Reverie Labs founders Jonah Kallenbach and Ankit Gupta

Roche and Genen­tech's lat­est AI col­lab­o­ra­tor rais­es $25M Se­ries A to rein­vent one of the old­est can­cer tar­gets

Jon­ah Kallen­bach spent the sum­mer be­fore his se­nior year with An­ton, the hulk­ing flu­o­res­cent su­per­com­put­er housed in the mid­town Man­hat­tan of­fices of hedge fund D.E. Shaw. Armed with 512 proces­sors run­ning in par­al­lel, it’s been used since 2008 to probe some of the biggest ques­tions in pro­tein fold­ing and struc­ture.

Kallen­bach can’t talk much about what he worked on, but he was hooked, and af­ter his last year at Har­vard, he want­ed to go in­to drug de­vel­op­ment. But when he went look­ing for phar­ma roles, he found few of the com­pa­nies had space for com­pu­ta­tion­als. Or they had space, but that space was small and cor­doned off from the rest of a mas­sive or­ga­ni­za­tion.

“No one was lis­ten­ing, no one was ac­tu­al­ly dri­ving de­ci­sions,” Kallen­bach told End­points News. That “was a light­bulb mo­ment.”

It’s a fa­mil­iar sto­ry by now for com­pu­ta­tion­al bi­ol­o­gists, as was what Kallen­bach did next: He found­ed his own com­pa­ny with a long­time col­lege friend and col­lab­o­ra­tor, Ankit Gup­ta. Brand­ed Rever­ie Labs, the Cam­bridge start­up land­ed seed fund­ing at Y Com­bi­na­tor and late last year a rare mul­ti-tar­get col­lab­o­ra­tion with Roche and Genen­tech. Now, they’ve raised their first sig­nif­i­cant cap­i­tal, rais­ing a $25 mil­lion Se­ries A led by Ridge­back Cap­i­tal to ad­vance a pipeline of tar­get­ed can­cer drugs.

The biotech will use ma­chine learn­ing and oth­er com­pu­ta­tion­al meth­ods to study the struc­ture of ki­nas­es and ul­ti­mate­ly de­sign drugs that can knock them out. The pro­teins — among the first-ever hit with tar­get­ed can­cer drugs — are an old fo­cus for a young com­pa­ny, and Kallen­bach says he ini­tial­ly faced push­back from in­vestors.

“A lot of peo­ple were like, ‘Who cares about ki­nas­es?'” Kallen­bach said. “Ki­nas­es are a solved prob­lem, ki­nas­es are easy.”

Kallen­bach ar­gued, though, that ki­nas­es are an ide­al fo­cus for a com­pu­ta­tion­al start­up. Be­cause they’ve been stud­ied vo­ra­cious­ly over the past few decades, re­searchers have de­vel­oped huge da­ta sets on their struc­ture and func­tion — da­ta sets that ma­chine learn­ing can turn in­to drug­gable in­sights.

Ki­nas­es are al­so an area where speci­fici­ty be­comes cru­cial; a “healthy” ki­nase and an onco­genic one may on­ly dif­fer by an amino acid or two, and a drug that hits both may run in­to the kind of safe­ty is­sues that plagued the Pi3K space for a decade. New tools can help dis­cern the dif­fer­ence.

Kallen­bach and Gup­ta hope that for their tar­gets, they can trun­cate the years of work and set­backs that went in­to the first Pi3K ap­proval. Al­ready work­ing with Roche, they want to even­tu­al­ly look some­thing like Nim­bus: A sought-af­ter dis­cov­ery en­gine that can de­vel­op mol­e­cules par­tial­ly in-house, be­fore large com­pa­nies bring them through the home stretch.

The en­gine will be par­tic­u­lar­ly im­por­tant, Kallen­bach said, as de­vel­op­ers push deep­er in­to com­bi­na­tion ap­proach­es that over­come re­sis­tance to in­di­vid­ual drugs. Every new drug in a com­bo brings the po­ten­tial of new tox­i­c­i­ties, rais­ing the bar for how safe each in­di­vid­ual mol­e­cule is.

“The fu­ture of can­cer ther­a­py is to ac­tu­al­ly be able to cure peo­ple of can­cer, and not just give them a 3 or 6-month boost in PFS,” he said. “And the on­ly way we can ac­tu­al­ly do that and have the pa­tient tol­er­ate that ther­a­py, is if those ther­a­pies are pret­ty spe­cif­ic.”

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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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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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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Andrew Hopkins, Exscientia

Black­Rock push­es Ex­sci­en­tia Se­ries C to $100M as AI biotech boom con­tin­ues

The jury’s still out on whether the first wave of AI companies can significantly change drug development, but investors are increasingly buying into the hype.

Exscientia, the decade-old UK machine learning outfit, announced Thursday that they’ve expanded their Series C, first announced in May, from $60 million to $100 million. The expansion most notably includes BlackRock, the private equity firm that has been wading deeper and deeper into biotech. They now join Novo Holdings, Bristol Myers Squibb and others among the company’s most recent backers.

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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