Scripps re­searchers add pow­er to an­tibi­ot­ic van­comycin, giv­ing it a third mech­a­nism to fight su­per­bugs

The emer­gence of an­tibi­ot­ic-re­sis­tant bac­te­ria is a ma­jor world­wide con­cern for health­care pro­fes­sion­als world­wide, who in some cas­es, have been ren­dered pow­er­less to help pa­tients sur­vive su­per­bug in­fec­tions that have out-evolved ex­ist­ing drugs. Progress has slowed on cre­at­ing new an­tibi­otics over sev­er­al decades as many com­pa­nies cal­cu­lat­ed their re­turn on in­vest­ment for de­vel­op­ing one won’t be suf­fi­cient, at least with­out spe­cial in­cen­tives. Ac­cord­ing to the World Health Or­ga­ni­za­tion, “With­out ur­gent ac­tion, we are head­ing for a post-an­tibi­ot­ic era, in which com­mon in­fec­tions and mi­nor in­juries can once again kill.”

Re­searchers at The Scripps Re­search In­sti­tute in La Jol­la, Cal­i­for­nia have a new plan to pre­vent that from hap­pen­ing.

Dale Boger

In a study pub­lished yes­ter­day in the jour­nal Pro­ceed­ings of the Na­tion­al Acad­e­my of Sci­ences, Dale Boger, co-chair of TSRI’s De­part­ment of Chem­istry, start­ed with van­comycin, an ex­ist­ing an­tibi­ot­ic that has stood up bet­ter than most to the growth of an­tibi­ot­ic re­sis­tance. The drug kills bac­te­ria by pre­vent­ing the cells from build­ing cell walls. Af­ter be­ing pre­scribed for over 60 years, very few of the or­gan­isms have man­aged to re­sist its cu­ra­tive pow­ers.  How­ev­er, some dan­ger­ous strains of gram-pos­i­tive bac­te­ria, such as En­te­ro­coc­ci, which was list­ed as a high pri­or­i­ty by WHO back in Feb­ru­ary, have re­cent­ly man­aged to evolve to evade the drug’s in­flu­ence.

Boger has been work­ing on mod­i­fy­ing and strength­en­ing the drug for sev­er­al years. In the cur­rent study, he has in­tro­duced a third mod­i­fi­ca­tion which makes the drug one thou­sand times more po­tent than it is in its orig­i­nal struc­ture. The new for­mu­la­tion kills bac­te­ria us­ing three sep­a­rate mech­a­nisms, mak­ing it high­ly un­like­ly that a bac­teri­um would evolve to dodge all three si­mul­ta­ne­ous­ly. In the study, the drug was ef­fec­tive in killing En­te­ro­coc­ci in both its orig­i­nal and van­comycin-re­sis­tant forms.

The drug still has a long way to go be­fore doc­tors will be able to pre­scribe it though. It takes 30 steps to prop­er­ly syn­the­size the mol­e­cule the team has de­signed. It won’t be ready for hu­man tri­als un­til it can be syn­the­sized more prac­ti­cal­ly, but Boger de­scribes this step as the “easy part.”

 

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.

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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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.

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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