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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.