AlphaTON (Nasdaq:ATON) and Cyncado Therapeutics: Preclinical Mesothelioma Data Show Direct A2B Tumor Activity; TT-4 Achieved >90% Tumor Growth Inhibition; First-Patient Dosing on Track for Q1 2026

Core Insights - The article highlights the promising results of TT-4, a selective A2B receptor antagonist, demonstrating over 90% tumor growth inhibition when combined with anti-PD-1 in mesothelioma models, and superior activity compared to anti-PD-1 monotherapy [1][3][10] - Cyncado Therapeutics is on track for first-patient dosing of TT-4 in Q1 2026, indicating progress in clinical development [2][5][11] Summary by Sections Anti-Tumor Activity - Selective A2B receptor inhibition shows direct anti-tumor effects in both epithelial and non-epithelioid mesothelioma models [2][10] - TT-4 monotherapy outperformed anti-PD-1, with additional benefits observed in combination therapy [2][10] Mechanistic Insights - The mechanism involves decreased pCREB leading to reduced PD-L1 expression in human mesothelioma cells, with TT-4 blocking NECA-induced pCREB in murine models [10][11] - Combination therapy resulted in increased immune-effector infiltration, suggesting potential for durable immune responses [10] Clinical Development - Cyncado is finalizing clinical development plans for TT-4, with first-patient dosing anticipated in Q1 2026 [5][11] - TT-4 is IND-enabled, indicating readiness for clinical trials [10][11]