Janux Therapeutics announces interim data for PSMA-TRACTr JANX007

Janux Therapeutics announced interim Phase 1 clinical data for PSMA-TRACTr JANX007 in adult subjects with metastatic castration-resistant prostate cancer, or mCRPC, and provided a pipeline update. The data from eight patients from the first three cohorts of the dose escalation portion of the Phase 1a clinical trial, as of June 28 show that JANX007 has been generally well tolerated, with no dose-limiting toxicities. JANX007 has been dosed at 300microgram flat dose, which is above the projected maximum tolerable dose of the parental T cell engagers. JANX007 showed clinical activity at both 100microgram and 300microgram flat doses and yielded best overall PSA reductions between 31% and 67% in four of the five patients who received a flat dose. Grade 1 or 2 cytokine release syndrome, or CRS, was observed only in patients who demonstrated PSA reductions, suggesting cytokine release resulting from anti-tumor activity was associated with CRS. No Grade 3 CRS has been observed. The most common, non-CRS related adverse event observations have been generally consistent with tumor-specific activity and reduced PSMA(+) healthy tissue activity. No transaminitis was observed. JANX007 clinical development has moved into step-dosing and dose optimization with the goal to enhance efficacy while maintaining suitable safety results. The TRACTr technology is designed to create potent T cell engagers by tumor-specific activation via mask cleavage by tumor proteases. Plasma levels in patients exhibited prolonged TRACTr exposure, clear evidence of activation as measured by a specific cleavage fragment, and lack of accumulation of the active TCE in the blood. The lack of TCE accumulation shows consistency with TRACTr design principles and suggest that observed PSA reductions have been a result of tumor activation and not systemic TCE exposure.