Target selectivity has the potential to significantly enhance efficacy of therapeutics while limiting their toxicity and side effects, therefore selectivity has long been the goal in the development of new therapeutics to treat inflammatory disease.
In the company’s research, its lead candidate, XPro 1595 DN-TNF, was shown to selectively inhibit the soluble form of tumor necrosis factor (TNF alpha) in both human and animal cell lines and blocked inflammation in animal models. TNF alpha is a cytokine protein with a very well-established role in autoimmune disease and inflammation.
The candidate did not, however, inhibit the cell membrane-bound form of TNF alpha and thereby preserved the key role of membrane-bound TNF alpha in infection resistance and immune function.
There are currently four marketed treatments that target TNF alpha and several other drug candidates in clinical development. Each non-selectively targets both soluble TNF alpha and membrane-bound TNF alpha. According to Xencor, these non-specific TNF alpha inhibitors have rare but severe side effects and are prescribed to patients only when other anti-inflammatory drugs do not work.
“Drug-associated adverse side effects, including severe infections and tuberculosis, continue to hamper effective treatment of many inflammatory diseases. Using our PDA technology, we engineered a first-in-class selective inhibitor of TNF alpha with enhanced pharmaceutical properties,” said Bassil Dahiyat, president and CEO of Xencor. “The selectivity of XPro 1595 DN-TNF has the potential to maintain the significant therapeutic benefits of targeting soluble TNF alpha without the adverse events from off-target inhibition.”