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.

Eli Casdin, Casdin Capital

Eli Cas­din backs Codex­is' plat­form tech with $50M eq­ui­ty buy

About a month af­ter Codex­is notched a deal with No­var­tis $NVS, the Cal­i­for­nia com­pa­ny $CDXS on Thurs­day said long-time in­vestor Cas­din Cap­i­tal is putting up $50 mil­lion in a pri­vate place­ment, which puts the New York-based in­vest­ment firm in con­trol of more than 5% of the pro­tein en­gi­neer­ing play­er’s stock.

Eli Cas­din start­ed his epony­mous in­vest­ment firm in 2012 and dates his re­la­tion­ship with Codex­is back to at least a decade. About three years ago, Cas­din Cap­i­tal be­gan in­vest­ing in the in­dus­tri­al biotech com­pa­ny, af­ter it piv­ot­ed its fo­cus to the life sci­ences — un­der the aus­pices of new chief John Nicols — away from the en­er­gy in­dus­try.

How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

In­vestors pony up $476M for the lat­est round of biotech IPOs to hit the Street

Three biotechs — and a genome se­quenc­ing play­er — have caught the lat­est tide to the Gold Coast of IPOs, round­ing out the first half of 2019 with 23 new drug de­vel­op­ers mak­ing it on Nas­daq.

Most of these com­pa­nies filed their IPOs al­most si­mul­ta­ne­ous­ly, though we’re still wait­ing on word of fel­low class­mate Bridge­Bio’s pric­ing af­ter CEO Neil Ku­mar set the terms at $14 to $16 a share on Mon­day in search of a $240 mil­lion (or so) wind­fall. If he’s suc­cess­ful, that would take the one-week haul past the $700 mil­lion mark, a fresh sign that in­vestors’ en­thu­si­asm for new­ly coined pub­lic biotechs hasn’t cooled.

In starved an­tibi­ot­ic field, Melin­ta soars as FDA grants speedy drug re­view

Such is the state of af­fairs in an­tibi­ot­ic land that the FDA agree­ing to pri­or­i­ty re­view an ap­pli­ca­tion to ex­pand the use of an an­tibi­ot­ic can rock­et up a stock more than two-fold.

On Wednes­day, Melin­ta Ther­a­peu­tics said its ap­proved an­tibi­ot­ic Baxdela had been grant­ed pri­or­i­ty re­view for use in com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia (CAPB). The FDA is ex­pect­ed to make its de­ci­sion by Oc­to­ber 24. Shares of the Con­necti­cut drug­mak­er $ML­NT cat­a­pult­ed, clos­ing up near­ly 224% at $6.41.

Brent Saunders at an Endpoints News event in 2017 — File photo

An­a­lyst call with Al­ler­gan ex­ecs stokes an­tic­i­pa­tion of a plan to split the com­pa­ny in ‘a month or two’

So what’s up at Al­ler­gan?

Ear­li­er this week the ubiq­ui­tous Ever­core ISI an­a­lyst Umer Raf­fat was on the line with com­pa­ny ex­ec­u­tives to probe in­to the lat­est on the num­bers as well as CEO Brent Saun­ders’ re­cent de­c­la­ra­tion that he’d be do­ing some­thing de­fin­i­tive to help long-suf­fer­ing in­vestors who have watched their shares dwin­dle in val­ue.

He came away with the im­pres­sion that a sig­nif­i­cant com­pa­ny split is on the way. And not on some dis­tant time hori­zon.

Robert Forrester, Verastem

Ve­rastem CEO For­rester steps to the ex­it as the board hunts com­mer­cial-savvy ex­ec for the be­lea­guered biotech

Robert For­rester is step­ping down as CEO of Ve­rastem On­col­o­gy $VSTM just 8 months af­ter the com­pa­ny nabbed an ap­proval for du­velis­ib, a PI3K drug with a sto­ried past — and what ap­pears as not much of a fu­ture.

The biotech put out word this morn­ing that For­rester will take an ad­vi­so­ry role with Ve­rastem while COO Dan Pa­ter­son steps up to take charge of the lead­er­ship team and the board looks around for a new CEO.

John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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Ken Frazier appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

Who’s next in line to suc­ceed Ken Fra­zier as CEO of the Keytru­da-blessed Mer­ck?

When Merck waved off a looming forced retirement for Ken Frazier last September, the board cited flexibility in CEO transition as a key factor in the decision. Having Frazier — who’s also chairman of the company — around beyond his 65th birthday in 2019 would ensure they install the best person at the best time, they said.

The board has evidently begun that process with a clear preference for internal candidates, sources told Bloomberg. CFO Robert Davis, chief marketing officer Michael Nally, and chief commercial officer Frank Clyburn are all in the running, according to an insider.

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