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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; 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.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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