As R&D set­backs mul­ti­ply, a pi­o­neer­ing CRISPR/Cas9 pro­gram for Duchenne MD con­tin­ues to im­press in new dog study

While one drug af­ter the next seems to get reg­u­lar­ly shot down in Duchenne mus­cu­lar dy­s­tro­phy, as we saw to­day with Pfiz­er’s failed Phase II, a pre­clin­i­cal CRISPR gene edit­ing pro­gram has been mak­ing some im­pres­sive progress in an­i­mal stud­ies.

Thurs­day af­ter­noon, Ex­on­ics pro­vid­ed some in­trigu­ing de­tails to show how their gene-edit­ing ap­proach works in dogs. Dis­patch­ing a Cas9 scalpel with guide RNA in­side an AAV de­liv­ery ve­hi­cle straight to mus­cle cells, the re­searchers say that their ap­proach was able to re­store dy­s­trophin pro­duc­tion that reached up to 92% of nor­mal in a ca­nine mod­el for the dis­ease.

That was for the high­est dose used.

John Rip­ple

“Typ­i­cal­ly,” Ex­on­ics CEO John Rip­ple tells me, the re­sponse in dy­s­trophin pro­duc­tion “was above 50%.”

That’s a big deal, he says, par­tic­u­lar­ly when re­searchers in the field see pa­tients turn asymp­to­matic at around 20% of nor­mal dy­s­trophin pro­duc­tion.

Ex­on­ics has been mak­ing mea­sured ad­vances in this field, start­ing with the lab work done by UT South­west­ern’s Er­ic Ol­son, who did the ear­ly sci­en­tif­ic in­ves­ti­ga­tion us­ing CRISPR on cells and mice. We made con­tact ear­ly on, as he dis­cussed the progress he had been mak­ing. Ol­son co-au­thored the study out to­day.

“Ca­nines have clin­i­cal and patho­log­i­cal fea­tures sim­i­lar to the hu­man pre­sen­ta­tion of Duchenne, in­clud­ing mus­cle weak­ness, at­ro­phy and fi­bro­sis,” Ol­son not­ed to­day, as the lat­est work ap­peared in Sci­ence.

Late last year a $40 mil­lion launch round helped the com­pa­ny get start­ed with a vir­tu­al crew, which is now grow­ing fast. From a hand­ful of staffers, Ex­on­ics ros­ter has now grown to 11, with plans to dou­ble that when they move in­to a new lab and of­fices in Wa­ter­town lat­er this year. 

In many ways, Duchenne MD could prove one of the best fields for a CRISPR team to work in — es­pe­cial­ly in the ear­ly days.

In this case, they’re look­ing for a sim­ple cut and re­pair re­sponse need­ed to cor­rect er­rant cells that trig­ger the ail­ment, which slow­ly but sure­ly crip­ples and then kills its vic­tims. Tar­get­ing mus­cles and heart tis­sue gives them a sta­ble group of non-di­vid­ing cells to work with, which may well re­duce the chances of any off-tar­get im­pact — a top­ic that rou­tine­ly sparks near pan­ic in CRISPR/Cas9 in­vest­ment cir­cles.

It should be not­ed, though, that be­fore we start spot­light­ing a po­ten­tial cure for Duchenne, or spe­cif­ic ge­net­ic pa­tient pop­u­la­tions with the dis­ease, the drug is still not ready for a prime time hu­man tri­al.

“Our next step is to con­tin­ue pre­clin­i­cal work, ad­vanc­ing in the clin­ic,” adds the CEO. “We need to do longer an­i­mal stud­ies, main­tain dy­s­trophin pro­tein over a long pe­ri­od of time.”

That way, by the time they sit down with reg­u­la­tors and start talk­ing hu­man stud­ies, they’ll be able to make a sol­id case built on ex­ten­sive pre­clin­i­cal work. When­ev­er that day ar­rives.

There’s not an un­lim­it­ed amount of time avail­able, though. Pa­tients are still in des­per­ate need, and oth­er biotechs are al­so work­ing on a cure.

Ex­on­ics is one of sev­er­al de­vel­op­ers look­ing to carve a new re­search path to this dis­ease. Mus­cle drugs have proven very prob­lem­at­ic in ad­dress­ing a se­vere dis­ease like this. And Sarep­ta’s eteplirsen was ap­proved with­out sig­nif­i­cant ef­fi­ca­cy da­ta, un­der­scor­ing a dra­mat­ic need for new drugs. Sarep­ta, Sol­id Bio and oth­ers are ex­plor­ing gene ther­a­py ap­proach­es, which have al­so high­light­ed some im­pres­sive ear­ly re­sults.

Im­age: Er­ic Ol­son. Jane Cof­fin Childs Memo­r­i­al Fund for Med­ical Re­search

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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Fangliang Zhang, AP Images

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.