In­censed by Chi­na CRISPR scan­dal, US con­sor­tium am­pli­fy glob­al call to sus­pend hu­man em­bryo edit­ing

In­spired by his bi­ol­o­gist broth­er, Al­dous Hux­ley laid out his dystopi­an vi­sion — re­plete with ge­net­i­cal­ly mod­i­fied cit­i­zens strat­i­fied by an in­tel­li­gence-based so­cial hi­er­ar­chy — in his 1932 book Brave New World. The emer­gence of mi­to­chon­dr­i­al re­place­ment ther­a­py or ‘three-par­ent IVF’ and one rogue Chi­nese sci­en­tist lat­er, fears that un­bri­dled hu­man em­bryo edit­ing could be dan­ger­ous from a sci­en­tif­ic, eth­i­cal, and so­ci­etal per­spec­tive have reignit­ed. On Wednes­day, a con­sor­tium of sci­en­tists, bioethi­cists, and biotech ex­ec­u­tives wrote to US HHS sec­re­tary Alex Azar, call­ing for a col­lab­o­ra­tion on a bind­ing glob­al mora­to­ri­um on hu­man clin­i­cal germline ex­per­i­men­ta­tion.

Alex Azar

Glob­al­ly, guide­lines vary wide­ly about the ex­tent (or lack there­of) of germline re­search — in­tro­duc­ing her­i­ta­ble changes to sperm, eggs or em­bryos — is per­mit­ted. Some re­gions ban it al­to­geth­er; some al­low lab re­search but not preg­nan­cies (like in the UK); while oth­ers have no poli­cies. In the US, the NIH does not fund germline re­search, but pri­vate fund­ing is sanc­tioned.

Last month, an in­ter­na­tion­al group of ethi­cists and re­searchers, in­clud­ing ex­perts who orig­i­nal­ly de­vel­oped CRISPR–Cas9 as a gene-edit­ing tool, called for a mora­to­ri­um on clin­i­cal use of hu­man germline edit­ing un­til the safe­ty of the tech­nique has been es­tab­lished and a con­sen­sus on ac­cept­able use has been reached.

(W)e call for the es­tab­lish­ment of an in­ter­na­tion­al frame­work in which na­tions, while re­tain­ing the right to make their own de­ci­sions, vol­un­tar­i­ly com­mit to not ap­prove any use of clin­i­cal germline edit­ing un­less cer­tain con­di­tions are met.

The NIH sup­port­ed the call.

The move fol­lowed last year’s news that con­tro­ver­sial Shen­zhen-based re­searcher Jiankui He ge­net­i­cal­ly edit­ed em­bryos us­ing CRISPR/Cas9 tools — with in­ten­tion of in­duc­ing HIV re­sis­tance —  which were im­plant­ed and re­sult­ed in the birth of twin in­fant girls, trig­ger­ing a tem­pest in sci­en­tif­ic cir­cles the world over. In the wake of the scan­dal, the Chi­nese gov­ern­ment tight­ened its over­sight of gene edit­ing and oth­er “high-risk bio­med­ical tech­nolo­gies” in March.

“He pro­ceed­ed with­out clear med­ical need, in a sur­rep­ti­tious man­ner lack­ing any mean­ing­ful pub­lic or sci­en­tif­ic com­mu­ni­ty dis­cus­sion or con­sen­sus, and with­out any reg­u­la­to­ry ap­proval,” the group of 62 de­cried in the let­ter, con­demn­ing such hu­man germline clin­i­cal ex­per­i­men­ta­tion as ir­re­spon­si­ble.

Feng Zhang

“Such hu­man ge­net­ic ma­nip­u­la­tion should be con­sid­ered un­ac­cept­able and sup­port a bind­ing glob­al mora­to­ri­um un­til se­ri­ous sci­en­tif­ic, so­ci­etal, and eth­i­cal con­cerns are ful­ly ad­dressed,” the ex­perts, in­clud­ing CRISPR/Cas9 co-in­ven­tor Feng Zhang, said.

They un­der­scored a myr­i­ad of is­sues such as off-tar­get ef­fects and mu­ta­tions, which apart from the med­ical im­pact could pose ma­jor eth­i­cal con­cerns, be­cause re­search sub­jects would in­clude, and not on­ly be lim­it­ed, to em­bryos and chil­dren, but al­so fu­ture gen­er­a­tions of de­scen­dants.

Clin­i­cal germline gene edit­ing is ap­pro­pri­ate­ly pro­hib­it­ed in the Unit­ed States, across much of Eu­rope, in Chi­na, and in many oth­er coun­tries…Be­fore this sta­tus quo is re­vis­it­ed, it is vi­tal that ex­ten­sive dis­cus­sions and en­gage­ment take place among all ma­jor stake­hold­ers, in­clud­ing mem­bers of the sci­en­tif­ic, med­ical, pa­tient, care­giv­er, pol­i­cy, le­gal, eth­i­cal, and faith com­mu­ni­ties.

But the group was clear that the mora­to­ri­um should be lim­it­ed to germline edit­ing, not so­mat­ic (cells in the body ex­cept sperm and egg cells) cells, which have sig­nif­i­cant reper­cus­sions in the un­der­stand­ing and treat­ment of hu­man dis­ease.

Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.
The biotech started by putting together an “arsenal” of technologies aimed at making cell therapies for cancer much, much better than the rather crude first-generation drugs that hit the market from Novartis and Kite.
Their drugs have become the baseline against which all others are being measured.
“The technology set we’re developing is independent of the chassis,” Drazan tells me. “It doesn’t have to be autologous (extracted from the patient) or allogeneic (off the shelf). It doesn’t have to be a T cell, it could be a B cell.” But they are starting out on the autologous side, where they have the most knowledge and insight into manufacturing techniques.
It also doesn’t have to be close to the clinic.
Drazan expects the biotech will be working its way through preclinical operations for “a few years,” with enough money from the $85 million launch round to get into humans.
By today’s superheated fundraising standards, that’s not a huge amount of cash. Lyell, another cell therapy 2.0 startup we featured last week, raised $600 million in a year, including a big chunk of cash from GlaxoSmithKline. Drazan is interested in dealmaking as well, but he also knows he has the cash necessary to support the company for a good run — a key part of what it takes to bring together a stellar team of top players.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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UP­DAT­ED: Alex­ion pays $930M to buy out Achillion and its promis­ing com­pan­ion drug to Soliris

After a series of stock-crunching setbacks over the years, Achillion enjoyed a turn in the sun a few weeks ago as the FDA blessed their lead drug danicopan (ACH-4471) — a complementary therapy for PNH patients taking Alexion’s Soliris — with a breakthrough drug designation after taking a look at some solid supporting Phase II data.

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From left to right: Lilian Kim, Associate Director Business Development; John Moller, CEO; Yooni Kim, Executive Director, Asia Operations; Michelle Park, Director South Korea Operations.

Novotech CRO sees 26% growth in Asia tri­al ac­tiv­i­ty from biotechs, but still plen­ty of ca­pac­i­ty

As the Asia-Pacific clinical trials sector continues to grow rapidly, Novotech the Asia-Pacific-based CRO is seeing biotech clinical activity up by 26%. But says there is still plenty of capacity in the region that features advanced medical facilities, supportive regulatory environments, and more than 2.3 billion people, largely treatment naïve, living in urban areas.

China, South Korea and Australia have the most studies registered as recruiting or about to recruit according to ClinicalTrials.Gov.