Ear­ly da­ta on NextCure's im­muno-on­col­o­gy drug in lung can­cer pa­tients de­lights in­vestors

Shares of fresh­ly pub­lic biotech NextCure sky­rock­et­ed on Tues­day af­ter the com­pa­ny pub­lished an ab­stract high­light­ing ini­tial da­ta from an ear­ly-stage study of its sole ex­per­i­men­tal im­muno-on­col­o­gy drug.

The ther­a­py, NC318, is en­gi­neered to in­hib­it Siglec-15 (S15), a key im­mune sup­pres­sor in cer­tain can­cer pa­tients whose tu­mors are re­sis­tant to the ex­ist­ing raft of check­point in­hibitors. S15 is found on cer­tain myeloid cells in the tu­mor mi­croen­vi­ron­ment and on cer­tain tu­mor types in­clud­ing lung, ovar­i­an and head, and neck can­cers.

Many pa­tients are re­frac­to­ry to check­point in­hibitors due to the pres­ence of cer­tain im­muno­sup­pres­sive fac­tors in their tu­mor mi­croen­vi­ron­ment. Re­searchers have been try­ing to har­ness dif­fer­ent mol­e­cules to stim­u­late the im­mune sys­tem, in­clud­ing toll-like re­cep­tor (TLR) ag­o­nists — spe­cial­ized pro­teins that ini­ti­ate an im­mune re­sponse to for­eign pathogens or, in this case, can­cer cells. NextCure is work­ing on “nor­mal­iz­ing” the im­mune sys­tem by snuff­ing out a fac­tor that thwarts it from per­form­ing its de­fen­sive du­ties.

Lieping Chen Yale

“Dif­fer­ent from im­mune check­point block­ade, can­cer im­munother­a­py based on nor­mal­iza­tion aims to re­store an im­paired im­mune sys­tem to a healthy state, so it de­tects and de­stroys can­cer­ous cells and avoids harm­ing healthy cells,” said Lieping Chen, Yale pro­fes­sor and sci­en­tif­ic founder of NextCure, in a state­ment in March. “(W)e iden­ti­fied S15 as a ma­jor im­mune sup­pres­sor in B7-H1 (PD-L1) neg­a­tive tu­mors, which are re­sis­tant to cur­rent­ly ap­proved an­ti-PD can­cer ther­a­pies.”

In an ab­stract for the So­ci­ety for Im­munother­a­py of Can­cer (SITC) con­fer­ence — the com­pa­ny dis­closed da­ta from a first-in-hu­man tri­al of NC318, in dos­es rang­ing from 8 mg to 800 mg.

As of Au­gust, 43 pa­tients in­clud­ing those with non-small cell lung, ovar­i­an, melanoma, breast, and col­orec­tal can­cer have been en­rolled. Tu­mor re­spons­es were evalu­able in 32 pa­tients, al­though 11 pa­tients have not reached their first as­sess­ment, and their ef­fi­ca­cy da­ta will be re­port­ed on Sat­ur­day at SITC.

How­ev­er, in pa­tients with NSCLC — the biggest (and most lu­cra­tive) form of lung can­cer, NC318 monother­a­py elicit­ed ac­tiv­i­ty in 5 of 7 sub­jects re­frac­to­ry to PD-1 ther­a­pies.

Da­ta showed 1 com­plete re­sponse (on­go­ing at 41 weeks), 1 par­tial re­sponse (on­go­ing at 14 weeks), 1 sta­ble dis­ease with tu­mor re­duc­tion (on­go­ing for 26 weeks), and 2 with sta­ble dis­ease. Over­all, the ther­a­py was al­so well-tol­er­at­ed, NextCure said.

The Beltsville, Mary­land drug de­vel­op­er’s shares $NXTC cat­a­pult­ed on Tues­day, clos­ing up near­ly 250% at $92.22. The stock be­gan to cor­rect it­self on Wednes­day, slip­ping more than 7% to $85.50 in pre­mar­ket trad­ing.

“Clear­ly, there is thirst for clear sig­nals of ac­tiv­i­ty in im­muno-on­col­o­gy (IO) af­ter years of dis­ap­point­ing da­ta from next-gen­er­a­tion check­points and dif­fi­cult-to-in­ter­pret com­bi­na­tion da­ta. While very in­ter­est­ing, two out of sev­en re­spon­ders (NSCLC, “re­frac­to­ry” to an­ti-PD(L)1) is a very ear­ly sig­nal, and the ab­stract did not make note of any sin­gle-agent ac­tiv­i­ty in oth­er sol­id tu­mors; as­sum­ing no re­spons­es out­side of NSCLC, the over­all re­sponse rate in the 21 evalu­able pa­tients that had reached fi­nal as­sess­ment would be 9.5%,” SVB Leerink an­a­lysts wrote in a note.

“(W)e will be look­ing for pos­i­tive sig­nals from the 11 ad­di­tion­al pa­tients (three in NSCLC), as well as pa­tient his­to­ry and bio­mark­er da­ta that is sup­port­ive of the bi­o­log­ic mech­a­nism and hy­poth­e­sis that Siglec-15 im­mune in­hi­bi­tion is not re­dun­dant with PD-1 in­hi­bi­tion.”

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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FDA Vas­cepa re­view spot­lights new safe­ty sig­nals, pos­si­ble min­er­al oil spoil­er as Amarin hunts a block­buster ap­proval

An in-house FDA review of Amarin’s Vascepa raises a set of hurdles the biotech will have to clear if the biotech expects to get the long-awaited FDA approval that could set it on a path to superstar status. But it appears that Amarin has survived another potential setback without introducing a major new threat to its prospects.
The stakes don’t get much higher, with analysts saying a win this week for Amarin could lead to billions in new sales — provided the agency stamps it with an OK. And investors liked what they say in the FDA review this morning, bumping the stock $AMRN 17%.
The insider take at the agency includes a note on two new safety signals seen in the big cardio outcomes study of the omega-3 fatty acid drug that shocked many analysts with a solid set of efficacy data. There’s a key concern over whether the use of mineral oil in the placebo skewed LDL levels in such a way that tilted the data in Amarin’s favor.
The FDA overview was written by John Sharretts, the acting deputy director in the Division of Metabolism and Endocrinology Products. 
On the safety side, the internal review focused on a 3.1% versus 2.1% rate of adjudicated events of atrial fibrillation or atrial flutter requiring hospitalization. But they also say a-fib shouldn’t confound the benefit-safety of the drug — given the improvement on MACE — or prevent its use. And then there was also a higher rate of bleeding events in the drug arm.

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Prakash Raman. Flagship

Flag­ship woos No­var­tis top deal­mak­er Prakash Ra­man in move to get the BD ball rolling ear­ly

Flagship Pioneering likes to be ahead of its times — so far ahead, perhaps, that it is often challenging to find partners for their startups while the scientific scaffolding is underway. But Prakash Raman is here to change that.

Raman, who most recently headed up business development at the Novartis Institutes for BioMedical Research, became Flagship’s first chief business development officer two weeks ago. By acting as a “central resource” for the 100 companies in the venture fund’s portfolio, he hopes to help entrepreneurs and management teams strategize about dealmaking to capture value beyond the near-term validation of their platform technologies, Raman told Endpoints News.

Bill Haney, Skyhawk

Cel­gene ex­ecs shell out $92M cash for a pair of R&D deals that will fit per­fect­ly in their new home at Bris­tol-My­ers

With Bristol-Myers Squibb’s Celgene buyout all but complete, the BD teams are working in perfect synchrony now. The Celgene side is going back to Skyhawk, a darling of the crowd that set out to drug RNA, and they’re adding a suite of new programs that mesh perfectly with the new regime in charge.

Celgene is shelling out $80 million in a cash upfront to add oncology, immuno-oncology and autoimmune diseases to the initial roundup of neurological targets mapped early in Skyhawk’s existence.

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Reata's bar­dox­olone of­fers promise in pa­tients with rare kid­ney dis­or­der

After surprising Wall Street with positive data on its drug, omaveloxolone, in patients suffering from a notoriously hard-to-treat degenerative neuromuscular disorder last month, Reata Pharma on Monday unveiled pivotal results from a trial testing another drug, bardoxolone, in patients with a rare, genetic form of chronic kidney disease for which there exist no approved therapies.

Bardoxolone, like Reata’s other lead drug — omaveloxolone — is a small molecule engineered to bind to a gene called Keap1 to enhance the activity of the protein Nrf2 in order to defuse inflammation.

FDA puts Sol­id Bio’s lead gene ther­a­py pro­gram on hold — again — af­ter an­oth­er pa­tient is hurt by SGT-001

Solid Biosciences continues to be plagued by safety issues.

Close to 18 months after the gene therapy biotech was able to quickly shed an FDA hold on their lead Duchenne muscular dystrophy program for SGT-001, regulators have stepped back in to force another halt after another patient was hit hard by a set of serious adverse events remarkably similar to the first set.

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Am­gen ax­es 149 of its staff in Cam­bridge of­fice; Evotec, Mil­li­pore­Sig­ma en­ter re­search pact

→ Amgen has submitted a Worker Adjustment and Retraining Act (WARN) — a warning of impending mass layoffs 60 days in advance of the date — to the state of Massachusetts in the wake of the company’s exodus from the neurosciences R&D sector. David Reese, the company’s R&D chief, said at the time that the company is cutting ties in the field to focus on other undisclosed areas. In its WARN notice, the Cambridge-based company stated that 149 of its employees would be affected — less than the 180 they previously announced. The terminations will take effect on December 31, 2019.

Kad­mon wax­es rhap­sod­ic on cGVHD re­sults as race with Jakafi heats up

A year ago, Kadmon piqued cautious interest and sent its stock up 20% when it announced positive results from a tiny proof-of-concept study on a new, chronic graft-versus-host-disease treatment. Now interim results are out on the pivotal, and not just the biotech’s executives are gushing about it.

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