An­ti­body strat­e­gy to aug­ment ver­sa­tile im­mune cells sparks in­vest­ment in French biotech

A small frac­tion of ver­sa­tile im­mune cells — prized for their abil­i­ty to hack the tu­mor mi­croen­vi­ron­ment — are shap­ing up to be the next wave of im­munother­a­pies. These gam­ma delta T cells, in con­trast to their pop­u­lar al­pha be­ta coun­ter­parts har­nessed by CAR-T ther­a­pies, do not re­ly on spe­cif­ic anti­gens but kill when pre­sent­ed with gener­ic ex­pres­sions of in­fec­tion or dis­ease.

Paul Frohna

Most play­ers in the field are work­ing on ways to im­prove ex­ist­ing cell ther­a­pies, by shoring up ef­fi­ca­cy, lim­it­ing tox­i­c­i­ty, mak­ing the tech­nol­o­gy more ac­ces­si­ble with “off-the-shelf” ap­proach­es ver­sus the ex­ist­ing com­plex au­tol­o­gous mod­el, and ex­pand­ing it to oth­er can­cer types be­yond hema­to­log­i­cal ma­lig­nan­cies by en­list­ing lym­pho­cytes such as gam­ma delta T cells. These ef­forts are not try­ing to rein­vent the CAR-T wheel, but in­deed smoothen it so it moves faster, bet­ter and stronger for a broad­er group of can­cer pa­tients.

The in­ter­est in gam­ma delta T cells is dri­ven by the un­der­stand­ing that their pres­ence in the tu­mor mi­croen­vi­ron­ment is typ­i­cal­ly linked to a bet­ter prog­no­sis. But in­stead of ex­tract­ing gam­ma delta T cells to en­hance their ac­tiv­i­ty, French biotech Im­Check Ther­a­peu­tics has de­vised an ap­proach that re­lies on bu­ty­rophilin (BTN) mol­e­cules — which are named af­ter the epony­mous pro­tein in cow’s milk — to boost the ac­tion of cer­tain gam­ma delta T cells.

“The beau­ty of it is that we’re us­ing the pa­tient’s in­ter­nal gam­ma delta T cells, are not tak­ing them out, but are us­ing a mon­o­clon­al (an­ti­body) that can be ad­min­is­tered once every three weeks quite sim­ply over 30 min­utes in an in­fu­sion,” Paul Frohna, Im­Check’s chief med­ical of­fi­cer, not­ed in an in­ter­view with End­points News.

“What we’re do­ing is just es­sen­tial­ly har­ness­ing that po­ten­tial that they (gam­ma delta T cells) in­nate­ly pos­sess and am­pli­fy­ing it to a point where they re­al­ly be­come ac­tive in search­ing out and de­stroy­ing the can­cer cells.”

Pierre d’Epe­noux

On Wednes­day, the com­pa­ny un­veiled it had se­cured $53 mil­lion in Se­ries B fi­nanc­ing, bring­ing the to­tal cap­i­tal raised in 2.5 years to near­ly $80 mil­lion. The mon­ey will be used to shep­herd its lead im­muno-on­col­o­gy pro­gram, ICT01, in­to the clin­ic next year.

The ther­a­py is en­gi­neered to work in two ways — to dri­ve the gam­ma delta T cells cir­cu­lat­ing in the blood­stream to look for in­fect­ed cells or tu­mors, while ac­ti­vat­ing the gam­ma delta T cells that are al­ready with­in the tu­mor mi­croen­vi­ron­ment, Frohna said.

The raft of drug de­vel­op­ers — in­clud­ing Gam­maDelta Ther­a­peu­tics and its new spin­off Adap­tate, Re­gen­eron-backed Adicet Bio, Nether­lands-based Gade­ta, and Scot­land’s TC Bio­Pharm — keen on gam­ma delta T cells is grow­ing. But Im­Check is con­vinced its ap­proach, though ear­ly in the test­ing phase, has tan­gi­ble ad­van­tages over the crop.

There are oth­er sci­en­tists cog­nizant of the im­pact of BTNs on gam­ma delta T cells, but Im­Check is the on­ly com­pa­ny em­ploy­ing the mon­o­clon­al an­ti­body ap­proach, chief Pierre d’Epe­noux sug­gest­ed.

De­spite the pro­found clin­i­cal re­spons­es in­duced by the in­fu­sion of ge­net­i­cal­ly-mod­i­fied al­pha be­ta T cells pack­aged as CAR-T ther­a­pies, the ex­ist­ing ap­proach is rid­dled with lim­i­ta­tions. They on­ly work in blood can­cers, don’t work for a num­ber of pa­tients, tox­i­c­i­ty is an is­sue, are time-con­sum­ing to pro­duce, and the man­u­fac­tur­ing ap­pa­ra­tus re­quired is im­mense. Sales of the pi­o­neer­ing CAR-Ts — No­var­tis’ Kym­ri­ah and Gilead’s Yescar­ta — which can cost up to $1 mil­lion per pa­tient, have un­der­whelmed as a re­sult.

Mean­while, mon­o­clon­al an­ti­bod­ies are fa­mil­iar tech­nol­o­gy and are rel­a­tive­ly eas­i­er to en­gi­neer, pro­duce and ma­neu­ver through the reg­u­la­to­ry sys­tem, d’Epe­noux said.

The Im­Check in­jec­tion was co-led by the ven­ture cap­i­tal arm of Pfiz­er, and Bpifrance — with par­tic­i­pa­tion from new in­vestors in­clud­ing Welling­ton Part­ners, Agent Cap­i­tal and Alexan­dria Ven­ture In­vest­ments, as well as ex­ist­ing back­ers such as Life Sci­ences Part­ners, Gimv, Id­in­vest Part­ners, Kur­ma Part­ners, and Boehringer In­gel­heim Ven­ture Fund.

A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Su­per-se­cre­tive an­ti-ag­ing biotech Cal­i­co tees up the first vis­i­ble clin­i­cal tri­al of an ex­per­i­men­tal drug. And it’s for can­cer?

Over the past 7 years, Calico has been so much more than your average, run-of-the-mill secretive biotech players. It’s a riddle, wrapped in a mystery, inside an enigma, to repurpose an old Winston Churchill line dating from the time he confronted the Iron Curtain surrounding Stalin’s thoughts.

Launched by industry legend Art Levinson of Genentech fame, with the infinitely deep pockets of Google for support, one of the few big headlines the anti-aging biotech has sparked focused on a major alliance with AbbVie — a giant outfit that conversely likes to show off its drug prospects whenever it can. Together, they’ve been focused on diseases that limit life span — quite an arc of ailments.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Derek Chalmers, Cara Ther

Cara lines up a $440M deal for US rights to its late-stage drug for se­vere itch, with $150M cash on the ta­ble

With plans afoot to file an NDA for what could be its first approved drug, Cara Therapeutics is pivoting its focus to commercialization. And Swiss company Vifor Pharma is willing to surrender up to $440 million to market the candidate in the US.

Cara $CARA CEO Derek Chalmers said an NDA submission is coming this quarter for their intravenous drug Korsuva in chronic kidney disease-associated pruritus (CKD-aP), a severe itching condition. The Stamford, CT-based biotech read out positive topline data from a Phase III pivotal study back in April, and announced plans to approach EMA regulators shortly after filing with the FDA.

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Covid-19 roundup: Pars­ing Bourla, a top an­a­lyst sees im­proved chances for Pfiz­er vac­cine; Fau­ci: No sur­prise that Trump was hit by Covid-19

With a medley of adverse events hobbling the late-stage development of vaccines and drugs, Pfizer CEO Albert Bourla’s latest — extended — timeline for the mRNA approach they’re working on with BioNTech is giving some top analysts added confidence that the pharma giant can come up with the regulatory goods next month.

Parsing Bourla’s language in his comments last week, SVB Leerink’s Geoffrey Porges notes that Bourla’s decision to say they “may” be able to nail down the positive efficacy of their vaccine in a matter of days — a big change from his earlier certainty — may also indicate a delay on that to early November.

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CAR-plus: Irish biotech re­cruits Kite alum Chris Now­ers to prep dual-tar­get­ing NK cell ther­a­py for the clin­ic

Soon after Chris Nowers left Cell Medica — freshly rebranded Kuur Therapeutics — in February, the Kite Pharma alum was introduced to another cell therapy player.

The basic idea of building an off-the-shelf allogeneic platform with a CAR-NK approach was familiar to him, riding on the same wave as Takeda, J&J-backed Fate, Nkarta and others. But then there was something else that stood out: a membrane-bound TNF related apoptosis inducing ligand variant, or TRAIL variant, that’s also engineered onto the NK cell for a dual-targeted attack.

New Dewpoint Therapeutics CEO Ameet Nathwani (Sanofi)

A long-haul biotech with some im­pres­sive back­ers and big goals re­cruits a ma­jor league R&D ex­ec to the helm. What’s next?

A few weeks ago Kite and Allogene founder Arie Belldegrun jumped into the expanded syndicate for a Boston-based biotech called Dewpoint Therapeutics — a Polaris-birthed venture that’s styled itself as a drug development pioneer out to craft a major pipeline.

That round — which also added deep-pocket player ARCH to the list of backers — came up with $77 million for the next step in the long journey toward the clinic, a nice add to the A round that launched the company. Now we hear that Dewpoint has recruited Ameet Nathwani to the executive suite as the new CEO, who’s taking the helm from Polaris managing partner Amir Nashat, who brought the company into existence.

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IN8bio CEO William Ho (IN8bio)

Bring­ing their ge­net­i­cal­ly mod­i­fied gam­ma delta T cells to Nas­daq, IN8bio files for $86M IPO

The biotech IPO parade continues marching forward as 2020 turns toward the fourth quarter.

IN8bio, a New York-based company focused on genetically modified gamma delta T cell therapies, filed to go public Friday seeking an $86 million raise. The company has two clinical-stage candidates being studied in glioblastoma and leukemia, respectively.

By any stretch of the imagination, 2020 has already been a huge year for biotech, and nowhere does it appear more obvious than the vast amounts of companies hitting the public market.

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Gilead feels the heat as close al­ly Gala­pa­gos re­ports a big set­back on one of their top ex­per­i­men­tal drugs

The bad news keeps stacking up at Galapagos — which quite likely just lost control of a billion-dollar deal — and by extension their close partners at Gilead.

The biotech $GLPG reported after the bell Thursday that GLPG1972, one of their top development programs, flat failed a mid-stage study for osteoarthritis, flunking the primary and all secondary endpoints.

Testing 3 different doses of their drug, which relies on ADAMTS-5 inhibition, investigators concluded that none of them triggered a statistically significant response — as measured by cartilage thickness.

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