AffyImmune CEO Moonsoo Jin (L) and COO Eric von Hofe

Tiny play­er picks up $30M to go af­ter CAR-T's biggest chal­lenges

Of all the chal­lenges as­so­ci­at­ed with reengi­neer­ing CAR-T ther­a­pies — which have been wild­ly suc­cess­ful in treat­ing cer­tain blood can­cers — to at­tack sol­id tu­mors, tox­i­c­i­ty of­ten ranks near the top.

“If there is no ther­a­peu­tic win­dow, the tri­al will be ter­mi­nat­ed,” Si­mone Song, founder and man­ag­ing part­ner at ORI Cap­i­tal, told End­points News.

Si­mone Song

It was the rea­son why ORI, a Hong Kong-based health­care VC firm fo­cused on can­cer, meta­bol­ic dis­or­ders and neu­rode­gen­er­a­tive dis­eases, de­cid­ed to in­cu­bate a start­up by the name of Affy­Im­mune back in 2017. And it’s why Song’s team is hand­ing over an­oth­er $30 mil­lion to fund a first-in-hu­man tri­al that kicked off late last year and send a sec­ond CAR-T ther­a­py in­to the clin­ic.

The is­sue un­der­ly­ing CAR-T’s tox­i­c­i­ty prob­lem has been well-doc­u­ment­ed. While hema­to­log­i­cal ma­lig­nan­cies can be eas­i­ly hunt­ed down by mark­ers like CD19 and BC­MA (and clin­i­cians can pre­vent side ef­fects sim­ply by wip­ing out B cells, the on­ly oth­er cell type ex­press­ing those anti­gens), it’s much hard­er to dis­tin­guish be­tween sol­id tu­mor cells and or­gans. Pro­gram­ming the CAR-T cells to at­tack any cell bear­ing those tu­mor-as­so­ci­at­ed anti­gens in­evitably hurts nor­mal cells, too. Tu­mor-spe­cif­ic anti­gens have been elu­sive.

Co-found­ed by two sci­en­tists who worked to­geth­er as post­docs at Tim Springer’s Har­vard lab, Affy­Im­mune’s pro­posed so­lu­tion ze­roes in on the binders on CAR-T.

Gang Song

When study­ing the in­ter­ac­tion be­tween an anti­gen called ICAM1 and its nat­ur­al lig­and, Moon­soo Jin and Gang Song test­ed mul­ti­ple “affin­i­ty vari­ants” — sin­gle chain mon­o­clon­al an­ti­bod­ies sport­ing dif­fer­ent struc­tures — against ICAM1. What they found was that the tight­est binders, which have tra­di­tion­al­ly been fa­vored, are not nec­es­sar­i­ly the best. Rather, some of the weak­er binders (which they de­scribe as be­ing in the nanomo­lar range) ap­peared to be bet­ter at elim­i­nat­ing tu­mors.

Be­sides, these weak­er binders would spare healthy cells with low ex­pres­sion of the tar­get in fa­vor of tu­mor cells, which tend to have much high­er ex­pres­sion, said Er­ic von Hofe, pres­i­dent and COO. By tai­lor­ing an affin­i­ty lev­el to each tar­get based on its ex­pres­sion on nor­mal cells, Affy­Im­mune be­lieves its tun­ing method draws that thin line for CAR-T cells to sep­a­rate friend from foe.

“For each tar­get we look at, es­sen­tial­ly we’re clean­ing them up,” he said.

They al­so just look more like the nat­ur­al re­cep­tors im­mune cells use to bind to tu­mors, said von Hofe, mim­ic­k­ing the phys­i­o­log­i­cal in­ter­ac­tion. That comes with oth­er in­di­rect ben­e­fits: The T cells don’t get over­stim­u­lat­ed or ex­haust­ed too quick­ly, and the­o­ret­i­cal­ly can func­tion for longer, killing more can­cer cells.

“It’s an easy con­cept, but to [get to] the ex­act lev­el it takes a lot of work,” Song said. “It has tak­en them a lot of work to find the ex­act right lev­el.”

The Se­ries A+ is ad­mit­ted­ly mod­est by CAR-T stan­dards these days, es­pe­cial­ly for a clin­i­cal-stage out­fit. Over the last four and a half years, von Hofe — the first em­ploy­ee to join Jin, now the CEO — has grown the crew to nine, main­tain­ing a lean op­er­a­tion fo­cused on se­cur­ing the first clin­i­cal proof-of-con­cept.

Affy­Im­mune is first test­ing its lead drug in thy­roid can­cer, but said ICAM1 is found in a range of oth­er can­cer types rang­ing from gas­tric can­cer to triple neg­a­tive breast can­cer. At the same time, there’s a sec­ond part to its “tune and track” plat­form — a so­mato­statin re­cep­tor that al­lows in­fused CAR-T cells to be “seen” in re­al time through an FDA-sanc­tioned ra­dio la­bel trac­er and PCP or CT scans.

“Down the road, I mean pos­si­bly we could see about com­bin­ing with oth­er tech­nolo­gies if there’s a true en­hance­ment, but we’ve been pret­ty — I wouldn’t say con­ser­v­a­tive, but we’ve just stuck with things that are known to work,” von Hofe said. “Some oth­er com­pa­nies are try­ing to do all kinds of very high tech things, and it’s very ex­cit­ing, and they bring in a lot of mon­ey do­ing it. As I men­tioned, Affy­Im­mune’s fo­cus has been get­ting func­tion­al CAR-T cells that are more func­tion­al than oth­er CAR-T cells out there, with this affin­i­ty tune, tracked, get those in­to the clin­ic, show there’s a ben­e­fit to the pa­tient, and then ex­pand on that.”

The Price of Re­lief: Ex­plor­ing So­lu­tions to the Ris­ing Costs of On­col­o­gy Drugs

In 2020, The National Cancer Institute estimated about 1.8 million new cases of cancer diagnosed in the United States, while the costs associated with treatment therapies continued to escalate. Given the current legislative climate on drug pricing, it’s never been more important to look at the evolution of drug pricing globally and control concerns of sustainable and affordable treatments in oncology.

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

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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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