David Brown: proteomics in drug discovery

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  • Was your time at Pfizer a highlight for youbecause of the success of Viagra?I have enjoyed all of the companies I haveworked for and there have been severalhighlights in addition to the drugs that made itto market.You never know whether any drug isgoing to make it, and Viagra was never easy, itwas always teetering on the edge of success orfailure. I cant complain about my career at all,Ive had a good time. I think the critical thing isthat Ive had a gradual expansion of experiencein many aspects of the pharma business. Myboss at Pfizer, Simon Campbell, was particularlyhelpful in ensuring this, as also was JonathanKnowles at Roche. I owe a lot to them. Inaddition to research, Ive been involved inclinical development and business development;the only parts of the business Ive not beeninvolved in are manufacturing, sales andmarketing. Joining Cellzome in September 2002was another highlight. Biotech really suits me.I enjoyed my time in pharma but the moresenior you get, the more committees you siton, and the more travel you do, and you startto wonder whether its what you really want todo for the rest of your career. Biotech is veryfast and stimulating and that suits me you can

    see a lot of progress month-by-month, which isvery satisfying.There is less politics and morefocus on developing the business anddiscovering drugs, which is where my interestis. Another thing Ive really enjoyed is that thebiotech community is very friendly. In bigcompanies you dont know much about whatsgoing on in other companies and its quiteinward looking, but the biotech community isvery open and companies help each other.There is a tremendous camaraderie in thebiotech community and I really enjoy that.Biotechs are also far more aware of theimmediate state of the market and howimportant it is to be productive.There are a lotof good people in biotech but if I had one hopefor biotech it would be that more good peoplewould move from pharma. I especially thinkthat biotech needs more experienced drugdiscoverers, clinical development expertiseand experienced senior leaders at CEO level.There is enormous potential in this industryand it needs people with highly developed skillsfrom pharma to move in. I think as biotechmatures well see more of those peoplecoming in and more drugs will be discovered,to the benefit of patients.

    Why did you decide to make the move tobiotech, and why Cellzome?I had always planned to move to biotech, butmy plan was to move in 2004.When I movedto Glaxo in the mid-1990s I bought a housenear Cambridge, UK, because Cambridge isthe biggest biotech centre in Europe. I reallyenjoyed my job at Roche and its a finecompany, but the travel 100 flights in my lastyear was exhausting. I became aware ofCellzome in 2002 and I thought it was a greatlittle biotech with enormous potential.Theywere looking for a CEO in 2002 and thereforeit was likely that the job might not be vacantin 2004. So I looked hard at the job. I alsoconsidered joining the venture capital world.However the people at Cellzome were goodand the technology that they had was reallybeginning to impress me.They had two verypowerful drug proteomics platforms and asuperb informatics platform, and I saw thatthese could have a very significant impact ondrug discovery.That was a good fit with what Iwanted to do. I did not just want to lead anybiotech, I wanted to lead one that would bothdiscover drugs and transform the efficiency ofdrug discovery. So, I took the leap and I dontregret the move at all.

    What main lessons from pharma have youtaken and used in biotech?The biggest drive for me is to get drugs intothe clinic to treat sick people. My grandmotherwas dying when I was a PhD student and thathad a big impact on me in my desire to helppeople by discovering medicines.The mainlesson for me is to maintain absolute focus ongetting drugs into clinical trials.Theeffectiveness of the various companies I haveworked for correlates directly with howeffective the senior management is in keepingthe organization focused on that goal.A second lesson is the need to constantlydeepen and broaden skills. I had studiedbiochemistry as part of my chemistry degreeand continued to do so during my PhD studies.That proved very helpful to my career. Itsdifficult to make progress in this industrywithout the knowledge and confidence to takeon ever broader scientific and managerialresponsibility, which means developing anever-broader scientific base.

    A third lesson is just how difficult it is todiscover drugs, a fact I think that is not fully

    TARGETS Vol. 2, No. 4 August 2003

    1477-3627/03/$ see front matter 2003 Elsevier Science Ltd. All rights reserved. PII: S1477-3627(03)02358-4134 www.drugdiscoverytoday.com

    UPDATE

    INTERVIEW

    David Brown:proteomics in drugdiscovery

    Interview by Joanna Owens

    David Brown, Chief Executive Officer, Cellzome

    David Brown has worked for four of the top ten pharmaceutical companies,beginning his 28 years in the pharma industry at ICI Pharmaceuticals (Zeneca),followed by a move to Pfizer at Sandwich, UK, where he spent a decade managingmedicinal chemistry. He was then headhunted by Glaxo just after they boughtWellcome to be responsible for a research division of 300 biologists and chemists.Most recently, he was Global Head of Drug Discovery for Roche Pharma, based in Basel,Switzerland, where he was responsible for the output of 2000 scientists across fiveresearch sites.At Roche he also served on the committee responsible for clinical drugdevelopment as well as on the business development committee responsible forin-licensing of products and for technology agreements and acquisitions. He wasclosely involved in the acquisition by Roche of Chugai.His career has included getting several drugs to market, including Viagra, of which hewas co-inventor, and he led the clinical development team to Phase II; and Relpax, Pfizersmigraine drug that was launched in 2002, and other drugs currently in clinical trials atGlaxoSmithKline. He joined Cellzome as Chief Executive Officer in September 2002and spends his time between their locations in Elstree, UK, and Heidelberg, Germany.

    If I had one hope for biotech itwould be that more good peoplewould move from pharma

  • appreciated by many people in biotech,especially those with an academic backgroundrather than a pharma background. It has beensaid that discovering a drug and getting it tomarket is more difficult and complicated thanputting a man on the moon! I particularly valuethe years I spent at Pfizer because I learnt somuch about drug discovery and its challenges.I worked with very talented people and gainedexperience of getting drugs into developmentand then leading the development teamsthrough from Phase I to Phase II. Having hadthat experience at Pfizer, I was placed on theclinical development committees at Glaxo andRoche, which was an enormous help to me indeveloping the skills to lead a researchorganization. From the perspective of theclinical development committee you see theproblems that molecules hit in clinicaldevelopment, and you try to avoid makingthose mistakes again and try to improvethings further back in discovery. So thoseexperiences have quite an influence on theway I lead Cellzome; we will try to ensure thatwe avoid the mistakes in discovery that lead toclinical failure.

    A fourth lesson from pharma is theimportance of general management skills. Ivebeen through many roles in highly professionalcompanies that invested heavily in training anddevelopment.You see good managers and poormanagers and learn from both! Those lessonsare essential as Cellzome recruits people andbuilds up the infrastructure for drug discovery.

    Would you ever return to pharma?I wouldnt say absolutely not, but I think itwould feel like going backwards. Im reallyenjoying biotech so a return to pharma doesntseem an obvious move at the moment.

    If you did, what have you learnt atCellzome so far that you take back topharma?Ive learnt a lot more about where genomicsand proteomics can actually impact drugdiscovery. I believe that a lot of pharmacompanies are struggling to figure how to applygenomics and proteomics technologies, withconsiderable waste of money and resources.Ive had to think very clearly over the past ninemonths about what value there is in Cellzomestechnology and what our competition is doing,and this has given me a clear view of where the

    major benefits of these technologies exist indrug discovery.

    How exactly is pharma wasting money ongenomics and proteomics technology?I wouldnt want to generalize about allpharma, Im sure there are some companiesdoing interesting things with this technology.But here are some of the issues. One is theuse of differential gene expression andassociated gene data from pathological versusnormal cells and tissues.That data is really justa symptomatic view of a disease, it doesntnecessarily capture the underlying diseasecause or mechanism. I think what you needto add is some mapping of individual diseasepathways. Ideally you would take hits fromdifferential display, work out from those theassociated proteins and map disease pathwaysaround those associated proteins.This allowsyou to interpret data at a functional level, andyou begin to see the disease context. Similarlywith disease-associated genes, you usually geta very weak association with a disease, whichalone isnt very convincing. However, thisassociation can be further validated, byworking out which pathways include thepredicted proteins encoded by these genes.What you will often find is that two or threegene products interact in the same pathway,and this gives you a high confidence that thepathway is relevant and youve actually got agenuine finding.Then there is the bigquestion of chemical tractability to be takeninto account, preferably right at thebeginning of thinking about the use ofgenomics and proteomics.

    Why do yo

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