CAR-T shows promise for lu­pus in mouse study — will it in­spire hope in a be­lea­guered field?

As one an­ti­body af­ter an­oth­er gets stacked on the grow­ing pile of failed at­tempts to tack­le lu­pus, sci­en­tists are flag­ging CAR-T ther­a­pies — which have done won­ders in the can­cer space — as a po­ten­tial one-off treat­ment for the au­toim­mune dis­ease, with some im­pres­sive mice da­ta now avail­able.

Their pre­clin­i­cal tri­al, the Uni­ver­si­ty of Ten­nessee Health Sci­ence Cen­ter re­searchers wrote in a Sci­ence pa­per, “pro­vid­ed un­am­bigu­ous con­fir­ma­tion that CAR T cell ther­a­py pro­found­ly af­fects au­toim­mune dis­ease pro­gres­sion in both NZB/W and MRL-lpr mice.”

Like rit­ux­imab — a Roche drug ap­proved for rheuma­toid arthri­tis but failed to make a dent in lu­pus — the CAR-T ther­a­py works by de­plet­ing B cells, which are be­lieved to cause a ram­page in the body with a swath of au­toan­ti­bod­ies. But un­like rit­ux­imab, the CAR-T cells in­duce tar­get cell death by a di­rect mech­a­nism, with­out re­quir­ing help from macrophages.

By tar­get­ing CD19, a mark­er present on al­most all B cells, CAR-T ther­a­py has shown re­mark­able po­ten­cy and last­ing ef­fect in a num­ber of blood can­cers like B cell lym­phoma.

That’s the ef­fect they want to repli­cate in the lu­pus mouse mod­els, and to a large ex­tend it’s what they ob­served: Most mice that re­ceived the CAR-T treat­ment lived sig­nif­i­cant­ly longer than the con­trol group, liv­ing as much as one year af­ter the in­jec­tion, with the CAR-T cells still ac­tive in vi­vo for that du­ra­tion. CD19 ex­pres­sion was al­so not de­tect­ed in spleens, skin and kid­ney of treat­ed mice.

Marko Radic

“Cell-based ther­a­pies pro­vide fur­ther ad­van­tages over an­ti­bod­ies be­cause CAR T cells re­quire on­ly a sin­gle ad­min­is­tra­tion, mi­grate to mul­ti­ple lym­phoid tis­sues and or­gans in the re­cip­i­ent, and de­vel­op in­to both ef­fec­tor and mem­o­ry cell pop­u­la­tions,” the re­searchers, led by Marko Radic, wrote.

Mean­while, the team al­so not­ed dif­fer­ences in the three murine vi­ral vec­tors used to ge­net­i­cal­ly en­gi­neer the T cells — with am­photrop­ic murine leukemia virus (A-MLV) retro­virus lead­ing the pack.

A quick check on clin­i­cal­tri­ sug­gests that Shang­hai GeneChem ini­ti­at­ed a 5-per­son tri­al to test a sim­i­lar ap­proach in Chi­na, though the re­sults are not avail­able.

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.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

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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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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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.