Aidan Finley

@drug_smolecules All of the problems with tazemetostat (PCH for peds 2’ malignancy, 2L FL) were at higher dose or extended duration. Unclear that a much more potent molecule is a good idea, yet that’s the profile from NVS / CNST, PFE, etc.

$ORIC Take a look at this slide and ask yourself why these drugs have no monotherapy activity Also reminder Tazverik was withdrawn

@ATabarrok Think you mean “merdeheads”

Têtes de merde

@shycollie @PTarantinoMD I always thought Moses came down from the mountain with 375mg/m2 on a stone tablet?

@PTarantinoMD That’s a terrific rabbit hole to go down. I always tell the story of Rituxan dosing, how did we decide on the dose? Well, we had two patients for the phase I so we split the jar in half

Less than 1% of the administered ADC dose reaches the tumor after each infusion

@Andrewnsnyder @MorlockP You want obvious allegory, CS Lewis is over here!

Right? At the very least, Tolkien could have included someone who willingly dies for his friends and comes back to life, or maybe a king who takes his place on the throne to bring peace and prosperity, or someone born in obscurity who bears the weight of the world.

@EganPeltan @contirena1 Could have also been the c-KIT TKI?

> “design” an mRNA vax for your dog > give dog α-PD-1 (doggie Keytruda) > see partial response! > tell the world it was the mRNA > tell everyone the AI did it > influencers RT before reading > it’s PR for AI dog mRNA vax co > it was the Keytruda Yeah - that’s pretty insane!

@nypost @MedicalQuack Yeah, but can you make airplane noises to yourself or hum the Top Gun theme?

American Airlines passengers shocked to learn their 'flights' were actually bus routes: 'There's no plane' trib.al/Vf75VeJ

@RampCapitalLLC Poor Plaxico Burress

Probably thought it was just gonna be a fart. Shit happens.

@DiscussingFilm Gosh, I hope Sam’s daughter founds an NGO and brings democracy and women’s rights to Angmar. We share the same sky, after all.

A sequel movie to the ‘LORD OF THE RINGS’ trilogy is officially in the works. Plot synopsis — 14 years after the passing of Frodo, Sam, Merry, and Pippin set out to retrace the first steps of their adventure. Meanwhile, Sam’s daughter, Elanor, has discovered a long-buried secret and is determined to uncover why the War of the Ring was very nearly lost before it even began. Stephen Colbert is co-writing the script.

@KlendathuCap It’s method? They had to take time off for all the weird British holidays like Michaelmas and Guy Fawkes Day?

The movies came out every year and cost more money to make. What are we doing here? The kids are gonna be older than Gandalf by the time the show’s over.

@thechosenberg This could be a sitcom: “Meet the Khans” (Genghis is an amusingly hepecked suburban dad who really likes his lawn…)

At least they got to share their hobby

@mckaycoppins @thegrugq But did you bet on it?

Last year, I met a Mexican athlete who told me an incredible story—that he’d been kidnapped in 2023 and forced to compete for his life in a secret tournament of cartels. Once I started reporting, the story only got more surreal. For the May issue: theatlantic.com/magazine/2026/…

@GarettJones @tylercowen youtube.com/watch?v=yikEEG…

Everyone is talking about personalized mRNA cancer vaccines. I want to share two recent Nature papers that cut through the excitement and reveal something the viral posts aren't telling you: the approach works — but only in patients whose immune system actually responds to the vaccine. In the PDAC trial, that was half. Papers: — TNBC-MERIT trial (Nature 2026): nature.com/articles/s4158… — PDAC 3-year follow-up (Nature 2025): nature.com/articles/s4158… Here's the exact number that explains why. The PDAC trial: at 3.2 years median follow-up, vaccine responders had median recurrence-free survival that was never reached. Non-responders: 13.4 months. HR = 0.14. The T cell memory is real — some clones are projected to persist for over a decade. The TNBC trial: 10 of 14 patients remained relapse-free at 5 years. One patient has been in remission for over 6 years, with neoantigen-specific T cells still circulating at ~2% of her CD8 repertoire. So what separates responders from non-responders? Across both trials: only 41 of 251 neoantigens actually triggered a T cell response. That's 16%. Each vaccine encodes up to 20 neoantigens — the algorithm's best guess at which tumor mutations will be immunogenic. Most don't work. Half the PDAC patients didn't respond — not because they couldn't mount an immune response (they responded fine to concurrent COVID vaccines) — but because their selected neoantigens happened to miss. This is the core unsolved problem: predicting, from sequence alone, which mutations will produce peptides that a specific patient's immune system will actually recognize. It sounds like an MHC binding problem. It isn't. Tools like NetMHCpan handle binding affinity reasonably well. What they miss is the full causal chain: 1. Proteasomal processing — will the protein actually be cleaved into this exact peptide? 2. TAP transport — will it reach the ER for MHC loading? 3. HLA-peptide stability — across the patient's specific HLA alleles (10,000+ variants in the population) 4. T cell repertoire availability — has central tolerance already deleted the clones that would recognize it? 5. Tumor clonal architecture — is this mutation in every tumor cell, or just 30%? Targeting subclonal neoantigens leaves most of the tumor untouched. Every step is a filter. Current prediction stops at step one. Compounding everything: average manufacturing time in the TNBC trial was 69 days (range: 34–125) from sample to vaccine release. For pancreatic cancer, where non-responders recur at 13.4 months post-surgery, that's not a footnote. It's a window closing. The good news: the T cell biology is sound. The mRNA platform works. The immunology is spectacular — when it works. The bottleneck is the first step: choosing which 20 neoantigens go in the vaccine. Get that prediction right, and the responder rate moves. This is where AI in cancer immunotherapy has to go next. Not mRNA design. Not LNP formulation. Immunogenicity prediction — integrating mutation calling, HLA typing, T cell repertoire sequencing, and single-cell tumor expression simultaneously, as a causal inference problem, not a binding affinity lookup. We don't have a model that does this well. That's the gap.

@owl_posting @maxhodak_ @iskander Custom, neoantigen-specific workflows are possible (if not commercially viable): pmc.ncbi.nlm.nih.gov/articles/PMC97… nature.com/articles/s4158…

@maxhodak_ @iskander i dont disagree at all with this and my impression is that the cancer vaccine folks i know (n=2) would agree dosing schedules, ideal adjuvants, etc are not figured out at all, but tough to believe the LLM knows the answer

i hope this is real but, given the information in the article, one of the following is true: the known problems with cancer vaccines are completely wrong, the tumor shrunk because mast cell tumors in dogs change size a lot, or a miracle occurred curious to get @iskander take

@PatrickHeizer Was going to say even the simplest oncogenic vaccine problem - HPV - is actually incredibly complicated clinically, not least because the set point of our immune system (at least vis-a-vis T cell responses) is to “off.”

Sorry to be the downer because this is an impressive story in some senses. But it is ~trivially easy to make a single mRNA vaccine. It's not hard. I cure mice of various cancers with various therapeutics all the time. I've made mice lose more weight in a month than tirzepatide does in a year. What is hard and expensive is proving its BOTH safe AND effective **in a randomized and controlled study in humans** while ALSO manufacturing it at clinical scale and grade. I am happy for this man and his dog. It is impressive. But y'all are overhyping it.

@exjon Apparently destroyers didn’t have ice cream machines and the carriers did. Destroyers were incentivized to pick up air crews by “ransom” of their weight in ice cream.

Good, he understands how morale works. Same reason troops were fed steak and eggs before WW2 beach landings. Same reason submarines have ice cream machines. Our troops don’t run on ramen.

@moorehn Boy, the “Menu” was a documentary!

On a story of an abusive boss, WHAT is this caption.

@iowahawkblog Correction: that’s Randall “Tex” Cobb as the bounty hunter “Leonard Smalls” (Raising Arizona, 1987)

Rhodes Scholar or Roads Scholar? Former Transportation Secretary Pete Buttigieg sits down with Vanity Fair for a candid talk on his decision between a 2028 presidential run or wandering the earth like Caine in Kung Fu on his filthy chopper to wreak vengeance on evildoers

Shocking security camera footage captures Mayor Pete maiming 17 members of the Mongols MC in bloody Gallup, NM biker bar melee; last seen pulling 10 mile wheelie on panhead chopper on I-40

What is the middlest name of them all? Ann! No other name is as disproportionally used as a middle name compared to as a first name. Great data work! Source: erdavis.com/2025/12/31/wha…

@growingwisdom youtube.com/watch?v=kXsIfp…

Let's see what the rest of the overnight brings. See you in the morning! We're not missing it. It's just a matter of intensity at this point.