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.”

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

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