Ku­ra flash­es pos­i­tive HRAS da­ta on once-failed J&J drug

Troy Wil­son was work­ing with J&J on their KRAS in­hibitor and pe­ri­od­i­cal­ly thumb­ing through their pub­li­ca­tions when he spot­ted an old drug called tip­i­farnib that looked promis­ing. So promis­ing, in fact, that the large phar­ma had run it through over 5,000 pa­tients across 70 tri­als, hop­ing they would at some point be able to nail down who were the small slice of pa­tients who re­spond­ed in some stud­ies.

“They did it the old-fash­ioned away,” Wil­son told End­points News. “They threw spaghet­ti against the wall, and the spaghet­ti didn’t stick.”

Troy Wil­son

By the ear­ly 2010s, though, when Wil­son was trawl­ing the Janssen archives, there was next-gen se­quenc­ing and mol­e­c­u­lar meth­ods to iden­ti­fy those pa­tients whose can­cers were dri­ven by the pro­tein tip­i­farnib tar­get­ed, HRAS. Wil­son asked the J&J sci­en­tists why they weren’t do­ing that. “Yeah it should work,” Wil­son re­calls them say­ing, but “Troy, we can’t do every­thing.”

So the se­r­i­al biotech ex­ec­u­tive, who had been work­ing with J&J as CEO of Well­spring Bio­sciences, li­censed the drug away and found­ed Ku­ra On­col­o­gy to push it for­ward as a tar­get­ed drug for can­cer pa­tients with HRAS mu­ta­tions or an over-abun­dance of HRAS.

Now for the first time in the 15-plus year his­to­ry of the com­pound, Ku­ra has ev­i­dence that, when giv­en to the right pa­tients, the drug can help pa­tients live longer.

In a re­lease ahead of an AS­CO oral pre­sen­ta­tion, the com­pa­ny re­port­ed Phase II da­ta show­ing that, across 18 pa­tients with HRAS mu­tant head and neck can­cer, the drug had an over­all re­sponse rate of 50% and led to a me­di­an over­all sur­vival of 15.4 months. That com­pares to a me­di­an OS of 5-8 months for sec­ond-line pa­tients, ac­cord­ing to fig­ures cit­ed by the com­pa­ny da­ta. The me­di­an pa­tient in the study had al­ready un­der­gone 2 lines of ther­a­py.

Ku­ra had shown in the fall that the drug could shrink tu­mors, but had yet to show any sur­vival ben­e­fit.

“Yes the pa­tient wants to see their tu­mors shrink, but at the end of the day, the physi­cians and the pa­tients, what they care most about it is that there’s ac­tu­al­ly a sur­vival ad­van­tage,” Wil­son said. “So this is mean­ing­ful when you look at the cur­rent­ly ap­proved ther­a­pies and it’s mean­ing­ful when you think to your­self that sur­vival of 15 months is greater than what you would see in the front­line ther­a­py set­ting.”

The two ad­verse events that ap­peared in more than 10% of pa­tients were cy­tope­nias and GI dis­tur­bances. Pro­gres­sion-free sur­vival was 5.9 months.

The com­pa­ny has al­ready be­gun a reg­is­tra­tional tri­al they hope will lay the ba­sis for an ac­cel­er­ate ap­proval with the FDA, the agency that in 2005 re­ject­ed a J&J ap­pli­ca­tion to ap­prove the drug for AML.

So­cial: Troy Wil­son, Ku­ra On­col­o­gy CEO (Ku­ra via YouTube)

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Sanofi and GSK reach deal with Cana­da for 72 mil­lion vac­cine dos­es

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the biotech.

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Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

J&J re­leas­es PhI­II safe­ty blue­print for Covid-19 vac­cine tri­al. How does it stack up to Mod­er­na, Pfiz­er and As­traZeneca?

Along with the initiation of its Phase III Covid-19 vaccine study announced Wednesday morning, Johnson & Johnson has also released its trial protocol, giving an inside look at how the company is conducting its late-stage research.

The move comes after the other three companies conducting Phase III’s in the US — Moderna, Pfizer and AstraZeneca — each disclosed their own trial blueprints within the last week. Though the release of such protocols is typically done after trials have been completed, drug developers had come under intensifying pressure to do so given the approaching November presidential election.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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