The Company’s product development programs have been conducted in collaboration with investigators at the University of Minnesota and the University of Maastricht. These relationships provide key skills that the Company employs to: 1) identify bioactive peptide drug leads through computational and structural peptide chemistry, 2) translate those leads via rational design into peptide mimetics, and 3) discover new small molecule chemical entities ("NCEs"). The PepTx discovery platform includes a productive pre-clinical program to document bioactivities by in vitro assays, evaluate therapeutic potential in animal models of disease states and prepare for Phase I human trials.

The Company’s founding scientist, Dr. Kevin Mayo, has centered his investigation on addressing the limitations of protein and peptide drugs. He has discovered peptides that constitute the therapeutic portion of a known anti-cancer protein, and then he has reduced the size of these peptide molecules by adding an organic chemical scaffold to portions of the peptide (partial peptidomimetic). In most such instances, he has been able to uncover a small organic NCE with the same activity. An academic organic chemist, Dr. Thomas Hoye, has conducted much of the organic chemistry experimentation, while Dr. Arjan Griffioen, a PepTx scientific co-founder and prominent Dutch cancer biologist, has been responsible for managing the pre-clinical evaluation of promising molecules.

PTX001, (referred to as Anginex in a number of publications), is a 33 amino acid peptide that exhibits potent anti-angiogenic and anti-tumor effects. In a series of in vitro and in vivo assays PTX001 was evaluated alone and in comparison to other drug leads and commercial therapeutics. The Company also studied PTX001 for potential synergistic effects when used in combination with other cancer treatments. The most dramatic clinical responses occurred in combination with other chemotherapies and radiation therapy. The mode of action of Anginex has been studied extensively in Maastricht, and these studies have identified a novel site of action.

A smaller, partial peptidomimetic, PTX004 (referred to as 6DBF7 in publications), is a derivative of PTX001 that has proven superior to PTX001 in several pre-clinical mouse studies. Most recently, the team of Mayo and Hoye have discovered through rational drug design a small organic molecule, PTX008. Preliminary in vivo tumor model studies demonstrate that PTX008 is at least as potent an anti-tumor drug as PTX004 in mice. Further experiments will compare the activity of PTX008 to and in combination with standard cancer therapies.

 Antimicrobials

Employing the same structural activity relationships (SAR) strategy used in the PepTx cancer program, Dr. Mayo designed a series of peptides with potent bactericidal and endotoxin-neutralizing properties. These molecules belong to a class of antimicrobial agents that effectively disintegrate bacterial cell membranes, thereby killing bacteria. The first lead peptide in this group is PTX002, (referred to as Prosep in publications); three subsequent variations are, PTX005 (referred to as SC-4 in the past), PTX006 and PTX007. The latter, PTX007, is a small, non-peptidic molecule NCE that shares structural similarity to PTX005 and thus supports the PepTx drug discovery engine strategy—moving from protein to peptide to NCE small molecule mimetic. These derivatives of Prosep show broad-spectrum antimicrobial activity in vitro, including a potent effect upon antibiotic resistant bacteria. In addition to demonstrating disintegration of bacterial cell membranes, PTX002 and PTX005 neutralize endotoxin lipopolysaccharide (LPS) in the blood and may prove effective in treating sepsis.