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.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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Image: Shutterstock

MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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Andrew Phillips, Nexo Therapeutics CEO

Scoop: Ver­sant, NEA launch new biotech helmed by ex-CEO of pro­tein de­grad­er C4 Ther­a­peu­tics

Long-time biotech venture firms Versant and New Enterprise Associates are backing a new startup run by former C4 Therapeutics chief executive Andrew Phillips.

The fledgling biotech has raised at least $30 million so far, according to paperwork filed with the SEC this week. The round could balloon to $60 million.

Phillips, who left protein degradation startup C4 in 2020 to be a managing director at Cormorant Asset Management, is running the show of the new venture as president, the SEC filing outlines. He also served as interim CEO of Cormorant-backed and Hansoh Pharmaceutical-partnered Blossom Bioscience last year.

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J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.

Dermavant Sciences' first consumer TV ad for its Vtama psoriasis med shows people ready for a new topical treatment.

Roivant’s Der­ma­vant de­buts first-ever TV com­mer­cial for pso­ri­a­sis cream Vta­ma

Dermavant Sciences has been marketing its first product, psoriasis med Vtama, to dermatologists for months, but on Tuesday it rolled out its first consumer campaign. The debut DTC effort including a streaming TV commercial encourages patients to a “Topical Uprising” in a nod to Vtama being a topical cream.

In the new commercial, a swell of people discards scarves and jacket coverings, gathering in the street to converge on a pharmacy to demand a steroid-free prescription. A moment of levity follows when a pharmacist says, “You know you can just talk to your doctor, right?” The gathered crowds collectively says, “Oh.”

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FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.