Af­ter Ro­va-T bust, Ab­b­Vie plans new sol­id tu­mor as­sault, li­cens­ing next-gen CAR-T tech from Cal­i­br

Af­ter its dis­ap­point­ing Ro­va-T flop last month, Ab­b­Vie is shoring up its sol­id tu­mor bets with a fresh­ly inked re­search deal that should elic­it new strate­gies for tu­mor at­tack. This time, Ab­b­Vie is hop­ing to use po­ten­tial­ly safer, next-gen CAR-Ts that have been cook­ing in the labs of a San Diego re­search in­sti­tute for the past few years.

The phar­ma gi­ant is buy­ing an ex­clu­sive four-year li­cense to tech de­vel­oped at the Cal­i­for­nia In­sti­tute for Bio­med­ical Re­search — bet­ter known as Cal­i­br — to in­ter­ro­gate some of its own can­cer tar­gets, in­clud­ing sol­id tu­mors. Cal­i­br is bring­ing to the ta­ble a plat­form based on a “switch­able” CAR-T cell. I talked with Travis Young, Cal­i­br’s di­rec­tor of pro­tein sci­ences, last Fri­day to find out what that ac­tu­al­ly means. Young tells me it’s about re­duc­ing tox­i­c­i­ty and get­ting a more durable re­sponse from CAR-Ts, which are known to cause safe­ty is­sues.

Travis Young

“CAR-Ts are po­tent, and they can cause tox­i­c­i­ty in the clin­ic,” Young said. “This is about tun­abil­i­ty. We’re call­ing this a switch, but it’s re­al­ly more like a light dim­mer. We want to tune ac­tiv­i­ty and elim­i­nate can­cer cells with­out caus­ing that tox­i­c­i­ty.”

They do that by us­ing an­ti­body-based switch mol­e­cules to con­trol the ac­ti­va­tion and anti­gen speci­fici­ty of CAR-T cells. Young said it’s im­por­tant to note this ap­proach dif­fers from the in­creas­ing­ly pop­u­lar “kill switch” tac­tic, which has been tout­ed as a way to make CAR-Ts safer.

“Rather than killing off the cells in the case of an ad­verse event, this is more proac­tive,” Young said.

The part­ner­ship has both Cal­i­br and Ab­b­Vie do­ing pre­clin­i­cal work, while Ab­b­Vie alone will be re­spon­si­ble for clin­i­cal de­vel­op­ment and com­mer­cial­iza­tion. Cal­i­br, of course, will get mile­stones and roy­al­ties if cer­tain tar­gets are met, but the duo was tight-lipped on fi­nan­cial de­tails of the deal.

The main fo­cus of the col­lab­o­ra­tion will be Ab­b­Vie’s can­cer tar­gets, but Cal­i­br is al­so work­ing on a liq­uid tu­mor pro­gram of its own that might come in­to play down the road. Young said the yet-named pro­gram is a CD19 tar­get­ed switch­able CAR-T ther­a­py, which the in­sti­tute plans to take in­to Phase I for lym­phoma in 2019. As part of the deal, Ab­b­Vie has the op­tion to li­cense that pro­gram (and oth­ers at Cal­i­br). That op­tion ex­pires in four years, how­ev­er.

You didn’t used to see re­search in­sti­tutes mov­ing pro­grams in­to the clin­ic, but its be­com­ing an in­creas­ing­ly pop­u­lar strat­e­gy for non-prof­it re­search cen­ters and uni­ver­si­ties. The idea is that it helps them cre­ate a source of rev­enue in­de­pen­dent from the fed­er­al gov­ern­ment and phil­an­thropy.

Matt Trem­blay

“We’re at the head of this new theme to take your as­sets — your IP orig­i­nat­ed at the in­sti­tute — and take them for­ward in­to clin­i­cal de­vel­op­ment,” Cal­i­br and Scripps Re­search COO Matt Trem­blay told me. 

This is some­thing I dis­cussed with Dave Gib­bons, who han­dles com­mer­cial li­cens­ing at the biotech-heavy cam­pus at UC San Diego, last year. By de-risk­ing pro­grams and de­vel­op­ing up to IND, “you’d have a tremen­dous­ly more valu­able as­set for li­cens­ing,” Gib­bons said.

Ab­b­Vie’s on­col­o­gy and clin­i­cal de­vel­op­ment ex­per­tise will be a boon to the re­source-slim Cal­i­br, but the phar­ma gi­ant was al­so in need of this deal. The com­pa­ny dis­ap­point­ed in­vestors in March when news that its Ro­va-T pro­gram post­ed poor mid-stage re­sults for third-line non-small cell lung can­cer. That was a re­al blow, con­sid­er­ing it was hoped to be a $5 bil­lion earn­er for the com­pa­ny.

Ge­of­frey Porges at Leerink post­ed a scathing as­sess­ment of Ab­b­Vie’s sit­u­a­tion short­ly af­ter the news.

“On­col­o­gy is the key growth busi­ness seg­ment for Ab­b­Vie af­ter the loss of ex­clu­siv­i­ty for Hu­mi­ra in 2023, and to­day’s re­sults and reg­u­la­to­ry de­ci­sion call in­to ques­tion the vi­a­bil­i­ty of the com­pa­ny’s cur­rent sol­id tu­mor strat­e­gy,” he wrote.

Per­haps Cal­i­br’s tech will give their sol­id tu­mor strat­e­gy more hope.

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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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.

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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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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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.