Some of the best ideas are the simple ones. But having a simple idea is no guarantee that translating it into a working commercial product is going to be easy. Ask Helen Maddock.
Helen is founder and Chief Scientific Officer of InoCardia and Professor of Cardiovascular Physiology & Pharmacology at Coventry University. It has taken years of painstaking work, some ten years altogether, but they are finally where they ought to be – able to offer the pharmaceutical industry a reliable tool for evaluating whether drugs in development are safe from the point of view of the cardiovascular system.
That is no mean feat. Being able to predict early in the drug development cycle whether a compound could potentially cause heart problems matters a great deal to pharmaceutical companies who are spending literally billions of dollars researching powerful new drugs to combat cancers and other complex diseases. It would also save countless lives.
A keen rugby fan and cyclist, Maddock is somewhat unique in being able to straddle both industry and academia. She began her career working in the pharmaceutical industry for the UK business which was to become part of pharma giant AstraZeneca before making the switch. It is that combination of research rigour and commercial nous which led to her realisation that there might be a solution to a serious industry problem.
Cardiovascular toxicity is the second biggest cause of potential drugs having to be dropped while in the research and development stage. “There are more than 20 different drug classes known to have cardiovascular liabilities,” says Maddock, “some of those can go on to cause heart failure.” So working out early in the process whether a drug could cause heart problems – and whether they would be severe enough to cancel out the potential benefits of a drug was a major headache for the industry.
Conventional lab testing using human heart cells wasn’t delivering the results and otherl testing methods werenot much better.
She began to realise that there was a very good reason why they might be so unreliable. Inspired by a colleague at Coventry University undertaking research into the functioning of skeletal muscles, it struck her that the problem with conventional toxicity testing on the heart was that it was static and didn’t mimic the dynamic function of the heart. The in vitro process failed to take into account the obvious fact that the heart is a muscle which expands and contracts in a regular rhythm, and what you are trying to ascertain is whether the compound is impeding that process. What was missing was a way of testing how the muscle reacted to a drug while in motion. Drawing on her colleagues work with other muscles she was able to devise a way to simulate what cardiologists call the pressure volume loop: “we’ve mimicked the biomechanics of the heart contracting and relaxing.”
Working closely with collaborators from leading pharma firms such as AstraZeneca and UCB, Maddock was able to translate her insight into something which genuinely met the needs of commercial drug developers. One of them, a former colleague from AstraZeneca, immediately saw the potential. One of their drugs had failed Phase One of FDA trials because of cardiovascular toxicity. Had the technique Maddock’s team was developing been available five years earlier they would have stopped work on the drug at a much earlier stage and saved themselves a fortune which could have gone to fund work on other compounds with a much better chance of viability.
Over 70 compounds have now passed through their testing regime (known as an assay in the pharmaceutical industry) with impressive results.
“Our assay is extremely sensitive and predictive compared with what is already out there. It is the gold standard,” she says.
None of this, she says, would have happened without Innovate UK, which has, through successive grants, provided the funding needed to prove the concept and turn it into something commercially viable. Part of the funding went towards developing an AI based engine which could model the process and analyse the data. “Turning an academic assay into a fully commercial assay, which is robust and industrialized and meets industry needs has been quite a journey.
“Each grant has driven us to improve, to scale and drive forward.”
InoCardia’s AI in-silico platform is faster (40x) and approximately 10% of the cost compared to traditional methods. By harnessing machine learning and high standards of representative scientific data a new toolset is now available for innovative Pharmaceutical companies to disrupt conventional drug discovery development methods.
Maddock’s view is that if had they relied solely on academic funding, they would have given up long ago. Reflecting her background in the pharmaceutical industry, the work was commercially driven from the start rather purely about the science. “When you are dealing with academic funding, the currency is mainly the number of research papers you can publish off the back of it, not commercial applications.”
In 2021, with InoCardia on the threshold of being able to commercialise its product, Maddock was selected by Innovate UK as one of their Women in Innovation. As well as a boost to morale at a critical point, it entitled Maddock to participate in the Women in Innovation programme which offered bootcamps to hone her business and entrepreneurial skills as well as providing valuable networking opportunities with industry partners and potential investors.
What Maddock found so useful in her dealings with Innovate UK was the associated support she received each step of the way. Of particular value, says Maddock was Innovate UK’s Knowledge Transfer Network which enabled her to learn from others as well as share her own insights. She herself is critical of the tendency among academics to hoard knowledge. More knowledge transfer would boost innovation and have positive knock-on effects for the economy, she says. Unfortunately, that is not the way conventional academic incentives tend to work.
Confident that they now have a genuinely world-beating product to offer the industry, InoCardia is currently on the hunt for investment to fund the infrastructure needed to truly scale. “There has been a lot of blood, sweat and tears to get here. Had it been an academic project, we would have given up years ago”. The fact that they did not, she attributes to Innovate UK and the fact that “there was a real need for the technology.”
“No other commercial company is capable of doing what we’ve done,” Maddock insists, adding: “The company would not be where we are today without Innovate UK. Their support has been absolutely fundamental.”
