Targeting Gene Delivery System (TDS)
a. General Introduction
Epeius Biotech’s proprietary TDS technology represents an enabling biotechnology platform for the development of targeted molecular and genetic medicines. The first targeted delivery system (TDS) if its kind, this pioneering technology operates within the human circulatory system to seek out the biochemical / histological hallmarks of disease: a property referred to as pathotropic (or disease-seeking) targeting. This biotechnology can be adapted for the strategic delivery of a broad range of therapeutic genes, RNAi, recombinant proteins, peptides, cytokines, and many other biopharmaceutical agents.
The targeted delivery of therapeutic genes and/or biomolecules is an emerging theme in the development of safe and more efficacious treatments for life-threatening diseases. Unfortunately, the goal of targeted gene delivery in vivo (in the body) has remained elusive, which previously hindered the clinical development of genetic medicine. With the advent of TDS technology and the adaptation of this sophisticated biotechnology to therapeutic gene delivery, Epeius has revolutionized the field of medical delivery.
This TDS technology is embodied in Epeius Biotech’s lead product, Rexin-G, the world’s first tumor-targeted genetic medicine to be successfully validated in the clinic. Injected intravenously, the TDS enables Rexin-G to seek out, penetrate deeply, and accumulate selectively in primary tumors and metastatic sites, delivering a payload of genetic medicine precisely where it is needed most—thereby Targeting Cancer from the Inside.
Conceptually, TDS technology consists of three separate and distinct components: (i) a “pathotropic” or disease seeking guidance system, (ii) a highly-engineered stealth nanoparticle / gene delivery vehicle or vector, and (iii) a designer “killer” gene that compels cancer cells and tumor-associated vasculature to self-destruct (by apoptosis) without causing collateral damage to non-target tissues. Combined together in a single medicinal unit (a therapeutic nanoparticle), these three components effectively navigate one of the long-standing hurdles in genetic medicine.
b. Major High-Tech Components
The Guidance System: Precision-targeted gene delivery is accomplished by incorporating a physiological surveillance function inherent in von Willebrand clotting factor, which is responsible for guiding platelets to exposed collagen in wounds, cancers, and areas of significant tissue disruption. When injected intravenously, this surveillance function guides the targeted gene delivery vehicle deep into the tumorous tissues, wherein collagenous matrix proteins are exposed and/or newly deposited as a result of tumor invasion, tumor-associated angiogenesis, and reactive stroma formation. This powerful yet elegant guidance system—designed to deliver the genetic medicine quickly (within minutes) and efficiently to the tumor site—is uniquely suited to function within the context of the human circulatory system.
The Stealth Nanoparticles: Incorporating years of basic research in molecular biology, genetics, and virology that has established the broad safety profile of retroviral vectors in a multitude of studies, Epeius employs highly-engineered retroviral vectors into the platform TDS technology of its anti-cancer agents. The resulting vectors have a set of virtues (efficiency of gene delivery and immunological stealth) and limitations (gene delivery to proliferative cells only), that act in concert with the tumor-targeting function to increase the overall safety and efficacy of the system, and in terms of avoiding non-target organs. Moreover, scientists at Epeius Biotechnologies have engineered these clinical-grade vector systems to the highest levels of safety and performance, ensuring that the vectors contain no viral genes and are certifiably replication incompetent (that is, capable of delivering a designated therapeutic gene once, and only once) while enhancing the therapeutic potency of the anti-cancer agent (titers) and the levels of therapeutic gene expression in the target cells. In cases where the therapeutic payload is not, by itself, cytocidal (as is Rexin-G), but intended to deliver a non-lethal immune-activating gene product (like Reximmune-C), an additional suicide gene is incorporated into the gene expression cassette to provide a fail-safe mechanism for eliminating residual target cells pharmacologically.
The Therapeutic Designer Gene: An extensive working knowledge of cellular growth control mechanisms, executive cell cycle control enzymes, proto-oncogenes, and their exquisite functions in the body has enabled Epeius to identify the most strategic and efficacious genetic payloads to destroy tumor cells and their associated blood supply, and to enhance the body’s own natural defenses against tumor tissues. In Rexin-G, Epeuis incorporates a dominant-negative mutant of the human cyclin-G1 gene, a powerful, essential, and primal component of the executive cell cycle control pathway. Targeting and disrupting this critical locus and regulatory component of the cancer cell’s universal replication machinery empowers Rexin-G to operate with striking tumoricidal activity in a wide variety of cancers. By targeting proliferative tumor-associated neovasculature, while sparing normal non-dividing blood vessels, Rexin-G exhibits potent anti-angiogenic properties, as well. Combining these powerful tumoricidal and anti-angiogenic activities in a single medicinal unit, Rexin-G exhibits unprecedented single-agent efficacy in a broad spectrum of different tumor types. Epeius is bringing the benefits of genetic medicine to the patient with Rexin-G, the world's first tumor-targeted gene delivery product that has been validated in the clinic.
