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.

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.

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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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Time for round 2: Il­lu­mi­na-backed VC snags $325M for its next fund

Illumina Ventures closed off its second investment fund with a total commitment of $325 million, offering fresh fuel to back a slate of startups that have already included a smorgasbord of companies, covering everything from diagnostics to biotech drug development and genomics.

Fund II brings the total investment under Illumina Ventures’ oversight to $560 million, which has been focused on early-stage companies. And it has a transatlantic portfolio that includes SQZ, Twist and Encoded Therapeutics.

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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Den­mark's Gubra to col­lab­o­rate with Bay­er on pep­tides; Sam­sung and Bio­gen re­ceive FDA ap­proval for Lu­cen­tis biosim­i­lar

Danish biotech Gubra announced a research collaboration and license agreement with Bayer to develop peptide therapeutics to treat cardiorenal diseases. The collaboration will utilize Gubra’s peptide drug discovery platform to identify potential candidates.

This is not the first time Gubra has partnered with a company on peptide therapeutics — they partnered with Boehringer Ingelheim back in 2017 to create peptide therapeutics to treat obesity.

Ex-My­lan em­ploy­ee pleads guilty to in­sid­er trad­ing, il­le­gal­ly deal­ing on FDA ap­provals, earn­ings and Up­john merg­er

A former Mylan IT executive pleaded guilty Friday to an insider trading scheme where he bought and sold stock options on another executive’s advice.

Prosecutors secured the plea from Dayakar Mallu, Mylan’s former VP of global operations information technology, after uncovering the plan. Mallu collaborated with an unnamed “senior manager,” the SEC said, to trade options ahead of Mylan public announcements regarding FDA approvals, revenue reports and its merger with the Pfizer generics subsidiary Upjohn. The two subsequently shared profits.

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