Pipeline

Clywedog Therapeutics Inc is a clinical-stage biopharmaceutical company developing first and best in class medicines to treat diabetes.

Co-founded and seed-funded by Orbimed Advisors and Torrey Pines Investment, with additional support from the Expert Systems hybrid AI/ML drug discovery and development accelerator.

Balomenib — First-in-class Menin PPI Inhibitor for Diabetes

Clywedog is developing Balomenib, a best-in-class, oral, reversible menin protein–protein interaction (PPI) inhibitor for the treatment of type 2 diabetes (T2D) and type 1 diabetes (T1D).

Mechanism in T2D

  • Menin normally binds transcriptional partners (e.g., JunD, MLL) to repress β-cell proliferation and function.

  • By blocking these interactions, menin inhibitors lift transcriptional repression, leading to:

    • β-cell regeneration

    • Enhanced insulin secretion

    • Improved glucose control

  • Unlike standard glucose-lowering agents, menin inhibitors represent a potential disease-modifying therapy by directly restoring β-cell capacity.

Synergy with GLP-1 Agonists

  • GLP-1 signaling phosphorylates menin at Ser487, sequestering it away from chromatin and transiently boosting insulin gene expression.

  • Menin inhibitors act pharmacologically and durably by preventing menin from recruiting epigenetic repressors.

  • Together, these mechanisms may be:

    • Additive — stronger or longer-lasting insulin expression

    • Complementary — GLP-1 agonists drive acute secretion, while menin inhibitors rebuild β-cell mass and function

  • Therapeutic implication: Menin inhibitors may prime β-cells for GLP-1 responsiveness, while GLP-1 agonists provide immediate glycemic benefit — a potentially synergistic approach for T2D.

Potential in T1D

  • In preclinical models, menin inhibition promotes β-cell de-repression, proliferation, and insulin production.

  • This suggests safe, tolerable menin inhibitors could help restore β-cell mass in T1D.

  • However, autoimmune destruction remains the core driver of T1D and will need to be addressed with complementary immunomodulatory therapies.

TYK2 Inhibitor — First-in-class Oral Therapy for T1D

Clywedog is also advancing the first-in-class, oral, small-molecule TYK2 inhibitor with an outstanding safety and tolerability profile, in clinical development for T1D prevention and early treatment.

Mechanistic Rationale

  • TYK2 is a genetically validated target in T1D, mediating type I interferon (IFN) and interleukin (IL-12/23) signaling.

  • Pathogenic TYK2 signaling drives:

    • Upregulation of HLA class I and chemokines in β-cells

    • β-cell stress and apoptosis

    • Priming and activation of autoreactive cytotoxic T cells

Preclinical Data

  • Clywedog’s nonclinical studies demonstrated that TYK2 inhibition:

    • Protects human β-cells and islets from IFN-driven damage

    • Reduces autoimmunity in vitro

    • Attenuates insulitis in vivo in both prevention and reversal models

Clinical Implication

  • TYK2 inhibitors offer a dual mechanism: direct β-cell protection plus modulation of autoimmune drivers.

  • This positions Clywedog’s program as a potential disease-modifying therapy for individuals at risk of, or newly diagnosed with, T1D