Scott Wolchko, Fate Therapeutics CEO

Fate's close­ly watched stem cell-de­rived NK pro­gram rais­es red flag over dura­bil­i­ty of re­sponse

At the cut­ting edge of on­col­o­gy re­search, biotechs like Fate Ther­a­peu­tics are look­ing for ways to craft next-gen cell ther­a­pies with­out re­ly­ing on pa­tients’ own cells. An ear­ly peek at the com­pa­ny’s clin­i­cal da­ta looks promis­ing, but will iffy dura­bil­i­ty re­sults prove a road­block?

Fate on Thurs­day re­vealed an ear­ly cut of Phase I da­ta for its FT596 and FT516 in­duced pluripo­tent stem cell-de­rived nat­ur­al killer cell pro­grams that re­vealed po­ten­tial red flags on one of the ther­a­pies’ dura­bil­i­ty over time.

At a three-month check in, eight of 11 B cell lym­phoma pa­tients who re­ceived FT516, off-the-shelf NK cells en­gi­neered with a “non-cleav­able” CD16 Fc re­cep­tor, re­port­ed an ob­jec­tive re­sponse with no ma­jor safe­ty sig­nals. But at a Ju­ly 7 cut­off, just five pa­tients (45%) main­tained those re­spons­es, with two com­plete re­spon­ders see­ing their dis­ease progress and a par­tial re­spon­der forced to re­ceive an “ad­di­tion­al an­ti-can­cer ther­a­py,” Fate said.

It’s a trou­bling sign for FT516’s dura­bil­i­ty but not a death knell for the pro­gram. The ther­a­py’s safe­ty pro­file, for in­stance, with no FT516-linked se­ri­ous side ef­fects and no FT516-re­lat­ed Grade 3 events or high­er, should warm in­vestors’ hearts some­what. But im­me­di­ate­ly fol­low­ing the news, shares of $FATE sunk around 10% af­ter the bell, po­ten­tial­ly un­der­scor­ing share­hold­ers’ wor­ries about the drug’s abil­i­ty to main­tain ef­fect.

On a call with an­a­lysts Thurs­day, the Fate team field­ed ques­tions on FT516’s dura­bil­i­ty, par­tic­u­lar­ly com­pared to re­sults from CD19 CAR-T ther­a­pies.

“It’s too ear­ly to know ul­ti­mate­ly what the long term dura­bil­i­ty of FT516 is and how that com­pares to CAR-T ther­a­py,” CEO Scott Wolchko said. “We’re very en­cour­aged by the dura­bil­i­ty we’ve seen as we fol­low these pa­tients.”

Fate is one of a group of biotechs lean­ing on the pos­si­bil­i­ty of en­gi­neer­ing donor stem cells to cre­ate pow­er­ful tu­mor fight­ers. NK cells, which are as­so­ci­at­ed with a low­er risk of cy­tokine re­lease syn­drome than T cell ther­a­pies, hold promise as an op­tion for late-stage can­cer pa­tients, many of whom have pre­vi­ous­ly failed on pri­or im­munother­a­pies and/or cell ther­a­pies.

The Phase I study for FT516 dosed the ther­a­py across co­horts up to two treat­ment cy­cles in­clud­ing a reg­i­men of three days of con­di­tion­al chemother­a­py fol­lowed by a sin­gle dose of Roche’s Rit­ux­an and three week­ly dos­es of vary­ing strength of FT516 and IL-2 cy­tokine sup­port. Pa­tients had re­ceived a me­di­an of three pri­or lines of ther­a­py and a me­di­an of two pri­or lines of CD20-tar­get­ed ther­a­py. Of the 11 pa­tients in the study, eight had ag­gres­sive B cell lym­phoma, five pa­tients didn’t re­spond to their most re­cent pri­or ther­a­py, and four pa­tients were pre­vi­ous­ly treat­ed with au­tol­o­gous CD19 CAR-T cell ther­a­py.

FT516’s re­sults in pa­tients with pri­or CD19 CAR-T ther­a­py — two of four post­ed a com­plete re­sponse — spurred Fate to an­nounce a dose-ex­pan­sion co­hort in that pop­u­la­tion, which the biotech thinks could ad­dress a grow­ing mar­ket need.

Mean­while, FT596 post­ed ear­ly da­ta of its own show­ing promis­ing ef­fi­ca­cy. The ther­a­py us­es the same plat­form as FT516 with an ad­di­tion­al CAR con­struct en­gi­neered on­to the cells in an at­tempt to ad­dress het­ero­ge­neous tu­mor types and anti­gen es­cape.

In­ter­im da­ta showed 10 of 14 pa­tients across two dose-es­ca­la­tion co­horts post­ed an ob­jec­tive re­sponse, in­clud­ing sev­en com­plete re­spon­ders, in­clud­ing two of three pa­tients who were treat­ed with a com­bo of FT596 and Rit­ux­an af­ter au­tol­o­gous CD19 CAR-T ther­a­py.

Fate ex­pects to present fur­ther da­ta from both stud­ies at the up­com­ing ASH con­fer­ence in De­cem­ber, in­clud­ing a first look at dura­bil­i­ty of re­sponse for FT596.

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.

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 rather narrow 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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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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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.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.