Add one fa­tal flaw to Jiankui He's litany of mis­takes in CRISPR ba­by de­ba­cle

Sci­en­tists the world over have found plen­ty of rea­sons to con­demn their Chi­nese col­league Jiankui He’s ex­per­i­ment with the world’s first CRISPR ba­bies late 2018: The al­leged med­ical need to con­fer HIV im­mu­ni­ty was un­found­ed, the con­sent process seemed du­bi­ous, the ac­tu­al gene edit­ing ap­peared spot­ty, just to name a few. But a new re­search pa­per may have un­cov­ered the most stag­ger­ing of them all.

Two re­searchers at UC Berke­ley has found that the ge­net­ic mu­ta­tion He at­tempt­ed to mim­ic in twins Lu­lu and Nana — known as CCR5-∆32 — is as­so­ci­at­ed with a high­er risk of pre­ma­ture death.

It’s been wide­ly re­port­ed that the mu­ta­tion, which in ef­fect knocked out the CCR5 gene, had al­ready been shown to ren­der peo­ple more sus­cep­ti­ble to the West Nile virus and more like­ly to suf­fer se­ri­ous com­pli­ca­tions, in­clud­ing death, from in­fluen­za. But the over­all ef­fect on mor­tal­i­ty has yet to be es­tab­lished.

By comb­ing through geno­type and death reg­is­ter de­tails of 410,000 in­di­vid­u­als UK Biobank, Berke­ley pro­fes­sor Ras­mus Nielsen and his post­doc Xinzhu Wei found a 21% in­crease in all-cause mor­tal­i­ty rate among peo­ple with two copies of the ∆32 mu­ta­tion, in which 32 base pairs are omit­ted from the gene.

Wei and Nielsen are quick to warn against over­in­ter­pret­ing their find­ings, not least be­cause they on­ly an­a­lyzed genomes of UK vol­un­teers, and they don’t nec­es­sar­i­ly trans­late to East Asians as “the ef­fect of the mu­ta­tion de­pends on the ge­net­ic back­ground and the en­vi­ron­ments,” Wei wrote to Na­tion­al Ge­o­graph­ic.

That said, a sim­i­lar point was al­so made with re­gards to the stud­ies that He cit­ed to jus­ti­fy in­tro­duc­ing the mu­ta­tion in the ba­bies in the first place. Signs that CCR5-∆32 had pro­tec­tive ef­fects against HIV, nat­u­ral­ly ob­served in Eu­ro­pean pop­u­la­tions, spurred him to en­gi­neer their trait in­to the em­bryos that even­tu­al­ly grew in­to twin ba­by girls.

No­tably, He didn’t ex­act­ly recre­ate the ∆32 mu­ta­tion in ei­ther em­bryo. Based on the slides he pre­sent­ed at a con­fer­ence in Hong Kong, Both in­fants ap­peared to still car­ry nor­mal copies of the CCR5 gene, and where the gene edit­ing did work it re­sult­ed in very dif­fer­ent mu­ta­tions whose ef­fects have nev­er been stud­ied.

Nonethe­less, these new find­ings once again lay bare the knowl­edge gap on the con­se­quences — good and bad — of gene vari­a­tions and, thus, the dan­gers of ap­ply­ing gene edit­ing tools on hu­man cells, es­pe­cial­ly when the al­ter­ations can be passed on­to fu­ture gen­er­a­tions as in the case of an em­bryo.

He him­self ex­pressed sec­ond thoughts about his ex­per­i­ment in an email ex­change with Stan­ford Uni­ver­si­ty bioethi­cist William Hurl­but, STAT’s Sharon Be­g­ley re­port­ed.

“I have been think­ing,” He wrote, “I rec­og­nize I pushed too quick­ly in­to a first-of-kind clin­i­cal study with­out the nec­es­sary open di­a­log with reg­u­la­tors, the sci­en­tif­ic com­mu­ni­ty, and the pub­lic.”

As gov­ern­ments and ex­perts rush to pro­pose new reg­u­la­tions on the bound­aries of gene edit­ing, with new stud­ies such as this, the world is fi­nal­ly hav­ing the con­ver­sa­tion that He — now com­plete­ly side­lined and close­ly mon­i­tored by Chi­nese au­thor­i­ties — didn’t have.


Im­age: Jiankui He in No­vem­ber 2018. KIN CHE­UNG for AP PHO­TO

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

David Meline (file photo)

Mod­er­na’s new CFO took a cut in salary to jump to the mR­NA rev­o­lu­tion­ary. But then there’s the rest of the com­pen­sa­tion pack­age

David Meline took a little off the top of his salary when he jumped from the CFO post at giant Amgen to become the numbers czar at the upstart vaccines revolutionary Moderna. But the SEC filing that goes with a major hire also illustrates how it puts him in line for a fortune — provided the biotech player makes good as a promising game changer.

To be sure, there’s nothing wrong with the base salary: $600,000. Or the up-to 50% annual cash bonus — an industry standard — that comes with it. True, the 62-year-old earned $999,000 at Amgen in 2019, but it’s the stock options that really count in the current market bliss for all things biopharma. And there Meline did well.

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Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.