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.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; 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.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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Yong Dai, Frontera Therapeutics CEO

Scoop: Lit­tle-known Or­biMed-backed biotech clos­es $160M round to start gene ther­a­py tri­al

Frontera Therapeutics, a China and US biotech, has closed a $160 million Series B and received regulatory clearance to test its first gene therapy stateside, Endpoints News has learned.

Led by the largest shareholder, OrbiMed, the biotech has secured $195 million total since its September 2019 founding, according to an email reviewed by Endpoints. The lead AAV gene therapy program is for an undisclosed rare eye disease, according to the source.

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De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

DEM BioPharma CEO David Donabedian (L) and executive chair Jan Skvarka

Long­wood sets an­oth­er 'don't eat me' biotech in­to gear with help of for­mer Tril­li­um CEO Jan Skvar­ka

Jonathan Weissman and team are out with a cancer-fighting biotech riding the appetite for those so-called “don’t eat me” and “eat me” signals.

The scientific co-founder — alongside fellow Whitehead Institute colleague Kipp Weiskopf and Stanford biologist Michael Bassik — has launched DEM BioPharma with incubator Longwood Fund and a crop of other investors.

In all, the nascent, 10-employee biotech has $70 million to bankroll hematology- and solid tumor-based programs, including a lead asset that could enter human trials in two to three years, CEO David Donabedian told Endpoints News.

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Spanish Prime Minister Pédro Sanchez and European Commission President Ursula von der Leyen (AP Photo/Geert Vanden Wijngaert)

EU to launch vac­cine de­vel­op­ment and man­u­fac­tur­ing part­ner­ship with Latin Amer­i­can and Caribbean coun­tries

While European companies, including BioNTech, are focused on increasing vaccine access to African countries by setting up vaccine manufacturing facilities, the European Union is looking westward to Latin America and the Caribbean.

Speaking at a press conference with Spanish Prime Minister Pédro Sanchez, EU Commission president Ursula von der Leyen said that the EU is launching a new initiative for vaccines and medicines manufacturing in Latin America, to get drugs to Latin America and the Caribbean faster.

GSK says its drug for chron­ic hep B could ‘lead to a func­tion­al cure’ — but will it be alone or in com­bi­na­tion?

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.