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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.