With $130 Million in Financing, NewLimit Uses Machine Learning to Guide Epigenetic Programming and Has Achieved Preliminary Results in Extending Human Healthy Lifespan
The prime of life will never come back, and the day will never come back. "Time" has always been like a trickle of water, never stopping and difficult to reverse. The aging caused by the passage of time has troubled generations. In ancient times, great emperors such as Qin Shihuang, Emperor Wu of Han, and Emperor Taizong of Tang sought immortality, and there was also the legendary King Arthur's Holy Grail, which could restore youth. When the pointer of the times fell on the 21st century, as people's research on life sciences continued to deepen, although few people mentioned "immortality", research on anti-aging has never stopped. Especially as the global aging problem intensifies, more and more research teams and companies have begun to apply fast-iterating AI technology to the research of related issues.
Not long ago,Biotech company NewLimit announced the completion of a $130 million Series B financing.This has once again ignited the market's attention to AI + anti-aging research. Since its establishment in 2021, this startup company focusing on the anti-aging track has received a $40 million Series A financing and the above-mentioned Series B financing in addition to the $105 million initial funding.The valuation has reached 810 million US dollars.The core reason why NewLimit continues to win the favor of investors is not only that it has entered this cutting-edge field with great development prospects, but also the "AI + Laboratory" closed loop it has built on the R&D side.The company has developed three prototype drugs based on this "Lab-in-a-loop" model.Capable of reprogramming liver cells.
Focus on epigenetic reprogramming and build an AI + experimental closed loop
It is true that there is a subtle difference between anti-aging and longevity in a broad sense, that is, health status. As we all know, most of the human body functions deteriorate with age, so some people reject "longevity" because they often associate it with the pain and despair brought about by the indefinite extension of a state of old age, physical weakness, or even illness.The core goal of anti-aging is to extend human healthspan and delay or even reverse physiological decline.
At present, the main directions of anti-aging research include delaying cellular senescence, epigenetic reprogramming, immune system remodeling, etc. Among them, epigenetics refers to affecting gene expression by regulating chemical modifications of DNA (such as methylation, histone modification, etc.) without changing the DNA sequence itself. "Epigenetic reprogramming" refers to resetting these modifications through human intervention, restoring cells to a younger, more plastic state.
Epigenetic reprogramming can be said to fundamentally reverse the "biological age" of cells, not only alleviating aging symptoms, but also improving cell structure and function. Specifically, the targets of epigenetic regulation are mainly regulatory proteins and modifying enzymes.This means that it is extremely easy to combine with advanced tools such as GenAI, mRNA technology, and drug screening platforms.For example, predicting the optimal combination of transcription factors through AI modeling, short-term controllable expression based on mRNA delivery technology, etc. At present, it has entered the preclinical or early clinical verification stage in many directions such as anti-aging, tissue regeneration, neurodegenerative diseases, and metabolic diseases.
For this reason, NewLimit plans to focus on epigenetic reprogramming methods and mechanisms in the early stages. Brian Armstrong, one of the company's founders and co-founder and CEO of cryptocurrency trading platform Coinbase, once introduced in the company's open letter announcing its establishment,NewLimit will begin by deeply studying the epigenetic drivers of aging and developing products that can regenerate tissue for the treatment of specific patient populations.“We will initially use human primary cells and reference species to build machine learning models to identify which chromatin features change with age, which of these changes may be causal for the aging process, and ultimately develop treatments that could slow, stop, or even reverse this process.”
On the technical level, the design of traditional reprogramming interventions usually relies on heuristic methods to select a set of transcription factors and then test whether these factors can induce "markers" associated with the target cell phenotype. This approach has been used to develop a variety of reprogramming technologies that can convert between different cell types. However, this method is limited by simplified readouts, small experimental scale, and hypothesis generation relying on experience.
NewLimit has built a technology platform that combines single-cell omics, pooled perturbation screening, and machine learning to overcome these challenges.
* Using single-cell omics to evaluate reprogramming effects
Subtle changes in epigenetic state (such as the difference between healthy and diseased cells of the same type) are usually not accurately captured by a few marker genes. Measuring the effects of reprogramming based on single-cell omics can use rich cell state data to evaluate intervention results and conduct far more experiments than traditional methods.
* Pooled reprogramming screening
Pooled screening technology enables hundreds to thousands of experiments to be performed simultaneously in the same cell population, including various combinations of reprogramming factors, without the need for cumbersome molecular biology workflows. Based on this, NewLimit can significantly expand the scope of exploration of reprogramming hypotheses.
* Machine learning guides epigenetic programming
Even with the support of single-cell omics and pooled screening technologies, the number of potential reprogramming strategies is still far beyond the scope of what can be tested in the laboratory. Machine learning methods can predict the results of new experiments, intelligently search the experimental space in a data-driven manner, and use past experimental data to guide the design of subsequent experiments, thereby achieving rigorous and efficient closed-loop optimization.
Jacob Kimmel, co-founder and president of the company, said:"We draw on the Design-Build-Test-Learn engineering framework, focusing on increasing the number of manually testable reprogramming hypotheses and the amount of information obtained from each experiment, and integrating historical experimental information so that each experiment can better guide the design of future experiments."He said, "The AI model allows us to run all experiments in a simulated environment and then only perform follow-up verification on a small number of the most promising ones." Data points from actual experiments are then used to retrain the AI model, a process the company calls Lab-in-a-loop.
Silicon Valley's super cross-border combination, covering technology, capital and scientific research
It is not difficult to find that the approach taken by NewLimit is different from that of traditional pharmaceutical companies. It does not look for molecules from the target, but is more like "cell engineering", that is, the AI model simulates and predicts thousands of gene regulatory pathways to design gene expression patterns that may have anti-aging effects. Subsequently, the experimental team used CRISPR, epigenetic regulators or small molecule drugs to induce these expression combinations and observe whether the performance of aging cells is improved.
This R&D model that spans AI and life sciences undoubtedly poses a great challenge to the composition of team results. Initially, NewLimit was composed of experts in the fields of cell biology, genomics, computational biology, and machine learning. Its founding team spanned the vertical fields of cutting-edge technology, venture capital, and epigenetic reprogramming.
in,Brian Armstrong is well known to the public as the co-founder of Coinbase, the first publicly traded cryptocurrency exchange in the United States.He received a double bachelor's degree in computer science and economics from Rice University in Texas, and went on to obtain a master's degree in computer science. After graduation, he worked as a developer at IBM and a software engineer at Airbnb.
In 2012, he joined Y Combinator's startup accelerator program and founded Coinbase with his $150,000 investment. In 2021, Coinbase went public on the Nasdaq exchange. In the same year, New Limit was established, and Armstrong invested the wealth gained from the company's IPO in this technology field that he believed was not yet fully developed.
* Brian Armstrong's personal homepage:https://www.brianarmstrong.org/home
Blake Byers, another veteran of the company,He combines rich experience as a scientist, investor and entrepreneur.In terms of academic research, he holds a Ph.D. and a master's degree in bioengineering from Stanford University, and a double bachelor's degree in biomedical engineering and economics from Duke University. His research covers the fields of atherosclerosis, induced pluripotent stem cells, neurodegenerative diseases, and optogenetic controlled human neural transplantation. In particular, his research during his doctoral studies focused on synthetic biology and bioinformatics.We have accumulated rich basic scientific research experience in gene regulation, protein engineering and other fields.
It was precisely these front-line scientific research experiences that helped him join Google Ventures (GV) as one of the youngest partners and lead the investment decisions of many well-known biotechnology startups. Blake Byers is particularly interested in companies that use AI to empower biological research.Such as gene editing company Editas Medicine, and Flatiron Health, a tumor data platform company later acquired by Roche. He also incubated PACT Pharma, a company focusing on neoantigen T cell therapy, and served as chairman of the board of directors of the company. During his 10 years as a partner at GV, he invested in 38 companies, of which: 10 companies have been successfully listed and 17 are still in operation.
*The above data is as of summer 2024.
*Blake Byers personal homepage:https://www.blakebyers.com/
In 2021, Byers left GV and founded his own investment company, Byers Capital.Focuses on early-stage investments in technology and biotechnology.His investment portfolio covers superintelligence, mathematical reasoning, code agents, large-scale drug development, brain-computer interfaces, and extending human healthy life expectancy, including some well-known companies such as SpaceX and Neuralink.
Unlike the first two, Jacob Kimmel focuses on his research career. He received his Ph.D. from the University of California, San Francisco (UCSF) under the supervision of Wallace Marshall and Andrew Brack.In his doctoral thesis, he began to study methods for inferring cell state changes from time series imaging data, and achieved the measurement of muscle stem cell activation rate.This provided a first glimpse into age-related changes in muscle stem cells.
Then,He joined Calico Life Sciences LLC, a company founded by Google in 2013 to study the mechanisms of human aging.Jacob Kimmel served as a principal investigator and computational fellow during his tenure, and worked as a data scientist in Calico's computing team. His laboratory focuses on repurposing developmental programs to restore young gene expression in aging cells. At the same time, his research also covers the differential manifestation of aging in different mammalian cell types, how stem cells age, and the development of time series imaging and single-cell RNA sequencing methods.
Final Thoughts
NewLimit mentioned in its open letter that aging, once thought to be irreversible, has now been proven to be plastic with the development of the emerging science of epigenetic reprogramming, which has brought unprecedented therapeutic opportunities to biotechnology, with a potential 100 times greater than any previous biopharmaceutical product. It can be said that the company's research on the historical problem of anti-aging has begun to emerge, but as Armstrong said, the company's research is still several years away from human trials.
Currently, it has been conducting trials on liver cells and cells related to immune function, with the goal of expanding the scope of the trials. Fortunately, the company's interim results have "attracted" more research and development funds to support this grand vision.
References:
3.https://blog.newlimit.com/p/developing-reprogramming-therapies