Jeffrey Goldberg

Tout­ing CD161 as a test case for sin­gle-cell tech, Long­wood-backed Im­mu­ni­tas bags $58M for next-gen I/O work

Back when Long­wood un­veiled its lat­est im­munother­a­py start­up, Im­mu­ni­tas, the VC’s co-founder Lea Hachi­gian talked at length about how its sin­gle-cell ge­nomics analy­sis plat­form could en­able re­searchers to “ask ques­tions of the im­mune sys­tem we weren’t able to ask be­fore,” un­der­stand hu­man bi­ol­o­gy on a much deep­er lev­el and iden­ti­fy tar­gets that no­body else was work­ing on. They just couldn’t dis­close the pre­cise tar­get for the lead pro­gram.

Kai Wucherpfen­nig

This Feb­ru­ary, Im­mu­ni­tas fi­nal­ly did — pub­lish­ing a pa­per in Cell that ze­roes in on CD161 as a re­cep­tor on T and NK cells that sup­press­es their abil­i­ty to kill glioma cells.

Months lat­er, the start­up is back with $58 mil­lion in fresh cash to steer a CD161-block­ing an­ti­body to­ward the clin­ic while fu­el­ing a slate of oth­er pro­grams be­hind it. The goal, Im­mu­ni­tas CEO Jef­frey Gold­berg told End­points News, is to keep ex­pand­ing the pipeline at a rate of about one pro­gram per year.

Kai Wucherpfen­nig, chair of Dana-Far­ber Can­cer In­sti­tute’s de­part­ment of can­cer im­munol­o­gy and vi­rol­o­gy, co-found­ed Im­mu­ni­tas with Aviv Regev (be­fore Roche’s Genen­tech re­cruit­ed her to run R&D), Dane Wit­trup of MIT and Mass Gen­er­al’s Mario Su­và.

For Wucherpfen­nig, the dis­cov­ery of CD161 was a tes­ta­ment to the key ad­van­tages of the sin­gle-cell plat­form he helped in­vent, which start­ed out an­a­lyz­ing hun­dreds of cells but can now work with hun­dreds of thou­sands at a time, at high res­o­lu­tion. Through iso­lat­ing T cells from pa­tients’ tu­mor sam­ples (sep­a­rate from, say, stro­mal cells, tu­mor cells, and so on), clus­ter­ing them by gene ex­pres­sion and then ex­am­in­ing dif­fer­ent pop­u­la­tions, his team es­sen­tial­ly came up with an at­las of im­mune cells in glioma — all based on hu­man sam­ples.

“We’ve been asked mul­ti­ple times, why do oth­er peo­ple not pick it up? And the rea­son ac­tu­al­ly is that the bi­ol­o­gy is very dif­fer­ent be­tween mice and hu­mans,” he said. “Most peo­ple start with mouse mod­els, and then in mice there are ac­tu­al­ly mul­ti­ple genes that en­code CD161 like mol­e­cules. Some of them are in­hibito­ry, some just are ac­ti­vat­ing re­cep­tors, and the bi­ol­o­gy is very con­fus­ing. And in hu­mans it’s ac­tu­al­ly more straight­for­ward. There’s a sin­gle gene that en­codes an in­hibito­ry re­cep­tor, OK. And so most peo­ple have looked at this — I know some peo­ple have looked at this and said, nev­er mind. And they nev­er re­al­ly looked at the hu­man bi­ol­o­gy.”

As Im­mu­ni­tas — now grown to 20-plus staffers — car­ried on the work, once again re­ly­ing on the sin­gle-cell se­quenc­ing and an­a­lyt­ics tech, they found out that the re­cep­tor is not just as­so­ci­at­ed with glioma. CD161 ap­pears to be in play in T and NK cell in­ter­ac­tions with mul­ti­ple can­cer types span­ning sol­id and liq­uid tu­mors, giv­ing the biotech mul­ti­ple op­tions to ex­plore in the first hu­man tri­als, with an IND slat­ed for the first half of next year.

Specif­i­cal­ly, Im­mu­ni­tas’ IMT-009 is de­signed to bind to CD161 on T and NK cells and pre­vent it from in­ter­act­ing with CLEC2D on tu­mor cells, there­by restor­ing the im­mune cells’ can­cer-killing pow­er.

Wucherpfen­nig and Gold­berg fig­ure there are many more im­muno-on­col­o­gy tar­gets out there sim­i­lar­ly lurk­ing in cor­ners tra­di­tion­al dis­cov­ery meth­ods can’t un­cov­er.

The promise has drawn a siz­able syn­di­cate. Agent Cap­i­tal led the round, which fea­tured Med­ical Ex­cel­lence Cap­i­tal, 120 Cap­i­tal, So­las­ta Ven­tures, Mi­rae As­set, Ono Ven­ture In­vest­ment, The Mark Foun­da­tion for Can­cer Re­search, NS In­vest­ment, Bright­Edge (Amer­i­can Can­cer So­ci­ety) and the Leukemia & Lym­phoma So­ci­ety Ther­a­py Ac­cel­er­a­tion Pro­gram. Ex­ist­ing back­ers al­so re­turned: They are Alexan­dria Ven­ture In­vest­ments, Evotec, Leaps by Bay­er, M Ven­tures, No­var­tis Ven­ture Fund and, of course, found­ing in­vestor Long­wood.

Be­yond that, the sci­en­tist al­so sees the up­com­ing work as part of a big­ger ex­per­i­ment to test the un­der­ly­ing plat­form as a com­pre­hen­sive tool to close the loop on trans­la­tion.

“We’re al­so think­ing about how we can use sin­gle cell tech­nolo­gies to ac­tu­al­ly un­der­stand what the drug does in pa­tients — you know, once we start a clin­i­cal tri­al,” he said. “There ob­vi­ous­ly are some lo­gis­ti­cal chal­lenges with sam­ple pro­cure­ment, et cetera, but it could ac­tu­al­ly be an ex­cit­ing op­por­tu­ni­ty. So we — we use sin­gle cell tech­nolo­gies to dis­cov­er it, we use sin­gle cell tech­nolo­gies to de­fine in­di­ca­tions, and then al­so study mech­a­nism of ac­tion in peo­ple.”

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.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

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For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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