A CRISPR/Cas9 start­up launch­es on the R&D fron­tier, work­ing on a one-time fix for Duchenne MD


Af­ter ex­per­i­ment­ing with CRISPR/Cas9 tech, per­fect­ing ge­net­ic surgery on mus­cle cells in mice to snip out the faulty ex­ons that are the cause of the lethal mus­cle wast­ing dis­ease, UT South­west­ern’s Er­ic Ol­son is ready to move in­to the late pre­clin­i­cal stage of de­vel­op­ment. His work is be­ing spun out in­to a start­up which Ol­son hopes will play a big role in even­tu­al­ly cor­rect­ing the fa­tal ge­net­ic flaws for most of the boys who have this dis­ease.

Cure­Duchenne Ven­tures is bankrolling the start­up — dubbed Ex­on­ics Ther­a­peu­tics — with $5 mil­lion in seed mon­ey. That’s not a huge amount in biotech these days. But it is enough to take their pro­gram for Duchenne’s in­to large an­i­mals, mon­keys as well as dogs, as they get a bet­ter grasp of the po­ten­tial ef­fi­ca­cy as well as a clean­er safe­ty pro­file on this ther­a­py.

“We’ve con­tin­ued to op­ti­mize the method for AAV de­liv­ery for cor­rec­tion of Duchenne mu­ta­tions in mouse mod­els,” Ol­son tells me. “We’re now look­ing at 80% restora­tion of dy­s­trophin.”

Even a much small­er, par­tial re­sponse in hu­mans would be a re­mark­able achieve­ment, as the ab­sence of dy­s­trophin is what trig­gers the dis­ease, which first puts these boys in­to a wheel­chair and then kills them.

Keep in mind, ro­dent mod­els can be a poor sub­sti­tute for hu­mans. And no one should think we’re right around the sci­en­tif­ic cor­ner from a cure. But Ol­son — who’s al­so been test­ing this tech on pa­tients’ cells — be­lieves that his hu­man­ized mice are a good in­di­ca­tor of fu­ture suc­cess for an ap­proach po­ten­tial­ly leagues ahead of the con­tro­ver­sial ex­on-skip­ping tech that’s been ad­vanced by Sarep­ta and PTC Ther­a­peu­tics.

Both of those ther­a­pies are now be­ing sold in the US and Eu­rope, re­spec­tive­ly, de­spite a lack of ef­fi­ca­cy da­ta. And Ol­son’s had a chance to per­fect the de­liv­ery method, to ex­pand the po­ten­tial tar­get group of pa­tients to a num­ber dra­mat­i­cal­ly high­er than the cur­rent ther­a­pies tar­get­ed at spe­cif­ic mu­ta­tions.

“You don’t have to have a pre­cise cor­rec­tion,” notes Ol­son. “You can use a sim­ple gene-edit­ing strat­e­gy to skip over mu­tant ex­on.”

Tai­lor­ing a gene-edit­ing fix for Duchenne seems like a nat­ur­al ear­ly tar­get for the field. If you can use CRISPR to guide Cas9 to ed­it out the ge­net­ic de­fects in pa­tients’ DNA, get­ting to a large enough con­cen­tra­tion of mus­cle cells to make a sig­nif­i­cant dif­fer­ence in dy­s­trophin pro­duc­tion, you have the po­ten­tial to cre­ate a once-and-done ther­a­peu­tic that could make a huge dif­fer­ence in the lives of many of the 15,000 boys in the US who have this dis­ease, along with the rest of the world’s pa­tients.

Based on his work so far, Ol­son be­lieves the pro­gram could large­ly fix Duchenne MD for 80% of the boys with this dis­ease.

Ol­son is about to pub­lish more about his re­search, fol­low­ing up a re­port in Sci­ence in late 2015 that marked his ear­ly progress and snared broad at­ten­tion in the biotech world for his work.

 

“Ex­on­ics is clear­ly well po­si­tioned, as we climb the species lad­der,” says Cristi­na Csim­ma, the for­mer CEO at Cy­dan who’s now ex­ec­u­tive chair­man at Ex­on­ics. And the com­pa­ny can take some time to bal­ance ei­ther a Se­ries A or pur­sue talks with oth­er play­ers in the field.

Jak Knowles, the man­ag­ing di­rec­tor of Cure Duchenne Ven­tures and VP of sci­en­tif­ic af­fairs at Cure­Duchenne, is tak­ing the reins as CEO of the com­pa­ny, now based in Boston near South Sta­tion.

No one is giv­ing out a time­line here on how long it’s go­ing to take to get through an IND-en­abling pro­gram and up to the thresh­old of a first-in-man study. But when Ol­son talked to MIT Tech­nol­o­gy Re­view late last year, he told An­to­nio Re­gal­a­do that a clin­i­cal ef­fort could get un­der­way in about two years, not out of line for a pro­gram en­ter­ing the late pre­clin­i­cal stage.

But they might not be alone. Ed­i­tas, one of the three pi­o­neers with CRISPR Ther­a­peu­tics and In­tel­lia to leap in­to the field with hun­dreds of mil­lions of dol­lars each in in­vestors’ cash, has point­ed to Duchenne MD as an area of in­ter­est. Ol­son al­so told Re­gal­a­do that he had been in touch with Ed­i­tas — which has been keep­ing its pipeline plans close to the vest — as he ex­plored a com­mer­cial deal with one of the ex­ist­ing play­ers.

One of the time­lines you hear a lot when talk­ing to peo­ple about CRISPR re­search is that it could eas­i­ly take 10 years be­fore you see the first new ther­a­py. And that could be am­bi­tious. This is a new and evolv­ing fo­cus in biotech, where re­searchers are still care­ful­ly look­ing for un­in­tend­ed off-tar­get ef­fects that could raise un­ex­pect­ed safe­ty is­sues. But in a few weeks we’ll see a new FDA com­mis­sion­er step in with a man­date to speed new reme­dies like this. Scott Got­tlieb has talked about cre­at­ing a kind of Skunkworks in the FDA for rare dis­eases that might sig­nif­i­cant­ly short­en the de­vel­op­ment time­lines for new drugs to treat lethal rare dis­eases.

So it’s con­ceiv­able that it could be done in less than 10 years.

The race is on. We just don’t know right now where the fin­ish line is.

On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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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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Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.

Den­mark's Gen­mab hits the jack­pot with $500M+ US IPO as small­er biotechs rake in a com­bined $147M

Danish drugmaker Genmab A/S is off to the races with perhaps one of the biggest biotech public listings in decades, having reaped over $500 million on the Nasdaq, as it positions itself as a bonafide player in antibody-based cancer therapies.

The company, which has long served as J&J’s $JNJ key partner on the blockbuster multiple myeloma therapy Darzalex, has asserted it has been looking to launch its own proprietary product — one it owns at least half of — by 2025.

FDA over­rides ad­comm opin­ions a fifth of the time, study finds — but why?

For drugmakers, FDA advisory panels are often an apprehended barometer of regulators’ final decisions. While the experts’ endorsement or criticism often translate directly to final outcomes, the FDA sometimes stun observers by diverging from recommendations.

A new paper out of Milbank Quarterly put a number on that trend by analyzing 376 voting meetings and subsequent actions from 2008 through 2015, confirming the general impression that regulators tend to agree with the adcomms most of the time — with discordances in only 22% of the cases.

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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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).

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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