One of the key hurdles in today’s drug development paradigm is the difficulty of mapping the underlying mechanics of disease: to identify root causes and define the levers that affect development.
This critical step typically takes more than ten years. But with our innovative human-based approach, we have completed the pre-discovery phase in flu in under one year’s time – reducing the duration by 90%.
In analysing the samples acquired during our studies, we have the unique opportunity not only to observe “disease in motion” but also to monitor and check the wiring in the body’s circuitry, or “pathomics” – a term we coined to describe this approach.
Severe Flu Mapping
In late 2014, hVIVO began its journey to fully exploit the power of the hVIVO platform to illuminate the underlying biology of disease in order to discover better treatments and diagnostics in areas of stubborn and persistent unmet medical need. We determined that our initial foray into the mining our ‘disease in motion’ samples would be in flu, given that hVIVO has more than 25 years of experience researching flu and there are significant gaps in existing treatments and vaccines which we believe can be overcome by better understanding the human body’s response to flu infection. In particular, we noted that there were no treatments for severe flu and indeed, no universal clinical definition for it either. This translates into a staggering economic reality: in the US alone, there are 200,000 cases of severe flu annually, 20% of which develop acute respiratory distress syndrome (ARDS) and cause $13.8 billion in hospital costs alone. These figures can be expected to increase exponentially in pandemic outbreaks. As such, hVIVO turned the power of the platform on severe flu, in order to illuminate the correct drug targets we should be focusing on to produce a positive therapeutic effect.
Within short order, our Discovery team produced a map of the pathophysiology associated with ‘normal’ flu (i.e. what should happen in flu when humans get sick and then recover on their own without intervention). We coined the term ‘pathomics’ to describe this process of describing the underlying biological pathways associated with a given disease state. Once we knew the pathways associated with recovery, we collected ‘field’ samples (in 2015) from people with severe flu or who were hospitalised with flu. We then compared the difference to zero on the pathways most associated with severe flu. From this informed vantage point, we commenced a rigorous qualification process involving in vitro and ex vivo laboratory studies that read out in March 2016. We consulted world leading clinicians, scientists and opinion leaders in influenza along the journey to ensure the clinical plausibility, and utility, of our candidate pathways and our qualification process. Through our industrialised pathomics process, we arrived at a qualified pathway component for our severe drug target in under 18 months.
Pathomics is a combination of“pathways,”or signalling networks, and “omics,” the collective technologies used to explore the various types of molecules that make up the cells of an organism. Pathomics involves data mining and analysis, disease-in-motion sample acquisition, product validation and disease research. We use these techniques to elucidate and define the most influential signalling human pathways that underpin the host response. We are in essence, providing a biological global positioning system (GPS) to define the key components that are directly involved in human disease, including drug targets and biomarkers.
In early 2015 we completed the first ever pathomics map of the human response to flu infection and then built out the critical pathways for severe flu. Initially, we charted biomarkers in those patients who contracted flu and returned to health after a few days. From there, we studied samples from patients with severe flu to complete the seminal task of identifying the biological “tipping point” when flu becomes severe. Knowing the tipping point is crucial, as it enables us to rationally select drug targets and essential predictive biomarkers.
We have completed our qualification process to determine drug targets, pathway biomarkers and disease activity biomarkers – a pivotal moment for hVIVO.
We are now positioned to advance our discoveries into candidate status in, with products that could include drugs to treat flu, biomarker tests to guide clinical product development, and predictive tests to identify flu susceptibility and patients at risk of severe flu.
Flu Data Mining
We continue with a committed focus on flu to explore and identify molecular signals and algorithms to target products covering the entire flu disease lifecycle, and we are working to answer questions such as :-
“Can we predict who is going to get sick or experience an exacerbation?”
“Can we identify potential novel biomarkers of severe influenza?”
“Can we predict who is going to become infected and who will not?”
“Can this biological insight help us to develop clinical endpoints for, for example, a universal flu vaccine?”
If you are interested to find out more about these and other hVIVO developments and innovations, and how there may be a collaborative or partnering opportunity with your organisation, then please use the “Contact Us” form on this website.