Barricade Science

We have discovered a new class of compounds, TASINs, that specifically kill cancer cells containing the mutated or truncated APC gene without toxicity to normal cells.

This discovery could be key to catching colorectal cancer (CRC) at its earliest stage, since more than 80% of the ~1.8 million annual CRC cases first present with a mutation to the adenomatous polyposis coli (APC) gene.

TASINs Cytotoxicity Overview:

TASIN disrupts intracellular cholesterol, which is critical for mutant-APC cancer cell survival.

1

TASIN binds to EBP, significantly reducing cholesterol levels within truncated APC cancer cells.

2

Cancer cells become stressed. Cellular defenses are disrupted. (ER stress observed: JNK activation, increase in ROS, inhibition of Akt “pro-survival” cell signaling.)

3

End Result: Colorectal cancer cell death (apoptosis)
  • Inhibition of EBP leads to a reduction of cholesterol levels within the cell resulting in ER stress and ultimately CRC cell death.
  • TASINs are orally bioavailable and have demonstrated to significantly reduce tumor size in preclinical APCtrunc mouse models.

Genetic Mouse Model:

TASIN-1 results in decreased number and size of polyps in the CPC;Apc genetic mouse model.

We’ve already seen outstanding activity in animal models leveraging synthetic lethality, without toxicity. 

TASIN Lead Program

Colorectal Cancer

  • Potent, first-in-class small molecules licensed from University of Texas Southwestern – Medical Center.
  • Selective for Truncated APC, an important and highly prevalent marker of colorectal cancer.
  • Strong preclinical POC; currently selecting lead molecule.
  • MOA via inhibition of EBP, intermediate enzyme in cholesterol biosynthesis.
  • Represents a unique and large commercial opportunity.

TASIN Secondary Program

Neurology

  • Recently, EBP has also been shown to be an important target in demyelinating diseases, such as multiple sclerosis. 
  • A recent Nature paper showed that Barricade’s compounds restored myelin in vitro. 
  • Barricade intends to rapidly advance a second TASIN for this high-value indication.

Moving Forward:

  • Our lead TASINs are protected by global patents, (composition of matter and method of use).
  • Barricade plans to submit its first IND in mid-2020 and initiate a Phase I clinical trial in patients with advanced CRC.
  • Human POC is projected in 2021.
  • Concurrently, we will advance a second TASIN for neurology applications to IND in 2021, with potential for rapid human POC.