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.”

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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CEO Khurem Farooq (Gyroscope)

Hours be­fore ex­pect­ed de­but, Gy­ro­scope post­pones its IPO as 2 oth­er biotechs hold the line on their march to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

In a surprising turn of events, UK-based Gyroscope Therapeutics has postponed its IPO mere hours before it was set to debut on Nasdaq.

Working on a gene therapy for wet AMD, Gyroscope was all set and ready to go public earlier this week, setting terms for a $142 million raise with a price range of $20 to $22. But in the wee hours of Friday morning, the company put out a press release saying they would delay their debut “in light of market conditions,” CEO Khurem Farooq said in a statement.

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Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

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An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.

In­cyte ponies up $12M to set­tle char­i­ty foun­da­tion kick­back claims; US ex­er­cis­es op­tion for more dos­es of mon­key­pox vac­cine

One in a string of lawsuits targeting copay charity foundations, the DOJ has been hunting drugmaker Incyte for what prosecutors alleged was a kickback scheme to court patients. Now, Incyte is clearing its name.

Incyte will shell out $12.6 million to settle claims it funneled funds through a charity foundation to cover federal copays for patients taking its JAK inhibitor Jakafi, the DOJ said this week.