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

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

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