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Introduction

SIWA Therapeutics, Inc. has developed a proprietary humanized monoclonal antibody, SIWA318H (“318H”), that selectively targets, for immune system destruction, a biomarker on cells exhibiting a combination of: (a) an abnormally high level of glycolysis (Warburg effect) and (b) oxidative stress. Cells with this biomarker include specifically: (1) cancer cells, (2) senescent cells (“SCs”), and (3) microbially-infected cells. We have demonstrated that 318H binds to all three cell types, including cancer cells from all types of cancers tested, human SCs from numerous tissues, including renal tubular epithelial cells made senescent, Alzheimer’s and Parkinson’s diseases cells and cells infected by SARS-CoV-2 (COVID-19) and Influenza A. We have a significant worldwide patent portfolio covering 318H and its applications (30+ patent families; at 12/31/20, approximately 25 patents had issued).
  • Pancreatic cancer is the initial development target for SIWA318H (“S18H”) – High unmet medical need and potential for FDA fast track/breakthrough designation
  • Pancreatic cancers show increased aerobic glycolysis and overexpression of surface proteins e.g. vimentin (Wei et. Al.; doi:10.1016/j.canlet.2109.03.009)
  • Aerobic glycolysis produces glyoxal which carboxymethylates lysines on vimentin and other proteins on cancer cells
  • Carboxymethyllysine is also highly increased on:
  • Stromal cells within the tumor microenvironment that support cancer cell growth and suppress local anti-tumor immunity
  • On cells infected with oncogenic viruses
  • Cells infected with other viruses (e.g. SARS-CoV-2, influenza A)
  • Senescent cells

SIWA MAB

  • 318H is a humanized IgG1 AB that selectively targets cancer cells expressing carboxymethyllysine (CML) epitopes
  • 318H binds CML with high affinity (Kd = 2.6 nM)
  • 318H binds to the FC receptor Gamma RIIIa with high affinity
  • 318H triggers ADCC
  • 318H, as an IgG1, activates C1q

Mechanisms of Action (MOA) for 318H

SIWA318H is a monoclonal antibody that selectively targets an advanced glycation end product found on the surface of cells exhibiting an abnormally high level of aerobic glycolysis and oxidative stress, processes linked to tumor genesis and metastasis. Targeted cell death is induced by SIWA318H through several different mechanisms of action, including the opsonization and phagocytosis of targeted cancer cells, antibody dependent cellular cytotoxicity through NK cells, complement dependent cell lysis, and the induction of tumor specific T and B cells resulting in the lysis of targeted cells.