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

An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Can an FDA hus­tle up on trastuzum­ab be far be­hind?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Mer­ck Serono’s Se­nior Vice Pres­i­dent and Glob­al Head of On­col­o­gy
EL­LIOTT LEVY — Am­gen’s Se­nior Vice Pres­i­dent of Glob­al De­vel­op­ment
CHRIS BOSHOFF — Pfiz­er On­col­o­gy’s Chief De­vel­op­ment Of­fi­cer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Ver­sant-backed Chi­nook gets a $65M launch round for its dis­cov­ery quest in a resur­gent kid­ney field

Versant is once again stepping off the beaten track in biotech to see if they can blaze a trail of their own in a field that has looked too thorny to many investors for years.

The venture group and their partners at Apple Tree are bringing their latest creation out of stealth mode today. Born in Versant’s Inception Sciences’ Chinook Therapeutics is betting that its preclinical take on kidney disease can get an early lead among the companies starting up in the field.

Sir An­drew Dil­lon, NICE's first — and on­ly — chief ex­ec­u­tive to step down next year

Using a laptop borrowed from his former employer, South London’s St George’s Hospital, Sir Andrew Dillon set about establishing NICE — launched by the then health secretary Frank Dobson — in 1999.  On Thursday, the UK cost-effectiveness watchdog said its first and only chief executive — Dillon — is stepping down in March 2020.

Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.

Eight weeks be­tween each HIV treat­ment? GSK notch­es PhI­II win as it chas­es OK for long-act­ing reg­i­men

GSK has cleared another test in its grand plan to topple Gilead’s HIV dominance by offering alternative treatments that consist of fewer drugs and last longer. A year after scoring positive Phase III data on a four-week course of cabotegravir and rilpivirine, its ViiV subsidiary now says that an eight-week regimen seem to work just as well.

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Finch grabs a $53M round de­signed to take their ‘break­through’ mi­cro­bio­me treat­ment through a po­ten­tial­ly piv­otal tri­al

With a breakthrough designation in one hand and a fresh $53 million in venture backing in the other, Somerville, MA-based Finch Therapeutics is taking a shot at a one-trial pathway to a possible FDA OK for their new treatment for preventing recurrent C. difficile infections.

The funding brings their total raise for the microbiome company to $130 million, CEO Mark Smith tells me — enough money to pave a runway past the FDA approval they’ve sketched into the most optimistic version for their near-term future. 

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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