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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Pfiz­er hits the brakes on their piv­otal tri­al for a BC­MA/CD3 bis­pe­cif­ic on safe­ty con­cerns while FDA road­block is hold­ing up Duchenne MD PhI­II

Pfizer’s ambitious plan to take a Phase II study of its BCMA CD3-targeted bispecific antibody elranatamab (PF-06863135) and run it through to an accelerated approval has derailed.

The pharma giant said in a release this morning that they have halted enrollment for their MagnetisMM-3 study after researchers tracked three cases of peripheral neuropathy in the ongoing Phase I. They are now sharing info with the FDA as they explore the red safety flag.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ex­tends re­search agree­ment with MIT-li­censed or­gan-on-chip sys­tems

The FDA on Wednesday extended its four-year agreement with CN Bio, a developer of single- and multi-organ-on-chip systems used for drug discovery, for another three years.

CN Bio said the scope of the research performed by the FDA’s Center for Drug Evaluation and Research has expanded to include the exploration of the company’s lung-on-a-chip system to help with the agency’s evaluation of inhaled drugs, in addition to the agency’s work on its liver model.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

In quest to meet user fee goals, FDA’s per­for­mance con­tin­ues down­ward trend

A recent update to the FDA’s running tally of how it’s meeting its user fee-related performance goals during the pandemic shows an agency that is not out of the woods yet.

The latest numbers reveal that for a second straight quarter in 2021, the FDA has met its user fee goal dates for 93% of original new drug applications, which compares with 94% and 98% for the previous two quarters in 2020, respectively.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Cynthia Butitta (L) and Joe Jimenez

Is that an­oth­er IPO in the mak­ing? Ex-No­var­tis CEO Joe Jimenez and a lead Kite play­er take up new posts at an off-the-shelf ri­val to 2 pi­o­neer­ing drugs

Right on the heels of taking on a $160 million crossover round in a likely leap to Nasdaq, Century Therapeutics CEO Lalo Flores is now pushing ahead with the high-profile ex-Novartis chief Joe Jimenez as chairman.

Jimenez’s greatest fame at Novartis was earned for one of its weakest products, as their pioneering personalized CAR-T Kymriah won the honors for the first such drug to make it to the market. Now a host of players, including Century, are barreling in behind the frontrunners with allogeneic rivals that can be created for off-the-shelf use.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.

Joe Wiley, Amryt CEO

A biotech with a yen for pricey rare dis­ease drugs — and bar­gain base­ment shop­ping — adopts an­oth­er or­phan in lat­est M&A pact

After making it through a long, painful haul to get past a CRL and on to an FDA approval last summer, little Chiasma has found a buyer.

Amryt $AMYT, a company known for its appetite for acquiring expensive drugs for rare diseases at bargain prices, snagged Chiasma and its acromegaly drug Mycapssa (octreotide) capsules in an all-stock deal — with an exchange of 0.396 shares of Amryt for every share of Chiasma.

Ngozi Okonjo-Iweala, Director general of WTO (AP Photo/Keystone/Alessandro Della Bella)

Opin­ion: Waiv­ing Covid-19 vac­cine IP could save lives, but where is the man­u­fac­tur­ing ca­pac­i­ty?

Droves of House Democrats in Washington and members of the European Parliament have now glommed onto a major push by India and South Africa at the WTO to abolish all IP around Covid-19 vaccines.

At first blush, waiving this IP sounds like an easy win: More Covid-19 vaccines made locally for more people means more lives saved. Simple enough, especially as low-income countries have received just a tiny fraction of the world’s vaccine allotment so far.

Thomas Schall, ChemoCentryx CEO (file photo)

Chemo­Cen­tryx plunges as FDA rais­es ques­tions about rare dis­ease drug ahead of ad­comm

ChemoCentryx’s stock price on Wednesday was cut in half by the release of FDA briefing documents ahead of a Thursday adcomm, raising questions on the company’s clinical data to support avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

ANCA-associated vasculitides (AAV) affect small to medium-size blood vessels that can be fatal in less than a year if left untreated, according to FDA. Only Roche’s Rituxan is currently FDA-approved for the treatment of AAV, while glucocorticoids are approved for the broader indication of vasculitis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,600+ biopharma pros reading Endpoints daily — and it's free.