Sapere Bio Files IPO Prospectus to Commercialize p16INK4a-Based Biomarker Platform for Detecting 'Invisible Aging' in Young Individuals

Over the past century, human life expectancy has increased by 30 years.

However, this has been accompanied by a sharp rise in age-related diseases and an urgent need to understand, prevent, and treat them. Although age-related diseases are diverse, growing evidence from in-depth research indicates that they share common biological underpinnings. Among these, cellular senescence is a key factor linking subcellular changes—such as epigenetic alterations, DNA damage, and mitochondrial dysfunction—to the decline in health caused by multiple diseases.

How, specifically, can the extent of cellular senescence be analyzed and quantified? What are the effective criteria for quantifying the degree of individual aging? Addressing these questions requires accurate detection of biomarkers that reflect the body’s aging status.

Sapere Bio is a company dedicated to the detection of aging biomarkers. Headquartered in Chapel Hill, North Carolina, USA, it focuses on measuring hallmarks of aging and predicting their impact on human aging and chronic diseases. The company employs proprietary sample collection methods, precise and reproducible measurement techniques for aging and immune biomarkers, and multi-analyte algorithms to measure and monitor aging trajectories and clinical risks.

The company’s founder, Norman Edward “Ned” Sharpless, is the former Director of the National Cancer Institute (NCI). Prior to this role, Dr. Sharpless served as Professor of Medicine and Genetics, Director of Molecular Therapeutics, and Wellcome Distinguished Professor of Cancer Research at the UNC Lineberger Comprehensive Cancer Center, University of North Carolina.

As a renowned medical researcher, Sharpless has published or co-authored more than 170 original articles, reviews, and book chapters in the PubMed.gov database, and has served as an editor for Aging Cell and the Journal of Clinical Investigation. He holds 12 patents that have been granted or are pending. In 2010, Sharpless received the Glenn Award for Research in Biological Mechanisms of Aging, and in 2012, he was named a “Health Care Hero” by Triangle Business Journal. He is an elected member of the American Society for Clinical Investigation (ASCI), a member of the Association of American Physicians, and an appointed member of the National Advisory Council on Aging at the National Institute on Aging.

During his student years, Sharpless earned his medical degree with honors from the University of North Carolina School of Medicine, where he began his enduring journey in the detection of aging biomarkers.

At the University of North Carolina at Chapel Hill, Sharpless operates a basic science laboratory that uses genetically engineered mice to study cancer and aging, and he is the co-founder and co-director of the UNC Lineberger Mouse Phase I Unit. His research focuses on investigating how normal cells age and undergo malignant transformation.

In 2009, Sharpless’s laboratory discovered that the expression of p16INK4a in human peripheral blood T lymphocytes serves as an easily measurable molecular biomarker of human aging, and developed a clinically applicable assay for personalized assessment of patients’ aging risk. This approach garnered attention from BBC News and other international news outlets due to its potential to predict human aging.

This finding is prominently highlighted in the paper “p16INK4a Expression in Peripheral Blood T Cells Is a Biomarker of Human Aging,” published by Sharpless et al. in the same year. The study found thatp16INK4a expression increases exponentially with the donor’s chronological age. p16INK4a expression in PBTLs is a robust biomarker of human molecular age, reflecting the donor’s physiological age and aging-related behaviors (e.g., smoking, physical inactivity).. Moreover, this detection method is simple to perform and cost-effective, requiring only a small volume of whole blood for testing, with a short turnaround time.

Measuring telomere length in unseparated peripheral blood is also considered a biomarker of molecular aging in humans, but scholars such as Sharpless have pointed out that p16INK4a testing has three major advantages:

First, without considering the biological basis of each method,p16INK4a expression is more dynamic, thus more reliably reflecting changes associated with aging; second, although telomere length can be measured using various methods of differing complexity, butqThe relative simplicity, low cost, and reproducibility of RT-PCR are advantages of the PBTL p16INK4a method.. Third, compared with telomere length,Log-transformed p16INK4a expression changes significantly with aging in young adults, indicating that this form of molecular "aging" is already evident before human "aging."^[1]

Therefore, p16INK4a can be used to predict the risk of donor-related adverse outcomes associated with aging, evaluate the efficacy of anti-aging therapies, and detect the impact of human germline genetics on the molecular rate of aging. Building on previous research, Sharpless collaborated with other scholars to develop a quantitative model of the age-dependent expression of the p16INK4a tumor suppressor, and has published multiple papers elucidating the role of p16INK4a in shutting down stem cells that replenish various tissues in the body.

In 2011, Sharpless and his team utilized a conditional p16INK4a gene knockout mouse model to discover that the cell cycle inhibitor P16INK4A protein exerts lineage-specific tumor-suppressive or pro-senescence effects within the immune system. This study provided the first genetic evidence for the pleiotropy of lineage-specific immunosenescence, thereby establishing a genetic basis for the heterogeneity observed in human aging and cancer susceptibility.

In 2016, Sharpless, together with Dr. Judith Campisi and her colleagues at the Buck Institute for Research on Aging, demonstrated how chemotherapy induces cellular senescence. This pro-inflammatory stress response contributes to the side effects of chemotherapy as well as cancer recurrence and metastasis, while the elimination of senescent cells in mice can prevent these adverse effects. He also conducted a meta-analysis of genome-wide association studies on aging and disease, revealing that the major histocompatibility complex and the p16INK4a/ARF locus are the most common disease-associated loci in humans.

In 2019, due to his appointment as Director of the National Cancer Institute, Sharpless ceased his involvement with Sapere Bio, and Natalia Mitin, a former Research Assistant Professor at the University of North Carolina, assumed the roles of Chief Executive Officer and President.

The body sends predictive signals long before aging sets in.

Molecular changes associated with aging begin as early as adulthood, with invisible damage accumulating in the body long before physical dysfunction, chronic diseases, and frailty become apparent. Biological damage that accelerates aging may occur at an early stage, even during childhood. In adulthood, cellular senescence and immunosenescence diminish the body’s resistance to biological stressors and its capacity for healing.

However, biological aging is rarely detectable before adulthood, making it impossible to implement effective early interventions against age-related changes. How can this dilemma be resolved? By revisiting the relentless pursuit of aging biomarkers by Sharpless, founder of Sapere Bio, we may gain some insights.

Sharpless has particularly noted that p16INK4a expression changes significantly with aging in young adults, a characteristic that may well resolve this challenge. Currently, the assay for this biomarker has been commercialized by Sapere Bio (formerly HealthSpan Dx), a company founded by Sharpless and his team.

This story dates back to 2013. Dr. Sharpless and Dr. Natalia Mitin founded Sapere Bio (formerly HealthSpan Diagnostics) based on Dr. Sharpless’s research at the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill.

Dr. Sharpless’s laboratory has been a pioneer in uncovering the mechanisms of aging and predicting the role of senescent cells in human aging and chronic diseases. Key work from his lab has demonstrated the dual role of p16INK4a in tumor suppression and aging.Building on these studies and the accumulation of knowledge, Sapere Bio has developed a series of products based on immunosenescence biomarkers, including p16INK4a, dedicated to transforming how the extent of aging is measured and applied in clinical decision-making.

Sapere Bio possesses clinically compliant analytical precision, quality assurance, proprietary blood preservation technologies, and the clinical context required for patient care. Meanwhile, its close collaboration with leading physician-scientists has laid the scientific foundation for understanding how to measure and modify senescent cell burden to improve clinical outcomes.

Sapere Bio leverages its proprietary sample collection technology to maintain the integrity of immune components during transport, ensuring that immune cells and factors remain undamaged after blood sample collection and facilitating shipment to laboratories. The company develops immunoassays and aging biomarker detection methods in accordance with clinical standards, conducts rigorous analytical testing, and fully utilizes multi-analyte algorithms for the detection of aging biomarkers. In prospective clinical studies, Sapere Bio has developed biostatistical and machine learning models that employ advanced mathematical and computational techniques to analyze data from multiple immune analytes, thereby predicting the extent and rate of aging as well as associated clinical risks.

Tailored to diverse clinical scenarios and needs—such as health management, disease prevention, and drug development—and grounded in practical feasibility, Sapere Bio generates corresponding risk reports that provide relevant information and recommendations to help users improve aging-related conditions and clinical outcomes.

According to the U.S. National Institute on Aging (NIA), the NIA’s Baltimore Longitudinal Study of Aging (BLSA) is the most comprehensive and longest-running longitudinal study of human aging in the world. In June 2021, Sapere Bio announced on its official website that it had become the sole provider of cellular senescence measurements for the Baltimore Longitudinal Study of Aging.

Furthermore, Sapere Bio participated as a collaborating institution in the trial “Patterns of Natural Aging and the Role of Aging-Related Biomarkers,” sponsored by the University of North Carolina at Chapel Hill. The primary objective of this study is to determine whether p16 mRNA expression measured in T cells reflects the overall aging burden of the organism; the secondary objective is to determine whether aging dynamics are influenced by age-related chronic diseases; and the exploratory objective is to assess the ability of computational models of aging to predict clinical and functional status.

In this registry study, investigators will assess the impact of aging, comorbidities, functional performance, and quality of life on the aging process, and determine the potential of these factors in aiding the development of a novel stochastic model. This model will be specifically formulated within the context of T-cell turnover and aging, thereby providing a mechanistic framework that describes p16INK4a accumulation at the cellular level and characterizes parameters associated with relevant physiological processes. The development of this new model will enable researchers to conduct quantitative, predictive, and mechanistic investigations into the role of aging at both the systemic and cellular levels.

In 2017, Sapere Bio participated as a collaborating institution in the “Feasibility of Isolating p16INK4a Expression” trial sponsored by St. Jude Children’s Research Hospital. The trial demonstrated that p16INK4a expression can predict physiological age rather than chronological age. These findings may have implications for the care of cancer survivors and treatment decision-making for cancer patients.

On September 15, 2021, the U.S. National Institute on Aging (NIA) awarded Sapere Bio a $2 million SBIR (Small Business Innovation Research) grant to develop a clinical product that leverages cellular senescence biomarkers to predict the risk of chemotherapy-induced peripheral neuropathy.

“Physiological aging is invisible,” CEO Natalia Mitin stated in an interview. “It is not about wrinkles and gray hair, but rather changes occurring within your tissues that clinicians may be unaware of.” Sapere Bio is changing this landscape. As the company develops new tools to predict biological age, physicians will soon be able to formulate treatment plans based on patients’ lifespan and quality of life.

References:
1. Liu, Y.; Sanoff, H. K.; Cho, H.; Burd, C. E.; Torrice, C.; Ibrahim, J.G.; Sharpless, N. E. (2009). "Expression of p16INK4a in peripheral blood T-cells is a biomarker of human aging". Aging Cell. 8 (4): 439–448.