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Oxford BioDynamics Advances Epigenetic Signatures for Breast Cancer, ALS

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NEW YORK (GenomeWeb) – Oxford BioDynamics has made progress toward developing and validating epigenetic signatures for breast cancer and amyotrophic lateral sclerosis.

In recent weeks, the British company has announced the completion of two studies showcasing the ability of its EpiSwitch platform to diagnose and stage breast cancer and ALS patients. Also this month, the US Patent and Trademark Office granted Oxford BioDynamics a patent covering its EpiSwitch platform, which should support the firm as it looks to build its business in the US.  

"We now have worldwide intellectual property coverage for our technology," said CEO Christian Hoyer Millar. "We are currently expanding our footprint in the States and that's a priority for us."

Scientists from the University of Oxford established Oxford BioDynamics in 2007, and the company currently employs about 30. Last year, it began to trade on AIM, the London Stock Exchange's international market for smaller companies. The firm currently has a market capitalization of £150 million ($198 million).

After years of honing its EpiSwitch platform for developing epigenetic signatures, the company has experienced a flurry of activity, taking part in roughly two dozen partnerships with drug development and biotechnology firms. Its pharma and biotech partners use the blood-based EpiSwitch platform to stratify cohorts, identify drug responders, and cut development costs and timelines, while rewarding the company with milestone payments.

Yet Oxford BioDynamics has its own diagnostics programs, according to Chief Scientific Officer Alexander Akoulitchev, who co-led the development of EpiSwitch at Oxford, with projects underway across a dozen indications, including breast cancer and neurodegenerative diseases.

"We are delivering a very robust screening platform as well as discovery, evaluation, validation, and monitoring of signatures important in patient stratification," said Akoulitchev. "Most of our signatures are used for stratification in various drug development and biotech projects, but we have several applications we are developing with a direct diagnostic approach."

The EpiSwitch platform is based around a class of epigenetic biomarkers known as chromosome conformation signatures (CCS), which the firm claims provide a framework for analyzing changes in genomic regulation before the results of epigenetic changes manifest themselves. The company employs microarrays, next-generation sequencing, and real-time PCR to characterize these markers.

In the design and discovery phases of a project it relies on array and NGS platforms to detect high-order chromosomal structures, which are moved to the PCR platform for validation in sample cohorts. According to Akoulitchev, Agilent Technologies manufactures the arrays that Oxford BioDynamics uses in its projects. The company's set up also include's Tecan's Freedom EvoWare automated liquid handling system, and PerkinElmer's LabChip GX Touch for RNA analysis. Oxford BioDynamics pursues its research programs at its laboratory in Oxford, as well as a reference laboratory in Penang, Malaysia, which Hoyer Millar called a "major center for medical tourism," with 10 hospitals in the region hosting 3,000 beds.

At the end of September, Oxford BioDynamics announced that it had validated an epigenetic signature for staging breast cancer patients that it developed while studying a cohort of 136 patients at the Maria Skłodowska Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland. The work was based in part on earlier studies done on Asian cohorts, Akoulitchev said.

"We have done quite extensive work in Asian breast cancer patients, and we wanted to look at prevalences for different types of breast cancer in Caucasian cohorts," said Akoulitchev. "We wanted to see how the biomarkers established with some fine tuning of the classifiers could be translated."

According to the firm, the EpiSwitch platform successfully stratified patients representing all four stages of breast cancer against healthy controls. The company referred to this as a "first milestone" for investigating the use of the signature in a European cohort, and said it planned to extend its analysis across the same cohort to develop follow-on epigenetic signatures for subtypes of breast cancer, prognosis, and predisposition risks.

"We would like to extend and look particularly at small cohorts representing familial cases of breast cancer with genetic predisposition," said Akoulitchev. "We want to see how, epigenetically we can capture ... genetic predisposition to breast cancer starting to manifest itself or remaining silent, and then stratify those cases," he said.

According to Hoyer Millar, Oxford BioDynamics plans to use the signature in its partnerships with pharma and biotech clients.

Besides oncology, the company sees EpiSwitch as a "very advantageous stratification tool that can tackle many phenotypes," such as neurodegenerative diseases, Akoulitchev said. Earlier this month, the company discussed one such project at the annual Northeast ALS Meeting  in Clearwater, Florida.

ALS, also called Lou Gehrig's Disease, is a neurodegenerative disease for which there is a current lack of prognostic tests. Oxford BioDynamics believes its platform might be used to improve care. In 2014, Innovate UK, the country's innovation agency, awarded £850,000 to a consortium including Oxford BioDynamics to, in part, develop and validate EpiSwitch blood-based test for ALS that could be used to diagnose ALS patients, provide insight into disease stratification, and determine if therapies are having a positive effect.

In a poster presented at the recent conference, Oxford BioDynamics outlined its collaboration with the clinical research group at the Oxford Motor Neuron Disorders Clinic at the University of Oxford, which used the EpiSwitch platform to study a cohort of 100 patients. The cohort was tested using two signatures — one diagnostic for ALS, the other a disease progression prognostic — and then revisited at three-month and six-month intervals for a follow up. Data from clinical assessments and 100 spousal controls was also collected.

According to the poster, a nine-gene diagnostic signature was employed to test the patients, while an eight-gene prognostic signature was used to stratify them into fast and slow progression subtypes. The researchers noted that four of the biomarkers in the prognostic signature were related to major histocompatibility complex 2 and acquired immunity, while three others are embedded in pathways associated with the innate immune system, "hinting at the involvement of neuroinflammmatory mechanisms in the pathogenesis of the disease."

The company concluded that the use of epigenetic biomarkers could improve time to diagnosis for ALS patients and help identify subtypes of disease progression, warranting further studies.

Oxford BioDynamics also announced this month that the USPTO granted it Patent No. 9,777,327, "DNA conformation (loop structures) in normal and abnormal gene expression," which covers the firm's methods for the discovering and monitoring regulatory conditional chromosome conformation signatures. Hoyer Millar said securing IP in the US was a "significant milestone" for the firm, which has similar patents granted in Europe, China, Japan, Australia, Hong Kong, New Zealand, Singapore, and South Africa.

Hoyer Millar noted that the company is trying to grow its business in the US, where it currently has three people based. Oxford BioDynamics is also seeking out new collaborations, and next year plans to release an online epigenetic portal where "researchers can see the value of our EpiSwitch platform in terms of deconvoluting data." He also said that the results of collaborations with partners that are relevant to the pharma and biotech industries would also be published in coming months, demonstrating the applicability of the EpiSwitch platform.

"The field is developing in tandem with us, and literally one can find something related to chromosome architecture in high-profile publications every week," said Hoyer Millar. "We are trying to help and empower these approaches with other modalities," he said. "These are still very early days."

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