Es­cap­ing an im­prob­a­ble up­bring­ing, Greg Ver­dine places his biggest ca­reer bets in drug­ging the ‘un­drug­gable’

In an­oth­er world, Greg Ver­dine would still be build­ing boats and tear­ing apart car en­gines in his New Jer­sey front yard.

Ver­dine, who start­ed ditch­ing school at age 7 to work on home projects at the in­sis­tence of his fa­ther, im­prob­a­bly built a ca­reer as a Har­vard Uni­ver­si­ty pro­fes­sor, se­r­i­al biotech en­tre­pre­neur and icon­o­clast. He’s gone to war with the in­dus­try’s con­ven­tion­al wis­dom that drugs sim­ply can’t reach some dis­ease-caus­ing pro­teins be­cause of their shape.

In his ca­reer-long ob­ses­sion to drug the un­drug­gable, a phrase he says he coined, he was de­nied grants and lost con­trol of past ven­tures. He left his long­time spot at Har­vard to ful­fill his quest and lead two star­tups, Fog­Phar­ma and LifeM­ine Ther­a­peu­tics, that have com­bined to raise over $600 mil­lion. Fog an­nounced Mon­day that it had dosed the first pa­tient with its lead drug can­di­date, tar­get­ing a com­mon dri­ver of can­cer that’s al­so a poster child for those im­pos­si­ble-to-hit pro­teins.

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“This is shame­ful that we just say, ‘Oh they’re un­drug­gable,'” Ver­dine said in an in­ter­view with End­points News. “That’s ca­pit­u­la­tion, that’s pa­thet­ic. That’s not a proud in­dus­try.”

Lead­ers and sci­en­tists who’ve worked with the 63-year-old de­scribe a brain over­flow­ing with ideas cou­pled with a mag­ne­tiz­ing abil­i­ty to pitch his vi­sion. But they al­so point out that the com­ing years will de­ter­mine whether he can leave a last­ing mark on biotech.

“It al­ways felt like a huge risk to hire Greg as CEO,” said Rick Klaus­ner, the for­mer Na­tion­al Can­cer In­sti­tute di­rec­tor and a friend of Ver­dine’s for decades who sits on Fog’s board. “Greg has this end­less cu­rios­i­ty. There was a re­al con­cern he was a starter, but not a fin­ish­er.”

But Klaus­ner added that Ver­dine has shown the abil­i­ty to grow in the CEO role.

“These are Greg’s biggest bets,” Klaus­ner said of the new star­tups. “He could have just been pub­lish­ing about this stuff, but Greg re­al­ly want­ed to make re­al drugs that go in­to peo­ple and solve prob­lems.”


Grow­ing up in the rur­al Pine Bar­rens of New Jer­sey, ed­u­ca­tion was not a pri­or­i­ty for the Verdines.

His fa­ther dropped out of school in the ninth grade and worked at a heavy-equip­ment com­pa­ny. Ver­dine’s three broth­ers fol­lowed sim­i­lar paths in­to blue-col­lar trades.

Ver­dine’s own life was up­end­ed when he was 5. His fa­ther dived in­to a neigh­bor’s pool and land­ed on his neck, leav­ing him quad­ri­pleg­ic and un­able to build with his hands.

So he turned to his son. Ver­dine learned to weld as a 7-year-old, and his dad start­ed keep­ing him home from school to work on in­creas­ing­ly am­bi­tious projects. The two built a 12-foot sail­boat, con­struct­ed a wheel­chair lift for a van, re­assem­bled Chevro­let Cor­vair en­gines, and even ren­o­vat­ed a 42-foot Chris-Craft boat blocked up on their front yard.

Greg Ver­dine’s fa­ther, Richard, in 1975

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His moth­er had dif­fer­ent ideas. Af­ter she found out he was miss­ing school, she con­vinced the high school’s as­sis­tant prin­ci­pal to take him in.

De­spite a poor at­ten­dance record, Ver­dine had a knack for school. His guid­ance coun­selor was im­pressed by his SAT score, but Ver­dine wasn’t plan­ning to go to col­lege. He thought he got some­one else’s mail by mis­take when he opened an ac­cep­tance let­ter from Saint Joseph’s Uni­ver­si­ty in Philadel­phia. When a sec­ond let­ter ar­rived with a full schol­ar­ship of­fer, he knew some­thing was up.

“My high school guid­ance coun­selor had gone be­hind my back, got me in­to col­lege and got me a schol­ar­ship be­cause he knew I couldn’t af­ford it,” Ver­dine said.

At col­lege, Ver­dine found his child­hood tin­ker­ing trans­lat­ed to the lab. Push­ing a chem­i­cal re­ac­tion was like tight­en­ing a bolt on an en­gine block.

“I’ve worked with a lot of sci­en­tists, and he’s re­al­ly in the top 1% as far as cre­ativ­i­ty, in­tel­li­gence and abil­i­ty to go around is­sues,” said Elias Zer­houni, a for­mer NIH di­rec­tor who worked with Ver­dine while run­ning R&D at Sanofi.

Ver­dine rapid­ly moved from Saint Joe’s to Co­lum­bia Uni­ver­si­ty and fi­nal­ly to a ju­nior fac­ul­ty spot at Har­vard in 1989. The $57,000 salary in those ear­ly years was his first taste of life-chang­ing mon­ey com­pared to his back­woods child­hood, and it would soon be cou­pled with an eye-open­ing trip to Switzer­land.


It was the mid-1990s and Ver­dine was there to see cut­ting-edge re­search by Hoff­mann-La Roche. The phar­ma gi­ant had built the first-ever au­to­mat­ed screen­ing sys­tem, test­ing its en­tire li­brary of over one mil­lion com­pounds against sev­er­al dozen top tar­gets. The end re­sult was sober­ing: ze­ro hits.

“That was the first time I heard the term un­drug­gable,” Ver­dine said.

He saw a con­sen­sus emerge, with re­searchers char­ac­ter­iz­ing pro­teins by drug­ga­bil­i­ty. And as more and more of his peers start­ed to use that lan­guage, Ver­dine re­belled.

“Greg’s brain is not at all bound­ed by the pos­si­ble,” said Bar­bara We­ber, CEO of Tan­go Ther­a­peu­tics and a board mem­ber of Fog. “He doesn’t care. He doesn’t even think about whether some­thing might be viewed as pos­si­ble to some­body else.”

Ver­dine says he coined the phrase “drug­ging the ‘un­drug­gable’” and start­ed lec­tur­ing on it in the ear­ly 2000s. He trav­eled from con­fer­ence to con­fer­ence flash­ing a provoca­tive slide en­ti­tled “The Wall of Shame.” Like a most-want­ed fugi­tive list, it showed the mugshots (or mol­e­c­u­lar struc­tures) of three ma­jor can­cer-dri­ving pro­teins: be­ta-catenin, Ras, and Myc. De­spite play­ing a ma­jor role in can­cer, they were writ­ten off as too hard to tar­get.

Ver­dine has pre­sent­ed a ver­sion of this “Wall of Shame” slide for years, high­light­ing a few so-called un­drug­gable can­cer tar­gets.

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Ver­dine set his lab on the prob­lem. Chris­t­ian Schafmeis­ter, now a chemist at Tem­ple Uni­ver­si­ty, joined to turn pep­tides, the build­ing blocks of pro­teins, in­to drugs. While Ver­dine says he nev­er got an NIH grant ap­proved for the re­search, they pub­lished their first work in 2000.

In 2001, that pep­tide re­search be­came Aileron Ther­a­peu­tics, one of the first com­pa­nies Ver­dine start­ed. But very quick­ly, he learned the val­ue of con­trol. He want­ed a sci­en­tist to be in charge; the com­pa­ny hired a CEO with a le­gal back­ground.

“It’s the on­ly com­pa­ny that I re­al­ly ever sev­ered ties with ear­ly on be­cause of a fun­da­men­tal dis­agree­ment with the phi­los­o­phy of the in­vestors,” Ver­dine said.

Ver­dine says Aileron made com­mon biotech mis­takes: nar­row­ing its fo­cus on its first pro­gram at the ex­pense of the plat­form and rush­ing to go pub­lic. Aileron now teeters on sur­vival, as its stock has plunged over 98% since go­ing pub­lic in 2017 and ter­mi­nat­ing that drug’s de­vel­op­ment ear­li­er this year.

Ver­dine found more suc­cess in oth­er ven­tures, like Glouces­ter Phar­ma­ceu­ti­cals, which won an FDA ap­proval and was bought by Cel­gene for about $450 mil­lion, pay­ing Ver­dine about $5 mil­lion. In 2010, he co-found­ed Warp Dri­ve Bio, which start­ed to de­vel­op drugs tar­get­ing Ras, a “Wall of Shame” can­cer-causer, when he ran the biotech from 2013 to 2015.

But he kept hit­ting Har­vard’s lim­its, hav­ing to leave Warp Dri­ve to re­turn to the uni­ver­si­ty af­ter max­ing his sab­bat­i­cal. Rev­o­lu­tion Med­i­cines ac­quired Warp Dri­ve a few years lat­er, and has start­ed test­ing some of those Ras drugs in the clin­ic. But he was feel­ing the lim­its of the sci­en­tif­ic founder role.

“I want­ed more con­trol,” Ver­dine said. “If I was go­ing to give up my fac­ul­ty job at Har­vard, I want­ed the time to make it work.”


Ver­dine is now tak­ing that big­ger swing, start­ing Fog­Phar­ma in 2016 to de­vel­op more pep­tide drugs. In his style, Fog is pur­su­ing the un­drug­gable mantra, which has be­come a com­mon in­dus­try re­frain that Ver­dine in­sists few ac­tu­al­ly fol­low.

“Most of them are bull­shit­ters,” he said. “It’s more like re­drug­ging the drug­gable.”

Fog picked a wor­thy first foe: be­ta-catenin. De­spite be­ing found in most cas­es of col­orec­tal can­cer, half of prostate can­cers, and about a third of melanoma cas­es, no drug com­pa­ny has been able to drug the pro­tein.

Be­ta-catenin’s no­to­ri­ety starts with its shape, which is the night­mare of chemists. Pro­teins that are easy to drug have nooks on their sur­face. Mol­e­cules slide in­to those crevices, like a plug go­ing in­to a sock­et. Be­ta-catenin lacks those pock­ets and is flat­ter than most pro­teins.

On top of its flat­ness, be­ta-catenin is nes­tled in­side cells. An­ti­body drugs look for pro­teins on the sur­face of cells, as they can’t pass through the cell mem­brane.

All told, be­ta-catenin is like a locked trea­sure chest with­out a key­hole to open it, buried un­der a sheet of ce­ment. The in­dus­try’s typ­i­cal tools — small mol­e­cules and bi­o­log­ics — couldn’t crack it, so phar­ma com­pa­nies set­tled for re­lat­ed, more ac­ces­si­ble tar­gets. Those pro­grams were rou­tine­ly aban­doned with tox­i­c­i­ty is­sues or mediocre clin­i­cal re­sults, leav­ing be­ta-catenin un­touched for decades.

Ver­dine be­lieves Fog can crack the pro­tein by pair­ing the spe­cial shape of his pep­tides with cut­ting-edge bi­ol­o­gy. It goes back to ear­ly re­search with Schafmeis­ter, shap­ing the pep­tides in­to spi­rals. They copied that shape from cell-mem­brane pro­teins that are al­so he­li­cal. The coils hide the pep­tide from cells, trick­ing them in­to let­ting the drug in­side. Once in­side, a pep­tide has greater bind­ing pow­ers than a small mol­e­cule to cling on­to be­ta-catenin.

Fog al­so leaned in­to cut­ting-edge re­search, work­ing with the Broad In­sti­tute to probe be­ta-catenin for vul­ner­a­bil­i­ties, us­ing the gene-edit­ing tool CRISPR-Cas9 to knock out genes and ob­serve the ef­fects on can­cer. Around 2019, that re­search led Fog to aban­don a pro­gram and start over, as it found its ini­tial tar­get, an in­ter­ac­tion site with an­oth­er pro­tein called BCL9, wouldn’t help fight can­cer.

Friends like Klaus­ner were sup­port­ive — but skep­ti­cal. “I thought he’d be able to find things that bind, but I was very skep­ti­cal that he could turn them in­to drugs,” he said.

By dig­ging deep in­to be­ta-catenin, Fog wound up with over 25 pos­si­ble places its pep­tides could bind to the pro­tein, in con­trast to con­ven­tion­al wis­dom that it lacked any­where to land a drug.

“It’s chock full of tar­getable sites, but on­ly one is the right one,” he said.

Many biotech boards would see these chal­lenges and de­mand a change in strat­e­gy to less risky re­search. But Ver­dine built Fog dif­fer­ent­ly in 2016, turn­ing to friends in­stead of VCs for greater con­trol. About 60% of Fog’s $11 mil­lion seed round came from high-net worth friends, while the oth­er 40% came from WuXi’s cor­po­rate in­vest­ment arm and Deer­field Man­age­ment. One of those friends and in­vestors, Jef­frey Leerink, sug­gest­ed the name: Fog, short for Friends of Greg.

“What you learn af­ter start­ing enough com­pa­nies is the found­ing ar­chi­tec­ture of a com­pa­ny stays with it, at least un­til it’s pub­lic,” Ver­dine said. “If you have a bas­tard birth, you end up with a bas­tard teenag­er and a bas­tard adult­hood. I didn’t want a bas­tard birth.”

Tak­ing on the CEO spot al­so brought Ver­dine’s run at Har­vard to a close. The uni­ver­si­ty didn’t want its pro­fes­sors to be full-time CEOs, and Ver­dine left Har­vard in 2020 to run his biotechs.

Af­ter years of grind­ing in the lab, Fog’s drug is now in the clin­ic. Ver­dine be­lieves they have found the right key­hole, with a tran­scrip­tion fac­tor called TCF4 that acts like an “ex­e­cu­tion­er” in set­ting off be­ta-catenin’s can­cer-dri­ving be­hav­ior.

Skep­tics like Klaus­ner have turned in­to be­liev­ers, rav­ing over pre­clin­i­cal re­sults, some of which were pre­sent­ed ear­li­er this year. An in­vest­ment fund run by Klaus­ner and the bil­lion­aire Yuri Mil­ner led Fog’s $178 mil­lion Se­ries D last year. Ver­dine will al­so hand over the CEO role in a few days to Math­ai Mam­men, for­mer­ly John­son & John­son’s R&D head and a teach­ing as­sis­tant of Ver­dine’s in the ear­ly 1990s. Ear­ly clin­i­cal re­sults are ex­pect­ed in the first half of 2024.


Much of Ver­dine’s biotech lega­cy will be writ­ten in the com­ing years. Clin­i­cal da­ta will de­cide what’s re­al and what re­mains the­o­ret­i­cal. Ver­dine is about to get a lot of those re­sults, with Rev­o­lu­tion’s Ras in­hibitors and Fog’s be­ta-catenin block­er in the clin­ic.

Pep­tides are al­ready hav­ing a qui­et resur­gence, dri­ven by weight loss drugs like Ozem­pic and Moun­jaro, which bind to re­cep­tors sit­ting on the sur­face of cells. Fog could break new ground if its pep­tides work in­side cells.

“The whole field is wait­ing for an ap­proved pep­tide-based drug tar­get­ing an in­tra­cel­lu­lar pro­tein,” said Tom Gross­mann, a Ger­man chemist who worked in Ver­dine’s lab as a post­doc­tor­al re­searcher and now runs his own lab in Am­s­ter­dam.

For Ver­dine, who turns 64 in a few days, he says he ex­pects to not slow down un­til he’s in his 70s, health per­mit­ting. The ideas haven’t stopped, as he con­tin­ues to run LifeM­ine, which is ex­plor­ing fun­gal genomes for new drugs, and al­so think­ing up new com­pa­ny ideas. He re­mains as fo­cused as ever on re­mov­ing “un­drug­gable” from the in­dus­try’s vo­cab­u­lary.

“God didn’t make it un­drug­gable,” he said. “It’s go­ing to be bi­ol­o­gy, un­met med­ical need, that de­cides what ac­tu­al­ly gets drugged, and not peo­ple’s no­tions.”


Andrew Dunn

Senior Biopharma Correspondent