Lee Kraus, UT Southwestern

PARP in­hibitors some­times work be­yond BR­CA-mu­ta­tions, re­searchers may fi­nal­ly know why

A class of po­tent can­cer treat­ments could shine brighter than pre­vi­ous­ly thought in a broad­er ar­ray of pa­tients, new re­search sug­gests.

PARP in­hibitors, in­clud­ing As­traZeneca’s $AZN pi­o­neer­ing Lyn­parza, Clo­vis’ $CLVS Rubra­ca and GSK’s $GSK Ze­ju­la — work by thwart­ing PARP pro­teins that help re­pair dam­aged DNA in cell — there­by steer­ing can­cer cells on­to a path of an­ni­hi­la­tion. So far, their use has pri­mar­i­ly been in ovar­i­an can­cers con­tain­ing BR­CA mu­ta­tions, rare ge­net­ic mu­ta­tions that dis­able a DNA re­pair path­way in can­cer cells, as well as BR­CA-mu­tat­ed breast can­cer. (Al­though last month, Ze­ju­la was grant­ed pri­or­i­ty re­view to ex­pand its use in late-stage ovar­i­an can­cer pa­tients with or with­out BR­CA mu­ta­tions).

While the as­sault on DNA re­pair is be­ing waged, these drugs are al­so at­tack­ing ri­bo­somes — the ma­chin­ery that makes pro­teins, said Lee Kraus, di­rec­tor of the Green Cen­ter for Re­pro­duc­tive Bi­ol­o­gy Sci­ences at UT South­west­ern. “These find­ings could in­crease the pa­tient pop­u­la­tion ben­e­fit­ing from these drugs by two, three, or four-fold. Up to 70 per­cent of breast can­cer pa­tients could now be good can­di­dates.”

The da­ta, pub­lished in the jour­nal Mol­e­c­u­lar Cell on Wednes­day, could ex­plain why breast can­cer pa­tients can be re­spon­sive to PARP in­hibitors, de­spite not car­ry­ing BR­CA mu­ta­tions.

Kraus and his team iden­ti­fied a po­ten­tial bio­mark­er — a pro­tein called DDX21, which is re­quired for the pro­duc­tion of ri­bo­somes in small sub­cel­lu­lar com­part­ments called nu­cle­oli. But DDX21 in the nu­cle­o­lus re­quires PARP-1, which is tar­get­ed by ex­ist­ing PARP in­hibitors. The use of these drugs, there­fore, blocks DDX21, there­by in­hibit­ing ri­bo­some pro­duc­tion. This means en­hanced DDX21 lev­els in the nu­cle­o­lus could in­di­cate can­cers that might be the most re­spon­sive to PARP in­hibitors, the re­searchers posit­ed.

“Can­cer cells are ad­dict­ed to ri­bo­somes. Can­cer cells grow fast and must make pro­teins to sup­port cell di­vi­sion and oth­er es­sen­tial process­es go­ing on in the cell. If you can slow down or in­hib­it the pro­duc­tion of ri­bo­somes, then you can slow down the growth of the can­cer cell,” Kraus said in a state­ment.

Kraus et al are now work­ing on de­sign­ing clin­i­cal tri­als with UT South­west­ern on­col­o­gists to test their the­o­ry.

Kraus is a founder and con­sul­tant of Ri­bon Ther­a­peu­tics, which ear­li­er this year raised $65 mil­lion to tar­get oth­er PARPs in the broad fam­i­ly of 17 en­zymes. The Cam­bridge, Mass­a­chu­setts-based biotech’s lead pro­gram is first go­ing af­ter PARP7, a pro­tein al­so sim­i­lar­ly ac­ti­vat­ed by stress and cel­lu­lar re­sponse mech­a­nisms.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA au­tho­rizes Pfiz­er's vac­cine boost­er for se­niors, those at high risk for se­vere Covid-19

The Biden administration’s goal of kicking off its booster shot drive for the entire US population this week is not quite going as planned.

First, Pfizer applied for approval of a supplemental application for the booster shots, but since last Friday’s adcomm reviewing them, the plan has devolved into an EUA, which the FDA issued late Thursday evening.

The population that is now eligible for the booster, six months after receiving the first pair of Pfizer-BioNTech vaccines, also narrowed from what Pfizer applied for (everyone who’s eligible for the initial Pfizer shots) to just those who are 65 or older, or at high-risk of a Covid infection, including health care workers and others with occupational hazards.

Stéphane Bancel, AP Images

Fi­nal analy­sis of US-fund­ed Mod­er­na Covid vac­cine tri­al shows 98% ef­fi­ca­cy against se­vere dis­ease

A final look at the results of the placebo-controlled Moderna trial in the New England Journal of Medicine, published Thursday afternoon, shows how the vaccine continues to prevent Covid-19 and severe cases after more than five months following the second shot.

Of the more than 30,000 enrolled in the trial that ultimately led to the vaccine’s EUA, only two people in the vaccine group got a severe form of the disease, compared to 106 in the placebo group — leading to an efficacy of 98%.

Emma Walmsley, GlaxoSmithKline CEO (Credit: Fang Zhe/Xinhua/Alamy Live News)

The fire un­der Glax­o­SmithK­line's Em­ma Walm­s­ley grows as an­oth­er well-known ac­tivist in­vestor grabs its pitch­fork — re­port

Bluebell Capital Partners, a proxy brawler fresh off a campaign to oust global food giant Danone’s CEO and most of its board of directors, has bought a stake in UK drugmaker GlaxoSmithKline with its eyes trained directly on Emma Walmsley, the Financial Times reported Wednesday.

The London-based hedge fund joins another notorious activist firm in Paul Singer’s Elliott Management, which earlier this year called for a shakeup in leadership at GSK to handle what the company described as a wealth of riches across the drug giant’s portfolio hindered by limited vision from top staff.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Joshua Liang, Clover Biopharmaceuticals CEO

With world still in sore need of dos­es, Clover says its Covid-19 vac­cine is 67% ef­fec­tive in Phase III

With concerns about the Delta variant rising and much of the world still in desperate need of vaccine doses, a Chinese biotech announced Wednesday that a new shot has shown positive results in a large trial against Covid-19, including new variants.

Clover Biopharmaceuticals announced Wednesday that its vaccine candidate showed 79% efficacy against the Delta variant in a Phase II/III trial dubbed Spectra, and 67% effective against Covid-19 overall.