Andy Plump (Jeff Rumans for Endpoints News @ JPM19)

MD An­der­son emerges with strong ev­i­dence for nat­ur­al killer cell ther­a­py, and Take­da looks like a win­ner

As far as bi­o­log­i­cal brand­ing goes, it’s hard to beat nat­ur­al killer cells.

Katay­oun Rez­vani

These im­mune re­spon­ders earned their moniker in the ’70s for their ap­par­ent abil­i­ty to kill virus­es and some tu­mor cells quick­ly and with­out ini­tial train­ing. And in re­cent years, as sci­en­tists be­gan re-en­gi­neer­ing T cells to at­tack eva­sive tu­mors and cre­at­ing the first CAR-T treat­ments, re­searchers start­ed se­ri­ous­ly ex­plor­ing how to do the same with nat­ur­al killers.

Now, MD An­der­son has emerged with some of the first clin­i­cal proof this can work. A team led by Katay­oun Rez­vani at­tached CARs – chimeric anti­gen re­cep­tors – for CD19 to nat­ur­al killer cells and in­ject­ed them in­to 11 pa­tients with ei­ther non-Hodgkin lym­phoma or chron­ic lym­pho­cyt­ic leukemia. Sev­en of them had a com­plete re­sponse; their tu­mors van­ished.

The news is a step for­ward in nat­ur­al killer cell re­search and for can­cer cell ther­a­py as a field. It’s al­so a good sign for Take­da, who li­censed the ther­a­py for an undis­closed sum in No­vem­ber as part of a broad push to reignite an ail­ing R&D en­gine. Re­sults from the Phase I/II study were pub­lished in the New Eng­land Jour­nal of Med­i­cine.

Much of the in­ter­est around nat­ur­al killer cell ther­a­py, or CAR-NK, stems from their po­ten­tial as a form of “off-the-shelf CAR-T.” CAR-T treat­ments such as Kite Phar­ma’s Yescar­ta and No­var­tis’ Kym­ri­ah have dis­ap­point­ed com­mer­cial­ly be­cause they have to be done us­ing a pa­tient’s own cells, set­ting off a long and cost­ly process that both lim­it the num­ber of pa­tients it can help and po­ten­tial prof­it. You can’t use donor T cells now in part be­cause it would like­ly trig­ger graft-ver­sus-host dis­ease, al­though there are on­go­ing ef­forts to get around that and make an al­lo­genic CAR-T.

But for­eign nat­ur­al killer cells don’t cause graft-ver­sus-host dis­ease. So rather than draw­ing mil­lions of a pa­tient’s cells, treat­ing them with a re­cep­tor over weeks or months and then rein­ject­ing them in­to a pa­tient, Rez­vani could use do­nat­ed um­bil­i­cal cord blood. For 9 of the 11 pa­tients, the team found a par­tial donor match and for the last 2, the cells were com­plete­ly mis­matched. None of the pa­tients ex­pe­ri­enced GVHD.

“We have shown that we can man­u­fac­ture hun­dreds of dos­es of CAR NK cells from a sin­gle unit of cord blood,” Rez­vani said in De­cem­ber. “Ul­ti­mate­ly, our plan is to freeze and store these CAR NK cells in a cell bank so that when a pa­tient comes to the clin­ic, we can take those CAR NK cells im­me­di­ate­ly from the bank to treat the pa­tients, mak­ing this a tru­ly off-the-shelf-prod­uct.”

Rez­vani’s team took iso­lat­ed nat­ur­al killers cells from the um­bil­i­cal cord blood, ge­net­i­cal­ly mod­i­fied them to iden­ti­fy can­cers that would oth­er­wise evade the cells, “ar­mored” the nat­ur­al killers with IL-15 and fi­nal­ly in­ject­ed them in­to 11 pa­tients who had al­ready been through a me­di­an of 4 lines of ther­a­py. Most be­gan to re­spond with­in 30 days. Af­ter 13.8 months, sev­en were still dis­ease-free, al­though the re­searchers said the ac­tu­al du­ra­tion of re­sponse couldn’t be mea­sured be­cause pa­tients went on oth­er ther­a­pies af­ter re­ceiv­ing the CAR-NK.

The oth­er ben­e­fit of nat­ur­al killer cells is that they ap­pear to not cause the main tox­i­c­i­ty that CAR-T can cause: cy­tokine re­lease syn­drome, a po­ten­tial­ly dead­ly sce­nario in which the mod­i­fied im­mune cells re­lease bil­lions of in­flam­ma­tion-caus­ing mol­e­cules. This syn­drome is thought to be caused by IL-6, and nat­ur­al killers give off far less of that pro­tein than T cells.

The ther­a­py could reach pa­tients soon, at least by the stan­dards of ear­ly-stage can­cer stud­ies. Take­da R&D chief Andy Plump told End­points News in No­vem­ber they were look­ing to ini­ti­ate a piv­otal tri­al in 2021.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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José Baselga, AstraZeneca cancer chief (Brent N. Clarke/FilmMagic via Getty Images)

As­traZeneca's Calquence nabs an­oth­er win against Im­bru­vi­ca, but Eli Lil­ly is on its heels

Three years after first launching Calquence as a second generation BTK inhibitor, AstraZeneca continues to tout new data to compete with J&J and AbbVie’s first generation blockbuster Imbruvica.

The British pharma announced on Monday that Calquence passed a head-to-head Phase III study against Imbruvica in chronic lymphocytic leukemia, proving non-inferior — i.e. just as good — as the older drug. Although AstraZeneca did not break down any of the numbers, they said the drug proved superior on safety, triggering fewer cases of atrial fibrillation, an irregular heartbeat that can lead to stroke or heart failure.

Ron Cooper, Albireo CEO

Al­bireo just ad­vanced down to the 10-yard line at the FDA. And Ron Coop­er’s team is get­ting prepped for the next big play

When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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Roche amps up its bis­pe­cif­ic at­tack on Eylea with more PhI­II da­ta — but just how threat­en­ing is it?

Roche has another stack of data to back up its longer-acting challenger to Eylea — although it’s still far from certain just how much they can threaten Regeneron’s dominance.

The latest Phase III results come from two trials that enrolled 1,329 patients with neovascular age-related macular degeneration. With 45% of people in both studies getting faricimab 16 weeks apart during the first year, the bispecific still induced the same level of gains in visual acuity as Eylea every 8 weeks did, Roche’s Genentech reported.

Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.