Pre­clin­i­cal study finds Gen­mab may hold the key to a next-gen triple fol­lowup to MEK/BRAF com­bos

A Gen­mab-spon­sored study touts pre­clin­i­cal ev­i­dence that one of its tar­get­ed an­ti­body-drug con­ju­gates can be ef­fec­tive against a spe­cif­ic type of melanoma where ex­ist­ing treat­ment is fail­ing, point­ing to a po­ten­tial new triple com­bi­na­tion strat­e­gy.

The BRAF gene is a well-stud­ied path­way in melanoma, as a mu­ta­tion in it caus­es tu­mor cells to pro­lif­er­ate. Tai­lored treat­ments com­bin­ing BRAF- and MEK-in­hibitors, the cur­rent stan­dard, are of­ten ef­fec­tive (Genen­tech has a com­bo in the mar­ket, while No­var­tis is hus­tling ahead with piv­otal stud­ies for its com­bo of Tafin­lar and Mekin­ist). How­ev­er, as the pa­per pub­lished to­day by Nether­lands Can­cer In­sti­tute (NKI) in Na­ture Med­i­cine points out, many tu­mors de­vel­op re­sis­tance to them. 

Daniel Peep­er

In their pre­vi­ous work, the NKI re­searchers — led by Daniel Peep­er — have dis­cov­ered these re­sis­tant melanomas start pro­duc­ing an­oth­er pro­tein called AXL. The fact that this pro­tein of­ten sits on the out­side of a tu­mor cell makes them prime tar­gets for the next gen­er­a­tion of melanoma drugs.

That’s where Gen­mab’s AXL-tar­get­ing an­ti­body-drug con­ju­gate comes in. De­vel­oped with an ADC tech­nol­o­gy plat­form li­censed from Seat­tle Ge­net­ics, Hu­Max-AXL-ADC binds to and kills tu­mor cells ex­press­ing the AXL pro­tein. The Dan­ish an­ti­body gi­ant is cur­rent­ly test­ing it in mul­ti­ple can­cer in­di­ca­tions in the clin­ic.

In melanoma, Peep­er’s team found that ap­ply­ing this ADC in mice “ef­fec­tive­ly elim­i­nat­ed” AXL-high tu­mors.

The take­away here isn’t sim­ply that the AXL drug could be an al­ter­na­tive to the BRAF/MEK com­bo. The re­searchers are ar­gu­ing that it is best used in com­bi­na­tion with those in­hibitors.

Ju­lia Boshuizen

A grad­u­ate stu­dent in the group ob­served that most tu­mors still con­tained con­sid­er­able num­bers of cells with lit­tle or no AXL (not a big sur­prise; tu­mors are of­ten made of groups of can­cer cells with dif­fer­en­tial drug sen­si­tiv­i­ties). On the oth­er hand, BRAF/MEK-in­hibitors stim­u­lat­ed the pro­duc­tion of AXL in tu­mor cells.

“The break­through here is that we demon­strate that while melanomas that progress on treat­ment sharply ac­cu­mu­late AXL+ cells, most if not all re­sis­tant melanomas re­main high­ly het­ero­ge­neous,” Peep­er told End­points.

The stu­dent, Ju­lia Boshuizen, com­pared the tu­mor to a buck­et of mar­bles where yel­low ones have lit­tle AXL and are sen­si­tive to BRAF- and MEK-in­hibitors, while red mar­bles ex­press lots of AXL and don’t re­spond to BRAF/MEK treat­ment.

“If you wipe out the yel­low mar­bles on­ly, the red ones re­main, and vice ver­sa,” she said. “So, to get rid of both col­ors, we thought it may be a good strat­e­gy to com­bine BRAF/MEK-in­hibitors with Hu­Max-AXL-ADC.”

If this mar­ble ap­proach goes through to the clin­ic, ac­cord­ing to the re­searchers, it could sig­nal the next step for per­son­al­ized can­cer med­i­cine.

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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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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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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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.