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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

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.

Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

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.

Work taking place in the clean rooms at Vor (Credit: Vor)

Vor Bio opts to keep man­u­fac­tur­ing op­er­a­tions in-house for de­vel­op­ing stem cell, CAR-T ther­a­pies

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.

Aim­ing for fourth nod, Sarep­ta files an­oth­er DMD gene ther­a­py to FDA; Ax­some head­ed to­ward mi­graine re­sub­mis­sion

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.

Phillip Gomez, Siga Technologies CEO

Siga nabs $10.7M from the US gov­ern­ment in deal for its mon­key­pox an­tivi­ral

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.

Renhong Tang, Simcere co-CEO

Almi­rall part­ners up with Sim­cere in po­ten­tial $500M+ deal — with plans to take IL-2 can­di­date glob­al

A Chinese pharma is looking to go international with one of its preclinical candidates, and it’s teaming up with a Spanish company in a new pact potentially worth half a billion dollars to do just that.

Simcere and Almirall announced Thursday that the two companies had reached a deal for Simcere’s IL-2 mutant fusion protein drug candidate, called SIM0278. According to a statement, Almirall gets an exclusive right to develop and commercialize the drug candidate in all indications and markets outside of China, Hong Kong, Taiwan and Macau.

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