A

@drrichjlaw Would you be able to follow me. Would like to chat.

Did a lady at Samsung just crack AI?

Very excited to see $QURE getting approved soon, great for patients.

@MidwestHedgie Are you short SOC?

it's entirely possible that we are wrong on $SOC and it's not a good short at all (it does have some real buyside longs), but fwiw this is one of the most entertaining collections of shareholders on twitter i've seen in a while. hard to beat "Weasel wearing a hardhat in bio"

@doctorveera It’s basically the genesis of the new VKTX pain drug

Today I stumbled upon a remarkable case report of a boy born with congenital insensitivity to pain who led to the discovery of a USP5, encoding a deubiquitinase enzyme, as an important regulator of pain sensitivity. The boy, born slightly early, initially appeared healthy but soon exhibited signs of congenital insensitivity to pain. This condition led him to unknowingly inflict severe injuries on himself, particularly to his mouth and fingers. He eradicated his entire lower lip by biting, and his tongue became partly destroyed and adhered to the floor of his mouth. Over time, he developed micrognathia and experienced progressive bone resorption in the lower jaw. His vision deteriorated due to corneal scarring, resulting in blindness in the right eye and significantly reduced vision in the left. At 15, he faced severe health complications, including septic knee arthritis with a leg abscess, which was treated but led to septic embolism of the lung and spleen, as well as abscesses and destruction of the distal right femur. These complications culminated in his sudden and unexpected death at 16 years of age. Initially, extensive genetic testing, including whole-exome sequencing and trio whole-exome sequencing, did not reveal any mutations associated with the boy's condition. However, a more detailed evaluation of the sequencing results, conducted as part of a research setting, identified a heterozygous de novo missense variant in the USP5 gene. It turned out USP5 already is known to play a role in pain sensitivity. Cav3.2 is a T-type calcium channel found in primary afferent neurons that helps transmit pain signals by regulating neuronal excitability and neurotransmitter release. A previous study showed that USP5 binds Cav3.2 and deubiquitinates it, preventing its degradation and amplifying pain signaling (through upregulation of Cav3.2 channels). Blocking this interaction reduces pain (cell.com/neuron/fulltex…). The authors created knock-in mouse models of USP5 mutation found in the boy and found that pain sensitivity was drastically reduced. The mutant mice showed blunted responses to acute, inflammatory and neuropathic pain--especially in males. When looking into how exactly the mutation affects the USP5 protein function, the authors found something fascinating. The mutation had two consequences. One, it inactivates the protein carrying the mutation resulting in loss of enzyme activity. Second, it makes the protein bind to the calcium channel with more affinity than the wild type, thereby preventing the wild type USP5 protein to perform its function. The consequence: full functional knockout effect. This case report is one of many that exemplifies how rare genetic mutations can illuminate critical pathways and mechanisms, offering profound insights into human biology and potential therapeutic targets. Antunes, Gandini, Garcia-Caballero, et al. J Exp Med 2025 rupress.org/jem/article/22…

CRISPR is used in landmark treatment to correct genetic misspelling of a single patient statnews.com/2025/05/15/cri… via @Jasonmmast

@YSuzuki_SLAer Hi I would like to discuss BTBGD. Saw your recent publication. Would you be able to DM me your email?

今回は大変貴重なセミナーの機会をいただき、ありがとうございました！200名以上の参加者がいらっしゃるとは驚きました。さまざまな校種で、英語を教える先生方ともお会いすることができ、私自身もISLA研究から文法指導について振り返る良い機会となりました。

Same opportunity again. Launch your fund now HAHA

Now sold for $30M lol

> independently discover a Zeno's paradox at age 3 > MIT at 17, grad level math in 1st year > graduate in 3 years > drive motor scooters from Boston to Bogotá with the boys > start a company in Colombia > start code breaking with the IDA for money > solve minimal varieties in riemannian manifolds > speak out against Vietnam War, get fired from IDA > take over math dept. at Stonybrook, make it a top-ranked program globally > develop Churn-Simons theory, accidentally contribute more to physics than most physicists > get bored with math, start modeling financial markets > return 60% for 4 decades straight > establish one of the most effective philanthropic organizations of all time > chain smoke cigarettes the entire time RIP Jim 🫡

@eperlste @celinehalioua How do you fund 3-6 patient study?

@celinehalioua Makes me realize I wish there existed a XCA pathway for kids with rare diseases where the reasonable expectation of effectiveness came from biomarker-powered n-of-1 studies of 3-6 patients, and then a sponsor has 3-5 years to conduct a registrational study.

the biggest "why now" of Loyal was the creation of a new regulatory pathway that made it logistically feasible to develop an FDA-approved dog longevity drug. FDA guidance was published September 2019, I incorporated Loyal October 2019 :)

Last 12 months if you are a L/S manager (under 1B) and couldn’t make money, you are a LO manager. Easiest money I have ever made.

AGLE - 90%

$ROIV triple off lows.

$DECK nearly on new highs, ONON will new at new lows within 30 days.

ROIV people finally waking up to they have sold $6B worth of companies in the last 2 years.

$ROIV how much will the company burn before hitting cash flow positive. Think stock is super cheap on sum of parts valuation.

Market doesn’t bottom unless real de-grossing occurs. First time in while you seen Apple sell off. That’s when you know the de-grossing has started. Start of the end is upon us.

FROM BURN ICU TO WHITE COAT CEREMONY AT MED SCHOOL 🙌🥼

@MadThunderdome BHVN acquired. What do I win?

@MadThunderdome AEYE (finally cheap enough to be bought out, doesn’t make sense as a stand-alone co) BHVN ITCI (single drug company never makes sense commercially)

Very proud of our study published in @NEJM. 100% clinical complete response with dostarlimab alone in mismatch repair-deficient locally advanced #RectalCancer. No radiation or surgery! @ASCO #ASCO22 @MSKCancerCenter nejm.org/doi/full/10.10…

Real reason why $LVMH has performed well in the last 2 decades. (I know Cartier not owned by LVMH but pricing elastic in upper luxury market)