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)

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

Some Celgene shareholders aren’t happy with how Bristol Myers Squibb’s takeover went down.

On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

When Bristol Myers put down $74 billion to scoop up Celgene back in 2019, liso-cel — the CAR-T lymphoma treatment now marketed as Breyanzi — was supposedly one of the centerpieces of the deal. After going back and forth on negotiations for about six months, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date.

David Hung, Nuvation Bio president and CEO (Nuvation Bio)

FDA places par­tial clin­i­cal hold on David Hung biotech af­ter cer­tain can­cer pa­tients ex­pe­ri­ence eye in­flam­ma­tion

Two and a half years after setting out on another foray into oncology R&D, a biotech headed by David Hung — of Medivation fame — has run into its first setback.

San Francisco-based Nuvation Bio announced early Monday the FDA placed a partial clinical hold on a Phase I dose-escalation study of NUV-422, its CDK inhibitor program for certain types of solid tumors. The trial began enrolling patients in December 2020, and, according to Nuvation, researchers were in the middle of exploring dose escalation and defining the maximum dose tolerable in patients.