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.

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.