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.

Boehringer Ingelheim uncorked some positive results suggesting that Spevigo can help prevent flare-ups in patients with a severe form of psoriasis, months after the drug was approved to treat existing flares.

Spevigo, an IL-36R antibody also known as spesolimab, met its primary and a key secondary endpoint in the Phase IIb EFFISAYIL 2 trial in patients with generalized pustular psoriasis (GPP), Boehringer announced on Monday. While the company is keeping the hard numbers under wraps until later this year, it said in a news release that it anticipates sharing the results with regulators.

AstraZeneca, Novo Nordisk, and Sanofi won an appeals court win on Monday, as the US Court of Appeals for the Third Circuit found that the companies cannot be forced to provide 340B-discounted drugs purchased by hospitals from an unlimited number of community and specialty pharmacies.

“Legal duties do not spring from silence,” the decision says as the court makes clear that the federal government’s interpretation of the “supposed requirement” that the 340B program compels drugmakers to supply their discounted drugs to an unlimited number of contract pharmacies is not correct, noting:

A US appeals court has ruled against Johnson & Johnson’s use of bankruptcy to deal with mounting talc lawsuits, deciding that doing so would “create a legal blind spot.”

The Third Circuit Court of Appeals reversed a previous bankruptcy court decision on Monday, calling for the dismissal of a Chapter 11 filing by J&J’s subsidiary LTL Management.

Faced with more than 38,000 lawsuits alleging its talc-based products caused cancer, J&J spun its talc liabilities into a separate company called LTL Management back in October 2021 and filed for bankruptcy, a controversial move colloquially referred to as a “Texas two-step” bankruptcy. Claimants argued that the strategy is a misuse of the US bankruptcy code — and on Monday, a panel of judges agreed.