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EXCLUSIVE LIFE SCIENCE FEATURE leaders LIFESCIENCELEADER.COM 26 NOVEMBER 2014 tion in drug development. All of the recent approvals are in GSK's established market areas, mirroring their relatively broad focus: COPD/asthma, diabetes, HIV, and cancer (melanoma), with the two molecular-pathway targeted drugs in the last category joining the exodus to Novartis. GSK's current pipeline reveals that the company, not unlike most of its competitors, is heading into niche-drug territories, driven and guided by a careful reading of scientific opportunities and the reimbursement landscape. At the same time, as heralded by Chairman Andrew Witty, GSK will seek to lead the industry in the trend toward sharply reduced R&D; budgets, attendant cost-cutting, and collaborations with all sorts of research entities in the quest for biotech-like innovation — without, of course, incurring the usual, though oft- ignored high failure rates of the startup biotech sector. To reduce the risk of dupli- cating the darker side of entrepreneurial biopharma, the company aims to make the best possible use of its natural assets, the "platforms" of drug discovery, devel- opment, and commercialization that only a Big Pharma like GSK can maintain. REPRODUCIBLE, RESILIENT, AND REAL It is useful to know how and why Vallance joined the company, because his responsi- bility ultimately came to encompass both affirmation and optimization of the orga- nization he would head. He was well along in an academic career at University College London, when he met GSK's then head of R&D;, Tadataka (Tachi) Yamada, and subse- quently answered Yamada's invitation to join the company in May 2006. "If you'd asked me the day before I decided to move to GSK, I would have said I absolutely had no intention of moving to industry," he recalls. "I was a clini- cal academic. I saw patients. I ran a big department. I knew my next job would be running the medical school. I had been on the research advisory board for GSK for a couple of years, which was eye-open- ing for me both scientifically and in the way people thought about treating major medical problems." After an advisory board meeting in London, Yamada asked Vallance to head GSK's drug discovery. Resisting the offer at first, Vallance later thought, "I could spend the rest of my career doing aca- demic research that might lead to drugs or even, as I was doing at the time, making molecules that interfere with biological processes — or I could go and do the real thing, seeing molecules all the way to becoming medicines. This looked like a really big, interesting career change, and I decided to do it. It was a decision with no great planning or logic behind it and one that I have never regretted for a single second since then." His initial revelations at the company were mainly positive: "One of the things that struck me was the outstanding qual- ity of the science that goes on and the attention to data reproducibility and integrity, a huge issue in many academic sectors and in the published literature. The dedication to more reproducible assays was very impressive. It was impor- tant for me to get to grips with what it means to have robust and reproducible data at this scale of R&D.;" Scale itself — the industrial scale of dis- covery and development activities at the company — also impressed Vallance, and at the same time led him to ponder an inherent conundrum in the large-pharma model. "The number of projects is big, and of course, that's good in one sense. But it leads to a question: What is the depth of understanding underpinning every project?" That thought became his mis- sion: finding a way to increase scientific understanding of drug mechanisms and drug interaction with the human body, so the company might focus on fewer projects in greater depth. Vallance saw a potential opportunity in the industrial setting to create an advan- tage that eluded the academic world. At its best, GSK allowed all the different R&D; disciplines — chemistry, biology, biophar- maceuticals, and so on — to interact in "an incredibly fluid way," he says. "Getting all of those elements together to work as an integrated, multidisciplinary team is frankly the dream of a lot of people in aca- demia, but it only seldom works." Again, over time he looked for a way to make the concept even more effective in practice. During the six years following his move to GSK, Vallance rose from head of drug discovery to senior vice president of medi- cines discovery and development, help- ing plan and implement the first major R&D; reforms driven by Witty and Moncef Slaoui, now chairman, Global R&D; & Vaccines. Those reforms began in dis- covery, involving the creation in 2008 of about 40 teams, consisting of 40 to 60 members, called Discovery Performance Units (DPUs), out of the six former dis- ease-area units. The DPUs were designed to integrate disciplines even more effec- tively than did the preexisting company culture. They were also to echo a new "open-research" philosophy of external collaboration, by re-creating start-up-style innovation internally. When Vallance was appointed head of Pharmaceuticals R&D; in January 2012, he continued to lead reforms reaching past discovery through all the stages of drug development. But in addition to the internal restructuring, GSK also began a campaign to shift much of the R&D; burden and risk to a massive external network of companies and institutions. Overall, Vallance believes the organiza- tional changes have reinforced a more bottom-up, scientifically driven approach to new drug development, moving the company away from the old top-down, We had to reintroduce personal accountability and individual leadership. GLAXOSMITHKLINE — REFOCUSING, RESHAPING ONCOLOGY R&D; By W. Koberstein D R . P A T R I C K V A L L A N C E President of Pharmaceuticals R&D; GlaxoSmithKline