Harpreet Singh (file photo)

TCR-fo­cused Im­mat­ics adds an­oth­er mar­quee name to its list of part­ners: GSK

Im­mat­ics, in its fe­cund deal spree, has lured GSK, as the British drug­mak­er re­fo­cus­es its at­ten­tion to the lu­cra­tive field of on­col­o­gy.

On Thurs­day, the pri­vate­ly-held im­muno-on­col­o­gy com­pa­ny se­cured $50 mil­lion up­front in a col­lab­o­ra­tion with GSK on two T cell re­cep­tor (TCR) ther­a­peu­tics fo­cused on sol­id tu­mors. If all goes well, Im­mat­ics stands to earn more than $550 mil­lion in mile­stone pay­ments, in ad­di­tion to tiered roy­al­ties for each prod­uct.

Cre­at­ed in 2000 as a spin­off of the Uni­ver­si­ty of Tübin­gen, Ger­many, Im­mat­ic cur­rent­ly op­er­ates in the re­gion, in Mu­nich and has a pres­ence in Hous­ton, Texas. Over the years, the biotech has joined forces with a num­ber of part­ners — Gen­mab, Am­gen, Mor­phosys, Roche, Cel­gene as well as Uni­ver­si­ty of Texas MD An­der­son Can­cer Cen­ter — in its quest to de­vel­op both adop­tive cell ther­a­pies and bis­pe­cif­ic an­ti­bod­ies.

The GSK deal comes as the in­dus­try’s ap­petite for TCR ther­a­pies and their po­ten­tial to tar­get sol­id tu­mors — a lim­i­ta­tion of ex­ist­ing cel­lu­lar ther­a­pies — is bur­geon­ing.

GSK has an ex­ist­ing part­ner­ship with UK-based Adap­ti­m­mune, an­oth­er TCR play­er. Their lead cell ther­a­py pro­gram, GSK3377794, em­ploys TCR tech­nol­o­gy and is in a piv­otal Phase II study in syn­ovial sar­co­ma.

GSK is one of the few phar­ma­ceu­ti­cal com­pa­nies with a clear TCR strat­e­gy. Apart from their Adap­ti­m­mune deal, they’re work­ing on how to re­al­ly make man­u­fac­tur­ing com­mer­cial­ly at­trac­tive and on cell en­gi­neer­ing tech­nol­o­gy, Im­mat­ics chief Harpreet Singh not­ed in an in­ter­view with End­points News. “And now with us, they have com­plet­ed, in our view, the third leg of a strat­e­gy, and that is bring­ing in the right tar­gets with Im­mat­ics.”

One of the key com­po­nents of the im­mune sys­tem are T cells, which oblit­er­ate can­cer cells by us­ing T cell re­cep­tor (TCR) recog­ni­tion of cell sur­face mark­ers known as anti­gens. When a T cell rec­og­nizes a tu­mor anti­gen via the TCR, it snuffs the ma­lig­nant cell on which it re­sides. TCR tech typ­i­cal­ly in­volves reengi­neer­ing T cell re­cep­tors so that they can bet­ter rec­og­nize can­cer pro­teins, spark­ing an as­sault on tu­mors. Un­like CAR-T cells that can rec­og­nize ab­nor­mal pro­teins ex­pressed on the sur­face, TCRs can rec­og­nize tu­mor-spe­cif­ic pro­teins in­side cells. That makes CAR-T ther­a­pies more amenable to blood can­cers, while TCR ther­a­pies-in-de­vel­op­ment have po­ten­tial across mul­ti­ple tu­mor types.

De­spite their abun­dant promise, the adop­tion of CAR-T ther­a­pies — No­var­tis’ Kym­ri­ah and Gilead’s Yescar­ta — has un­der­whelmed ini­tial ex­pec­ta­tions. The up­take of Kym­ri­ah was plagued by man­u­fac­tur­ing prob­lems, and de­spite No­var­tis’ at­tempt to ex­pand its ca­pac­i­ty, sales con­tin­ue to dis­ap­point com­mer­cial­ly, giv­ing Yescar­ta an edge in the mar­ket. Mean­while, no­table side ef­fects, as well as the ther­a­pies’ ex­pen­sive price tags, have al­so lim­it­ed their use. A raft of drug de­vel­op­ers is work­ing on a fix for some of these con­straints by de­vel­op­ing off-the-shelf CAR-T ther­a­pies, de­signed to smoothen man­u­fac­tur­ing com­plex­i­ties by us­ing healthy donor cells.

In this Im­mat­ics/GSK deal, the part­ners will ini­tial­ly de­vel­op au­tol­o­gous T cell ther­a­pies with the op­tion to add off-the-shelf cell ther­a­pies.

Im­mat­ics has an edge in the TCR land­scape by virtue of its tar­get dis­cov­ery plat­form, Singh sug­gest­ed. “I would say the dif­fer­en­ti­a­tion isn’t, per se, in the TCR dis­cov­ery plat­form — there are a num­ber of com­pa­nies that can do this very well — its by com­bin­ing our unique tar­get dis­cov­ery data­base.”

The com­pa­ny al­so has inked a num­ber of li­cens­ing pacts fo­cused on bis­pecifics, a class of emerg­ing ther­a­pies that work in a dual ca­pac­i­ty — to rec­og­nize an anti­gen tar­get on tu­mor cells in tan­dem with rec­og­niz­ing a re­cep­tor on T cells, in or­der to cat­alyze the oblit­er­a­tion of the can­cer cell by the T cell.

The Cel­gene deal of 2019, like this GSK deal, is based on TCR ther­a­pies. But Im­mat­ics is now off the mar­ket for deals of this sort, Singh said. “We do not en­vi­sion that we will do fur­ther tar­get by tar­get deals…our fo­cus is to move for­ward and ad­vance our pro­pri­etary pipeline.”

In its life­time — and in­clud­ing the $50 mil­lion up­front from GSK — Im­mat­ics has raised around $475 mil­lion in ven­ture cap­i­tal, strate­gic part­ner­ships, and grants.

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AstraZeneca and Daiichi Sankyo made waves with their nearly $7 billion collaboration back in spring 2019, but at that point, Enhertu was already nearing the FDA’s doors with clinical data. The latest ADC tie-up to enter the biopharma fray centers around a preclinical asset, Mersana Therapeutics’ XMT-2056.

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The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

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For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

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Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

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