Lalo Flores (Century)

As al­lo­gene­ic cell ther­a­py ap­proach­es flour­ish, Cen­tu­ry loads up $160M to scale iP­SC plat­form for CAR-T, CAR-NK

La­lo Flo­res is con­fi­dent he’s found the way for­ward in cell ther­a­py.

The feel­ing, to be sure, is not ex­clu­sive. Thanks to splashy com­pa­nies like Al­lo­gene and Arti­va, bio­phar­ma is well aware of the promis­es of al­lo­gene­ic ther­a­pies as next-gen­er­a­tion al­ter­na­tives to the au­tol­o­gous CAR-Ts that have al­ready made it to the mar­ket. But few­er are talk­ing about a fin­er dis­tinc­tion with­in that al­lo­gene­ic group: Where do you find the cells to en­gi­neer and turn in­to a fi­nal off-the-shelf prod­uct?

While most have opt­ed for donor cells, Cen­tu­ry Ther­a­peu­tics — where Flo­res is CEO — is bank­ing on in­duced pluripo­tent stem cells.

Al­most two years af­ter launch­ing with $250 mil­lion in cash and three em­ploy­ees, it’s col­lect­ed $160 mil­lion to fu­el the now 100-per­son team’s dash to the clin­ic.

In par­al­lel with all the ad­vances in cell en­gi­neer­ing over the years, there’s been a sim­i­lar evo­lu­tion in the sci­ence of re­pro­gram­ming skin or blood cells in­to an em­bry­on­ic-like state and coax­ing them in­to T or NK cells. Fate Ther­a­peu­tics, a J&J-part­nered pi­o­neer now in the clin­ic, has done much to ed­u­cate the field about it, and more re­cent­ly we’ve seen star­tups like Notch emerge; Cen­tu­ry wants to join them in the lead­ing spot, Flo­res said.

The room for im­prove­ment, af­ter all, is sig­nif­i­cant. Even in the few lym­phoma in­di­ca­tions where Kym­ri­ah and Yescar­ta have been ap­proved, not all pa­tients achieve a com­plete re­sponse and many who do would re­lapse.

“So clear­ly what that means is that there was not enough pres­sure on the tu­mor, there were enough cells that sur­vived that treat­ment […] and that’s the rea­son pa­tients re­lapse,” Flo­res said. “Our goal at Cen­tu­ry is to in­crease the dura­bil­i­ty of the re­spons­es.”

Cen­tu­ry is “plat­form ag­nos­tic” and there­fore de­vel­op­ing both CAR-T and CAR-NKs cre­at­ed with its iP­SCs. The lead pro­gram is a CD19 CAR-T that they hope to steer in­to a hu­man tri­al by 2022.

In ad­di­tion to the anti­gen tar­gets, the biotech has de­vised a com­bi­na­tion of three ge­net­ic ed­its to pre­vent im­mune re­jec­tion of the ther­a­peu­tic cells — open­ing up the pos­si­bil­i­ty to dose sev­er­al times un­til the pa­tient re­sponds.

With each new pro­gram, once they fi­nal­ize all the mod­i­fi­ca­tions Cen­tu­ry would iso­late a sin­gle clone to start what they call a mas­ter cell bank.

“It may take you a cou­ple of years to get to that point,” Flo­res said. “But once you have a mas­ter cell bank, that is the be­gin­ning of your man­u­fac­tur­ing process. And from there it on­ly takes you 30 days to make a man­u­fac­tur­ing run that will sup­ply thou­sands of dos­es.”

Ul­ti­mate­ly, he en­vi­sions Cen­tu­ry’s ther­a­pies to be stored as a frozen prod­uct in hos­pi­tals. The pre­clin­i­cal pipeline goes af­ter a slate of hema­to­log­i­cal ma­lig­nan­cies as well as sol­id tu­mors like glioblas­toma, where they would de­ploy a bis­pe­cif­ic CAR. The sub­stan­tial back­ing from Ver­sant and Bay­er in its Se­ries B has helped Flo­res re­cruit a ex­perts in pro­tein en­gi­neer­ing, gene edit­ing and man­u­fac­tur­ing, with him man­ag­ing the head­quar­ters in Philadel­phia, R&D chief Hyam Lev­it­sky lead­ing a team in Seat­tle and the group that was for­mer­ly Em­pir­i­ca Ther­a­peu­tics set­ting up a third of­fice in Cana­da af­ter Cen­tu­ry ac­quired the com­pa­ny.

More re­cent­ly, it’s leased the space for an man­u­fac­tur­ing fa­cil­i­ty in New Jer­sey, just 45 min­utes from the HQ, adding in-house ca­pac­i­ty to com­ple­ment the ex­ist­ing pro­duc­tion un­der a part­ner­ship with Fu­ji­film Cel­lu­lar Dy­nam­ics.

“Each time you de­vel­op a prod­uct, you be­gin the whole process of learn­ing how to scale up man­u­fac­tur­ing,” he said. “Go­ing to this jour­ney, there’s many learn­ings and it’s re­al­ly im­por­tant to cap­ture all those learn­ings with­in your own em­ploy­ees, your own sci­en­tists, or with­in your close part­ner as we have in FC­DI.”

They could be tak­ing those learn­ings to Nas­daq soon. Though Flo­res notes Cen­tu­ry now has two to three years of run­way, the Se­ries C syn­di­cate — Fi­deli­ty, the Fed­er­at­ed Her­mes Kauff­man Funds, RA Cap­i­tal, Lo­gos Cap­i­tal, Or­biMed, Mar­shall Wace, Qatar In­vest­ment Au­thor­i­ty, Avid­i­ty Part­ners, and Oc­ta­gon Cap­i­tal — fea­tures well-known crossover play­ers with whom he will be ex­plor­ing an IPO.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Chris Gibson (Photo By Vaughn Ridley/Sportsfile for Web Summit via Getty Images)

Re­cur­sion founders gin for­tunes as IPO back­ers show­er $436M on one of the biggest boasts in AI -- based on some very small deals

In the AI drug development world, boasting often comes with the territory. Yet few can rival Recursion when it comes to claiming the lead role in what company execs like to call the industrialization of drug development, with promises of continued exponential growth in the number of drugs it has in the pipeline.

On Friday, the Salt Lake City-based biotech translated its unicorn-sized boasts into a killer IPO, pricing more than 24 million shares at the high end of its range and bringing in $436 million — with a large chunk of that promised by some deep-pocket backers.

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Covid-19 vac­cine halt drags on, an FDA ap­point­ment at long last, the great CRO con­sol­i­da­tion, 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.

Conference season is upon us, and while we’d much prefer to be wandering down the hallways and presentation rooms in person, the team is ready to cover the most consequential data coming out of these scientific meetings. Get in touch early if you have news to share.

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Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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