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

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

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Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Charlie Silver (Mission Bio)

'We want to be every­where.' Mis­sion Bio rais­es $70M be­hind re­sis­tance-hunt­ing se­quenc­ing plat­form

Charlie Silver wants to look really, really closely at a lot of your cells. And he just got a lot of money to do so.

Silver’s startup, Mission Bio, raised $70 million in a Series C round Thursday led by Novo Holdings. The money, which brings Mission Bio to $120 million raised since its 2012 founding, will be used to advance the single-cell sequencing platform they built to detect early response or resistance to new cancer therapies.

Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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