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.

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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UP­DAT­ED: Three biotechs price hefty IPOs just be­fore the week­end, while a fourth and a SPAC seek spots on Wall Street

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

A handful of biotechs are hitting Wall Street just before the start of the weekend, with three companies — Caribou Biosciences, Sophia Genetics and Absci — all pricing big raises Wednesday and Thursday. Gamma delta T cell-focused IN8bio relaunched its IPO campaign months after postponing it last November, seeking a slightly lower raise. And another SPAC has filed for a public debut.

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Victor Perlroth, Kodiak Sciences CEO

Ko­di­ak turns down $125M pay­ment from Bak­er Bros. deal, slash­es roy­al­ty cap by 55%

Following a massive public raise last November, Kodiak Sciences has re-worked a royalty sale agreement with an old partner — and declined new funds in the process.

Kodiak is turning down a planned $125 million payment from Baker Bros. Advisors, according to an SEC filing, cutting short an agreement that saw the biotech hand over a 4.5% stream of royalty sales on its experimental anti-VEGF therapy KSI-301 for retinal vascular diseases. In conjunction with the move, Kodiak is shrinking the royalty cap from just over $1 billion to $450 million.

EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many people around the world, my life has been profoundly shaped by cancer. Those personal experiences, along with a deep love of clinical laboratory science and a passion to apply the power of genomics in medicine, motivated me to launch a company that would improve cancer care through better diagnostics. Thirteen years later, I am proud that we are delivering more accurate information at multiple points along the patient journey, with a focus on eight of the 10 cancers that are most commonly diagnosed in the United States.