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.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Am­gen lays off about 300 work­ers, cit­ing 'in­dus­try head­wind­s'

Amgen has laid off about 300 employees, a company spokesperson confirmed to Endpoints News via email Sunday night.

Employees posted to LinkedIn in recent days about layoffs hitting Amgen last week. The Thousand Oaks, CA-based biopharma, which employs about 24,000 people, said the reduction “mainly” impacted US-based workers on its commercial team.

Drug developers of all sizes, including small upstarts and pharma giants, have let employees go in recent months as the biopharma market drags through a quarters-long winter doldrum.

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Boehringer In­gel­heim touts pre­ven­tion re­sults in rarest form of pso­ri­a­sis

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 score 340B-re­lat­ed ap­peals court win over HHS

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:

Ap­peals court toss­es J&J's con­tro­ver­sial 'Texas two-step' bank­rupt­cy case

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.

Chad Mirkin, Flashpoint co-founder

‘The field is at a flash­point’: New Chad Mirkin-found­ed biotech hopes to make more ef­fec­tive can­cer vac­cines

Following the success of the mRNA Covid vaccines, cancer vaccines are seeing renewed interest after years of middling results. But a group of researchers suggests that more attention needs to be paid not to what goes into those vaccines, but how the parts are put together.

In a recent paper published in Nature Biomedical Engineering, researchers led by Northwestern University’s Chad Mirkin describe how the placement of different antigens in a cancer vaccine impacts its efficacy. The paper builds on past work done by Mirkin’s lab that suggests the structure, or how the parts of a vaccine are arranged, impact a vaccine’s efficacy, not just its components.

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#JPM23: Reg­u­la­to­ry un­cer­tain­ty? What about M&A? Da­ta rule? Alessan­dro Masel­li and John Car­roll take out their crys­tal balls

Endpoints editor and founder John Carroll sat down the Catalent CEO Alessandro Maselli to talk about what’s ahead in 2023. Right or wrong, this covers all the big issues faced by biopharma. This transcript has been edited for brevity and clarity.

John Carroll:

I think 2022 had to be one of the worst years ever for crystal balls. You went into 2022 thinking all sorts of nice things about what was ahead, not thinking about a European land war, maybe not thinking that the Federal Reserve was going to be jacking up interest rates as fast as they could to get ahead of inflation. Just a tremendous number of macroeconomic issues that were out there. The sudden and complete collapse of support on the markets in Nasdaq for biotech. A lot of darlings in the industry that had been out there for a while suddenly found themselves moving from a really hot market to a really cold market all of a sudden and had to make a lot of different changes in terms of strategizing.

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Richard Gonzalez, AbbVie CEO (Chris Kleponis/picture-alliance/dpa/AP Images)

Up­dat­ed: $100B+ in sav­ings? Why the in­com­ing Hu­mi­ra biosim­i­lars will take time to catch on

The 20-year reign of AbbVie’s best-selling biologic of all time — the autoimmune disease biologic Humira (adalimumab) that has brought in upwards of $200 billion during its monopoly — is coming to an end tomorrow with the launch of Amgen’s biosimilar Amjevita.

The launch comes more than four years after Europe saw the exact same competition, leading to steep discounts in price, higher uptake, and big cost savings across the board.

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A new Genentech 'MS Visibility' campaign video features Black women living with or connected to MS talking about their experiences. (Genentech)

Roche’s Genen­tech de­buts next it­er­a­tion of MS cam­paign, high­lights ex­pe­ri­ences in Black com­mu­ni­ty

Roche’s Genentech is tackling diversity in multiple sclerosis again, this time with a focus on the Black community. Its “MS Visibility” effort, debuted in 2021, is now adding to the awareness campaign with new work that includes a set of videos featuring discussions among Black women and healthcare professionals.

“They’re incredibly inspiring Black women living with or connected to MS and they’re having just honest conversation about their experience and the unique barriers that their community faces,” said Jennifer Kim, head of neuroimmunology at Genentech marketing.

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