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.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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