.
Consumer Health Program
RXi’s consumer health compound RXI-231 targets tyrosinase, a key player in the production of melanin. A formulation has been developed at RXi that allows delivery of the compound into the epidermis. We are in the process of finalizing the first two protocols for testing in volunteers. To support these initial studies, RXI-231 was manufactured and is being formulated for topical use.
Ophthalmology
As in dermal scarring, CTGF is known to play a role in retinal scarring. Reduction of CTGF in the eye by RXI-109 treatment may reduce the formation of retinal fibrosis that often accompanies late stage AMD and contributes to permanent vision loss. Enrollment in the first two cohorts in the Company’s Phase 1/2 trial, RXI-109-1501, is complete. RXI-109 has been well-tolerated in the eye to date; enrollment into the third cohort at the next higher dose level is ongoing.

On March 30, 2017 Third Rock Ventures, LLC reported the launch of Tango Therapeutics, a new cancer therapeutics company discovering and developing novel medicines designed to target cancer vulnerabilities beyond mutated oncogenes to deliver transformational new therapies for patients (Press release, Tango Therapeutics, MAR 30, 2017, View Source [SID1234520724]).

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Tango was launched with a $55 million Series A investment from Third Rock Ventures. The company has established a robust product engine that leverages advances in DNA sequencing and CRISPR-based target discovery to generate breakthrough medicines that will provide deeper, more sustained benefit than today’s targeted therapies, and extend the benefit of available immuno-oncology agents.

"Cancers are complex genetic diseases marked by multiple lesions in each tumor. These include genes that are turned on to drive cancer growth and those that are inactivated and thus, unable to function as tumor suppressors," said Barbara Weber, M.D., Tango’s interim Chief Executive Officer and a Venture Partner at Third Rock Ventures. "Loss of tumor suppressor genes is a hallmark of cancer, but the genes, themselves, are not tractable targets for drug discovery. The availability of comprehensive DNA sequencing, coupled with CRISPR-enabled target discovery, provides us with new paths to identify novel drug targets and combinations that take advantage of vulnerabilities created by loss of tumor suppressor gene function — something we have been unable to do effectively in the past. With the sophisticated genomics tools now available, the time is right for Tango to take on this challenge and focus on patients without effective treatment options."

Tango is focused on three areas of drug development, each in well-defined patient populations currently lacking effective treatment options, and each with hallmarks of cancer that have not been targeted yet. These include:

Loss of tumor suppressor gene function: A universal feature of cancer is the inactivation of genes which normally protect against tumor development. Tango is working to turn tumor suppressor gene loss from cancer’s strength into a weakness by identifying associated targetable vulnerabilities, an effect known as synthetic lethality. Drugs against synthetic lethal targets have the potential added benefit of effectiveness against cancer cells without damaging normal cells.

Multiple oncogenic drivers: To address the multiple genetic changes that give rise to cancer, Tango is working to identify novel targets for rational combinations that will offer more robust treatment effects than is possible with single-agent approaches. Decades of cancer research have shown that with the right drug combinations in the right patients, cancers can be curable.

Immune evasion: Complementing current, immune-cell-directed cancer therapies, Tango is working to identify and target the genetic alterations in cancer cells responsible for helping them avoid immune destruction. Drugs against these targets could substantially increase the benefit of current immuno-oncology drugs without increasing immune damage to normal tissues.

Tango product engine: Putting patient selection first to accelerate discovery

What fuels each of Tango’s programs is an increasingly sophisticated ability to utilize synthetic lethality, the interaction between two genes that causes cell death when both are inactivated. In cancer cells, one of these genes is inactivated by mutation; the other will be inactivated by a drug. This approach leaves normal cells largely unaffected, with the potential to greatly enhance anti-tumor efficacy and reduce associated toxicity.

The first FDA-approved example of synthetic lethality in cancer treatment is the use of PARP inhibitors for BRCA-mutant ovarian cancer. Alan Ashworth, Ph.D., a scientific Founder of Tango, discovered that combining a BRCA1/2 mutation and PARP inhibition creates synthetic lethality. Recent data show that continuing treatment with a PARP inhibitor after chemotherapy in patients with BRCA-mutant ovarian cancer extends progression-free survival for more than two years, compared to placebo. The Tango product engine is designed to systematically discover other such context-specific vulnerabilities, uncovering weaknesses created by genetic alterations in cancer and targeting them for therapeutic benefit.

In executing this strategy, Tango will upend the traditional paradigm by doing target discovery in cancer subgroups with a pre-defined patient selection approach. The company will use data from DNA sequencing of patient-derived tumor samples to define genetic contexts, and deploy CRISPR-based target discovery techniques in those cancer subtypes to identify novel drug targets.

Tango’s success will be driven by its depth of understanding of the genetic subtypes of cancer, and corresponding insights into novel drug targets and combinations uniquely relevant to each subtype. By shaping discovery efforts in this way, Tango has the potential to reach the clinic quickly, and with a clear plan for identifying the patients most likely to benefit from each new treatment, an approach that will increase both speed and probability of success in translating novel target discoveries into transformational new medicines for patients.

World-leading team spanning diverse disciplines

The Tango management team includes recognized leaders in target discovery, cancer biology, functional genomics, translational medicine and company building. Company leaders include Barbara Weber, M.D., interim Chief Executive Officer; Cary Pfeffer, M.D., interim Chief Business Officer; Daniella Beckman, C.P.A., Chief Financial Officer; Alan Huang, Ph.D., Senior Vice President, Head of Biology; John Maxwell, Ph.D., Vice President, Head of Chemistry; and Janid Ali, Ph.D., Vice President, Head of Biochemistry.

The Tango founders are a group of internationally recognized scientists and clinicians who have shaped the current state of knowledge and practice in cancer biology and genetics, translational medicine and CRISPR technology:

Alan Ashworth, Ph.D., FRS, President of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center

José Baselga, M.D., Ph.D., Physician-in-Chief at Memorial Sloan Kettering Cancer Center

Levi Garraway, M.D., Ph.D., Senior Vice President of Global Oncology at Eli Lilly and Company

William Kaelin, M.D., Professor in the Department of Medicine at the Dana-Farber Cancer Institute, Harvard Medical School and a Howard Hughes Medical Institute Investigator

Timothy K. Lu, M.D., Ph.D., Associate Professor of Biological Engineering, Electrical Engineering and Computer Science at the Massachusetts Institute of Technology

Antoni Ribas, M.D., Ph.D., Professor of Medicine, Surgery, and Molecular and Medical Pharmacology at the University of California Los Angeles

About Tango Therapeutics

Tango Therapeutics is a biotechnology company developing novel medicines for patients by discovering and drugging context-dependent vulnerabilities in cancers. Tango was launched in 2017 by Third Rock Ventures and is headquartered in Cambridge, Mass.

On March 29, 2017 Navidea Biopharmaceuticals, Inc. (NYSE MKT:NAVB) reported business and financial highlights for the fourth quarter and year ended December 31, 2016 (Press release, Navidea Biopharmaceuticals, MAR 29, 2017, View Source;p=RssLanding&cat=news&id=2257395 [SID1234518381]).

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2016 Top Highlights

Achieved $1 million in Lymphoseek (technetium Tc 99m tilmanocept) injection commercial milestones upon sale of 100,000th patient dose and receipt of European approval to manufacture a reduced-mass vial
Completed sale of Lymphoseek to Cardinal Health 414, LLC ("Cardinal Health 414") and received approximately $83 million in upfront payments including an advance of $3 million of future earnout payments, with up to $227 million in potential additional earnout payments through 2026
Initiated intravenous ("IV") dose escalation Phase 1 imaging/disease-finding study in rheumatoid arthritis ("RA") of ten cohorts with three dose cohorts completed with major escalations and imaging of active RA
Completed nine-subject cardiovascular imaging disease-finding study in HIV/CV patients and published clinical results in The Journal of Infectious Diseases
Awarded $1.8 million Fast-track Small Business Innovation Research ("SBIR") Grant for Manocept-based treatment for Kaposi’s Sarcoma ("KS")
Appointed Michael M. Goldberg, M.D., as President and Chief Executive Officer and Eric K. Rowinsky, M.D., as Chairman of the Board of Directors
Business and Product Development Update

This past year and first quarter of 2017 were positively transformative for us. We refocused Navidea from investing in developing the commercial infrastructure to sell its sole commercial imaging product to a late-stage development company focused on several very large imaging market opportunities, and through its Macrophage Therapeutics, Inc. ("MT") subsidiary successfully advanced a number of novel immunotherapy products through proof of concept studies in animals. In the process, we transformed our capital structure by paying down our high interest and very covenant restrictive debt. The Company has gone from losing close to $28 million in 2015 to a net loss of $14 million in 2016 to operating at cash flow positive projected for 2017 not including discretionary research projects. Furthermore the Company, which had no excess cash flow for discretionary, non grant related research, now has sufficient cash to advance all of our existing imaging and MT ongoing initiatives.

While transforming our business model, balance sheet and income statements, we made significant progress with our technology and pipeline. We are fortunate that both our imaging and therapeutic product candidates are based on the same drug delivery system that targets activated macrophages, even when an additional agent is chemically attached. In humans, we advanced two new delivery approaches and confirmed their utility when dosed subcutaneously or intravenously. In animals, we initiated development of an oral delivery formulation for our therapeutic product candidates.

Additionally, we confirmed that in humans we can target the classically-activated or M1 macrophage in patients with RA and atherosclerosis. This is a major advance, as the alternative activation state, or M2 macrophage, is well known to have significantly higher cell surface expression of the mannose receptor (CD206) than the M1 macrophage in the activated state. Clinical results clearly demonstrate sufficient CD206 expression on M1 activated macrophages to target this receptor with our technology. Our animal studies confirmed as well that targeting either M1 or M2 macrophages implicated in disease is feasible with the appropriate therapeutic linked to our delivery system. In animal models we verified the activity of our product candidates in both M1-based diseases as well as M2-based diseases. Finally, working with various academic groups we demonstrated that by targeting the host macrophage that acts as an incubator we can eliminate viral reservoirs containing Zika, dengue, human immunodeficiency virus ("HIV"), human herpesvirus 8 ("HHV8"), and other infectious agents such as leishmaniosis. We are also currently working with National Institutes of Health ("NIH")-funded labs, at no cost to Navidea, to explore our antiviral and anti-infective performance in appropriate animal models.

Financial Results

Revenues for the year ended December 31, 2016 were $22.0 million compared to $13.2 million for 2015. Navidea’s revenues for 2016 consisted of $17.0 million in sales of Lymphoseek, $3.1 million from various federal grants and other revenue, and $1.8 million related to license agreements, compared to $10.3 million, $1.9 million and $1.1 million, respectively, for 2015.

Operating expenses for the year ended December 31, 2016 were approximately $21.9 million compared to $30.0 million for 2015. Research and development expenses were $8.9 million during 2016 compared to $12.8 million during 2015. The net decrease was primarily a result of reductions in NAV4694, Lymphoseek and NAV5001 product development costs coupled with reduced headcount and related support costs, offset by increased Manocept diagnostic and therapeutic product development costs. Selling, general and administrative expenses were approximately $13.0 million for 2016 compared to $17.3 million for 2015. The net decrease was primarily due to reduced headcount and related support costs, contracted medical science liaisons, business development consulting services, market development expenses related to Lymphoseek, and investor relations, offset by increased legal and professional services.

Navidea’s loss from operations for the year ended December 31, 2016 was $2.2 million compared to $18.6 million for 2015. For the year ended December 31, 2016, Navidea reported a loss attributable to common stockholders of $14.3 million, or $0.09 per share, compared to a loss attributable to common stockholders of $27.6 million, or $0.18 per share, for the same period in 2015.

Revenues for the fourth quarter of 2016 were $3.4 million compared to $4.3 million for the same period in 2015. Navidea’s revenues for the fourth quarter of 2016 consisted of $2.3 million in sales of Lymphoseek and $1.0 million from various federal grants and other revenue, compared to $3.5 million and $541,000, respectively, coupled with $250,000 related to license agreements, for the same period in 2015. Additionally, approximately $2 million in sales of Lymphoseek to Cardinal Health 414 recorded in the third quarter of 2016 was accelerated to help facilitate the transaction that was ultimately closed in March 2017. Without acceleration of such, the related sales would have occurred in the fourth quarter of 2016.

Fourth quarter 2016 operating expenses were $5.5 million compared to $6.4 million for the fourth quarter of 2015. Research and development expenses were $2.4 million during the fourth quarter of 2016 compared to $2.6 million during the fourth quarter of 2015. The net decrease from 2015 to 2016 was primarily a result of reduced headcount and related support costs coupled with decreased NAV4694 product development costs, offset by increased Manocept diagnostic and Lymphoseek product development costs. Selling, general and administrative expenses were $3.1 million for the fourth quarter of 2016 compared to $3.8 million for the same period in 2015. The net decrease was primarily due to reduced headcount and related support costs, market development expenses related to Lymphoseek and investor relations, offset by increased legal and professional services.

Navidea’s loss from operations for the fourth quarter of 2016 was $2.4 million compared to $2.6 million for the fourth quarter of 2015. For the fourth quarter of 2016, Navidea reported a loss attributable to common stockholders of $3.9 million, or $0.02 per share, compared to a loss attributable to common stockholders of $2.5 million, or $0.02 per share, for the fourth quarter of 2015.

Detailed Highlights

Navidea and Cardinal Health 414
Completed sale of Lymphoseek to Cardinal Health 414 for lymphatic mapping, lymph node biopsy and the diagnosis of metastatic spread to lymph nodes for the staging of cancer in North America
Received approximately $83 million in upfront payments including an advance of $3 million of future earnout payments, with up to $227 million in potential additional earnout payments through 2026, $17.1 million of which is guaranteed over the next three years
CRG et al
Entered into a Global Settlement Agreement between the Company, MT, Capital Royalty Partners II L.P. and its affiliates ("CRG"), and Cardinal Health 414 in which Navidea repaid $59 million (the "Deposit Amount") of its indebtedness and other obligations outstanding under the CRG Term Loan.
Platinum et al
Concurrently with payment of the Deposit Amount to CRG, the Company also paid to Platinum Partners Credit Opportunities Master Fund, LP ("PPCO") an aggregate of $7.7 million in partial satisfaction of the Company’s liabilities, obligations and indebtedness under that certain Loan Agreement, dated July 25, 2012 (as amended) by and between the Company and Platinum-Montaur Life Sciences, LLC, which, to the extent of such payment, were transferred by Platinum-Montaur to PPCO. Approximately $1.9 million remains outstanding under the Platinum Loan Agreement.
U.S. Food and Drug Administration ("FDA")
Held several discussions/meetings with the FDA significantly expediting development and approval timelines for Manocept-RA disease-finding approaches to rheumatoid arthritis
Cardiovascular ("CV") Initiative
Completed nine-subject cardiovascular imaging disease-finding study in HIV/CV patients
Presented clinical results at CROI-2017 and published in the Journal of Infectious Disease
Additional planned studies include a large potential partner evaluating product in their proprietary animal models
Rheumatoid Arthritis
Completed 18-subject subcutaneous ("SC") Manocept RA study
Initiated RA intravenous ("IV") dose escalation Phase 1 imaging/disease-finding study of 10 cohorts with three dose cohorts completed with major escalations and imaging of active RA
Appointed strategic clinical and regulatory consulting firm to optimize clinical development plan for RA imaging candidate
Non-Alcoholic Steatohepatitis (NASH) Therapy
Completed three in vivo studies employing two Manocept conjugate agents and three different dosing regimens demonstrating effectiveness at preventing non-alcoholic fatty liver disease ("NAFLD") progression to NASH and NASH’s progression to liver cirrhosis
A poster presentation on certain of our NASH results will be presented at a meeting next week and will be posted on the MT website
Cancer Therapy
Completed three preclinical studies, two single agent and one in combination with a well-established therapeutic antibody (two confirmatory in vivo studies – murine human tumor model). All three studies confirmed a positive impact on the tumor progression and inhibition/tumor kill.
Cancer Imaging to Treatment
Colorectal Cancer and Liver Cancer – completed preclinical testing for the requirements to administer the Manocept imaging agent for colorectal cancer and colorectal cancer with synchronous liver metastases.
Cervical Cancer – completed a significant portion of the clinical testing for a new indication for imaging of metastatic disease (lymph node metastasis) in cervical cancer. Navidea’s portion of the study will be completed in Q1 2017.
Lipid Storage Disease (Neuro)
Initiated in vitro cell culture study in which Manocept conjugates demonstrated substantial protective effect of glial cells exposed to toxic metabolite
Anti-Infectives
Zika Virus – Initiated and completed four in vitro studies in human tissue demonstrating a highly effective reduction in Zika infectivity and antiviral activity by multiple Manocept conjugates
Dengue Virus – Initiated and completed four in vitro studies in human tissue demonstrating a highly effective reduction in dengue infectivity and antiviral activity by multiple Manocept conjugates
Leishmaniosis – Initiated and completed two in vivo studies demonstrating a highly effective targeting in Leishmaniosis infectivity and parasite activity by multiple Manocept conjugates
Cytomegalovirus ("CMV") – Held discussions with NIH/NIAID on testing of key Manocept conjugates in CMV infection and disease progression with preclinical studies to be initiated in H2 2017
Kaposi’s Sarcoma
Received NIH/NCI funding to support the therapeutic development of anticancer (Anti-KS) Manocept conjugates
Phase 1 of the grant completed and Phase 2 clinical protocols are IRB-approved with study initiation anticipated shortly
Human Herpes Virus 8 – The testing of Manocept agents against HHV8 are an integral part of the Kaposi’s Sarcoma therapy initiatives
Human Immunodeficiency Virus – The testing of Manocept agents against HIV is an integral part of the KS therapy initiatives
Completed Preclinical FDA requirements for IV administration of tilmanocept for all radio-diagnostic applications
Inflammatory Bowel Disease and Crohn’s Disease ("BD/C")
Initiated partnership with major pharma group to assess the efficacy of Manocept conjugates in appropriate in vivo models with results anticipated in the coming months.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!