Doing business with the big boys

So, you're a small biotech looking to get into bed with Big Pharma. Kate McDonald spoke to Merck's head of research Ismail Kola about life on the dark side.

Most people will remember Professor Ismail Kola from the 15-odd years he spent at Monash University, working initially in embryology and reproductive research before moving into molecular genetics and genomics.

Kola is now firmly ensconced at the famous laboratories in New Jersey of pharma giant Merck & Co, where he is senior vice president for basic research. At Merck, he has the rare privilege of overseeing a staff of 1100 scientists and an annual budget of US$420 million.

Originally from South Africa, he was encouraged to come to Australia in 1985 by IVF pioneer Alan Trounson, who with Carl Wood was then "setting the world on fire" in reproductive health.

"Alan Trounson came out to South Africa to do a talk, we met and he thought I'd be a good addition to the team," Kola told ALS on a recent visit home. "I had met Carl Wood at a conference and they offered me a job. I thought it was important to come out because Australia was leading the world at that time."

Kola spent 14 and a half years at Monash, where he made his reputation in the identification of specific genes that cause abnormalities in people with Down syndrome and later studied inflammatory disorders and osteoporosis, doing important work on cathepsin K, a member of the papain cysteine protease family.

While his academic career was highly successful - he holds a lifelong personal chair in genetics and genomics at Monash - it was the challenge of a new world that drew him to the dark side that is Big Pharma.

"The thing that drew me was that firstly in academia I had conquered a lot of the challenges. I left here with a big NHMRC program grant, I had a NIH grant, lots of postdocs, but I wanted some additional challenges.

"I was fascinated by the drug industry, which was in the first instance was not only working out what a gene does in disease - which is what we were doing in academia - but then taking it right through, finding molecules and getting therapies that [affect] patients' lives. Also I was very drawn to the commercial part of it."

He was on the international genomics advisory board for SmithKline Beecham from 1993 to 1998, and in 2000 joined Pharmacia, where he was vice president of research and global head of genomics and biotechnology.

Then Merck came along with an offer he couldn't refuse in 2003.

"I got a call from the headhunters one day - I usually don't answer headhunters' calls because in America they call all the time - but they were from Merck, and when I was in South Africa, Merck Sharp & Dohme gave me a scholarship that paid my way through university, so I thought I owed these guys a call.

"I was told that they were really interested in me and would I take the job. I didn't mean to take the job but I started flirting with them, and you know when you start flirting you often fall in love."

Kola admits that for many years Merck concentrated mainly on internal drug discovery, which is still a hugely important part of the company. It has become a little more outwardly focused these days, however.

"Merck has always been the industry leader in internal drug discovery," he says. "The labs have been extremely productive - Merck discovered the first statin and then went on to develop the first bisphosphonates for osteoporosis and some hypertensives. So the Merck labs have had a tremendous track record in drug discovery.

"We realise at Merck that even though we have a tremendous drug discovery engine - we had this track record and then went through a period of reduced productivity but we have really pushed it back now so the pipeline is really filling up - but even despite our internal drug discovery engine we only do less than one per cent of the world's research.

"It's important for us to try to access the other 99 per cent of global research. We think of it as in every country and we just want the best irrespective of the source - whether it's academia, biotech or whatever."

Kola estimates that only one in 10 molecules that are in clinical trials actually make it to market, and one in 1000 from basic research, so choosing a winner is a big part of his job. For Merck, there are a number of important areas of research to be targeted.

"We at Merck have prioritised our areas of research that we think have obvious medical need and clearly ones that patients need in therapies. These are the areas of atherosclerosis, diabetes, obesity, hypertension and cardio-vascular diseases, Alzheimer's disease, novel vaccines, cancer and antivirals - infectious diseases in general."

Merck itself is a little excited about its new diabetes drug Januvia, one of new class of drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors, which enhance the incretin system to better regulate glucose levels. It received FDA approval on October 17.

"This drug was developed at record speed," he says. "The first time the basic research labs did the experiment was in April 2000 and by the 15th of December 2005 we had already filed the drug."