No­var­tis inks a $2.5B bis­pe­cif­ic can­cer drug de­vel­op­ment al­liance with Xen­cor

No­var­tis is jump­ing on board Xen­cor’s grow­ing bis­pe­cif­ic on­col­o­gy plat­form. The phar­ma gi­ant is pay­ing $150 mil­lion up­front for a tick­et to ride, be­gin­ning at the pre­clin­i­cal stage of de­vel­op­ment. And No­var­tis ($NVS) is promis­ing up to $2.4 bil­lion in mile­stones as it paves the way for a ma­jor new al­liance for Jay Brad­ner’s No­var­tis In­sti­tutes for Bio­Med­ical Re­search in Cam­bridge, MA.

The phar­ma gi­ant an­nounced the pact with the Mon­rovia, CA-based biotech ear­ly Tues­day. In re­turn No­var­tis gains ex-U.S. rights on two pre­clin­i­cal pro­grams — the AML drug XmAb14045 and XmAb13676 for B-cell ma­lig­nan­cies, both head­ed to the clin­ic lat­er this year — as well as non-ex­clu­sive use of the tech for up to 10 more pro­grams.

In ad­di­tion to shar­ing de­vel­op­ment costs, Xen­cor has an opt-in on co-com­mer­cial­iz­ing one of the phar­ma gi­ant’s drugs de­vel­oped from an ex­clu­sive use of the tech on four undis­closed tar­gets.

No­var­tis marks the lat­est in a string of heavy­weight part­ners for Xen­cor. Am­gen paid $45 mil­lion up­front to part­ner last fall in a $1.7 bil­lion deal, fol­low­ing the likes of Mer­ck, No­vo Nordisk, J&J, Boehringer and Alex­ion.

No­var­tis is an ag­gres­sive play­er in the on­col­o­gy are­na. It moved de­ci­sive­ly to al­ly it­self with in­ves­ti­ga­tors at the Uni­ver­si­ty of Penn­syl­va­nia on CAR-T and swift­ly moved from in­vestor to part­ner with In­tel­lia on gene edit­ing tech. Gen­er­al­ly cir­cum­spect about what it will pay in any deal, the com­pa­ny has sig­naled time and again that it will fork over what it needs to to get the tech that it wants. In this case the com­pa­nies didn’t an­nounce the up­side on the hefty mile­stone pack­age, but Xen­cor in­clud­ed the num­ber in its SEC fil­ing.

Xen­cor is by no means alone in bis­pecifics, but the biotech says it’s sep­a­rate from the pack.

“What dis­tin­guish­es us is plug-and-play sim­plic­i­ty,” Xen­cor CEO Bassil Dahiy­at tells me in an email.  “Mak­ing a bis­pe­cif­ic is just as easy as mak­ing a reg­u­lar an­ti­body can­di­date. And the man­u­fac­tur­ing is stan­dard Ab man­u­fac­tur­ing with stan­dard process­es and great yields. Half-life is long like an an­ti­body. And we’ve tuned their po­ten­cy so they can bring T-cell killing against tu­mors while be­ing tol­er­at­ed, com­pared to the de­gree of tox seen with ear­li­er plat­forms. We make it faster and sim­pler to do bis­pecifics and to give them to pa­tients.”

Bassil Dahiy­at, Xen­cor CEO

Xen­cor’s lead in-house drug is the mid-stage bis­pe­cif­ic XmAb5871, which tar­gets CD-19 and the FcγRI­Ib re­cep­tor to block B cell ac­ti­va­tion with­out elim­i­nat­ing them. That kind of dou­ble team work could dis­tin­guish it from oth­er au­toim­mune drugs. And the biotech has been at work test­ing it for rheuma­toid arthri­tis.

In to­day’s deal, No­var­tis is fol­low­ing up with a pact that puts it in the lab with a group of Xen­cor sci­en­tists who have spent years re­fin­ing a bis­pe­cif­ic an­ti­body ap­proach to can­cer ther­a­py. While one seg­ment of the an­ti­body binds to a tu­mor cell, the Fc re­gion flags an im­mune re­sponse, re­cruit­ing T cells to the tar­get. And that’s a field that No­var­tis has been spe­cial­iz­ing in.

Can­cer R&D has al­so been chang­ing dra­mat­i­cal­ly in re­cent years, com­press­ing years of Phase I-through-Phase III work in­to one rel­a­tive­ly quick lunge for ac­cel­er­at­ed ap­provals of the most promis­ing pro­grams. Chang­ing that time­line has made it pos­si­ble to do big-mon­ey up fronts for new can­cer drugs.

“The crit­i­cal as­pect of this deal is we kept full U.S. com­mer­cial­iza­tion rights and 50/50 world­wide de­vel­op­ment with No­var­tis,” notes Dahiy­at. “So their cap­i­tal and the up­front/mile­stones, com­bined with their ex­per­tise and scale, will help us in our am­bi­tions to one day be a com­mer­cial com­pa­ny, if a lot of steps in be­tween go well! This deal is a great help and we made sure not to li­cense away our fu­ture.  No­var­tis is an ex­cel­lent part­ner be­cause they can de­rive a lot of val­ue of these pro­grams and the re­search pro­grams of theirs that we en­able.”

Xen­cor has just over 60 em­ploy­ees now and ex­pects to add an­oth­er 15 to 20 in the next 12 months, pri­mar­i­ly to con­tin­ue to scale up clin­i­cal de­vel­op­ment ca­pa­bil­i­ty.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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