- Just under a year ago, Roche's Genentech unit dropped the development of the IDO inhibitor navoximod, paring back a collaboration deal with NewLink Genetics that had granted the Swiss pharma rights to the compound.
- Now, Roche has terminated the deal entirely, ceasing work on "next-generation IDO/TDO inhibitors" that had continued on after the pull back on navoximod, NewLink revealed on May 15 in a Securities and Exchange Commission filing.
- The termination will go into effect within 180 days and all rights will revert to NewLink. The biotech will owe a low single-digit royalty to Genentech if it decides to develop and commercialize any of the compounds that were discovered under the partnership.
With checkpoint inhibitors flooding the market, all of the major players in the space are searching for ways to differentiate from rivals and boost the effectiveness of their respective immunotherapies. Combining PD-1/L1 inhibitors with other drugs has become a favorite approach, ballooning pipelines with new clinical trials.
One mechanism initially seen as a promising partner for PD-1/L1 blockers was inhibiting an enzyme known as IDO and its related pathway. Over the last several years, many of the large oncology players — including Merck & Co., Bristol-Myers Squibb and Roche — all inked deals in the space. Roche had originally hooked up with NewLink on its programs in October 2014.
Yet, the recent failure of Incyte's IDO inhibitor epacadostat in combination with Merck's Keytruda (pembrolizumab) has cooled enthusiasm for further research into the pathway. Merck, Bristol-Myers and AstraZeneca all scaled back their partnerships with Incyte — discontinuing enrollment, stopping ongoing trials or choosing not to start studies at all.
NewLink only has two drugs in its pipeline, its IDO inhibitor indoximod and a produg of indoximod. After the failure of the Merck/Incyte combo, though, NewLink announced it would reevaluate its situation and said it would not pursue a Phase 3 trial of indoximod and a PD-1 inhibitor.
"We made this decision notwithstanding our strong view that indoximod's manifestly differentiated mechanism of action, set forth in detail in our presentation at AACR, has the potential to show efficacy in clinical settings that have not shown promise for direct enzymatic inhibitors," said NewLink CEO Charles Link during a May 3 earnings call.
"We believe that indoximod influences the IDO pathway so differently from direct enzymatic inhibitors, that it ought to be assessed separately. Accordingly, we announced a detailed review of our clinical programs to validate indoximod at lower cost and within our financial horizon," he added.
Shares of NewLink are trading just over $5 per share, down nearly 50% since early January, and well off its 52-week high of $19.30.