Joseph DeCorte

Vandy MSTP | Interests: math, chemistry, immunology. Inferring based on the nonsense I was trained on

[Oded Rechavi @OdedRechavi]

It’s still unclear whether Hantavirus is scary enough to guarantee 1,000 publications in Nature.

[Gavin Brown @gavinrbrown1]

Mathematicians defined "Riemann-integrable" to keep track of which integrals Bernhard Riemann (1826-1866) could do.

Henri Lebesgue was born after Riemann died and presumably knew more about calculus, which is while Lesbesgue-integrable is the weaker condition.

[Aaron Ring @aaronmring]

@Biomaven CD47 antagonists looked great in xenograft models where the NOD SIRPα was the main feature keeping the tumors alive (ever wonder why NSG >> SCID?). But in syngeneic models with murine reactive molecules, the efficacy was wimpy if not absent.

That was the tell in retrospect.

[Jing Liang 🇺🇦 @AppleHelix]

I find the ODAC vote on camizestrant a bit depressing. This is what futuristic cancer treatment looks like.

You develop a drug that targets a key resistance mechanism for breast cancer. You develop a non-invasive ctDNA blood test to surveil the emergence of this resistance mutation.

You only give this drug when this mutation was detected, but cancer is still being controlled. "Nip it in the bud" so to speak.

You demonstrate much better PFS than SOC (HR 0.44-0.46). The drug obviously works!

But you have FDA and some ODAC members using the red-herring which are basically:

- How can you ensure there is a OS benefit after patients moving onto subsequent lines treatments

- How do you know if you should give this drug early (at detection of resistance mutations) or when it is full blown progression

To answer both of these questions, you need a much larger trials.

If this is the bar for cancer drug approvals, there will be fewer MOAs investigated. The total amount of R&D dollars investors and pharma companies willing to deploy is relatively fixed.

On top of that, there are only so many patients you can recruit. If you demand large trials for a particular MOA, this means fewer patients available for other trials.

The regulatory bar that drives the most human progress is not necessarily the bar that gives you the most certainty.

https://t.co/kRsKurjVdi

[Katherine Argent @effthealgorithm]

Search is full of ads and wrong answers. Every other email is an ad. Prime Video charges you and shows ads. Paramount? Ads. Peacock? YouTube? Hulu? Ads followed by more ads. Netflix full of ads. Meta and X, every other thing is an ad. Pinterest is nothing but ads. AI is in everything. AI finishes sentences incorrectly and won’t stop. AI reads your email and search history to target you with more ads. Every time you open an app or visit a site there’s an update making it worse. In a hurry? First, click here to agree to terms you don’t have time to read and must accept. You need an account to do that. Change your temporary password. Enter your 2FA code. Check your email and enter that code. Now use a passkey. Your password is too simple to remember. Change it. No, not like that. Now log on. Enter your 2FA code. Check your email for a code… Welcome back! We’ve updated our terms of service and privacy policy (you have none). Subscribe to the site. Subscribe to Netflix. Subscribe to toilet paper. Subscribe to these groceries. Pay a membership fee for the right to subscribe then tip your driver who delivers the subscriptions your membership lets you subscribe to. Time to work? We’ve got to update your laptop and will slow down everything you do until you agree to update. But first, click here to agree. Update installed — your laptop’s broken now. It doesn’t matter, since your boss just replaced you with AI. Go to your phone to complain on social media. Wait, your phone needs an update so we can add more AI. Click here. Oh sorry, your phone can’t handle this update. Now it’s useless. Go get the newest phone. Here’s a text from a friend, an email, a voice mail they left three days ago but you didn’t see until now because of sync problems with the cloud. It’s their GoFundMe. Their MLM. Their Patreon. Never mind, you didn’t respond to their text within 9 minutes and now you’re no longer friends. They blocked you. Make new friends. Download this app to find people in your area. In your neighborhood. On your street. Two doors down from you. Do you know this person yet, we think you’d get along. You need an account to use this app. That username is taken. Enter a password. Not that one, you used it on another site. You need to be connected to WiFi to download the app. Allow the app to connect to other devices on your network. Allow the app to access your contacts, know your precise location, store your credit card details. Oops, sorry, we got hacked now all that info is available on the web. There’s a class action suit. You can join. It’ll take a decade to get your $3.73 share of the ten billion settlement. We’ll send it via PayPal or deposit it to your bank, just tell us those details. Oh no, another hack. That info is circulating now, too. Here’s a spam call, a spam email, a spam text. Why are you angry? Why are you talking about getting rid of your phone? Why don’t you like AI, it lets us make all of this easier? Do you know how ridiculous that sounds? This is progress. You’ll be left behind. Do you want to be left behind? Do you???

[Kenneth Loi @kenjmloi]

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR.

We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets.

Thread + link below.

[Banana Oncology @Banana_Oncology]

It's time for all drug developers to reconsider heavily relying on Wuxi to synthesize their proprietary compounds

How $ERAS obtained ERAS-0015 from Wuxi>Joyo>$ERAS should be a case study

$RVMD used Wuxi to synthesize their very early pan-RAS compounds, and guess what? Wuxi imminently came up with the nearly identical structures as Darax and tried to patent that...

[Joseph DeCorte @DecorteJoseph]

@markkaplan20 I’m not implying insulin dynamics don’t play a role in AD pathogenesis. But “same mechanism, different organ” and “the brain cannot use glucose” are incorrect statements.

[Joseph DeCorte @DecorteJoseph]

@markkaplan20 But brain uptake of glucose is insulin independent (via GLUT-1/3… the rest of the body uses GLUT-4, which is insulin-dependent). Insulin receptors do exist in the brain, but they play a largely neuromodulatory role (e.g., synaptic plasticity, pathways related to memory, etc)

[Anirban Maitra @Aiims1742]

New compound from @RevMedicines RM-055 disclosed at #AACR26
They took a subtle finding 👉🏽Daraxonrasib-CYPA complex modestly increasing RAS GTP hydrolysis 👉🏽 to build a RAS GAP on steroids. RM-055 flattens Daraxonrasib resistant tumors including RAS amplified cases across models.

[Joseph DeCorte @DecorteJoseph]

@DrNeilStone Diprivan- DI isopropyl IV ANesthetic

[Bilim Dünyası @dunyasalbilim]

Almanya’daki Sprengel Müzesi’nde sergilenen sıra dışı bir kinetik enstalasyon:

Havada sallanan bir şamandıra, Atlantik Okyanusu’ndaki gerçek ikiziyle eşzamanlı hareket ediyor ve dalgalar üzerindeki salınımını birebir taklit ediyor.

[ilyas sahin, MD @ilyassahinMD]

New promising phase 1 study for lung cancer @NEJM *

Zongertinib in HER2-Mutant NSCLC

-ORR 76% (tumor shrinkage in most patients)
-PFS 14.4 mo (disease control)
-Brain mets: 47% response
✅

[William Gibson @wgibson]

RevMed just doubled overall survival in pancreatic cancer by using CypA-targeting molecular glues to potently drug oncogenic KRAS-ON, long deemed untouchable.

One funny thing is that probably the most fundamental insight for daraxonrasib sits in a PNAS paper that's been cited merely 84 times. This showed that molecular glues can coax an endogenous protein to wrap itself around utterly featureless surface. The other is a 2017 Cell Reports paper (just 68 citations) on how Sanglifehrin A can be used to repurpose CypA's surface. A lot of the game-changing stuff seems niche and unglamorous at first.

Greg Verdine is having a chembio Annus Mirabilis for his 2025-2026 streak: FOG-001, Daraxonrasib. He provided much of the foundational conceptual work behind taking out both Beta-catenin and KRAS*.

*of course many others contributed immensely, but let's give some credit where credit is due!

[NASA @NASA]

Make new friends, but keep the old.

A new photo captures the Moon's near side on the right (the side we see from Earth, identifiable by its dark splotches) and its far side on the left. The Artemis II crew are the first to see the far side with human eyes.

[National Geographic @NatGeo]

Just 1,500 feet (457 m) from the Artemis II launch, we deployed our special high-resolution, slow-motion camera to record the blast-off in jaw-dropping detail at 2,000 frames per second. Find out how we did it: https://t.co/MxKSqR5zes

[Jia (Jenny) Liu MD PhD @JiaJennyLiu]

The TIGIT catastrophe‼️
30 agents
220 trials
~50,000 patients
>$3B+ invested

0 approvals.

This is herding in drug development.
In BMJ Oncol we examine why it happens, the hidden costs, and what needs to change.
It’s already happening again in ADCs...
🔗:https://t.co/dvbS49jGkF

[The Scientific Lens @LensScientific]

A method of drawing infinitely many touching circles

Credit: Matt Henderson

[Pavlos Msaouel @PavlosMsaouel]

@f2harrell @elmir1omerovic To claim that Bayesian methods are more likely to compromise research integrity than frequentist ones is a textbook example of what @StatModeling calls: “straining on the gnat of the prior distribution while swallowing the camel that is the likelihood”: https://t.co/iQr6Sfyvdx

[Wungki Park, MD MS @CentralParkWMD]

1/n

Setidegrasib the first-in-human, first-in-class, KRAS G12D-targeted protein degrader #TPD

Our KRAS G12D degrader study is now published in the New England Journal of Medicine @NEJM
https://t.co/8Juil6VN42

A new way to target KRAS G12D - one of the most common oncogenic drivers across cancers.