A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Take­da spun out a pipeline of ex­per­i­men­tal psy­chi­a­try drugs to Neu­ro­crine in a $2 bil­lion deal amid a post-merg­er shake­out, R&D chief Andy Plump de­scribed the ther­a­pies as “very in­ter­est­ing but still dif­fi­cult.”

On Tues­day, we got some idea of how dif­fi­cult.

Eiry Roberts

San Diego-based Neu­ro­crine re­vealed that one of the three spot­light clin­i­cal pro­grams they’d ac­quired failed the pri­ma­ry end­point in a Phase II tri­al for schiz­o­phre­nia, reg­is­ter­ing a neg­a­tive out­come on the change from base­line in the pos­i­tive and neg­a­tive syn­drome scale/neg­a­tive symp­tom fac­tor score (PANSS NS­FS).

CMO Eiry Roberts not­ed the IN­TER­ACT study, which en­rolled 256 pa­tients and test­ed three dos­ing lev­els of lu­vadax­i­s­tat in a place­bo-con­trolled set­ting, was “well-de­signed and ex­e­cut­ed” — leav­ing lit­tle room to ma­neu­ver in that end­point. The PANSS score is de­signed to as­sess sever­i­ty of schiz­o­phre­nia symp­toms.

From RBC an­a­lyst Bri­an Abra­hams:

Our sense is that the miss on the pri­ma­ry end­point, the PANSS neg­a­tive score, was like­ly due to a true lack of ef­fi­ca­cy, rather than any con­duct is­sues such as base­line im­bal­ances, glob­al site vari­abil­i­ty or high place­bo ef­fect, though the com­pa­ny has not yet com­plet­ed full analy­sis of PK char­ac­ter­i­za­tion (re­call there is a mod­est food ef­fect). The com­pa­ny is not re­port­ing whether there were any no­table trends or dose de­pen­dent sig­nals, sug­gest­ing there like­ly were none.

There is, though, still a sil­ver lin­ing. The drug — al­so known as TAK-831 — met the sec­ond end­points as­sess­ing cog­ni­tive per­for­mance, and the side ef­fects ap­peared con­sis­tent with pre­vi­ous stud­ies.

All of that backs fur­ther clin­i­cal work with the help of Take­da, Roberts added.

Neu­ro­crine had put down $120 mil­lion up­front to get its hands on a pack­age of three clin­i­cal-stage drugs, plus four more pre­clin­i­cal ther­a­pies. Take­da is then in line for $495 mil­lion in de­vel­op­ment mile­stones plus $1.4 bil­lion in com­mer­cial goal cash as well as roy­al­ties. Or it can trade in some of those mile­stones in fa­vor of a 50:50 prof­it share — should it choose to opt-in.

The deal marked one of the last steps of a ma­jor R&D re­org at Take­da, which was look­ing to shed some weight and earn some cash af­ter pay­ing $62 bil­lion to merge with Shire.

And the turn to fo­cus on sec­ondary end­points was an op­tion baked in­to the lu­vadax­i­s­tat pro­gram, ex­ecs told Stifel an­a­lyst Paul Mat­teis.

“(A)t the out­set of this pro­gram, Take­da had been de­bat­ing on whether to de­vel­op in schiz­o­phre­nia neg­a­tive symp­toms or cog­ni­tion, so a sig­nal on the lat­ter does align with some of the orig­i­nal sci­en­tif­ic hy­pothe­ses,” he wrote, adding that they al­so em­pha­sized “cog­ni­tive im­pair­ment in schiz­o­phre­nia is a big un­met need and worth pur­su­ing. That said, there’s al­so a lot of opac­i­ty here and ze­ro da­ta to an­a­lyze, so while the sec­ondary end­point sig­nal seems in­ter­est­ing and may cush­ion the hit to the stock, it will take a full pre­sen­ta­tion/pub­li­ca­tion to re­al­ly un­der­stand the prospects of ‘831.”

Shares in Neu­ro­crine $NBIX end­ed up falling 7.05% to $101.71.

We will have to wait for the da­ta. The com­pa­ny says it’s eval­u­at­ing the re­sults to de­ter­mine the next steps.

Kevin Gor­man, Neu­ro­crine CEO

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

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Sergio Traversa, Relmada Therapeutics CEO

Rel­ma­da makes 'crit­i­cal changes' to PhI­II tri­al to try and save de­pres­sion drug

Relmada Therapeutics is making changes to its Phase III study of its lead drug for major depressive disorder, in an attempt to avoid problems with a prior trial that showed little difference between the drug and a placebo.

That failure in October wiped 80% from Relmada’s stock price, and was followed by another negative readout a few months later. In both cases, the company said that there had been trial sites that were associated with what it called surprising placebo effects that skewed the results compared with the drug, REL-1017.

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Peter Hecht, Cyclerion Therapeutics CEO

Hard pressed for cash, Cy­cle­ri­on looks for help fund­ing rare dis­ease drug

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Geoff McDonough, Generation Bio president and CEO

Mod­er­na part­ners on non-vi­ral gene ther­a­py with Gen­er­a­tion Bio af­ter swing­ing gene edit­ing deals

Moderna has inked a five-year partnership with gene therapy biotech Generation Bio, it announced Thursday morning, wading deeper into the genetic medicines space as it navigates beyond its vaccine work.

Moderna will pay Generation Bio $40 million upfront and invest another $36 million into the gene therapy biotech. In exchange, Moderna can license Generation Bio’s non-viral gene therapy platforms for two immune cell programs and two liver programs, with an option for a fifth program. Moderna will fund all the research work under the partnership, and could be on the hook for milestone, fee and royalty payments totaling up to $1.8 billion, a company spokesperson tells Endpoints News.

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Paul Song, NKGen Biotech CEO

NK cell ther­a­py-fo­cused biotech eyes SPAC deal

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

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The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”