End-2-End Translation from Data-Driven Hypotheses to Preclinical Validation
Indication Expansion Workflow
INDICATION EXPANSION IS ONE OF THE MOST SUCCESSFUL LIFECYCLE MANAGEMENT STRATEGIES BUT TRADITIONAL APPROACHES ARE VERY COSTLY AND TAKE A LONG TIME. NETWORK-BASED INDICATION EXPANSION PRIORITIZES INDICATIONS BY SAFETY & EFFICACY AS WELL AS UNMET MEDICAL NEED AT A FRACTION OF THE TIME AND COSTS OF TRADITIONAL APPROACHES. THIS ENABLES MONOTHERAPEUTICS AND MULTITHERAPEUTICS TO BE FILED FOR ORPHAN DISEASES, EXTENSION OF CURRENT PATENT TIMELINES AND MAXIMIZES RETURN OF INVESTMENT.
Life Cycle Management
BioXplor was tasked with identifying novel indications for an IL17A inhibitor, Cosentyx, for Novartis. The objective was to identify and prioritize novel indications for further clinical studies in inflammatory diseases, and to incorporate potential signals to explain adverse events. BioXplor analysed the pathogenic pathway of the disease and compared the treatment strategy with competing drug-target pathways in inflammation pathways. BioXplor's team utilized it's biomedical and drug disocvery knowledebase consisting of 250 databases and billions of structured biomedical literature sentences using natural language processing and machine learning models, to prioritize several novel indications based on safety and efficacy.
Case Study - Indication Expansion for Cosentyx
Indication Expansion, Adverse Events, Mechanisms
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BioXplor set out to elucidate a novel pathogenic pathway for a rare disease called Lipedema, which is an inflammatory fat disorder, with very little published research. The team elucidated the pathway based on an initial gene found to be strongly associated with a rare genetic disease, and built out the pathway using indirect literature evidence supporting the genetic and clinical features that are known. The team proposed a novel therapeutic hypothesis with evidence to support drug repositioning. The identified target was then found to be highly-expressed in Lipedema patient tissues, and a leading Lipedema expert, an endocrinologist at University of Arizona, confirmed that the proposed candidate for drug repositioning was effective and safe for treatment of Lipedema patients, and was already being prescribed, even though this finding is not to be found in the biomedical literature. This is one of many examples of novel insights discovered using BioXplor's for novel pathway elucidation and drug target identification.
Case Study - Lipedema Drug Repositioning
Novel Pathway Elucidation, Drug Targets, Mechanisms of Action
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As part of an ongoing collaboration with a leading cancer research team studying a rare and particularly aggressive form of Leukemia (ETP-ALL), BioXplor set out to analyse the ZEB2 pathway to identify an optimal therapeutic strategy using systematic drug repositioning. BioXplor's proprietary ABCD feature engineering model was employed for pathway analysis to further elucidate obvious and non-obvious knowledge on the topic. The team identified some novel druggable targets for ETP-ALL, and then used literature analysis to identify supporting evidence for the novel hypotheses from in vitro and in Vivo studies. A novel drug was identified with supporting evidence to be effective in treating ETP-ALL. This drug will be screened in vitro and in vivo to validate the mechanisms, safety and efficacy profile using patient tissue and transgenic models. The validation work is ongoing.
Case Study - Leukemia Drug Repositioning
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Pathway Analysis, Mechanisms of Action, Efficacy
The integrated network pharmacology platform has particular advantages for complex immuno/inflammation-based diseases. It works by generating obvious and non-obvious knowledge on the immuno/inflammation interactome, diseases and drug targets from structured and unstructured data. This is achieved using proprietary natural language processing, machine learning and feature engineering algorithms which integrate data from public and private sources. BioXplor leverages it's network pharmacology platform to prioritize optimal multi-therapeutic/multi-target strategies, novel indications, and clinical responders and non-responders, based on safety and efficacy evidence. The platform has been optimized and successfully validated with top tier clients including Novartis, Bayer and Merck, for Biomarker ID and Clinical Responder ID, Drug Combinations, Indication Expansion, Drug Repositioning, Target and Multi-Target ID, Pathway Analysis and DNA/RNA Sequencing Data Interpretation.
BioXplor delivers high-quality and rapid-turnaround contract research services from data-driven discovery to wet lab validation for clinical responder ID, indication expansion and drug combinations. The detailed recommendation report can be purely data-driven using BioXplor's proprietary knowledge discovery platform only, or integrate client data for additional analysis. Via our trusted external partner network, the workflow can be extended to generate and integrate new data from single-cell sequencing analysis, cell-based assays and preclinical animal model studies.
For co-development partnerships we form joint ventures together with select academic and biotech teams to combine domain, target and/or platform synergies to rapidly develop programs from hypotheses to validation at a fraction of the time and cost of traditional approaches. BioXplor is actively engaged in programs in inflammation, autoimmunity and immuno-oncology.
Contract Research & Drug Discovery Partnerships