Kim Schleich

[Mike Vernon @M_Vernon]

BIFM.

BIFMMMMMMMMM.

HE IS

FRANK MASON

[Kim Schleich @KimSchleich]

@M_Vernon BIFM!!💙❤️

[Mike Vernon @M_Vernon]

Frank Mason.

[RedditCFB @RedditCFB]

Sad read, hope it works out for him. The NCAA Transfer Portal rules are bad and are actively preventing a guy who took some time to grieve his dead mom from completing his degree.

Hope there’s someone with an ounce of common sense or leadership at the NCAA who steps in here. 🙏

[Mike Bales 🫡🇺🇸 @MikeBales]

Boycotting your country’s 250th birthday because you hate the current President is like refusing to celebrate your own child’s birthday because you despise their father.

[Sanjay Sujanthakumar @tha_Real_Kumar]

#USMNT striker Folarin Balogun on his immediate reaction to red card:

“I think it was just important to stay calm. I never want to react out of anger and out of emotion. There’s still lots of people we’re inspiring, little kids, boys and girls who are watching, and we have to show them the correct way to handle things, even when you think it's unjust.”

On shaking ref’s hand postgame:

“As said, you can feel like something, injustice can happen to you. It’s not an excuse to be disrespectful… I'm aware that the World Cup might be the first time a lot of American viewers are tuning in. So it's important just to show people, whether things happen to you, good or bad, just to continue to be yourself.”

[Crystal Hope @CrystalHope1979]

An 11-year-old boy. One crochet hook. 60 skeins of yarn. No pattern. Two weeks. 🇺🇸

While juggling tennis camps and baseball games, Grayson poured his heart into crocheting this stunning American flag blanket—just in time to celebrate America’s 250th Independence Day. 🧨

No fancy instructions, just pure determination and love for his country. The result is a beautiful family heirloom that proves some of life’s greatest treasures are still made by hand. 🇺🇸✨

Proud of this kid and the quiet power of creativity in the next generation.
What an inspiration! 👏

[Doog @doogadoo11]

One thing I know for sure.

Caitlin Clark is tougher than LeBron James.

[Tāy @cheesencoke]

Only in the WNBA is a clap a technical foul, but a punch to the throat is somehow a no-call.

[Brett L. Tolman @tolmanbrett]

Worth the read.

[𝘼𝙪𝙨𝙩𝙞𝙣 𝙀𝙘𝙠𝙚𝙧𝙩 🇺🇸🇩🇿 @AustinCEckert]

The world’s loudest indoor AND outdoor sports stadiums in the world are only 50 miles apart from each other and that doesn’t get talked about enough

[End3of6Days9 (Helen) 🇺🇸 @end3of6days9]

This woman went to a new doctor because she’d been feeling awful — exhausted, no energy, and just generally terrible. Her previous bloodwork had shown high liver enzymes and high cholesterol, but no one had really dug into why.

Within minutes of meeting her, the new doctor looked at her and asked one simple question: “Do you drink energy drinks?”

She admitted she had one every single day — Celsius, Alani, Bloom, Monster, whatever she could get her hands on. She knew they weren’t great for her, but she drank them anyway because she was “fighting for her life” trying to get through the day.

The doctor told her it wasn’t the caffeine that was the problem. It was all the other synthetic ingredients in those drinks that her body couldn’t properly process. Those were what was throwing off her liver enzymes and affecting her cholesterol.

She’s now on day three without them… and she already says she feels so much better.

Quick PSA: Those energy drinks might be doing more damage than we realize.

Have you ever stopped doing something you thought was "helping" you, only to realize you actually felt better without it?

[Freedom @ActionFixesFear]

A man walks out of his oncologist's office with a normal-looking blood test. Hemoglobin: fine. Neutrophils: fine. There is a third line on that same sheet almost nobody reads back to him. It is the one that tracks whether he lives.

On Saturday, in a room of urologists at the AUA annual meeting, @DrPatrick stood up and explained why that line goes untreated. Then he kept going - announcement after announcement, on a stage, on the record. Here is what he said.

THE THIRD LINE

On the AUA stage Saturday, Soon-Shiong said: "We've addressed anemia, we've addressed neutropenia, we've never addressed lymphopenia. And ironically... chemo and radiation causes lymphopenia. Now you begin to see the frustration and the madness of what we are doing."

That is the whole thesis in three sentences. Every routine blood test counts three things chemo and radiation knock down: red cells, infection-fighting neutrophils, and lymphocytes - the T cells and NK cells that kill cancer. Medicine built a drug to rebuild the red cells. A drug to rebuild the neutrophils. For the third - the cancer-killing one - nothing. The drugs given so patients can tolerate more chemo never touched the cell line chemo itself depletes.

How much does that third line matter? Not a company number - a 31,178-person US population study (Zidar et al., JAMA Network Open, 2019):

- Severe lymphopenia, all-cause death: about 1.8x the risk (age- and sex-adjusted).

- Cause-specific at severe lymphopenia: roughly 3x death from cancer, 4x from cardiovascular disease, 7x from infection and pneumonia.

In plain English: a $10 line on a standard blood count, that almost no oncologist treats, sorts who lives from who dies - across cancer, the heart, and infection at once. From the stage Soon-Shiong put it harder than the paper does ("if your ALC is below 2,000, your chances of dying early from all cause is 200 to 300%") - that is his framing; the published, adjusted figures are the ones above. They are damning without rounding up.

JUST A NUMBER

And here is what he says the agency said back. By his account, at a regulatory meeting with the FDA, the response to all of this was that the absolute lymphocyte count "is just a number." His reply from the podium: "PO2 is just a number - do you need oxygen? Hemoglobin A1C is just a number. Blood sugar is just a number." The same line a 31,178-person study ties to dying early at up to seven times the rate, waved off as not worth treating.

And look at which of those figures is largest. Not cancer. Infection. That is why Soon-Shiong does not present this as only a cancer drug - he extended the same logic to sepsis and infectious disease: one collapsed immune line, several different ways to die.

WHY IT EVEN WORKS

This is the part that makes the rest click, and it is textbook immunology, not a company theory. Tumors hide from the immune system's T cells by deleting a surface ID tag called MHC-I. That is why checkpoint drugs like Keytruda eventually fail: they rev up T cells, but a tumor wearing no tag is invisible to T cells no matter how revved. Loss of that tag is a documented mechanism of checkpoint-inhibitor resistance.

Now the elegant part, known to immunology for thirty years. NK cells run the opposite logic. A normal cell shows the tag and the NK cell passes it by. A cell that has dropped the tag screams "missing self" - and the NK cell destroys it. The tumor's single best trick against T cells is the exact signal that turns NK cells loose.

In plain English: every cell wears one ID badge. The T cell is a guard who can only grab a troublemaker he matches to his list, and the only way he checks is by reading that badge. A cancer cell that rips its badge off goes invisible to him. No badge, nothing to read, nothing he can do. Giving that guard more muscle (checkpoint drugs like Keytruda) changes nothing, because there is still no badge to read. The NK cell is the opposite kind of guard, with one rule: no badge, you are out. So the cancer's smartest escape from the first guard is the exact thing the second guard exists to catch.

ANKTIVA is the growth factor for those NK cells and T cells. It comes through the door the tumor opens when it slams the other shut. That mechanism is written into the federal label - section 12.1 states it is an IL-15 receptor agonist that stimulates CD8+ and CD4+ T cells and NK cells without expanding the regulatory T cells that would otherwise blunt the response. Soon-Shiong told the room he worked "desperately hard" to get that sentence into the label and is "not aware of any medicine in the history of medicine" carrying it. The cell line the death-predicting blood test measures is the cell line the label says the drug rebuilds.

THE FIRST PROOF IT MOVES THE LINE

For the first time, on that stage, he showed a randomized comparison from a lung-cancer trial: ANKTIVA plus Keytruda against Keytruda alone, with the same starting lymphocyte count. Over 27 weeks the ANKTIVA arm's count rose and held while the control arm's drifted down (P=0.0065). In the subgroup with the highest level of a key tumor marker, the ANKTIVA patients also went longer before their cancer progressed - a median of 7.0 months versus 2.2 (hazard ratio 0.40). It is his data, shown for the first time and not yet peer-reviewed - but it is the first randomized human signal that the drug raises the exact line that predicts who lives, and that raising it tracks with the patient doing better. (In a separate, earlier lung study he showed the patients whose count recovered lived a median 17.4 months versus 11.8 for those whose did not - he flagged that one himself as a correlation, not a randomized proof. The honest weight is on the randomized result above.)

In plain English: imagine a patient, Tom, with advanced lung cancer. Tom and a matched group all start the standard immunotherapy, Keytruda, with their cancer-killing lymphocyte count at the same level. Half of them, Tom included, also get ANKTIVA. Over the next six months Tom's group sees that count climb and hold; the Keytruda-only group watches theirs sag - and that split was not chance (the odds of a fluke were well under one in a hundred). Among the patients whose tumors carried the most of the marker immunotherapy keys off, Tom's group went about three times longer before the cancer started growing again, roughly seven months instead of two. It is a first look at his own data, not yet peer-reviewed. But it is the first time, with the comparison built in, that the drug has been shown to lift the very line that tracks who survives - and for that lift to move with the patient doing better.

THE DOCUMENT, AGAIN

So the drug raises the line, and raising the line tracks with living longer. The question that should follow - then why is it not everywhere? - has an answer, and it does not start with the drug. It starts in 2007.

In 2007 the US government answered a question oncology rarely asks out loud: of every immune molecule known, which has the best shot at curing cancer? The National Cancer Institute polled the field - NIH, the FDA, the major cancer societies. Out of more than a hundred, one came first: in Soon-Shiong's words from the AUA podium Saturday, "the number one that could address cancer is IL-15." ANKTIVA is built on it.

Then he added the part that should stop you. He had discussed that government ranking on the Sean Spicer show, and, he said, "I got a warning later about talking about a nice NCI document."

Sit with that.

Nearly two decades after the FDA sat among the bodies that ranked this molecule number one, the agency sent the man building it a warning letter for citing that ranking on air.

The ranking went to print in 2008 under a title the agency cannot take back: Mac Cheever, Immunological Reviews, "Twelve immunotherapy drugs that could cure cancers." IL-15 at the top. He didn't write that list. The government did, and the FDA was in the room.

On that same list, checkpoint inhibitors ranked second. The industry poured itself into number two - by his account more than forty approvals across tumor types, many of them won on the kind of single-arm trial we are about to come back to. Number one waited twenty years for someone to build it.

THE RULE THEY SAID DIDN'T BEND

Still in the same talk: "When the previous heads of the FDA, Dr. Prasad and Dr. Makary said... no trial has ever been approved for single arm, that's not true... Merck got it approved for single arm trial for 149 patients for all tumor types."

He is right, and this one is fully checkable. On May 23, 2017 the FDA gave Keytruda the first-ever tissue-agnostic cancer approval on 149 patients across five single-arm trials. The standard the prior CBER leadership held ANKTIVA to is one the agency itself waived for the market leader, on 149 single-arm patients. We built the file on that asymmetry; he said it to a room of urologists.

Stay on that for a second.

The two people who pressed that standard ran US drug approval. Dr. Vinay Prasad was Director of CBER, the FDA center that regulates biologics, which is to say the center that regulates ANKTIVA. Dr. Marty Makary was the FDA Commissioner.

What they said was untrue was not some obscure footnote. It was their own agency's most famous modern cancer approval. How do the two officials gatekeeping this drug get the single most checkable fact in their own building wrong, and then invoke it as the reason to make the drug wait?

And by the time Soon-Shiong called them "the previous heads" on Saturday, both were already gone. Prasad left the FDA at the end of April. Makary resigned on May 12, four days before the talk, and the day before he was scheduled to testify before a Senate subcommittee. The men who set the standard against this drug were out the door while the FDA's own record kept disproving it.

And it is not only that 2017 record. By his account on that stage, the same FDA has already granted ANKTIVA Expanded Access for any patient who has failed chemotherapy, radiation, and a checkpoint inhibitor, across cancers. Expanded Access is not a verdict on whether a drug works; it is the agency judging it safe enough to give patients with nothing left to try. So the FDA has opened a broad door to this drug for those patients, while the narrow approval that would let earlier ones through still sits unanswered. His objection to that sequence was the obvious one: why force a patient to fail everything else before being allowed this at all? That is his account from the stage, not an FDA letter we have read.

THE SECOND SOURCE

ANKTIVA is only approved given together with BCG. No BCG, no ANKTIVA - that is the label, not a preference. And BCG in the US has been a one-company, one-strain shortage for over a decade. We walked through that history yesterday.

So on Saturday he announced he had locked exclusive US rights to a second strain, Tokyo-172. The obvious doubt writes itself: a company secures its own backup and naturally swears it works. Here is why that doubt does not hold. He did not run the trial that proves it. The US government did - SWOG, the NCI-funded cooperative group, in a nine-year randomized head-to-head (Svatek et al., 2026): Tokyo-172 against the only US-approved strain. Result: non-inferior.

The part his own slide left out, kept here: that result held for the standard way of giving it; a second dosing schedule in the same trial did not work; and serious side effects ran somewhat higher with Tokyo-172. A proven equal, not a gentler one - and the government, not the company, paid for the proof.

Which is why his one blunt line on stage matters: "our approval just says any BCG. It doesn't say TICE." Hear what he is signalling. ANKTIVA's label never named Merck's strain, and the government's own nine-year trial just proved a second strain works. Tokyo-172 still needs the FDA to clear it. And Seth Lerner, the SWOG genitourinary chair he credited for that trial, is on the program at this week's FDA workshop: the proof is already in the FDA's own room, and so is the man who oversaw it.

WHAT THE SECOND SOURCE WAS REALLY FOR

The supply is not the prize. It is the runway for the prize. ANKTIVA today is approved only for patients whose cancer already came back after BCG - a fraction of the disease. BCG is given far earlier, first-line, to almost everyone who gets it. That first-line population is several times larger than the one the drug reaches today. By his account: the first-line trial, QUILT-2.005, finished enrolling in February, an independent committee reviewed it and said it had seen enough, and the application is ready to file. He says it; the FDA has not confirmed it. But the sequence is deliberate - lock a proven, government-validated BCG supply first, then file the first-line regimen that cannot exist without it, for a population many times the size of the one ANKTIVA serves now.

THE QUESTION THAT IS GENUINELY OPEN

Bladder cancer shows up in two shapes. Flat patches in the bladder lining, which doctors call carcinoma in situ, or CIS. And little finger-like growths, called papillary. ANKTIVA is already approved when CIS is present. The application that has been stuck is the one for the papillary-only form. So everything hangs on a single question: are these two shapes the same disease, or two different ones?

Soon-Shiong argues they are one - a single rogue cell line that just grows in two patterns. The science is genuinely split: some genetic studies show a shared origin; others find real molecular differences. It is honestly unsettled. That is not a footnote - it is the whole ballgame for the stuck application. And it is one of exactly two items on the agenda of the FDA's public workshop this Monday. The other item is the BCG shortage and what it does to clinical-trial design - the fight running through the rest of this post. The FDA did not convene a meeting on a side issue. It put on its agenda the two questions this drug's future turns on.

A BUREAUCRATIC RUT

And while that question waits on a workshop, the FDA's answer for the stuck application, by his account, is a randomized trial against chemotherapy.

Sit with what that asks.

Chemotherapy is the thing that causes lymphopenia - the collapsed third line a 31,178-person study ties to dying early. The comparator the agency wants is itself a driver of the harm. The problem he raised was ethical, not regulatory: how do you look a patient in the eye and randomize them into the chemotherapy arm - chemotherapy the FDA itself approved this past September, with serious adverse reactions in roughly a quarter of patients on its label - when chemotherapy is the very thing that collapses the cells keeping them alive? He said he would still run the trial. He also said he did not know how he could ethically recruit for it. He had a phrase for the loop: "a bureaucratic rut," he said. "It's not biology."

He spelled it out himself: the workshop asks "exactly the question we posed to the FDA group that's reviewing our BLA six months ago."

Sit with the timing.

Two days before the FDA sits down to decide whether CIS and papillary are one disease, the man whose stuck application hangs on that answer made the case for it - in public, to a room of the urologists who treat the disease. We called this pre-positioning before he said so. Then he said so.

THE BODY THAT ALREADY SAID YES

Here is what makes the wait extraordinary. While that question sits "open" at the FDA, it is not open at the body that writes the treatment guidelines American oncologists actually follow. This past March the NCCN added ANKTIVA plus BCG for BCG-unresponsive papillary-only disease - the exact stuck indication - as a Category 2A recommendation.

That is not a company press release.

By federal statute, Social Security Act section 1861(t)(2), a Category 1 or 2A listing in NCCN's drug compendium is a medically-accepted indication for Medicare coverage. In plain terms: the federal payer's own statutory test for what counts as covered cancer care is already met - while the FDA approval it would normally follow is not. Soon-Shiong's stage framing for it - "unanimous," "30 independent comprehensive cancer center directors," "bigger than an ODAC" - is his characterization; the guideline change and the statute are not.

THE MISSING LINK

One thing he could not announce that day: "The 60 days have passed. We've not heard anything from the FDA. We're awaiting some response. I'm hopeful."

That is the honest center of an enormous day. The first randomized proof the drug raises the line. The first-line filing ready to go. A government-validated second BCG supply locked. Saudi Arabia already approving it for lung cancer the US has not. Everything moving - except the one application that would let the next patient actually reach it. On one clinic's list, by his count, fifteen thousand of them are waiting.

The story was never whether the science works. It was whether anyone would treat the line on the blood test that decides who lives, and whether the agency that ranked this molecule number one would let the patient have it.

A foreign regulator already crossed that line - by his account the Saudi FDA accepted the whole frame, that the root cause is the collapse of the immune system and the cancer is only its symptom.

On Saturday the man who built it answered the first question, on the record, in a room of the doctors who will use it. The second answer is still sitting on a desk at the FDA, sixty days unanswered - on the very day the agency finally sits down to debate the very questions it turns on.

He gave Saturday its own name: "maybe we've actually closed the missing link." Everything in this post says he did. The last word on whether the patient ever gets it is not his.

[Dante 🇺🇸 @DanteTheDon]

Was not ready for Eric Church to deliver the best commencement speech I’ve ever heard.

Six guitar strings. Six pillars of a life.

Faith. Family. Spouse. Ambition. Community. You.

Tune them when you’re whole, not just when you’re broken.

Watch the whole thing.

[Big Brain Business @BigBrainBizness]

Jerry Seinfeld on why chasing your "passion" is embarrassing, and what to do instead:

Seinfeld pushes back against the popular advice to find your one great passion in life.

In his view, it's not just unnecessary, it's a little ridiculous.

"Let go of this idea that you have to find this one great thing that is my passion. My great passion with your shirt torn open and your heaving pec muscles. It's embarrassing."

Instead of chasing something dramatic, he offers a quieter alternative:

"Find fascination. Fascination is way better than passion. It's not so sweaty."

He explains why the heavy-breathing version of passion is actually counterproductive:

"Just be willing to do your work as hard as you can with the ability you have. We don't need the heavy breathing and the outstretched arm from your passion. It makes co-workers uncomfortable in the cubicle next to you."

Then Seinfeld offers what he calls his three real keys to life, no jokes:

"Number one, bust your ass. Number two, pay attention. Number three, fall in love."

@JerrySeinfeld elaborates on the first one:

"You obviously already know whatever you're doing, I don't care if it's your job, your hobby, a relationship, getting a reservation at M Sushi, make an effort. Just pure stupid… effort."

And here's the part worth sitting with:

"Effort always yields a positive value even if the outcome of the effort is absolute failure of the desired result. This is a rule of life. Just swing the bat and pray is not a bad approach to a lot of things."

[Kim Schleich @KimSchleich]

@MarchMadnessMBB Good to see the continued lopsided posts for UCONN from this account.🙄

[College Sports Only @CSOonX]

Whoever thought having a Chainsmokers concert in between Final Four games was a good idea needs to be fired.

[Phantom Friar @ThePhantomFriar]

There was a time when after the 1st game of the Final 4 the other teams came out, warmed up and then they played the game. It was great