With Take­da’s mass, over-the-counter sell-off near­ing com­ple­tion, the Japan­ese drug­mak­er is beef­ing up the dis­cov­ery en­gine it wants to be the core part of the post-Shire com­pa­ny. On Tues­day, that meant their most re­cent for­ay in­to NASH — a dis­ease that they have tried with lit­tle ad­vanced suc­cess to de­vel­op drugs for in the past, but which re­mains a gold-mine for any com­pa­ny that can find an ef­fec­tive ther­a­py.

Take­da signed a col­lab­o­ra­tion to­day with Lon­don-based biotech En­gi­tix to de­vel­op drugs for ad­vanced fi­brot­ic liv­er dis­eases, in­clud­ing NASH. Up­front pay­ments weren’t dis­closed but En­gi­tix will be el­i­gi­ble for up to $500 mil­lion in mile­stones.

The deal emerges out of En­gi­tix’s on­go­ing work with Take­da. Take­da spon­sored the 4-year-old start­up with a Lab­Cen­tral “Gold­en Tick­et” last year, giv­ing them ac­cess to lab space, lab per­son­nel, and de­vel­op­ment pro­grams in Cam­bridge. The idea now is to com­bine En­gi­tix’s ex­tra-cel­lu­lar ma­trix plat­form with Take­da’s ex­pe­ri­ence in gas­troen­terol­o­gy.

En­gi­tix is based on the idea that com­pa­nies of­ten fail to trans­late their pre­clin­i­cal work be­cause they use cell lines that don’t take in­to ac­count that ma­trix — the net­works of pro­teins and car­bo­hy­drates that pass be­tween cells, com­mu­ni­cat­ing and as­sur­ing the whole sys­tem func­tions. So far, they’ve built ECM mod­els by tak­ing re­sect­ed tis­sues, break­ing them down “de­cel­lu­lar­iz­ing” them — lit­er­al­ly re­mov­ing the cells — and then lat­er grow­ing cell lines in what’s left­over.

Al­though the com­pa­ny is al­so fo­cused on sol­id tu­mors, the first pub­li­ca­tion on their plat­form, in Sci­en­tif­ic Re­ports, was a pa­per on the first suc­cess­ful de­cel­lu­lar­iza­tion and re­pop­u­la­tion of a hu­man liv­er ex­tra-cel­lu­lar ma­trix.  The com­pa­ny’s lead in­di­ca­tions are in pri­ma­ry scle­ros­ing cholan­gi­tis and NASH, al­though both re­main in the dis­cov­ery phase.

The deal hard­ly marks Take­da’s first ear­ly-stage biotech tie-in for NASH. In 2016, they teamed up for an undis­closed sum with the RNA biotech Arc­turus on NASH and GI dis­cov­ery, and ten months lat­er, they signed an up to $470 mil­lion deal with He­mo­S­hear to use their dis­ease mod­el­ing plat­form for liv­er tar­gets.

So far, those have yet to yield any clin­i­cal can­di­dates or named pre-clin­i­cal can­di­dates, ac­cord­ing to the com­pa­ny’s of­fi­cial pipeline and the data­base on clin­i­cal­tri­als.gov. Still, Take­da opt­ed to ex­pand both part­ner­ships in 2018 and 2019, adding in last year’s He­mo­S­hear re­lease that their ef­forts have yield­ed sev­er­al pre­clin­i­cal can­di­dates.

With the ma­jor clin­i­cal NASH can­di­dates tak­ing hit af­ter hit, the Japan­ese drug­mak­er may have plen­ty of time to de­vel­op those. Lead­er­ship has been seek­ing to move to­ward in­no­va­tion and high-prof­it prod­ucts. The first drug for a dis­ease es­ti­mat­ed to af­fect mil­lions of Amer­i­cans would cer­tain­ly fit the bill.

The FDA on Tuesday released a warning letter sent earlier this month to the Mason, OH-based site of Procter & Gamble Manufactura, raising questions about the list of ingredients on the label and in the electronic filing.

The warning says that for P&G’s over-the-counter Vicks Nyquil Severe Hot Remedy Cold and Flu Plus Congestion, there’s a “mismatched” list of active ingredients between the labeling and the electronic listing file. The listing file for the active ingredients did not match the active ingredients in the electronic file.