Mitra Bio Submits IPO Prospectus: Pioneering Non-Invasive Skin Aging Diagnostics with Epigenetic Biomarkers

As skin ages, DNA methylation patterns undergo characteristic changes. By analyzing the DNA methylation patterns of specific genes associated with skin health, it is possible to determine the skin’s biological age and overall health status, as well as predict the efficacy of skincare interventions.

Before conducting skin aging assessment, the issue of sampling must first be addressed.

As the largest organ of the human body and the one in most direct contact with the external environment, the skin exhibits epigenetic modifications that differ significantly from those of other internal tissues. These modifications are closely associated with specific anatomical sites and pathological conditions, meaning that different skin cells or tissues may possess distinct epigenetic profiles. Consequently, unlike common sampling methods such as buccal swabs or fingerstick blood tests, skin sampling requires biopsy to obtain DNA, RNA, or protein samples from specific skin tissues for epigenetic analysis. However, this invasive approach causes pain and discomfort, limits the scalability of sample collection, and hinders repeated sampling, thereby posing challenges to the discovery of biomarkers related to skin aging and the development of epigenetic clocks.

To address the challenges of skin sampling and subsequent biological age estimation, Mitra Bio has entered the field.

Mitra Bio, founded in 2020 and headquartered in London, UK, is a startup focused on skin genomics, dedicated to leveraging genomics to mitigate skin aging and enable precision dermatological treatments. The company has developed a non-invasive skin diagnostic platform that facilitates non-invasive sampling and conducts in-depth genomic and epigenetic analyses, allowing for the assessment of skin aging levels and intervention efficacy. By integrating clinical trials, non-invasive skin sampling, next-generation sequencing technologies, and advanced data science, Mitra Bio is poised to directly guide the development and design of novel skincare compounds.

Shakiba Kaveh, Co-founder and CEO of the company, completed her undergraduate studies in Materials Science and earned a Master’s degree in Engineering at Imperial College London, before obtaining a Ph.D. in Materials Science from the University of Cambridge.

In 2015, Shakiba served as a Research Scientist at L'Oréal, where he was specifically responsible for developing the My Skin Track UV product for the L'Oréal Beauty Tech incubator. During this period, he accumulated substantial industry expertise in skincare and embarked on his entrepreneurial journey.

In 2019, Shakiba joined Entrepreneur First as a fellow, participating in its accelerator program. In 2020, she founded Mitra Bio and, one year later, joined the Oxford University Innovation Centre as an entrepreneur-in-residence, where she was selected to participate in the OXFO Elevate accelerator.

In the course of his ongoing interdisciplinary and cross-sector learning and exploration, Shakiba happened to meet like-minded partner Dr. Cristiana Banila.

Dr. Cristiana Banila currently serves as the Chief Operating Officer of Mitra Bio. She graduated from St John’s College in 2013 with a major in Biochemistry, earned a Master’s degree in Tumor Virology from Princeton University, and obtained a Ph.D. in Molecular Diagnostic Development from Queen Mary University of London. She specializes in developing self-sampling molecular detection methods for early cancer discovery, which are currently undergoing trials by the UK National Health Service (NHS).

Subsequently, Cristiana transitioned into the business sector. After meeting Shakiba, they discovered a shared interest in exploring the potential of epigenetics for early cancer detection and aging prediction, which led them to jointly establish a company for commercialization efforts. Thus, Mitra Bio was founded. The company combines Shakiba’s experience in the skincare industry with Cristiana’s expertise in diagnostic development, positioning itself as “a provider of high-efficacy anti-aging skincare products and services.”

Notably, Dr. Cristiana Banila, Chief Operating Officer, was named to the 2023 Forbes 30 Under 30 list. This recognition honors her contributions to developing non-invasive diagnostic technologies for early cervical cancer screening within the National Health Service (NHS), as well as her work in creating non-invasive skin tests at Mitra Bio.

Currently, sampling methods for measuring the degree of skin aging are predominantly invasive. Biopsy is the primary method currently used for large-scale collection of skin epigenetic data; however, this approach causes significant discomfort to patients, limiting population coverage and the feasibility of repeated sampling, thereby hindering large-scale data acquisition for biomarker identification and disease prediction.

Moreover, although biopsies are performed by professionals, the isolated samples often consist of dermal and epidermal mixtures with undefined proportions. The epidermis is highly homogeneous, composed of approximately 95% keratinocytes, whereas the dermis is more heterogeneous.

Among the various layers of the skin, the epidermis interacts most extensively with the environment; therefore, it holds significant promise for investigating the relationship between intrinsic and extrinsic factors influencing DNA methylation levels. Leveraging the characteristics of skin biology, Mitra Bio has developed a non-invasive skin sampling method known as tape stripping. By collecting the outermost layer of the human epidermis through tape stripping, this approach is expected to yield more homogeneous samples and enable successful whole-genome methylation analysis. Previously, tape stripping was predominantly used in dermatology and had rarely been applied to epigenetic data collection.

Mitra Bio’s tape-stripping method enables the easy collection of biological materials without the need for professional medical personnel, offering a simple, painless, and non-damaging approach to the skin. This technique captures global and local DNA methylation profiles from a large number of participants, facilitating the assessment of skin aging, environmental exposure, and the effects of targeted interventions across different body sites.

From March to May 2021, Mitra Bio conducted a clinical study in collaboration with the Centre for Infectious Disease Epidemiology and Research at University College London and the Centre for Gene Therapy and Regenerative Medicine at King’s College London to assess the feasibility of non-invasive data collection. This was the first study to demonstrate the feasibility of combining tape stripping with whole-genome sequencing as a non-invasive approach to investigate DNA methylation changes in healthy skin. The results revealed that the global DNA methylation profiles of tape-stripped samples were highly consistent with those of traditional invasive biopsy samples. The experiment also validated that skin samples collected via tape stripping exhibited good reproducibility and consistent global methylation profiles, successfully capturing changes in skin DNA methylation patterns associated with environmental exposures and intrinsic aging processes, across cohorts spanning diverse ages, ethnicities, and skin types.

Furthermore, the experiment demonstrated that samples collected from the superficial layers of the skin may be sufficient to provide representative DNA methylation information from deeper tissue layers, a finding supported by the concordant results between tape stripping and biopsy methods. To date, many epidermal components, including RNA, proteins, and lipids, have been shown to be biomarkers extractable via tape stripping. Mitra Bio aims to identify markers and predictors for various dermatological pathologies, environmental exposures, and aging processes using large-scale datasets collected through tape stripping.

Mitra Bio employs advanced next-generation sequencing technology to analyze epigenetic changes in the skin. Its proprietary aging clock quantifies biological skin aging by leveraging clinical indicators such as wrinkles and pigmentation, longevity biomarkers including ELOVL2, and lifestyle factors like sun exposure, smoking, and diet. To date, the company has sequenced thousands of skin samples. Additionally, Mitra Bio can develop predictive biomarkers to identify optimal responders to specific formulations, thereby enabling highly personalized skin treatments.

Mitra Bio’s DNA methylation biomarkers are dynamic and tissue-specific, enabling the differentiation between clinically active and inactive components, prediction of individual responses to various compounds, and assessment of dosage requirements for such compounds. Its epigenetic profiling analysis not only facilitates patient classification and diagnosis but also supports skin cancer detection, monitoring of treatment response, recurrence detection, and disease progression prediction.

Mitra Bio and Avon jointly conducted a 28-day clinical trial to evaluate the efficacy of a topical cream enriched with Protinol, utilizing Mitra Bio’s tape-stripping method for pre- and post-treatment measurements.

According to Mitra Bio, this study represents a significant milestone, marking the first in vivo epigenetic analysis of facial skin before and after the use of specific ingredients. Mitra Bio analyzed changes in DNA methylation before and after treatment and found that key CpG sites affected by the treatment were associated with biomarkers identified in its earlier studies. This demonstrates the reliability and accuracy of using its biomarkers to assess the degree of skin aging.

Furthermore, Mitra Bio conducted an extensive analysis of the genes exhibiting the most significant changes in DNA methylation biomarkers following the application of topical formulations. Methylation alterations were observed in several key genes, including CARD9/11 (associated with immune response and inflammation), COL26A1 (related to structural support), ZFHX3 (involved in skin development and function), OCA3 (critical for predicting skin function and pigmentation), and IRF2BPPL (playing a role in the regulation of immune responses). These findings reveal specific genetic factors influenced by topical formulations, providing valuable insights into their potential impact on skin health and function.

On February 8, 2021, Mitra Bio received investment from Illumina, Inc. (NASDAQ: ILMN). As a global corporate incubation engine, Illumina focuses on collaborating with entrepreneurs to build groundbreaking genomics startups. After joining the portfolio of the Illumina Accelerator’s Cambridge branch, Mitra Bio secured seed funding, access to Illumina sequencing systems and reagents, as well as commercial guidance, genomics expertise, and fully operational laboratory space. These facilities are located adjacent to Illumina’s campuses in Cambridge, UK, or the San Francisco Bay Area, facilitating Mitra Bio’s engagement with cutting-edge academic and technological innovations.

On June 1, 2022, Mitra Bio announced that it had secured £530,000 in project funding from Innovate UK to collaborate with Guy’s and St Thomas’ Hospital on the development of a molecular screening tool for melanoma. As the most severe form of skin cancer, melanoma has seen its incidence rate surpass that of any other top-ten cancer in recent years. Early detection is crucial for reversing disease progression, reducing unnecessary referrals, and conserving medical resources. This research aims to develop epigenetic and molecular biomarkers capable of distinguishing melanoma from benign nevi using non-invasive sampling kits, and to evaluate the Mitra Bio platform’s ability to identify cancer at early stages.

To date, Mitra Bio has gained recognition and support from several investment institutions and universities, including investments from Entrepreneur First, the Illumina Accelerator, and the Oxford University Foundry. Currently, the company is still in the early clinical stages. Whether Mitra Bio will emerge as a dark horse in the field of skin anti-aging remains to be seen.