AlphaTON Capital Corp and its oncology-focused subsidiary Cyncado Therapeutics have unveiled new findings on their investigational drug TT-4 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. The data, presented by researchers from the Italian Group for Mesothelioma (G.I.Me) and their collaborators, indicates that selective inhibition of the adenosine A2B receptor can directly combat tumor growth in mesothelioma, a rare and aggressive cancer.
The results demonstrate a significant reduction in the expression of PD-L1, a protein often associated with immune evasion in tumors, alongside decreased levels of phosphorylated CREB (pCREB). This suggests a potential mechanism through which TT-4 may exert its therapeutic effects. Furthermore, the findings show that TT-4 not only performs effectively on its own but also enhances the effects of anti-PD-1 therapy, leading to improved tumor control and increased immune cell infiltration.
The preclinical studies reveal that in hypoxic conditions, which are common in mesothelioma, adenosine signaling can stimulate tumor growth and upregulate PD-L1. However, the inhibition of the A2B receptor by TT-4 not only curtailed cell proliferation but also diminished PD-L1 levels via reduced CREB phosphorylation. In animal models, TT-4 effectively blocked the growth-promoting signals in mesothelioma cells, and when used in combination with anti-PD-1 treatment, it further inhibited tumor development.
“Mesothelioma is characterized by a hypoxic and adenosine-rich environment, making the A2B receptor a compelling target,” stated Rob Kramer, PhD, Chief Scientific Officer at Cyncado Therapeutics. “We are on track to initiate first-patient dosing of TT-4 in Q1 2026, translating these promising preclinical signals into clinical practice.”
Brittany Kaiser, CEO of AlphaTON Capital, emphasized the significance of these findings, stating, “This initial evidence reinforces our confidence in TT-4 as a viable treatment option for mesothelioma and guides our resource allocation towards achieving proof of concept in human trials.”
The current status of clinical programs includes ongoing Phase 1 dose escalation trials for TT-10, an A2A receptor antagonist, and preparations for the IND-enabled TT-4 program aimed at first-patient dosing.
The poster presentation, titled “ADORA2B Inhibition in Mesothelioma (MMe) Cells Affects PD-L1 Expression and Exerts an Effective Response on AKT Signaling and Anti-Tumor Immune Response,” was showcased during Poster Session C.
AlphaTON Capital is also known for its strategic investments in the TON ecosystem, focusing on generating sustainable returns for shareholders while advancing innovative therapeutic solutions. Cyncado Therapeutics, a clinical-stage subsidiary, is dedicated to developing small molecule adenosine receptor antagonists to counteract immune suppression in oncology, with TT-4 being a primary focus.
As the companies move forward, these findings pave the way for potential advancements in the treatment of mesothelioma, a disease with limited therapeutic options and a dire need for effective interventions.
