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.”

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.