SM-88 is a combination therapy utilizing our proprietary dysfunctional tyrosine derivative as the backbone. Tyrosine is a non-essential amino acid that is readily consumed by cancer cells but has shown minimal uptake by normal healthy cells. SM-88’s tyrosine derivative is designed to be absorbed by cancer cell as if it were a functional tyrosine, but after uptake, interrupt metabolic processes like protein synthesis. This breaks down key defenses of the cancer cell, making it vulnerable to oxidative stress and apoptosis.

The key target we aim to disrupt within the cancer cell is mucin, specifically mucin 1, produced by the MUC1 oncogene. Mucin is highly overexpressed by most cancer cells and acts as a protective layer on the outside of each cancer cell, offering multiple defenses to the harsh tumor microenvironment and shielding it from the immune system.

The internal environment of cancer cells is also harsh, with elevated levels of free radicals or reactive oxygen species (ROS) created from the altered metabolism that cancers utilize (aerobic glycolysis). MUC1 has also been shown to be pivotal in balancing the elevated ROS by triggering the upregulation of key antioxidant defenses of the cell and preventing cancer from triggering its own death (apoptosis).

Therefore, SM-88’s disruption of the mucin coating exposes the cell to the acidic tumor environment and to the host immune system. Internally, the cell experiences building levels of ROS, triggering cell death (apoptosis).

There are three active non-tyrosine derivative components to SM-88: sirolimus, phenytoin, and methoxsalen, which are used at sub-therapeutic levels to both complement and augment the activity of the tyrosine derivative. Each agent is FDA approved, generic, and have years of research behind the mechanisms for which they are employed in our therapy.

  • Rapamycin (mTOR inhibitor approved for transplant rejection)
    The purpose is to trick cancer into thinking it is low in amino acids and drive increased uptake, including our dysfunctional tyrosine.
  • Phenytoin (P450 3A4 inducer approved for epilepsy)
    This drug causes the liver to release reactive lipid species that can accumulate in the tumor microenvironment. Cancer cells readily absorb lipids and this could further offset the ROS balance inside the cell.
  • Methoxsalen (Inducer of melanocyte production- approved for psoriasis) 10mg
    Melanocytes produce melanin which acts as an electron donor. We believe having a patient in a catalytic state could further drive the oxidative reactions occurring at the tumor.

We believe combinational approaches to adjust different aspects of tumor biology or microenvironment are more optimally positioned than targeted therapies that frequently are associated with driving resistance. Our approach of using low doses of repurposed agents, together with a product aimed to be selective to tumor cells to date has shown encouraging efficacy and there have been no drug-related serious adverse effects (“SAE”) in over 100 patients treated with SM-88.