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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Yao-Chang Xu, Abbisko Therapeutics founder and CEO

Qim­ing-backed Ab­bisko makes $200M+ Hong Kong de­but, as a SPAC and Agenus spin­out al­so price on Nas­daq

Three new entities priced their public debuts late Thursday and early Friday, including a SPAC, a traditional Nasdaq IPO and a Chinese biotech joining the Hong Kong Index.

Shanghai-based Abbisko Therapeutics raised the most money of the triumvirate, garnering $226 million in its Hong Kong debut and pricing at HK$12.46, or roughly $1.60 in US dollars. The blank check company followed up with a $150 million raise, while MiNK Therapeutics priced on Nasdaq at $12 per share and a $40 million raise.

Paul Grayson, Tentarix CEO (Versant)

Phar­ma vet­er­ans re­group with $50M and a plan to dis­cov­er new mul­ti-specifics

While a horde of drugmakers develops bispecific antibodies to more directly target tumor cells — there were about 100 programs in or nearing clinical trials back in May — a new company is emerging to go one step further.

On Thursday, Tentarix Biotherapeutics unveiled a $50 million Series A round to support its next-gen multi-specifics platform. While the field has largely focused on bispecifics, which engage two targets, Tentarix believes its multifunctional programs have the potential to be even more specific, since more conditions must be met for potent activity to occur.

Tillman Gerngross, Adagio CEO

Q&A: Till­man Gern­gross ex­plains why his Covid mAb will have an edge over an al­ready crowd­ed field

If anyone knows about monoclonal antibodies, it’s serial entrepreneur, Adimab CEO, and Dartmouth professor of bioengineering Tillman Gerngross.

Even the name of Gerngross’ new antibody startup Adagio Therapeutics is meant to reflect his vision behind the development of his Covid-19 mAb: slowly, he said, explaining that “everyone else, whether it’s Regeneron, Lilly, or AstraZeneca, Vir, they all valued speed over everything.”

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