CD206 x TAM family

Navidea Biopharmaceuticals (NYSE American: NAVB) (“Navidea” or the “Company”), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, today announced the signing of a Sponsored Research Agreement with the University of Pennsylvania (“Penn”) for a project to evaluate the use of Tc99m tilmanocept imaging in glioblastoma as a prognostic agent for tumor growth rate and overall survival. The research is led by Principal Investigator Ali Nabavizadeh, MD, of the Department of Radiology in the Perelman School of Medicine at Penn. Glioblastoma (“GBM”) is the most aggressive and most common primary central nervous system tumor in adults and there is an urgent need for new therapies. Macrophages play an important role in tumor biology. They are a major population of non-cancer cells in GBM, representing as many as half of all cells in some cases. These Tumor Associated Macrophages (“TAMs”) may then be a viable target for tumor therapies or serve as a biomarker for monitoring tumor status. Broadly, active macrophages can be of a tumor suppressing type (M1 macrophages) or of a tumor promoting type (M2 macrophages). The TAMs are typically M2-like and are known to express high levels of CD206, the macrophage mannose receptor that Tc99m tilmanocept targets. This research has as its hypothesis that the M2 TAMs in GBM can be imaged with Tc99m tilmanocept, and that this imaging can serve as a predictive tool for outcome with and without use of an immunotherapy that works in part to change the M2-like macrophage population to a more M1-like state, promoting tumor killing. In these preclinical studies, Tc99m tilmanocept imaging will be evaluated in correlation with tumor growth rate, and in separate studies Tc99m tilmanocept imaging will be performed before and after anti-interleukin-6 therapy, which has been shown to promote TAM switching from the M2 to M1 state. Study endpoints will include quantitative imaging compared to pathology and overall survival. Dr. Michael Rosol, Chief Medical Officer for Navidea, said, “We are pleased to sponsor this important work with Dr. Nabavizadeh at Penn. This is another in a line of research collaborations we have had with the highest level of researchers at top tier institutions.” Dr. Rosol continued, “Today’s announcement exemplifies the broad reach of our tilmanocept platform. The development of applications of Tc99m tilmanocept as a prognostic biomarker in cancers could have far-reaching implications for monitoring patient treatment and making decisions about therapeutic benefit. We are excited to continue to develop new and valuable applications for our core technology.” “TAMs are a very important component of immune microenvironment in GBM, and it is crucial to have reliable imaging biomarkers to quantify and monitor TAMs during the course of treatment,” Dr. Nabavizadeh said. “The advantage of Tc99m tilmanocept is that it is already being used in patients for another research indication which means that we can move forward to human GBM patients under an Investigational New Drug Application (IND) if our preclinical studies show promising results.” About Navidea Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) is a biopharmaceutical company focused on the development of precision immunodiagnostic agents and immunotherapeutics. Navidea is developing multiple precision-targeted products based on its Manocept™ platform to enhance patient care by identifying the sites and pathways of 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. Navidea’s strategy is to deliver superior growth and shareholder return by bringing to market novel products and advancing the Company’s pipeline through global partnering and commercialization efforts.

Riptide Bioscience, Inc., announces the publication in Science Translational Medicine of a seminal article establishing a novel immune checkpoint, potentially useful in the treatment of both cancer and fibrosis. The article is entitled “Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and immune antitumor immune responses.” ( Riptide originated the development program and collaborated with Tuskegee University’s Cancer Research Center and the National Institutes of Health under separate research agreements. First author, Dr. Jesse Jaynes, Professor of Integrative Biosciences at Tuskegee, was joined by 42 co-authors from the National Cancer Institute, the National Center for Advancing Translational Sciences, and Tuskegee in this publication. The article documents extensive research to evaluate the efficacy and confirm the mechanism of Riptide drug candidate RP-182. RP-182 is the first of several engineered peptides emerging from a years-long effort to enhance the activity of naturally occurring host defense peptides (HDPs) with immunomodulatory properties. HDPs have the capacity to directly kill invasive microbes by forming pores in their membranes. However, certain HDPs also activate the immune system to fight the invaders – an activity which Riptide scientists discovered could be turned against “non-self” cancer cells. Jaynes commented, “We did an extensive search for the cellular target of these peptides. Surprisingly it turned out to be CD206, the canonical biomarker for M2-polarized tumor-associated macrophages (TAMs). That made these small proteins really promising as potential drugs, since CD206 is many times more highly expressed on M2 macrophages than on any other somatic cell type.” TAMs are the most common immune cells in the tumor microenvironment, often outnumbering cancer cells themselves in solid tumors. TAMs produce a tumor-promoting tissue environment. Riptide scientists demonstrated that engaging a specific set of amino acids in a particular domain of CD206, returned the macrophage population from M2-dominant to M1-dominant, restoring a tumor-inhibiting microenvironment. Jaynes’ colleague, Dr. Clayton Yates, Director of Tuskegee’s Cancer Research Center, added, “CD206 is a perfect narrow target for an exquisitely specific therapy. Our team was the first to show that this receptor could serve as a ‘toggle switch’ between macrophage phenotypes. We think it’s accurate to consider it a novel immune checkpoint – a completely natural mechanism that can have a profound effect on tumor etiology, without significant toxicity.” Yates continued, “We demonstrated that both in vitro and in vivo, the RP class of peptides are able to repolarize the macrophage population, and that once repolarized, the macrophages return to phagocytic activity and begin consuming cancer cells. They also send downstream signals to the T-cell, NK-cell and B-cell populations to attack the tumor.” Riptide President Dr. George Martin commented, “The results in animal models of organ cancers have been spectacular. RP-182, administered in combination with gemcitabine, produced the best results ever shown in NCI’s KRAS-p16 pancreatic cancer model. Also, with its distinctive mechanism, it has been shown to powerfully complement both chemotherapy and checkpoint inhibitor immunotherapy.” Dr. Martin continued, “Riptide has built very solid intellectual property around this program, and following the promising early work with RP-182, has developed two other peptide candidates with even better efficacy and excellent pharmacokinetics. These have demonstrated striking results in preclinical models of colon, breast, prostate, and skin cancers.“ Riptide Executive Vice President Dr. Henry Lopez added, “Also, since M2 macrophages are important in the progress of certain fibroses, including scleroderma and IPF, we anticipated – and have recently confirmed – potent efficacy in animal models of those diseases.” Dr. Martin concluded, “We’re now engaging with larger pharmaceutical companies to move this important program into clinic. I see a real opportunity, similar in many ways to the discovery of the first checkpoint inhibitors, to make a major impact on clinical practice.” Riptide Bioscience, Inc., with laboratories in Vallejo, California, maintains an intensive program of research into peptide-based therapeutics. View source version on businesswire.com: Charles Garvin, CEO, cgarvin@riptidebio.com NEXT ARTICLE More From BioPortfolio on "Riptide Bioscience Announces Discovery of Novel Immune Checkpoint" Related Companies Related Clinical Trials Related PubMed Entries Related Medications