New publication details the characterization of novel scaffold proteins that can enable engineered exosomes with defined therapeutic properties

Codiak BioSciences, a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, today announced the advance online publication of a new manuscript. The paper, entitled “A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties,” by Dooley et al, will appear in an upcoming print issue of Molecular Therapythe journal of the American Society of Gene and Cell Therapy. The publication describes the identification and characterization of two novel exosome-associated proteins, PTGFRN and BASP1, that enable Codiak’s proprietary engEx Platform and facilitate precise design and engineering of exosomes for potential therapeutic purposes.

PTGFRN and BASP1 are highly abundant, naturally-occurring proteins that, through Codiak’s research, have been found to enable high-density exosome surface display and luminal loading of a wide range of macromolecules that can be directed to specific target cells of interest. In preclinical models, the use of PTGFRN and BASP1 to display biologically active molecules on the surface of or inside exosomes, respectively, resulted in uniform incorporation and increased potency, suggesting the potential utility of these engineered exosomes in a wide variety of therapeutic settings. These two proteins can also be used in combination, which further broadens the utility and modular approach to designing engineered exosomes for targeted delivery of numerous drug payloads to specific cells.

“The identification and characterization of PTGFRN and BASP1 by our scientific team provided us with versatile scaffolds to precisely and reliably design exosome therapeutic candidates with intentionally chosen properties, thus forming the backbone of our engineering platform,” said Douglas E. Williams, Ph.D., President and Chief Executive Officer of Codiak. “The ability to functionalize exosomes with diverse macromolecules at a high density represents a significant advance toward unlocking the therapeutic potential of these extracellular vesicles.”

To identify potential scaffold proteins for engineering exosomes, Codiak scientists first developed a methodology to stringently purify a population of exosomes. Detailed characterization of these high-purity exosomes enabled the identification of exosome-specific proteins, PTGFRN and BASP1. When used as scaffold proteins to incorporate biologically active payloads either on or in exosomes, PTGFRN and BASP1 were shown to be superior to previously reported exosome scaffolds with respect to copy number and uniformity. These proteins enabled functional display of cytokines, antibodies/fragments, TNF superfamily members, enzymes, RNA binding proteins and vaccine antigens, all of which retained pharmacodynamic activity in vivo.

Codiak is advancing a broad pipeline of product candidates generated using its engEx Platform. Codiak’s most advanced programs use PTGFRN to display biologically active molecules and/or direct tropism to specific cellular targets for precise delivery of drug payloads. Codiak’s two clinical programs, exoIL-12™ and exoSTING™, are the first engineered exosomes to be evaluated in humans. Initial results from the Phase 1 exoIL-12 program demonstrated tolerability and absence of systemic IL-12 exposure in healthy volunteers. Safety, biomarker and preliminary anti-tumor efficacy results for both clinical programs are anticipated in mid-2021.

About the engEx™ Platform
Codiak’s proprietary engEx Platform is designed to enable the development of engineered exosome therapeutics for a wide spectrum of diseases and to manufacture them reproducibly and at scale to pharmaceutical standards. By leveraging the inherent biology, function and tolerability profile of exosomes, Codiak is developing engEx exosomes designed to carry and protect potent drug molecules, provide selective delivery and elicit the desired pharmacology at the desired tissue and cellular sites. Through its engEx Platform, Codiak seeks to direct tropism and distribution by engineering exosomes to carry on their surface specific targeting drug moieties, such as proteins, antibodies/fragments, and peptides, individually or in combination. Codiak scientists have identified two exosomal proteins that serve as surface and luminal scaffolds. By engineering the exosome surface or lumen and optimizing the route of administration, Codiak aims to deliver engEx exosomes to the desired cell and tissue to more selectively engage the drug target, potentially enhancing the therapeutic index by improving potency and reducing toxicity.

Source – Globe Newswire

Dooley K, McConnell RE, Xu K et al . (2021) A Versatile Platform for Generating Engineered Extracellular Vesicles with Defined Therapeutic Properties. Molecular Therapy [Epub ahead of ptint]. [abstract]

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