SAR-001
Selective Degrader
A precision therapeutic targeting the ASPSCR1-TFE3 fusion driver in Alveolar Soft Part Sarcoma.
The Target
ASPSCR1-TFE3 Fusion
Alveolar Soft Part Sarcoma (ASPS) is driven by a single, defining molecular event: the t(X;17)(p11;q25) translocation. This creates the ASPSCR1-TFE3 fusion protein, a constitutively active transcription factor that drives tumor growth, angiogenesis, and immune evasion.
Unlike other cancers with complex mutational landscapes, ASPS is addicted to this single driver, making it an ideal candidate for precision targeting.
The Modality
Targeted Protein Degradation (PROTACs)
Traditional inhibitors often fail to block transcription factors like TFE3 because they lack deep binding pockets. SAR-001 utilizes Targeted Protein Degradation.
Instead of just blocking the protein, SAR-001 recruits the cell's own waste disposal system (the ubiquitin-proteasome system) to physically destroy the ASPSCR1-TFE3 protein, removing the driver of the disease entirely.
Differentiation
VCP Inhibition (e.g., CB-5083)
Broad mechanism. High systemic toxicity. Failed in clinic due to off-target effects (visual disturbances).
SAR-001 Degradation
Selective precision. Targets only the fusion protein. Designed to spare wild-type TFE3 and minimize systemic toxicity.
The Unmet Need
Current Standard of Care
Patients currently rely on Atezolizumab (immunotherapy) and TKIs. While these can stabilize disease, they are rarely curative and response rates vary. There is no approved therapy targeting the underlying genetic driver.
Previous Failures
Previous attempts to target the pathway via VCP inhibitors (like CB-5083) failed due to unacceptable toxicity. A more precise approach is required.