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First-in-class bi-functional METTL3-14 complex activator restoring m6A RNA balance for disease-modifying treatment of anxiety

Objective

Generalised anxiety disorder (GAD) affects over 5% of Europeans, yet current treatments are slow, often poorly tolerated, and frequently fail to provide lasting relief. No approved therapies target the molecular pathways underlying stress dysregulation. CALM6A introduces a first-in-class small-molecule approach designed to activate the METTL3–14 RNA methylation complex, a central regulator of m6A-dependent gene expression linked to neuronal plasticity and stress adaptation. Chemestmed’s discovery studies show that activating this complex restores m6A levels, normalises monoamine signalling, and produces anxiolytic-like effects in validated preclinical models.

This project advances CALM6A from TRL 4 to TRL 5 through an integrated scientific and translational programme. It will design and synthesise bifunctional METTL3–14 activators with improved potency and pharmacokinetic properties; validate their biological activity using enzymatic, biophysical, and neuronal-cell assays; and generate preliminary non-GLP toxicology and pharmacokinetic data, including brain penetration, to select a lead compound suitable for later GLP planning and regulatory consultation. Biomarker-linked readouts will ensure mechanism-based differentiation and provide a solid foundation for future clinical progression.

In parallel, the project will establish key elements for downstream translation. A Target Product Profile will be refined with external experts, pharmaceutical partners, and investors. Intellectual-property protection will be strengthened through additional filings and portfolio review. A business plan, financial model, and investor-ready package will be developed, together with a regulatory and clinical-readiness roadmap defining the next steps toward IND/CTA preparation.

By combining mechanistic innovation with rigorous validation and early market alignment, CALM6A aims to enable the future clinical development of a new therapeutic option for anxiety disorders.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-CSA - HORIZON Coordination and Support Actions

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Call for proposal

(opens in new window) HORIZON-WIDERA-2025-02

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Coordinator

OÜ CHEMESTMED
Net EU contribution
€ 445 558,75
Address
RIIA TN 130 B/2
50411 TARTU LINN
Estonia
SME
Yes
Region
Eesti Eesti Lõuna-Eesti
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
Total cost
No data