Robin Mansukhani, Deciduous Therapeutics CEO (Deciduous)

Can a rare im­mune cell of­fer the key to slow­ing down senes­cence? A Bay Area start­up looks to find out

For years, sci­en­tists have looked to curb ag­ing and chron­ic dis­eases by clear­ing de­funct cells with ir­repara­ble dam­age, al­so known as senes­cent cells. Drug­mak­ers like Bris­tol My­ers Squibb and Uni­ty Biotech­nol­o­gy have toiled over senolyt­ics to kill the stub­born cells. So when Robin Man­sukhani was told it could be done us­ing reawak­ened im­mune cells, he was in­trigued.

Senes­cence serves a pro­tec­tive func­tion. It oc­curs when cells are too dam­aged to keep di­vid­ing — for ex­am­ple, if they de­vel­op a can­cer­ous mu­ta­tion. But senes­cent cells al­so con­tribute to ag­ing and oth­er dis­eases, emit­ting tox­ic mol­e­cules that cause in­flam­ma­tion and tis­sue dam­age.

Anil Bhushan

Back in 2018, Man­sukhani was in­tro­duced to Anil Bhushan, a pro­fes­sor at the Uni­ver­si­ty of Cal­i­for­nia, San Fran­cis­co, who was work­ing on a way to weaponize in­vari­ant Nat­ur­al Killer T (iNKT) cells against senes­cent cells to treat type 1 di­a­betes. iNKT cells act as a sort of sur­veil­lance sys­tem, elim­i­nat­ing for­eign cells, but be­come less ac­tive with age and oth­er fac­tors.

“I fol­lowed senes­cence for a long time, but I nev­er ever thought about it in the con­text of type 1 di­a­betes. So that da­ta just kind of knocked me aside,” Man­sukhani said.

He did his own re­search, then about six weeks lat­er teamed up with Bhushan to launch De­cid­u­ous Ther­a­peu­tics. While the team is no longer go­ing af­ter di­a­betes, they pub­lished a pa­per on Mon­day in Med link­ing in vi­vo iNKT cells with clear­ing senes­cent cells.

“These cells have long been of in­ter­est to peo­ple — they just, you know, haven’t re­al­ly fig­ured out what to do with them or what they re­al­ly do,” Man­sukhani, now CEO, said. “There was some­thing in the senes­cent cell that said, OK, there’s a foot­print here to an im­mune cell that’s go­ing to talk to this senes­cent cell and clear it out. And that’s where things get ex­cit­ing.”

iNK­Ts have two main at­trib­ut­es that make them an ap­peal­ing tar­get, Man­sukhani ex­plained. First, they have the same re­cep­tor, which doesn’t ap­pear on any oth­er cell in the body, al­low­ing a high lev­el of speci­fici­ty. And they al­so op­er­ate in a nat­ur­al neg­a­tive feed­back loop, that re­turns them to dor­man­cy af­ter a pe­ri­od of ac­tiv­i­ty.

“Us­ing iNKT-tar­get­ed ther­a­py can pig­gy­back on their ex­quis­ite, built-in speci­fici­ty,” Bhushan said in a state­ment.

Us­ing the ap­proach, the sci­en­tists were able to im­prove blood glu­cose lev­els in mice with di­et-in­duced obe­si­ty, and ex­tend the lives of mice with lung fi­bro­sis. Go­ing forth, Man­sukhani said the team is go­ing to look at things like chron­ic kid­ney dis­ease and car­diac fi­bro­sis. He ex­pects to hit the clin­ic in mid-to-late 2023.

“The ra­tio­nale here was that, if this hap­pens nat­u­ral­ly in the body by the im­mune sys­tem, let’s just go back and un­der­stand that first, and then we can fig­ure out what to do with that in­for­ma­tion once we ac­tu­al­ly un­der­stand that un­der­ly­ing first prin­ci­ple,” he said.

Un­lock­ing ESG strate­gies for growth with Gilead Sci­ences

RBC Capital Markets explores what is material in ESG for biopharma companies with the ESG leads at Gilead Sciences. Gilead has long focused on sustainability but recognized a more robust framework was needed. Based on a materiality assessment, Gilead’s ESG strategy today focuses first on drug access and pricing, while also addressing D&I and climate change. Find out why Gilead’s board is “acutely aware” of the contribution that ESG makes to firm’s overall success.

On the hunt for the next Mod­er­na, in­vestors have pumped 'plat­form plays' with cash. Can any­thing slow the run­away train?

It didn’t take an expert to see that mRNA platforms could be huge.

Julie Sunderland partnered with both Moderna and BioNTech about a decade ago while she was running program-related investments for the Bill & Melinda Gates Foundation — and even then the potential for their platforms was obvious despite some well-founded concerns about whether the next-gen tech would ever cross the finish line.

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Sen. Ron Wyden (D-OR) with reporters in the Senate Subway (Graeme Sloan/Sipa via AP Images)

Top Wyden pri­or­i­ty for drug price re­forms: Medicare ne­go­ti­a­tions

As the Biden administration tries to wrangle the details of its infrastructure bill, Senate Finance Committee Chair Ron Wyden (D-OR) took a concrete step forward on drug pricing reforms on Tuesday and unveiled five principles for such reforms, including providing Medicare with the ability to negotiate prices.

“Allowing the Secretary of HHS to negotiate the price Medicare will pay creates a much needed mechanism to achieve fairer prices when the market has failed to do so,” Wyden wrote.

End­points News is now 5 years old. Here's how you can sup­port us for the next phase of growth

Endpoints News turned five years old over the weekend. I wanted to mark the happy occasion by extending our deepest gratitude to Endpoints’ premium subscribers while outlining several other ways to support us as we go broader and get bigger this year and beyond.

Same as any business, we’ve got to create value and get paid for delivering it. So if you depend on Endpoints to stay abreast on biopharma developments, we depend on you too.

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

Ac­tivist in­vestor El­liott in talks with oth­er Glax­o­SmithK­line in­vestors about re­plac­ing Em­ma Walm­s­ley, spin­ning off vac­cine busi­ness — re­port

As Emma Walmsley reveals details this Wednesday about the upcoming split of GlaxoSmithKline’s pharma and consumer units, some tough questions may be coming her way.

Elliott Management, the activist investor that’s previously threatened an attack on GSK (but eventually backed off), is floating more radical changes like replacing the CEO, further breaking up the company and spinning out the vaccine unit, or reviewing the focus on cancer drugs, the Financial Times reported.

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Fred Upton and Diana DeGette

New DARPA-like NIH agency preps for re­al­i­ty as E&C un­veils bi­par­ti­san Cures 2.0 draft bill

House Energy & Commerce leaders Fred Upton (R-MI) and Diana DeGette (D-CO) on Tuesday released new draft legislation with wide-ranging implications for public health, the FDA, NIH, and that would create a new, $6.5 billion federal advanced research agency under NIH, with an aim to cure cancer, Alzheimer’s and other difficult diseases.

Similar to DARPA, the new NIH division to be known as ARPA-H, would be run by a small group of program managers with more latitude to pursue high-risk, high-reward projects that other government agencies would likely shy away from.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

Mer­ck­'s Keytru­da blazes a path in first-line cer­vi­cal can­cer, mak­ing good on drug­mak­er's push for ear­li­er pa­tients

In the years since I/O wonder drug Keytruda’s initial approval, Merck has struck an aggressive clinical trial program, which is now firmly focused on earlier lines of therapy. The drugmaker has scored some success there so far, and now it’s earned one of its biggest wins yet.

Keytruda plus chemotherapy with or without background Avastin significantly extended patients’ lives over those dosed with a placebo control in first-line patients with persistent, recurrent or metastatic cervical cancer, according to top-line data from the Phase III KEYNOTE-826 study revealed Tuesday.

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Kimberly Smith, ViiV via Youtube

They went from dai­ly to once every two months. But how much longer act­ing can HIV meds be? Vi­iV en­lists Halozyme's tech to find out

It wasn’t easy navigating the manufacturing and controls issues that had led the FDA to reject ViiV Healthcare’s first pitch for the once-monthly HIV regimen cabotegravir and rilpivirine. But even as Kimberly Smith was knee-deep in sorting out those problems and putting together a new package that finally won the regulators over this January, her business development team kept looking for things that would take them to the next level.

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Roche's Alzheimer's drug spurred bio­mark­er changes but no cog­ni­tive im­pact — pa­per; vTv out-li­cens­es for­mer lead pro­gram

More than a year ago, Roche and Eli Lilly were forced to contend with a Phase II/III failure of their respective Alzheimer’s drugs. But while Eli Lilly essentially threw in the towels, Roche wasn’t ready to give up yet.

The Swiss drugmaker now has some biomarker data to spotlight as investigators continue monitoring patients in an open-label extension study.

Dubbed DIAN-TU, the study had been designed to see whether Roche’s gantenerumab and Lilly’s solanezumab could spur a cognitive benefit for a group of patients who had a rare, inherited form of Alzheimer’s that’d tied to early-onset. In short, they didn’t: Both failed the primary endpoint.