Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes weeks af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.

The two treat­ments be­long to a fam­i­ly of drugs that ac­ti­vate pro­teins called per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tors (PPARs), which reg­u­late gene ex­pres­sion. Ex­ist­ing ev­i­dence sug­gests that in the liv­er, PPAR ag­o­nists play a role in bile acid syn­the­sis, in­flam­ma­tion, fi­bro­sis and lipid me­tab­o­lism.

NASH is an un­treat­ed fat­ty liv­er dis­ease that has rav­aged the de­vel­oped world, cre­at­ing a lu­cra­tive tar­get that has sparked a flur­ry of drug de­vel­op­ment from bio­phar­ma firms big and small. It is char­ac­ter­ized by a buildup of ex­cess fat in the liv­er that in­duces chron­ic in­flam­ma­tion and even­tu­al­ly cul­mi­nates in scar­ring that can lead to cir­rho­sis, liv­er fail­ure, can­cer and death.

Pas­cal Pri­gen LinkedIn

Dubbed the silent dis­ease, it is hard to di­ag­nose in the ear­ly stages, mak­ing it dif­fi­cult to es­ti­mate its preva­lence, but stud­ies show that it af­flicts up to 12% of the adult pop­u­la­tion in de­vel­oped coun­tries. Al­though there are no ap­proved drugs for the dis­ease, the size of the NASH mar­ket is ex­pect­ed to cross $20 bil­lion by 2025.

While oth­er ma­jor NASH con­tenders — Gilead $GILD (fail in Phase III) and In­ter­cept $ICPT (mixed win in Phase III) — have dis­closed the top-line num­bers of their late-stage tri­als, Gen­fit is ex­pect­ed to come out with its Phase III in­ter­im re­sults by the end of 2019, or ear­ly 2020.

Late-stage da­ta on In­ter­cept’s drug — obeti­cholic acid (OCA) — showed it in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in fi­bro­sis, but not NASH res­o­lu­tion, and a high­er-than-ex­pect­ed num­ber of pa­tients dropped out due to the pesky side-ef­fect of itch­ing. In con­trast to In­ter­cept, Gen­fit has em­pha­sized that elafi­bra­nor’s po­ten­tial in NASH res­o­lu­tion and re­duc­ing CV risk along with a be­nign safe­ty and tol­er­a­bil­i­ty pro­file have set it apart.

“We think we’re go­ing to be the first drug on the mar­ket that can re­solve NASH,” Gen­fit’s COO Dean Hum stressed in an in­ter­view with End­points News.

He sug­gest­ed that Cymabay had “made a mis­take” to fo­cus on liv­er fat, when they should have con­cen­trat­ed on in­flam­ma­tion and fi­bro­sis — the fac­tors that con­sti­tute NASH res­o­lu­tion.

But some an­a­lysts are not quite as con­vinced.

In the af­ter­math of the Cymabay da­ta, Baird’s Bri­an Sko­r­ney sug­gest­ed se­ladel­par and elafi­bra­nor are be­gin­ning to ap­pear more sim­i­lar than dif­fer­ent.

“Though the two med­ica­tions were thought to have dif­fer­en­ti­at­ed mech­a­nisms of ac­tion, it seems that this may not be the case, as se­ladel­par’s da­ta sug­gest that the med­ica­tion does not re­duce liv­er fat, which is sim­i­lar to what we have seen from ear­li­er tri­als of elafi­bra­nor. This leads us to be­lieve that these two PPARs look much more sim­i­lar than dif­fer­ent. Hence, CymaBay may be at a sig­nif­i­cant dis­ad­van­tage mov­ing for­ward as we be­lieve that even if PPAR ag­o­nism is suc­cess­ful in Gen­fit‘s Phase 3 tri­al, with­out any clear signs of dif­fer­en­ti­a­tion, CymaBay may have an up­hill bat­tle as they work to catch up to Gen­fit in NASH. If elafi­bra­nor fails in NASH, it would prob­a­bly be pre­dic­tive of the out­come of se­ladel­par in NASH. Ei­ther way, we think this makes the PPAR class, as a whole, look like a less sig­nif­i­cant com­pet­i­tive threat to OCA.”

While the bulk of obe­si­ty and re­lat­ed dis­eases have tra­di­tion­al­ly been the wheel­house of the West­ern world, rapid ur­ban­iza­tion in parts of Asia has nor­mal­ized seden­tary lifestyles and over­nu­tri­tion, set­ting the stage for obe­si­ty in epi­dem­ic pro­por­tions. A study pub­lished in 2017 sug­gests the in­ci­dence of obe­si­ty has been in­creas­ing at an alarm­ing rate, par­tic­u­lar­ly in Chi­na, Japan and In­dia. “The num­ber of obese Chi­nese peo­ple was be­low 0.1 mil­lion in 1975, ris­ing to 43.2 mil­lion in 2014 and ac­count­ing for 16.3% of glob­al obe­si­ty,” re­searchers found.

Gen­fit’s new part­ner Terns is well versed in NASH. Last year, it joined forces with Eli Lil­ly to de­vel­op the US drug­mak­er’s ear­ly-stage NASH as­sets, in ad­di­tion to its own.

Un­der the deal, Terns — which has op­er­a­tions in Cal­i­for­nia, as well as a set­up in Chi­na — will hand over $35 mil­lion up­front, in ad­di­tion to up to $193 mil­lion in po­ten­tial mile­stone pay­ments to de­vel­op Gen­fit’s late-stage as­set elafi­bra­nor for use in NASH and pri­ma­ry bil­iary cholan­gi­tis (PBC).

A key rea­son be­hind the deal was that since elafi­bra­nor’s ex­ist­ing late-stage study does not in­clude Chi­nese pa­tients, an­oth­er Phase III study in­clud­ing such pa­tients would be re­quired for Chi­nese ap­proval, Pas­cal Pri­gent, Gen­fit’s ex­ec­u­tive VP of mar­ket­ing and com­mer­cial de­vel­op­ment, told End­points News.

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Everest Medicines is on a roll with two licensing deals in one week.

The Shanghai-based biotech has paid Sinovent and SinoMab $12 million upfront for the rights to a BTK inhibitor for renal diseases, the company announced Thursday. The deal comes just days after Everest came away with rights to a Covid-19 vaccine in China, Taiwan, Singapore, Thailand and Indonesia.

Everest will pay Sinovent and SinoMab up to $549 million in milestone payments and royalties. The agreement includes tech transfer of Sinovent and SinoMab’s manufacturing process for the candidate, named XNW1011.