Senescence, or cellular aging, is like a silent epidemic spreading through our bodies as we grow older. Triggered by unrepaired DNA damage, these aged cells accumulate over time, evading our immune system, and cause nearby healthy cells to prematurely age, gradually driving tissue decline.
(02) How DNA Damage and Senescence Drives Disease and Aging
Cells throughout the body accumulate DNA damage over time. This can be driven by normal cellular replication or environmental damage. Our cells have the ability to repair DNA damage, however, this repair process is error-prone with repeated damage leading to DNA that can no longer be repaired, termed DNA scars. When too much DNA damage destabilises a cell's normal function, they normally destroy themselves by apoptosis or prevent their own replication by becoming senescent. This protects the body from accumulating cells with an unstable genome leading to further damage in the body.
As we age more cells accumulate irreparable DNA damage. Over time, more non-replicating senescent cells are present with a subset, through random DNA damage, acquiring the ability to continue replicating and make a safe environment for themselves in the body. This accumulation of senescent cells, and sub-populations of senescent cells that continue to divide, contributes to the formation of chronic disease, like cancer and fibrosis, and is a key driver in aging. Supporting our body's DNA repair and clearance mechanisms is fundamental to preventing disease onset and extending our lifespan.
Senescent cells, which have permanently exited the cell cycle but evade apoptosis, contribute significantly to the aging process. These cells persist in tissues and secrete a pro-inflammatory and tissue-degrading mix of cytokines, chemokines, proteases, and growth factors known collectively as the Senescence-Associated Secretory Phenotype (SASP). The SASP disrupts the extracellular matrix, alters tissue structure, and induces senescence in neighbouring cells, creating a feedback loop that exacerbates cellular dysfunction.
This pro-inflammatory environment is a key driver of chronic inflammation, also known as "inflammaging," which underlies many age-related diseases. The accumulation of stochastic DNA damage disrupts gene transcription driving the formation of senescent cells. This accelerates a decline in tissue integrity and function, contributing to the overall deterioration observed in aging.
By focusing on repairing DNA damage and targeting senescent cell populations for removal, we aim to break the cycle of chronic inflammation and cellular dysfunction. Addressing these root causes is key to fundamentally treating chronic diseases and extending healthy lifespan.
Our Approach
(04) Breaking Senescence into its Essential Components
VB/001
Understanding DNA Damage with Advanced Methods and Disease Models
At Valley Biosciences, we employ cutting-edge methods like single-cell RNA sequencing, proteomics, and advanced imaging to study DNA damage and cellular senescence at unprecedented resolution. These methods are applied to our gold standard disease models that recapitulate DNA damage driven disease and aging. This powerful combination allows us to identify new drug targets in this emerging therapeutic area.
VB/002
Exploring Senescent Cell Heterogeneity and their Role in Disease
A cornerstone of our research is exploring the continuum from DNA damage to senescence. For example, understanding the heterogeneity within senescent cell populations and their diverse role in disease. We recognise that senescent cells are not all identical, and this diversity is crucial to their varied impact on health and disease. Our studies aim to categorise different subpopulations based on their molecular profiles, secretory patterns, and functional effects on surrounding tissues. We investigate how these subpopulations contribute to conditions like fibrosis, cancer progression, and aging-related disorders.
VB/003
Identifying Targets for Intervention
By understanding DNA repair pathways and characterising senescent cell heterogeneity, we aim to repair structural DNA damage and remove pathogenic subpopulations of senescence. We believe repairing the underlying cause of cellular dysfunction and targeting particular types of senescent cells, rather than eliminating all senescent cells, could lead to more effective and safer therapies. This nuanced approach allows us to move beyond a one-size-fits-all view of senescence and develop more precise strategies for intervention.
VB/004
Developing Unique Targeted Therapies
The ultimate goal of our research is to translate our findings into targeted therapies. By leveraging our deep understanding of the specific characteristics and impacts of different senescent cell subpopulations, we aim to develop interventions that prevent the onset of senescence, selectively remove subpopulations of senescence, and treat age associated inflammation. This approach has the potential to mitigate the negative effects of cellular aging while minimising side effects. Our work is driven by the vision of creating more effective treatments for a range of age-related diseases, like fibrosis and cancer, potentially revolutionising the field of age-related medicine and slowing the aging process.
Solving
Senescence
(05) Targeting DNA Damage and Senescence
Valley Biosciences is developing groundbreaking therapies that address key areas in the continuum of cellular aging, from DNA damage to senescent cell formation, to combat age-related diseases. Our pipeline includes innovative approaches to regulate DNA repair, remove pathogenic senescent cell populations, and reduce age associated inflammation.
While our treatments are progressing through clinical development, we envision a future where they become standard preventive care, potentially extending human lifespan. This bold vision drives our diverse research pipeline.
Indications
MOA
Stage
Progress
VB197
Undisclosed
Regulation of DNA repair pathways
Preclinical
VB212
Undisclosed
Immune mediated clearance of pathogenic sub-population of senescence
Thomas Mitchell is a seasoned biotechnology executive with extensive experience in cofounding and leading innovative biotech companies across the globe, including Boston (USA), Cambridge (UK), Australia, and the Netherlands. With a robust background spanning multiple therapeutic areas, Thomas has played a pivotal role in the development of cutting-edge drug discovery platforms, steering programs from early discovery phases through to market approval, including achieving first-in-class market authorisations.
Thomas is recognised for his deep expertise in antibody, cell, and gene-based therapies. His work is driven by a commitment to enhancing biological integrity and improving the human health span, aiming to deliver transformative therapies that extend and improve quality of life. Thomas has successfully raised capital, led both corporate and scientific strategy, and continues to advance the biotechnology sector with a focus on making a global impact on human health.
Gabriel Hammond (Co-Founder & Lead Investor)
Gabriel Hammond is an accomplished international life science investor with a strong focus on translational research aimed at enhancing biological integrity and extending human lifespan. With a deep commitment to advancing scientific breakthroughs, Gabriel has co-founded several innovative financial companies, pioneering new fund structures that have set industry benchmarks.
Gabriel has also played a crucial role in establishing and growing companies across a diverse range of industries, leveraging his extensive experience as a financial and corporate strategy professional. His expertise lies in identifying and nurturing high-potential opportunities that bridge the gap between cutting-edge research and real-world applications, driving significant impact across the life sciences sector.
Advised By
Professor Samir El Andaloussi
Leader in drug delivery, cell engineering, and extracellular vesicles
Professor Ernst Wolvetang
Leader in stem cell biology and functional genomics
Professor Björn Schumacher
Director of the Institute of Genome Stability in Aging and Disease
(07) A Letter From The Founders
Dear Friends,
We have always been deeply intrigued by biological aging, not just as an inevitable part of life, but as a disease that can be understood and treated. Aging, like many other diseases, is heterogeneous—driven by various molecular mechanisms, or endotypes, each contributing to the overall process in unique ways. By breaking down aging into these components, much like solving a complex puzzle, we can identify specific targets for therapy and develop more effective treatments.
One of the most significant contributors to aging and its associated diseases is DNA damage and the formation of senescent cells—cells that have stopped dividing but refuse to die. These cells behave much like an infectious disease, adapting to evade the immune system and causing widespread damage in the body. Their role in conditions such as cancer and fibrosis is increasingly recognised, making them a critical target for next-generation therapies. Our experience in DNA repair, senescence, immunotherapy, epigenetics, and drug development has uniquely positioned us to address these challenges and advance the fight against aging at its core.
I firmly believe that targeting DNA damage, senescence, and inflammation, as the underlying mechanisms of aging will revolutionise healthcare. By focusing on prevention rather than treatment, we can reduce people's reliance on the healthcare system and help to equalise healthcare access. In the future, people will take these therapies proactively to prevent the onset of disease and aging, creating a world where health is maintained, and hospitals are no longer the first line of defense against illness. This vision drives our work at Valley Biosciences, and we are excited to share this journey with you.
Sincerely,
Thomas Mitchell Co-Founder and CEO, Valley Biosciences
