From L to R: Manifold Bio co-founders Gleb Kuznetsov (CEO), Shane Lofgren (head of BD) and Pierce Ogden (CSO)

Pro­tein ther­a­peu­tics biotech us­ing 'pro­tein bar­codes' in drug de­vel­op­ment se­cures new fi­nanc­ing — led by Jeff Hu­ber

Two years af­ter kick­ing things off with $5.4 mil­lion, a George Church spin­out is re­fill­ing its cof­fers to fu­el its ef­forts tack­ling pro­tein ther­a­peu­tics R&D.

Boston biotech Man­i­fold Bio an­nounced the new Se­ries A Thurs­day, led by new VC Tri­atom­ic Cap­i­tal, rais­ing $40 mil­lion to ad­vance its in­ter­nal pipeline and ex­pand its plat­form ca­pa­bil­i­ties. CEO and co-founder Gleb Kuznetsov tells End­points News that the fi­nanc­ing should last the biotech close to 2.5 years, de­pend­ing on how fast the com­pa­ny spends it.

Jeff Hu­ber

The biotech was Tri­atom­ic’s first in­vest­ment, Man­i­fold said in a state­ment. The VC was found­ed by none oth­er than Jeff Hu­ber, the for­mer Google ex­ec and once-CEO of Sil­i­con Val­ley can­cer test­ing start­up Grail be­fore it got bought out by Il­lu­mi­na last year. Hu­ber will be join­ing Man­i­fold’s board of di­rec­tors.

The com­pa­ny got its start when Kuznetsov and an­oth­er co-founder, Man­i­fold’s CSO Pierce Og­den, were grad­u­ate stu­dents in famed ge­neti­cist George Church’s lab. Ac­cord­ing to Kuznetsov, the pair were very in­ter­est­ed in pro­teins and pro­tein de­sign — which led them to talk to dif­fer­ent in­dus­try folks about the over­all price and ther­a­peu­tics process, and see­ing if there was a way to in­cor­po­rate more tech­nol­o­gy in­to it.

Kuznetsov orig­i­nal­ly grad­u­at­ed from MIT with a Bach­e­lor’s and then a Mas­ter’s in Com­put­er Sci­ence and spent a year at Google as a soft­ware en­gi­neer. Sev­er­al years lat­er, he went back to MIT for a PhD in Bio­physics.

“We didn’t want to just kind of bring for­ward, you know, a new drug, and, you know, kind of go the stan­dard route of pick­ing one drug and de­vel­op it,” Kuznetsov said — ref­er­enc­ing a mind­set he had seen about “you just kind of dog­mat­i­cal­ly test one mol­e­cule in an an­i­mal even­tu­al­ly, and that sort of make it or break it for a pro­gram.” That said, that led to Man­i­fold’s whole ob­jec­tive: to use tech­nol­o­gy to re­de­fine the pro­tein ther­a­peu­tic dis­cov­ery process.

The biotech first got off the ground in 2020 with $5.4 mil­lion in seed fund­ing.

As for what ex­act­ly Man­i­fold does, Kuznetsov said that the biotech wants to ad­dress what he called “bot­tle­necks” in drug cre­ation, with a spe­cif­ic pipeline fo­cus on can­cer tu­mors. One ex­am­ple was tar­get­ing — how to get a drug to start killing can­cer cells with­out harm­ing the rest of the pa­tient. Speci­fici­ty and com­plex­i­ty of which tar­gets a drug go af­ter were al­so key ques­tions at Man­i­fold.

To tack­le these bot­tle­necks, the biotech us­es “pro­tein bar­cod­ing” to track its drugs.

“From an en­gi­neer­ing per­spec­tive, you want to make these en­gi­neer mol­e­cules nav­i­gate this com­plex mam­malian en­vi­ron­ment and get just to those can­cer cells,” the CEO said. Af­ter mak­ing the drug com­po­nents in-house, the biotech then adds the pro­tein bar­codes — tiny bits of pro­tein that track how the drugs work and how ef­fec­tive the pro­tein ther­a­peu­tics are. Kuznetsov then gave an ex­am­ple, say a mouse mod­el that has a can­cer tu­mor.

Af­ter re­searchers put the drug can­di­dates in­to the tu­mor and an­a­lyze the re­sults, they count, us­ing pro­tein bar­codes plus some pro­pri­etary tech, which of the com­pa­ny’s drug de­signs end up ac­tu­al­ly be­ing suc­cess­ful.

Be­yond that, Man­i­fold has been in­ves­ti­gat­ing com­bin­ing mul­ti­ple binders to bet­ter tar­get can­cer cells that ex­press dif­fer­ent com­bi­na­tions of tar­gets. How­ev­er, the CEO not­ed that as you add this kind of com­plex­i­ty, the en­gi­neer­ing re­quired goes up too.

Kuznetsov al­so men­tioned that he has worked with Church di­rect­ly for a decade — start­ing in the ge­neti­cist’s lab back in 2012 as a re­search en­gi­neer be­fore start­ing his PhD in 2014. And be­cause of that re­la­tion­ship, Church meets with Man­i­fold once a month where the founders “ba­si­cal­ly pri­or­i­tize what we’re try­ing to do. And then George brings forth his own view of things,” the CEO not­ed.

The biotech, cur­rent­ly 15 strong, is plan­ning on dou­bling in size through­out the Se­ries A.

Kuznetsov added that while the biotech is not cur­rent­ly look­ing at ex­pand­ing its pipeline be­yond on­col­o­gy, it is in dis­cus­sions with a num­ber of oth­er com­pa­nies for pos­si­ble part­ner­ships. The biotech al­so not­ed that it start­ed work­ing on the Se­ries A just ear­li­er this year — and that it on­ly took a few months to se­cure in­vest­ments in light of how the biotech mar­ket has per­formed since Jan­u­ary.

New in­vestors for the Se­ries round in­clude Sec­tion 32, FPV, Hori­zons and Ten­cent. Pre­vi­ous in­vestors that al­so par­tic­i­pat­ed in this round in­clude Fifty Years, Play­ground Glob­al and FAST by GET­TY­LAB.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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Andrew Phillips, Nexo Therapeutics CEO

Scoop: Ver­sant, NEA launch new biotech helmed by ex-CEO of pro­tein de­grad­er C4 Ther­a­peu­tics

Long-time biotech venture firms Versant and New Enterprise Associates are backing a new startup run by former C4 Therapeutics chief executive Andrew Phillips.

The fledgling biotech has raised at least $30 million so far, according to paperwork filed with the SEC this week. The round could balloon to $60 million.

Phillips, who left protein degradation startup C4 in 2020 to be a managing director at Cormorant Asset Management, is running the show of the new venture as president, the SEC filing outlines. He also served as interim CEO of Cormorant-backed and Hansoh Pharmaceutical-partnered Blossom Bioscience last year.

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Phil L’Huillier, CatalYm CEO

Ger­man biotech CatalYm rais­es $50M to flip weight loss tar­get for can­cer

GDF15 might sound familiar. It’s a protein that Amgen, Merck and Eli Lilly built analogs for in attempts to make new weight loss drugs. But those drugs largely failed — and Amgen, the last standing of the three — quietly pulled the plug on its GDF15 program in January.

But GDF15 is not dead. The science behind the weight loss drugs goes back to the observation that some cancer patients have high levels of GDF15 and lose a lot of weight, so cancer researchers have been making antibodies that inhibit the protein instead of mimicking it.

Szabolcs Nagy, Turbine co-founder and CEO

Sim­u­la­tions for ex­per­i­ments: Bay­er-backed start­up lands $20M to test out its tech

How do you get the attention of Big Pharma when you’re a small biotech startup working out of Budapest, Hungary?

For Szabolcs Nagy and his co-founders at Turbine, the golden ticket came through Bayer’s grant program for digital health, G4A, for which the company was selected a few years back.

“We roamed around the building and sort of just knocked on a whole bunch of doors after a lot of introductions,” Nagy told Endpoints News.

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J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.