Oxford Biodyn Regulatory News (OBD)

08 November 2019

Oxford BioDynamics Plc

("OBD" or the "Company" and, together with its subsidiaries, the "Group")

Oxford BioDynamics' EpiSwitch™ Featured in Presentations on Development and Validation of Blood-Based Predictive Biomarkers in Immune Checkpoint Inhibitor Programs

·; Data from study of EpiSwitch™ Suggest Independent Predictive Power of the 3D Genome Architecture Technology Platform in Immuno-Oncology

·; Posters presented at Society for Immunotherapy of Cancer (SITC) Annual Meeting co-authored by scientists from Merck KGaA, Darmstadt, Germany, Pfizer and Mayo Clinic

Oxford BioDynamics Plc (AIM: OBD), a biotechnology company focused on the discovery and development of epigenetic biomarkers for the pharmaceutical and biotechnology industry, today announced that data yielded by application of its 3D genome architecture technology platform, EpiSwitch™, will be presented at The Society for Immunotherapy of Cancer's 34th Annual Meeting. The poster presentations indicate that the biomarkers identified by EpiSwitch, using blood samples from patients treated with immune checkpoint inhibitors, provide information that can be used to understand various disease states and has the potential to shed light on the impact of treatment to improve clinical outcomes. The posters were co-authored with collaborating scientists from EMD Serono (the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the US and Canada), Pfizer, Oxford Biodynamics and the Mayo Clinic.

In the studies, researchers profiled patients with non-small cell lung cancer (NSCLC) or melanoma treated with avelumab (an anti-PD-L1 antibody), pembrolizumab (an anti-PD-1 antibody), or pembrolizumab in combination with a non-platinum chemotherapeutic agent, and generated models to differentiate responders from non-responders using machine learning methods. All computational analyses for identification of classification models was performed by Oxford Biodynamics.

The findings are being presented as part of the following two posters:

·; (P142) "Development and Validation of Baseline Predictive Biomarkers for Response to Avelumab in second-line (2L) non-small cell lung cancer (NSCLC)"*

·; (P143) "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"

Findings from both posters indicate that the chromosome conformation signatures identified retrospectively by EpiSwitch represent strong systemic cellular network deregulations associated with differences in clinical phenotypes and outcomes. Full results are being submitted for publication.

"These findings show that immuno-oncology biomarker development with EpiSwitch yielded robust exclusion of non-responders across indications and combinations, provided asset-specific classifiers with high PPV, and may enable IO drug development programs to advance with smaller patient cohorts," said Alexandre Akoulitchev, Director and Chief Scientific Officer of Oxford Biodynamics. "While this initial single-arm study design doesn't permit differentiation between the prognostic and predictive values of the EpiSwitch classifiers, the rationale for a blinded, comparator arm test is compelling. The ability to stratify patients based on their genomic architecture to reduce the risk, cost and time to market for therapeutic development programmes would be a game changer in immune-oncology."

The EpiSwitch research was funded by Merck KGaA, Darmstadt, Germany as part of an alliance with Pfizer. 

*Avelumab is not approved for the treatment of non-small cell lung cancer or melanoma.

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About EpiSwitch

EpiSwitch is a novel epigenetic-based technology platform that supports precision medicine initiatives including: prediction of response to therapy, patient prognosis, disease diagnosis & subtyping and residual disease monitoring. The result of robust, validated, award-winning technology and methodology, EpiSwitch stratifies patients based on their genomic architecture to reduce the risk, cost and time to market for therapeutic development programmes, provide significant insights into disease mechanisms and help personalize therapeutics to ensure better outcomes. To learn more about EpiSwitch, please visit https://www.oxfordbiodynamics.com/technology/.

About Oxford BioDynamics Plc

Oxford BioDynamics Plc (AIM: OBD) ("Oxford BioDynamics") is a biotechnology company focused on the discovery and development of epigenetic biomarkers for use within the pharmaceutical and biotechnology industry.

The Company's award-winning, proprietary technology platform, EpiSwitch™, aims to accelerate the drug discovery and development process, improve the success rate of therapeutic product development and take advantage of the increasing importance of personalised medicine.

In particular, EpiSwitch™ can reduce time to market, failure rates and the costs at every stage of drug discovery. Additionally, the technology provides significant insights into disease mechanisms for drug discovery and product re‐positioning programmes and enables the personalisation of therapeutics for patients in the context of challenging pricing environments where improved clinical outcomes are critical.

Oxford BioDynamics is headquartered in the UK, and listed on the London Stock Exchange's AIM under the ticker "OBD". For more information please visit www.oxfordbiodynamics.com.

Avelumab Approved Indications

Avelumab (BAVENCIO®) in combination with axitinib is indicated in the US and EU for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

The US Food and Drug Administration (FDA) also granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis and renal dysfunction and other severe and potentially fatal immune-mediated adverse reactions involving other organs, infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO® monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO® in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache.

Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were lymphopenia, anemia, increased aspartate aminotransferase (AST), thrombocytopenia and increased alanine aminotransferase (ALT). Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were hyponatremia, increased gamma-glutamyltransferase (GGT), lymphopenia, hyperglycemia, increased alkaline phosphatase, anemia, increased lipase, hyperkalemia and increased AST.

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased, blood creatinine increased, blood cholesterol increased, increased ALT, increased AST, blood sodium decreased, lipase increased, blood potassium increased, platelet count decreased, blood bilirubin increased and hemoglobin decreased.

For full Prescribing Information and Medication Guide for BAVENCIO®, please see www.BAVENCIO.com.