In an­oth­er CRISPR first, Penn re­searchers dose US can­cer pa­tients with gene-edit­ed T cell ther­a­py

CRISPR has been test­ed in US pa­tients for the first time — but per­haps not in the man­ner you imag­ined.

The Uni­ver­si­ty of Penn­syl­va­nia has led the way dos­ing two pa­tients with re­lapsed can­cers — one with mul­ti­ple myelo­ma and one with sar­co­ma — with a T cell ther­a­py in which the T cell re­cep­tor and PD-1 pro­tein are edit­ed out.

Us­man “Oz” Azam

Fund­ing for the tri­al came part­ly from Tmu­ni­ty, a biotech co-found­ed by Penn’s CAR-T vi­sion­ary Carl June and helmed by No­var­tis vet Us­man “Oz” Azam. Park­er In­sti­tute for Can­cer Im­munother­a­py, an ear­ly in­vestor in Tmu­ni­ty, is al­so bankrolling the tri­al. A Penn spokesper­son con­firmed the news, which was first re­port­ed by NPR.

The ba­sic idea here is not un­like CAR-T, ex­cept with dif­fer­ent el­e­ments and tech­nolo­gies: Take a pa­tient’s T cells, en­gi­neer it to ex­press NY-ESO-1 TCR, while elim­i­nat­ing TCR and PD-1 orig­i­nal­ly on the sur­face us­ing CRISPR.

A group of UCLA and UCSF sci­en­tists backed by the Park­er In­sti­tute has been study­ing new tech­niques to get new genes in­to T cells — not just elim­i­nat­ing them — with CRISPR.

That’s not the most straight­for­ward way of ap­ply­ing the gene edit­ing tech, which has en­ticed oth­er drug de­vel­op­ers with the po­ten­tial to el­e­gant­ly fix ge­net­ic er­rors lead­ing to dis­ease. But it does speak to the ver­sa­til­i­ty of CRISPR, now a pop­u­lar­ized tool that’s spawned up­starts rang­ing from di­ag­nos­tics to tar­get­ed bac­te­ria erad­i­ca­tion.

Carl June

Nev­er­the­less, the trio of CRISPR pi­o­neers as­so­ci­at­ed — Ed­i­tas Med­i­cines, In­tel­lia Ther­a­peu­tics and CRISPR Ther­a­peu­tics — re­main the ones to watch for first-in-hu­man test­ing. In fact, just two months ago CRISPR Ther­a­peu­tics dosed the first pa­tient with its Ver­tex-part­nered be­ta tha­lassemia drug. It is al­so plan­ning to treat a sick­le cell dis­ease pa­tient with the same drug in mid-2019 for a sep­a­rate tri­al.

Of course, that’s as­sum­ing we’re talk­ing out­side of Chi­na, where in­fu­sions of CRISPR-edit­ed T cells in can­cer pa­tients have been tak­ing place for more than a year. In a stun­ner, Chi­nese sci­en­tist Jiankui He claimed the birth of ba­by twins who were ge­net­i­cal­ly mod­i­fied as fe­tus­es, stir­ring up wide­spread con­dem­na­tion and soul search­ing in the sci­en­tif­ic com­mu­ni­ty.

“2019 is the year when the train­ing wheels come off and the world gets to see what CRISPR can re­al­ly do for the world in the most pos­i­tive sense,” Fy­o­dor Urnov, a gene-edit­ing sci­en­tist at the Al­tius In­sti­tute for Bio­med­ical Sci­ences in Seat­tle and the Uni­ver­si­ty of Cal­i­for­nia, Berke­ley, told NPR.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Alec­tor cuts 11% of work­force as it dou­bles down on late-stage neu­ro pro­grams part­nered with GSK, Ab­b­Vie

A month after revealing plans to concentrate on its late-stage immuno-neurology pipeline, Alector is trimming its headcount by 11%.

The layoffs will impact around 30 employees across the organization, the company disclosed in an SEC filing, adding that the plan will “better align the company’s resources” with the new strategy. With $712.9 million in cash, cash equivalents and investments as of the end of 2022, Alector believes the reserves will now get it through 2025.

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Hugo Peris, Spiral Therapeutics CEO

Hear­ing-fo­cused biotech grabs trio of pro­grams from Oton­o­my's fire sale

Otonomy may be shutting down, but the lessons learned there will live on at another biotech working on new treatments for hearing loss.

San Francisco-based Spiral Therapeutics has bought certain assets related to three of Otonomy’s programs, ranging from data, patent rights, and know-how to inventory. That includes data around Otonomy’s twice-failed lead program, OTO-104 (Otividex), a sustained-exposure formulation of dexamethasone.

Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.

Boehringer re­ports ro­bust sales led by type 2 di­a­betes and pul­monary drugs, promis­es more to come high­light­ing obe­si­ty

Boehringer Ingelheim reported human pharma sales of €18.5 billion on Wednesday, led by type 2 diabetes and heart failure drug Jardiance and pulmonary fibrosis med Ofev. Jardiance sales reached €5.8 billion, growing 39% year over year, while Ofev took in €3.2 billion, notching its own 20.6% annual jump.

However, Boehringer is also looking ahead with its pipeline, estimating “In the next seven years the company expects about 20 regulatory approvals in human pharma.”

FDA ap­proves Nar­can opi­oid over­dose re­ver­sal spray for over-the-counter sale

The FDA today approved Emergent BioSolutions’ Narcan brand naloxone nasal spray for over-the-counter sales. The nod was expected and comes on the heels of a unanimous 19-0 advisory committee vote in favor of approval last month.

The move to OTC means the opioid overdose reversal agent will now be available on grocery, convenience and gas stations shelves, as well as potentially for purchase online.