Immunoproteasome Inhibition

We are exploring early-stage selective inhibition of immunoproteasome subunits with potential utility in immune-mediated diseases.

Principia is focused on oral therapies that bring the power of proteasome inhibition safely into the field of immunology.

The immunoproteasome is a distinct class of the proteasome that is abundant in immune cells and therefore plays an important role in immune response. We believe that by targeting immunoproteasome subunits we may be able to selectively block immune cells and inhibit damaging inflammation.

By selectively blocking unique targets in the immunoproteasome, our molecule is designed to alter undesired immune responses including pro-inflammatory cytokine production, aberrant T cell function, and effects on antigen presentation.

The graphic below illustrates how Principia is developing highly selective, oral inhibitors of the immunoproteasome to treat immune-mediated diseases while avoiding the toxicities of non-selective proteasome inhibitors (such as Velcade®, Kyprolis®, and Ninlaro®) that block both the immuno- and the constitutive proteasomes.

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Ongoing Clinical Studies