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

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,000+ biopharma pros reading Endpoints daily — and it's free.

José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,000+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,000+ biopharma pros reading Endpoints daily — and it's free.

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.