Codiak BioSciences, the leading exosome therapeutics company, today announced results from preclinical studies demonstrating the potential of Codiak’s proprietary engineered exosome therapeutic, exoSTING. exoSTING is composed of precision engineered exosomes loaded with a potent small molecule STING (stimulator of interferon genes) agonist. The precision engineering of exoSTING provides for selective, preferential STING delivery to antigen presenting cells (APCs). In these preclinical studies, exoSTING generated potent, targeted, and sustained antitumor immunity – including in metastatic tumors – without systemic elevation of toxic cytokines. These data will be presented at 12:20 p.m. ET on Saturday, November 10th at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Washington, D.C., in a poster entitled, “Selective delivery of exosome-mediated STING agonist to antigen presenting cells results in significantly improved potency and reduced toxicity” (#P618 ).
“These studies highlight the unique profile of exoSTING to selectively activate the STING pathway in tumor-resident APCs without toxic systemic cytokine elevation,” said Douglas Williams, Ph.D., President and CEO of Codiak. “The potent T cell-mediated antitumor immune responses elicited with very low doses of STING agonists are the result of the rational drug design of exoSTING created using our proprietary exosome engineering platform, engEX™. In contrast with free STING agonists, exoSTING is highly potent, is not compromised by systemic cytokine production, and preserves the viability of T cells and antigen presenting cells, thereby markedly improving the therapeutic window. exoSTING highlights the potential of the engEx™ platform to create novel medicines through precision exosome engineering.”
STING is a sensor of cytosolic nucleotides from both invading pathogens and tumor cells and is ubiquitously expressed by a majority of normal cells. STING activation in normal cells can stimulate stress response and cell death. Recent insights in cancer immunology show that activation of the STING pathway within tumor-resident APCs leads to a potent T cell-mediated antitumor immune response.
Codiak’s data highlight the unique profile of exoSTING, where the STING agonist is selectively delivered to tumor-resident APCs by using Codiak’s precision exosome platform to leverage the natural biology of exosomes, which carry macromolecules between tumor and immune cells. In nature, DNA from tumor cells are delivered to the cytosol of APCs by tumor-derived exosomes, thereby activating the STING pathway. exoSTING is surface engineered to enhance uptake in APCs and luminally loaded with a STING agonist, which elicits a potent type I IFN response. exoSTING selectively activates the STING pathway in APCs, limiting STING activation to the desired immune cells in the tumor microenvironment and producing a potent antitumor immune response without systemic effects.
The data show multi-log potency increases in IFNb production for exoSTING compared to free STING agonist, due to selective uptake and activation of APCs, preserved viability of T cells and APCs, and production of systemic T cell-mediated antitumor immunity resulting in tumor cures in checkpoint refractory tumor models. The Codiak engEX™ exosome engineering platform is being applied broadly to create a pipeline of precision-targeted therapies that offer potential in diseases that are challenging to treat using existing methodologies.
The poster will available on the Publications page of the www.codiakbio.com website following the presentation at SITC’s 33rd Annual Meeting.
Exosomes are nanometer-sized membrane sacs, or vesicles, that are released and received by nearly all cells. Exosomes are an ancient system of intercellular communication, through which they deliver various molecules (DNA, RNA, proteins, lipids) from cell to cell. Upon delivery, exosomal cargo can change biological functions in recipient cells according to the instructions encoded by the payload. Exosomes traffic to specific cellular targets, thereby offering the potential to deliver diverse therapies to specific cells and modulate cellular function to achieve therapeutic benefit.
Codiak BioSciences is taking advantage of the natural propensity of exosomes to deliver macromolecule payloads either on or in the exosome to cells to treat a variety of human diseases.
About Codiak BioSciences
Codiak BioSciences is the leader in the emerging field of exosome therapeutics. Founded in 2015 and headquartered in Cambridge, Mass., Codiak has built a proprietary technology platform for exosome engineering and manufacturing that allows for precise therapeutic targeting — opening the door to the development of therapies to treat a diverse array of diseases that are currently difficult or impossible to treat using existing methodologies.
Source – PR Newswire