Our Science

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.

Using this strategy, we have identified our lead product candidate AXT107, and additional product candidates AXT201, AXT301 and AXT501.

AXT107 is a synthetic 20-mer peptide, derived from non-collagenous sequences of the collagen IV protein, and which are normally released during the wound healing process to turn off angiogenesis. It has exhibited activity in vitro as well as demonstrating efficacy in 10 different animal models of retinal disease. Our initial therapeutic focus is on diabetic macular edema (DME), age-related macular degeneration (wet AMD), and macular edema due to retinal vein occlusion (RVO), which are the leading causes of blindness in the western world.

AXT107 inhibits VEGFR2 and activates Tie2, the two prominent validated pathways for the treatment of retinal vascular diseases. AXT201, a peptide also derived from collagen IV, is our clinical candidate for the treatment of solid tumors. AXT301, a peptide derived from CXC chemokines, and AXT501, a peptide derived from the somatotropin class of peptides, are clinical candidates also for the treatment of solid tumors.

AXT107 self-assembles into a gel depot that slowly releases active AXT107 over months

Asclepix AXT107 Intravitre Injection

Although the process of identifying and developing AXT107 was geared toward maximal efficacy in blocking angiogenesis, fortuitously, the resulting peptide drug has unique properties that allow prolonged efficacy and safety with a single injection. AXT107 consists of all-natural amino acids and is highly soluble in aqueous solutions at a low pH.  However upon injection into the higher pH vitreous, it self-assembles into a small gel-like depot. The gel formed when AXT107 is injected into the inferior part of the eye is compact, does not break apart, and stays below the visual axis, releasing active levels of the peptide slowly over many months. This potentially may allow AXT107 to be dosed only once per year or even less frequently, compared with every 1 to 3 months as is required for the currently products approved and those in clinical development for the treatment of retinal vascular diseases.

Once formed into a gel after injection, it slowly releases active AXT107 peptide which diffuses to adjacent tissue in a process driven by the washout of the peptide through the choroidal vasculature. During this transport process, AXT107 passes through the vitreous and is sequestered in the retina, where it binds to and saturates integrins within the retinal tissue of the eye to induce long-lasting inhibition of pathological vascular leakage and neovascularization.