On March 24, 2021 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported its financial results for the fourth quarter and full year for the period ended December 31, 2020 (Press release, Lucence, MAR 24, 2021, View Source [SID1234577098]).

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"We are very excited about the progress we have made, completing all the patients in the Phase 2B NAV3-31 trial and submitting our briefing book to the FDA were milestone accomplishments this past year," said Mr. Jed A. Latkin, Chief Executive Officer of Navidea. "We are looking forward to hearing back from the FDA and continuing our due diligence discussions with Jubilant over the near term."

Fourth Quarter 2020 Highlights and Subsequent Events

Announced positive results from continued analysis of subjects who have completed Arm 3 of the Company’s NAV3-31 Phase 2B study. These data further corroborated Navidea’s hypotheses that Tc99m tilmanocept imaging can provide robust, quantitative imaging in patients with active rheumatoid arthritis ("RA") and that this imaging can provide an early indicator of treatment efficacy.
Submitted a formal Type B Meeting Request to the U.S. Food and Drug Administration ("FDA"). The FDA granted the Type B meeting and the Company has submitted the Briefing Book. The FDA is currently reviewing these formal briefing documents containing results from the NAV3-31 Phase 2B study and the proposed Phase 3 design and protocol.
Achieved last patient, last visit in the Company’s NAV3-31 Phase 2B study. Study closeout and data analysis are ongoing.
Opened the first US site, Northwestern University, for enrollment in the Company’s NAV3-32 Phase 2B trial comparing Tc99m tilmanocept imaging to histopathology of joints of patients with active RA.
Continued enrollment in the Investigator Initiated Phase 2 trial being run at the Massachusetts General Hospital evaluating Tc99m tilmanocept uptake in atherosclerotic plaques of HIV-infected individuals.
Received notice of patent grant from the USPTO for US 10,806,803: "Compositions for targeting macrophages and other CD206 high expressing cells and methods of treating and diagnosis."
Received a notice of allowance from the USPTO for the patent application: "Compounds and methods for diagnosis and treatment of viral infections" (US Patent Application 15/729,635).
Performed preclinical studies that demonstrate macrophage phenotype change from an immunosuppressive to a pro-inflammatory state and a synergistic effect on tumor growth reduction using the Company’s doxorubicin-containing construct with an approved checkpoint inhibitor therapy.
Appointed Malcolm G. Witter to the Company’s Board of Directors. Mr. Witter brings decades of financial and corporate governance experience to the board.
Entered into a Stock Purchase Agreement and Letter of Investment Intent with an existing investor, pursuant to which the Company issued to the investor 50,000 shares of newly-designated Series E Redeemable Convertible Preferred Stock (the "Series E Preferred Stock") for an aggregate purchase price of $5.0 million. The Series E Preferred Stock is convertible into a maximum of 2,173,913 shares of Common Stock.
Michael Rosol, Ph.D., Chief Medical Officer for Navidea, said, "The clinical research team is working diligently to advance the technology in key disease areas, with an emphasis on our RA program. We have completed all patients and all visits in our NAV3-31 Phase 2B trial and we are eagerly anticipating feedback from the FDA on our briefing package and design of the Phase 3 trial. We continue to prepare for initiation of this trial and have also opened up enrollment for the NAV3-32 Phase 2B trial comparing tilmanocept imaging to synovial tissue biopsy samples of RA patients. Concurrent with all of this, we have made exciting progress in our therapeutics pipeline and will continue to advance these towards the clinic."

Financial Results

Total net revenues for the fourth quarter 2020 were $219,000, compared to $119,000 for the same period in 2019. Total net revenues for the full year of 2020 were $914,000, compared to $651,000 for 2019. The increases were primarily due to increased grant revenue related to Small Business Innovation Research grants from the National Institutes of Health supporting Manocept development coupled with increased license revenue from net transitional sales in Europe.
Research and development ("R&D") expenses for the fourth quarter of 2020 were $1.3 million, compared to $1.7 million in the same period in 2019. R&D expenses for the full year of 2020 were $4.9 million, compared to $5.3 million in the same period in 2019. The decreases were primarily due to net decreases in drug project expenses, including decreased Manocept therapeutic development costs, decreased Manocept diagnostic development costs, and decreased Tc99m development costs, offset by increased NAV4694 development costs. The net decreases also included decreased regulatory consulting and travel expenses offset by increased employee compensation.
Selling, general and administrative ("SG&A") expenses for the fourth quarter of 2020 were $1.7 million, compared to $1.2 million in the same period in 2019. SG&A expenses for the full year of 2020 were $6.7 million, compared to $6.3 million in 2019. The net increases were primarily due to increased legal and professional services, employee compensation, European Medicines Agency annual fees for Lymphoseek, and franchise taxes, offset by decreased travel, depreciation and amortization, losses on disposal of assets, insurance, and investor relations services.
Navidea’s net loss attributable to common stockholders for the fourth quarter of 2020 was $3.0 million, or $0.11 per share, compared to $2.8 million, or $0.15 per share, for the same period in 2019. Navidea’s net loss attributable to common stockholders for the full year of 2020 was $11.4 million, or $0.48 per share, compared to $10.9 million, or $0.76 per share, for 2019.
Navidea ended the fourth quarter of 2020 with $2.7 million in cash and cash equivalents. Since December 31, 2020, the Company has received $7.9 million of cash related to the Series D and Series E Preferred Stock funding transactions. To date, the Company has received over $14 million of proceeds from the issuance of Series C, Series D and Series E Preferred stock.
Conference Call Details

Investors and the public are invited to dial into the earnings call through the information listed below, or participate via the audio webcast on the company website. Participants who would like to ask questions during the question and answer session will be prompted by the moderator, who will provide instructions.

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website.

On March 24, 2021 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company,reported with leading patient advocacy groups to expand the Clear Your View initiative to raise awareness of the important role complete biomarker testing plays in guiding initial treatment decisions for newly diagnosed advanced colorectal cancer (CRC) patients (Press release, Guardant Health, MAR 24, 2021, View Source [SID1234577097]). Current medical guidelines call for testing all six biomarkers in advanced CRC before starting treatment,2 yet more than 60 percent of patients are not receiving complete testing which puts them at risk for inappropriate therapy.1

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Now in its second year, the Clear Your View campaign encourages oncologists to "stop, test, and wait" for complete biomarker testing results before starting first-line treatment. Last year, the campaign focused on improving biomarker testing rates in advanced non-small cell lung cancer (NSCLC), which remains suboptimal at 20 percent,3 and garnered support from patient advocacy groups GO2 Foundation for Lung Cancer, LUNGevity Foundation, ALK Positive, and Lung Cancer Action Network. Now the campaign expands its focus to colorectal cancer, the second leading cause of cancer death and third most commonly diagnosed cancer in the US,4 and garners support from Colorectal Cancer Alliance, Fight CRC, Global Colon Cancer Association, KRAS Kickers, and PALTOWN.

Targeted therapy matched to a patient’s genomic profile has been shown to significantly extend median overall survival rate for advanced CRC patients5 as well as NSCLC patients.7-13 Testing for all recommended biomarkers can help predict which patients are most likely to respond to a certain treatment and which will not respond, and is one of the best ways to ensure that the patient receives the best treatment from the start. For example, while over 60 percent of metastatic CRC patients have a biomarker that may predict poor response to anti-EGFR monoclonal antibody therapy, 72 percent of patients who received anti-EGFR therapy did not first complete guideline-aligned RAS and BRAF biomarker testing to determine eligibility – resulting in patients potentially receiving less efficacious, costly treatment.1 The growing number of targetable CRC biomarkers makes it imperative that all patients receive complete biomarker testing before starting first-line treatment.5

"For patients with advanced colorectal cancer, time is of the essence and receiving the best treatment from the start is critical in extending progression-free survival," said Andrew Spiegel, co-founder and executive director of the Global Colon Cancer Association. "We are proud to support the Clear Your View campaign and stand committed alongside Guardant Health, Colorectal Cancer Alliance, Fight CRC, KRAS Kickers, and PALTOWN to raising awareness and urgency around the importance of complete biomarker testing to improve survival for patients."

"Incredible progress has been made in personalized treatments for advanced colorectal cancer, including not only medicines in clinical trials, but available FDA-approved medicines, yet too many patients are missing out on these potentially life-changing treatments due to suboptimal biomarker testing rates," said Helmy Eltoukhy, Guardant Health CEO. "Additionally, many patients are being treated with potentially less efficacious treatments. Through the expansion of the Clear Your View initiative, we join the colorectal cancer community in urging wider adoption of complete biomarker testing to help ensure the best treatments for all patients suffering from advanced cancer."

On March 24, 2021 Bruker Corporation (Nasdaq: BRKR), a leading supplier of single-plane illumination microscopy (SPIM) technology for research on live cells and cleared biological samples, reported that two Luxendo MuVi and LCS SPIM light-sheet microscopes have been installed by Memorial Sloan Kettering Cancer Center (MSK) (Press release, Bruker, MAR 24, 2021, View Source [SID1234577096]). The funding for the two light-sheet fluorescence microscopes was supported by Cycle for Survival (View Source). The new SPIM microscopes will help researchers visualize the cellular and tissue hallmarks of cancer and translate those findings into better cancer treatment methods.

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"By understanding how cells mobilize to build organs, researchers can glean insights into why some cells become cancerous and lead to organ destruction," said Dr. Anna-Katerina Hadjantonakis, MSK Chair of the Developmental Biology Program. "Instruments such as these are useful for imaging across differing length scales — from subcellular to single cells to tissue-level processes — allowing researchers to study cellular dynamics and cellular motion, processes that enable cells to metastasize."

"Light-sheet fluorescence microscopy has emerged as a uniquely powerful method for high-resolution, cleared-sample and dynamic biological imaging," added Dr. Lars Hufnagel, Vice President and General Manager of Bruker’s Luxendo light-sheet microscopy business. "We couldn’t be more pleased that our technology will be assisting the great MSK researchers and programs in such important work."

About the MuVi and LCS SPIM Systems
Bruker’s SPIM systems avoid sample phototoxicity by sequentially illuminating a stack of small slices of the organism, allowing scientists to observe living organisms for extended periods of time without photodamage. In particular, MuVi SPIM allows fast 3D imaging of live cells and living objects, such as spheroids and whole specimens, without the need of sample rotation. Despite the fact that sample rotation is not necessarily needed for a non-isotropic acquisition, the MuVi SPIM system provides this degree of freedom such that isotropic resolution can be achieved.

The modular LCS SPIM for large, cleared samples has been designed to be compatible with a broad variety of clearing solutions and sample sizes. Its new sample mounting approach and innovative optical design enables unprecedented acquisition times and minimizes sample distortions while seamlessly integrating into existing clearing and sample preparation pipelines. To handle the vast amount of data produced by the light-sheet technique, Lux DATA comprehensive data processing and storage provides fast transfer and large-capacity storage and leverages multi-core- and multi-GPU-based processing.

On March 24, 2021 BiomX Inc. (NYSE American: PHGE) ("BiomX" or the "Company"), a clinical-stage microbiome company advancing natural and engineered phage therapies that target specific pathogenic bacteria, reported that the Company will host a conference call and live audio webcast on Wednesday, March 31, 2021, at 8:00 a.m. EDT, to report fourth quarter and full year 2020 financial results (Press release, BiomX, MAR 24, 2021, View Source [SID1234577095]). To participate in the conference call, please dial 1-877-407-0724 (U.S.), 1-809-406-247 (Israel) or 1-201-389-0898 (International). The live and archived webcast will be available in the Investors section of the Company’s website at www.biomx.com.

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On March 24, 2021 InteRNA Technologies, a clinical-stage biotech company developing microRNA (miRNA)-based therapeutics with a focus on cancer, reported that preclinical data investigating the Company’s lead candidate, INT-1B3, have been published in the peer-reviewed journals Molecular Therapy – Nucleic Acids and Oncotarget (Press release, InteRNA Technologies, MAR 24, 2021, View Source [SID1234577094]). INT-1B3 is a mimic of the tumor suppressor miRNA-193a-3p and has the potential to address multiple hallmarks of cancer at the same time. The published results include data from tumor cell lines and experimental tumor models and support the high therapeutic potential of INT-1B3 in solid tumor indications.

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"Publications of our preclinical data with INT-1B3 in two highly-ranked, peer-reviewed journals represent a major milestone for our research and development team, and recognition of the innovative scientific research conducted at InteRNA in the last few years," said Dr. Michel Janicot, Chief Development Officer of InteRNA Technologies. "Documenting the molecular mechanism of action of our miR-193a-3p mimic and consequent downstream biology in cancer cells strongly supports INT-1B3 as novel promising candidate for therapeutic intervention in oncology."

In the publication in Molecular Therapy – Nucleic Acids, results of extended RNA-sequencing and transcriptome-wide analysis after transfection of the miR-193a-3p mimic (1B3) in human tumor cell lines were presented, revealing insights into the underlying molecular pathways of 1B3’s tumor suppressor functions. Differentially expressed genes mapped by Ingenuity Pathway Analysis strongly indicated upregulation of the tumor suppressive PTEN pathway as well as downregulation of many oncogenic growth factor signaling pathways. Furthermore, the analysis pointed to an extensive link of 1B3 with cancer, based on predicted negative effects on tumor cell survival, proliferation and migration as well as induction of cell death in tumor cells. These data strongly suggest that 1B3 is a potent tumor suppressor agent which targets various key hallmark pathways across cancer types.

In the publication in Oncotarget, preclinical data from different tumor cell-based assays demonstrated multi-modal effects of 1B3 on cancer cells. 1B3 was shown to efficiently reduce target gene expression in tumor cells, leading to diminished cell proliferation and survival, induction of cell cycle arrest and apoptosis, increased cell senescence, DNA damage and inhibition of cell migration. In addition, the novel lipid nanoparticle (LNP)-based formulation of 1B3, INT-1B3, demonstrated pronounced anti-tumor activity as a single agent upon systemic administration in tumor-bearing mice at well-tolerated doses.

These preclinical results contributed to the decision by InteRNA to initiate a first-in-human clinical study with INT-1B3 in patients with advanced solid tumors. The first patient in the study was dosed in February 2021. The trial is conducted in clinical study centers in the Netherlands and Belgium and topline results from the dose escalation part of the study are expected by the end of 2021.

About INT-1B3

INT-1B3’s unique mechanism of action addresses multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in inhibition of proliferation and migration and induction of cell cycle arrest and apoptosis. The triggering of the immunogenic tumor cell death (ICD) process as well as downregulation of the adenosine-A2A receptor pathway through inhibition of CD39/CD73 leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs), and maturation of dendritic cells. As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ effector T cells leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment.