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.”

Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

The biotech industry is getting a landlord, unlike anything it’s ever known before.

Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

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John McHutchison in 2012. Getty Images

The $1.1M good­bye: Gilead CSO John McHutchi­son is out as Daniel O’Day shakes up the se­nior team

Just a little more than a year after John McHutchison grabbed a promotion to become CSO at Gilead in the wake of Norbert Bischofberger’s exit, he’s out amid a shakeup of the senior team that is also triggering the departure of two other top execs.

Gilead stated that McHutchison “has decided to step down” from the job as of August 2nd. And their SEC filing notes that he’ll be getting a $1.1 million check to settle up on his contract.

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Thomas Gajewski, David Steinberg. (CRI, Pyxis)

Bay­er, Long­wood back star re­searcher's deep dive in­to the tu­mor mi­croen­vi­ron­ment for new I/O tar­gets

From PD-1 targeting to the RAS pathway to the STING complex, Thomas Gajewski has spent the past two decades of his career decoding the various ways the immune system can be unleashed to defend against cancer. So when the University of Chicago professor comes around to putting all his findings into a new platform for finding new targets, VCs and pharma groups alike pay attention.

“He’s been studying T cells for 20 years, plus he’s one of the world’s leaders if not the world leader in the space,” David Steinberg, partner at Longwood Fund, said. “Furthermore, let me add he did a lot of the foundational research and also some of the seminal clinical trials in the existing set of I/O agents. He understands the space really well, he understands the current strengths, and I think he understood really well what was missing, so he knew where to look.”

Kamala Harris speaking yesterday at the Des Moines Register Iowa Presidential Candidate Forum [via Getty]

Who’s the tough­est on drug prices? A game of po­lit­i­cal one-up­man­ship is dri­ving the pol­i­cy de­bate in Wash­ing­ton

Earlier this week we got a look at Senator Kamala Harris’ position on drug prices. She’s proposing that HHS take an average price from single-payer systems like the UK, Germany and Canada — which leverage market access for lower prices — and use that to set the US price. Anything drug companies collect above that would be taxed at a rate of 100%.

And the rhetoric is scathing:
While families struggle to make it to the end of the month, pharmaceutical companies are turning record profits. They’re spending nearly as much on advertising as R&D. They’re manipulating their market power to hike prices on lifesaving generic drugs. They’re making twice the profit of the average industry in America and still increased drug prices by 10.5% over the past six months alone. Meanwhile, they are charging dramatically higher prices to American consumers.
That’s an escalation on Joe Biden’s plan, which includes drug importation from those cheaper markets as well as allowing Medicare to negotiate prices — something that virtually all Dems agree on now.

SJ Lee [File photo]

Go­ing in­side cells, Sung Joo Lee has sketched some big goals for his small — but glob­al — team of drug hunters

For a small biotech based in South Korea with a research arm in Cambridge, MA, Orum Therapeutics has sketched out some big goals aimed at developing antibodies for intracellular targets. And now they have a new $30 million round to push the work forward, aiming at a slate of currently undruggable quests.

Orum has been working on a platform tech out of Ajou University that relies on endocytosis to smuggle antibodies and their cargo inside a cell. They’ve published work in Nature that illustrates its preclinical potential in RAS mutations, and KRAS is on their list of targets. 

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Astel­las buys in­to Fre­quen­cy's re­gen­er­a­tive med strat­e­gy with a $625M al­liance on hear­ing loss

The executive team at Frequency Therapeutics never oversold the results of their maiden Phase I/II study for a new drug to rectify hearing loss. It was, they said back in April, primarily about safety and tolerability, where their drug FX-322 performed as they had hoped. 

That early glimpse of efficacy everyone searches for in their first try on humans? 

(I)mprovements in hearing function, including audiometry and word scores, were observed in multiple FX-322 treated patients.

We don’t know exactly what that means. But whatever the details, Astellas found enough in the data to jump in with a sizable collaboration deal.

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