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

Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

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Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

UP­DAT­ED: Pfiz­er fields a CRL for a $295M rare dis­ease play, giv­ing ri­val a big head start

Pfizer won’t be adding a new rare disease drug to the franchise club — for now, anyway.

The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

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A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

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Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.

Not cheap­er by the dozen: Bris­tol My­ers be­comes the 12th phar­ma com­pa­ny to re­strict 340B sales

Bristol Myers Squibb recently joined 11 of its peer pharma companies in limiting how many contract pharmacies can access certain drugs discounted by a federal program known as 340B.

Bristol Myers is just the latest in a series of high-profile pharma companies moving in their own direction as the Biden administration’s Health Resources and Services Administration struggles to rein in the drug discount program for the neediest Americans.

Joaquin Duato, J&J CEO (Photo by Charles Sykes/Invision/AP)

New J&J CEO Joaquin Du­a­to promis­es an ag­gres­sive M&A hunt in quest to grow phar­ma sales

Joaquin Duato stepped away from the sideline and directly into the spotlight on Tuesday, delivering his first quarterly review for J&J as its newly-tapped CEO after an 11-year run in senior posts. And he had some mixed financial news to deliver today while laying claim to a string of blockbuster drugs in the making and outlining an appetite for small and medium-sized M&A deals.

Duato also didn’t exactly shun large buyouts when asked about the future of the company’s medtech business — where they look to be in either the top or number 2 position in every segment they’re in — even though the bar for getting those deals done is so much higher.

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Amgen's Twitter campaign #DearAsthma inspired thousands of people to express struggles and frustrations with the disease

Am­gen’s #Dear­Asth­ma spon­sored tweet lands big on game day, spark­ing thou­sands to re­spond

Amgen wanted to know how people with asthma really felt about daily life with the disease. So it bought a promoted tweet on Twitter noting the not-so-simple realities of life with asthma and ended the post with a #DearAsthma hashtag, a megaphone emoji and a re-tweet button.

That was just over one week ago and the responses haven’t stopped. More than 7,000 posts so far on Twitter replied to #DearAsthma to detail struggles of daily life, expressing humor, frustration and sometimes anger. More than a few f-bombs have been typed or gif-ed in reply to communicate just how much many people “hate” the disease.

Roy Baynes, Merck

FDA bats back Mer­ck’s ‘pipeline in a prod­uct,’ de­mands more ef­fi­ca­cy da­ta

Despite some heavy blowback from analysts, Merck execs maintained an upbeat attitude about the market potential of its chronic cough drug gefapixant. But the confidence may be fading somewhat today as Merck puts out news that the FDA is handing back its application with a CRL.

Dubbed by Merck’s development chief Roy Baynes as a “pipeline in a product” with a variety of potential uses, Merck had fielded positive late-stage data demonstrating the drug’s ability to combat chronic cough. The drug dramatically reduced chronic cough in Phase III, but so did placebo, leaving Merck’s research team with a marginal success on the p-value side of the equation.

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