AlphaTON Capital and Cyncado Therapeutics Share New Mesothelioma Data Supporting TT-4’s Path to First- Patient Dosing

Rhea-AI Summary

AlphaTON Capital (Nasdaq: ATON) and Cyncado Therapeutics presented preclinical mesothelioma data on Oct 25, 2025 showing that selective A2B receptor antagonist TT-4 produced direct anti-tumor activity in epithelial and non-epithelial models, reduced pCREB and tumor PD-L1, modulated YAP signaling, and increased immune infiltration and tertiary lymphoid structures.

The poster reports TT-4 monotherapy exceeding anti-PD-1 in models and combination treatment further improving tumor control. The program is described as IND-enabled and on track for first-patient dosing in Q1 2026.

Positive

• Direct anti-tumor activity of TT-4 in epithelial and non-epithelial models
• TT-4 reduced pCREB and lowered tumor PD-L1 protein
• TT-4 monotherapy outperformed anti-PD-1 in models
• Combination with anti-PD-1 increased tumor growth inhibition and T-cell infiltration
• Program IND-enabled and preparing for first-patient dosing in Q1 2026

Negative

• None.

Insights

Translational oncology expert

Preclinical mesothelioma data for TT-4 show tumor-intrinsic and immune-mediated activity and support a planned first‑patient dosing in Q1 2026.

Selective A2B receptor blockade with TT-4 produced direct anti‑tumor effects in epithelial and non‑epithelial mesothelioma models, reduced pCREB with an associated drop in PD‑L1 protein, modulated YAP signaling, and increased immune infiltration and tertiary lymphoid structures. These mechanistic links explain how tumor‑intrinsic signaling (pCREB/PD‑L1 and YAP) and immune changes could together drive the observed monotherapy efficacy and the added benefit when combined with anti‑PD‑1.

Key dependencies and risks include the usual translation gap from murine and spheroid systems to humans and the need to confirm safety and pharmacodynamics in patients; the content states only preclinical and IND‑enabling status. Critical items to watch are confirmation of an IND clearance, initiation of first‑patient dosing in Q1 2026, early human pharmacodynamic evidence of reduced pCREB/PD‑L1 or increased immune infiltration, and any monotherapy or combination signals in initial cohorts within the first year after dosing.

Poster presented today in Boston shows direct anti-tumor activity in mesothelioma models, reduced tumor PD-L1 alongside decreased pCREB, and strong TT-4 monotherapy activity with added benefit in anti-PD-1 combinations; TT-4 remains on track for Q1 2026 first-patient dosing

Dover, DE, Oct. 25, 2025 (GLOBE NEWSWIRE) -- AlphaTON Capital Corp (Nasdaq: ATON) and its wholly owned oncology-focused subsidiary Tarus Therapeutics, LLC, operating as Cyncado Therapeutics, today announced that a new poster is live at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. The work, conducted with investigators from the Italian Group for Mesothelioma (G.I.Me) and collaborators, provides the first evidence that selective adenosine A2B receptor inhibition exerts a direct anti-tumor effect in both epithelial and non-epithelial mesothelioma cells, decreases in pCREB with an associated reduction in PD-L1 expression, and modulates YAP signaling consistent with proteomic shifts, alongside immune-mediated growth inhibition.

These findings reinforce earlier preclinical results with Cyncado’s selective A2B receptor antagonist TT-4 in mesothelioma, where monotherapy activity exceeded anti-PD-1 and the combination with anti-PD-1 further improved tumor control, accompanied by increased immune infiltration and tertiary lymphoid structures. The new mechanistic data help explain the previously observed efficacy profile and support translation into first-in-human evaluation.

In human mesothelioma spheroid systems, hypoxia-linked adenosine signaling increased tumor growth and PD-L1 expression. Selective A2B receptor inhibition reduced cell growth and lowered PD-L1 protein through reduced CREB phosphorylation (pCREB). In murine models, TT-4 blocked NECA-induced pCREB activation and growth stimulation in AB1 and AB22 mesothelioma cells. In vivo, TT-4 demonstrated meaningful monotherapy activity in an immunocompetent mesothelioma model, and combination treatment with anti-PD-1 further increased tumor growth inhibition, with immunohistochemistry showing higher T-cell infiltration.

“Mesothelioma is a hypoxic, adenosine-rich disease, and these data add a clear tumor-intrinsic mechanism to the case for targeting the A2B receptor,” said Rob Kramer, PhD, Chief Scientific Officer at Cyncado Therapeutics. “We are advancing TT-4 toward first-patient dosing in Q1 2026 to translate these signals clinically.”

“AlphaTON focuses on programs where biology and translational markers converge,” said Brittany Kaiser, Chief Executive Officer of AlphaTON Capital. “This first-evidence package strengthens our conviction in TT-4 for mesothelioma and informs how we prioritize resources to reach proof of concept in patients.”

Clinical program status
 • TT-10 (A2A receptor antagonist): Phase 1 dose escalation is ongoing in advanced solid tumors.
 • TT-4 (A2B receptor antagonist): IND-enabled program preparing for first-patient dosing in Q1 2026.

AACR-NCI-EORTC Poster details
Title: ADORA2B inhibition in Mesothelioma (MMe) cells affects PD-L1 expression and exerts an effective response on AKT signaling and anti-tumor immune response
Session: Poster Session C
Date and time: Today, Saturday, October 25, 2025, 12:30–4:00 pm
Presenting group: G.I.Me with collaborators from University of L’Aquila, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, St. James’s Hospital Dublin, and Cyncado Therapeutics

About AlphaTON Capital Corp
AlphaTON Capital is a specialized digital asset treasury company focused on building and managing a strategic reserve of TON tokens and developing the Telegram ecosystem. The Company implements a comprehensive treasury strategy that combines direct token acquisition, validator operations, and strategic ecosystem investments to generate sustainable returns for shareholders. Through its operations, AlphaTON Capital provides public market investors with institutional-grade exposure to the TON ecosystem and Telegram's billion user platform while maintaining the governance standards and reporting transparency of a Nasdaq-listed company.

Led by Chief Executive Officer Brittany Kaiser and Chief Investment Officer, Enzo Villani, the company's activities span network validation and staking operations, development of Telegram-based applications, and potential strategic investments in TON-based decentralized finance protocols, gaming platforms, and business applications. AlphaTON Capital Corp is incorporated in the British Virgin Islands and trades on Nasdaq under the ticker symbol ATON.

AlphaTON Capital, through its legacy business, is also advancing potentially first-in-class therapies that target known checkpoint resistance pathways to potentially achieve durable treatment response and improve quality of life for patients. AlphaTON Capital actively engages in the drug development process and provides strategic counsel to guide development of novel immunotherapy assets and asset combinations.

About Cyncado Therapeutics
Tarus Therapeutics, LLC (operating as Cyncado Therapeutics), a clinical stage, wholly owned subsidiary of AlphaTON Capital Corp, is developing potentially best-in-class small molecule adenosine receptor antagonists targeting A2A and A2B receptors to overcome immune suppression in oncology. The Company's lead program, TT-4, is an oral, ultra-selective A2B receptor antagonist with an initial focus on mesothelioma, advancing toward first-patient dosing in Q1 2026. Cyncado is also developing dual-antagonist strategies designed to achieve comprehensive blockade of adenosine-mediated immune evasion, potentially unlocking synergistic anti-tumor effects and durable patient responses.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of applicable securities laws. All statements other than statements of historical fact, including statements regarding the Company's business strategy, plans and objectives, future operations, clinical development timelines, TON ecosystem growth, therapeutic development outcomes, regulatory approvals, and statements preceded by, followed by, or including words such as "believe," "expects," "anticipates," "intends," "estimates," "will," "may," "plans," "potential," "targets," or similar expressions, are forward-looking statements.

These forward-looking statements are subject to substantial risks and uncertainties, including but not limited to: regarding clinical trial outcomes and regulatory approvals; uncertainty of the Company's investment in TON and digital assets; regulatory and legal risks associated with digital assets; risks related to Telegram's platform and the TON ecosystem; market volatility; competitive risks in both digital assets and therapeutics development; and other factors described in "Item 3 – Key Information-Risk Factors" in the Company's Annual Report on Form 20-F for the year ended March 31, 2025, and subsequent reports filed with the Securities and Exchange Commission.

Although the Company believes the expectations reflected in these forward-looking statements are reasonable, actual results may differ materially. The Company undertakes no obligation to update publicly or revise any forward-looking statements, except as required by law.

Contact Information

Investor Relations
 AlphaTON Capital Corp
 AlphaTON@icrinc.com
 (203) 682-8200

Media Inquiries
 Richard Laermer
 RLM PR
 AlphaTON@rlmpr.com
 (212) 741-5106 X 216

 Richard Laermer
 AlphaTON (at) rlmpr.com

FAQ

What did AlphaTON/Cyncado announce about TT-4 mesothelioma data on Oct 25, 2025?

They presented preclinical data showing TT-4 produced direct anti-tumor effects, reduced pCREB and PD-L1, modulated YAP, and improved tumor control alone and with anti-PD-1.

When is TT-4 expected to reach first-patient dosing for ATON's program?

The company said the TT-4 program is IND-enabled and preparing for first-patient dosing in Q1 2026.

How did TT-4 perform compared with anti-PD-1 in the reported models?

TT-4 monotherapy exceeded anti-PD-1 activity in models, and the TT-4 plus anti-PD-1 combination further improved tumor control and immune infiltration.

What mechanistic effects did the Oct 25, 2025 poster attribute to A2B inhibition by TT-4?

The poster reported reduced CREB phosphorylation (pCREB), decreased tumor PD-L1, modulation of YAP signaling, and proteomic shifts consistent with immune-mediated growth inhibition.

Where and when was the TT-4 mesothelioma poster presented for ATON?

The poster was presented at the AACR-NCI-EORTC conference in Boston on October 25, 2025 during Poster Session C (12:30–4:00 pm).