Getting to an in vivo active compound

Its been an incredibly fast paced year and hence my posting frequency has suffered. Perhaps its time to get back to writing . Today we had a press release with SRI so that triggered me to fill in the back story.

Rewind back to 2014 and the Ebola outbreak was in full flow – see this post from just over 3 years ago. Well that lead ultimately to another paper a year later in 2015 describing machine learning models used to identify in vitro active compounds against the virus. This preliminary work then enabled us to obtain an R21  in 2016. Now we describe the testing in vivo of one of three candidate compounds, namely tilorone.  This particular part of the study was led by Peter Madrid at SRI. He took a gamble back in 2015 on buying the 3 compounds I proposed with a Bayesian model based on his data from 2013. Robert Davey at Texas Biomedical Research Institute did the initial in vitro testing which got the ball rolling as well.

There is still a fair way to go, perhaps we look in Guinea Pig or non human primate next, but these are expensive studies. However, tilorone is a compound that is widely used in Russia as an antiviral and actually available over the counter. The drugs being evaluated so far for Ebola are novel molecules that have had to undergo extensive preclinical testing for toxicity etc.

Sure it would be great if come the next outbreak of Ebola we could have a molecule that could be used to prevent infection as well as treat those infected. The current work is a step closer. We have two back up compounds if this fails and have started to collect a whole array of additional compounds as well with promising in vitro activity that have never been reported.

As a small company focused on rare and neglected diseases this project ticks all the boxes. The molecule was discovered with machine learning, the work involves close collaborations with different groups and the molecule is repurposed. While it may not be a hugely profitable area I think we may have proven more than one point. We have shown how the different patchwork of funding in the US can enable screens, which can lead to models and then optimization to get to an in vivo active compound We have taken advantage of different NIH funding and testing resources and so are very grateful for this support. While Ebola is no longer a hot topic we have also shown that realistically it may take a good amount of time to find novel compounds for antiviral outbreaks. And this is a virus we have known about since the 1970’s and there is still no approved efficacious treatment! Here is hoping we have taken a step further to addressing this.

So bottom line – watch this space we may have more to come. Our pipeline of projects includes molecules for TB, Chagas and HIV and that is just the NIH funded projects.

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