Xiling Shen (Xilis)

A Mubadala-backed biotech is us­ing pa­tient tu­mor tis­sue grown in a petri dish to change pre­ci­sion on­col­o­gy

As Duke pro­fes­sor Xil­ing Shen tells it, the idea for his new biotech Xilis dates all the way back to 2009. Shen taught at Cor­nell at the time, re­search­ing cir­cuit de­sign in the uni­ver­si­ty’s bio­engi­neer­ing de­part­ment, when he came across a pa­per from Dutch bi­ol­o­gist Hans Clevers about a tech­nol­o­gy called “organoids,” or tis­sue cul­tures made up of “3D gel.”

Shen tells End­points News he saw the ther­a­peu­tic po­ten­tial here, al­low­ing sci­en­tists to test drugs on re­al pa­tient tis­sue in petri dish­es in what would be a first, but al­so won­dered about the lim­i­ta­tions of such tech­nol­o­gy. Could this process be ac­com­plished quick­ly and cheap­ly? And how chal­leng­ing would it be to scale up the tech to the point where it could be wide­ly used?

Ay­man Al­Ab­dal­lah

The lim­i­ta­tions have os­ten­si­bly been over­come enough to re­cruit blue-chip sov­er­eign wealth fund Mubadala to lead a $70 mil­lion Se­ries A for the biotech, putting a seal of ap­proval on the plat­form Shen be­lieves will trans­form the pre­ci­sion ther­a­py space. Us­ing organoid tech­nol­o­gy, Xilis is aim­ing to an­a­lyze pa­tients’ tu­mors in their na­tive mi­croen­vi­ron­ments in or­der to pro­vide more per­son­al­ized and bet­ter tar­get­ed can­cer treat­ments.

In the can­cer space, where it can be dif­fi­cult to pre­dict how any giv­en ther­a­py might work for each in­di­vid­ual pa­tient, mod­el­ing tools like these are go­ing to be among the next wave of in­no­v­a­tive tech­nolo­gies, Mubadala in­vestor Ay­man Al­Ab­dal­lah said.

“Less than one out of 10 can­cer drugs make it to mar­ket,” Al­Ab­dal­lah told End­points. “The con­nect­ed prob­lem here is once a drug is ap­proved it does not nec­es­sar­i­ly ben­e­fit all the pa­tients it’s ad­min­is­tered to … un­der­ly­ing this chal­lenge or bar­ri­er is the lack of tools to pre­cise­ly mod­el hu­man dis­ease out­side the body.”

Shen had help bring­ing the tech­nol­o­gy to where it is to­day, he says. In 2014 he met co-founder David Hsu, a GI clin­i­cian at Duke, and the two teamed up. The per­spec­tive Hsu brought work­ing with pa­tients helped shape their shared vi­sion, and Shen moved his lab to Duke in 2015 to bet­ter fo­cus on build­ing out the plat­form.

Hans Clevers

Things came to a head in 2019 when Clevers vis­it­ed Duke to give a keynote speech. Shen and Hsu grabbed lunch with Clevers af­ter­wards, and Clevers not­ed some of the same lim­i­ta­tions Shen said he’d thought of all those years ear­li­er. By the next morn­ing, af­ter lis­ten­ing to how Shen worked to try over­com­ing them, Clevers agreed to join the com­pa­ny.

At the heart of Xilis is a sim­ple, key con­cept: By tak­ing a piece of a pa­tient’s tu­mor tis­sue and grow­ing it as an organoid in a petri dish, Shen says re­searchers can test thou­sands of ther­a­pies or drug com­bi­na­tions to see how the tu­mor might re­act. By mod­el­ing tu­mors in such a way, Xilis can al­so get clin­i­cian in­put for how they’d pre­fer to treat their pa­tients.

“It’s not just the cells but the in­volve­ment of the tu­mor, in­clud­ing im­mune cells, that’s re­al­ly mim­ic­k­ing the en­tire en­vi­ron­ment,” Shen told End­points. “For phar­ma, it’s al­so a sig­nif­i­cant ad­van­tage be­cause we’re the first that can en­cap­su­late the tu­mor with its orig­i­nal im­mune en­vi­ron­ment out­side the body.”

The sci­en­tists got start­ed with a seed round back in No­vem­ber 2019 and start­ed look­ing for the Se­ries A this past April af­ter re­cruit­ing sev­er­al part­ners in the phar­ma space to use their tech­nol­o­gy. Xilis doesn’t have its own pipeline yet, but Shen says the biotech is cur­rent­ly fo­cused on help­ing these com­pa­nies com­plete their re­search faster.

And the organoids can be used at any stage of the dis­cov­ery process, Shen adds, from the pre­clin­i­cal stage to in-hu­man tri­als. That could help bio­phar­mas de­sign smarter clin­i­cal tri­als down the road if they have a bet­ter idea of how their ex­per­i­men­tal drugs work.

For now, Xilis plans to use the cash to fur­ther de­vel­op the plat­form and its AI ca­pa­bil­i­ties, as well as re­cruit­ing more part­ners. If every­thing goes ac­cord­ing to plan, the biotech hopes to shake up dif­fer­ent kinds of treat­ments across the cell ther­a­py space, Shen said.

“The en­tire field right now faces a big chal­lenge dif­fer­ent from con­ven­tion­al drugs,” Shen said. “But these are very high­ly in­di­vid­u­al­ized ther­a­pies. How do you know you’ve en­gi­neered T cells that treat as many pa­tients as pos­si­ble? So we are pro­vid­ing the first en­abling tech­nolo­gies to test en­gi­neered T cells on the same pa­tients’ tu­mor be­fore they put it in­to the pa­tients.”

Thurs­day’s Se­ries A was joined by new in­vestors in­clud­ing GV, LSP, Catalio Cap­i­tal Man­age­ment, and Duke An­gel Net­work. Cur­rent in­vestors Fe­li­cis Ven­tures, Two Sig­ma Ven­tures, Pear VC, KdT Ven­tures, and Al­ix Ven­tures al­so par­tic­i­pat­ed.

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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