Af­ter pi­lot project, Take­da inks $500M pact to tap in­to a Ke­van Shokat pro­tégé's co­va­lent small mol­e­cule fish­ing plat­form

As new tech­nolo­gies open up new av­enues to­ward tar­gets wide­ly con­sid­ered un­drug­gable by small mol­e­cules, Take­da is tak­ing a chance on a low-pro­file drug dis­cov­ery play­er with promis­es of up to $500 mil­lion in biobucks.

Ping Cao

Over the next two years, Sun­ny­vale, CA-based Brid­Gene will de­ploy its chem­i­cal pro­teomics-based plat­form for five pro­grams against tar­gets of in­ter­est, start­ing with one im­pli­cat­ed in neu­rode­gen­er­a­tive dis­eases.

It all start­ed, ac­cord­ing to Brid­Gene CEO Ping Cao, with an in-per­son meet­ing at JP Mor­gan last Jan­u­ary.

“If you talk to a chemist or sci­en­tist in a large firm, they al­ways say we are tar­get hun­gry,” he said.

Cao, who spent enough years at Am­gen’s San Fran­cis­co site to be ap­proach­ing lif­er sta­tus, knew the is­sue well. With the low-hang­ing fruit al­ready picked, re­main­ing dis­ease-caus­ing pro­teins of­ten have pock­ets that are ei­ther too shal­low (think KRAS) or tran­sient, pre­sent­ing them­selves on­ly in live cells (think tran­scrip­tion fac­tor).

Take­da was no dif­fer­ent. The phar­ma gi­ant has a large phe­no­typ­ic screen­ing fa­cil­i­ty in Japan where sci­en­tists iden­ti­fy phe­no­typ­ic changes caused by mol­e­cules in their li­brary, but there’s a ma­jor hur­dle in fig­ur­ing out what ex­act­ly caused the change. Once Cao pre­sent­ed their tech­nol­o­gy, it took lit­tle time to kick­start a pi­lot project in which Take­da hand­ed over some of their clin­i­cal can­di­dates for Brid­Gene to pro­file.

“We use co­va­lent small mol­e­cules as a bait,” he said. “So we fish in­side live cells. So live cells are like an ocean; each pro­tein is just like a fish there. Dif­fer­ent small mol­e­cules, they will fish out dif­fer­ent tar­gets or dif­fer­ent pro­teins.”

Chao Zhang

The core tech­ni­cal ex­per­tise came from sci­en­tif­ic founder Chao Zhang’s lab at the Uni­ver­si­ty of South­ern Cal­i­for­nia. Hav­ing trained with Ke­van Shokat, the in­ven­tor of one of the ear­li­est KRAS G12C in­hibitors, Zhang came up with his own method of min­ing co­va­lent ki­nase in­hibitors, col­lab­o­rat­ing with Prin­cip­ia co-founder Jack Taunton along the way. That com­pa­ny, which boasts of BTK in­hibitors, sold to Sanofi for $3.7 bil­lion. Shokat, mean­while, is on the sci­en­tif­ic ad­vi­so­ry board.

From March to Sep­tem­ber, Brid­Gene’s team of 10 put sev­er­al Take­da can­cer drugs through its plat­form and came up with a re­port de­tail­ing how many pro­teins bound to those small mol­e­cules — some pre­vi­ous­ly un­known to the phar­ma part­ner.

“Take­da was re­al­ly hap­py with the re­sults be­cause this re­port helped them to — they can de­cide if they want to pur­sue oth­er in­di­ca­tions that cov­er oth­er tar­gets they didn’t know be­fore,” he said. “It al­so gave them (a) broad full view of the po­ten­tial tox­i­c­i­ty con­cerns down the road.”

It paved the way for the cur­rent col­lab­o­ra­tion, Cao said, which takes the same tech­nol­o­gy in a slight­ly dif­fer­ent di­rec­tion. The biotech will be tasked with iden­ti­fy­ing new tar­gets that are re­spon­si­ble for a spe­cif­ic dis­ease phe­no­type that Take­da pin­points as un­der­ly­ing a neu­rode­gen­er­a­tive con­di­tion, or oth­er ail­ments in the fu­ture phas­es of the pact.

The undis­closed up­front cash, added to a pre-A round they’ve raised, would help fund Brid­Gene’s in­ter­nal pipeline of on­col­o­gy pro­grams, Cao added.

For Take­da, the al­liance marks the lat­est in a dis­cov­ery deal spree cov­er­ing every­thing from RNA-bind­ing small mol­e­cules and ri­bo­some drug test­ing ma­chines to CRISPR-screened cell ther­a­pies and LNP gene de­liv­ery.

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Bio­gen has a shaky end to H1 with a $542M write-off adding to its woes — but an­a­lysts see big rev­enue ahead for Aduhelm

All eyes at Biogen’s Q2 earnings call Thursday were on Aduhelm, but investors also got a glimpse of what Biogen would have faced had the FDA not opted to approve their controversial Alzheimer’s drug.

That glimpse, revealing a combination of declining sales, growing competition and failed medicines, underscores the stakes of the big biotech’s Aduhelm efforts, as execs punch back at the criticism they’ve engendered in the political and medical world and vigorously pushes its sales staff to roll out the drug as fast as possible.

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John Houston, Arvinas CEO

Pfiz­er bets $1B cash on the orig­i­nal pro­tein de­graders as tech­nol­o­gy nears prime time

As one of the largest multinational corporations in the world, Pfizer has its tendrils in everything. The Big Pharma has potentially hundreds of billions of dollars to play with, and when it decides to go big, it can go as big as it wants.

And did Pfizer ever on Thursday.

Returning to one of its partners in protein degradation, Pfizer is teaming up again with Arvinas to advance and vastly expand a program for breast cancer. As part of the deal, Pfizer is handing over $1 billion immediately — $650 million in upfront cash and $350 million in an equity investment — and promising up to another $1.4 billion in regulatory and commercial milestones.

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Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many people around the world, my life has been profoundly shaped by cancer. Those personal experiences, along with a deep love of clinical laboratory science and a passion to apply the power of genomics in medicine, motivated me to launch a company that would improve cancer care through better diagnostics. Thirteen years later, I am proud that we are delivering more accurate information at multiple points along the patient journey, with a focus on eight of the 10 cancers that are most commonly diagnosed in the United States.