Scathing short at­tack from an ob­scure source ac­cus­es Nan­jing Leg­end of ma­nip­u­lat­ing CAR-T da­ta — Gen­script shares nose­dive

Gen­script, the Chi­nese com­pa­ny be­hind overnight CAR-T star Nan­jing Leg­end Biotech, has seen its stock nose­dive af­ter a damn­ing short re­port ques­tioned its da­ta in­tegri­ty, R&D ex­per­tise, safe­ty record and man­u­fac­tur­ing ca­pa­bil­i­ty.

The stock dipped as much as 47% on the Hong Kong Stock Ex­change be­fore trad­ing was sus­pend­ed at around a 26% loss — or $1 bil­lion.

While Gen­script has yet to is­sue an of­fi­cial re­sponse, the com­pa­ny told Na­tion­al Busi­ness Dai­ly that the short re­port “con­tains mul­ti­ple flaws that are in­ac­cu­rate, and the com­pa­ny will pub­lish a clar­i­fi­ca­tion state­ment as soon as pos­si­ble.”

Xi­ao­hu (Frank) Fan

Once a vir­tu­al un­known con­tract re­search or­ga­ni­za­tion, Gen­script came in­to the glob­al spot­light when its sub­sidiary Leg­end pre­sent­ed some jaw-drop­ping re­sults for its BC­MA-tar­get­ing CAR-T at 2017 AS­CO. Then J&J of­fered a high pro­file en­dorse­ment through its Janssen unit by hand­ing $350 mil­lion up­front to part­ner on LCAR-B38M for mul­ti­ple myelo­ma.

But ac­cord­ing to the re­port writ­ten in Chi­nese and at­trib­uted to Flam­ing Re­search — an ob­scure firm whose web­site lists on­ly one re­port on Ti­bet Wa­ter — Leg­end like­ly forged the da­ta, and Janssen missed out on key due dili­gence in haste to catch up with Cel­gene as the two gi­ants fight for dom­i­nance in mul­ti­ple myelo­ma.

Here’s how they got to that con­clu­sion: Leg­end’s CAR-T da­ta came from three “well rec­og­nized hema­tol­ogy hos­pi­tals” in Shang­hai and Jiang­su, and one mediocre hos­pi­tal in Xi’an. But it was the re­searchers in Xi’an who of­fered the most com­pelling da­ta, where­as the da­ta from the oth­er sites didn’t hold up.

“Giv­en that Xi’an da­ta were over­all bet­ter than Shang­hai da­ta, choos­ing to se­lec­tive­ly dis­close Xi’an da­ta is clear­ly fraud­u­lent be­hav­ior,” the re­port reads. “Like­wise, doc­tors in Shang­hai have doubts about the Xi’an da­ta: On one hand Leg­end was more con­cerned with treat­ment ef­fects than safe­ty, on the oth­er the Xi’an hos­pi­tal didn’t have suf­fi­cient record on safe­ty da­ta.”

The in­ci­dent, wide­ly re­port­ed by Chi­nese me­dia, al­so rais­es ques­tions about the volatil­i­ty of the HKEX at a crit­i­cal time as non-rev­enue biotechs start go­ing pub­lic on the ex­change.

Gen­script the CRO was first list­ed in 2015 but got its big break this year in the wake of Leg­end’s stel­lar CAR-T re­sults, surg­ing as much as 500%. Now that its stock is close­ly tied to the per­for­mance of its biotech sub­sidiary, what­ev­er hap­pens here could serve as a cau­tion­ary tale for the pre-rev­enue biotechs that have on­ly re­cent­ly been al­lowed on­to the city’s ex­change.

The 14-page re­port starts with the the­sis that it’s worth less than a quar­ter of its cur­rent price. Aside from is­sues with the da­ta, it high­lights a pa­tient death that oc­curred at a Shang­hai site in 2017, which Gen­script dis­closed but hasn’t fol­lowed up on, as an il­lus­tra­tion of the ther­a­py’s po­ten­tial risk. It fur­ther at­tacks Frank (Xi­ao­hu) Fan, Leg­end’s R&D chief, for his lack of cre­den­tials in drug de­vel­op­ment and the “se­ri­ous chal­lenges” he’s faced in ap­ply­ing for patents — in ad­di­tion to the gen­er­al lack of ex­per­tise in his team.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

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Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Anthony Fauci, NIAID director (AP Images)

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The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.

Florian Brand (L) and Srinivas Rao (ATAI)

Psy­che­del­ic biotech ATAI hopes to ex­pand port­fo­lio through re­search part­ner­ship with Mass Gen­er­al

Psychedelics have made a comeback for mental health research, with companies like startup biotech ATAI Life Sciences raising millions and earning the backing of prominent investors like Peter Thiel, but there’s a hole at the heart of the resurgence: Researchers still don’t fully understand how they work.

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Bomb squad called to As­traZeneca vac­cine plant; Lu­men nabs CARB-X award for low-cost an­tidiar­rheal

A plant located in Wrexham, Wales that is packing the Oxford/AstraZeneca Covid-19 vaccine into vials was surrounded by a bomb squad after officials called police to report a suspicious package.

The alert caused a partial evacuation of the plant, the BBC was among those to report Wednesday. The owner of the plant, British drugmaker Wockhardt UK, said it was cooperating with local authorities and that there were no reports of any injuries.