Park­er In­sti­tute sci­en­tists her­ald a cell ther­a­py break­through in the lab, us­ing next-gen CRISPR tech to en­gi­neer T cells

The two pi­o­neer­ing CAR-T ther­a­pies on the mar­ket — Kym­ri­ah and Yescar­ta — re­ly on vi­ral vec­tors to com­plete the en­gi­neer­ing work need­ed to make a can­cer pa­tient’s T cells in­to a ther­a­py. But a group of Park­er In­sti­tute for Can­cer Im­munother­a­py-backed sci­en­tists at UCSF and UCLA say they have per­fect­ed a new ap­proach us­ing CRISPR gene edit­ing tech that they be­lieve will trans­form the field — open­ing the door to a range of cell ther­a­pies that can be built and man­u­fac­tured far more eas­i­ly than the first-gen crowd.

An­toni Ribas

There’s noth­ing new about CRISPR, of course. The sim­ple, some­what blunt gene edit­ing tech­nol­o­gy — gen­er­al­ly fo­cused on cut­ting in­to genes while strug­gling with past­ing DNA — has tak­en aca­d­e­m­ic labs, and quite a few com­mer­cial ones, by storm in re­cent years. But the sci­en­tists in­volved in this project, in­clud­ing not­ed UCLA re­searcher An­toni Ribas, say they’ve come up with some new tech­niques that could make it a wide­ly used al­ter­na­tive to vi­ral vec­tors — which have some­times been in short sup­ply.

Fred Rams­dell

And they say it fits all the hall­marks of a tech ad­vance: Faster, bet­ter, cheap­er.

“What takes months or even a year may now take a cou­ple weeks us­ing this new tech­nol­o­gy,” not­ed Fred Rams­dell, vice pres­i­dent of re­search at PI­CI. “If you are a can­cer pa­tient, weeks ver­sus months could make a huge dif­fer­ence.”

The same goes for the com­pa­nies in­volved.

The re­searchers say this new ap­proach makes it pos­si­ble to in­sert long stretch­es of DNA in­to genes, open­ing the door to more pre­cise ther­a­pies that could be far more ef­fec­tive in tack­ling can­cer or some oth­er T cell tar­get­ed dis­ease.

Alex Mar­son

Up to now, says Alex Mar­son, as­so­ciate pro­fes­sor of mi­cro­bi­ol­o­gy and im­munol­o­gy at UCSF, CRISPR has been ef­fec­tive in knock­ing genes out — by cut­ting and in­ter­rupt­ing. “You could change a few nu­cleotides at a time,” he not­ed, “but if you put in big­ger da­ta, it would kill the cells.”

This new de­vel­op­ment of theirs us­es elec­tro­po­ra­tion to con­di­tion cell mem­branes and has been used in the lab to go much fur­ther — not just past­ing in­to ran­dom places, but be­ing far more pre­cise. 

“This is sort of a flex­i­ble thing to change the way T cells work,” Mar­son adds, and the teams in­volved used it in the lab to work ex vi­vo on a rare and se­vere form of pe­di­atric au­toim­mune dis­ease, cor­rect­ing mu­ta­tions. A sec­ond project used the tech­nol­o­gy to cre­ate a new T cell ther­a­py for melanoma, suc­cess­ful­ly test­ing it in mice.

Theo Roth

Now the fo­cus will shift to mov­ing this in­to hu­mans.

“This is some­thing we’re very ac­tive­ly work­ing to­ward now,” says Mar­son, who’s pur­su­ing con­ver­sa­tions with the FDA as well as com­mer­cial part­ners to lay out the next steps of get­ting this moved to­ward the clin­ic.

“There has been thir­ty years of work try­ing to get new genes in­to T cells,” said UCSF stu­dent and lead au­thor Theo Roth, who’s been do­ing much of the fine tun­ing work in the lab. “Now there should no longer be a need to have six or sev­en peo­ple in a lab work­ing with virus­es just to en­gi­neer T cells, and if we be­gin to see hun­dreds of labs en­gi­neer­ing these cells in­stead of just a few, and work­ing with in­creas­ing­ly more com­plex DNA se­quences, we’ll be try­ing so many more pos­si­bil­i­ties that it will sig­nif­i­cant­ly speed up the de­vel­op­ment of fu­ture gen­er­a­tions of cell ther­a­py.”

Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

FDA side­lines Paul Hud­son's $3.7B MS drug af­ter es­tab­lish­ing link to liv­er dam­age

One of Sanofi CEO Paul Hudson’s top picks in the pipeline — picked up in a $3.7 billion buyout 2 years ago — has just been sidelined in the US by a safety issue.

The pharma giant put out word early Thursday that the FDA has put their Phase III studies of tolebrutinib in multiple sclerosis and myasthenia gravis on partial clinical hold, halting enrollment and suspending dosing for patients who have been on the drug for less than 60 days. Patients who have completed at least 60 days of treatment can continue therapy as researchers explore a “limited” — but unspecified in Sanofi’s statement — number of cases of liver injury.

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Bo Cumbo, AavantiBio CEO

Scoop: A small gene ther­a­py biotech, flush with ex-Sarep­ta and blue­bird lead­ers, guts CMC

En route to entering the clinic with its first AAV-based gene therapy for a rare neuromuscular disease, AavantiBio has let go of 30 employees, Endpoints News has learned.

The move comes after a year stacking its executive bench with ex-Sarepta and bluebird bio leaders and inking multiple partnerships with the likes of Aldevron, Catalent and Resilience. The biotech also formed a scientific advisory board in February.

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Emer Cooke, ICRMA chair (AP Photo/Geert Vanden Wijngaert)

ICM­RA to launch sev­er­al reg­u­la­to­ry pi­lot pro­grams cen­tered around man­u­fac­tur­ing in­spec­tions

As regulatory agencies look to catch up on inspections amid the Covid-19 pandemic, ICMRA is unveiling several pilot programs to address industry applications and inspections.

ICMRA, which is made up of the world’s top drug regulators, is launching multiple pilot programs, including two regulatory pilots addressing facility inspections for chemistry and manufacturing controls (CMC) and post-approval change (PAC) submission assessments and related regulatory actions.

Man­u­fac­tur­ing Roundup: Teru­mo BCT part­ners with Bio­Bridge sub­sidiary to man­u­fac­ture cell and gene ther­a­pies; WuXi STA opens plant for HPA­PI pro­duc­tion

As the manufacturing of cell and gene therapies is ramping up and companies are starting to invest in their manufacturing capabilities, Terumo Blood and Cell Technologies have formed a partnership to stay in the game.

According to the company, it has signed a new collaborative agreement with GenCure, a subsidiary of BioBridge Global, to extend and unify cell and gene therapy manufacturing solutions.

No­var­tis to re­sume the pro­duc­tion of two ra­di­oli­gand ther­a­pies af­ter re­solv­ing qual­i­ty is­sues

Earlier this year, Novartis touted its radioligand as a major piece to counter competition in the cancer space. However, the physical production of its products has had anything but a smooth ride.

In May, Novartis had to suspend production of Lutathera and Pluvicto, its two primary radiotherapies. According to the company, this was done out of an abundance of caution as a result of potential quality issues identified in its manufacturing. The production suspension impacts the commercial and clinical trial supply of the products.

Roche, Pfiz­er top list of ESG lead­ers in pa­tient group­s' view, but many still think phar­mas can do bet­ter

The rise of pharma environmental, social and governance (ESG) efforts in the past two years has been meteoric as investors turn their attention to sustainable funding. However, investors aren’t the only ones watching. Patients are beginning to tune into pharmas’ ESG promises too.

Patient advocacy groups familiar with ESG regard it as an important issue and want to be included in helping pharma companies set ESG policies and targets, according to a new report from PatientView. That’s quite different from what the investment community wants across a variety of Gartner’s defined financial, competitive, strategic and perception goals.

Kate Haviland, Blueprint Medicines CEO

What bear mar­ket? Blue­print lines up $1.25B to ex­pand la­bels, maybe tack on more drugs

As it works to pad the case for expanding its Ayvakit and Gavreto labels, Blueprint Medicines has lined up $1.25 billion in funding, with some of that money seemingly earmarked for acquisitions or pipeline expansion projects.

Following the likes of BioCryst, Cytokinetics and MorphoSys, Blueprint is aiming to monetize the royalties of its RET+ non-small cell lung cancer and thyroid cancer drug Gavreto with Royalty Pharma. The investment group will dole out $175 million upfront and might tack on another $165 million in biobucks as part of Blueprint’s royalties receivable from net sales of the drug by Roche outside the US, sans China.

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FDA slaps warn­ing let­ter on Min­neso­ta API fa­cil­i­ty af­ter em­ploy­ee de­stroys clean­ing log

A manufacturing facility belonging to the Netherlands-based API producer Fagron Group has entered the FDA’s crosshairs after an employee destroyed a cleaning log, among other violations.

One of its plants in Saint Paul, MN received a warning letter on June 14, following an inspection last November that uncovered cross-contamination concerns.

“In your response, you provided a follow-up cleaning validation report in which you only assessed the carryover of niacin swab samples but not progesterone, which was included in your initial cleaning validation,” FDA says in the letter. “The lack of progesterone (b)(4) [commercially confidential information] is concerning considering the failing residue results you provided to investigators would yield unacceptable levels of progesterone cross-contamination.”

Albert Bourla (Photo by JOHN THYS/POOL/AFP via Getty Images)

As boost­er sea­son awaits, US re-ups sup­ply of Pfiz­er Covid-19 vac­cine with new $3.2B deal

The US government said late Wednesday that it will pay Pfizer and its partner BioNTech $3.2 billion upon receipt of the first 105 million Covid-19 vaccine doses, potentially the new Omicron-adapted boosters pending EUA.

Under this agreement, the US government also has the option to purchase up to 195 million additional doses, bringing the total number of potential new doses to 300 million. The US has now spent almost $15 billion on Pfizer’s Covid-19 vaccine.