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.

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

While it is not uncommon for a biotech to go down the route of having the product manufactured by a contract organization, one small biotech is looking to keep its card close to its chest.

Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

Sarepta Therapeutics has filed the data needed for an FDA accelerated approval, which would be the biotech’s fourth if granted by the agency.

The biotech has yet to complete confirmatory trials for those first three conditional nods. The filing for its fourth Duchenne muscular dystrophy treatment, disclosed Thursday, is not a surprise. Sarepta said in late-July it would do so after releasing positive results for the Roche-partnered gene therapy.

The US government is all set to buy $10.7 million worth of Siga Technologies’ monkeypox oral antiviral, the company announced Thursday.

Of the total doses, $5.1 million worth of oral antivirals called Tpoxx (tecovirimat) will be delivered this year, with the US Department of Defense having the option of buying the rest at a later point.

The new contract follows an earlier one in which the government had purchased $7.4 million worth of Tpoxx from the company.