About PRTX-100

PRTX-100 is a formulation of a proprietary, highly purified form of the Staphylococcal Protein A, which is an immunomodulatory protein produced by Staphylococcus aureus bacteria. PRTX-100 has the ability, at very low concentrations, to bind to human B-lymphocytes and macrophages and to modulate immune processes that mediate inflammation in certain autoimmune diseases. Laboratory studies indicate that the mechanism involves interaction with specific immunologic signaling pathways. Pre-clinical animal studies also demonstrate that very low doses of PRTX-100 have potent therapeutic effects in certain models of immune mediated inflammatory diseases. To date, human clinical studies indicate that PRTX-100 is generally safe and well tolerated at all dose levels evaluated.

Staphylococcal protein A (SpA) is a bacterial virulence factor which structurally consists of five homologous immunoglobulin (Ig) binding domains placed in tandem.1 Each SpA domain is capable of binding with high affinity to the Fc region of human IgG and also binds to the Fab framework region of Igs in the mammalian VH3 gene family.2 This ability to bind to VH3 Igs results in SpA being one of the best characterized mammalian B-cell superantigens.

Non-clinical papers suggest that SpA, in the presence of excess serum IgG, may form small complexes of SpA and IgG, 3 which in vitro and in vivo can induce ‘alternatively activated’ or ‘regulatory’ macrophages. These have an anti-inflammatory phenotype, and such complexes may have activity in the mouse collagen induced arthritis model.4 SpA also interacts directly with VH3 B cells in mice and, at doses of 5 or 50 mg/kg, can cause activation followed by apoptosis of VH3 expressing B-cells.5

1. Moks T, Abrahmsen L, Nilsson B, et al. Eur J Biochem 1986;156:637–43.
2. Langone JJ, Das C, Mainwaring R, Shearer WT. Mol Cell Biochem 1985;65:159–70.
3. Graille M, Stura E, Corper L, et al. Proc Natl Acad Sci USA 2000;97:5399–404.
4. MacLellan L, Montgomery J, Sugiyama F, et al. Arthritis Rheum 2011;63:3897–907.
5. Goodyear C, Silverman G. J Exp Med 2003;197:1125–39.

PRTX-100 Clinical Experience

The Company has completed five clinical studies in man. In January 2012 Protalex completed a Phase 1b clinical trial in adult patients with active rheumatoid arthritis (RA) in South Africa (Study PRTX-100-103) which demonstrated that PRTX-100 was generally safe and well tolerated at all dose levels, and at the higher doses, more patients showed improvement in their CDAI (Clinical Disease Activity Index) for RA than did patients at the lower dose or placebo cohorts. In November 2012, Protalex commenced a new Phase 1b double blind, placebo controlled, multicenter, multiple-dose, dose escalation study (Study PRTX-100-104) in patients with active RA at nine U.S. sites to investigate safety and possible treatment effects at higher doses. Protalex completed dosing of the final cohort in this U.S. Study in July 2014 and reported top line data from the fifth and final cohort in the fourth quarter of 2014. The Company has commenced enrollment of PRTX-100-203.