Mayo team spot­lights the role of senes­cent cells in neu­rode­gen­er­a­tion, start­ing down a path­way that may lead to Alzheimer’s

As an­ti-ag­ing re­search grows around the world, there’s been a big fo­cus on clear­ing away the “senes­cent” cells that clut­ter bod­ies as peo­ple grow old­er. These ag­ing cells lose the abil­i­ty to di­vide and mouse stud­ies have of­fered a pre­clin­i­cal the­o­ry that sweep­ing them away with new drugs can of­fer peo­ple longer, health­i­er lives.

Now a re­search team at the Mayo Clin­ic is of­fer­ing more an­i­mal da­ta to back that up, and they’re shin­ing a light on a new path­way in neu­rode­gen­er­a­tion and specif­i­cal­ly Parkin­son’s and Alzheimer’s — per­haps the sin­gle most frus­trat­ing field in drug de­vel­op­ment.

Ac­cord­ing to the Mayo team, they were able to de­ter­mine that mi­croglia and as­tro­cyte cells were most like­ly to turn in­to rogue zom­bies. By clear­ing these senes­cent cells from the brains of mice, they tar­get­ed a key path­way im­pli­cat­ed in Alzheimer’s, tamped down on in­flam­ma­tion and had an im­pact on mem­o­ry.

“We used a mouse mod­el that pro­duces sticky, cob­web like tan­gles of tau pro­tein in neu­rons and has ge­net­ic mod­i­fi­ca­tions to al­low for senes­cent cell elim­i­na­tion,” ex­plains first au­thor Tyler Buss­ian, a Mayo Clin­ic Grad­u­ate School of Bio­med­ical Sci­ences stu­dent. “When senes­cent cells were re­moved, we found that the dis­eased an­i­mals re­tained the abil­i­ty to form mem­o­ries, elim­i­nat­ed signs of in­flam­ma­tion, did not de­vel­op neu­rofib­ril­lary tan­gles, and had main­tained nor­mal brain mass.”

The work was pub­lished in Na­ture.

It’s a big leap — and an in­cred­i­bly com­plex chal­lenge — to go from a dis­ease mod­el in pre­clin­i­cal stud­ies to test­ing this con­cept in hu­mans. But bil­lions have been spent on Alzheimer’s with noth­ing but fail­ure to show for it. The theme now is try­ing new things, with a bet­ter un­der­stand­ing that bend­ing the curve of neu­rode­gen­er­a­tion in pa­tients who ex­hib­it symp­toms of their dis­ease will be ex­tra­or­di­nar­i­ly dif­fi­cult.

The most ad­vanced biotech in the senes­cence field is an up­start called Uni­ty, which was able to trans­late their pre­clin­i­cal work in­to a Phase I which starts with os­teoarthri­tis. But in­ves­ti­ga­tors in the field — in­clud­ing the team at Uni­ty — be­lieve they’re on a trail that leads to a host of ail­ments.

Alzheimer’s just may be one of them.

Im­age: Dar­ren Bak­er, se­nior au­thor, and Tyler Buss­ian.MAYO CLIN­IC

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.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? 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.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.