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.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

Immunocore CEO Bahija Jallal (L) and Gadeta CEO Marcel Zwaal

In search for a 'u­ni­ver­sal T cell en­gager', Im­muno­core inks deal with Gilead-backed Gade­ta

Immunocore, which became the first company to win approval for a TCR therapy earlier this year, has penned a deal with gamma delta T cell specialist Gadeta to develop treatments for solid tumors, starting with colorectal cancer.

Immunocore R&D head David Berman told Endpoints News the deal is part of the company’s efforts to develop a “universal T cell engager.” TCR therapies made from typical T cells, like Immunocore’s TCR therapy Kimmtrak, are restricted to patients with certain HLA types, a kind of marker that helps the body separate friend and foe. Kimmtrak, for instance, is indicated only for patients with unresectable or metastatic uveal melanoma, a rare form of cancer that happens in the eye, who have the tissue type HLA-A*02:01, one of the more common HLA types which by Berman’s estimate includes around 40-50% of the population.