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.”

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

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Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

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Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

Some Celgene shareholders aren’t happy with how Bristol Myers Squibb’s takeover went down.

On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

When Bristol Myers put down $74 billion to scoop up Celgene back in 2019, liso-cel — the CAR-T lymphoma treatment now marketed as Breyanzi — was supposedly one of the centerpieces of the deal. After going back and forth on negotiations for about six months, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date.

David Hung, Nuvation Bio president and CEO (Nuvation Bio)

FDA places par­tial clin­i­cal hold on David Hung biotech af­ter cer­tain can­cer pa­tients ex­pe­ri­ence eye in­flam­ma­tion

Two and a half years after setting out on another foray into oncology R&D, a biotech headed by David Hung — of Medivation fame — has run into its first setback.

San Francisco-based Nuvation Bio announced early Monday the FDA placed a partial clinical hold on a Phase I dose-escalation study of NUV-422, its CDK inhibitor program for certain types of solid tumors. The trial began enrolling patients in December 2020, and, according to Nuvation, researchers were in the middle of exploring dose escalation and defining the maximum dose tolerable in patients.