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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.

Madhu Natarajan, Takeda rare disease development head

Drawn to the idea of turn­ing B cells in­to 'pro­tein fac­to­ries,' Take­da jumps in­to a mile­stone-heavy, $900M pact

Madhu Natarajan can trace his fascination with the idea of taking B cells and turning them into protein factories back 20 years, when he had his own lab at UT Southwestern. So when Natarajan, now the rare disease development head for Takeda, sat down for a meet-up with execs from Seattle-based Immusoft at the last in-person JP Morgan conference, they went straight into a brainstorming session.

“That B cells can take up residence and do what they do for a long time,” says Natarajan, pumping out proteins and “leveraging it into a therapeutic context,” hits his sweet spot for discovery deals. And he was deeply impressed by what he heard.

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Samarth Kulkarni, CRISPR CEO

CRISPR Ther­a­peu­tics claims safe­ty ad­van­tage in first big look at off-the-shelf CAR-T da­ta, but dura­bil­i­ty in ques­tion

CRISPR Therapeutics CEO Samarth Kulkarni thinks his company might have built the safest CAR-T therapy yet.

The gene editing biotech announced the first major batch of data from its off-the-shelf CAR-T program, showing that 58% of the 26 large B-cell lymphoma patients who received the therapy saw their tumors shrink and that 38% had no signs of cancer whatsoever.

Those response rates, outside experts say, are broadly in the range seen in trials for autologous CAR-T therapies such as Novartis’s Kymriah and Gilead’s Yescarta, bolstering the chance that off-the-shelf could eventually make the benefits of such therapies far more widely available. Uptake of the first-generation of CAR-Ts continues to be limited by the cost, time and infrastructure required to handle each person’s cells.

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