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.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; 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.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Fu­ji­film con­tin­ues CD­MO ex­pan­sion, break­ing ground on $435M UK site

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.

An­oth­er Cipla site lands a Form 483 over clean­ing is­sues and QC con­trols

A Cipla drug manufacturing site in India has once again landed in the crosshairs of FDA inspectors.

The facility in question is Cipla’s drug manufacturing facility in the village of Verna, in the state of Goa in India’s southwest. In a sign that foreign inspections might ramp up again, the FDA’s visit from Aug. 16 to Aug. 22 uncovered six observations.

The 11-page report noted that environmental monitoring at the site did not properly ensure that microbial contaminants were not making any impact in the aseptic filling areas. It also found that procedures meant to stop microbial contamination were not adequately conducted in aseptic areas of the facility.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

Klick Health gath­ers biotech and phar­ma lu­mi­nar­ies to dis­cuss in­dus­try in­no­va­tions, in­vest­ments and fu­ture

At Klick Health’s first Ideas Exchange conference with biotech and pharma industry insiders since before the pandemic began, it was no surprise many conversations included Covid topics. Yet while vaccines and treatments were discussed, so too were the effects on drug development, federal responses, health inequities — and what to do now and next.

George Yancopoulos, chief scientist and cofounder of Regeneron, opened the conference responding to a question from Acorda CEO Ron Cohen about the spotlight on the industry during Covid and some of the “flak” biopharma has taken in the past.