A new in­ter­leukin tar­get for NASH spawns Sin­ga­pore­an biotech steered by well known play­ers

A Sin­ga­pore­an biotech look­ing to break in­to the big NASH field has of­fered a glimpse of the pre­clin­i­cal da­ta that’s stoked its con­fi­dence in tar­get­ing an oft-over­looked cy­tokine.

Anis­sa Wid­ja­ja Twit­ter

Re­searchers from Duke-NUS Med­ical School and Na­tion­al Heart Cen­tre Sin­ga­pore start­ed with he­pat­ic stel­late cells, which “are piv­otal in the patho­gen­e­sis of NASH and give rise to up to 95%” of dis­ease dri­ving cells known as liv­er my­ofi­brob­lasts. Here’s how they sum­ma­rized the cur­rent NASH land­scape, from their new pa­per in Gas­troen­terol­o­gy:

A num­ber of fac­tors are im­pli­cat­ed in HSC ac­ti­va­tion and trans­for­ma­tion, in­clud­ing the canon­i­cal pro-fi­brot­ic fac­tors trans­form­ing growth fac­tor-B1 (TGFB1) and platelet de­rived growth fac­tor (PDGF) and al­so pro-in­flam­ma­to­ry fac­tors such as CCL2, TN­FA and CCL5.. Per­haps re­flect­ing this com­plex­i­ty and im­plic­it re­dun­dan­cy, no sin­gle up­stream ini­ti­at­ing fac­tor has been tar­get­ed suc­cess­ful­ly in NASH and there are no ap­proved NASH drugs. Cur­rent­ly, there are a num­ber of drugs in clin­i­cal tri­als for NASH but many of these tar­get me­tab­o­lism and it is not clear if they will im­prove liv­er fi­bro­sis, which pre­dicts clin­i­cal out­comes.

To si­mul­ta­ne­ous­ly get at the fat ac­cu­mu­la­tion, in­flam­ma­tion and scar­ring present in NASH, they need a bet­ter tar­get. And the sci­en­tists be­lieve they have found the an­swer in in­ter­leukin 11, or IL11.

By in­hibit­ing the pro­tein in mice that have been fed a di­et full of fat­ty food and sug­ary drinks, the sci­en­tists found that they were able not on­ly to pre­vent fat­ty liv­er dis­ease but al­so re­verse its course, ac­cord­ing to first au­thor Anis­sa Wid­ja­ja.

Stu­art Cook A*Star

“In­trigu­ing­ly, ge­net­ic or phar­ma­co­log­ic in­hi­bi­tion of IL11 is as­so­ci­at­ed with low­er serum triglyc­erides, cho­les­terol and glu­cose,” the re­searchers added. “This as­pect of IL11 in­hi­bi­tion is a de­sir­able fea­ture for a po­ten­tial NASH ther­a­py, as pa­tients with NASH of­ten suf­fer from car­dio­vas­cu­lar dis­eases.”

It will take years for En­le­ofen, the biotech spin­out en­trust­ed to bear this the­o­ry out, to catch up with fron­trun­ners like In­ter­cept (armed with mixed Phase III da­ta) and NGM (sup­port­ed by a deep-pock­et­ed Mer­ck). But un­til — or even when — a new drug is ap­proved, you can be sure to see big and small play­ers an­gling for a slice of the enor­mous mar­ket. Last month, Gilead pun­gled up $50 mil­lion to kick­start a part­ner­ship with the AI ex­perts at In­sitro, which in­volves as many as 5 new NASH drugs — and that’s in ad­di­tion to sev­er­al as­sets it’s al­ready blend­ing to­geth­er in a cock­tail.

Stu­art Cook, an au­thor of the study and a pro­fes­sor in car­dio­vas­cu­lar med­i­cine at Duke-NUS, is a co-founder at En­le­ofen along­side Se­bas­t­ian Schäfer. Like him, An­drew Khoo of Tes­sa Ther­a­peu­tics and Jef­frey Lu of En­gine Bio­sciences are al­so di­rec­tors, adding some star pow­er from two of the small coun­try’s biotech stars. Tim Lu, a pi­o­neer in the syn­thet­ic bi­ol­o­gy field who’s had plen­ty of ex­pe­ri­ence launch­ing his own star­tups, is al­so on board as an ad­vis­er.


Im­age: Shut­ter­stock

Daphne Koller, Getty

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