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Profile feature: Tim Hart

9 August 2009

Bioentrepreneur Tim Hart talks about how BBSRC funding opened the doors of the business world and led to a new commercial spin out company.

Tim Hart, CEO of Zyoxel Ltd.

What does your new spin-out company Zyoxel do?

Zyoxel is a bioengineering business that is developing microbioreactors that will enable cells to be grown as tissue rather than as single cell layers. The primary application is for drug testing, and what we are producing is an easy to use, low cost consumable-based system to routinely test cells in a more in vivo-like state than previously possible.

What’s unique about your system?

One, the cells are grown in a 3D matrix using a scaffold to mimic tissues. Two, each well is individually perfused, so it’s maintaining a more constant chemostat-like environment. Other people have developed perfused 3D bioreactors, but no one else has been able to develop such a simple, easy to set up consumable which combines both aspects for multi-sample testing and routine use.

How have you managed that?

It’s all to do with the nature of the material we’re using, a silicon-based polymer that forms the casing, like the actual plastic of a Petri dish. Using this class of material brings certain features which are very useful for growing cells. For example, this system can be made by simple moulding processes so you haven’t got complex microfabrication techniques or expensive manipulation and assembly. It comprises just two seal-sealing pieces, you push the parts together and it forms a very good liquid- and gas-tight seal that makes it easy to inject and remove samples. It’s transparent so enables in situ microscopy and completely gas permeable so there’s no need for an external gas supply; the gases just diffuse in and out.

You say you can reduce the cost of drug discovery by 10%. How did you arrive at that figure?

One of the problems with drug discovery is that you get lots of drugs that get so far down the process and then they prove toxic or ineffective in humans. We believe that if we could be testing drugs earlier in vitro in a more realistic state, we may be able to improve the accuracy of the process. 10% has come from a range of ball-park estimates and the figure is derived from literature on established industry market research. More accuracy and details around these statements will come as we move forward.

And you say you can reduce the amount of animal testing by 10%. How so?

The prime application is in the pharmaceutical sector, and the 10% comes from published estimated information on how many animals are used and typical failure rates. There are other applications in individual chemical testing and there is a big drive to eliminate animal testing on cosmetics where there will be a complete ban in Europe by 2013.

And do these alternative testing systems work?

There’s lots of interest in using skin models grown in vitro. One company, EpiSkin, leads the market in producing valid and accurate artificial skin models. There’s much more information on the NC3Rs website, see Related links. There is also the pharmaceutical sector. If we could capture failing drugs earlier you could eliminate a lot of unnecessary animal testing. Also, animal models have their own inherent limits. If we can produce more accurate models there will be some elements of replacement. But we will never get to the point where we can replace animal testing with techniques such as this. There will always be a place for whole organism animal toxicity testing, but hopefully the process will be more efficient, with the overall aim of reducing the total number of animals required per developed drug.

What kind of tissue do you put in your bioreactor to capture that?

Liver and bone marrow toxicity are two key areas that are currently being chased – they’re hot areas. But trying to recreate liver tissue is extremely difficult, but the focus of intense research across the world. It’s the pot of gold at the end of the rainbow but progress is being made.

How far you got?

We haven’t done any liver work yet. Most work we do is on bone marrow because there are issues in the pharmaceutical sector about late problems with bone marrow toxicity. We’ve also used breast cancer microtumours as more simple models to validate our system and are engaging with leading research groups in the area of liver tissue to set up collaborative programmes.

What progress have you made culturing stem cells?

We’ve grown a range of stem cells in this system: mouse, rat, bovine, human embryonic stem cells, and human bone marrow stem cells. The big issue is that although stem-cell science offers potentially powerful therapeutic treatments in the future there are still significant gaps in our knowledge on how these cells can be cultured and differentiated reliably – and there is a need for more appropriate testing platforms.

 

Zhanfeng Cui (left) is Zyoxel’s chief scientist.

So how does yours perform?

That would be talking about experimental data, but if you take total metabolic activity and cell numbers, in our system after exposure to certain compounds the effects we see are more like what you would expect in vivo compared to what we see in standard monolayer testing formats.

Talk us through how all this was funded

I’m not the academic founder. The science has been led by Professor Zhanfeng Cui and his colleagues at Oxford who have received significant funding from BBSRC. My commercial experience developed out of the Young Entrepreneurs Scheme (YES), of which I remain a great fan and supporter.

When did your business experience begin?

It started back in 1992 when the YES scheme was in a prototype format when I was an undergraduate at the University of Nottingham and I started to become interested. Later I was asked to compete in a team in 1997 and I was part of a team from the University of Surrey as the managing director of our entry. It was a company called ABV, which stood for ‘Alcohol By Volume’, and it was all about producing yeast that could ferment sugar to 40% alcohol so people could produce spirits at home.

I bet that was fun

It was hysterical fun, yes. We had whisky as props and I learnt an awful lot more about business planning and how interested I was in the area. We managed to progress to the national finals and it really was that experience that took me over the edge and led me to develop a career as a bioentrepreneur. So the YES scheme has been a key influence in the development of my professional scientific career and from 1997 onwards every year I have supported that scheme as a mentor, presenter and judge because I fundamentally believe in the value it brings in developing our young scientists in whatever career they pursue.

Does the YES scheme get real results?

Yes, I believe it does. I think it broadens postgrad and postdoc researchers’ understanding of where they can take their career. On the one hand, yes, we want to find next bio-entrepreneurs for the UK, but it’s more than that, it enables researchers to understand a whole range of career options from accounting to patents to technology transfer to sales and marketing that otherwise they would not be able to experience. And the way it’s designed to be more of an experience than a direct education makes it a more enriching and personal learning experience. It’s a novel format that works.

And after YES?

After YES I wanted to pursue a career commercialising science in small biotech businesses and within three years I had the opportunity to spin out my own company, Cybersense Biosystems Ltd., from the University of Surrey in 2001. I developed the business and sold it in 2008.

For how much?

I can’t tell you the figures as the deal is based on an earn-out over time. We sold it to produce the best return possible for our shareholders. After Cybersense I went to talk to Isis Innovation in Oxford to discuss opportunities to do an other spin-out with them.

And that’s where you are still based?

Yes. There is always a shortage of start-up CEOs [Chief Executive Officers] and I recognised this many years ago and decided to specialise in this area. I started to work with Professor Cui on what is now Zyoxel and also within Isis Enterprise working as a consultant providing expertise in commercialising technology and creating new businesses on a wide range of projects and technologies across the world.

Do you now prefer business to science?

I prefer business with science.

Some people say we should start teaching business at science undergraduate level – do you agree?

Yes, I think it’s absolutely crucial. There shouldn’t be a career that science graduates get involved with that doesn’t have some input and requirement for knowledge of business. I think times have changed in academia and the commercial sector. It’s a balance because people generally do science degrees because they want to pursue an academic career, but there are some scientists that pursue an academic route like I did and realise that commercial research is far more exciting and they are perhaps more suited to it.

Your hardest moment so far?

[Long pause] Hmmmm, there’s been so many! Finding cash for new start ups is never easy. And restructuring a business when investors pull out can be an unpleasant experience. I had an investor that pulled out at the last minute and it got very serious – the business nearly collapsed – but it’s all part of the learning process.

And your best moment?

Getting businesses to be sustainable and then to profit is a true high point and key focus for me.

What are your hopes for Zyoxel in the next 2-3 years?

Zyoxel is a real platform technology so it has applications in a wide range of sectors that can go in different directions and you need options and flexibility in early-stage technology businesses. Because our investors are based in Hong Kong we have a lot of potential opportunities in the Asian markets both for manufacturing, research and business development opportunities.

Asia – that’s where it’s at, right?

No, I don’t necessarily think that’s the case. Asia has as many opportunities, albeit them different perhaps, to any of the other major markets. One has to approach Asia with caution. It’s even more difficult than the US market and if you’re going to work in Asia you have to work very closely with the right Asian partners so I wouldn’t say its next big thing. There are some great opportunities in Asia but they need to be very carefully managed.

What do you love apart from science and business?

Outside of work I play a lot of kendo. It’s traditional Japanese fencing that I’ve been practising for a couple of years now. I’m a bit of a Japanophile and it’s a high spirited past time. I guess it’s always appealed to me to spend time bashing people over the head with a big stick. And it keeps me fit, teaches me a lot, and is good for soul!

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