Can virus-like par­ti­cles un­leash a new wave of CRISPR treat­ments?; Fo­s­un Phar­ma and In­sil­i­co team up in AI dis­cov­ery deal

The biggest chal­lenges in genome edit­ing to­day have a lot less to do with how to build tools that can cut, paste or rewrite DNA and a lot more to do with how to get the tools we have to the right parts of the body.

One method is to em­ploy the vi­ral vec­tors com­mon­ly used in gene ther­a­py, but CRISPR-Cas9 sys­tems are of­ten too large and cum­ber­some to fit in­side these virus­es, which al­so come with their own safe­ty is­sues. Vi­ral vec­tors al­so leave the genome-edit­ing tool per­ma­nent­ly ex­pressed in­side cells, even af­ter it’s made the re­quired ed­it, po­ten­tial­ly lead­ing to un­want­ed changes and oth­er types of cell dam­age.

An­oth­er is to use the lipid-nanopar­ti­cles, or LNPs, made fa­mous in mR­NA Covid-19 vac­cines. One com­pa­ny, In­tel­lia, has al­ready done so ef­fec­tive­ly, but it’s still dif­fi­cult to tar­get these par­ti­cles any­where but the liv­er.

In the last cou­ple of years, though, re­searchers from lead­ing CRISPR labs have ze­roed in on an­oth­er ap­proach: Virus-like par­ti­cles, or VLPs. Orig­i­nal­ly — and still — used as a vac­cine plat­form, VLPs are par­ti­cles that look like a virus and can, when en­gi­neered a cer­tain way, en­ter a wide va­ri­ety of cells as virus­es do but don’t ac­tu­al­ly con­tain any ge­net­ic ma­te­r­i­al.

As a Texas Tech lab showed in 2016, you can en­gi­neer HIV-like par­ti­cles that de­liv­er Cas9 in­to T cells with min­i­mal off-tar­get ef­fects. Jen­nifer Doud­na’s group and oth­ers have since demon­strat­ed the same, large­ly with an eye to­ward mak­ing CAR-T can­cer ther­a­pies or a sick­le cell gene ther­a­py that can be giv­en by sim­ple in­fu­sion, in­stead of through a cost­ly and in­ten­sive pro­ce­dure.

Large­ly, though, these VLPs have been in­ef­fi­cient, edit­ing on­ly a small num­ber of the tar­get­ed cells. But on Tues­day in Cell, David Liu’s lab at the Broad In­sti­tute showed they en­gi­neered VLPs that can de­liv­er base ed­i­tors with sig­nif­i­cant­ly im­proved ef­fi­cien­cy.

Al­though the work re­mains quite ear­ly, they showed they could knock down a key gene in liv­er cells in mice at sim­i­lar lev­els to what Verve Ther­a­peu­tics showed with an ex­per­i­men­tal LNP-de­liv­ered heart dis­ease treat­ment. Po­ten­tial­ly more im­pact­ful­ly, they were able to show edit­ing in the cen­tral ner­vous sys­tem and eye, nei­ther of which can be treat­ed with the cur­rent gen­er­a­tion LNPs.

“These re­sults es­tab­lish eVLPs as promis­ing ve­hi­cles for ther­a­peu­tic macro­mol­e­cule de­liv­ery that com­bine ad­van­tages of both vi­ral and non-vi­ral de­liv­ery,” Liu said in an email. — Ja­son Mast

Fo­s­un Phar­ma and In­sil­i­co team up in AI dis­cov­ery deal

Two Asian biotechs an­nounced a part­ner­ship this morn­ing — fo­cus­ing on four bi­o­log­i­cal tar­gets.

In­sil­i­co will re­ceive $13 mil­lion up­front from Fo­s­un Phar­ma for the R&D col­lab­o­ra­tion projects as part of the deal, which in­cludes co-de­vel­op­ment of In­sil­i­co’s QPCTL pro­gram, po­ten­tial mile­stone-based pay­ments, and shar­ing com­mer­cial­iza­tion prof­its from the QPCTL pro­gram. In ad­di­tion, Fo­s­un will make an eq­ui­ty in­vest­ment of an undis­closed amount in­to In­sil­i­co.

The col­lab­o­ra­tion takes shape on two “tracks:” One, In­sil­i­co will take re­spon­si­bil­i­ty for de­liv­er­ing a pre­clin­i­cal can­di­date for the QPCTL pro­gram and ad­vanc­ing it to the IND stage. Af­ter which, Fo­s­un Phar­ma will take the can­di­dates, con­duct clin­i­cal tri­als and co-de­vel­op the can­di­date glob­al­ly.

On the sec­ond track, Fo­s­un will nom­i­nate four ther­a­peu­tic tar­gets to be as­sessed by In­sil­i­co’s AI plat­form and R&D team, who are re­spon­si­ble for ad­vanc­ing drug can­di­dates to the IND stage.

As part of the col­lab­o­ra­tion, Fo­s­un will se­cure ac­cess to In­sil­i­co’s plat­forms in or­der to ad­vance their own in­ter­nal AI-pow­ered dis­cov­ery and de­vel­op­ment ef­forts. — Paul Schloess­er

Al­lo­gene strikes cell ther­a­py deal with Swiss biotech An­tion Bio­sciences 

Days af­ter the FDA lift­ed its hold on Al­lo­gene’s off-the-shelf CAR-Ts, the com­pa­ny has more good news to share in the cell ther­a­py space.

Al­lo­gene has inked a deal with Swiss biotech An­tion Bio­sciences for its mi­croR­NA (miR­NA) tech­nol­o­gy to ad­vance mul­ti­plex gene si­lenc­ing as an ad­di­tion­al tool for mak­ing next-gen al­lo­gene­ic CAR-Ts, the part­ners an­nounced on Tues­day.

The South San Fran­cis­co-based com­pa­ny is putting down an undis­closed amount of cash up­front, plus an eq­ui­ty in­vest­ment, mile­stones, and a sin­gle-dig­it roy­al­ty on sales. In re­turn, An­tion will col­lab­o­rate with Al­lo­gene on on­col­o­gy prod­ucts for “a de­fined pe­ri­od,” and Al­lo­gene gets the glob­al com­mer­cial­iza­tion rights to any prod­ucts de­vel­oped us­ing An­tion’s tech­nol­o­gy.

An­tion says the plat­form, dubbed miCAR, was shown in pre­clin­i­cal stud­ies to si­lence mul­ti­ple gene tar­gets in a sin­gle step and has the po­ten­tial for broad ap­pli­ca­tion across cell and gene en­gi­neer­ing.

“We are ex­cit­ed to be work­ing with An­tion to ex­plore how their miCAR tech­nol­o­gy may ad­vance and ac­cel­er­ate Al­lo­gene’s re­search ef­forts aimed at cre­at­ing best in class al­lo­gene­ic cell ther­a­pies,” Rafael Ama­do, Al­lo­gene’s CMO and ex­ec­u­tive VP of R&D, said in a state­ment.

Late last week, the FDA agreed to lift the hold it had placed on Al­lo­gene’s full set of off-the-shelf CAR-Ts af­ter ev­i­dence of chro­mo­so­mal changes in one of the pa­tients trig­gered a safe­ty alert. CEO David Chang said in an in­ter­view that the com­pa­ny worked through the last 3 months with reg­u­la­tors to ze­ro in on the ex­act trig­ger of the chro­mo­so­mal mu­ta­tions, and de­ter­mined that the drug wasn’t in­volved. — Nicole De­Feud­is 

Less than a month af­ter a PhI­II flop, Aldeyra re­leas­es new PhII da­ta back­ing its dry eye can­di­date

Aldeyra took a big hit at the end of last year when its dry eye can­di­date re­prox­alap missed the pri­ma­ry end­point in a topline Phase III read­out. Now, the com­pa­ny’s back with sep­a­rate Phase II da­ta that sug­gest the so­lu­tion can con­tend with No­var­tis’ cur­rent­ly ap­proved Xi­idra.

Pa­tient-re­port­ed oc­u­lar dis­com­fort and itch­ing were sta­tis­ti­cal­ly low­er in the re­prox­alap group than the Xi­idra group, Aldeyra an­nounced on Tues­day. While the com­pa­ny didn’t re­lease any hard num­bers, it did say dis­com­fort and itch­ing reached p-val­ues of 0.002 and 0.01, re­spec­tive­ly.

“The com­bi­na­tion of rapid ac­tiv­i­ty and im­proved tol­er­a­bil­i­ty ev­i­denced by re­prox­alap in clin­i­cal test­ing has the po­ten­tial to ad­dress sig­nif­i­cant com­pli­ance is­sues with cur­rent­ly avail­able ther­a­py, the me­di­an dis­con­tin­u­a­tion rates of which are ap­prox­i­mate­ly one month,” CEO Todd Brady said in a state­ment.

While re­prox­alap met the pri­ma­ry end­point of oc­u­lar red­ness in a dif­fer­ent Phase II tri­al, the end­point didn’t reach sta­tis­ti­cal sig­nif­i­cance in the Phase III TRAN­QUIL­I­TY read­out, Aldeyra an­nounced at the end of De­cem­ber. It did, how­ev­er, meet the sec­ondary end­point for dry eye dis­ease based on the Schirmer test, which de­ter­mines whether a pa­tient’s eye pro­duces enough tears.

The Schirmer test has been ac­cept­ed by the FDA as part of the ba­sis for ap­proval of oth­er dry eye prod­ucts, Aldeyra said. The Lex­ing­ton, MA-based com­pa­ny is go­ing forth with an­oth­er Phase III study, dubbed TRAN­QUIL­I­TY-2, but it’s mod­i­fy­ing the tri­al so that the pri­ma­ry end­point will be met if sta­tis­ti­cal sig­nif­i­cance is achieved in ei­ther oc­u­lar red­ness or the Schirmer test. — Nicole De­Feud­is

On­col­o­gy di­ag­nos­tics biotech gets ma­jor Roche in­vest­ment — to the tune of $290 mil­lion

Mul­ti­omics biotech Freenome an­nounced a sub­stan­tial in­vest­ment from Roche this morn­ing, send­ing their to­tal cap­i­tal raised over the $1 bil­lion mark.

Roche in­vest­ed $290 mil­lion in­to the Cal­i­for­nia biotech, bring­ing Freenome’s to­tal fund­ing to more than $1.1 bil­lion since the com­pa­ny was found­ed in 2014. This cash in­fu­sion fol­lows Freenome’s re­cent Se­ries D fi­nanc­ing of $300 mil­lion last month.

The com­pa­ny was ex­tend­ing its mul­ti­omics plat­form from the raise last month — adding bio­mark­ers for oth­er can­cer types cur­rent­ly em­bed­ded to de­vel­op tests in new in­di­ca­tions and re­cent­ly pre­sent­ed promis­ing da­ta in the de­tec­tion of pan­cre­at­ic can­cer.

Next month, Freenome will ex­pand and launch ad­di­tion­al mul­ti-can­cer clin­i­cal stud­ies fo­cused on more tai­lored bas­kets of screen­ing tests, based on an in­di­vid­ual’s risk.

“With Roche’s in­vest­ment and ex­per­tise, we’ll be able to fur­ther ac­cel­er­ate and aug­ment the de­vel­op­ment of our plat­form to test for ad­di­tion­al can­cers, and ex­pand our re­al-world da­ta pro­grams,” said Freenome’s CEO Mike Nolan in a state­ment. — Paul Schloess­er

Illustration: Assistant Editor Kathy Wong for Endpoints News

How Pur­due's $272M ad­dic­tion pay­out fund­ed a new home for its dis­card­ed non-opi­oid re­search

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

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President Joe Biden at the State of the Union address with Vice President Kamala Harris and House Speaker Kevin McCarthy (Patrick Semansky/AP Images)

The drug pric­ing pres­i­dent: Biden warns of ve­to for any IRA re­peal at­tempts

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

Rupert Vessey, Bristol Myers Squibb head of research and early development

Up­dat­ed: R&D tur­bu­lence at Bris­tol My­ers now in­cludes the end of a $650M al­liance and the de­par­ture of a top re­search cham­pi­on

This morning biotech Dragonfly put out word that Bristol Myers Squibb has handed back all rights to its IL-12 clinical-stage drug after spending $650 million to advance it into the clinic.

The news arrives amid a turbulent R&D stage for the pharma giant, which late last week highlighted Rupert Vessey’s decision to depart this summer as head of early-stage R&D following a crucial three-year stretch after he jumped to Bristol Myers in the big Celgene buyout. During that time he struck a series of deals for Bristol Myers, and also shepherded a number of Celgene programs down the pipeline, playing a major role for a lineup of biotechs which depended on him to champion their drugs.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

Drag­on­fly chief: Bris­tol My­ers shouldn’t blame IL-12’s clin­i­cal per­for­mance for de­ci­sion to scrap the deal — eco­nom­ics played a key role

Bristol Myers Squibb says the IL-12 drug they were developing out of Dragonfly Therapeutics was scrubbed from the pipeline for a simple reason: It didn’t measure up on clinical performance.

But Bill Haney, the CEO of Dragonfly, is taking issue with that.

The early-stage drug, still in Phase I development, has passed muster with Bristol Myers’ general clinical expectations, advancing successfully while still in Phase I, he says.

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Utpal Koppikar, new Verily CFO

Ex­clu­sive: Ver­i­ly wel­comes Atara Bio­ther­a­peu­tics vet­er­an as new CFO

Verily, Alphabet’s life sciences outfit, has plucked a new CFO from the ranks of Atara Biotherapeutics, the company announced on Wednesday.

Utpal Koppikar joins Verily after a nearly five-year stint as CFO and senior VP at Atara, though his résumé also boasts roles at Gilead and Amgen.

The news follows a major reshuffling at Verily, including several senior departures earlier this year and a round of layoffs.

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Singer Nick Jonas is back at work for Dexcom, this time for its new G7 glucose monitor.

Dex­com's spokescelebri­ty Nick Jonas re­turns to Su­per Bowl in new glu­cose mon­i­tor com­mer­cial

Dexcom is going back to the Super Bowl with its pop singer and patient spokesperson Nick Jonas. Jonas takes center stage as the lone figure in the 30-second commercial showcasing Dexcom’s next-generation G7 continuous glucose monitoring (CGM) device.

Jonas’ sleight-of-hand tricks populate the commercial — he pinches his empty fingers together and pops them open to reveal the small CGM — even as he ends the ad, saying, “It’s not magic. It just feels that way.” Jonas then disappears in a puff of smoke.

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Richard Francis, newly-appointed Teva CEO (Novartis via Facebook)

New Te­va CEO Richard Fran­cis repri­or­i­tizes to 'get back to growth'

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.

FDA Commissioner Robert Califf on Capitol Hill, Feb. 8, 2023 (Drew Angerer/Getty Images)

FDA com­mis­sion­er floats ideas on how to bet­ter han­dle the pan­dem­ic

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

Sanofi is renewing its #VaccinesForDreams campaign with more stories, such as Juan's in Argentina (Sanofi)

Sanofi re­news so­cial cam­paign to re­mind that vac­cines let peo­ple ‘Dream Big’

Sanofi is highlighting people’s dreams — both big and small — to make the point that vaccines make them possible.

The renewed “Dream Big” global social media campaign’s newest dreamer is Juan, a teacher in the Misiones rainforest in Argentina whose story is told through videos on Instagram and Sanofi’s website with the hashtag #VaccinesForDreams.

The campaign ties to Sanofi’s broader umbrella initiative “Vaccine Stories” to promote the value of vaccines and drive awareness of the need for improved vaccination coverage.

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