A TBXT Inhibitor for Chordoma Therapy

Chordoma is a rare malignant sarcoma originating from residual embryonic notochord cells. Chordomas are challenging to treat due to their proximity to the spinal cord, and pose a high likelihood of recurrence following surgery and radiation. There are no approved systemic therapies for chordoma, and patients with advanced disease face poor prognoses. The TBXT gene is commonly overexpressed and believed to be a key driver of this cancer. Thus a systemically delivered compound that directly inhibits TBXT has enormous potential to revolutionize the chordoma treatment paradigm. We are developing a direct inhibitor of TBXT expression. Antisense oligonucleotides (ASOs) represent a powerful strategy for targeting transcription factors such as TBXT that are otherwise not easily druggable. Instead of binding to protein, ASOs base-pair specifically with encoding mRNA, thereby preventing its translation into protein. We have demonstrated that ASOs delivered systemically can accumulate in solid tumors without accompanying toxicities. Our targeted technology aims to establish a new treatment paradigm applicable to nearly all patients with advanced chordoma and other TBXT-dependent cancers. As TBXT is turned off in non-cancerous cells, the specificity of our compound should afford a broad therapeutic window with minimal harm to healthy tissue. Our technology has the power to halt chordoma tumor growth and disrupt the therapeutic landscape for this disease with a high unmet medical need Project Number: 75N91025C00011-0-9999-1 | Fiscal Year: 2025 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: STUART HWANG | Institution: ASO THERAPEUTICS, INC., SAN RAFAEL, CA | Award Amount: $354,991 | Activity Code: N43 View on NIH RePORTER: https://reporter.nih.gov/project-details/11458987