David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The re­searcher be­hind base-edit­ing is out with what some sci­en­tists are hail­ing as the biggest ad­vance­ment in CRISPR tech­nol­o­gy since that 2016 break­through: “prime edit­ing.” The new mol­e­c­u­lar gad­get is ca­pa­ble of eras­ing any base pair and sten­cil­ing in an­oth­er and cut­ting or adding long seg­ments of DNA with­out break­ing both strands of the he­lix.

Luke Dow Dow Lab

David Liu, base edit­ing pi­o­neer and founder of Beam Ther­a­peu­tics, pub­lished the find­ings in Na­ture along­side An­drew An­za­lone. They es­ti­mat­ed that the break­through “in prin­ci­ple” puts 89% of hu­man dis­eases in purview — al­though ex­perts cau­tioned that hu­man ther­a­pies were a long way off.

“This is a big ad­vance,” Luke Dow, a Cor­nell can­cer re­searcher who was not in­volved in the study,  told End­points News. “The ev­i­dence in this case for cor­rect­ing those dis­ease al­le­les is the first step and that’s a long way off from the last step.”

To piv­ot the tech in­to ther­a­peu­tic ap­pli­ca­tions, Liu al­so launched Prime Med­i­cine with the back­ing of Arch Ven­ture Part­ners, GV, New­path Part­ners and F-Prime.  That could spell trou­ble for Beam, which filed for a $100 mil­lion in Sep­tem­ber and may now see some of their sci­ence out­paced, al­though the prime edit­ing tech has been sub­li­censed to Beam for some fields.

The ear­ly CRISPR tech­nol­o­gy, for all its her­ald­ed pre­ci­sion, was some­thing of a blunt force ob­ject. It tears open DNA, cre­at­ing what are called dou­ble-strand breaks, and then leaves the DNA to patch it­self back up, by knit­ting the two strands to­geth­er, tak­ing ran­dom nu­cleotides from with­in the cell to fill the gap or splic­ing in patch­es of DNA sup­plied by sci­en­tists. It’s of­ten loathe to do the lat­ter, a ma­jor ob­sta­cle in ap­ply­ing CRISPR to dis­eases that re­quire not on­ly re­mov­ing faulty genes but putting in the right ones. Even when it does, it can of­ten cause off-tar­get ef­fects.

Liu made a ma­jor break­through in 2016 when he in­tro­duced base edit­ing – the abil­i­ty to di­rect­ly rewrite the nu­cleotides that make up DNA’s 4-let­ter al­pha­bet. News cov­er­age talked about the po­ten­tial to cure dis­eases such as sick­le cell, caused by a sin­gle nu­cleotide in the gene for he­mo­glo­bin.

The prob­lem was Liu’s first dis­cov­ery –and Beam Ther­a­peu­tics, the com­pa­ny he launched around it – had ma­jor dif­fi­cul­ty at­tack­ing sick­le cell, be­cause that first gad­get could on­ly make four switch­es: C-to-T, T-to-C, A-to-G, and G-to-A. A sick­le cell treat­ment would re­quire switch­ing T to A on the right gene.

In yes­ter­day’s Na­ture pa­per, Liu and his coau­thors switched T to A. They al­so switched every oth­er of the 12 pos­si­bil­i­ties.

“It doesn’t im­prove on base-edit­ing,” Dow said.  “The orig­i­nal base edit­ing tool the Liu lab de­scribed a few years ago with a few mod­i­fi­ca­tions be­came very ef­fi­cient. What this does is open up a lot of dif­fer­ent types of mu­ta­tions that weren’t avail­able pre­vi­ous­ly.

Liu de­scribed the new tech as a “search-and-re­place” tool – es­sen­tial­ly con­trol F for the hu­man genome. That’s prob­a­bly over­selling where the tech is to­day – Dow said they on­ly test­ed it on four hu­man cell types, leav­ing ques­tions on how it will fare in the rest – but it gets at the po­ten­tial. In ad­di­tion to sick­le cell, re­searchers spliced out the 4-let­ter se­quence that caus­es Tay-Sachs. Over­all, they made 175 ed­its in mouse and hu­man mod­els.

The au­thors re­port­ed be­ing able to do 44 in­ser­tions and said more was pos­si­ble. They al­so were able to ed­it in non-di­vid­ing such as neu­rons and liv­er cells.

Rather than break­ing the cell DNA on both sides and pro­vid­ing an­oth­er piece of DNA for the cell to in­cor­po­rate, the new tech­nol­o­gy breaks on­ly one strand and us­es RNA to sup­ply the nu­cleotides. By not caus­ing dou­ble-strand breaks, it lim­its off-tar­get ef­fects on oth­er parts of the genome – one of the big­ger risks of CRISPR tech­nol­o­gy.

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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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.