Groundbreaking work
in cancer research.

Preclinical Programs

Extensive Preclinical Studies and Model Systems: APX3330 is a targeted inhibitor of the APE1/Ref-1 protein. APX3330 single-agent effect  has been tested in a broad variety of disease models including:

► Over 27 cancer cell lines (in vitro established cell lines, co-cultures and patient derived tumor cells) tested with APX3330 and APX20XX pipeline agents.

► In vivo xenograft and orthotopic models, including orthotopic models of metastasis and tumor-stromal cell-containing models using APX3330 and pipeline agents in:

  • Colon
  • PDAC
  • Bladder cancer
  • Prostate cancer
  • In vivo models of AML
  • Malignant peripheral nerve sheath tumors (MPNST)

► In vivo models for chemotherapy-induced peripheral neuropathy (CIPN) using APX3303.

► Numerous 3D-spheroid tumor micro-environment models (using patient derived cells and tumor microenvironment cellular components) with APX3330

► Other disease models in non-cancer indications. Given APX3330’s targeted effect on the APE1/Ref-1 protein, research is focused on understanding its effect on diseases in which the HIF, STAT3 or NFkB pathways are a major driving force, including:

  • Ocular neovascularization inhibition in vivo (Diabetic macular edema (DME) and age-related macular degeneration (AMD)
  • Prevention and reversal of Inflammatory bowel disease (IBD)
  • Malignant Peripheral Nerve Sheath Tumors (MPNST)
  • Models of cachexia

► CIPN studies: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating side effects of anti-cancer therapy. Indeed, anti-cancer drugs used for the six most common malignancies pose a substantial risk for CIPN. These drugs include, but are not limited to platinum agents, taxanes, vinca alkaloids, proteasome inhibitors, targeted therapeutic agents and even new, immune-modulators. There is currently no effective therapy to prevent or reverse CIPN making it an area of high unmet medical need for cancer patients world-wide. Using state of the art in vivo models, our data indicate that APX3330 protects sensory neurons from developing CIPN without compromising the anti-tumor effect of these drugs and that APX3330 actually reverses existing CIPN.

Combination studies:

We have conducted combination pre-clinical studies in a variety of backgrounds including:

► Inhibition of APE1/Ref-1 with APX3330 in combination with other agents blocking APE1/Ref-1 confluent pathways have provided synergistic anti-tumor effect in 3D-spheroid tumor-microenvironment models of cancer creating a “drug synthetic lethality” effect.

► Combination studies with clinical anti-metabolism drugs demonstrating synergy.

► Studies combining APX compounds with JAK/STAT pathway inhibitors demonstrate combination synergy

► APX3330 demonstrates combination effects with 5-FU and bevacizumab in colon and other preclinical models.