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.
- 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
- 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
- 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.