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

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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FDA+ roundup: Marks on Wood­cock­'s tenure as act­ing com­mis­sion­er; FDA lead­ers of­fer per­spec­tive on bar­ri­ers to di­ver­si­ty in re­search

CBER director Peter Marks praised Janet Woodcock’s work as acting FDA commissioner, and while noting that Biden needs to nominate someone to fill the role permanently by Nov. 16, he said he has “no idea” when that actually might occur.

“Dr. Woodcock has been at the agency for over three decades and she, during that time, has proven herself to be a remarkably capable manager,” Marks said at the Alliance for Regenerative Medicine’s meeting Tuesday. “And she’s been managing as if she’s commissioner, unlike some previous acting [commissioners] who are afraid to actually do things. She doesn’t appear to be afraid to do things. I have not felt any different now from when we had a commissioner in place,” he added.

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FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.