In the field of drug discovery and development, Prof Dr Chas Bountra believes that there are certain areas the pharmaceutical industry excels in and others that academicians have the advantage in.
“Industry is brilliant at things that require scale and infrastructure.
“So it’s great at doing high throughput screening with two million compounds; lead optimisation; identifying clinical molecules; doing toxicology, regulatory and the really big clinical studies – the phase 2b and phase 3; and then, marketing the drug,” he said.
“But there are many things that are easier to do in an academic setting.”
This includes accessing clinicians, patients, patient materials and patient databases; collaborating with other academics; focusing on one target or pathway their entire career; doing risky things – “and innovation is risky”; and working with engineers, computational scientists, Big Data experts and statisticians, who are predicted to have a huge transformational effect on medicine in the decades to come.
“In academia, it is also easier to leverage funds from patient groups, philanthropists and governments.
“It is also easier to use large government-funded infrastructure, like, for example, in the United Kingdom, the National Health Service,” said the University of Oxford Nuffield Department of Clinical Medicine professor of translational medicine.
Prof Bountra is also the chief scientist of the Structural Genomics Consortium (SGC) at Oxford.
This public-private partnership aims to combine the strengths of industry and academia in order to increase the probability of discovering new drugs.
“We’ve tried to do basically four things,” he shared.
“Firstly, we’ve tried to pool resources to share risk.”
This means that they are funded by various sources, including nine major pharmaceutical companies who have put in more than US$5mil (RM20mil) each; the Wellcome Trust, which has contributed over £60mil (RM326mil); and five patient organisations.
This way, the financial risk is spread out over the various funders.
“The second thing we do is, we only work on completely novel genes or novel proteins that we think could be drug targets in the future.
“I’m not interested in working on a target where there’s already 10,000 publications or already 100 labs working on it,” he said.
He added that they deliberately focus on targets that are considered undruggable. “We work on those because I believe our job in academia is to drive innovation.”
Prof Bountra explained: “When we work on these novel genes and proteins, what we do is we purify the human protein; we work out the three-dimensional X-ray structure of the protein; we generate biophysical and biochemical assays for that protein; and we generate small molecule inhibitors, antibodies and Crispr reagents.”
He noted that all these reagents and tools are of high quality because they are able to leverage the infrastructure and resources of their nine pharmaceutical partners.
“The third thing we do, and this is probably what makes us most unique, is that all of these reagents, which are essentially starting points for drug discovery, we give them away freely to anyone in academia, biotech and pharma.
“Because I believe that’s the best thing I can do to accelerate science, and therefore, accelerate drug discovery,” he said, adding that they are now working with more than 300 academic labs around the world.
“So, what we are doing is that we are crowdsourcing science on these novel proteins.”
The fourth thing they do is to share all their data and reagents immediately with whoever wants it.
“We don’t sit on it for 12 months while we are writing the manuscript (for publication), because we don’t want other people to waste their time and resources if we’ve already done it.
“If we’ve already sorted out the structure of that protein or generated a small molecule inhibitor, what’s the point of 20 other labs across the world trying to repeat it?
“So, by releasing everything immediately, we’re trying to reduce duplication and wastage (of resources),” he explained.
Small molecule, big impact
To illustrate the impact this policy has had, Prof Bountra shared the story of the first small molecule inhibitor they developed.
GSC started work on the bromodomain protein family, which was deemed intractable, in 2009.
Working with GlaxoSmithKline and Dr Jay Bradner, then with Harvard’s Dana-Farber Cancer Institute, they managed to develop an inhibitor for the BRD4 protein, a member of the bromodomain family, a year later; however, they did not know what it could treat.
Based on two 2010 publications on the protein, Dr Bradner obtained cell lines from patients with a very rare cancer known as NUT midline carcinoma and unleashed the inhibitor on them.
The inhibitor stopped the cancer cells from multiplying and induced apoptosis (cell death), which also occurred in the mouse models.
“When we got that data initially, Jay wanted to take this molecule we had generated straight into patients, because he knew that anyone who is diagnosed with NUT midline carcinoma, within three to six months, they are dead.
“There is nothing out there that treats this cancer,” said Prof Bountra.
As per their policy, the inhibitor was made freely available to any academic or pharmaceutical company that was interested.
Today, seven years later, more than 2,000 academic labs across the world have used the inhibitor, resulting in over 500 publications in diseases as wide-ranging as cancers, sepsis, fibrosis, cardiac hypertrophy, and even male contraception, according to Prof Bountra.
He added that 10 pharmaceutical companies have also developed their own molecules based off of this inhibitor, and are testing them in over 20 clinical trials.
“So, we’ve also accelerated translational studies,” he said, adding that now, GSC has generated more than 60 inhibitors that are available to any researcher who wants to use them.
Prof Bountra was in town on Nov 21-22, 2017, for the 2nd Cambridge-Oxford-Sunway Biomedical Symposium held at Sunway University in Selangor, where he spoke on How We Are Transforming the Discovery of New Medicines.