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]

Core Insights - AlphaTON Capital Corp and its subsidiary Cyncado Therapeutics presented new findings at the AACR-NCI-EORTC conference, demonstrating the anti-tumor activity of their selective A2B receptor antagonist TT-4 in mesothelioma models, with plans for first-patient dosing in Q1 2026 [1][4][10] Group 1: Research Findings - The study provides evidence that selective adenosine A2B receptor inhibition has a direct anti-tumor effect in mesothelioma cells, reducing PD-L1 expression and pCREB levels, and modulating YAP signaling [1][2][3] - In preclinical models, TT-4 showed superior monotherapy activity compared to anti-PD-1, and the combination of TT-4 with anti-PD-1 further enhanced tumor control and immune infiltration [2][3] - In human mesothelioma spheroid systems, hypoxia-linked adenosine signaling was found to increase tumor growth and PD-L1 expression, while TT-4 effectively reduced cell growth and PD-L1 protein levels [3] Group 2: Clinical Development - TT-4 is advancing towards first-patient dosing scheduled for Q1 2026, with the current data supporting its clinical translation [4][10] - The clinical program is focused on targeting known checkpoint resistance pathways to improve treatment responses and patient quality of life [9][10] Group 3: Company Overview - AlphaTON Capital is a digital asset treasury company that also engages in drug development, focusing on oncology and immunotherapy assets [6][9] - Cyncado Therapeutics is developing small molecule adenosine receptor antagonists, with TT-4 being the lead program aimed at overcoming immune suppression in oncology [10]

Core Insights - AlphaTON Capital Corp and its subsidiary Cyncado Therapeutics have announced promising results regarding the efficacy of TT-4, an A2B receptor antagonist, in treating human epithelioid mesothelioma, showing superior performance compared to anti-PD-1 therapy [1][2][3] Group 1: Research Findings - The abstract published indicates that A2B receptor inhibition leads to a reduction in adenosine-mediated PD-L1 expression in mesothelioma cells, which is associated with decreased CREB phosphorylation [1][2] - In vivo studies demonstrated that TT-4 monotherapy outperformed anti-PD-1, and the combination of TT-4 with anti-PD-1 exhibited significantly enhanced anti-tumor activity compared to either treatment alone, with increased T-cell infiltration observed [2][3] Group 2: Presentation Details - The findings will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on October 25, 2025, in Boston, Massachusetts [4] Group 3: Company Overview - AlphaTON Capital is focused on building a strategic reserve of TON tokens and developing the Telegram ecosystem, providing institutional-grade exposure to the TON ecosystem while maintaining governance standards of a Nasdaq-listed company [5][6] - Cyncado Therapeutics is developing small molecule adenosine receptor antagonists targeting A2A and A2B receptors, with TT-4 being the lead program aimed at overcoming immune suppression in oncology, particularly mesothelioma [8]