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Ensemble's IL-17 antagonist program is in collaborative development with Novartis.

Ensemble has identified a series of unique small molecule macrocycles, or Ensemblins, that are antagonists of Interleukin-17, a pro-inflammatory cytokine implicated in multiple inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, Crohn’s and intestinal bowel disease. These Ensemblins represent first-in-class orally-bioavailable small molecule antagonists of this important, clinically validated protein-protein-interaction target that has proven impervious to traditional small molecule pharmaceutical approaches and has only been addressed to date with protein therapeutics.  A small orally-active inhibitor of IL-17 would have significant delivery and therapeutic advantages over the current class of clinical stage anti-IL-17 antibody products. 

In November 2012, Ensemble announced positive preclinical oral efficacy data with its first-in-class small molecule Interleukin-17 antagonists. A presentation at the American College of Rheumatology (ACR) 2012 Annual Meeting in Washington, DC, revealed that the company’s Ensemblins have strong oral activity as antagonists of IL-17, a pro-inflammatory cytokine implicated in multiple inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, Crohn’s disease and inflammatory bowel disease.   In the poster entitled “Identification and Characterization of Synthetic Small Molecule Macrocycle Antagonists of Human IL17A”, Dr. David J. Livingston, Ensemble SVP Biology, presented preclinical data on oral anti-IL-17A Ensemblins demonstrating:

  • High selectivity to the cytokine target
  • Comparable anti-inflammatory efficacy to an anti-IL-17 antibody
  • Protection from arthritic joint degradation
  • Significant in Vivo Activity

Ensemble knows of no other IL-17 small molecule antagonists, in spite of the active efforts of a number of major pharmaceutical and biotechnology companies to identify such compounds.  The discovery of a series of small molecule macrocycles that exhibit single-digit nanomolar potency, and are selective and druggable with excellent potential for oral administration, is a compelling example of the power of Ensemble’s drug discovery platform against a most challenging and significant drug target. The company expects this rapidly advancing IL-17 program to produce an orally active development candidate in early 2013.