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.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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