Gilead shores up hope for NASH cock­tail with a glimpse at pos­i­tive proof-of-con­cept da­ta

When Gilead con­ced­ed fail­ure in its high-pro­file Phase III study for top late-stage NASH drug selon­sert­ib, CSO John McHutchi­son point­ed dis­ap­point­ed in­vestors to a com­bi­na­tion ap­proach be­ing test­ed in a mid-stage tri­al. Those da­ta are not ready just yet, but to­day the big biotech un­veiled some ear­ly num­bers to bol­ster their case for a cock­tail.

John McHutchi­son

On dis­play to­day at the In­ter­na­tion­al Liv­er Con­gress are topline re­sults from a proof-of-con­cept study test­ing cilofex­or (non­s­teroidal far­ne­soid X re­cep­tor or FXR ag­o­nist) and fir­so­co­stat (acetyl-CoA car­boxy­lase or ACC in­hibitor). Out of 20 pa­tients who were treat­ed with the oral reg­i­men once dai­ly for 12 weeks, 74% ex­pe­ri­enced “a sig­nif­i­cant de­cline of at least 30 per­cent in he­pat­ic fat” — a hall­mark of the dis­ease.

Re­searchers al­so doc­u­ment­ed im­prove­ments in oth­er bio­mark­ers, in­clud­ing “serum ALT (me­di­an rel­a­tive re­duc­tion, -37%; p<0.001) and GGT (-32%; p<0.001), along with mark­ers of re­duced bile acid syn­the­sis.”

Cilofex­or and fir­so­co­stat are al­so part of a triplet com­bo with the ASK1 in­hibitor selon­sert­ib, at the cen­ter of the Phase II AT­LAS study that McHutchi­son high­light­ed. In gen­er­al, FXR ac­ti­va­tion is thought to fight liv­er fi­bro­sis, ACC in­hibitors block fat­ty acid syn­the­sis, while ASK1 in­hibitor al­so helps re­duce in­flam­ma­tion.

“NASH is a com­plex dis­ease with mul­ti­ple bi­o­log­i­cal path­ways that in­flu­ence its pro­gres­sion. Com­bi­na­tion ther­a­peu­tic ap­proach­es which tar­get these path­ways, are like­ly to be need­ed to ef­fec­tive­ly treat pa­tients liv­ing with NASH, par­tic­u­lar­ly those with ad­vanced fi­bro­sis who have the great­est un­met need,” said McHutchi­son in a state­ment.

Gilead took a hit when selon­sert­ib flopped in its close­ly-watched STEL­LAR-4, out­per­formed by the place­bo at the low dose, though an­a­lysts ac­knowl­edged that fi­bro­sis was a tough tar­get to tack­le.

With a flock of small­er play­ers — in­clud­ing In­ter­cept, Gen­fit, Madri­gal and NGM Bio, which is part­nered with Mer­ck — con­tend­ing for the still va­cant NASH throne, Gilead has been pick­ing up ear­ly-stage as­sets in pur­suit of a sus­tain­ing fran­chise. In fact, cilofex­or came from the buy­out of Phenex Phar­ma and you might re­mem­ber fir­so­co­stat as GS-0976, which Gilead paid Nim­bus $600 mil­lion for.

It won’t be easy. But the pull is strong: NASH, which is typ­i­cal­ly as­so­ci­at­ed with obe­si­ty and di­a­betes, is set to eclipse he­pati­tis C as the lead­ing rea­son for liv­er trans­plants by 2020.

At the con­fer­ence, Gilead al­so pre­sent­ed screen­ing da­ta in sup­port of non-in­va­sive tests to iden­ti­fy NASH pa­tients with ad­vanced fi­bro­sis. Re­duc­ing the need for the cost­ly and risky liv­er biop­sies typ­i­cal­ly need­ed for the di­ag­no­sis can pave a smoother path for pa­tients to­ward treat­ment — ul­ti­mate­ly when they get ap­proved.


Im­age: Shut­ter­stock

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

(Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Bay­er plots a ma­jor facelift at Berke­ley cam­pus, un­cork­ing a 30-year, $1.2B plan to dri­ve cell and gene ther­a­pies

Bayer first set roots in Berkeley back in 1974, when it was still operating as Miles Labs. The site has pumped out three hemophilia A treatments for distribution worldwide; but now, as the pharma continues its cell and gene therapy push, it has something bigger in mind.

Bayer is planning a 30-year revamp at the campus, which includes 918,000 square feet in new buildings and double the jobs, according to a report by the Bay Area Council Economic Institute.

Jenny Rooke (Genoa Ventures)

Ear­ly Zymer­gen in­vestor Jen­ny Rooke re­flects on 'chimeras' in biotech, what it takes to spot a $500M gem

When Jenny Rooke first heard of Zymergen back in 2014, she knew she was looking at something different and exciting. The Emeryville, CA biotech held the promise of blending biology and technology to solve a huge unmet need for cost-effective chemicals — of all things — and a stellar founding team to boot.

But back then, West Coast venture capitalists didn’t see in Zymergen the one thing they were looking for in a winning biotech: therapeutic potential. Rooke, however, saw an opportunity and made her bets. Seven years later, that bet is paying off in a big way.

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