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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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Bris­tol-My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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