Gene edit­ing stocks get bush­whacked as new stud­ies high­light CRISPR/Cas9 can­cer risks

Gene edit­ing stocks have a habit of run­ning up and down when some new piece of re­search un­der­scores their po­ten­tial or the risks as­so­ci­at­ed with the tech.

To­day the num­bers were plung­ing in­to the red for CRISPR Ther­a­peu­tics $CR­SP, In­tel­lia $NT­LA and Ed­i­tas $ED­IT as some top-lev­el in­ves­ti­ga­tors spot­light­ed a con­nec­tion be­tween CRISPR-Cas9 and an added risk of can­cer as­so­ci­at­ed with the tech­nol­o­gy. And soon af­ter the stud­ies hit, the biotechs in­volved be­gan to strike back at the re­searchers’ con­clu­sions.

Jus­si Taipale

The prob­lem, says Pro­fes­sor Jus­si Taipale, now at the De­part­ment of Bio­chem­istry, Cam­bridge, is that edit­ing cells with p53 is hard be­cause it ac­ti­vates a sys­tem that flags the cell for DNA dam­age. As a re­sults, there’s a nat­ur­al pref­er­ence for cells that lack the p53 path­way, which are more vul­ner­a­ble to can­cer, giv­ing rise to vul­ner­a­ble cell pop­u­la­tions. 

De­press­ing p53 ac­tiv­i­ty in cells may well have the same risks, as they are stripped of their nat­ur­al de­fens­es.

Taipale worked with in­ves­ti­ga­tors at the pres­ti­gious Karolin­s­ka In­sti­tute in Swe­den.

“Al­though we don’t yet un­der­stand the mech­a­nisms be­hind the ac­ti­va­tion of p53, we be­lieve that re­searchers need to be aware of the po­ten­tial risks when de­vel­op­ing new treat­ments,” Taipale says. “This is why we de­cid­ed to pub­lish our find­ings as soon as we dis­cov­ered that cells edit­ed with CRISPR-Cas9 can go on to be­come can­cer­ous.”

Si­mul­ta­ne­ous­ly, a group at the No­var­tis In­sti­tutes for Bio­Med­ical Re­search al­so raised the same is­sue with p53, un­der­scor­ing some of the risks in­volved with CRISPR/Cas9 tech­nol­o­gy and spook­ing in­vestors who were gam­bling that this tech­nol­o­gy will de­liv­er a whole new gen­er­a­tion of drugs.

Dar­ren Grif­fin

Dar­ren Grif­fin, a ge­net­ics ex­pert at Kent Uni­ver­si­ty who was not in­volved in ei­ther study, told Reuters that the study rais­es “rea­son for cau­tion, but not nec­es­sar­i­ly alarm”.

“Al­most any treat­ment that has the pow­er to do good, has the pow­er to do harm and this find­ing should be con­sid­ered in this broad­er con­text,” he added. “As we learn more about the CRISPR-Cas9 sys­tem and how it can be used, this study will in­evitably be con­sid­ered a sig­nif­i­cant find­ing.”

In­tel­lia was one of the first to re­spond to the re­port, and the droop­ing stock price. In an email to me the biotech not­ed:

We’ve ob­served no signs of this type of tox­i­c­i­ty or cells trans­form­ing in­to can­cer or tu­mors in In­tel­lia’s in vi­vo and ex vi­vo pro­grams.

In­tel­lia has not found this type of ef­fect in any of our in vi­vo stud­ies us­ing our lipid nanopar­ti­cle de­liv­ery sys­tem, in­clud­ing our 52-week study of suc­cess­ful TTR knock­down in mice and our on­go­ing stud­ies of non-hu­man pri­mates. For In­tel­lia’s ex vi­vo work, we have achieved ef­fi­cient edit­ing (>90 per­cent) in HSCs and T-cells and have not seen the type of tox­i­c­i­ty or tu­mor­genic­i­ty be­ing re­port­ed in these pa­pers. De­spite ex­tend­ed ob­ser­va­tion in an­i­mals and in vit­ro cul­tures, we have not seen this ef­fect. In­tel­lia’s cur­rent ap­proach­es are di­rect­ed at dif­fer­ent cell types.

CRISPR shares were down 13% Mon­day af­ter­noon, In­tel­lia was off 9% and Ed­i­tas shed 10% of its val­ue.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

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With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

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Rob Davis, Merck CEO

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Merck’s cancer immunotherapy Keytruda notched sales of $20.9 billion in 2022, cementing its status as one of the world’s top-selling drugs. However, it’s far from resting on that accomplishment.

Merck executives touted nine ongoing trials in its annual earnings call on Thursday, including five studies in Phase III, for Keytruda (pembrolizumab) in combination with other immuno-oncology drugs. The trials include combinations with Merck’s own developments as well as other pharma companies’ candidates, including its melanoma collaboration with Moderna and its mRNA technology plus Keytruda, aimed at creating a personalized vaccine treatment to reduce the risk of cancer recurrence or death.

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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

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German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

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Lars Fruergaard Jørgensen, Novo Nordisk CEO (Christopher Goodney/Bloomberg via Getty Images)

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The new prescriptions come on top of the overall momentum of Novo obesity drug sales in 2022, although the then supply-constrained Wegovy was only part of that. Sibling obesity med Saxenda accounted for DKK 10.7 billion ($1.58 billion) of the total DKK 16.9 billion ($2.49 billion), or about 63%, in Novo Nordisk’s reported obesity segment sales.

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CEO Vas Narasimhan underscored Novartis’ upcoming transformation into a “pure-play” company, reiterating across a series of calls — one with reporters, two with investors and analysts — that the new structure would boost its R&D productivity and sharpen its focus on big, new medicines.

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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