NewLimit

Working toward radical extension of human healthspan using epigenetic reprogramming.

[NewLimit @newlimit]

Following breakthrough results, we’re bringing longevity medicine to human trials.

We’ve raised a $435M Series C led by @foundersfund to make it happen.

Reprogramming cell age has the potential to create more healthy years for everyone. We're closer than ever to realizing it.

[Ashlee Vance @ashleevance]

New Limit just raised $435 million. This is, in part, because they've had a massive breakthrough on reversing the age of the liver with their new brand of genetic reprogramming drugs.

For the first time, NewLimit's co-founder and president Jacob Kimmel details the company's breakthrough here.

We also get into the longevity and bio-tech fields more broadly to explain where aging science and AI are heading.

If nothing else, come to see some mice get drunk.

The Core Memory podcast is available wherever you pod, and I'll put the YouTube link down below in the replies.

Our show is sponsored by Brex and SendCutSend. They are both wise and benevolent.

Timestamps
0:00 Intro
3:50 What Is Epigenetic Reprogramming?
7:16 Growing a Whole Animal From One Old Cell
13:06 Meet Ambrosia, the AI Hunting for Youth
22:44 $435 Million and the Race to Human Trials
29:26 The Drunk Mice That Skip the Hangover
36:48 Inside the First Human Trial
43:14 Will There Ever Be a Hangover Pen?
49:39 Beyond the Liver: The Delivery Problem
1:03:27 Answering the Skeptics
1:12:42 Will OpenAI Become a Drug Company?
1:23:53 The Health Story Bigger Than AI?
1:35:00 How Far Behind Is the US vs China?
1:53:10 Can We Build Computers From Neurons?

[Ashlee Vance @ashleevance]

Your reminder that we have a glorious video taking a look inside @newlimit's labs. https://t.co/jeX59XAHly

[Andrew Dunn @AndrewE_Dunn]

NewLimit, the anti-aging startup co-founded by Coinbase CEO Brian Armstrong, has closed the 2nd largest round in biotech for 2026: https://t.co/NBjbMOH8bX

[Patrick Hsu @pdhsu]

Human trials next year for @newlimit's first aging reprogramming medicine with an exciting pipeline behind it. An honor to be a partner to @jacobkimmel @byersblake @brian_armstrong and NewLimit's stellar scientists

[Ilya Fushman @ilyaf]

Congratulations @byersblake @jacobkimmel @brian_armstrong and the entire @newlimit team!

[Blake Byers @byersblake]

The aging research will continue. Thank you @foundersfund for leading, @ThriveCapital, @Greenoaks and @QuietCapital for joining and all our insiders for coming back.

[Brian Armstrong @brian_armstrong]

Aging is arguably the root cause of most major diseases (loss of function in our cells). Four years ago, we made a bet that aging was treatable, and NewLimit was born.

NewLimit now has a prototype drug that reverses the age of some human cells (restores function they had when they were younger), and a clinical trial scheduled for next year (with more drug candidates in the pipeline).

Grateful to Founders Fund, Thrive, Greenoaks, and the rest of the investors for this latest round. @jacobkimmel and the team are just getting started.

[Jacob Kimmel @jacobkimmel]

on day 1 @newlimit, we imagined it would take 10+ years to invent real medicines.

our recent results have accelerated the timeline to next year. we've raised a Series C led by @foundersfund alongside @ThriveCapital, @Greenoaks, and many others to bring therapies to the clinic.

medicines for aging are among the most valuable possible technologies. we are grateful to our partners for the opportunity to pursue this mission.

[NewLimit @newlimit]

Alongside Founders Fund, we're privileged to welcome @ThriveCapital, @Greenoaks, @QuietCapital as partners alongside returning investors @AbstractVC, @kleinerperkins, NFDG, Eli Lilly Ventures, @valor and many more.

We are grateful to each of them for joining us on this journey.

[NewLimit @newlimit]

Following breakthrough results, we’re bringing longevity medicine to human trials.

We’ve raised a $435M Series C led by @foundersfund to make it happen.

Reprogramming cell age has the potential to create more healthy years for everyone. We're closer than ever to realizing it.

[Dwarkesh Patel @dwarkesh_sp]

If animals live longer, they can have more kids, and pass on more of their genes. So why hasn't evolution solved aging?

@jacobkimmel explained the three evolutionary reasons why we still grow old:

(1) Longevity doesn't actually help that much. Most of our primate ancestors didn't die of natural causes: if you are probably going to be eaten by a tiger, a naturally long lifespan is pointless.

(2) Some genes might benefit from aging! If an older animal dies, often the resources they would have consumed are instead consumed by younger kin, who are genetically similar to them but more likely to reproduce.

(3) Even if the two other arguments are wrong and there's selection against aging, there might be even stronger selection on other traits. Evolution just might not prioritise longevity.

[Jacob Kimmel @jacobkimmel]

.@newlimit's first reprogramming medicines will enter the clinic in the coming years.

we're recruiting a clinical leader to guide these trials for a new class of medicines intended to keep patients healthier, longer.

reach out if you or a colleague are a good fit.

[BiotechTV @BiotechTV]

𝐄𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜𝐬: BiotechTV visited @newlimit in South San Francisco and heard from Co-Founder & President @jacobkimmel how they are trying to tackle diseases of aging through epigenetic reprogramming.

[Jacob Kimmel @jacobkimmel]

we created the first reprogramming asset @newlimit last year. we're now recruiting an executive to lead our early development efforts.

this role will work closely with me, own our pipeline, & help pioneer a new class of medicines.

please reach out if you know an excellent fit!

[Jacob Kimmel @jacobkimmel]

2025 @newlimit:
- 0 -> 1 candidate medicine that restores multiple youthful functions in old livers
- 2X discoveries/$ with our frontier AI system
- >1000X more TF payloads tested vs. the field

we built our 1st medicine & began development

2026: we move toward the clinic
# discovery cadence

@newlimit is built around a set of core technologies we call our Engine.

our Engine discovers transcriptions factor (TF) payloads that make old cells look and act young. the Engine prioritizes payloads using:

AI systems -> large-scale genomics screens -> functional assays -> animal models of aging & disease

in 2025, we increased the scale & fidelity of the Engine many fold.

key outputs:

- >1000X more TF payloads tested than the field, combined
- 16 payloads restore function in animal models
- 36 payloads restore function in cells
- 600+ make old cells look young based on gene expression
- $/function hit down 17X, headcount only up 1.4X

# entering early development

therapeutic discovery transitions into development once an optimized prototype medicine known as a preclinical candidate is chosen for in-depth evaluation.

we imagined at the founding of NewLimit that it would take 5+ years to create one. the science advanced faster than we thought, so we delivered ahead of schedule after just 3 years of operations.

our first candidate is based on a payload with pleiotropic activity, making old hepatocytes both look young and act young across multiple dimensions. we discovered the candidate in a humanized liver screen, where it made old human hepatocytes look younger & regenerate like young cells too.

one function in one assay isn't enough to say we truly reversed cell age, so we checked others. we found our candidate also restored regenerative function in mice after surgical injury and resilience to alcohol diet. the candidate was also safe -- the liver tolerated it well, and there were no signs of neoplasia (think, cancer).

we ran our first lead optimization campaign and generated a candidate with 8X more specific expression and 1.6X the potency of our initial prototype. this became our preclinical candidate and we're moving it toward the clinic now.

# AI systems accelerate therapeutic discovery

there are >10^16 TF payloads we might test. no matter how many experiments we run, we'll never search the space completely.

to discover an optimal reprogramming medicine, we need to effectively prioritize which hypotheses we test before ever entering the lab.

only a few years ago, this problem was intractable. humans can't reason through a hypothesis space of this scale. AI systems by contrast can incorporate a plurality of prior knowledge to design experiments that maximize our rate of discovery.

this year, we introduced Ambrosia, the 1st AI system that can accelerate the design of reprogramming payloads. Ambrosia builds atop knowledge captured in foundational models of molecular biology and natural language, initializing our system with a strong prior derived from both human languages and nature’s languages.

our system first learns to predict the effect of arbitrary reprogramming payloads on both the state and function of old cells. given this discriminative model, Ambrosia can design reprogramming payloads that induce a target cell state or phenotype. the design process can even learn continually from sequential experiments.

using Ambrosia to design our experiments, we can improve our discoveries/$ by >2X. we believe this is among the first AI systems that has been integrated effectively into a large scale target discovery process.
the complexity of human pathology far exceeds the sophistication of most therapeutics. our medicines have been constrained by our intelligence.

reprogramming medicines are only now entering the realm of the possible due to the advent of AI systems that remove this intelligence constraint. if successful, the design of reprogramming medicines that extend human health will represent one of the more dramatic impacts of AI on our world.

# diversifying lineages

@newlimit's ultimate ambition is to create reprogramming medicines to restore function across most cell types in the body. this year, our progress in hepatocytes & T cells convinced us it was time to add a 3rd type to the portfolio.

in August, we launched a Vascular program focused on restoring function in endothelial cells, the cell type that lines blood vessels. endothelial cells are everywhere in the body, and their aging contributes to disease in the kidneys, heart, and even the brain.

in just four months, our team

- transferred our Engine tech with 0 modifications & executed discovery screens
- built 2 functional assays for endothelial cell age
- developed a lipid nanoparticle delivery method that delivers TFs to >60% of kidney endothelial cells

we never expected this program to move so quickly. by next year, we imagine we'll be able to reprogram old endothelium back to a youthful state.

# 2026

@newlimit's first 2 years were focused on a set of fundamental research and technology problems. We built a system to search for reprogramming medicines, discovered the first payloads that can reprogram cell age, and demonstrated that restoring youthful function in old cells was possible.

in 2025, we created the first medicine we hope to bring to human trials and showed that it can rescue multiple youthful functions in old cells.

2026 will be the year that we transition from purely a research enterprise to an integrated research & development organization. effective execution in this next stage will allow us to bring reprogramming technology into human patients.

if these medicines are successful, we believe they are among the most valuable products possible.

[Jacob Kimmel @jacobkimmel]

enjoyed this conversation with @NWischoff on @newlimit, aging biology, & the economics of biotech a couple weeks back

[NewLimit @newlimit]

https://t.co/ESwCVqiLmK

[NewLimit @newlimit]

Our fall progress update is live 📈

Full link in thread 👇

[Jacob Kimmel @jacobkimmel]

autumn @newlimit -- we've advanced our 1st reprogramming medicine through optimization

highlights
- 8X specificity, 1.6X potency for our lead prototype medicine
- +2 TF sets that restore liver function, +20 that restore phenotype
- 0 -> 1 preclinical models of endothelial age

# engineering therapeutic molecules

in september, we selected our first prototype medicine for liver aging to advance toward the clinic. this initiated our first lead optimization campaign to improve the potency & specificity of our prototype.

our RNA medicines allow for engineering at the sequence level. RNAs are not translated into proteins equally across cell types, and we can design sequences to maximize activity in our target cells (hepatocytes) and minimize activity elsewhere.

our campaign achieved an 8X increase in the specificity of our prototype & a 1.6X increase in the potency within hepatocytes. we believe these optimizations will yield a safer, more effective medicine.

# restoring youthful resilience

alongside progressing our first asset, we've continued to discover reprogramming payloads that restore youthful function.

in october, we discovered +2 payloads that restore youthful resilience to alcohol damage in old livers. these payloads emerged from our discovery screens & validated as prototype RNA medicines.

each month, more of these payloads emerge from Discovery Engine, giving us confidence that the well of potential reprogramming medicines is deep.

# in vivo T cell reprogramming

hepatic reprogramming is only one of several therapeutic applications we’re pursuing. we’ve previously discovered reprogramming payloads that restore youthful cytotoxic capacity and stem-like states to old human T cells.

the next stage in the development of these payloads is to test whether they can rescue function in a more complex animal model. before we can test their effects directly, we need to build molecular tools to deliver reprogramming payloads to T cells in vivo.

after a series of engineering iterations, we've developed a lipid chemistry that can carry our RNA medicines into T cells in animals. our chemistry is now nearly matching the current state-of-the-art.

# measuring endothelial cell age

our most recent therapeutic program is focused on restoring function in endothelial cells of the vasculature. we believe improving endothelial function could create renal, cardiovascular, and cognitive health.

endothelial cell aging is dramatic enough that we’ve been able to discover functional impairments in just our first few experiments. human endothelial cells are less regenerative in simple in vitro systems, and endothelial injury leads to more dramatic renal damage in old animals.

even these early tools allow us to start testing the effect of reprogramming on aged endothelial function, in addition to phenotypes.

# join our team

we're recruiting talented scientists & engineers across our therapeutic programs and technology teams. reach out if you're excited to create a new class of medicines that add healthy, happy years for ~everyone.

[Jacob Kimmel @jacobkimmel]

.@newlimit has raised an additional $45M from new investors including Lilly Ventures, Duke University, @S32_VC, @AbstractVC & others.

Insiders including @kleinerperkins, @_DimensionCap, @humancapital, @BoostVC also participated.

This round was catalyzed by technical breakthroughs since our Series B just 5 months ago. Advances in our lead program to restore youthful liver function now give us the confidence to start planning clinical studies in the next few years.

We're grateful to all the new & returning capital partners for supporting our mission.