99.9% of all bio AI companies going straight to 0. This is what happens when you think you can extrapolate your technology knowledge to drug development
Tommy retweeted
AI will cure cancer and it will kill us all are not contradictory positions, they are both rhetorical methods to make the exact same argument: the future is defined by AI. You are a satellite revolving around the AI sun, at best.
These undefined prognostications of future omnipotence distract from accountability in the present. This rhetoric has two effects 1) it distracts from today’s upside down value capture versus value creation equation 2) it forces a psychological centering of AI and AI companies at the expense of humans and the rest of the world’s institutions.
Any technology’s utility is a function of our ability to control it, not its raw hypothetical power without controls. Chemotherapy requires precision to kill cancer and not kill a host. Nuclear reactors are defined by their controls more than the reaction itself. That a given technology’s utility is bound by the precision of its controls was Palantir’s fundamental insight at its inception: the amount of security the US government can guarantee its citizenry is defined by how much it can guarantee rights to privacy more so than the raw capability to identify threats. If you do not enhance both privacy and security, your product is a toy. AI is not the first technology that couples control with utility.
In the present, the models are voraciously consuming knowhow like a parasite eating its host until both die. Every company I speak to is sprinting to control a spend:outcomes ratio that exploded on them before they could learn how to govern it. They are observing their intellectual assets eroding like a sand castle into the ocean. They are stuck between being upside down on value leakage, yet being told they have no agency over their future.
The inevitability of the arrival of a deity forces individuals to define themselves as a function of that deity. Nobody wants to be that luddite who tells you the Wright Brothers will never fly. Nobody wants to run Polaroid or Blockbuster. No young person wants to be a part of the permanent underclass. Forward leaning humans are psychologically berated into defining their skillsets and objectives as a function of AI. Their careers are lottery tickets. They define utility through how good they are at tickling a model. “Ride the exponential” is a mantra that allows you to be “good” in a moral sense, without earning it.
If you dare to expose yourself as a luddite that is not getting results today, well that is a “skill issue,” or you simply aren’t using enough tokens. This propaganda pursues an inevitable centering of AI, with humans as peripherals. The only thing you have real agency over in the future? Using more tokens of course.
I think if you are going to virtue signal about protecting our future, you should also own the implied vice that comes with your position. Prognostications of armageddon are inextricably linked with acceptance of the bad things that exist in the world today.
350,000 people die of sepsis in hospital settings in the US alone every year. Life expectancy in the US has flatlined over the last 20 years while healthcare spending per person has doubled. 30-40% of the food supply is wasted while 18% of households with children experience food insecurity. 19.5% of drinking water is lost in transit to consumers. A significant portion of the world’s energy supply is threatened by a fanatical regime because the strait of Hormuz is still contested. Putin’s death machine continues to slaughter Ukranians every single day as technological efficacy literally defines meter over meter of protected or conquered land. The CCP has 230 times the shipbuilding capacity of the United States and the implied ability to control the world’s commerce and security. $1.7 trillion of excess, unproductive working capital is locked up in the top 1000 companies in the US, capital that is not producing goods and services for every day Americans. Americans paid over $250 billion in credit card interest at over 20% APR last year and more than half of savers earn less than 3% interest on their savings. Real wages have stagnated, middle-wage workers real income is up only 6% since 1979 while low-wage workers are down 5%. We have a shortage of ~7 million homes in the US. 8.5 million acres burned in wildfires so far this year. As of year end 2025 2,060 gigawatts of generation and storage capacity were waiting for grid interconnects (double the capacity of the existing power fleet). I digress.
We are making real progress against each of these miseries, and many more, because of the incredible progress in AI systems over the last several years.
Perhaps ironically, success in all of these domains is a function of how precisely controlled the models are. For the cognitive labor humans know how to wield to achieve real world outcomes today, open source or off-frontier small models are already at parity for at least a plurality of use cases on a price/performance basis. Those customers reliably outperform the frontier when they incorporate their own proprietary data and decision traces. The most consistent pattern I see over and over again is real world use cases shrink their reliance on general purpose AI’s over time. They encode deterministic knowledge and/or post-trained models on smaller model footprints. It is empirically a wildly optimistic future with AI as an accelerant for the pluralistic, wonderfully diverse means of advancing the human condition against problems you can measure and make progress against today.
We should also own that these horrible challenges persist because these systems are not yet good enough to fully solve them. They are worth improving.
The bay area is abdicating responsibility for the world as it is today while claiming ownership of the world as it might be tomorrow. DC and our political leaders are polarizing into zero sum positions. These are the luxury beliefs of children. Build something people need today, at a price they are willing to pay when not pressured by the social herd, if you want the opportunity to do it again in the future.
$BIIB should run a small P2b of diranersen vs pbo on background maintenance lecanemab in parallel to P3. lecanemab reduce upstream amyloid path + diranersen suppress downstream tau prod
Tommy retweeted
Replying to @GrondResearch @A_May_MD
Even for a "Merger of Equals" like Supernus x Indivior, it's quite obvious who won out in the transaction
AZ + BMS would be devastating internally. Two mid cultures combining to create a Frankenstein org that will take years to integrate everything from pipeline, systems, people, and processes. If this deal goes through, just like any deals this size, only bankers (at least 5 underwriters), consultants (<10 firms), and lawyers (at least 3) win.
Not in this game anymore but the primary takeaway from working at successful funds is risk management
I’ve never met Leo, and from all I can gather he was an exceptional student. Well above top 1%. Probably > 1/10,000.
That said I don’t think he was a “student of finance.” I asked ChatGPT to name the top 25 investing books of all time. And then asked what percentage of those books discussed leverage and tail risk. The answer below.
Quite unusual to chose a career where you are smart at everything else perhaps, but ignorant about one of the most discussed elements of the practice. You have to be willfully uneducated.
It’s dangerous to talk about this execution as anything other than reckless and careless. Simply because that’s the only lesson the future investors need to hear.
Nothing surprising happened here. Just what you would expect from running a portfolio that leveraged. Was just a matter of time. Very “simple” math.
Lipfendra (enlicitide) looks good- congrats to Merck! Commercial success almost seems obvious... convenient, broad label, & the outcomes trial is probably going to be positive in line w/ other PCSK9s
Good drug still
My contrarian belief is that Cytokinetics is probably overvalued on the basis of their unproven commercial execution ability. If they can execute properly, they should be fairly valued.
Aficamten (Myqorzo) received FDA approval last month for symptomatic obstructive HCM, competing directly with BMS’ Mavacamten (Camzyos), a FIC drug.
It looks to me that Aficamten is a BIC drug, with a pretty clear advantage: half-life, time-to-steady state, drug-drug interactions which mostly point to superior safety & convenience for patients. Efficacy looks similar to Mavacamten.
The class effect concern with myosin inhibitors is excessive suppression of contractility leading to systolic dysfunction. Aficamten looks superior in that aspect with no interruptions in their SEQUOIA trial.
Commercially, Camzyos has been absolutely crushing it, and about to hit a $billy+ for 2025. Demand looks good, international expansion looks to be working as expected. I think Myqorzo is going to favor new patient starts over switching since stable patients on Camzyos have limited incentives to change. The question is prescriber preference for treatment-naive patients requiring CMI therapy. Let's keep an eye on the safety profile in post-marketing world.
TAM/SAM/SOM also looks to be growing as is usual for underdiagnosed therapy, and with a potential **nHCM label expansion, there are some positive tailwinds in this market.
I think the biggest thesis on investing in this company would be the confidence in commercial execution. Selling is hard. Only a handful of first time launchers exceed commercial expectations vs. established ones. Peak sales are typically larger for big pharma. The bull case is that BMS did all the market dev/physician ed work and building out the REMS infra. I want to think that Aficamten would win on the basis of better data but I’ve personally seen companies like Sage Therapeutics do terribly in executing their PPD asset.
I’m definitely not short Cytokinetics as a company given M&A risk and how much BMS paid for MyoKardia ($13 billy). However, it doesn’t seem to me that the market has already priced in the commercial risk.
Devil is in the execution.







