Mr. Leigh Berryman, Chief Executive Officer, Maccine Pte Ltd
18 May 2011
By Ai San Yip, and Larry Lim
Edited by Cheryl Ma, Shou Yi Poon
Photo creative Larry Lim, Macro Studio
From Left to Right: Dr. Alex Wilson, Chief Scientific Officer, Mr.Â Leigh Berryman, Chief Executive Officer and Ms. Choy-Siong Wu, Chief Operating Officer.
Maccine is a Singapore-based pre-clinical contract research organisation providing innovative discovery research and quality safety assessment services to the global biotechnology and pharmaceutical industry. Its primary focus is on creating translational value in the pre-clinical research. Maccineâ€™s significant investment in technology, people and science has ensured its position at the forefront of global pre-clinical research.
1. Share with us your background and the innovation behind drug discovery research.
I consider myself to be a fairly international citizen - born in New Zealand, educated in United Kingdom (UK), speak Dutch/ English, have multiple citizenships, including Canada, and am currently living (working) in Singapore. Professionally, I am a toxicologist who has been working in drug development for 35 years. I started my career in UK, moved to Holland, settled in Canada, subsequently worked in US and have finally arrived in Singapore. My whole professional life has been in the drug development industry and I have been involved in over 300+ Investigational New Drug (IND) submissions to US FDA.Â Probably, one of my highest profile involvements was as a toxicologist working with EpogenÂ®.Â
Drug development has gone through significant changes over the last forty years. Forty years ago, the aim of drug development was to make thousands of new molecules and screen them for biological activity. A hundred of these new molecules will show some activity. They are re-screened to determine useful activity and, if fortunate, one of them might have an activity that had not been discovered by others. To conclude, of the thousands of molecules that begin the development process, only a few made it to the next stage of development. Early stage drug discovery was very much a â€œhit-and-missâ€ process.
The industry moved on to rational drug design. Combinatorial chemistry strategies and computer assisted design were used in drug development to match designer molecules to targets in disease states.
The next wave of innovation came with the advent of genomic technologies. We now have a greater knowledge and understanding of how diseases work at the genetic and molecular level. Screening and identifying endogenous molecules with known activities became the norm in the bio-pharmaceutical industry. Identifying the gene sequences encoding the molecules was the next logical step. The gene sequences were inserted into production â€˜enginesâ€™ and fermentation processes allowed for the manufacturing of these molecules. Consequently, a very active product (biologics) or potent drug would be produced. When you are dealing with biologic-derived materials, the potency and biological activity is almost assured. Thus, innovation in molecular sciences has driven the auxiliary science of toxicological evaluation, ie human safety, in drug development.
In the modern context, Aspirin might never have reached the commercial market today, simply because of high toxicity. Aspirin is an example of small molecule drug that could well not have passed todayâ€™s safety criteria and standards. Safety is very important in the drug development world. In the regulatory world, you can go a long way down the process developing a drug of no or limited efficacy, but regulatory requirements generally ensures the new drug will not cause harm.
Subsequently, drug development processes place more emphasis on ensuring human safety. FDA and EMEA major focus is on the safety profiles of drugs. Commercial companies are driven to put in substantial effort to determine product safety before it enters human trials.
Human safety has become a very expensive value proposition in business world. Drugs launching into the market can cost between USD 1 â€“ 1.4 billion from drug discovery to clinical trials. It is not until a company spends USD 300 â€“ 600 million that they know whether the developed product is safe.Â
2. How does Maccine know there is an effective value proposition in drug discovery services amidst the conventional drug discovery approaches?
This is a phenomenally good question! The drug discovery processes can be a unique business by itself.
In 2004, there was limited incentive to revolutionise what had become the conventional drug discovery/development route as cost was considered acceptable and the market was willing to bear the resultant cost of the product on the market.Â However, there was a tipping point circa 2004 where cost of development started to be the subject of many questions, not least the resultant ethical issue of making treatment available that was only affordable by very few.Â The recognition of a need for a lower cost development became very clear.Â This resulted in increased focus on translational research (a relatively new term for a well-established philosophy), ie. increase confidence that it WILL work in man before spending the substantial sums of money in Phase II human trials (the usual point at which there is a clear signal as to efficacy or not).
Singapore has recognised and embraced the concept of translational research as very high value / high knowledge.Â Maccine moved into Singapore as Singapore started supporting translational research.Â At that time, there were no dedicated Contract Research Organisations (CROs) supporting high-end models for drug discovery services. Singapore has also brought in bio-pharmaceutical companies that have a high scientific component to their drug discovery research. By leveraging Singaporeâ€™s government support and the high science of the global pharmaceutical companies, Maccine was able to establish itself as a center of excellence in translational research service.Â By 2008, Maccine had established a range of technologies and highly credible models of human disease that can be used to reduce the risk of failure of the expensive Phase II human trials.
Maccine has models of Epilepsy, Atherosclerosis, Schizophrenia, Neuropathic Pain, Alzheimerâ€™s, Parkinsonâ€™s, Diabetes, Endometriosis, Osteoporosis etc.Â We have models of the human condition that are similar to or identical to the disease in human. If the potential drug has been shown to be safe and efficacious in our models, the probability that it would be safe and efficacious in humans is high â€¦ not guaranteed, but very high.Â Â At an economic level, we find our clients more than happy to invest half a million to a million on a high-end translational model to de-risk the USD 100-150 million Phase II clinical trial.
Mr. LeighÂ is alsoÂ aÂ Chairman on BioSingapore Organisation, a non-profit entity, thatÂ hosts BioBusiness Breakfast Networking Session.Â Â
3. What is your own perspective of Singapore and its Biomedical landscape?
What is done very nicely in Singapore is the incentivising of global pharmaceutical companies to come to Singapore to establish a base of operation, both scientific and operational.
EDB, NUS, A*STAR have been successful in developing intellectual property and technologies, and attracting bio-pharmaceutical companies. However, what Singapore is really bad at is taking risk!Â In the drug development industry, you have to embrace failure and be in the business of failure. Statistically, you are going to develop ten products knowing that nine of them are going to fail. As a society, Americans love risk and are enthusiastic at funding multiple biotechnology developments with full awareness of the risks involved. If Singapore wants to create a biotechnology community, Singapore Pte Ltd has to get over its fear of failure of individual developments and concentrate on the larger picture.
If you take a snap-shot of the biotech companies in U.S. (for example,Â San Diego) this year and observe the same community one to two years later, maybe 25% of the original companies would have ceased to exist, but another 25% would have emerged.Â The people, however, would remain the same because the people just re-focus on the next technology (ie. company). The venture capitalists (VCs) do not like failures, but they know the biotech game. Of course, VCs will try to cherry-pick the ones they think are going to succeed to increase their odds of a higher return.
Singapore is on the tipping point now. Singapore has to accept the fact that if we want to create a bio-community, there has to be an acceptance of risk. In terms of funding, there has to be recognition that most of what was funded is probably going to fail. Singapore needs to develop the culture of supporting tech-based companies and biotech start-ups. Interestingly enough, in Quebec, Canada, the VCs community was mostly funded by the government in one form or another.Â There could be something to be learned there for Singapore.
4. If there is one word of advice you can give to aspiring technopreneurs who are looking to start their business in the biomedical industry, what would that be?
There are three things that you absolutely have to have in order to succeed.
The first is an overwhelming passion and belief that what you have got is going to be successful. You cannot do this part-time; you have to be very engaged and committed.
The second important element is a solid, well-defined and very professional business plan. During fund raising, the investment community are definitely going to speak to the founders. Founders are very enthusiastic and will claim that success is fore-ordained.Â The VCs are of course looking for the passion and belief, but having ticked that box, will then put most focus on the numbers to support the belief.Â Thus, a smart entrepreneur should find someone who has the financial acumen and experience to develop the business plan AND defend it in front of the financially very savvy investment community.Â Few individuals encapsulate the needed levels of scientific and financial ability.
Third piece of advice is not to give up. You will face countless rejections.