AU409 transcription regulator (TATA-box modulation) shows 11% PR and multi-month disease control in pretreated HCC

AU409 is a first-in-class oral small molecule designed to modulate transcription at TATA-box regulatory elements, evaluated as monotherapy across two ongoing Phase 1 dose-escalation studies in advanced solid tumors with liver-dominant disease (US; NCT05791448) and HCC-only (Asia; NCT06374485). In 18 treated patients (US n=10; Asia n=8; HCC n=15 overall), all HCC patients had prior immunotherapy (median 1 prior line in both studies); no DLTs were observed and MTD was not reached (currently dosing to 420mg QD US; 300mg QD Asia). Among 9 evaluable US patients, 1 HCC patient had an ongoing partial response at 12 months (ORR 11%) and 5/9 had stable disease (DCR 67%; 4 SD ≥4 months); in Asia, 4/6 evaluable had SD (DCR 67%; 1 SD ≥10 months)—a disease-control rate broadly in the same ballpark as approved 2L/3L TKIs like cabozantinib (ORR ~4%) in CELESTIAL, though AU409’s confirmed response depth/rate remains early and sample-limited; grade 3–4 events were limited to AST/ALT elevations in the US (n=3) with no grade 3–4 TRAEs reported in Asia. Paired tumor biopsies (n=3 HCC at 300mg) showed downregulation of multiple TATA-regulated transcripts (including MYC, AFP, CCL20), with the strongest suppression in the patient achieving PR, supporting early on-target proof-of-mechanism.