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.

Australia’s Avance Clinical: no IND required and a 43.5% rebate on clinical spend for CGT biotechs

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The cell and gene therapies (CGT) sector offers unprecedented opportunities for patient disease management across virtually all therapeutic areas. However, finding the right accredited clinical teams to take a therapy through to the clinic and manage the regulatory process can be a major challenge for biotechs with a CGT product.

Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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Troy Wilson, Kura CEO

UP­DAT­ED: FDA hits the red light on an ear­ly-stage AML study af­ter a pa­tient dies

The FDA has slapped a clinical hold on the early-stage program for one of Kura Oncology’s cancer drugs following a patient’s death in a clinical trial.

The biotech $KURA reported early Wednesday that the Phase Ib study of KO-539 for acute myeloid leukemia would be halted, suspending enrollment, while researchers and the FDA probed the death. Patients already on the drug can continue taking it.

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What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

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Mar­ket­ingRx roundup: Am­gen, Lil­ly, Bio­haven mi­graine brand re­call low, study says; No­var­tis looks to re­make drug launch mod­el

Forget the migraine marketing brand wars. When it comes to patients, many can’t even name one despite substantial advertising efforts, according to a new study from Phreesia that concludes CGRP migraine drugmakers still need to work on brand recognition.

Almost half (47%) of the patients Phreesia surveyed couldn’t name one preventative migraine brand. The best performer was Topamax, a small molecule anticonvulsant that’s been around since 2004, which 26% of migraine patients could recall. Among the new CGRP brand names recognized, Amgen’s Aimovig ranked highest with 8% recall, while Eli Lilly’s Emgality and Biohaven’s Nurtec tied at 7% and Teva’s Ajovy was remembered by 3% of patients.

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Emma Walmsley, GlaxoSmithKline CEO (Fang Zhe/Xinhua/Alamy Live News)

Glax­o­SmithK­line places a risky bet on Ar­row­head­'s RNA drug in the fail­ure-strewn NASH field

As activist investors champ at the bit for change at drug giant GlaxoSmithKline, the pharma giant has turned over many rocks to find an R&D success to present to its detractors. In NASH, a field strewn with failures, GSK hopes a new license deal can churn out a much-needed winner.

GSK will pay $120 million in upfront cash and $910 million in downstream milestones to develop and sell ARO-HSD, Arrowhead Pharmaceuticals’ RNA interference drug targeting fatty liver disease nonalcoholic steatohepatitis (NASH), the companies said Monday.

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Name that vac­cine: From Comir­naty to Spike­vax to Nu­vax­ovid, Covid-19 shot­s' brand names re­main lit­tle-known

Most people know if they’re “Team Pfizer” or “Team Moderna,” but few know if they got the Comirnaty or Spikevax Covid-19 vaccine. Those are the brand names of Pfizer and Moderna vaccines, respectively, however they have yet to take hold with consumers, media or even medical professionals.

And there are others. Covid vaccine brand names also include AstraZeneca’s Vaxzevria, Novavax’s Nuvaxovid, and Sanofi and GlaxoSmithKline’s Vidprevtyn. J&J’s Janssen-developed Covid vaccine is the lone major holdout and is still yet to be named, if ever. In EMA filings approving its conditional use, the brand name is listed simply as “Covid-19 Vaccine Janssen.”

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Joan Perelló, Sanifit CEO

Joan Perel­ló set out 17 years ago to de­vel­op a drug. And to­day he's be­ing re­ward­ed with a $424M biotech buy­out

Joan Perelló beat all the odds with his little Spanish biotech startup Sanifit.

Working on the far perimeter of the big US/European drug development scene, he took a drug born out of his PhD work and got enough seed cash to get started. That’s one near miracle. In the second near miracle he gathered a previously unheard of venture raise in Spain — helping build an industry ecosystem from scratch — to pursue a successful search for solid human data for his drug, SNF472. And while gathering a virtual team of developers from Europe and the US, the CEO/co-founder steered it into the late-stage arena.

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