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.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UP­DAT­ED: Roivant bumps stake in Im­muno­vant with a $200M deal. But with M&A off the ta­ble, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

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Sanofi preps a multi­bil­lion-dol­lar buy­out of an mR­NA pi­o­neer af­ter falling be­hind in the race for a Covid-19 jab — re­port

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

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Anthony Sun, Zentalis and Zentera CEO (Zentalis)

With clin­i­cal tri­als lined up for Zen­tal­is drugs, Chi­na's Zen­tera sets its sights on more deal­mak­ing and an IPO

As Zentalis geared up for an AACR presentation of early data on its WEE1 inhibitor earlier this year, its Chinese joint venture Zentera wasn’t idle, either.

Zentera, which has headquarters in Shanghai, had already nabbed clearance to start clinical trials in China for three of the parent company’s drugs. In May — just a month after Zentalis touted three “exceptional responses” out of 55 patients for their shared lead drug, ZN-c3 — it got a fourth CTA approval.

Thomas Soloway, T-knife CEO

What hap­pens when you give a mouse a hu­man self-anti­gen? In­vestors bet $110M to find out

T-knife Therapeutics launched last August on a mission to isolate T cell receptors not from human donors, but from mice. Now, with a new CEO and a candidate bound for the clinic, the Versant-backed company is reloading with a fresh $110 million.

“What we are trying to do for the field of TCR therapy and solid tumor therapy is very analogous to what the murine platforms have done in antibody development,” CEO Thomas Soloway told Endpoints News. 

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UP­DAT­ED: Watch out Glax­o­SmithK­line: As­traZeneca's once-failed lu­pus drug is now ap­proved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

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Not all mR­NA vac­cines are cre­at­ed equal. Does it mat­ter?; Neu­ro is back; Pri­vate M&A af­fair; 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.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

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Bris­tol My­ers pulls lym­phoma in­di­ca­tion for Is­to­dax af­ter con­fir­ma­to­ry tri­al falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

Rick Pazdur (via AACR)

FDA's on­col­o­gy head Rick Paz­dur de­fends the ac­cel­er­at­ed ap­proval path­way, claim­ing it is 'un­der at­tack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

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