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.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,100+ biopharma pros reading Endpoints daily — and it's free.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

Endpoints Premium

Premium subscription required

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

News brief­ing: Gilead part­ner Gala­pa­gos sells off CRO for $37M; Polyphor bags $3.3M from CF Foun­da­tion

Close Gilead ally Galapagos is selling off one of its contract research organizations to a Polish pharma company.

Galapagos has agreed to sell 100% of the outstanding shares in the CRO Fidelta to Selvita, in a deal worth roughly $37 million expected to close in the first week of January. The acquisition is expected to nearly double Selvita’s revenues, the company says, as well as expand its drug discovery efforts.

Michelle Longmire, Medable CEO (Jeff Rumans)

Med­able gets $91M for vir­tu­al clin­i­cal tri­als, bring­ing to­tal raise to $136M

As biotechs look to get clinical studies back on track amid the pandemic, Medable returned to the venture well for the second time this year, bagging a $91 million Series C to build out its virtual trial platform.

The software provider recently launched three new apps for decentralizing clinical trials, and saw a 500% revenue spike this year. And it isn’t alone. Back in August, Science 37 secured a $40 million round for its virtual trial tech, with support from Novartis, Sanofi Ventures and Amgen. Patients and researchers are taking a liking to the online approach, suggesting regulators could allow it to become a new normal even after the pandemic is over.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

Endpoints Premium

Premium subscription required

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