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.

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

You can add Amgen and GSK to the list of deep-pocket drug R&D players who are tailoring their pipeline work to fit a new age of coronavirus.

Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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Covid-19 roundup: J&J, BAR­DA set ear­ly 2021 fin­ish line for $1B vac­cine race; FDA al­lows emer­gency drug use, ahead of piv­otal da­ta

J&J has zeroed in on a Covid-19 vaccine candidate that it hopes to begin testing in humans by September this year — with the extraordinary goal of getting it ready for emergency use in early 2021. And together with BARDA, it’s committing $1 billion to make it happen.

That kind of accelerated timeline would fall on the fast side of NIAID director Anthony Fauci’s well-publicized prediction that it would be another 12 to 18 months before a vaccine can be available for public use. A Phase I trial of Moderna’s mRNA vaccine began two weeks ago, and both the biotech and fellow mRNA player CureVac have discussed similar, if not even faster, timelines for emergency use among healthcare workers.

Mene Pangalos via YouTube

As­traZeneca says its block­buster Farx­i­ga proved to be a game-chang­er in CKD — wrap­ping PhI­II ear­ly

If the FDA can still hold up its end of the bargain, AstraZeneca is already on a short path to scooping up a cutting-edge win with a likely approval for their SGLT2 drug Farxiga in cutting the risk of heart failure. Now the pharma giant says it can point to solid evidence that the drug — initially restricted to diabetes — also works for chronic kidney disease, potentially adding a blockbuster indication for the franchise.

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It is 'kind of a proven tech­nol­o­gy': Hep B vac­cine mak­er joins glob­al hunt for coro­n­avirus vac­cine

Using lab-grown proteins that are engineered to mimic the architecture of viruses to induce an immune response, VBI Vaccines is joining the hunt for a coronavirus vaccine — harnessing technology that has initially been proved safe in early trials as a prophylactic for cytomegalovirus (CMV) infection.

Unlike the raft of the companies in the Covid-19 vaccine race — including Moderna, CureVac and J&J — VBI is taking a pan-coronavirus approach, by developing a vaccine that will encompass Covid-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS).

Can a pair of top AveX­is alum­ni steer a new gene ther­a­py up­start to R&D glo­ry? 3 VCs bet $60M on it

VCs love few things more than a proven executive team when it comes to launching a new company. And now a group of A-listers has turned to a pair of top execs out of AveXis to steer the latest gene therapy player into the clinic.

The biotech is Waltham, MA-based Affinia and the two execs are Sean Nolan and Rick Modi — the former CEO and CBO respectively of AveXis, the gene therapy pioneer that fetched $8.7 billion in a sale to Novartis. Nolan has now taken the chairman’s role at Affinia while Modi moves up to the CEO post at the company.

Un­de­terred by a pan­dem­ic, Gilde Health­care rais­es their largest fund yet

When Pieter van der Meer started raising the capital for Gilde Healthcare’s fifth fund in the waning months of 2019, he had his eyes on a different chain of events that could change the healthcare system and perhaps even play to his firm’s advantage: The US presidential election.

Since raising their third fund in 2011, the 34-year-old Dutch firm had focused on value-based care. They chose late-stage biotechs that came up with new devices and delivery systems for de-risked established compounds, and when they chose preclinical biotechs, they spoke with potential pharma partners, payers and regulators to ask where and at what prices the drug made sense. As the Democratic primary became a contest over how to lower healthcare costs, it looked like a strategy that could pay off.

Daniel O'Day (AP Images)

Gilead CEO Dan O'­Day of­fers a de­tailed ex­pla­na­tion on remde­sivir ac­cess — re­as­sur­ing an­a­lysts that Covid-19 da­ta are com­ing fast

After coming under heavy fire from consumer groups ready to pummel them for grabbing the FDA’s orphan status for remdesivir — reserved to encourage the development of rare disease therapies — Gilead CEO Daniel O’Day had some explaining to do about the company’s approach to providing access to this drug to patients suffering from Covid-19. And he set aside time over the weekend to patiently explain how they are making their potential pandemic drug available in a new program — one he feels can better be used to address a growing pack of infected patients desperately seeking remdesivir under compassionate use provisions.

In addition to trying to reassure patients that they will once again have an avenue to pursue access, O’Day also reassured some analysts who had been fretting that China’s quick comeback from the coronavirus outbreak could derail its ultra-fast schedule for testing the drug in patients. The data are still expected in a few weeks, he says in the letter, putting the readout in April.

O’Day emphasizes that Gilead intends to pursue a pricing approach that will make this drug widely available — if it proves effective and safe. But no one is quite sure just what the longterm value would be, given the work being done on a variety of vaccines that may be rolled out as early as this fall — at least to the most heavily threatened groups.

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