Derek Jantz, Precision Biosciences

Jim Wilson's team hands Pre­ci­sion Bio a big proxy win for its PC­SK9 gene edit­ing tech with 3-year mon­key da­ta

James Wil­son

James Wil­son and his gene edit­ing team at UPenn have pub­lished a new pa­per in­to a one-time PC­SK9 ther­a­py, one that Pre­ci­sion Bio­sciences hopes can turn up the heat on its com­peti­tors at Verve.

Us­ing Pre­ci­sion’s pro­pri­etary AR­CUS gene edit­ing plat­form, Wil­son was able to demon­strate that PC­SK9 pro­tein and LDL cho­les­terol re­duc­tions could be sus­tained in mon­keys for at least three years af­ter treat­ment, Pre­ci­sion an­nounced Fri­day. Re­searchers ad­min­is­tered the ther­a­py to 10 mon­keys back in 2017 and re­port­ed re­duc­tions of up to 85% in PC­SK9 pro­tein lev­els and a 56% re­duc­tion of LDL cho­les­terol lev­els.

Those lev­els are slight­ly low­er than the fig­ures post­ed by Verve last month at JP Mor­gan, when the Sek Kathire­san-led biotech said it ob­served a 61% LDL cho­les­terol re­duc­tion and 89% cut in av­er­age blood PC­SK9 pro­tein lev­el. But Verve’s da­ta was record­ed af­ter on­ly six months — or one-sixth the time of Pre­ci­sion’s.

That dif­fer­ence in time is sig­nif­i­cant be­cause Pre­ci­sion’s mon­keys have had the chance to go through sev­er­al gen­er­a­tions of liv­er cell turnover, and the cho­les­terol and PC­SK9 pro­tein re­duc­tions have re­mained sta­ble, CSO Derek Jantz told End­points News. Liv­er cells, or he­pa­to­cytes, typ­i­cal­ly on­ly live for about 200 days be­fore they die off and are re­plen­ished.

“What we’ve been able to show is that those sub­se­quent gen­er­a­tions of cells are in­her­it­ing the gene ed­it,” Jantz said. “We are be­yond the life­time of a typ­i­cal non-hu­man pri­mate he­pa­to­cyte.”

Fri­day’s study is a fol­low-up from a pa­per pub­lished in 2018, which Jantz said demon­strat­ed short-term ben­e­fits of their gene edit­ing treat­ment. At that time, Pre­ci­sion saw PC­SK9 re­duc­tions of more than 90% at the high­est dose, af­ter which they fell slight­ly over the first nine months when the first liv­er cells were be­ing re­placed.

Since then, the lev­els have plateaued, giv­ing Pre­ci­sion what it says is ear­ly ev­i­dence that the treat­ment can be per­ma­nent. Even more promis­ing is that re­searchers didn’t see any ma­jor safe­ty is­sues man­i­fest in the three years since the mon­keys were dosed, Jantz said.

Pre­ci­sion used its AR­CUS genome edit­ing plat­form, com­ing from a group of North Car­oli­na sci­en­tists, which they claim has a bet­ter way to ac­com­plish DNA hack­ing than the gene edit­ing pro­mot­ed by biotechs work­ing on CRISPR/Cas9 tech­nolo­gies. AR­CUS deals with what’s known as the ARC nu­cle­ase, and the com­pa­ny says it pro­vides a sim­pler, more ef­fec­tive way of com­plet­ing the gene edit­ing process to al­low for low­er costs when pro­duc­tion even­tu­al­ly has to scale up, as well as low­er rates of off-tar­get edit­ing.

AR­CUS can be used to ei­ther in­sert, re­move or re­pair DNA in in vi­vo set­tings. In this in­stance, the PC­SK9 gene was “knocked out,” re­sult­ing in low­er lev­els of the pro­tein, Jantz said.

That’s a dif­fer­ent ap­proach than the one used by Verve, which is aim­ing to uti­lize the next-gen­er­a­tion gene edit­ing tool called base edit­ing. Where­as the first gen­er­a­tion of CRISPR gene edit­ing mol­e­cules would snip the DNA se­quence and let it re­pair on its own, base edit­ing works by con­vert­ing one let­ter on the genome to an­oth­er.

In Verve’s case, re­searchers made a sin­gle change from A to G in the ge­net­ic se­quence of the PC­SK9 gene in the liv­er.

Both com­pa­nies are look­ing at fa­mil­ial hy­per­c­ho­les­terolemia as a po­ten­tial in­di­ca­tion, with Verve aim­ing to dose its first pa­tient in the het­erozy­gous form of the dis­ease some­time in 2022. Pre­ci­sion, how­ev­er, isn’t giv­ing any timeta­bles as to when it could launch an in-hu­man tri­al, with Jantz say­ing any such study is still “a ways away.” Both are aim­ing to re­place chron­ic treat­ments for dis­ease with one-time in­jec­tions.

Though ex­cit­ed by Fri­day’s re­sults, Pre­ci­sion is not tar­get­ing PC­SK9 as its lead pro­gram. That would be an off-the-shelf CAR-T ther­a­py for acute lym­phoblas­tic leukemia and non-Hodgkin lym­phoma, aim­ing to tar­get CD19. The pro­gram read out in­ter­im re­sults from a Phase I/IIa tri­al last De­cem­ber.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.

Photo: Shutterstock

Bio­phar­ma's suc­cess rate in bring­ing drugs to mar­ket has long been abysmal. Can new tools help rewrite that trou­bled past?

In 2011, a team of researchers at British drugmaker AstraZeneca had a problem they were looking to solve.

For years, drug discovery and development were a wasteland for innovation. Novel drugs largely fell into one of two categories — monoclonal antibodies and small molecules — and new therapeutic modalities were hard to come by. After a rush of promising approvals in the late 1990s — including then-Biogen’s CD20 targeting antibody breakthrough Rituxan — the field stagnated and attrition rates stayed sky-high. What exactly is the industry doing wrong? AstraZeneca asked itself.

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