Young an­ti-ag­ing field takes big step with Mayo Clin­ic senolyt­ics show­case

The idea that flush­ing senes­cent cells — those old, fa­tigued cells that cease to di­vide — from the body may rid the body of harm­ful pro­teins has been one of the promi­nent pro­pos­als in the an­ti-ag­ing sphere. Hav­ing gen­er­at­ed a stream of an­i­mal da­ta to sup­port the hy­poth­e­sis, the Mayo Clin­ic now has re­sults from an ear­ly hu­man study sug­gest­ing they have found drugs that can do ex­act­ly that.

Latonya Hick­son

To be sure, the main goal of the Phase I tri­al wasn’t to show the ef­fects of de­creas­ing senes­cent cells in the body; rather, the sci­en­tists were keen to prove that a senolyt­ic reg­i­men they’ve test­ed in mice works the same way in hu­mans.

This is sig­nif­i­cant be­cause de­spite the pub­li­ca­tion of first-in-hu­man da­ta in Jan­u­ary, “so far, there has been no di­rect demon­stra­tion of senes­cent cell clear­ance by senolyt­ic drugs in peer-re­viewed pub­lished hu­man clin­i­cal tri­als,” the au­thors wrote in EBio­Med­i­cine.

For the small tri­al, re­searchers de­ployed dasa­tinib and quercetin; the for­mer is a can­cer drug al­so known as Spry­cel while the lat­ter is a plant de­riv­a­tive. Nine pa­tients with di­a­betes-re­lat­ed chron­ic kid­ney dis­ease were re­cruit­ed and giv­en the treat­ments for three days.

Laris­sa Langhi Pra­ta

While the drugs were out of the sys­tem with­in a few days, the ef­fects ap­peared to per­sist, the team — with LaTonya Hick­son and Laris­sa Langhi Pra­ta as the co-first au­thors — re­port­ed:

Key mark­ers of senes­cent cell bur­den were de­creased in adi­pose tis­sue and skin biop­sied from sub­jects 11 days af­ter com­plet­ing the 3-day course of D + Q, as were key cir­cu­lat­ing SASP fac­tors, com­pared to be­fore ad­min­is­tra­tion of these senolyt­ic drugs.

Such proof about the mech­a­nism of ac­tion bol­sters their pre­vi­ous work sug­gest­ing that a brief course of dasa­tinib plus quercetin im­proved phys­i­cal func­tions for pa­tients with id­io­path­ic pul­monary fi­bro­sis — a tough-to-treat dis­ease.

While small-scale, the tri­al is a sig­nif­i­cant step for­ward for the trans­la­tion of senolyt­ic ther­a­pies, ac­cord­ing to Ronald Ko­han­s­ki, deputy di­rec­tor of the di­vi­sion of ag­ing bi­ol­o­gy at the Na­tion­al In­sti­tute of Ag­ing.

“The demon­stra­tion that senes­cent cell num­bers can be re­duced in two tis­sues in hu­mans is an im­por­tant ad­vance based on the com­pelling ev­i­dence from stud­ies in lab­o­ra­to­ry mice,” he said in a state­ment.

James Kirk­land

Chron­ic kid­ney dis­ease is just one of many age-re­lat­ed ail­ments that the team be­lieves senolyt­ics can de­lay, pre­vent or treat, said se­nior au­thor James Kirk­land (who heads Mayo’s Robert and Ar­lene Ko­god Cen­ter on Ag­ing).

His col­leagues at Mayo have pre­vi­ous­ly flagged Alzheimer’s and Parkin­son’s as dis­eases where purg­ing senes­cent cells can make a big dif­fer­ence.

In case any­one gets over­ly ex­cit­ed, though, the sci­en­tists felt the need to con­clude their pa­per with a note of cau­tion:

The field of senolyt­ics is new. The first clin­i­cal tri­al of senolyt­ic agents was on­ly re­port­ed in Jan­u­ary 2019. The find­ings re­port­ed here are pre­lim­i­nary re­sults from an on­go­ing clin­i­cal tri­al of senolyt­ics for treat­ing dys­func­tion in pa­tients with di­a­bet­ic chron­ic kid­ney dis­ease. Few­er than 150 sub­jects have been treat­ed with these drugs in the con­text of clin­i­cal tri­als that we are aware of so far. In ad­di­tion to side ef­fects re­lat­ed to in­di­vid­ual senolyt­ic drugs known from oth­er con­texts in which those drugs have been used, there could turn out to be se­ri­ous side-ef­fects of senolyt­ics as a class, which are not yet known. We cau­tion against the use of senolyt­ic agents out­side the con­text of clin­i­cal tri­als un­til more is known about their ef­fects and side ef­fects.

The 20 un­der 40: In­side the next gen­er­a­tion of bio­phar­ma lead­ers

“Each generation needs a new music,” Francis Crick wrote in 1988, reflecting back on his landmark discovery. Crick was 35, then, in 1953, when he began working with a 23-year-old named James Watson, and 37 when the pair unveiled the double helix. Rosalind Franklin, whose diffraction work undergirded their metal model, was 32.

The model would become the score for a new era in biology, one devoted to cracking the basic structures turning inside life. Subsequent years would bring new conductors and new rhythms: Robert Swanson, 29 when he convinced a 39-year-old Herb Boyer to build a company off his work and call it Genentech; Phillip Sharp, 29 when he discovered RNA splicing and 34 when he co-founded Biogen; Frances Arnold, 36 when she pioneered directed evolution; Feng Zhang, 31 when he published his CRISPR paper.

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Chart-top­ping ven­ture cash? Strong deal flow? In the month Covid-19 ripped around the globe? Yup

It turns out that even sending everyone from the CEO to rank-and-file staffers home to work in the middle of a Category 5 pandemic wasn’t enough to put a crimp in the flow of venture cash into biopharma. And even dealmaking held its own against the howling winds of misfortune — largely because a group of savvy players was quick to adjust to the new reality.

Our deal expert Chris Dokomajilar ran the numbers for us on a month-to-month basis and found that not only was venture money flowing during the panicky month of March, but it was also hitting home in record sums compared to the last 26 months of deal flow.

Say what?

As you can see in the top chart below, Dokomajilar outlined how the industry racked up $2.41 billion in total for March, just barely ahead of one other topper during the heady days of August 2018.

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FDA Commissioner Stephen Hahn and President Donald Trump at a press briefing on March 19, 2020. (AP Images)

Biotech ex­ecs warn that the FDA is fum­bling their re­sponse to the Covid-19 open-door promise, de­lay­ing progress

A few days ago the FDA touted a procedure for Covid-19 meds that committed the agency to immediate action for developers, formalizing a high-speed response that’s been promised for weeks.

Bioregnum Opinion Column by John Carroll

Decisions that once required months would be measured in hours under the Coronavirus Treatment Acceleration Program. “In many cases” trial protocols could be hammered out in less than a single day. If you had a potential solution to the crisis, the appropriate staffer would be in touch “to get studies underway quickly.”

It would be the ultimate high-speed regulatory pathway from Phase I to approval. Red tape was banished.

But it’s clear that for some — and quite likely many — biopharma execs, the actual agency response has not measured up to the promise. Beyond the front ranks of advanced companies in the field, like Gilead, or for drugs endorsed by President Trump, it may not even come close.

“The first response is this form letter everyone gets,” says one biotech CEO who’s reached out to the FDA on Covid-19. And when you try to cut through that, the ball gets dropped as it is passed from top officials to the frontline staff actually charged with getting things done.

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GSK's Hal Bar­ron buys a $250M stake in George Scan­gos' Vir and makes a bee­line to the clin­ic with Covid-19 an­ti­bod­ies

GlaxoSmithKline is diving straight into the swirling waters of Covid-19 R&D work, and investing $250 million to grab a chunk of equity in one of the emerging stars in infectious disease research to make it official.

GSK put out word this morning that it is partnering with Vir Biotechnology $VIR, the infectious disease startup founded in the Bay Area by former Biogen CEO George Scangos. They’re planning a leap into Phase II studies for 2 preclinical antibody candidates — VIR-7831 and VIR-7832 — that have been engineered to target the SARS-CoV-2 spike protein.

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UP­DAT­ED: A small, ob­scure biotech just won big with their IPO. In this mar­ket. Are you kid­ding me?

How could a small, largely unknown biotech that emerged from stealth mode just months ago with early-stage cancer programs jump onto Wall Street in the middle of a Category 6 financial hurricane and sail through with a $165 million IPO?

And what does that mean for the rest of the industry waiting to see just how much damage global lockdowns will wreak on clinical development?

The biotech is a company called Zentalis. The crew there nabbed an $85 million crossover round late last year — notably waiting 5 years before waving the numbers around to attract attention, according to my read of a FierceBiotech story. Perceptive joined in, but the syndicate was not in general the kind of marquee affair that gets tongues wagging.

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Ready to de­clare a de­fin­i­tive come­back in two months, Im­munomedics stops PhI­II ear­ly, re­cruits new CEO

More than a year ago, hit by a surprise complete response letter from the FDA, Immunomedics bid its then-CEO, Michael Pehl, adieu and began a 15-month quest to resolve the manufacturing issues cited in the CRL and seek a new leader — all the while moving forward with a Phase III study on its lead drug for metastatic triple-negative breast cancer.

Today the biotech said their stars are finally aligning. Not only is Novartis Oncology vet Harout Semerjian coming on board as CEO to steer what they believe will be a smooth sail to a new PDUFA date in June, Immunomedics has also been informed that their late-stage trial can be stopped early due to “compelling evidence of efficacy.”

An­oth­er day, an­oth­er boat­load for biotech. Deer­field adds $840M to rush of ven­ture dol­lars

The biotech dollars just keep rolling in.

Even as the world economy faces an economic contraction unprecedented in nature, biotech venture capital firms are announcing huge new investment pots. The latest? Deerfield Management Co.

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Small mol­e­cules, bi­o­log­ics and now gene ther­a­pies: Ger­many's Evotec adds an­oth­er feath­er to its R&D cap

German drug discovery company Evotec — which has a thriving rolodex of biopharma partners such as Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda — is now venturing into gene therapies.

The company swallowed Seattle-based Just Biotherapeutics, a company focused on reducing the cost of manufacturing protein therapies last year. It is now setting up a dedicated R&D site for gene therapies in Austria, in an effort to achieve a “modality-agnostic” repertoire — small molecules, biologics and now gene therapies.

A pair of PhI­II fail­ures spells last rites for Men­lo’s once-promis­ing Mer­ck drug

Four months after an intercontinental merger, Menlo Therapeutics is counting yet another pair of trial failures — ones with significant consequences for the companies, their shareholders and the drug.

In two pivotal Phase III trials, Menlo’s lead drug serlopitant failed to treat pruritus associated with prurigo nodularis — basically itchiness from a particular skin disease that causes red lesions on a person’s arms or legs. Serlopitant has long been the company’s only drug and as recently as 2018, it looked promising enough to support a stock price of $37. In April of that year, a Phase II failure demolished the stock price overnight: $35 to $9. Other subsequent stumbles trickled the ticker down to just above $2.