William Cao (Bloomberg via Getty)

Nas­daq rings in its first biotech IPOs of 2021: a CAR-T spe­cial­ist from Chi­na, a can­cer port­fo­lio play, and a SPAC

There was once a time when stel­lar CAR-T da­ta from Chi­na would come — in a sense — out of nowhere and be greet­ed with sur­prise, or even out­right skep­ti­cism.

It wasn’t that long ago, but those days are now gone. This is a time a CAR-T ther­a­py orig­i­nat­ing from Chi­na can be de­vel­oped in the pub­lic eye, down to every cut of da­ta, by a com­pa­ny bound by Amer­i­can rules of dis­clo­sure.

Case in point: Gra­cell Biotech­nolo­gies, a Shang­hai-based out­fit that’s grab­bing Nas­daq’s first biotech IPO list­ing along­side Cam­bridge, MA-based Cul­li­nan On­col­o­gy.

“We know val­u­a­tion at Nas­daq is prob­a­bly the low­est (com­pared to Hong Kong or Shang­hai), but the rea­son for us to go for Nas­daq was — is still — very clear,” co-founder and CEO William Cao told End­points News. “We’re a tech­nol­o­gy play com­pa­ny; in­no­va­tion is our soul and spir­it.”

By to­day’s stan­dards, Gra­cell’s raise of $209 mil­lion is some­what mod­est. But with the back­ing of mar­quee in­vestors like Lil­ly Asia Ven­tures, Morn­ing­side, Or­biMed, Temasek, Vi­vo Cap­i­tal and Welling­ton, Cao is less con­cerned about the mon­ey than gain­ing pres­ence in the US, where he is plan­ning an R&D cen­ter and mul­ti­ple tri­als.

The break­through suc­cess­es of No­var­tis, Kite and — per­haps to a less­er ex­tent — Juno back in 2016 and 2017 did much more than in­spire the next gen­er­a­tion of US and Eu­ro­pean star­tups bran­dish­ing new tech­nolo­gies to make more durable cell ther­a­pies, faster, Cao re­flect­ed. Af­ter re­tir­ing from the helm of CB­MG, the com­pa­ny he co-found­ed which in 2018 be­came No­var­tis’ man­u­fac­tur­ing part­ner in Chi­na, he took a stint as a ven­ture part­ner at 6 Di­men­sions, look­ing for start­up ideas to in­vest in.

Mar­ti­na Ser­sch

The fan­cy new ideas and great sci­en­tists teams he en­coun­tered, though, lacked the busi­ness acu­men to solve what he termed in­dus­tri­al chal­lenges — bot­tle­necks such as lengthy pro­duc­tion times and a “clum­sy” process were much more press­ing to him.

“I’m less in­ter­est­ed in ad­vanc­ing very fu­tur­is­tic CAR-T de­sign or TCR de­sign and I’m more in­ter­est­ed in how to solve the prac­ti­cal is­sues,” he said.

He soon got to work set­ting up his own shop, con­fer­ence-hop­ping around the US and Chi­na to ac­quaint him­self with the lat­est sci­ence as well as top tal­ent that he lat­er hand­picked for his team. Gra­cell was built on two tech­nolo­gies: FasT­CAR, which promis­es to short­en man­u­fac­tur­ing turn­around time to 22-36 hours; and Tru­U­CAR, its take on al­lo­gene­ic CAR-T. It has its own pro­duc­tion site in Suzhou to keep the key process­es in-house.

The C-suite now fea­tures Kevin Xie, the for­mer pres­i­dent at Fo­s­un Health­care, as CFO and Mar­ti­na Ser­sch as CMO.

“So I saw the mul­ti­ple myelo­ma da­ta,” said Ser­sch, who helped Am­gen de­vel­op its mul­ti­ple myelo­ma strat­e­gy be­fore jump­ing to Mus­tang Bio. “And at the time, I re­mem­ber William was not con­vinced of the da­ta. But when I saw the da­ta I said, wow, this looks very promis­ing. If this is hold­ing through and true through a cou­ple of more months for fol­lowup, you may have some­thing re­al­ly mean­ing­ful.”

Kevin Xie

In its F-1 fil­ing, Gra­cell re­port­ed that GC012F, its au­tol­o­gous CAR-T ther­a­py tar­get­ing both BC­MA and CD19, has treat­ed 16 pa­tients with re­lapsed/re­frac­to­ry MM and that 15 of them achieved and main­tained a re­sponse. The high­est dose co­hort record­ed a 100% strin­gent com­plete re­sponse rate for the six evalu­able pa­tients.

“Most pa­tients ex­pe­ri­enced Grade 1 or Grade 2 CRS, on­ly two pa­tients ex­pe­ri­enced Grade 3, and no pa­tient ex­pe­ri­enced Grade 4 or Grade 5 CRS or ICANS of any grade,” the com­pa­ny wrote.

It will be no easy task com­pet­ing with ei­ther the well-fund­ed US play­ers from Al­lo­gene to Lyell and Sana, or the ti­tan-backed joint ven­tures like JW, Fo­s­un/Kite and Al­lo­gene/Over­land. But Gra­cell is plung­ing full speed ahead with a reg­is­tra­tional tri­al in Chi­na that it just got cleared for and plans to start US tri­als in 2021.

For Cao, Chi­na’s in­fra­struc­ture for in­ves­ti­ga­tor-ini­ti­at­ed tri­als is Gra­cell’s se­cret trans­la­tion­al weapon, al­low­ing for quick first-in-hu­man tests of prod­uct de­sign.

“To a cer­tain ex­tent, that’s the most im­por­tant fac­tor we’ve been en­joy­ing that re­al­ly en­abled us. I don’t think every­body — all the peo­ple re­al­ize how pow­er­ful it is for im­mune cell ther­a­py,” Cao said.

Patrick Baeuer­le’s hub-and-spoke mod­el earns Cul­li­nan $249M pub­lic de­but

In chip­ping in­to Cul­li­nan On­col­o­gy’s up­sized $249.9 mil­lion raise, in­vestors are nei­ther buy­ing in­to a sin­gle drug nor a plat­form. Rather, they are lav­ish­ing on a taster menu of some of the hottest ideas on fight­ing can­cer.

Patrick Baeuer­le

The ethos of the com­pa­ny, which was found­ed by biotech vet and MPM part­ner Patrick Baeuer­le, is per­haps summed up in this line from the prospec­tus: “(W)e think about cap­i­tal al­lo­ca­tion and risk as much as we think about drug de­vel­op­ment.”

That means cen­tral­iz­ing R&D, BD and ad­min­is­tra­tive work in one hold­ing com­pa­ny while bet­ting on as many dif­fer­ent ap­proach­es as pos­si­ble — and cut­ting any weak­lings loose mer­ci­less­ly. The 17 full-time staffers (along­side one part-timer and two con­sul­tants) are de­ployed to the sev­en pro­grams as need­ed.

CLN-081 is the first drug in the clin­ic and the on­ly tar­get­ed ther­a­py in the mix, tar­get­ing NSCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions. Oth­er tech ap­proach­es rep­re­sent­ed in­clude bis­pecifics, NK cell-en­gag­ing an­ti­body, cy­tokine fu­sion pro­tein, as well as TCR-based ther­a­py.

Cul­li­nan filed for its IPO short­ly af­ter pre­sent­ing what they called ini­tial clin­i­cal da­ta on it, and just on the heels of an­nounc­ing a $131 mil­lion Se­ries C.

With $153M SPAC, Lo­cust Walk grabs a seat the head of the deal ta­ble

Hav­ing long billed it­self as a life sci­ence trans­ac­tion firm, Lo­cust Walk is ready to strike a deal of its own.

Chris Ehrlich

Its blank check com­pa­ny, Lo­cust Walk Ac­qui­si­tion Corp, is the first SPAC to gain a list­ing on Nas­daq through an IPO that brought in $153 mil­lion. The mon­ey will now go to­ward snap­ping up a promis­ing pri­vate com­pa­ny to be merged with the new­ly pub­lic shell.

As with oth­er deals of this kind, the peo­ple are re­al­ly what in­vestors are putting their mon­ey be­hind. In this case, Chris Ehrlich, Lo­cust Walk’s se­nior man­ag­ing di­rec­tor and glob­al head of strate­gic trans­ac­tions, is grab­bing the CEO post and tak­ing the lead on the quest to find a suit­able ac­qui­si­tion tar­get.

He will be joined by Daniel Gef­fken, the founder and man­ag­ing di­rec­tor at Dan­forth Ad­vi­sors, as CFO; Brain At­wood of Ver­sant as chair­man; as well as a hand­ful of di­rec­tors in­clud­ing Bar­bara Kosacz, Kro­nos’ COO and Eliz­a­beth Bhatt, the chief busi­ness and strat­e­gy of­fi­cer of Ap­plied Mol­e­c­u­lar Trans­port.

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?

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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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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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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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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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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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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Alex Leech, Alchemab CEO (SV Health Investors)

Alchemab bags fresh round of in­vestor for tar­get-ag­nos­tic an­ti­body de­vel­op­ment for Hunt­ing­ton's, Covid-19

With a “target-agnostic” approach to antibody development, the UK’s Alchemab has used lessons learned from patients with resistance to certain diseases to chase after conditions as far apart as Huntington’s and Covid-19. Now, investors are jumping on board the concept with an $86 million Series A.

The proceeds will go toward advancing the company’s target-agnostic drug discovery program, a release said. That approach looks at the antibody repertoires of patients who show resistance to typically destructive diseases regardless of genetic disposition.

Craig Parker, Surrozen CEO

The world of Wnt heads to Nas­daq as Sur­rozen an­nounces a $212M SPAC deal

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Another day, another SPAC merger in the world of biotech.

Less than 24 hours after Tango Therapeutics announced its own leap to Nasdaq through the blank check route, Surrozen has decided to take a similar step. The Wnt pathway-focused biotech is reverse-merging with Consonance Capital Management’s SPAC in a $212 million deal, which includes $92 million from the shell company and $120 million in PIPE financing.