Regulatory setbacks. Expiring patents. Huge layoffs. What’s an R&D chief to do? Glaxo’s Moncef Slaoui tells Nature that he hopes to turn the corner next year…

Nature: What have been the most significant changes at Glaxo recently?
Slaoui: I would say the biggest change in the past five years is an acute and profound realization of the major challenges in front of us. And the willingness to grab them by the horns and deal with them, rather than pretend that we will spend a bit more money and try a little harder and find this big blockbuster that’s going to save the situation.

Nature: What are those major challenges?
Slaoui: On the one hand, science has become extraordinarily powerful from a technological standpoint. It is generating huge amounts of information and data, but it’s harder to integrate that information into a meaningful biological or clinical conclusion. So, much more money goes to generating information, but that information doesn’t tell us remarkably more.

On the other hand, there are a number of medical needs that are not fully addressed, but are partially addressed. That puts the bar higher for any newer medicine to come in and have a meaningful clinical impact. Also, regulators have moved the pendulum around the safety-benefit equation of medicine a little bit too far to the safety side in some instances. They’re putting the hurdle higher.

And finally, the diseases that we called with one name ten years ago are now called five different diseases, and tomorrow will be called 15 different diseases. We’re slicing them into smaller subpopulations that probably require different medicines. That also slices the market potential and therefore the return on investment.

Nature: One way to address that is with genetically targeted therapies. Are they a priority?
Slaoui: In the field of oncology, yes, because the medicine is targeting those mutated proteins that are responsible for the cancer phenotype. I would say it’s an obligation to slice your population that way. More and more I think we will not be talking about ‘lung cancer’ or ‘breast cancer’. We will be talking about cancer driven by [specific proteins like] mTor or Myc or Ras.

In areas other than oncology, I have to say I’m not a strong believer today. Maybe 40 to 50 years from now genetics will let us identify diabetes patients that will respond better to medicine number one versus medicine number five. Today, I don’t think the science is there; therefore we’re not investing heavily in that direction.

Nature: Pharma has shifted its resources heavily into biologics, such as therapeutic antibodies, as opposed to small-molecule drugs. Why?
Slaoui: I wouldn’t say we are moving away from small molecules. I would say we are integrating biopharmaceuticals as a key part of the platform with which we make medicines. This is something I have pushed very hard. We have just recently announced the creation of an integrated R&D unit around biopharmaceutical drug discovery and development with the very ambitious objective to have more or less 20% of our pipeline derived from biologics by the year 2015.

There is a scientific driver and a business driver. In some cases [biopharmaceuticals] are more effective than a new chemical entity. Strategically, I do not think that biopharmaceuticals will experience the same cliff when the patent expires as new chemical entities. It is extremely complex to make an identical biopharmaceutical.

Nature: How many researchers have been laid off at GSK in the past year?
Slaoui: I think a few hundred have been laid off across all the disciplines involved in the R&D process, from biologists to physicians to science writers, et cetera. Overall, 2008 is the year of change for R&D. 2009 is the year of consolidation and moving forward. Most of the changes and job losses will be behind us. (Later, Glaxo confirmed plans to lay off about 1,500 R&D employees this year).