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.

Spe­cial re­port: Meet 20 ex­tra­or­di­nary women who are su­per­charg­ing bio­phar­ma R&D

Even though many biopharma leaders have come together in recent years to address its gender gap, the consensus is clear: We still have a long way to go.

Companies this year were 2.5 times more likely than last year to have a diversity and inclusion program in place, according to a recent BIO survey, but women are still largely absent from executive roles. Getting women to enter the industry isn’t the problem — studies show that they represent just under half of all biotech employees around the world. But climbing through the ranks can be challenging, as women still report facing stereotypes, and, unfortunately, harassment.

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Op­ti­miz­ing Oral Drug De­liv­ery us­ing Zy­dis® Oral­ly Dis­in­te­grat­ing Tablet Tech­nol­o­gy to Ad­dress Pa­tient Chal­lenges

KEY POINTS

Patients prefer oral dosing, but swallowing tablets can be a challenge for many patients.
The Zydis® orally disintegrating tablet (ODT) platform addresses challenges associated with oral dosing, expanding benefits for patients and options for healthcare providers.
A strong growth trajectory is expected for ODTs given therapeutic innovation and continued technology development.

Many patients prefer conventional tablets for the administration of medications, but some geriatric and pediatric patients and those with altered mental status and physical impairments find swallowing tablets to be difficult. Orally disintegrating tablets (ODTs), which dissolve completely without chewing or sucking, offer a patient-friendly dosage form for the administration of small-molecule drugs, peptides and proteins. With the potential for multiple sites of drug absorption, often faster onset action for the active pharmaceutical ingredient (API), and potentially greater bioavailability, ODTs are an attractive option for drug developers considering first-to-market formulations or product line extensions of existing drugs with compatible API. In this report, we look at how innovation in the industry-leading Zydis ODT platform is expanding oral formulation options and bringing benefits to patients.

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Geoffrey Porges (SVB Leerink)

The 2022 wave com­ing? Top an­a­lyst says Big Phar­ma will have more than $1T avail­able to sat­is­fy its grow­ing ap­petite for biotech M&A

All through this year you could practically feel the frustration of the biotech investor class as M&A activity continued to drag behind expectations — or desires. Buyouts of public companies provide the essential juice for keeping stocks lively, and there’s been a notable lack of juice in 2021.

So is all that about to change, big time?

SVB Leerink’s Geoffrey Porges, a longtime student of biotech M&A, thinks so. In a lengthy analysis he put out last week, Porges totted up the cash flow of the major pharmas and determined that there was a good long list of industry buyers who would have around a half trillion dollars of cash to play with in 2022. Leverage that up with added debt and you could get that deal cache to $1.6 trillion.

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Róbert Wessman, Alvotech chairman and founder

Ice­landic bil­lionare's biosim­i­lar com­pa­ny rais­es $450M, preps for Nas­daq launch with SPAC merg­er

As Icelandic billionaire Róbert Wessman tries to take down AbbVie’s megablockbuster Humira in court, he’s also taking his biosimilar upstart to the big time with a $2.25 billion SPAC merger, Nasdaq launch and $450 million raise announced early Tuesday.

While Wessman’s Alvotech has not won FDA approval for any of its biosimilar candidates yet, the company was the first to file with the FDA for approval of its high-concentration Humira biosimilar and to have successfully conducted a switching study in support of a highly-coveted interchangeability designation. But other companies like Amgen, Boehringer Ingelheim and Pfizer have since caught up ahead of the launches of their own Humira biosimilar competitors in 2023.

Mar­ket­ingRx Matchup: How Ab­b­Vie and Bio­haven ads rank in head-to-head mi­graine chal­lenge

Are you ready to rumble? DTC brands that is. MarketingRx is launching a new monthly feature today called MarketingRx Matchup. We’re pitting two pharma brands’ DTC advertising in the same therapeutic category against each other to find out what consumers and patients really think.

Market research company Leger is handling the polling and analysis each month, and I’ll be writing up the results — along with my own take — inside MRx on the first Tuesday of the month.

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Wendy Lund, Organon chief communications officer

Q&A: Organon chief com­mu­ni­ca­tions of­fi­cer Wendy Lund talks about the Mer­ck spin­off, women’s health and why it mat­ters

One of Wendy Lund’s earliest jobs was head of marketing at Planned Parenthood. As the youngest person on its management team, she introduced them to emerging new technologies, and in return, she learned the importance of fighting for what you believe in.

Now as chief communications officer at Organon, the women’s health company recently spun off by Merck, Lund is keeping that point top of mind. That’s in part because women’s health hasn’t been a spotlight therapy area for Big Pharma in years. Several companies have spun off, sold or at least considered selling women’s health assets to focus on “core” products.

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Mar­ket­ingRx roundup: Pfiz­er re-ups pneu­mo­nia ads as Mer­ck threat looms; Re­al Chem­istry founder CEO Jim Weiss steps back

Every autumn, leaves fall from the trees and people start holiday shopping – and for the last few years Pfizer debuts a new “Know Pneumonia” awareness TV ad. This year the commercial, launched a week ago, features different people who talk about why they got vaccinated against pneumococcal pneumonia. Actors portray a young female firefighter with asthma, a mechanic with heart disease and an older woman with her grandchild. A Pfizer spokesperson declined comment on the latest iteration of the long-running campaign.

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Mer­ck pumps the brakes on two more PhI­II tri­als for its lead an­ti-HIV drug

After trial investigators flagged a drop in immune cell counts that an external committee determined was related to treatment last month, Merck has been pausing HIV-related Phase II and III trials ever since.

On Monday, the biopharma company announced it’s pausing enrollment in two of its Phase III trials evaluating its leading anti-HIV drug candidate, which is the once-monthly, oral islatravir.

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Covid-19 roundup: Plant-based shot proves safe, 71% ef­fi­ca­cious in PhI­II; Bourla ex­pects an­tivi­ral to launch this month

Quebec-based Medicago and its adjuvant partner GlaxoSmithKline said Tuesday that their plant-based Covid-19 vaccine candidate proved to be 71% efficacious against all variants of SARS-CoV-2 in a Phase III trial of more than 24,000 adults in Canada, the US, UK, Mexico, Argentina and Brazil.

In addition to showing 75% efficacy against the Delta variant specifically, the companies also said the vaccine proved to be generally safe, with no serious adverse events reported and reactogenicity generally being mild to moderate. The results mean that a regulatory submission will be filed with Health Canada imminently, they said.