Dun Yang (Anticancer Bioscience)

A syn­thet­ic lethal­i­ty play­er emerges in Chi­na, armed with lessons on un­drug­gable onco­gene from No­bel lau­re­ate's lab

As a long­time post­doc in the UCSF lab of Michael Bish­op — the No­bel lau­re­ate known, among oth­er things, for cloning the onco­gene MYC — Dun Yang knew the can­cer tar­get like an archer knows the bulls­eye.

“I al­ways talk about if we need­ed to nom­i­nate the most im­por­tant onco­gene […] that should be MYC,” he told End­points News. “The sec­ond one would be RAS. Be­cause more than 50% of hu­man can­cer over­ex­press MYC onco­gene.”

All those years of re­search al­so gave him in­ti­mate knowl­edge about the pit­falls of try­ing to de­vel­op can­cer ther­a­pies around the MYC pro­tein. The con­sen­sus had been that MYC, a tran­scrip­tion fac­tor, is un­drug­gable; even if you some­how man­age to hit it, the po­ten­tial ben­e­fit would like­ly be off­set by the po­ten­tial side ef­fects that come with block­ing its es­sen­tial phys­i­o­log­i­cal func­tions.

So in 2010 — just as PARP in­hibitors were gain­ing trac­tion — he and sev­er­al oth­er sci­en­tists in the lab pro­posed some­thing new.

Thad­deus Allen

“A lot of peo­ple have of course heard of (Bish­op),” said Thad­deus Allen, whose tenure as a re­search sci­en­tist at UCSF over­lapped with Yang’s. “But I think what peo­ple don’t re­al­ize is the last 10 to 15 years of re­search that went on in Mike Bish­op’s lab was re­al­ly fo­cused on syn­thet­ic lethal­i­ty and re­al­ly Dun Yang was at the cen­ter of that re­search that was go­ing on.”

In­stead of tar­get­ing MYC di­rect­ly, they tried go­ing af­ter a ki­nase that tu­mors over­ex­press­ing MYC tend to re­ly on, and showed in mice that the com­pound they test­ed could kill can­cer cells while spar­ing nor­mal ones.

Yang would even­tu­al­ly leave San Fran­cis­co to re­turn to his home­town of Cheng­du, Chi­na, to start a can­cer re­search in­sti­tute epony­mous with Bish­op and see if he can go big­ger with that idea.

Now, more than a decade af­ter pub­lish­ing that pa­per, he’s se­cured a to­tal of $21 mil­lion from pri­vate Chi­nese in­vestors to build a com­pa­ny that doesn’t just stand shoul­der to shoul­der with US syn­thet­ic lethal­i­ty play­ers like Re­pare, Ar­tios, Cyteir and Ideaya, but some­day grow up to be the Genen­tech of Chi­na.

An­ti­cancer Bio­science is the de­vel­op­ment and com­mer­cial­iza­tion arm of the J. Michael Bish­op In­sti­tute of Can­cer Re­search, Yang said, and the 50 em­ploy­ees tech­ni­cal­ly work for both en­ti­ties. The team is spread across Chi­na, the US, the UK and In­dia — where the CEO re­cruit­ed his med­i­c­i­nal chemists.

With two drugs, one of them in MYC, poised to com­plete IND-en­abling stud­ies this year and en­ter the clin­ic in 2022, the biotech is busy jug­gling a to­tal of five pre­clin­i­cal pipeline pro­grams, which they say span the ar­eas of tu­mor sup­pres­sor syn­thet­ic lethal­i­ty, poly­ploid cell syn­thet­ic lethal­i­ty, cen­tro­some am­pli­fi­ca­tion/declus­ter­ing ther­a­py and restora­tion of con­tact in­hi­bi­tion.

Jing Zhang

Build­ing nov­el screen­ings — led by VP Jing Zhang in the UK — that ze­ro in on the right vul­ner­a­bil­i­ties that can be tar­get­ed are core to An­ti­cancer’s ex­per­tise, said Allen, the com­pa­ny’s VP of trans­la­tion­al bi­ol­o­gy. In ad­di­tion to screen­ing on syn­thet­ic li­braries, An­ti­cancer is al­so keen on find­ing com­pounds from na­ture li­braries — col­lec­tions of plant sam­ples from a province that Yang said ac­counts for 60% of the plant di­ver­si­ty in the coun­try.

“What’s new about our plat­form is we col­lect­ed from nov­el places,” added Allen, who’s al­so one of on­ly two staffers based in Cal­i­for­nia. “The com­pa­ny is in Cheng­du for a rea­son.”

“We have an un­matched nat­ur­al prod­ucts li­brary,” Yang wrote, “com­posed of over 17,500 crude ex­tracts, over 1,200 par­tial­ly pu­ri­fied frac­tions and around 2,500 pure nat­ur­al com­pounds. These sam­ples are made from over 2,600 plants, rep­re­sent­ing more than 1,500 plant species used in tra­di­tion­al Chi­nese med­i­cine.”

Illustration: Assistant Editor Kathy Wong for Endpoints News

How Pur­due's $272M ad­dic­tion pay­out fund­ed a new home for its dis­card­ed non-opi­oid re­search

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

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President Joe Biden at the State of the Union address with Vice President Kamala Harris and House Speaker Kevin McCarthy (Patrick Semansky/AP Images)

The drug pric­ing pres­i­dent: Biden warns of ve­to for any IRA re­peal at­tempts

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

Rupert Vessey, Bristol Myers Squibb head of research and early development

Up­dat­ed: R&D tur­bu­lence at Bris­tol My­ers now in­cludes the end of a $650M al­liance and the de­par­ture of a top re­search cham­pi­on

This morning biotech Dragonfly put out word that Bristol Myers Squibb has handed back all rights to its IL-12 clinical-stage drug after spending $650 million to advance it into the clinic.

The news arrives amid a turbulent R&D stage for the pharma giant, which late last week highlighted Rupert Vessey’s decision to depart this summer as head of early-stage R&D following a crucial three-year stretch after he jumped to Bristol Myers in the big Celgene buyout. During that time he struck a series of deals for Bristol Myers, and also shepherded a number of Celgene programs down the pipeline, playing a major role for a lineup of biotechs which depended on him to champion their drugs.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

Drag­on­fly chief: Bris­tol My­ers shouldn’t blame IL-12’s clin­i­cal per­for­mance for de­ci­sion to scrap the deal — eco­nom­ics played a key role

Bristol Myers Squibb says the IL-12 drug they were developing out of Dragonfly Therapeutics was scrubbed from the pipeline for a simple reason: It didn’t measure up on clinical performance.

But Bill Haney, the CEO of Dragonfly, is taking issue with that.

The early-stage drug, still in Phase I development, has passed muster with Bristol Myers’ general clinical expectations, advancing successfully while still in Phase I, he says.

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Utpal Koppikar, new Verily CFO

Ex­clu­sive: Ver­i­ly wel­comes Atara Bio­ther­a­peu­tics vet­er­an as new CFO

Verily, Alphabet’s life sciences outfit, has plucked a new CFO from the ranks of Atara Biotherapeutics, the company announced on Wednesday.

Utpal Koppikar joins Verily after a nearly five-year stint as CFO and senior VP at Atara, though his résumé also boasts roles at Gilead and Amgen.

The news follows a major reshuffling at Verily, including several senior departures earlier this year and a round of layoffs.

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Singer Nick Jonas is back at work for Dexcom, this time for its new G7 glucose monitor.

Dex­com's spokescelebri­ty Nick Jonas re­turns to Su­per Bowl in new glu­cose mon­i­tor com­mer­cial

Dexcom is going back to the Super Bowl with its pop singer and patient spokesperson Nick Jonas. Jonas takes center stage as the lone figure in the 30-second commercial showcasing Dexcom’s next-generation G7 continuous glucose monitoring (CGM) device.

Jonas’ sleight-of-hand tricks populate the commercial — he pinches his empty fingers together and pops them open to reveal the small CGM — even as he ends the ad, saying, “It’s not magic. It just feels that way.” Jonas then disappears in a puff of smoke.

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Richard Francis, newly-appointed Teva CEO (Novartis via Facebook)

New Te­va CEO Richard Fran­cis repri­or­i­tizes to 'get back to growth'

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.

FDA Commissioner Robert Califf on Capitol Hill, Feb. 8, 2023 (Drew Angerer/Getty Images)

FDA com­mis­sion­er floats ideas on how to bet­ter han­dle the pan­dem­ic

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

Sanofi is renewing its #VaccinesForDreams campaign with more stories, such as Juan's in Argentina (Sanofi)

Sanofi re­news so­cial cam­paign to re­mind that vac­cines let peo­ple ‘Dream Big’

Sanofi is highlighting people’s dreams — both big and small — to make the point that vaccines make them possible.

The renewed “Dream Big” global social media campaign’s newest dreamer is Juan, a teacher in the Misiones rainforest in Argentina whose story is told through videos on Instagram and Sanofi’s website with the hashtag #VaccinesForDreams.

The campaign ties to Sanofi’s broader umbrella initiative “Vaccine Stories” to promote the value of vaccines and drive awareness of the need for improved vaccination coverage.

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