Ebenezer

Private biotech

[Ronald Witteles @Ron_Witteles]

🚨🚨🚨 CARDIO-TTRansform data presented at @escardio #ESCCongress and simultaneously published in @NEJM. The (very surprising!) topline data was released last month – now we get the full data release. Much to break down – it’s all here in the 🧵 below. (1/25) https://t.co/l2gue8or6u

[Andrew Pannu @andrewpannu]

Biopharma leaders - if you're developing or investing in immunology & inflammation, we just dropped a report mapping >15K active programs, the strategies of top Pharma today and the mechanisms reshaping major markets.

Here's the headline: I&I is moving from chronic immune suppression toward durable remission and, for the most refractory patients, immune reset.

This is not an immature space (>$100B in total revenue), but patients still cycle through therapies that interrupt just a portion of the inflammatory cascade, and thus work for only a fraction and for a limited time.

IBD is a great example - despite multiple generations of treatment (TNF, integrin, IL-23, S1P and JAK), induction remission rates are stubborn, and many initial responders eventually relapse.

As we think about how we'll close these treatment gaps, it's helpful to look to oncology drug development for precedent. There, we've learned to activate, redirect and deplete immune cells, and then match those interventions to molecularly defined patients. We're seeing many of the same tools redeployed in I&I:

• CD19 CAR-T and other cell-depletion strategies
• Off-the-shelf T-cell engagers and bispecifics
• Targeted protein degraders
• Predictive biomarkers and patient selection

And while 1st gen programs leveraging these tools were mainly oncology programs repurposed for autoimmune disease, a wave of purpose-built I&I companies have emerged over the past few years (including many Sleuth customers!).

Pharma is all over I&I - with 2026 M&A in the space on pace to exceed $100B in annualized deal value.

The "pipeline-in-a-product" dream is uniquely alive here, given the degree of shared biology across multiple large indications, with drugs like Humira and Dupixent demonstrating the power of that model.

But the heterogeneity of I&I also means no single mechanism will win everywhere. That's why we see every major Pharma assembling mechanism stacks designed to work across diseases - recognizing that owning a ladder of interventions and matching patients to each rung will be key as the I&I space fractures in much the same way oncology did.

Other topics covered in the report:
• How efficacy headroom is determining where white space remains
• How a target’s position in the immune cascade shapes its ability to migrate across indications
• Where oral therapies can truly beat biologics, and where convenience isn't enough

This is part of Sleuth’s intelligence report series: comprehensive landscape analyses across the therapeutic areas, modalities, and mechanisms shaping biopharma strategy.

Comment “Sleuth” (or just ask below) and we’ll send you the full, unblinded report. And let us know how you see this space evolving!

[Ebenezer @BackwaterBio]

@andrewpannu Sleuth

[Daphne Zohar @daphnezohar]

Useful free tool tracks a number of key parameters in one place based on regulatory filings rather than press releases (changes to endpoints/timelines, funding runway and catalyst timing discrepancies, ownership etc). https://t.co/IPQJznahPD by @insidepharma $XBI $IBB $BBC

[Billy Binion @billybinion]

AI helped create a cancer vaccine. Data centers are lowering people’s property taxes, revitalizing dying towns by flushing them with revenue, and…helping power the infrastructure to cure cancer.

Every data center hater should explain why any costs outweigh those benefits.

[Bill Ackman @BillAckman]

At midnight on February 6th, earlier this year, the doorbell to our apartment rang. The doorbell was followed by a pounding on the door. I answered the door and a security person in our building handed me his phone. It was my oldest daughter Eloise. She had found my 26-year-old daughter unconscious on the floor of her apartment and had called 911. The EMT team was already there, but they did not know what was wrong with Lucy or to which hospital they would take her.

I threw on some clothes and jumped in an Uber heading east toward Brooklyn. (Lucy lived alone in Williamsburg.) On the way, I learned that they were taking her to Elmhurst, a City trauma hospital in Queens. I arrived about five minutes after the ambulance to join Eloise, Lucy’s mom, and a friend, and waited to learn what was wrong.

After about 15 minutes, I asked a nurse where she was. I looked over his shoulder to his computer. Next to her name, it said “non-responsive.” I walked into the emergency room and wandered around looking for her until I found her unconscious on a gurney surrounded by several doctors and nurses.

By about 2:30am with the results from a CAT scan, Lucy’s doctors had determined that she had a massive brain hemorrhage and would need an emergency hemicraniectomy to release the pressure on her brain and remove the blood from the hemorrhage. I called our wonderful friend and family doctor Eddie Fisher and explained what was going on. He woke up Josh Bederson, Chairman of Neurosurgery at Mount Sinai, to find out more about Zach Hickman, the neurosurgeon on call that night. Dr. Bederson said Hickman was an excellent surgeon, which was comforting as we had no choice.

The surgery to save Lucy’s life began around 3:15am and finished around 5:30am. It was successful.

The following day, I joined Lucy in an ambulance while she was being transferred to Mount Sinai on Madison Avenue. Later that day, we determined from Lucy’s Oura ring that her hemorrhage had occurred around 9am, which meant that more than 19 hours had passed from the time of the hemorrhage to the completion of the surgery to release the pressure on her brain (I only wish @ouraring had an alert for this kind of a medical event. Imagine it could call a family member if the wearer doesn’t cancel the alert).

I later learned that the standard of care is not to do surgery to save a patient with a large brain bleed if more than five hours have passed since the hemorrhage. Even when the surgery is done, I was told that the likely outcome for the patient is a few months in a nursing home and death from pneumonia.

When I met Lucy’s doctors, I did my best to inspire them: “Let’s see what can be accomplished if we give her the best care possible and we invest unlimited resources to restore her to life.” And I promised that whatever we learned we would make available to everyone.

Dr. Chris Kellner, her neurosurgeon, and Dr. David Putrino, Director of Rehabilitation Innovation for the Mount Sinai Health System have led Lucy’s care team since that day. Words cannot describe the remarkable and compassionate care that she has received beginning with the EMT team and then from nurses, doctors, therapists, and the army of people who have worked to save her and return her to life. To this day, we have a daily Zoom where we discuss her progress and make adjustments to her care. While her care and oversight have been incredible, the learnings for the Mount Sinai team have also been elucidating and will assist in the care of many others.

Lucy began in a bad place. She was in a coma for several weeks and then awoke not being able to breathe on her own, unable to walk, see or speak.

Over the last six months, she has recovered her cognition – she understands everything including her circumstance – is able to walk a hundred or more steps at a time with assistance, is making progress with sounds, vowels and consonants and the beginnings of speech, but she remains unable to see.

Each day, she makes a little progress, and daily progress compounds. Every day I tell her that she just needs to make a little progress and it won’t be long before she is back.

We remain optimistic that Lucy will return to normal function. It will likely take years, but I believe it is only a matter of time, hard work, and technological progress, along with some, and perhaps a lot, of divine intervention.

Many people have been praying for Lucy and we are incredibly grateful for the prayers and remarkable support she has received. Lucy’s friends have been with her every day since the beginning, and their presence and friendship have saved her life and helped to rebuild and maintain her spirit. And on a very positive note, Lucy’s challenge has brought together our entire modern family who have all been incredibly devoted to her care and recovery.

Lucy's vision and other faculties may require some form of brain computer interface, work that is underway at Neuralink, Precision Neuroscience, Science, Synchron, Nudge, and other companies in the space.

If you are going to have a devastating brain injury, now is the best time in history for that to happen. We are living in a world when you can be confident that the blind will soon see again. We are going to do everything we can to help make that happen, including by assisting existing companies in the space.

With respect to our promise to make Lucy’s care available to others, we have made good progress. In May, a real estate colleague made me aware of a 93% vacant, brand new, 400,000 square foot Class A+ purpose-built biotech facility on West End Avenue between 65th and 66th Streets that missed the market and was available for sale. The Pershing Square Foundation acquired the building 60 days later.

We also put under contract an adjoining 130,000 square foot building at 320 West 66th Street that is currently being used by Saturday Night Live for studio space. The building has 35-foot ceilings with massive column-free spaces that can be converted into superb rehabilitation facilities. We will close on the SNL building in December.

We are also acquiring an adjoining vacant lot with additional air rights. With just the existing zoning rights, we can add a 150,000 square feet for a total of 680,000 square feet, a lab footprint larger than Rockefeller University, and that’s without including the potential for an upzoning that would allow for substantially more buildable area on the site’s 3.4 acres with spectacular views of the Hudson.

Our goal is to build the world’s greatest brain research, rehabilitation, recovery, human optimization, and longevity institute. We have named it The Ackman Oxman Institute or the AOI for lack of a better name, but also to reinforce the point that Neri and I and our family are all-in on the mission.

The AOI will be patient-centric. It will not be an academic research institute that produces lots of papers, a Nobel Prize winner or two, but little if any results for patients. We will be laser-focused on cures, treatments, devices, rehabilitation and exercise equipment, and targeted and basic research with a goal of massively accelerating the time from idea to innovation to production to helping a patient.

While the AOI will be a non-profit, it will have highly commercial instincts. The AOI will have its own venture funding and will work to develop innovations to create companies that we will seed, assist, and spinout to ensure technologies, treatments, techniques, and drugs get to patients as promptly as possible.

On one 3.4 acre campus in what is still the greatest city in the world, we will do neurosurgery, neuroscience, rehabilitation, nutrition, BCI and device development, human trials, hyperbaric oxygen treatments, and life extension programs, and we will mandate and incentivize collaboration among the teams with no silos, politics, bureaucracy, or any other constraint that is inconsistent with the mission.

Mount Sinai will be an important partner and deservedly so, but it won’t be our only hospital or medical school partner as we don’t believe any institution has a monopoly on the best ideas or the best talent. We don’t believe in exclusive relationships because that is not in the best interest of patients.

Five years ago, we considered launching a brain institute inspired by Neri’s mom who sadly died from Alzheimer’s. We couldn’t make the math work as the real estate was too expensive and we believed it would be too difficult to recruit the best talent from universities to our effort.

Since then, the real estate became available at a 70% discount, universities became a much less attractive place to work due to politics outweighing meritocracy, protests that disrupt learning, the curse of antisemitism, and a decline in funding. Fortunately, during the same time, I made sufficient personal economic progress to make the AOI possible.

The advance of AI in the last few years will also enable us to greatly accelerate our mission. AI still has a lot to learn about human intelligence and the brain, and the AOI should be at the forefront of the interplay between the brain and AI.

Today, I am making a public filing disclosing a gift from Neri and me of ~$400 million or 10,000,000 shares of Pershing Square Inc. (PS) to the AOI. It is very early days for Pershing Square so these shares are intended to anchor the long-term work of the AOI as the shares compound over time while generating what we expect will be a growing stream of quarterly dividends to fund the Institute.

We will also be announcing an additional gift of similar and potentially greater size which won’t be in the form of Pershing Square stock to provide the AOI with the short- and intermediate-term runway necessary to enable it to achieve its goal of becoming a self-sustaining institute, which reinvests all of its revenues, royalties, and the economic rewards of company formation to advance the fields of brain health and human longevity.

Neri and I have chosen to anchor the funding of the AOI to maintain vision alignment and limit the need for the organization to focus on fundraising. We expect the AOI to be the best-resourced brain, rehab, recovery, and longevity institute in the world.

We are grateful to have been able to form a board which includes Dean Kamen (our generation’s Thomas Edison), George Yancopoulus (CEO of Regeneron), James Rothman (Nobel Laureate), Bernardo Sabatini (neuroscientist), Chris Kellner (neurosurgeon), Olivia Flatto (CEO Pershing Square Foundation), Neri Oxman, and myself.

We have recently identified a CEO who we expect to announce by October along with other key hires, and are beginning searches for a Chief Scientific Officer, a Chief AI/Technology Officer, a Chief Operating Officer, a Chief Financial Officer, and other key leadership roles.

If you find what we are building compelling and want to be part of the leadership team that creates and builds the AOI from a standing start, please send an email to: [email protected] with a short note as to why you believe you can help. Please include your best three ideas for the AOI along with a summary of your background and your most important accomplishments.

We promise strict confidentiality to those expressing interest in working with us.

We have learned from Lucy that the brain can recover from even catastrophic injury. There is so much more work to be done as the mind is a terrible thing to waste.

For details from my Pershing Square SEC filing see:

https://t.co/gZKafCw6Ia

[Ebenezer @BackwaterBio]

Q2 13-F's with new initiations for $AMLX

[OldGrape @OldgrapeX]

Thirty most owned tickers across 32 healthcare specialist funds - 13F-HR filings/ Filed 14 Aug 2026
$COGT, $TNGX, $CLDX, $PHVS, $RVMD, $ORKA, $PCVX, $ABVX, $ELVN, $GPCR, $AVTX, $EWTX, $SYRE, $RLAY, $MBX, $CYTK, $IRON, $XENE, $PRAX, $INSM, $PRBL, $ALMS, $DNTH, $VRDN, $VERA, $NRIX, $BCRX, $DFTX, $DYN, $AURA

https://t.co/BYSL7zPgGi

[Seedy19 @seedy19tron]

Remaining catalysts from Cowen and UBS reports

$xbi $bbc $GMAB $tenx $eypt

[Anthony @anthonystaj]

one of the funny facts about AIs i found out this week was that a 1M token context window is like ~100 papers. if you actually use the context window that's obviously smaller could be that a couple dozen papers is all a model can have in its head at a given time. so what happens when someone uploads millions of papers?

the AI/ agents just summarize things and try to do it right. but if you go back and read the original papers you inevitably find massive holes in the proposed AI workflow.

i mean just conceptually think about the fact that your brilliant AI can only keep like a dozen papers in its head at a given time. i read a dozen papers the past few days.

we all know this is true, because when you chat with an AI, ask it to summarize a topic you actually know you have to tell it the 5 ways it messed up the interpretation of the subject. i find that in my own work I can't *ever* take an AIs opinion at face value. i *have to* push back, find the flaws in its argument before I sense we're actually doing any work

this is what I mean when I say that all these frontier models don't really have any edge over well reasoned human judgement. they are overfitting narratives to stupid stuff because they're just playing glorified telephone with their agents and missing key facts of the story like which experimental conditions lead to some assay lighting up a gene and how that condition is completely irreproducible and you know it because you read a paper from 1997 that showed that and the AI didn't have that in its context window and its a total sycophant for anything published in a peer-reviewed journal so it missed that fact.

these AIs are just tools. this AI tool is literally no better than an undergrad with a library card. and even if it makes some alleged insight, who cares? what's it going to do? make money grow on trees to test it out? go ahead, set some money on fire for all i care

there are so many actually tractable engineering problems in biology that hypothesis generation is really a waste of time for the most part (says the engineer)

[Alex Kesin @alexkesin]

@approvedfm Spotify https://t.co/U6PZzqhZTG

[Jing Liang 🇺🇦 @AppleHelix]

SG&A is $17B for BMS and $32B for AZ.
R&D is $10B BMS $14B AZ.

If you save 20% on SG&A and 10% on R&D, you have about $12.5B incremental to spend on M&A each year.

[Ebenezer @BackwaterBio]

@Biohazard3737

[Ebenezer @BackwaterBio]

@satvik_93 From a sell-side report this morning

[rohit @rohitarorayyc]

Introducing PG-LLM, a benchmark testing if general-purpose LLMs can predict protein variant effects.

Across 217 tasks, Claude Opus 5 (Max) leads all tested LLMs at ρ = 0.406 and outperforms 49 of 95 specialized protein predictors when ranking 50 variants.

[Ebenezer @BackwaterBio]

@PersimmonTI Post-HORIZON readout should be interesting

[Adu @plainyogurt21]

Slightly late, but here's some 2H catalysts with some notes. See images for Sell side catalyst trackers

[Ebenezer @BackwaterBio]

Thank you - hadn't seen this comment elsewhere. Curious too with the hsCRP lower by >50%, calls into question IL-6/NLRP3?

[Adam May @A_May_MD]

So, uhhh?
$LLY $NVO

[Director Michael Kratsios @mkratsios47]

In response to @POTUS's call for a revival of America's scientific enterprise, today I’m releasing Science: A New Golden Age.

This report is a blueprint for renewing American scientific leadership for the 21st century.

[Ebenezer @BackwaterBio]

@satvik_93 Great point, especially given the CANTOS results where the IL-6 cutoff subgroup saw MACE correlation benefits but there was no such change for IL-18.