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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of face plants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Jean Bennett (Brent N. Clarke/Invision/AP Images)

Lux­tur­na in­ven­tor Jean Ben­nett starts a new gene ther­a­py com­pa­ny to tack­le rare dis­eases left be­hind by phar­ma, VCs

A few years ago Jean Bennett found herself in a surprising place for a woman who invented the first gene therapy ever approved in the United States: No one, it seemed, wanted her work.

Bennett, who designed and co-developed Luxturna, approved in 2018 for a rare form of blindness, had kept building new gene therapies for eye diseases at her University of Pennsylvania lab. But although the results in animals looked promising, pharma companies and investors kept turning down the pedigreed ophthalmology professor.

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Maureen Hillenmeyer, Hexagon Bio CEO

Hexa­gon Bio rais­es $61M to con­tin­ue ef­forts to turn fun­gi in­to drugs

A year after raising a $47 million launch round, the fungi-loving drug hunters at Hexagon Bio have more than doubled their coffers.

Hexagon announced today that it raised another $61 million for its efforts to design cancer and infectious disease drugs based on insights mined from the DNA in millions of species of fungi. The new financing brings Hexagon’s committed funding to over $108 million.

Blue­bird sends blood dis­or­der drug to FDA for ap­proval; CG On­col­o­gy en­ters col­lab­o­ra­tion with Roche for Tecen­triq

Bluebird bio announced it completed the rolling submission of its BLA to the FDA for betibeglogene autotemcel gene therapy.

The therapy, designed for patients with beta-thalassemia who require regular red blood cell transfusions, was previously granted breakthrough therapy designation for treating transfusion-dependent beta-thalassemia (TDT). If approved, beti-cel will be the first hematopoietic stem cell ex-vivo gene therapy for patients in the US.