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

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.

At Klick Health’s first Ideas Exchange conference with biotech and pharma industry insiders since before the pandemic began, it was no surprise many conversations included Covid topics. Yet while vaccines and treatments were discussed, so too were the effects on drug development, federal responses, health inequities — and what to do now and next.

George Yancopoulos, chief scientist and cofounder of Regeneron, opened the conference responding to a question from Acorda CEO Ron Cohen about the spotlight on the industry during Covid and some of the “flak” biopharma has taken in the past.