Molecular Partners CEO Patrick Amstutz

With hopes for an­ti­bod­ies wan­ing, the NIH will test No­var­tis part­ner's nov­el an­tivi­ral in hos­pi­tal­ized Covid-19 pa­tients

Af­ter a slew of fail­ures, the NIH’s AC­TIV-3 tri­al for hos­pi­tal­ized Covid-19 pa­tients has earned its rep­u­ta­tion as a grave­yard for big-name an­ti­bod­ies. Now, with its op­tions run­ning out, the NIH is turn­ing to a No­var­tis-backed an­ti­body al­ter­na­tive — but is this déjà vu all over again?

Mol­e­c­u­lar Part­ners and part­ner No­var­tis will try out their “trispe­cif­ic” DARPin an­tivi­ral enso­vibep in AC­TIV-3, the hos­pi­tal­ized mild-to-mod­er­ate pa­tient arm of the NIH’s AC­TIV “mas­ter pro­to­col” against Covid-19, the pair said Mon­day.

The mol­e­cule is one of a nov­el class of ther­a­peu­tics de­vel­oped by Mol­e­c­u­lar Part­ners that aims to per­form the same func­tions as an­ti­bod­ies with far more tar­get speci­fici­ty and an­tivi­ral pro­tec­tion. The drug­mak­er is per­haps best known for its mac­u­lar de­gen­er­a­tion DARPin pact with Ab­b­Vie, which the FDA hit with a CRL back in June.

But now, with No­var­tis on board to help its piv­ot to­ward Covid-19, Mol­e­c­u­lar Part­ners thinks it has the win­ning ear­ly-stage da­ta to suc­ceed where big drug­mak­ers haven’t in AC­TIV-3, which has proven to be a waste­land for an­ti­bod­ies. Enso­vibep, pre­vi­ous­ly known as MP0420, is one of two mol­e­cules at the cen­ter of a $231 mil­lion deal with No­var­tis signed in Oc­to­ber and de­signed to chart a new path at Covid-19 ther­a­peu­tics.

“What we know from the pre­clin­i­cal da­ta is we ac­tu­al­ly get in­to the lungs very fast, we block the virus very fast so there is no in­fec­tiv­i­ty, no ac­tiv­i­ty, and we don’t clear as fast as the an­ti­bod­ies,” CEO Patrick Am­stutz told End­points News. Mol­e­c­u­lar Part­ners al­so ar­gues that its high-affin­i­ty DARPins bind much bet­ter to the SARS-Cov-2 spike pro­tein than an­ti­bod­ies with­out spurring im­mune side ef­fects.

But it’s still not a sure thing, Am­stutz said.

“If those dif­fer­ences will lead to ac­tiv­i­ty in this set­ting, we just don’t know,” he said. “I would say the prob­a­bil­i­ty of suc­cess is high­er than an an­ti­body, but it’s still a rough tri­al. In this sit­u­a­tion, we have to try — there is ra­tio­nale to be­lieve, (but) the bar is very high.”

AC­TIV-3 will ini­tial­ly ran­dom­ize 300 hos­pi­tal­ized pa­tients with mild-to-mod­er­ate Covid-19 who have ex­pe­ri­enced less than 13 days of symp­toms on enso­vibep and place­bo on top of stan­dard of care. Five days af­ter dos­ing, pa­tients’ con­di­tion will be as­sessed on the need for sup­ple­men­tal oxy­gen, me­chan­i­cal ven­ti­la­tion, or oth­er sup­port­ive care. If enso­vibep shows promise at that ear­ly check in, the NIH will en­roll an ad­di­tion­al 700 pa­tients, who will be fol­lowed for 90 days with a pri­ma­ry end­point of sus­tained re­cov­ery over stan­dard of care 14 days af­ter leav­ing the hos­pi­tal.

Ear­li­er this month, Glax­o­SmithK­line and Vir Biotech­nol­o­gy closed en­roll­ment for their part­nered an­ti­body VIR-7831 in AC­TIV-3 tri­al af­ter the drug showed neg­li­gi­ble ef­fect in achiev­ing sus­tained re­cov­ery in hos­pi­tal­ized Covid-19 pa­tients. At a pre­de­ter­mined 300-pa­tient in­ter­im check-in, an in­de­pen­dent da­ta com­mit­tee “raised con­cerns about the mag­ni­tude of po­ten­tial ben­e­fit” for the an­ti­body and de­cid­ed to halt en­roll­ment as the da­ta “ma­ture.’

Just days lat­er, the NIH shut down en­roll­ment for Brii Bio­sciences’ two an­ti­bod­ies in the study. Eli Lil­ly and its an­ti­body LY-CoV555 were boot­ed from the study way back in Oc­to­ber with the drug­mak­er cit­ing study de­sign is­sues — in­clud­ing the tall task of prov­ing ben­e­fit on top of Gilead’s remde­sivir — as a po­ten­tial bar­ri­er to suc­cess.

Those fail­ures may have paved the way for the NIH to give enso­vibep a try de­spite its rel­a­tive­ly un­known clin­i­cal pro­file. Tak­ing a shot at a high-pro­file study and suc­ceed­ing would be a big boost for Mol­e­c­u­lar Part­ners’ pro­file, but Am­stutz is still man­ag­ing ex­pec­ta­tions.

“For us, we’re bring­ing the first non-an­ti­body to the tri­al, and that’s al­ready an achieve­ment for us,” he said. “I know what you know: All an­ti­bod­ies have failed. As a sci­en­tist, you can’t run the same ex­per­i­ment in the same set­ting and ex­pect dif­fer­ent re­sults. That’s not what we do so you need to change some­thing.”

Due to the high bar for suc­cess, Mol­e­c­u­lar Part­ners is hold­ing out more hope for enso­vibep in its oth­er clin­i­cal tri­als, which in­cludes a Phase II study fo­cused on in­fec­tiv­i­ty and Phase II/III test, dubbed EM­PA­THY, for mild-to-mod­er­ate pa­tients in the out­pa­tient set­ting. The part­ners hope to be­gin­ning en­rolling that study, which will in­clude 2,400 pa­tients, in ear­ly 2021 with eyes on a po­ten­tial emer­gency use au­tho­riza­tion with­in the year.

Else­where, Mol­e­c­u­lar Part­ners is try­ing in­tra­venous enso­vibep in a Phase I safe­ty and dose es­ca­la­tion tri­al. Ear­ly re­sults from that study showed the ther­a­py had a two- to three-week half-life in pa­tients with no se­ri­ous side ef­fects.

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.

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.

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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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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Emma Walmsley, GlaxoSmithKline CEO (Kevin Dietsch/Pool via CNP/Alamy)

Glax­o­SmithK­line hus­tles the 7th PD-1 past the fin­ish line with Jem­per­li. But how big will up­take be?

Everything came up sevens for GlaxoSmithKline on Thursday as the pharma notched the seventh PD-1 approval seven years after the first such drugs were OK’ed in Keytruda and Opdivo. But will it bring GSK good fortune?

The FDA granted accelerated approval to dostarlimab, to be branded Jemperli, to treat recurrent or advanced endometrial cancer in a specific subset of patients following platinum-based chemo. It’s a drug that came to GSK through its buyout of Tesaro, which it snapped up for $5.1 billion back in December 2018.

JP Gabriel, Ocugen

JP Gabriel watched from the bleach­ers as the pan­dem­ic raged. Now head of sup­ply chain at Ocu­gen, he's ready to bat

The world was in the middle of the most pressing public health risk his generation had ever seen, and JP Gabriel felt like he was sitting on the sidelines. As a VP of biologics and mRNA manufacturing at Ultragenyx, Gabriel watched from the sidelines as players like Pfizer/BioNTech and Moderna used mRNA tech to chase their own Covid-19 vaccines.

This month, Gabriel got the chance to get his hands dirty against the pandemic — but it won’t be with mRNA.

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Sen. Patty Murray (D-WA) (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.”

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.