Feng Zhang, MIT

Broad star Feng Zhang un­veils a new CRISPR plat­form, edit­ing RNA and elim­i­nat­ing Alzheimer's threat — in cells

Broad In­sti­tute star sci­en­tist Feng Zhang is back in the spot­light, adapt­ing CRISPR tech­nol­o­gy in a shift from per­ma­nent­ly edit­ing DNA to re­vis­ing RNA — tem­porar­i­ly if need­ed. And he il­lus­trat­ed the promise of this ap­proach by de­ac­ti­vat­ing APOE4, which may be a tick­ing time bomb for peo­ple at risk of de­vel­op­ing Alzheimer’s.

Jen­nifer Doud­na

CRISPR/Cas9 gene edit­ing tech has tak­en the lab by storm, in part be­cause of the work Zhang and his one-time col­leagues Jen­nifer Doud­na and Em­manuelle Char­p­en­tier ac­com­plished. They’re still scrap­ping over the patents to the orig­i­nal Cas9 work. But Zhang, who found­ed Beam Ther­a­peu­tics with David Liu and Kei­th Joung, has moved on in search of bet­ter tech, and in a pa­per pub­lished in Sci­ence, says they have made re­al progress in switch­ing from DNA to RNA edit­ing.

They call this new ad­vance RES­CUE: RNA Edit­ing for Spe­cif­ic C to U Ex­change. And it builds on RE­PAIR: RNA Edit­ing for Pro­gram­ma­ble A to I.

Us­ing Cas13, Zhang’s team was able to take the APOE4 gene — be­lieved to car­ry the added risk of spurring Alzheimer’s — and changed it to a be­nign APOE2. The RNA ed­i­tors con­vert­ed “the nu­cleotide base ade­nine to in­o­sine, or let­ters A to I. Zhang and col­leagues took the RE­PAIR fu­sion and evolved it in the lab un­til it could change cy­to­sine to uri­dine, or C to U.”

But there are al­so ways to achieve a tem­po­rary change that could ben­e­fit pa­tients with­out cre­at­ing po­ten­tial risks.

Em­manuelle Char­p­en­tier

In a sep­a­rate cell ex­per­i­ment, Zhang and his group were able to or­ches­trate a tran­si­to­ry spike in β-catenin ac­ti­va­tion and cell growth. That kind of tem­po­rary im­pact could erase threats of can­cer, as­so­ci­at­ed with un­con­trolled cell growth while treat­ing wounds.

“To treat the di­ver­si­ty of ge­net­ic changes that cause dis­ease, we need an ar­ray of pre­cise tech­nolo­gies to choose from. By de­vel­op­ing this new en­zyme and com­bin­ing it with the pro­gram­ma­bil­i­ty and pre­ci­sion of CRISPR, we were able to fill a crit­i­cal gap in the tool­box,” says Zhang, the James and Pa­tri­cia Poitras Pro­fes­sor of Neu­ro­science at MIT.

It’s an in­trigu­ing ex­per­i­ment, but don’t look for the ex­per­i­ment in cells to make the leap in­to prac­tice any­time soon. MIT’s Jonathan Gooten­berg summed it up for WBUR:

“It’s a first step in a very large jour­ney. We’re still at the base of the moun­tain, you might say.”

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Michel Vounatsos, Getty Images

UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.