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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Scoop: Gilead ter­mi­nates ear­ly-stage FLT3 tri­al in sol­id tu­mors

Gilead chopped a Phase Ib dose escalation study in recent days, with an update to the federal trials database saying the premature termination followed an “internal safety assessment.”

The IV-administered FLT3 agonist, dubbed GS-3583, was being tested as a monotherapy in 13 patients with advanced solid tumors. The goal of the trial was to find out what dose to test in a Phase II, or maximum tolerated dose.

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Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

As­traZeneca’s Su­san Gal­braith high­lights twin wins for the can­cer drug pipeline at SABCS, as oral SERD ex­cels

It’s a good time to be the head of R&D for oncology at AstraZeneca. And no one gets that quite like Susan Galbraith.

Today, Galbraith is at the San Antonio Breast Cancer Symposium, highlighting the data on two key drugs in the cancer pipeline: mid-stage results for its oral SERD camizestrant among patients after one line of therapy, and the AKT drug capivasertib, wrapping the Phase III. Both fall neatly into the range of successes, beating out fulvestrant in hormone receptor-positive, HER2-negative breast cancer.

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