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)

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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.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

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Feng Tian, Ambrx CEO (Ambrx)

Af­ter 5 qui­et years, a for­mer Scripps spin­out rais­es $200M and an­nounces plans to try again at an IPO

The first time San Diego biotech Ambrx tried to go public in 2014, they failed and the company’s board switched to a radically different strategy: They sold themselves for an undisclosed amount to a syndicate of Chinese investors and pharma companies.

Now, after 5 quiet years, that syndicate has raised a mountain of cash and indicated they’ll soon make another bid to go public.

Earlier this month, Ambrx raised $200 million in what they billed as a crossover round financed by Fidelity, BlackRock, Cormorant Asset Management, HBM Healthcare Investments, Invus, Adage Capital Partners and Suvretta Capital Management. It’s the largest amount they’ve ever raised and, according to Crunchbase figures, more than doubles the total amount of VC capital collected since their launch 17 years ago.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

Bob Nelsen rais­es $800M and re­cruits a star-stud­ded board to build the 'Fox­con­n' of biotech

Bob Nelsen spent his pandemic spring in his Seattle home, talking on the phone with Luciana Borio, the scientist who used to run pandemic preparedness on the National Security Council, and fuming with her about the dire state of American manufacturing.

Companies were rushing to develop vaccines and antibodies for the new virus, but even if they succeeded, there was no immediate supply chain or infrastructure to mass-produce them in a way that could make a dent in the outbreak.

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Michelle Longmire, Medable CEO (Jeff Rumans)

Med­able gets $91M for vir­tu­al clin­i­cal tri­als, bring­ing to­tal raise to $136M

As biotechs look to get clinical studies back on track amid the pandemic, Medable returned to the venture well for the second time this year, bagging a $91 million Series C to build out its virtual trial platform.

The software provider recently launched three new apps for decentralizing clinical trials, and saw a 500% revenue spike this year. And it isn’t alone. Back in August, Science 37 secured a $40 million round for its virtual trial tech, with support from Novartis, Sanofi Ventures and Amgen. Patients and researchers are taking a liking to the online approach, suggesting regulators could allow it to become a new normal even after the pandemic is over.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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Pur­due Phar­ma pleads guilty in fed­er­al Oxy­Con­tin probe, for­mal­ly rec­og­niz­ing it played a part in the opi­oid cri­sis

Purdue Pharma, the producer of the prescription painkiller OxyContin, admitted Tuesday that, yes, it did contribute to America’s opioid epidemic.

The drugmaker formally pleaded guilty to three criminal charges, the AP reported, including getting in the way of the DEA’s efforts to combat the crisis, failing to prevent the painkillers from ending up on the black market and encouraging doctors to write more painkiller prescriptions through two methods: paying them in a speakers program and directing a medical records company to send them certain patient information. Purdue’s plea deal calls for $8.3 billion in criminal fines and penalties, but the company is only liable for a fraction of that total — $225 million.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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