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.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

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AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

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Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

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Peter Greenleaf, Aurinia CEO

Af­ter pass­ing on Ac­celeron, Bris­tol My­ers eyes bolt-on ac­qui­si­tion of au­toim­mune spe­cial­ist — re­port

Bristol Myers Squibb is looking to beef up its autoimmune portfolio by scooping up Aurinia Pharmaceuticals, Bloomberg reported.

The recent overtures to Aurinia, relayed by anonymous insiders, came just as Bristol Myers turned down buyout talks with partners at Acceleron — which Merck ultimately struck a deal to acquire for $11.5 billion. Bristol Myers has reportedly decided to cash out on its minority stake, likely bagging $1.3 billion in the process, while keeping the royalty deals on two of Acceleron’s blood disorder drugs.

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So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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