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

Rhea-AI Summary

AlphaTON (Nasdaq: ATON) subsidiary Cyncado Therapeutics presented preclinical mesothelioma data showing selective A2B receptor inhibition produced direct anti-tumor effects across epithelial and non-epithelioid models. TT-4 monotherapy outperformed anti-PD-1 and TT-4 + anti-PD-1 achieved >90% tumor growth inhibition in vivo. Mechanistic readouts showed decreased pCREB and reduced tumor PD-L1. TT-4 is reported as IND-enabled and remains on track for first-patient dosing in Q1 2026. Cyncado will use these data to finalize clinical plans for mesothelioma.

Positive

• TT-4 + anti-PD-1 achieved >90% tumor growth inhibition in vivo
• TT-4 monotherapy outperformed anti-PD-1 in preclinical models
• Selective A2B inhibition reduced pCREB and tumor PD-L1 in human mesothelioma spheroids
• TT-4 is reported IND-enabled and on track for first-patient dosing in Q1 2026

Negative

• Data are preclinical; no human clinical efficacy reported yet
• First-patient dosing is on track but not guaranteed and subject to regulatory/operational steps

Insights

Translational Oncology Scientist

Preclinical A2B inhibition shows strong anti-tumor signals and supports an IND-enabled move to first‑in‑human dosing.

Selective A2B receptor blockade with TT-4 produced direct tumor effects across epithelial and non-epithelioid mesothelioma models and reduced PD-L1 via decreased pCREB in human spheroids. The data include quantified in vivo efficacy: TT-4 plus anti-PD-1 achieved >90% tumor growth inhibition and TT-4 monotherapy outperformed anti-PD-1, with additive benefit when combined.

Risks and dependencies include translation from murine/spheroid models to human tumors and whether the PD-L1/pCREB mechanism will predict clinical immune durability; those limits are intrinsic to preclinical work and are not addressed by these experiments. Watch for IND acceptance, first‑patient dosing in Q1 2026, and early pharmacodynamic readouts (PD-L1/pCREB modulation and immune-effector infiltration) in initial clinical cohorts over the first 6–12 months after dosing.

Clinical Development Strategist

Data justify progressing TT-4 into a first‑in‑human study, with clear go/no-go signals to monitor around IND and early biomarker effects.

The program is described as IND-enabled and remains on track for first‑patient dosing in Q1 2026, which aligns operationally with advancing to clinical testing. The reported >90% tumor growth inhibition for the combination and superior monotherapy activity provide concrete preclinical efficacy metrics to support a clinical protocol focused on monotherapy and combination cohorts.

Key near-term milestones to track are IND filing/acceptance, the actual date of first patient dosing, and early on-treatment biomarker changes (tumor PD-L1 and pCREB, plus immune-effector infiltration) in the initial patients; these will be the first clinical evidence that the preclinical mechanism maps to humans within 6–12 months post‑dosing.

Post-conference recap highlights direct anti-tumor effects in epithelial and non-epithelioid mesothelioma models, >90% tumor growth inhibition in vivo when TT-4 was combined with anti-PD-1, and superior monotherapy activity versus anti-PD-1 alone, reduced tumor PD-L1 correlated with decreased pCREB

Dover, DE, Oct. 27, 2025 (GLOBE NEWSWIRE) -- AlphaTON Capital Corp (Nasdaq: ATON) and its wholly owned oncology-focused subsidiary Tarus Therapeutics, LLC, operating as Cyncado Therapeutics (Cyncado), today issued a recap of data presented on Saturday at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

The poster showed that selective A2B receptor inhibition produces direct anti-tumor activity in both epithelial and non-epithelioid mesothelioma models, reduces tumor PD-L1 alongside decreased pCREB in a human epithelioid mesothelioma cell system, and that TT-4 monotherapy outperformed anti-PD-1 with additional activity in combination. TT-4 remains on track for first-patient dosing in Q1 2026.

“With data now in the public domain showing >90% tumor growth inhibition for TT-4 plus anti-PD-1 and TT-4 monotherapy outperforming anti-PD-1, we are executing toward first-patient dosing in Q1 2026,” said Peter Molloy, Chief Executive Officer of Cyncado Therapeutics. “These findings confirm that selective A2B inhibition exerts a direct anti-tumor effect across mesothelioma subtypes, reduces PD-L1, and drives immune activation consistent with durable response potential.

Key takeaways from the poster

• Direct tumor effect across subtypes: Blocking the A2B receptor produced direct anti-tumor activity in both epithelial and non-epithelioid mesothelioma models
• Quantified anti-tumor activity: TT-4 + anti-PD-1 cut tumor growth by more than 90% in vivo; TT-4 alone outperformed anti-PD-1, with additive benefit in combination
• Mechanistic evidence: Selective A2B inhibition decreased pCREB resulting in lowered PD-L1 expression in human mesothelioma spheroids; in murine models TT-4 blocked NECA-induced pCREB and drove in-vivo tumor control
• Immune activation: Combination therapy was associated with increased immune-effector infiltration, consistent with durable immune response
• Advancing to clinic: TT-4 is IND-enabled and remains on track for first-patient dosing in Q1 2026

Next steps

Cyncado is using these findings to finalize clinical development plans for TT-4 in mesothelioma, with first patient dosing on track for Q1 2026.

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

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AlphaTON@icrinc.com
(203) 682-8200

Media Inquiries
Richard Laermer
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(212) 741-5106 X 216

Richard Laermer
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FAQ

What preclinical result did AlphaTON (ATON) report for TT-4 at AACR-NCI-EORTC on October 27, 2025?

Cyncado reported that TT-4 + anti-PD-1 reduced tumor growth by >90% in vivo and that TT-4 monotherapy outperformed anti-PD-1 in mesothelioma models.

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

TT-4 is reported as on track for first-patient dosing in Q1 2026.

How did TT-4 affect PD-L1 and pCREB in the reported preclinical studies?

Selective A2B inhibition with TT-4 decreased pCREB and lowered tumor PD-L1 in human mesothelioma spheroids and related models.

Does the October 27, 2025 data indicate clinical benefit for ATON investors now?

No; the data are preclinical, showing promising biological activity but not clinical human efficacy yet.

What mechanism of action did Cyncado highlight for TT-4 in mesothelioma models?

Cyncado highlighted selective A2B receptor inhibition producing direct anti-tumor effects and immune-effector infiltration in models.

Is TT-4 cleared by regulators or already in human trials for ATON?

The release states TT-4 is IND-enabled and on track for first-patient dosing, but it does not state that human trials have started or that regulators have cleared clinical dosing.