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| Oncology Market PTX001 In collaboration with Dr. Arjan Griffioen at the University of Maastricht, The Netherlands, Dr. Mayo discovered that one bpep peptide was strongly anti-angiogenic in animals models of tumor growth. PTX001 and related molecules inhibit, and in some cases cause regression of, tumor growth. Subsequent research in Dr. Griffioen’s lab led to the putative identification of the PTX001 target on endothelial cells. This is a novel target in oncology research and is unlike more well known targets, e.g. EGF receptor and VEGF. PTX001 inhibits endothelial cell growth in newly-forming blood vessels and exhibits potent anti-tumor activity in many in vivo models using mostly human-derived carcinoma in mice and rats. PTX001 was generally delivered effectively by using a subcutaneous osmotic pump but may be effective in lower doses as a bolus injection or IV drip. PTX001 is stable in solution and as a dried powder for prolonged storage at room temperature. The serum half-life in mice of PTX001 is 50-90 minutes, rather long for a peptide. PTX004 In collaboration with Dr. Thomas Hoye, Dr. Mayo applied SAR information to design a series of smaller variants using organic chemical scaffolds to maintain the bioactive structure or topology (shape) of PTX001. The bioactive structure of PTX001 is defined by an amphipathic b-sheet structure with one hydrophobic surface and one hydrophilic surface possessing numerous positively-charged amino acid residues. One such variant, PTX004, contains a b-turn mimetic (dibenzofuran, DBF) and two short sequences of amino acid residues from PTX001. In this regard, PTX004 contains only 13 amino acid residues and maintains the functionally key amphipathic b-sheet conformation of PTX001. PTX008 Following on the success of PTX004, an effort was made to design a completely non-peptidic mimetic of PTX001. The resulting small molecule PTX008 is very active in preliminary studies using a mouse tumor model. The potential advantages of PTX008 are less expensive manufacturing cost and the potential for oral availability. The Company is presently in discussions with the University of Minnesota to append our licensing agreement to include for PTX008, according to the provisions established in the Company’s master agreement with the University. Pre-clinical evaluations Pre-clinical evaluation of the PepTx drug leads were conducted within the laboratories of the University of Minnesota and the University of Maastricht. Much of the work was directed by Drs. Mayo and Griffioen and executed by a graduate student, Ruud P. M. Dings. The studies form the basis for his published Ph.D. thesis. The Company now supports Dr. Dings at the University of Minnesota, as he continues to evaluate the PepTx drug leads. |
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