Vimentin

Aluda Pharmaceuticals has developed small molecule therapeutics that represents a significant new way to intervene in the fundamental biology of how disease takes over cell machinery. The target vimentin, an intermediate filament, is ‘hijacked’ by disease to mobilize, become invasive, or otherwise exacerbate disease pathology. Binding to vimentin (‘inhibition’) interrupts disease movement inside the cell and its’ signaling outside the cell —both depend critically and irreplaceably on vimentin.

Extensive literature shows potent and specific effects across autoimmune disease, cancer, viral infection, and fibrosis through 20 years of comprehensive academic research of both disease and normal cell. This shows vimentin is only essential under abnormal (‘emergency’) conditions, and under normal conditions does not have any essential roles that cause toxicity when blocked. Vimentin inhibition therefore can block disease without any mechanistic basis for toxicity. Aluda’s expert advisor in vimentin biology has written some of the most cited literature in the field that has cataloged all these roles, findings, and controversy.

This unusual biology has led to an extremely clean safety and tolerability profile throughout preclinical development of ALD-R491 and points to its suitability for a wide range of patient types including elderly/fragile, steroid-unsuitable, and pediatric.

Aluda has developed a full series of vimentin inhibitor compounds with:

• A confirmed and unique binding site on vimentin
• High specificity: no off-target binding
• High drug exposure in organs targeted by disease

References

• Zanin-Zhorov. Protein kinase C-theta mediates negative feedback on regulatory T cell function. Science 2010.
• McDonald-Hyman. Vimentin network restrains Treg cell suppression of graft-versus-host disease. J Clin Invest. 2018.
• de Santos. Vimentin regulates activation of the NLRP3 inflammasome. Nature Communications. 2015.
• Aluda data.
• Colucci-Guyon, E. Mice lacking Vimentin Develop & Reproduce without an Obvious Phenotype. Cell, Nov. 1994
• Danielsson, F. et. al. Vimentin Diversity in Health and Disease. Cells. 2018 Sep 21;7(10).
  Aluda advisor Dr. Annica Gad is the senior author.

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