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 Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; 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.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Fu­ji­film con­tin­ues CD­MO ex­pan­sion, break­ing ground on $435M UK site

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.

An­oth­er Cipla site lands a Form 483 over clean­ing is­sues and QC con­trols

A Cipla drug manufacturing site in India has once again landed in the crosshairs of FDA inspectors.

The facility in question is Cipla’s drug manufacturing facility in the village of Verna, in the state of Goa in India’s southwest. In a sign that foreign inspections might ramp up again, the FDA’s visit from Aug. 16 to Aug. 22 uncovered six observations.

The 11-page report noted that environmental monitoring at the site did not properly ensure that microbial contaminants were not making any impact in the aseptic filling areas. It also found that procedures meant to stop microbial contamination were not adequately conducted in aseptic areas of the facility.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

Klick Health gath­ers biotech and phar­ma lu­mi­nar­ies to dis­cuss in­dus­try in­no­va­tions, in­vest­ments and fu­ture

At Klick Health’s first Ideas Exchange conference with biotech and pharma industry insiders since before the pandemic began, it was no surprise many conversations included Covid topics. Yet while vaccines and treatments were discussed, so too were the effects on drug development, federal responses, health inequities — and what to do now and next.

George Yancopoulos, chief scientist and cofounder of Regeneron, opened the conference responding to a question from Acorda CEO Ron Cohen about the spotlight on the industry during Covid and some of the “flak” biopharma has taken in the past.