Hack­ing in­to macrophage at­tack cir­cuits, Stan­ford sci­en­tists pitch a bet­ter ear­ly-warn­ing alert sys­tem for tu­mors

Af­ter years of fine tun­ing ways to en­list the im­mune sys­tem in the fight against can­cer, im­munother­a­py has tak­en the field by storm, with a No­bel prize and a pair of block­buster check­point drugs to boast. But can im­mune cells help in an even broad­er ef­fort — flag­ging ma­lig­nant tu­mors be­fore they are de­tectable by tra­di­tion­al in­stru­ments?

Push­ing the thresh­old of can­cer di­ag­noses to ear­li­er and ear­li­er stages of the dis­ease is one of the Holy Grails in on­col­o­gy, in­spir­ing mul­ti­mil­lion-dol­lar in­vest­ments in­to star­tups like Grail. This week, a team from Stan­ford has chipped in with their own pitch and some mouse da­ta to show for it.

Pi­o­neer­ing a new de­f­i­n­i­tion of the con­cept “im­mun­odi­ag­notics,” San­jiv “Sam” Gamb­hir of Stan­ford’s Ca­nary Cen­ter for Ear­ly De­tec­tion re­pur­posed macrophages to re­port the pres­ence of dis­ease or dam­aged cells, achiev­ing de­tec­tion of tu­mors as small as 4 mil­lime­ters in di­am­e­ter, out­per­form­ing “some of the most ad­vanced ear­ly tu­mor de­tec­tion meth­ods out there.”


Im­age: San­jiv “Sam” Gamb­hir. Steve Fisch, STAN­FORD

His tech­nique, re­port­ed in Na­ture Biotech­nol­o­gy, makes use of macrophages’ in­nate abil­i­ty to find (and eat) mal­func­tion­ing or dead cells. That’s sim­ple; the big chal­lenge is to hack the process in a way such that these im­mune cells emit a de­tectable sig­nal be­fore they be­gin to feast.

To do that, Gamb­hir’s team tagged a mol­e­c­u­lar mark­er to a gene pro­mot­er that awak­ens and ac­ti­vates the gene di­rect­ing the macrophage on­slaught in the pres­ence of a tu­mor.

“The mol­e­c­u­lar mark­er is called Gaus­sia lu­ciferase, and un­der cer­tain chem­i­cal cir­cum­stances, it glows,” Gamb­hir said in a state­ment. “So the idea is, we pick a gene that turns on when a macrophage sens­es a tu­mor cell, we link that gene’s pro­mot­er to Gaus­sia lucer­iferase and fi­nal­ly, we in­te­grate it in­to the macrophages.”

Macrophages have been a key im­mune cell type of in­ter­est, at­tract­ing a num­ber of biotechs to re­move the “don’t eat me” sig­nal that tu­mors of­ten de­ploy to pre­vent an at­tack.

There are, of course, lim­i­ta­tions with the method. For one, macrophages don’t just re­spond to can­cer­ous tar­gets, so a “hit” on this test rep­re­sents a call for oth­er, con­fir­ma­to­ry tests rather than a de­fin­i­tive di­ag­no­sis. But the ap­proach, which in­volves cre­at­ing a syn­thet­ic bio­mark­er, is a ma­jor de­par­ture from the tra­di­tion­al prac­tice, which re­lies on iden­ti­fy­ing bio­mark­ers in the body.

The syn­thet­ic na­ture of this tech­nique means the strat­e­gy can be ap­plied to mul­ti­ple in­stru­ments and im­mune cells — all pos­si­bil­i­ties that Gamb­hir is ex­plor­ing with his start­up, Ear­li.

Mov­ing for­ward, Gamb­hir plans to test the method in oth­er types of can­cers and an­i­mal mod­els, while re­fin­ing the tech­nique to home in on just tu­mor cells, not cells with oth­er types of dam­age.

On the heels of promis­ing MCL da­ta, Kite hus­tles its 2nd CAR-T to the FDA as the next big race in the field draws to the fin­ish line

Three days after Gilead’s Kite subsidiary showed off stellar data on their number 2 CAR-T KTE-X19 at ASH, the executive team has pivoted straight to the FDA with a BLA filing and a shot at a near-term approval.

In a small, 74-patient Phase II trial reported out at the beginning of the week, investigators tracked a 93% response rate with two out of three mantle cell lymphoma patients experiencing a complete response.

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Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Cor­re­vio is putting it­self up on the auc­tion block af­ter FDA re­view pan­el points to an­oth­er re­jec­tion

For 13 years, the Canadian biotech Correvio tried to get the FDA to accept a heart drug since abandoned by Merck and Astellas. Yesterday, the agency’s outside experts voted 11-2 against approval, all but assuring another rejection for the atrial fibrillation compound vernakalant.

And today Correvio announced that Correvio may soon be no more. The company said it is looking to sell itself as its stock plummets into penny-stock territory $CORV and its potential moneymaker sputters once more.

Psilocybin mushrooms (via The Denver Post)

In a key step for psy­che­del­ic re­search, mag­ic mush­room com­pound clears first clin­i­cal safe­ty hur­dle

Exasperated with the often-ineffective existing slate of antidepressants, COMPASS Pathways set up shop in London 2016 — and made a beeline for psilocybin, the psychoactive ingredient in magic mushrooms.

On Wednesday, the startup said its man-made version of the chemical — which is illegal across geographies in its natural fungi form — had been well-tolerated in an early-stage, placebo-controlled trial in 89 healthy volunteers.

Al­pham­ab On­col­o­gy rounds out HKEX's sec­ond biotech IPO year with $230M raise and high lo­cal in­ter­est

Alphamab Oncology has inspired a surge of local interest in what will likely be the Hong Kong Stock Exchange’s last biotech run of the year, pricing its IPO on the high end of the range and raising over $230 million (HK$1.83 billion).

After rejigging the offering structure and making up to 50% available for enthusiastic local investors, the biotech sold 179.4 million shares at $1.31 (HK$10.2) and saw its stock rise to $1.77 ($13.8) on the first day of trading.

For sale: Long-act­ing PhI­II GLP-1 di­a­betes drug that’s way be­hind ri­vals, now spurned by Sanofi

Almost exactly 4 years ago Sanofi came to the bargaining table with South Korea’s Hanmi bearing $434 million dollars in cash and offering about $4 billion in milestones to in-license their once-weekly GLP-1 injectable. The pact was intended to revive their ailing diabetes division. Instead, it turned into a very expensive grave to mark the end of Sanofi’s R&D ambitions in the field.

Sanofi CEO Paul Hudson used efpeglenatide’s demise — while committing to paying hundreds of millions of more dollars to push it through 5 late-stage studies — as a marker of the company’s determination to stay focused on first and best-in-class drugs.

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Parkin­son's trans­plants emerge as stem cell pi­o­neer Jeanne Lor­ing joins R&D race

Jeanne Loring hadn’t studied Parkinson’s in 22 years when she got an email from a local neurologist.

The neurologist, Melissa Houser, didn’t know Loring had ever published on the disease. She was just looking for a stem cell researcher who might hear her out. 

“I think I was just picked out of a hat,” Loring told Endpoints News. 

At a meeting in Loring’s Scripps Research office, Houser and a Parkinson’s nurse practitioner, Sherrie Gould, asked her why there was so much research done in stem cell transplants for other neurodegenerative diseases but not Parkinson’s. They wanted to know if she would work on one. 

Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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