Operating Plan

Cell reprogramming

NewLimit is a biotech developing epigenetic reprogramming therapies to extend human healthspan.

Overview

NewLimit was founded to significantly extend healthy human healthspan.

We are developing epigenetic reprogramming medicines to treat age-related diseases on our way to medicines that address the aging that occurs in everyone. The core of our approach is rooted in epigenetic control of gene expression. All of our cells experience functional decline as we age, and it appears possible to reverse this decline through epigenetic reprogramming. By turning on just four transcription factor (TF) genes (“pluripotent reprogramming factors”), we can turn an old, adult cell into a young, embryonic stem cell. This pluripotent reprogramming process reverses cellular “age” while also reversing cell type. NewLimit’s aim is to reprogram cellular “age” without altering cell type.

To achieve this goal, we’ve built discovery technology to search for combinations of TFs – payloads – that make old cells “look” and “act” young based on their gene expression and functional performance. We believe these reprogramming payloads could make powerful medicines for diseases of aging caused by the decline of a specific cell type. We are focusing our initial work in hepatocytes, T cells, and endothelial cells with specific indications in mind as we iterate towards more general purpose medicines for the broader population.

Scientific Background

Epigenetic Control of Aging

More than a decade ago, scientists discovered that we can rewind the clock of animal development in adult cells by activating just a handful of regulatory genes, “reprogramming” adult cells to their embryonic state. Reprogramming works by rewriting the epigenome, changing the rules that dictate which genes can be turned on and off. Remarkably, reprogramming to an embryonic state reverses many features of aging – reprogrammed cells from young and old animals become nearly indistinguishable.

Early experiments have shown that even partial activation of these embryonic programs can restore function in old cells without erasing their unique identities, improving outcomes in disease and injury models. These results are early and more work is required to validate the magnitude of effect, but they do serve as a hint that robust partial reprogramming is possible. Taken in totality with pluripotent reprogramming, the work suggest that many aspects of aging may be the result of plastic, reversible, changes in the epigenome. If we can construct the right epigenetic program, we could conceivably reverse these changes and restore youthful function to old cells. This rejuvenation could have beneficial impacts across a number of diseases with large, unmet clinical needs.

What’s holding us back? There are both unanswered biological questions and unsolved engineering challenges between us and the first reprogramming therapies. We don’t yet know exactly where partial reprogramming will be most impactful, what programs to execute, or what safety risks reprogramming might present. After those questions are answered, we require a delivery system that can execute our programs in the right cells, at the right time, with the right dose.

None of these challenges are trivial, but all are surmountable.

Scientific Approach

NewLimit’s therapeutic programs begin by building molecular tools to measure the loss of function in a cell type with age. We then discover therapeutic payloads using in silico reprogramming AI models, genomics screens, and functional assays. Products emerge when we formulate these factors into RNA medicines.

Payload discovery

Our discovery campaigns employ a tiered screening strategy, beginning with pooled single cell genomics screens to find reprogramming payloads that restore functional molecular states. Most effective reprogramming payloads require a combination of factors. Even a small hypothesis space contains an intractable number of combinations, so an exhaustive search is infeasible (e.g. ~10^16 combinations of up to six human TFs). This has traditionally been a roadblock for the field, but AI methods now allow us to efficiently search the combinatorial hypothesis space and find effective combinations using a tractable number of experiments.

Functional validation

Given hits from these initial screens, we perform validation using functional assays and pre-clinical disease models. Our functional assays are inherently unique to each therapeutic program. As we acquire more data spanning each of these assay tiers, we develop AI models to infer later stage assay results from molecular profiles, improving both interpretability and utility of our first-tier screens.

Biological model systems

We believe that performing payload discovery in human cells improves the chance that our medicines will treat human disease. Wherever possible, we use primary human cells for our payload discovery screens and functional assays, transitioning to animal models for physiological endpoints. We’ve developed first-in-class humanized animal models to bridge the gap between these two systems.

Indications

We are developing reprogramming medicines for multiple cell types. We believe that developing differentiated medicines addressing unmet clinical needs with few available treatment options is the best path for NewLimit to deliver value to patients in the short run, while building a product first organization that can deliver on our ambitious mission over the long run. We’re more interested in being the first option available for patients than the N-th. This philosophy guides our indication selection, alongside technical considerations of delivery, safety, and efficacy.

Metabolism

The liver is a central hub of human metabolism composed largely by hepatocytes. Aged hepatocytes become more susceptible to damage from dietary insults like alcohol and fat, lose their ability to regenerate, and metabolize substrates less readily than younger cells. These deficiencies contribute to higher rates of liver disease and metabolic syndromes. 

Our Metabolism program is developing reprogramming medicines to restore youthful function in aged hepatocytes. We’ve developed humanized liver screening systems to discover these medicines, and we’ve built a host of functional assays to measure our progress toward restoring youthful function. In vivo delivery of LNP-RNA medicines to hepatocytes has been demonstrated clinically for nearly ten years, derisking a therapeutic path. We’re targeting alcohol-related liver disease (ALD) as an initial indication with expansion opportunities in broader aging populations to follow.

Immunology










Vascular

Our ability to combat infectious diseases, prevent the rise of cancers, and avoid autoimmune reactions. Much of this decline can be traced to the aging of T cells. Our Immunology program is developing medicines to rescue T cell function in the elderly, allowing us to reduce the burden of these age-related challenges. We’re initially pursuing opportunities in autoimmunity and infectious disease leveraging emerging in vivo LNP-RNA delivery tools for T cells.






Human tissues are supported by nutrients and signals carried in our circulatory system. The walls of veins, arteries, and capillaries are composed of endothelial cells. Endothelial cells are in a sense a component of every other tissue. As endothelial cells age, they lose the ability to maintain a deep vascular network and robust barrier function. This dysfunction contributes to the onset of diverse disease, including renal, cardiovascular, and cognitive impairments. Our Vascular program is initially targeting chronic kidney disease leveraging emerging LNP-RNA delivery for the endothelial compartment.

Company strategy

We believe that you can’t build a company on a multi-decade ambition alone. Rather, we are committed to developing products that meaningfully benefit patients in the nearer term. Focus is imperative not only for our technical approach, but also for the selection of our therapeutic opportunities. We are committed to building an enduring business so that we can continue to develop therapies for patients.

Financing

NewLimit was founded with an initial commitment of $110M from the founders.

In 2023, we raised an additional $40M Series A round from Dimension, Founders Fund, and Kleiner Perkins with participation from leading angels.

Team

NewLimit currently consists of 34 scientists, engineers and operators as of May 2025, >90% of whom serve in technical roles.

Scientific Advisors

Mark Davis, Markus Grompe, Alex Marson, E. John Wherry, Hao Zhu

A different approach for a different outcome.

Explore Our Science

NewLimit is committed to increasing the number of healthy years in each human life. We'll do that by advancing the most imperative areas of the science of aging and formulating practical medicines along the way.

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