Technology - AsclepiX Therapeutics

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AsclepiX Therapeutics Technology

A fundamental principle of biology is homeostasis: the ability of the body to seek and maintain a condition of equilibrium or stability. Using computational biology to identify multiple families of peptides that are potent regulators of vascular homeostasis, our clinical candidate peptides tap into these naturally existing self-regulating mechanisms that the body uses to maintain homeostasis and thus restore and maintain health.

Tapping into the powerful natural mechanisms of homeostasis

Maintaining homeostasis is an important characteristic of living things and critical for survival. Angiogenesis, also referred to as neovascularization, is one such tightly regulated, homeostatic process that occurs very rarely under normal physiological conditions, such as wound healing. Deregulation of this homeostatic process, and consequently the occurrence of uncontrolled neovascularization, has been correlated with the occurrence of several serious pathologies termed “angiogenic diseases.” All of these angiogenic diseases are characterized by the aberrant and unrestricted growth of new micro vessels and their propensity to exhibit altered properties, e.g. “leakiness” of blood and fluid.

In a healthy response to such processes, the body unleashes self-regulating mechanisms to restore homeostasis and health. Extracellular proteolysis, and the release of biologically active peptides from the basement membrane is one such important biochemical and cellular homeostatic regulator of neovascularization that occurs during wound healing. The basement membrane is comprised of many structural proteins such as various types of collagen. The breakdown products of these structural proteins are peptides that function to maintain homeostasis, turning off and thus reining in excessive neovascularization, inflammation, and scar formation.

Our clinical candidate peptides tap into these naturally

existing self-regulating mechanisms that the body uses to maintain homeostasis and thus restore and maintain health.

Using pioneering methods of computational biology to identify families of peptides that are potent regulators of vascular homeostasis.

We used an unbiased computational method to discover anti-angiogenic homeostatic peptide sequences in the human proteome. By mining the human proteome for peptide sequences proven in the literature to have anti-angiogenic properties and using powerful bioinformatics tools, we discovered hundreds of novel anti-angiogenic peptides in cryptic regions of 9 different classes of proteins. The proteins in which we found these anti-angiogenic peptide sequences span a wide array of protein types including structural proteins, anti-angiogenic proteins, pro-angiogenic proteins, chemokines, metalloproteases, and growth hormones.

Using endothelial cell proliferation and migration assays in vitro, we confirmed the anti-angiogenic properties of peptides from each class. Many of the most potent peptides in these in vitro assays also potently inhibited neovascularization in ocular models and inhibited tumor growth in multiple tumor types in mice. We identified the receptors and characterized the mechanism of action of the most promising candidates to understand their in vitro and in vivo activities. We further modified the sequences of these leading peptides using rational drug design to make them more drug-like using structure activity relationship (SAR) studies.