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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

No­vo Nordisk re­mains un­der UK scruti­ny as MHRA con­ducts its own re­view in 'in­cred­i­bly rare' case

The UK’s Medicines and Healthcare products Regulatory Agency is now reviewing Novo Nordisk’s marketing violation that resulted in its loss of UK trade group membership last week. Novo Nordisk was suspended on Thursday from the Association of the British Pharmaceutical Industry (ABPI) for two years after an investigation by its regulatory arm found the pharma broke its conduct rules.

MHRA said on Tuesday that its review of the Prescription Medicines Code of Practice Authority (PMCPA) investigation is standard practice. An MHRA spokesperson emphasized in an email to Endpoints News that the situation with Novo Nordisk is “incredibly rare” while also noting ABPI took “swift and proportionate action.”

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Andy Plump, Takeda R&D chief (Jeff Rumans for Endpoints News)

What kind of PhI­Ib da­ta is worth $4B cash? Take­da’s Andy Plump has some thoughts on that

A few months back, when Takeda caused jaws to drop with its eye-watering $4 billion cash upfront for a mid-stage TYK2 drug from Nimbus, it had already taken a deep dive on the solid Phase IIb data Nimbus had assembled from its dose-ranging study in psoriasis.

Now, it’s rolling that data out, eager to demonstrate what inspired the global biopharma to go long in a neighboring, but new, disease arena for the pipeline. And the most avid students of the numbers will likely be at Bristol Myers Squibb, who will have a multi-year head start on pioneering the TYK2 space with Sotyktu (deucravacitinib) as Takeda makes its lunge for best-in-class status.

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FTC says patent bat­tle over Parkin­son's drug could have 'sig­nif­i­cant im­pli­ca­tion­s' for pa­tients

The Federal Trade Commission has gotten involved in a patent feud over Supernus’ Parkinson’s drug Apokyn, a case the agency said may have ‘‘significant implications” for patients who rely on the drug.

Sage Chemical won the first generic approval for its Apokyn formulation (also known as apomorphine hydrochloride injection) back in 2022. The non-ergoline dopamine agonist is approved to treat Parkinson’s symptoms during “off episodes,” such as difficulty moving, tremors and intense cramping. However, regulators specified that the approval pertained to the generic drug cartridges only, not the injector pen required for administration.

Growth hor­mone from No­vo Nordisk is in short­age over man­u­fac­tur­ing de­lays

Novo Nordisk’s growth hormone Norditropin is in shortage because of manufacturing delays, according to an FDA site that tracks drug shortages as well as the American Society of Health-System Pharmacists’ shortages list.

The FDA has shortages of the drug listed for its 5, 10, 15 and 30 mg doses, while the pharmacists’ group, also known as ASHP, reported shortages of the same doses, except for the 15 mg version.

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PhRMA calls for more di­verse in­fra­struc­ture up­grades to US emer­gency tri­als frame­work

The White House’s Office of Science and Technology Policy (OSTP) last year sought to find ways to better coordinate large-scale clinical trials in the US — as the UK lead by example during the pandemic — especially for these emergency clinical trials.

The lobbying group PhRMA Tuesday called for more clinical trial diversity in underserved areas, including by making participation less of a burden, and expanding eligibility criteria when appropriate.

FDA in­di­cates will­ing­ness to ap­prove Bio­gen ALS drug de­spite failed PhI­II study

Ahead of Wednesday’s advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show.

Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease.

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President Joe Biden (AP Photo/Susan Walsh)

Biden signs law re­quir­ing more de­clas­si­fi­ca­tions on Covid-19's ori­gins

President Joe Biden yesterday signed into law a bill requiring the Office of the Director of National Intelligence to declassify information on the origins of Covid-19 within 90 days.

The new law directs the federal government to “declassify any and all information relating to potential links between the Wuhan Institute of Virology and the origin of the Coronavirus Disease 2019”, including information regarding researchers at the lab who fell ill in the fall of 2019 like names, symptoms, and job roles.

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Just as pharma marketers finally make moves into TikTok, the threat of a US ban on the social media channel is now looming. Already banned on federal employee phones by an initial Congressional act, more bills and maybe bans are on the way. With rare bipartisan agreement, lawmakers have introduced legislation that would give the US president the power to ban TikTok (although not mentioned by name) and other foreign-owned technology platforms that represent a security threat to the US.

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