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)

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Ed Kaye, Stoke Therapeutics CEO

Stoke touts ear­ly signs of ef­fi­ca­cy for Dravet syn­drome drug

Two and a half years after driving his antisense oligonucleotide platform to Wall Street, Stoke Therapeutics CEO Ed Kaye is painting a fuller picture of the company’s first clinical data. And though the trial wasn’t powered to detect statistical significance, Kaye says the readout shows early signs of efficacy in kids with a rare, drug-resistant form of epilepsy

STK-001 was well-tolerated in single and multiple doses in 22 Dravet syndrome patients between the ages of 2 and 18 years old, Stoke announced on Friday. What’s more, 12 of the 17 evaluable patients at the time (70.6%) saw reductions from baseline in convulsive seizure frequency, according to the company.