Results published of biomarker discovery program

Oxford BioDynamics publishes results of biomarker discovery program
being used for development of its EpiSwitch® Covid-19 Severity Test

·    Publication describes use of EpiSwitch® 3D genomics platform for genome-wide biomarker discovery
to enable early identification of Covid-19 high-risk group

·    Results show strong biological links to well-established and new regulatory pathways specific to severe outcomes in Covid-19 patients

·    Data provides important physiological insights to guide clinical management of Covid-19

·    Top 50 immune-related markers show good separation of mild and severe outcomes with an
accuracy of 92%

·    Provides strong clinical and statistical foundation for the validation stage of the developed test,
to be published separately in medRxiv

Oxford, UK - 17 March 2021 - Oxford BioDynamics Plc (AIM: OBD, the Company), a biotechnology company developing precision medicine tests for personalized healthcare based on the EpiSwitch® 3D genomics platform, has published results supporting development of its prognostic test to identify high-risk individuals who, if exposed to SARS-CoV-2 virus, are likely to experience the severest Covid-19 complications, requiring intensive care unit (ICU) support.

The paper describes the biomarker discovery stage of OBD's EpiSwitch® disease severity program for Covid-19, supported by an international group of experts in the UK and US, including West Hertfordshire NHS Trust, the Universities of Oxford and East Anglia, and Oregon Health & Science University, USA.

Access the paper on bioRxiv here.

Rationale for developing a Covid-19 Severity Test (CST)

As of today, over 2.6 million people have died from complications of Covid-19 disease, from over 120 million infected worldwide [1].  Covid-19 infection can induce highly variable clinical symptoms, ranging from asymptomatic to severe and critical reactions in need of hospitalization and ICU support. While progress has been made in developing rapid Covid-19 testing (for infection) and rolling out vaccinations, robust and early forecasting of high-risk clinical outcomes has remained a difficult challenge.

Technology used for developing a Covid-19 Severity Test (CST)

The EpiSwitch® biomarker technology used in this paper is a well-established 3D genomics platform. It has been used by leading pharma and clinical research teams for patient stratification in prognostic, predictive and early diagnostic applications in immuno-oncology, autoimmune and neurodegenerative indications [2-10]. The paper published today effectively applies this 3D genomic biomarker modality, to successfully screen, discover and evaluate clinically relevant prognostic biomarkers.  These biomarkers are associated with an individual's risk of severe Covid-19 disease in advance of infection.

Process used for developing a Covid-19 Severity Test (CST)

OBD used the EpiSwitch® biomarker discovery array to analyse blood from a global cohort of Covid-19 patients, obtained at the time of diagnosis. Over 1 million data points across the whole genome were generated for each patient and used to identify the most informative EpiSwitch® markers that were associated with different severities of clinical disease outcomes.

Benefits of developing a Covid-19 Severity Test (CST)

In depth analysis of the EpiSwitch® markers in individual patients has improved understanding of the disease, confirming earlier independent observations and pointing to important new Covid-19-related pathways. These pathways link together dysregulations in innate and adaptive immunity, olfactory (smell) receptors, ACE2, hypoxia, calcium signalling and blood clotting.

Next steps and applications for OBD's Covid-19 Severity Test (CST)

OBD is validating the 3D genomic markers discovered in this work as a deployable qPCR test. This will be launched soon as the EpiSwitch® Covid-19 Severity Test (CST). The EpiSwitch® CST will help assess an individual's level of risk and help to predict those adults who would most likely require critical care should they become infected with the virus. It has the potential to be applied by physicians for risk evaluation, including of individuals free of infection or early in the infection cycle. It also represents a valuable tool to support informed clinical decisions, lifestyle choices and workplace strategies.

Dr Jon Burrows, CEO of Oxford BioDynamics, said:
"EpiSwitch® is a liquid biopsy technology that has consistently shown the strong and robust link between 3D genomic readouts and clinical outcomes. Our plans to launch the EpiSwitch® Covid-19 Severity Test (CST) based on this groundbreaking biomarker discovery work by the end of Q1 2021, are on track."

Prof. Jane Mellor, Department of Biochemistry, University of Oxford, commented: "I am encouraged that the 3D genomic biomarkers shown by this data to define Covid-19 severity of response are also tightly associated with distinct known clinical outcomes - they make sense. This is another illustration of how fundamental genome architecture regulation is. OBD's EpiSwitch® technology has great potential, both as a Covid-19 prognostic test and to continue improving our understanding of this deadly disease."

Prof Dmitry Pshezhetskiy, Norwich Medical School, University of East Anglia, said: "A test capable of predicting patients who will respond severely to Covid-19 ahead of infection will be highly valuable irrespective of the vaccine rollout. It will help to inform risk mitigation decisions and optimize acute and long-term treatment, and, because it is based on the host response, it will also be relevant for any new variants of Covid-19."

Dr Bill Messer, MD, School of Medicine, Oregon Health & Science University, commented: "I was impressed by the capacity of the 3D biomarkers to discriminate disease severity in Covid-19 patients. The EpiSwitch platform has prognostic potential for Covid-19 disease. I would imagine that similar machine learning approaches could also be engaged for other established diseases of high public health importance where we currently lack good prognostic predictors."

-Ends-

FOR MORE INFORMATION:

NOTES TO EDITORS:

About Oxford BioDynamics Plc

Oxford BioDynamics Plc (AIM: OBD) is a global biotechnology company, advancing personalized healthcare by developing and commercializing precision medicine tests for life-changing diseases.

The Company has developed a proprietary 3D genomic biomarker platform, EpiSwitch®, which can build molecular diagnostic classifiers for prediction of response to therapy, patient prognosis, disease diagnosis and subtyping, and residual disease monitoring in a wide range of indications.

Oxford BioDynamics has participated in more than 40 partnerships with big pharma and leading institutions including Pfizer, EMD Serono, Genentech, Roche, Biogen, Mayo Clinic, Massachusetts General Hospital and Mitsubishi Tanabe Pharma.

The Company has created a valuable technology portfolio, including biomarker arrays, molecular diagnostic tests, bioinformatic tools for 3D genomics and an expertly curated 3D genome knowledgebase comprising hundreds of millions of data points from over 10,000 samples in more than 30 human diseases.

OBD is headquartered in Oxford, UK and is listed on AIM of the London Stock Exchange. It also has a commercial team in the US and a reference laboratory in Penang, Malaysia.

For more information, please visit the Company's website, www.oxfordbiodynamics.com, or follow on Twitter or LinkedIn.
 

About EpiSwitch®

The 3D configuration of the genome plays a crucial role in gene regulation. By mapping this architecture and identifying abnormal configurations, EpiSwitch® can be used to diagnose patients or determine how individuals might respond to a disease or treatment.

Built on over 10 years of research, EpiSwitch® is Oxford Biodynamics' award-winning, proprietary platform that enables screening, evaluation, validation and monitoring of 3D genomic biomarkers. The technology is fully developed, based on testing of over 10,000 samples in 30 disease areas, and reduced to practice.

In addition to stratifying patients with respect to anticipated clinical outcome, EpiSwitch® data offer insights into systems biology and the physiological manifestation of disease that are beyond the scope of other molecular modalities. The technology has performed well in academic medical research settings and has been validated through its integration in biomarker discovery and clinical development with big pharma.

References

1. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases. 2020.

2. Jakub JW, Grotz TE, et al. A pilot study of chromosomal aberrations and epigenetic changes in peripheral blood samples to identify patients with melanoma. Melanoma Res. 2015.

3. Carini C, Hunter E, et al. Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis. J Transl Med. 2018.

4. Salter M, Corfield E, et al. Initial Identification of a Blood-Based Chromosome Conformation Signature for Aiding in the Diagnosis of Amyotrophic Lateral Sclerosis. EBioMedicine. 2018.

5. Yan H, Hunter E, et al. Epigenetic chromatin conformation changes in peripheral blood can detect thyroid cancer. Surg (United States). 2019.

6. Hunter E, McCord R, et al. Comparative molecular cell-of-origin classification of diffuse large B-cell lymphoma based on liquid and tissue biopsies. Transl Med Commun. 2020;5.

7. Salter M, Powell R, et al. Genomic architecture differences at the HTT locus underlie symptomatic and pre-symptomatic cases of Huntington's disease. Fac 1000 Res. 2018;7.

8. Shah P, Hunter E, et al. Development and validation of baseline predictive biomarkers for response to immuno-checkpoint treatments in the context of multi-line and multi-therapy cohorts using EpiSwitch epigenetic profiling. J Immunother Cancer. 2019;7.

9. Cao F, Fang Y, et al. Super-enhancers and broad h3k4me3 domains form complex gene regulatory circuits involving chromatin interactions. Sci Rep. 2017.

10. Alshaker H, Mills R, et al. Chromatin conformation changes in peripheral blood can detect prostate cancer and stratify disease risk groups. J Transl Med. 2021.