In race for in vi­vo sick­le cell cure, In­tel­lia un­veils (very) ear­ly proof-of-con­cept

Ver­tex and CRISPR Ther­a­peu­tics have shown they can use the gene edit­ing tool to cure, for at least a cou­ple years, a hand­ful of pa­tients with sick­le cell dis­ease and are now en­ter­ing late-stage de­vel­op­ment.

It’s a ma­jor ad­vance, but it comes with the same caveats that have plagued oth­er gene ther­a­pies for sick­le cell. You have to give pa­tients what amounts to a bone mar­row trans­plant: a la­bo­ri­ous, ex­pen­sive and oc­ca­sion­al­ly risky pro­ce­dure that in­volves re­mov­ing stem cells from their mar­row, edit­ing them in a fa­cil­i­ty and then re-in­ject­ing them. Any com­pa­ny that could find a way to ed­it cells with a sim­ple IV in­fu­sion could make those old­er ap­proach­es ob­so­lete.

In­tel­lia, one of the first big CRISPR com­pa­nies, un­veiled one new ap­proach to reach­ing that sim­ple IV at a sci­en­tif­ic con­fer­ence Wednes­day. The biotech used cus­tom lipid nanopar­ti­cles — those nowfa­mous tiny bub­bles of fat — to car­ry CRISPR in­to the bone mar­row of mice and ed­it stem cells there. Af­ter re­peat­ed dos­ing, the com­pa­ny’s sci­en­tists said they were able to ed­it more than enough cells to pro­vide a func­tion­al cure for sick­le cell.

John Leonard

“This new da­ta sup­ports the pos­si­bil­i­ty of de­liv­er­ing a safer so­lu­tion to treat blood dis­or­ders, in­clud­ing sick­le cell dis­ease, by avoid­ing the need for bone mar­row trans­plan­ta­tion,” In­tel­lia CEO John Leonard said in a state­ment.

The re­sults pro­vide a (very) ear­ly proof of con­cept for an ap­proach the Gates Foun­da­tion has al­ready bet on. In the fall, they award­ed In­tel­lia a grant of $2.8 mil­lion to de­vel­op their lipid nanopar­ti­cle CRISPR sys­tem for sick­le cell dis­ease and HIV, an­oth­er dead­ly dis­ease that might be cured by edit­ing stem cells in the bone mar­row.

Still, In­tel­lia is far from alone in that race. Their cross-town gene edit­ing ri­vals CRISPR Ther­a­peu­tics al­so re­ceived a sim­i­lar­ly sized grant from the foun­da­tion to de­vel­op lipid nanopar­ti­cles that tar­get the bone mar­row, al­though theirs is ex­clu­sive­ly HIV-fo­cused. And oth­ers, most no­tably Fred Hutch’s Hans Pe­ter-Kiem and Uni­ver­si­ty of Wash­ing­ton’s An­dré Lieber, have gone much fur­ther on an ap­proach that us­es a mod­i­fied virus to de­liv­er a gene for func­tion­ing he­mo­glo­bin di­rect­ly in­to pa­tients’ stem cells, show­ing proof-of-con­cept in mon­keys. A well-heeled biotech called En­so­ma, launched last month, is de­vel­op­ing their ap­proach fur­ther.

In­tel­lia, though, is the on­ly com­pa­ny to date to use lipid nanopar­ti­cles for gene edit­ing or gene ther­a­py in pa­tients. Last year, they start­ed dos­ing pa­tients with a CRISPR ther­a­py meant to knock out the cen­tral gene in a rare liv­er dis­ease.

While gene ther­a­py com­pa­nies have re­lied large­ly on mod­i­fied virus­es to de­liv­er new genes in­to hu­man cells, gene edit­ing com­pa­nies have re­lied much more heav­i­ly on nanopar­ti­cles. CRISPR ma­chin­ery is of­ten too large and clunky to fit in­to those virus­es. And al­though gene ther­a­py com­pa­nies need virus­es to get the ther­a­peu­tic gene to stay in­side a cell for years, CRISPR com­pa­nies just need their ther­a­py to hit once and per­ma­nent­ly al­ter the DNA.

The biggest hur­dle is that most lipid nanopar­ti­cles go di­rect­ly to the liv­er. Com­pa­nies have spent hun­dreds of mil­lions of dol­lars try­ing to de­vel­op ones that are tar­get­ed to oth­er re­gions of the body, such as the brain or mus­cle. Beam Ther­a­peu­tics re­cent­ly spent up to $420 mil­lion to pur­chase an aca­d­e­m­ic spin­out de­vot­ed sole­ly to build­ing tar­get­ed lipid nanopar­ti­cles.

In­tel­lia de­vel­oped lipid nanopar­ti­cles that tar­get the bone mar­row. They pre­dict, based on stud­ies from ear­ly sick­le cell gene ther­a­pies, that they would need to ed­it 20% of cells to of­fer a func­tion­al cure. Af­ter a sin­gle dose in­to mice, they were able to ed­it about 10%.

Un­like oth­er de­liv­ery meth­ods, lipid nanopar­ti­cles can be giv­en re­peat­ed­ly. Af­ter a sec­ond dose, they had edit­ed about 25% of bone mar­row cells. Af­ter the 4th dose, they had edit­ed more than 40% of cells.

In a note to in­vestors, Chardan’s Geu­lah Livshits said the da­ta were quite ear­ly but en­cour­ag­ing.

“We could en­vi­sion such strate­gies emerg­ing in com­ing years and, while many un­knowns re­main, see In­tel­lia’s ear­ly da­ta as a step in that di­rec­tion,” she said.

How one start­up fore­told the neu­ro­science re­nais­sance af­ter '50 years of shit­show'

In the past couple of years, something curious has happened: Pharma and VC dollars started gushing into neuroscience research.

Biogen’s controversial new Alzheimer’s drug Aduhelm has been approved on the basis of removing amyloid plaque from the brain, but the new neuro-focused pharma and biotechs have much loftier aims. Significantly curbing or even curing the most notorious disorders would prove the Holy Grail for a complex system that has tied the world’s best drug developers in knots for decades.

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Bob Bradway, Amgen CEO (Scott Eisen/Bloomberg via Getty Images)

Am­gen bel­lies back up to the M&A ta­ble for an­oth­er biotech buy­out, this time with a $2.5B deal for an an­ti­body play­er fo­cused on PS­MA

Five months after Amgen CEO Bob Bradway stepped up to the M&A table and acquired Five Prime for $1.9 billion, following up with the smaller Rodeo acquisition, he’s gone back in for another biotech buyout.

This time around, Amgen is paying $900 million cash while committing up to $1.6 billion in milestones to bag the privately held Teneobio, an antibody drug developer that has expertise in developing new bispecifics and multispecifics. In addition, Amgen cited Teneobio’s “T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform.”

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Ryan Watts, Denali CEO

De­nali slips as a snap­shot of ear­ly da­ta rais­es some trou­bling ques­tions on its pi­o­neer­ing blood-brain bar­ri­er neu­ro work

Denali Therapeutics had drummed up considerable hype for their blood-brain barrier technology since launching over six years ago, hype that’s only intensified in the last 14 months following the publications of a pair of papers last spring and proof of concept data earlier this year. On Sunday, the South San Francisco-based biotech gave the biopharma world the next look at in-human data for its lead candidate in Hunter syndrome.

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Why is On­col­o­gy Drug De­vel­op­ment Re­search Late to the Dig­i­tal Bio­mark­ers Game?

During the recent Annual ASCO Meeting, thousands of cancer researchers and clinicians from across the globe joined together virtually to present and discuss the latest findings and breakthroughs in cancer research and care. There were more than 5000+ scientific abstracts presented during this event, yet only a handful involved the use of motion-tracking wearables to collect digital measures relating to activity, sleep, mobility, functional status, and/or quality of life. Although these results were a bit disappointing, they should come as no surprise to those of us in the wearable technology field.

Art Levinson (Calico)

Google-backed Cal­i­co dou­bles down on an­ti-ag­ing R&D pact with Ab­b­Vie as part­ners ante up $1B, start to de­tail drug tar­gets

Seven years after striking up a major R&D alliance, AbbVie and Google-backed anti-aging specialist Calico are doubling down on their work with a joint, $1 billion commitment to continuing their work together. And they’re also beginning to offer some details on where this project is taking them in the clinic.

According to their statement, each of the two players is putting up $500 million more to keep the labs humming.

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Busi­ness­es and schools can man­date the use of Covid-19 vac­cines un­der EUAs, DOJ says

As public and private companies stare down the reality of the Delta variant, many are now requiring that their employees or students be vaccinated against Covid-19 prior to attending school or to returning or starting a new job. Claims that such mandates are illegal or cannot be used for vaccines under emergency use authorizations have now been dismissed.

Setting the record straight, the Department of Justice on Monday called the mandates legal in a new memo, even when used for people with vaccines that remain subject to EUAs.

Ugur Sahin, BioNTech CEO (Bernd von Jutrczenka/dpa via AP Images)

BioN­Tech is spear­head­ing an mR­NA vac­cine de­vel­op­ment pro­gram for malar­ia, with a tech trans­fer planned for Africa

Flush with the success of its mRNA Covid-19 vaccine, BioNTech is now gearing up for one of the biggest challenges in vaccine development — which comes without potential profit.

The German mRNA pioneer says it plans to work on a jab for malaria, then transfer the tech to the African continent, where it will work with partners on developing the manufacturing ops needed to make this and other vaccines.

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No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Andrea Pfeifer, AC Immune CEO (AC Immune)

Look­ing to repli­cate Covid-19 suc­cess in neu­ro, BioN­Tech back­ers bet on AC Im­mune and its new­ly-ac­quired Parkin­son's vac­cine

The German billionaires behind BioNTech have found a new vaccine project to back.

Through their family office Athos Service, twin brothers Thomas and Andreas Strüngmann are leading a $25 million private placement into Switzerland’s AC Immune — which concurrently announced that it’s shelling out $58.7 million worth of stock to acquire Affiris’ portfolio of therapies targeting alpha-synuclein, including a vaccine candidate, for Parkinson’s disease.