Senior executives from Pfizer, Wyeth, Merck & Co. and Novartis sat down at last week's Drug Discovery and Development of Innovative Therapeutics (DDT) conference in Boston, US, to discuss what areas they are looking to expand in, both through internal research and new partnerships. The cost of licensing deals in the pharma industry may be increasing all the time but big pharma is still willing to take the risk in the face of dwindling innovation and key drugs coming off patent. However, the crucial question on the lips of smaller companies is: what exactly are the big firms looking for? As well as each company divulging areas of rising and falling importance, they also explained why and crucially, what external factors might cause this thinking to change. Merck & Co. Dr Mervyn Turner, senior vice president of worldwide licensing and external research at Merck Research Laboratories revealed that the rapidly growing oncology market has become increasingly important to the company. He said: "[Others] might not have thought of Merck in the past as an oncology company and that really changed with the arrival of [oncologist] Stephen Friend, when we bought Rosetta [Inpharmatics]...and we just gave him carte blanche to rethink the oncology area." The move also "sits well with Merck's thinking on targeted therapies, a direction we think the industry will go in general," added Turner. This thinking would only change if there was a major change in pricing capability, given that there are over 800 molecules in clinical development, according to Turner. He also said the company is very interesting in increasing its advanced data mining capabilities, which was also evidenced by Merck's acquisition of Rosetta. Meanwhile, the large hurdles for success and large clinical trials associated with potential thrombosis therapies require an investment so large that Merck will not be investigating that therapeutic area. In terms of mechanisms, Merck & Co. has invested heavily in RNA interference (RNAi) - they recently bought Sirna Therapeutics for $1.1bn (€850m). The pharma giant sees this as an attractive area due to the technology's ability to "expand the druggable universe" and its potential for a persistent effect - Merck & Co. has already seen effects lasting beyond three weeks from a single administration in preclinical models. This, and other advantages of RNAi, can increase the probability of success of potential drugs. This interest could only be weakened if RNAi therapies continue to be difficult to deliver. However, despite around a decade's research in amma-aminobutyric acid (GABA) biology, the firm is ready to give up on the protein as a drug target. The only thing that might lead this to change is if another company can show differential clinical proof of concept; this is also true for thrombosis therapies. Wyeth Dr Thomas Hofstaetter, senior vice president of global business development for Wyeth, said that Alzheimer's disease is "the one largest increasing R&D area for Wyeth." He added that the company now has over 15 programmes in Alzheimer's from discovery through to one drug that is about to enter Phase III clinical trials. The company is leveraging its expertise in small molecules, vaccines and biologics to attack the disease. However, Wyeth sees its presence in the oral contraceptives market as complete following the recent approval of Lybel (levonorgestrel). The pharma giant has been involved in bio-molecules for a long time, including antibodies, but is now looking into antibody-like therapies. These are modified antibodies or molecules with novel scaffolds where scientist can tailor different drug properties. Hofstaetter explained that this area is interesting as new targets can be studied and also, novel molecules could avoid what he described as the main problem with antibodies, which is royalty stacking. Hofstaetter went on to say that Wyeth has stopped all research efforts in antisense and cell therapy, largely because delivery problems limit their efficacy. Unless this problem can be solved, the company plans to leave these mechanisms alone. Pfizer Dr BJ Bormann, head of worldwide strategic alliances for Pfizer explained that the world's largest pharma company is increasingly interested in ophthalmology and pain therapeutics, while gastrointestinal and dermatology indications have waned in the eyes of the company. This is because the latter two markets are seen as limited by the pharma giant and, according to Bormann, it is difficult to find drugs to compete with over the counter drugs. Mechanisms that Pfizer is losing interest in are anything with systemic delivery issues such as antisense - although the company do have a "productive" ophthalmology antisense collaboration it is still actively pursuing. The company is also disappointed with the concept of black box screening, where Pfizer has a number of expensive collaborations that were "productive but the science didn't actually fulfil what our hopes was," said Bormann. As an example, she went on to mention a partnership with Aurora where the companies looked at different types of wholesale screening technologies but that "just didn't deliver clean enough data in order for us to make decisions as far as proof of concept." She also explained that companion diagnostics are seen as an integral part of Pfizer's future. Novartis Dr Jeremy Levy is the global head of business development and strategic alliances for Novartis Institutes for Biomedical research. He explained to delegates that Novartis has recently increased their research in the area of diseases that relate to an excess of interleukin-1 and are looking to expand in this area further. Levy explained that there are "very few therapeutic areas not of importance," and the company is willing to look into any and all diseases, especially once proof of concept has been established. "We are set on a course and that course was to change the way we do research," he said. "Fundamental to that is opening ourselves up to as many different ideas as possible." In terms of mechanistic approaches to therapy, Novartis is increasing its R&D into biologics since it intends to become a leader in this field, while at the same time stopping cell therapy research. This latter decision is due to difficulties in scaling cell therapies. Much left to do While each of the companies look to new therapeutic areas and mechanisms to fill their pipelines and ensure a continual flow of novel drugs, Merck's Dr Turner concluded by sounding a warning for the industry that there is still much left to do. "We're working in a business model that is under incredible pressure, whether you are in the biotech or pharma industry," he said. "The solution lies...with coming up with novel business models, which allow us to capitalise on the incredible science that is taking place at the dawn of what is the 'century of biology', to turn it into new therapies in a way that is cost efficient for both the industry and the payers. We can do it but it will require a fundamental rethinking in the way in which we do business."