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.

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.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

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?

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jeffrey Nau, Oyster Point Pharma CEO

FDA OKs an in­haled ver­sion of smok­ing ces­sa­tion drug Chan­tix — for a com­mon eye dis­ease

Oyster Point Pharma now has its first FDA-approved product — Tyrvaya. And the biotech has taken a unique route to get there by using an old drug with a storied past.

The New Jersey biotech announced this morning that the FDA has approved their nasal spray product for dry eye disease on Friday — the first nasal spray to be approved for the disease. The product’s active ingredient is 0.03 mg of varenicline, also known as smoking cessation aid Chantix.