George Church (Mary Altaffer/AP Images)

Bay­er backs a George Church spin­out try­ing to turn lab-in­vent­ed amino acids in­to a new class of pro­tein ther­a­pies

Six years ago, Daniel Man­dell ap­peared on NPR to talk about an in­ven­tion out of Juras­sic Park.

As Crich­ton and Gold­blum fans re­call, In­ter­na­tion­al Ge­net­ic Tech­nolo­gies, Inc.’s con­tin­gency plan to make sure di­nosaurs didn’t es­cape was to take away their abil­i­ty to make the amino acid ly­sine, forc­ing them to re­ly on ly­sine sup­ple­ments from the park staff for sur­vival.

Dan Man­dell

Man­dell, a fel­low at George Church’s Har­vard lab, took the idea a step fur­ther. He, Church and a team of sci­en­tists en­gi­neered a bac­te­ria de­pen­dent on an ar­ti­fi­cial amino acid that didn’t ex­ist any­where; sci­en­tists had in­vent­ed it.

In the­o­ry, you could ex­ploit that re­liance to make sure ge­net­i­cal­ly en­gi­neered or­gan­isms didn’t spread out­side their in­tend­ed use. For ex­am­ple, you could use the mod­i­fied bac­te­ria to clean up an oil spill and then get rid of the bac­te­ria.

“While ly­sine is a nat­ur­al amino acid that is found every­where in na­ture,” Man­dell ex­plained on Sci­ence Fri­day, “our amino acid ex­ists on­ly where we put it.”

Their bac­te­ria nev­er de­ployed to clean up oil spills, but that was on­ly one in a long list of po­ten­tial ap­pli­ca­tions for an or­gan­ism that can re­ly on and churn out ar­ti­fi­cial amino acids. And af­ter years of fine-tun­ing and in­dus­tri­al­iz­ing the aca­d­e­m­ic bac­te­ria, Man­dell has man­aged to raise mon­ey from blue chip in­vestors to use his or­gan­isms else­where: build­ing new kinds of ther­a­peu­tics.

On Wednes­day , GRO Bio­sciences, the com­pa­ny he co-found­ed short­ly af­ter the orig­i­nal work ap­peared in Na­ture, an­nounced a $25 mil­lion Se­ries A led by Leaps by Bay­er and Red­mile Group to de­vel­op ther­a­pies with ar­ti­fi­cial amino acids. The new round adds to ear­li­er seed cash from Dig­i­tal­is and In­no­va­tion En­deav­ors, for­mer Google CEO Er­ic Schmidt’s VC.

Amino acids are the ba­sic build­ing blocks of pro­teins, so it’s per­haps un­sur­pris­ing that GRO will fo­cus on pro­tein-based ther­a­pies. On­ly 20 amino acids oc­cur in na­ture, each com­ing to­geth­er in var­i­ous se­quences and con­for­ma­tions to form the pro­teins that make up all life.

By adding new types of amino acids, Man­dell and his CSO and co-founder Christo­pher Gregg — and a long list of aca­d­e­mics and a few biotechs, in­clud­ing the $2.5 bil­lion Sanofi sub­sidiary Syn­thorx — think they can make pro­teins with new prop­er­ties.

Chris Gregg

“As a de­sign­er, one is of­ten struck by a fun­da­men­tal lim­i­ta­tion of pro­teins, which is that they’re all com­prised of the same 20 amino acid build­ing blocks,” Man­dell, now CEO, said in an in­ter­view. Adding new amino acids “re­al­ly opens up an in­cred­i­bly ex­cit­ing chem­i­cal uni­verse.”

GRO claims that its ad­van­tage will come from its syn­thet­ic or­gan­isms. It can be dif­fi­cult to get bac­te­ria to man­u­fac­ture these ar­ti­fi­cial build­ing blocks; pic­ture a fac­to­ry try­ing to put to­geth­er a car from mis­shapen parts.

GRO can make bac­te­ria that are not on­ly re­liant on syn­thet­ic amino acids to sur­vive, but Man­dell said, are al­so unique­ly adept at churn­ing out pro­teins with syn­thet­ic amino acids.

“All this leads to very high ef­fi­cien­cy, pro­duc­tion and scal­a­bil­i­ty,” he said.

The first ap­proach is the most in­tu­itive. GRO will try to use the ar­ti­fi­cial amino acids, tech­ni­cal­ly known as non-stan­dard or non-canon­i­cal amino acids, to build ther­a­peu­tic pro­teins that can last longer than cur­rent pro­tein-based ther­a­pies.

Nu­mer­ous meta­bol­ic dis­eases can be treat­ed by giv­ing pa­tients ar­ti­fi­cial ver­sions of a hu­man pro­tein: re­place­ments for en­zymes pa­tients with ge­net­ic dis­or­ders such as Fab­ry dis­ease are miss­ing, or var­i­ous treat­ments for di­a­betes. These drugs, though, of­ten have to be dosed week­ly or even dai­ly.

It’s “oner­ous,” Man­dell said. And it “caus­es non-com­pli­ance in pa­tients.”

In the­o­ry, GRO’s pro­teins can be in­fused and re­main in the body at rough­ly the same con­cen­tra­tion for an ex­tend­ed pe­ri­od. That would both ease dos­ing and pre­vent the big spike and de­cline in pro­tein lev­els pa­tients of­ten see.

The sec­ond ap­proach in­volves au­toim­mune dis­eases. Syn­thet­ic amino acids can al­so be used to cre­ate pro­teins with dif­fer­ent so-called post-trans­la­tion­al mod­i­fi­ca­tions — i.e. the var­i­ous dec­o­ra­tions and ac­cou­trements that cells of­ten place on top of pro­teins to serve dif­fer­ent func­tions.

Coro­n­avirus­es, for ex­am­ple, use a coat of sug­ary mol­e­cules called gly­cans to shield them­selves from the im­mune sys­tem. Gly­cans, though, can al­so be used to train the hu­man im­mune sys­tem.

In an au­toim­mune dis­ease like mul­ti­ple scle­ro­sis, a pa­tient’s im­mune cells be­gin at­tack­ing myelin pro­teins in their ner­vous sys­tem. By giv­ing that pa­tient lab-made myelin pro­teins stud­ded with the right gly­can coat, GRO hopes to coax the im­mune sys­tem to learn to tol­er­ate myelin again.

Nei­ther of these ideas are en­tire­ly unique to GRO, al­though syn­thet­ic amino acids have most­ly been used in the past for con­ju­ga­tion.

The com­pa­ny, though, is still in its ear­ly stages. They plan to put their first ther­a­pies in the clin­ic in 2024, while al­so de­vel­op­ing new mi­crobes that po­ten­tial­ly can build pro­teins with mul­ti­ple ar­ti­fi­cial amino acids, al­low­ing for fur­ther de­sign.

Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

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Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

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The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

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The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

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Alexander Lefterov/Endpoints News

A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

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Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.

Brian Thomas, Metagenomi CEO

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This morning Metagenomi, allied with one of the biggest names in the mRNA field with a company DNA that includes the ubiquitous Jennifer Doudna, is showing off a $175 million B round that will pay for a rapid swelling of its staff in pursuit of some of the cutting-edge tech that keeps this field in the spotlight. And they’re aligning themselves with some major industry players with an eye on the clinic while getting behind some startups to help expand the work into new fields.

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Not cheap­er by the dozen: Bris­tol My­ers be­comes the 12th phar­ma com­pa­ny to re­strict 340B sales

Bristol Myers Squibb recently joined 11 of its peer pharma companies in limiting how many contract pharmacies can access certain drugs discounted by a federal program known as 340B.

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Joaquin Duato, J&J CEO (Photo by Charles Sykes/Invision/AP)

New J&J CEO Joaquin Du­a­to promis­es an ag­gres­sive M&A hunt in quest to grow phar­ma sales

Joaquin Duato stepped away from the sideline and directly into the spotlight on Tuesday, delivering his first quarterly review for J&J as its newly-tapped CEO after an 11-year run in senior posts. And he had some mixed financial news to deliver today while laying claim to a string of blockbuster drugs in the making and outlining an appetite for small and medium-sized M&A deals.

Duato also didn’t exactly shun large buyouts when asked about the future of the company’s medtech business — where they look to be in either the top or number 2 position in every segment they’re in — even though the bar for getting those deals done is so much higher.

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Amgen's Twitter campaign #DearAsthma inspired thousands of people to express struggles and frustrations with the disease

Am­gen’s #Dear­Asth­ma spon­sored tweet lands big on game day, spark­ing thou­sands to re­spond

Amgen wanted to know how people with asthma really felt about daily life with the disease. So it bought a promoted tweet on Twitter noting the not-so-simple realities of life with asthma and ended the post with a #DearAsthma hashtag, a megaphone emoji and a re-tweet button.

That was just over one week ago and the responses haven’t stopped. More than 7,000 posts so far on Twitter replied to #DearAsthma to detail struggles of daily life, expressing humor, frustration and sometimes anger. More than a few f-bombs have been typed or gif-ed in reply to communicate just how much many people “hate” the disease.