The top win­ners and losers on AS­CO ab­stract night: Loxo, Blue­print, Jounce, Mer­ck KGaA and more

Let the joust­ing be­gin.

The big ab­stract drop ahead of AS­CO — the an­nu­al Olympics of can­cer R&D — pro­vid­ed some ear­ly, quick snap­shots that helped dri­ve stocks up or down, or sim­ply pro­vid­ed a chance to tout some po­ten­tial in a hot­ly con­test­ed field.

As more and more bio­phar­ma mon­ey has been in­vest­ed in the on­col­o­gy field in re­cent years, AS­CO has been at­tract­ing a big­ger range of en­trants, and ab­stract night will help de­ter­mine who comes out on top dur­ing the melee ahead. I’ve picked out a few of the most no­tice­able ab­stracts, which you can see be­low.

Loxo takes an­oth­er round in its bruis­ing, toe-to-toe fight with Blue­print

Josh Bilenker

Loxo On­col­o­gy $LOXO was the big win­ner Wednes­day night as in­vestors be­gan to pick through a pile of AS­CO ab­stracts to see what gems could be culled from the num­bers.

The biotech’s stock soared 18% overnight as in­vestors spot­light­ed a 69% over­all re­sponse rate among 32 evalu­able RET-fu­sion pos­i­tive pa­tients tak­ing LOXO-292. Loxo’s claim to fame is that it de­vel­ops can­cer drugs that tar­get small, ge­net­i­cal­ly de­fined pa­tient groups with an ag­nos­tic ap­proach to tu­mor types. Reg­u­la­tors at the FDA have been en­thu­si­as­tic about this emerg­ing field, which bodes well for Loxo. And they backed that en­thu­si­asm up with da­ta demon­strat­ing a 65% re­sponse rate in NSCLC and 83% for pap­il­lary thy­roid can­cer. 84% (27/32) of the pa­tients had ra­di­ograph­ic tu­mor re­duc­tion rang­ing from 19% to 67%.

That’s good, but it may well get bet­ter. Loxo CEO Josh Bilenker has flagged that since the Jan­u­ary cut­off date for the ab­stract the da­ta are even bet­ter now, which we’ll see at AS­CO. Loxo helped stoke the en­thu­si­asm with a note high­light­ing that LOXO-292 has been se­lect­ed for best of show at AS­CO, which will keep the com­pa­ny in the spot­light.

Can­cer R&D, though, is the ul­ti­mate blood sport in biotech. And when some­thing goes up, it’s of­ten at the ex­pense of a ri­val. In this case, that’s Blue­print Med­i­cines — again — which has al­ready felt the sting of a neg­a­tive com­par­i­son with Loxo.

Blue­print Med­i­cines $BPMC has been ad­vanc­ing BLU-667, which has been at­tract­ing warm re­views by an­a­lysts — un­less they start com­par­ing it to the ri­val. That side-by-side com­par­i­son knocked their stock back at AACR, and it did it again last night as the num­bers once again fa­vored Loxo. Shares are down about 8% in pre-mar­ket trad­ing Thurs­day.

No­var­tis vs Gilead/Kite: Is Kym­ri­ah bet­ter and safer than Yescar­ta?

Few ri­val­ries have been as in­tense as the show­down be­tween these two pi­o­neers in the CAR-T field. No­var­tis’ Kym­ri­ah $NVS still has to over­come a nag­ging is­sue with one-time man­u­fac­tur­ing is­sues, but Gilead’s Yescar­ta $GILD is now be­ing com­pared with its ri­val, and at first blush may have some ex­plain­ing to do. 

A group in Bei­jing ran a small com­par­i­son study of the two types of CAR-Ts — which use the 4-1BB and CD28 co-stim­u­la­to­ry sig­nal­ing do­mains — for CD19-pos­i­tive B-cell acute lym­phoblas­tic leukemia and found that the Kym­ri­ah/4-1BB ap­proach ap­pears to have a dis­tinct set of ad­van­tages. 

In that 4-1BB arm there was a 100% over­all ob­jec­tive re­sponse rate, com­pared to 89% in the CD28 arm. In ad­di­tion, and more im­por­tant­ly, all 5 of the pa­tients suf­fer­ing from se­ri­ous Grade 3 or 4 cy­tokine re­lease syn­drome were in the CD28/Yescar­ta group. This ar­gu­ment has a long way to run, and Gilead won’t con­cede an inch of the race. But the com­par­isons have just be­gun.

On Mon­day, Gilead con­tact­ed us to of­fer this state­ment:

It is im­por­tant to note that Yescar­ta was not eval­u­at­ed in this study. The ab­stract dis­cuss­es da­ta from a study eval­u­at­ing oth­er CAR T prod­ucts us­ing 4-1BB and CD28 co-stim­u­la­to­ry sig­nal­ing do­mains, re­spec­tive­ly. Im­por­tant­ly, Yescar­ta is en­gi­neered us­ing Kite’s man­u­fac­tur­ing process. The CD28 CAR T eval­u­at­ed in this tri­al was not man­u­fac­tured by Kite and there have been no head-to-head stud­ies of Yescar­ta com­pared to ti­s­agen­le­cleu­cel.

Ever­core ISI an­a­lyst Umer Raf­fat this morn­ing called the re­sults of this study provoca­tive, but wants to see the de­tails. So do I.

Jounce shares plunge on the lat­est da­ta cut for JTX-2011

Eliz­a­beth Tre­hu

The biggest los­er overnight was Jounce Ther­a­peu­tics $JNCE, which took a nasty hit af­ter post­ing their up­date on their lead ther­a­py — JTX-2011. As a monother­a­py, 1 out of 7 pa­tients with gas­tric can­cer re­spond­ed, com­pared to 2 out of 19 who got the com­bo with Op­di­vo — an 11% re­sponse rate. The rate wasn’t much bet­ter in triple-neg­a­tive breast can­cer. 

In a re­lease, re­searchers hit the theme that these were heav­i­ly pre­treat­ed pa­tients, but on­look­ers were in a can­tan­ker­ous mood and didn’t like the un­der­whelm­ing num­bers. Shares plunged 26% and Wells Far­go down­grad­ed the stock.

Cel­gene struck a ma­jor deal to col­lab­o­rate with Jounce on this drug, and that wasn’t ig­nored this morn­ing.

“The pre­lim­i­nary da­ta from pa­tients across mul­ti­ple sol­id tu­mor types en­rolled in the ICON­IC tri­al show that JTX-2011 is well-tol­er­at­ed alone and in com­bi­na­tion with nivolum­ab and has demon­strat­ed ev­i­dence of bi­o­log­ic ac­tiv­i­ty and tu­mor re­duc­tions in heav­i­ly pre-treat­ed pa­tients who have failed all avail­able ther­a­pies. In ad­di­tion, a po­ten­tial sur­ro­gate bio­mark­er of re­sponse has been iden­ti­fied that may help to guide JTX-2011 de­vel­op­ment,” said Eliz­a­beth Tre­hu, chief med­ical of­fi­cer of Jounce Ther­a­peu­tics.

Nek­tar sees a big ero­sion in re­sponse rates for close­ly-watched I/O star NK­TR-214

Nek­tar $NK­TR scored one of the biggest deals in bio­phar­ma so far this year when Bris­tol-My­ers came in with a $3.6 bil­lion deal to part­ner on NK­TR-214. That part­ner­ship was an­nounced in the wake of the first glimpse of how ef­fec­tive a pair­ing of their drug could be with Op­di­vo, with 63% of a small group of ad­vanced melanoma pa­tients re­spond­ing to first-line ther­a­py. But in Nek­tar’s up­date this week re­searchers note that the re­sponse rate in the bas­ket study showed a re­duced melanoma im­pact, with a 52% re­sponse rate.

Re­nal cell car­ci­no­ma al­so dropped, falling to 54%, down from 71% re­port­ed in the com­pa­ny’s Q4 call in ear­ly March.

That’s by no means the kiss of death. Re­sponse rates tend to de­cline over time. But an­a­lysts will be watch­ing these num­bers close­ly to see just how far they drop for a drug that is now front and cen­ter in the late-stage on­col­o­gy pipeline. The stock is down 3% in pre-mar­ket trad­ing, with the ju­ry still out on this promis­ing ther­a­py.

Mer­ck KGaA plans to shine a light on its can­cer pipeline at AS­CO — with Pfiz­er jump­ing in

Mer­ck KGaA will be back at AS­CO look­ing to earn some re­spect for its can­cer drug pipeline. So far the bulk of the at­ten­tion has gone to Baven­cio, its PD-L1 check­point in­hibitor part­nered with Pfiz­er, which is fight­ing an up­hill bat­tle to gain mar­ket share against the lead­ers in the field. But the Ger­man Mer­ck has a pipeline in on­col­o­gy, and they will do their best to high­light their chances on a range of ther­a­pies in Chica­go.

Its c-Met re­cep­tor ty­ro­sine ki­nase in­hibitor tepo­tinib has earned some ku­dos from Bern­stein. And re­searchers post­ed da­ta on 15 pa­tients with ad­vanced non-small cell lung can­cer har­bor­ing MET ex­on 14 skip­ping mu­ta­tions, with 60% demon­strat­ing a con­firmed par­tial re­sponse. An­a­lysts be­lieve this drug could hit $650 mil­lion in sales by 2030 — not a block­buster but a sol­id suc­cess, which the com­pa­ny bad­ly needs af­ter a long drought in clin­i­cal de­vel­op­ment suc­cess­es.

On the com­bo front, where all the PD-1/PD-L1 play­ers are fo­cus­ing on in a va­ri­ety of ways, Mer­ck KGaA tout­ed their M7824, a TGF-ß trap/an­ti-PD-L1 bi-func­tion­al im­munother­a­py fu­sion pro­tein. High PD-L1 ex­press­ing pa­tients ex­hib­it­ed an ORR of 71.4%.

The next big step on Baven­cio lies in com­bo ther­a­pies, and there Mer­ck KGaA says it gained some ear­ly-stage ev­i­dence to back up a com­bi­na­tion of the check­point with lor­la­tinib in non-small cell lung can­cer — a key com­pet­i­tive front for these play­ers. And their com­bo came out way ahead in the JAVELIN Lung 101 study, which com­pared their check­point with Xalko­ri (crizo­tinib) and the lor­la­tinib match-up. Lor­la­tinib — a drug Pfiz­er has high hopes for — came out way ahead. From the ab­stract:

The con­firmed ob­jec­tive re­sponse rate with A+C in ALK− pts was 16.7% (95% CI, 2.1-48.4; par­tial re­sponse [PR] in 2 pts), and with A+L in ALK+ pts was 46.4% (95% CI, 27.5-66.1; PR in 12 pts; com­plete re­sponse in 1 pt).


Im­age: Poster ses­sion at AS­CO 2017. AS­CO

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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Pascal Soriot (AP Images)

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.

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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.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

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.

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.

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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.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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