The power of crowdsourced R&D

Drug development is still dogged by attrition, duplication and waste. Chas Bountra, chief scientist & head of the Structural Genomics Consortium at the University of Oxford, thinks the answer lies in opening up discoveries to everyone and collaborating at all levels.

Bountra is a veteran of life sciences, having worked at Oxford University in the mid-1980s before joining Glaxo and staying on as the company became GlaxoSmithKline. He returned to Oxford in 2008, where his work at the Structural Genomics Consortium (SGC) has been focused on coming up with new targets for drug discovery.

“We’re not interested in the targets that everybody else is working on,” he says. “We’re trying to open up completely new areas of biology. That’s where the big breakthroughs are going to come.”

Bountra says that one of the major challenges in drug development at the moment is the fact that many academics, biotech companies and pharma companies “are all working on the same few things”.

“This is because they all read the same literature – they go to the same conferences, they talk to the same opinion leaders. Then they go back to their labs and end up working on the same things in parallel, in secret.

“When 20 companies are working on the same thing, if one of them fails the other 19 are going to fail as well. That is an incredible waste of money, of people’s careers and, most importantly, a waste of patients. The way we’re doing drug discovery today, we’re actually exposing patients to molecules that other people already know are destined for failure.”

In order to combat this secrecy, competition and duplication, Bountra wants to see all areas of the industry coming together.

“Drug development is risky. We can’t do it on our own. We want people to come together and generate novel tools for novel targets, then make them freely available to the world.”

Novel targets

To this end, a large part of the SGC’s work focuses on generating novel, high-quality tools for tackling rare and genetic diseases.

“We all have around 20,000 genes,” says Bountra. “Currently, we can only target about 1,000 of them with drugs. There are probably around 13,000 genes that we don’t know anything about, and therefore there aren’t any tools for them – no protein, no assay, no structure, no inhibitor, no antibody.

“If we generate tools for these genes, we can help the community to identify new drug targets for all the diseases that are out there.”

Bountra adds that this work is particularly important in rare diseases.

“Most pharma companies are not going to work on most rare diseases. It’s up to people like us, working in academia – working with philanthropists, charities and governments – to try and open up this area. Otherwise, in 10 years there will still be 350 million rare disease patients and 95% of them still won’t have a treatment.”

The SGC even works on protein targets that others think are intractable.

“Most companies are not going to work on a target they think is undruggable. I think the primary job of academia is to try and do things that other people believe are impossible. That’s what innovation is.”

He uses the example of the family of proteins called bromodomains.

“Many people told us that this family was intractable. But we worked together with the Diamond Light Source synchrotron at Harwell, who are using crystallography to identify low-affinity binders, and we were able to generate the first inhibitor for a bromodomain. Since then, we’ve generated probably another 20 inhibitors for different bromodomains, and now we’re moving on to different families. That is exactly the kind of thing we in academia should be doing.”

Crowdsourcing science

Perhaps the most interesting aspect of the SGC’s work, though, is that they don’t take out any intellectual property on the tools that they develop.

“We make them freely available to anybody in academia, pharma, etc.,” Bountra explains. “That way we can tap into global academia, who can take those tools, test them in whatever disease model they want, and then publish.”

He adds that everything the SGC does is released to the world immediately.

“We don’t sit on it and keep it quiet for 12 months while we’re writing up our manuscript, because in those 12 months there might be people elsewhere doing something that we’ve already done, and that’s just a waste of time and resources.”

Bountra describes the model as essentially “crowdsourcing science”.

“That transparency creates a lot of trust, which is great for collaboration, great for science, and great for drug discovery. We’re now collaborating with more than 300 academic labs all over the world, with 10 large pharmaceutical companies, and with seven different patient organisations.”

This collaborative approach allows organisations to pool resources together to share risks and conduct larger, more expensive trials, Bountra says.

“Often, when pharma companies try and reproduce academic publications, they are unable to do it. The reason is that many academics are under so much pressure to publish that they try and get their study out there as quickly as they can, and as a result might not have big enough N numbers.

“By working together, we can have larger trials and can afford to make sure any data we generate is absolutely rock solid and easily reproducible. This way, we can help drive innovation.”

Bountra thinks that this attitude is becoming more common across the industry.

“Many companies are realising that they can’t do this on their own. Drug development is too difficult, too expensive, and takes too long, so it’s incredibly risky. No matter how big they are, they’re going to have to work with academic groups, charities, governments, etc.”

Bountra also hopes such collaborations can address attrition issues that are driving up drug costs and creating massive affordability issues.

“I don’t know any other industry where you can work on a target for seven years and still have up to a 95% chance of failure when you first take it into the clinic. I don’t know any other industry that could survive that, and affordability is becoming a massive issue.”

He adds: “Some people have said to me, ‘Chas, you’re just trying to help the industry.’ I say to them, ‘What’s wrong with that?’

“I’m trying to help the industry discover new medicines for patients. I’m not helping the industry to help them make more money. I’m doing it because I recognise that we can’t do many of these clinical trials in academia. We have to work with big pharma.

“Whenever you work with somebody you’ve got to give something to get something. We have to work together. If we don’t work together then we won’t get any new medicines for some of these horrendous conditions.”

Chas Bountra

Chas is pro-vice chancellor for innovation at the University of Oxford, professor of translational medicine in the Nuffield Department of Clinical Medicine, CSO for the SGC, academic lead for the Dementia Drug Discovery Institute and professorial fellow at Keble College, Oxford. Prior to coming back to Oxford in 2008, Chas was vice president and head of biology at GlaxoSmithKline. In 2012 he was voted one of the top innovators in the industry, in 2014 received the Rita and John Cornforth Award from the Royal Society of Chemistry, in 2017 and 2018 was voted Master of the Bench from the Medicine Maker Power List, and in 2018 was awarded the Order of the British Empire in the New Year’s Honours List.

George

George Underwood is a senior member of the pharmaphorum editorial team, having previously worked at PharmaTimes and prior to this at Pharmafocus. He is a trained journalist, with a degree from Bournemouth University and current specialisms that include R&D, digital and M&A.

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