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

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”