Jerel Davis and Marcelo Bigal (Versant)

'It's pure art': Ver­sant, GV re­veal $60M bet that a clear­er look at in­flam­ma­somes can lead to bet­ter drugs

For years, sci­en­tists had known about the myr­i­ad ways NL­RP3 push­es the in­nate im­mune sys­tem to go over­board and trig­ger au­toim­mune or in­flam­ma­to­ry dis­eases. But un­til Hao Wu and her Har­vard lab came along, no­body re­al­ly had a good idea of what the pro­tein looks like.

Like oth­er in­flam­ma­somes, NL­RP3 tends to clump to­geth­er in vit­ro, shield­ing its shape from re­searchers. Wu’s team — com­pris­ing some of the best struc­tur­al bi­ol­o­gists in the world — com­bined some new pro­tein en­gi­neer­ing with the cryo-elec­tron mi­croscopy tech­niques they know well to crack the prob­lem.

“It’s re­al­ly sat­is­fy­ing that we got an an­swer,” Wu said last June, when the find­ing was pub­lished in Na­ture. “I feel like this means that it doesn’t mat­ter how dif­fi­cult a prob­lem is; if you put in enough ef­fort, you’ll get it.”

And they didn’t stop at that. The group has elu­ci­dat­ed the struc­tures of over 10 more in­flam­ma­somes and nu­cle­ic acid-sens­ing tar­gets, and Ver­sant Ven­tures is now draw­ing the cur­tain from Ven­tus Ther­a­peu­tics, the biotech start­up tasked with bring­ing for­ward small mol­e­cule drugs against these tar­gets.

Eigh­teen months af­ter the sea­soned team at the Mon­tre­al branch of its In­cep­tion Dis­cov­ery En­gine start­ed ham­mer­ing away, Ver­sant has brought in GV to com­plete a $60 mil­lion Se­ries A.

“We have been look­ing for knowl­edge­able in­vestors who un­der­stand and ap­pre­ci­ate the sci­ence be­hind the new in­nate im­mune tar­gets,” Wu told End­points News in an email. “Ver­sant, es­pe­cial­ly Jer­el Davis, is vi­sion­ary in this re­gard.”

Hao Wu (Boston Chil­dren’s Hos­pi­tal)

Click on the im­age to see the full-sized ver­sion

With some of the pre­vi­ous pro­grams — most re­cent­ly at Je­cure Ther­a­peu­tics, whose pre­clin­i­cal pipeline was quick­ly snapped up by Roche — the VC firm has learned first hand how chal­leng­ing these tar­gets could be, Davis said. Giv­en the elu­sive mol­e­c­u­lar struc­tures and the lack of bio­chem­i­cal or bio­phys­i­cal as­says, “in some ways we’re in the 1980s or 1990s with re­spect to how we did drug dis­cov­ery on these tar­gets.”

How big of a help turn­ing the lights on in the de­vel­op­ment process, as CEO Marce­lo Bi­gal com­pared Ven­tus’ ap­proach to, re­mains to be seen.

“Of­ten­times it’s a nice-to-have but it’s not nec­es­sar­i­ly a must-have,” Gary Glick, who found­ed IFM Ther­a­peu­tics to pur­sue a broad range of in­flam­ma­somes and nu­cle­ic acid sens­ing tar­gets, said. “In­flam­ma­somes in par­tic­u­lar, which are large mul­ti-pro­tein com­plex­es, one could ar­gue there’s de­bate on how much you need the struc­ture ver­sus how much you may not need the struc­ture.”

That said, he ac­knowl­edged that know­ing the bind­ing site of a par­tic­u­lar mol­e­cule can fa­cil­i­tate op­ti­miza­tion, un­der­stand se­lec­tiv­i­ty of po­ten­tial drug can­di­dates and shed light on the mech­a­nism. Wu is al­so an “ex­treme­ly nice per­son and an ex­treme­ly good sci­en­tist” from his few in­ter­ac­tions with her, he added.

Im­por­tant­ly, Bi­gal stressed, Wu’s break­through wasn’t just about un­earthing the struc­tures. It’s al­so about ex­press­ing, pu­ri­fy­ing and sta­bi­liz­ing the pro­teins for drug screens.

“It’s pure art,” he said. “For each of them, it’s a dif­fer­ent recipe.”

The ap­pli­ca­tions can be broad, cap­tur­ing every­thing from ge­net­ic dis­eases to NASH. With­in au­toim­mune and in­flam­ma­to­ry dis­eases, where you’d want to tamp down the in­nate im­mu­ni­ty, it can span cer­tain neu­rode­gen­er­a­tive dis­or­ders, asth­ma and con­di­tions trig­gered by in­fec­tions; in some cas­es you might want to crank sig­nal­ing up to at­tack can­cer.

Wu’s pro­tégé Feng Shao has joined her as a co-founder, fill­ing a line­up of promi­nent aca­d­e­m­ic in­ves­ti­ga­tors who are serv­ing as ad­vi­sors: Yale im­mu­nol­o­gist Richard Flavell; Judy Lieber­man of Har­vard, who stud­ies im­mune path­ways that trig­ger cell death; Thomas Tuschl of Rock­e­feller, a pi­o­neer in nu­cle­ic acid bi­ol­o­gy; Dou­glas Green, a co-lead of the can­cer bi­ol­o­gy pro­gram at St. Jude Chil­dren’s Re­search Hos­pi­tal; and Rus­sell Vance at UC Berke­ley, whose work on NL­RP1 was high­light­ed.

For now, Ven­tus has ze­roed in on three pro­grams to pri­or­i­tize ini­tial­ly.

“In due course tar­gets de­clare them­selves,” he said, cit­ing years of drug de­vel­op­ment ex­pe­ri­ence, in­clud­ing a stint lead­ing R&D at Te­va. “What the plat­form al­lows us is to get tar­gets at our dis­pos­al.”

Work is well un­der­way at Ven­tus’ labs in Mon­tre­al and Boston, where sci­en­tists are work­ing in shifts and stay 10 feet apart. Cog­nizant of both the fears and the sense of mis­sion that the coro­n­avirus cri­sis is in­still­ing in his sci­en­tists, Bi­gal has start­ed a rit­u­al to meet every Mon­day to share as a group. And he makes sure the team, which is set to grow past 30 by the end of the year, jumps on a vir­tu­al hap­py hour every Fri­day.

“It’s ac­tu­al­ly quite re­mark­able how much progress some of our pre­clin­i­cal com­pa­nies are mak­ing de­spite Covid,” Davis said.

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, 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.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.

Paul Hudson, Getty Images

How does Paul Hud­son's $13.5M comp pack­age stack up against oth­er CEOs? He's in the 'first quar­tile'

Paul Hudson arrived at Sanofi like a hurricane, chopping off duds in the pipeline, shaking up the C-suite, striking big M&A deals and jumping into the Covid-19 vaccine race — all in an attempt to reboot a pharma giant notorious for its setbacks.

Now, we’re getting a look at what the CEO brought home in his first year on the job.

When all is said and done, Hudson will have made about $6.7 million in 2020, about $2.5 million of which has already been paid. The bigger figure includes a $2.3 million bonus that’s subject to approval at an April meeting, and another $1.8 million in variable compensation that has yet to be paid.

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An Ar­ray co-founder re-emerges as CEO of a small aca­d­e­m­ic spin­out, look­ing to re­make an old class of can­cer drugs

Tony Piscopio hadn’t worked as a bench scientist in years when, around 2011, he got put in touch with a team at the University of Colorado trying to revitalize an old approach to treating cancer.

Piscopio, who had co-founded Array Biopharma before heading to South Korea to launch a new company, was back in the states, unattached and intrigued. He founded a three-person company with two professors, Xuedong Liu and Gail Eckhardt, and while they worked on the biology side, he returned to his old chemist chair and began drawing up potential compounds on a computer, along with manufacturing processes to make them. Outsourcing companies synthesized or analyzed the results.

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Af­ter three years of courtship (and turn­downs), Mer­ck pounced on the first glance of clin­i­cal da­ta in $1.85B Pan­dion takeover

It’s almost become cliché for biotech executives to talk about the importance of keeping your options open and being prepared to go all the way. But when it comes to negotiating with a giant like Merck, a little patience can indeed go a long way.

Just ask Pandion Therapeutics.

Days ago we already learned that Merck is shelling out $1.85 billion to pick up the biotech and its slate of autoimmune hopefuls. What we didn’t know until the SEC disclosure dropped Thursday is that the deal comes after Pandion turned down two other proposals from Merck over the past three years and held out until the last minute for a sweetened deal.

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