Merck & Co and Harvard Medical School Discuss their Exciting Bone Science Collaboration

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Video title: Merck & Co and Harvard Medical School Discuss their Exciting Bone Science Collaboration
Released on: December 01, 2010. © PharmaTelevision Ltd
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In this episode of PharmaTelevision News Review, Fintan Walton talks to Laurie H Glimcher, M.D., Irene Heinz Given Professor of Immunology at Harvard School of Public Health in Boston, and Alan Ezekowitz, MBChB, D.Phil., Senior Vice President & Franchise Head, Immunology, Respiratory & Endocrine, Merck Research Laboratories (MRL). They discuss:

• Collaboration between Merck and Harvard Medical School in area of osteoporosis

• Importance of collaboration with Merck

• Alan B. Ezekowitz 's perspective: Reasons for success of the collaboration

• Stage of research

• Merck's paradigm for future collaborations
Collaboration between Merck and Harvard Medical School in area of osteoporosis
Fintan Walton:
Hello and welcome to PharmaTelevision News Review here at BioPharm America in Boston. On this show I have two guests, I have Dr. Alan B. Ezekowitz , who is a Senior Vice President at Merck, I'll come back to you Alan B. Ezekowitz in a moment and Professor Laurie H. Glimcher , who is a Professor of Immunology at Harvard Medical School , welcome to the show both of you.
Fintan Walton:
Alan B. Ezekowitz , you are responsible for a range of therapeutic areas at Merck Research Laboratories, but we are here to talk about the bone research collaboration between yourself and the Merck and with Professor Laurie H. Glimcher here at Harvard Medical School [PharmaDeals ID = 30100] now I want to talk about that research, and your discovery, because your discovery was somewhat of a surprise to you, could you just tell us what part of your discovery that surprised you, could you describe how that happened and where it's placed you out of immunology and into the area of bone research?
Laurie H. Glimcher:
Sure will be happy too. We are actually primarily an immunology laboratory and we were looking for a novel transcription factor that's a regulatory protein that controls gene expression in the immune system. We isolated an interesting candidate and to figure out what it really did by knocking it out in mice so you understand that's one of the gold standard for figuring out what any given gene does, to our disappointment there was no interesting phenotype in the immune system that looked pretty normal, but we did note that it was very difficult to extract bone marrow from these mice and I remember the day that my graduate student and my postdoc came into my office and said you know there is really no immune system phenotype here and I asked them have you looked at every single organ, did you look at the bone marrow and they said well you know that's the problem is that we can't really extract cells from the bone marrow it seems to be included, and I said why you don't go down the street to my father's laboratories who is a bonafide skeletal biologist and take an X-ray of the mice and knowing behold the mice had very high bone mass, but the bones looked normal in shape so we did a number of experiments over the next year to figure out the mechanism and to figure out more about it and we found that the function of this protein which we call Schnurri-3 mapped to the osteoblast which is the bone forming cell. So it's deletion increases bone formation it activates the osteoblast to make more bone synthetic proteins and it is a process that increases over time so that the older the mice get the more bone they have, so this immediately appeared to us to be an exciting target for osteoporosis.
Fintan Walton:
Sure, so it's not a transcription factor it's an adapter protein cell?
Laurie H. Glimcher:
It was thought to be a transcription factor, but in all the experiments that we've done we have seen no evidence that it has the classic characteristics of a transcription factor which is to bind two DNA regulatory elements. So we think it is actually more of an adapter protein and it probably has a number of different sub straight targets in the osteoblast which may be one reason why it's such a powerful regulator of osteoblast activation and differentiation.
Importance of collaboration with Merck
Fintan Walton:
Right, so the collaboration with Merck is to better understand this pathway and in that and so doing to discovery new targets potentially for osteoporosis is that correct?
Laurie H. Glimcher:
I think that's the overall goal, one possibility is that this protein itself would be a very good direct target and we have recently obtained some evidence suggesting that is the case. The other way to go, the other avenue we explored we've done this extensively with Merck has been to understand the whole signaling systems that stem from this factor in the osteoblast by doing extensive genetic profiling, protein profiling, Phosphoproteomics making additional genetic mutant mice to layout the whole pathway of single transductioning in the osteoblast that is governed by this important factor.
Fintan Walton:
So Laurie H. Glimcher, for you and your research how important was the Merck collaboration, I mean clearly there is several aspects there obviously it is a hopefully it's a money component to it, but does it allow you to get access to further research within from the Merck organization?
Laurie H. Glimcher:
You know for us it was absolutely critical there is no way that we could have made the progress we've made over the last two and a half years without Merck as our partner and Merck is really a true partner this is not a situation where Merck writes a cheque and says good luck this is day-to-day communication between the scientist at Merck and the scientist in my laboratory literally everyday communication by email, by phone with monthly meetings face-to-face to go over milestones accomplishments where we need to go what else needs to be done, we've had a wonderful project manager at Merck who has really put his heart and soul into this and it's been incredibly productive for both of us.
Alan B. Ezekowitz 's perspective: Reasons for success of the collaboration
Fintan Walton:
So Alan , you know pharmaceutical companies have lots of collaborations with university professors some of them are successful, some of them are not successful, from your perspective and Merck's perspective why is this collaboration worked well? What is it that makes a different besides obviously Professor Laurie H. Glimcher here been an excellent scientist?
Alan B. Ezekowitz :
Right, I think having come from academic I understood what the strengths are in terms of what is done extremely well in academia and having experienced what the pharmaceutical industry can do, the old model would have been that Merck scientist would have read the paper and then separately try to recapitulate the results, build all the genetic models and sort of worked on the parallel path. And Second what we decided to do was why wouldn't we want to do that, why don't we just go to the people who are the experts and provide them with the expertise of what they know how to do best which is to understand the innovation and how the pathway works and we will provide them with the tools that they need to actually translate that as discovery as well as for us to make progress in terms of the way we gonna address things, and I think that there were skeptics within Merck when we entered into this collaboration just like there were skeptics within academia and I think that the model and the paradigm that I represented and understood was first of all we protect the academic freedom of the people working in Laurie's lab the postdocs and the graduate students are free at any time to talk about the information that they produce to publish it in peer-reviewed journals and so that this is a really good attempt to actually further their career. And the other important partner in this was Harvard who actually understood that they were it was very important for the university to protect its mission, but also that Merck had a mission too which is to make drugs and that part of that mission includes protecting intellectual property around some of the small molecules that we developed and obviously that's also in the interest of the university, because there is a royalty that string that goes with successful inventions if they are reduced to practice.
Stage of research
Fintan Walton:
Right, so how does the science actually work, is the science actually done at Harvard or is it done at Merck Laboratories?
Laurie H. Glimcher:
It's done at both places which is really one of the I think key components of this that we do a 100% of research in our laboratories and then Merck uses it's fantastic resources which we really wouldn't have access to otherwise to do more research, this is a complete partnership. And you know in selecting our partner and we were approached by a number of different companies who were interested in it you know become obvious to us very quickly that Merck was the right partner to choose, because they know how to carry out collaborations with academia where you harvest the best from both. So we are not doing high throughput drug screening in our laboratory that's what Merck really does well. What we do is help them think of new screens and help set up such assays and then to go back once we have a smaller list of interesting lead candidates and test them in our secondary and Tertiary assays of bone development.
Fintan Walton:
So where are you now on the collaboration, you clearly have moved down the path quite far, you are actually doing some form of drug assessment, but importantly as I understand it it's still you are still at the stage of target identification, target validation is that correct?
Laurie H. Glimcher:
Several screens have been carried out, there are some compounds of interest that we are looking at and there are some novel targets that stem from the signaling pathways who's phenotype we are also examining. I would say we have several lead candidates.
Fintan Walton:
On the research?
Laurie H. Glimcher:
On the research that we are actively pursuing.
Merck's paradigm for future collaborations
Fintan Walton:
And Alan , back to you I mean this you've described this as a paradigm, I mean is this for a company like Merck is this a reproducible type of collaboration? Can you escalate this or develop it for other collaborations or is it always gonna be down to individual cases?
Alan B. Ezekowitz :
Well I think what we learnt from this is obviously Laurie H. Glimcher is a very special scientist and she has a very keen understanding of how you translate science, and so what I think we take home from this is yes this is a paradigm, but just like Laurie H. Glimcher have to choose the right partner we've also have to be cognizant we have to choose the right academic partner to work with so that all the incentives are really aligned and the plans are aligned and we've certainly learnt how to do that, and yes we have replicated in other disease areas which I oversee and also other disease areas within the company, so we have a similar collaboration in the respiratory area two of them actually and along these lines. From my perspective there is a limit to how many of these things you can do, because you need to manage them very carefully and so that it's important to focus and to be selective.
Fintan Walton:
And I thank you both for coming on the show and telling me all about the collaboration. Thank you very much indeed.
Alan B. Ezekowitz :
You're welcome.
Laurie H. Glimcher:
It's a pleasure.
Fintan Walton
Dr Fintan Walton is the Founder and CEO of PharmaTelevision. After completing his doctoral research on the genetics of cell proliferation at the University of Michigan (US) and Trinity College (Dublin, Ireland), Dr Walton gained broad commercial experience in biotechnology in management positions at Bass and Celltech plc (1982-1992).
Alan B Ezekowitz
Senior Vice President
Alan B. Ezekowitz comes to Merck Research Laboratories (MRL) from Massachusetts General Hospital, where he has served as chief of Pediatric Services and has chaired the Executive Committee on Research. It was Dr. Alan B. Ezekowitz 's vision that led to the creation of the Massachusetts General Hospital for Children, a 'hospital within a hospital' providing world-class care for infants, children and adolescents. He has also been chief of Pediatric Services for the Partners HealthCare System in Boston and the Charles Wilder Professor of Pediatrics at Harvard Medical School . Prior to joining the staff of Massachusetts General Hospital in 1995, Dr. Alan B. Ezekowitz served on the staff of Children's Hospital in Boston for 11 years. Dr. Alan B. Ezekowitz received his medical training at the University of Cape Town in South Africa and the University of Oxford, United Kingdom, where he was awarded a Doctor of Philosophy degree.
Laurie H Glimcher
Laurie H. Glimcher M.D. is the Irene Heinz Given Professor of Immunology at the Harvard School of Public Health, and Professor of Medicine at Harvard Medical School . She received her B.A. degree from Radcliffe College and her M.D. from Harvard Medical School . She received her postdoctoral training at Harvard and in the Laboratory of Immunology at the Institute of Allergy and Infectious Diseases in Bethesda. She is board certified in Internal Medicine and Rheumatology, and is a Senior Rheumatologist at the Brigham and Woman's Hospital. She heads the Immunology Program at Harvard Medical School and the Division of Biological Sciences program at the Harvard School of Public Health. Dr. Laurie H. Glimcher received the Soma Weiss Award for Undergraduate Research, the Distinguished Young Investigator Award from the American College of Rheumatology, the Leukemia Society's Stohlman Memorial Scholar Award, the Arthritis Foundation's Lee S. Howley Award, the FASEB Excellence in Science Award, the American Society of Clinical Investigation Investigator Award, the Klemperer Award, the AAUW Senior Scholar award, the Huang Meritorious Career Award, and the American College of Rheumatology Distinguished Investigator Award. She is a Fellow of the American Academy of Arts and Sciences, a Member of the Institute of Medicine of the National Academy of Sciences and a Member of the National Academy of Sciences. She is the former President of the American Association of Immunologists. Dr. Glimcher is a member of the American Asthma Foundation, Immune Diseases Institute, Health Care Ventures, Burroughs Wellcome Fund and Memorial Sloan Kettering Cancer Center Scientific Advisory Boards and serves on the cancer Research Institute Fellowship Committee. She is on the Corporate Board of Directors of the Bristol-Myers Squibb Pharmaceutical Corporation and the Waters Corporation.
PharmaVentures is a corporate finance and transactions advisory firm that has served hundreds of clients worldwide in relation to their strategic deal making in the pharmaceutical, life science and healthcare sectors. Our key offerings include: Transactions / deal negotiations; Product / technology valuations; Deal term advice; Due diligence & expert reports; Strategy formulation; Alliance management; and Expert opinion for litigation/arbitration cases. PharmaVentures provides the global expertise to ensure our clients generate the highest possible return on investment from all their deal making activities. We have experience of all therapeutic areas and can offer advice on both product and technology commercialization.
Merck Research Laboratories
Merck&Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. Merck Research Laboratories is the Research and Development division of Merck. With nearly 10,000 employees and ten major research centers worldwide, MRL is building upon a rich tradition of turning cutting-edge science into novel medicines and vaccines that truly advance patient care. At MRL , the pipeline to tomorrow's discoveries is driven by a culture founded upon scientific excellence and the highest standards of patient safety. Research is expanding into an ever-growing number of therapeutic areas, including diabetes, Alzheimer's, obesity, and cancer, generating breakthrough discoveries like Emend for the treatment of chemotherapy-induced nausea and vomiting. As they have since 1933, the extraordinary people of MRL will continue to unlock the mysteries of disease and design new medicines and vaccines that will improve patient care around the world.
Harvard Medical School
Since 1922, the Harvard School of Public Health has led the world in public health research and education. It has guided an ever-expanding field and embodied the highest standards of scientific rigor and social commitment. Its landmark discoveries and world-class graduates have saved lives and lifted the burden of disease around the globe. The School traces its roots to public health activism at the turn of the last century, a time of energetic social reform. HSPH is the direct descendant of the first professional training program of public health in America, a joint venture forged in 1913 between Harvard University and the Massachusetts Institute of Technology, and known as the Harvard-MIT School for Health Officers. The partnership offered courses in preventive medicine at Harvard Medical School , sanitary engineering at Harvard University and allied subjects at MIT . In 1922, the School split off from MIT , helped by a sizeable grant from the Rockefeller Foundation. From the start, faculties were expected to commit themselves to research as well as teaching. In 1946, no longer affiliated with the medical school, HSPH became an independent, degree-granting body. Many of the changes that unfolded in public health over the 20th century trace their origins to HSPH . Initially, researchers were preoccupied by deadly epidemic infections and by the scourges of unfettered industrialization. During the School's first 50 years, the public health enterprise matured, drawing on a full range of analytic, scientific and policy disciplines. Today, the School's purview extends from the gene to the globe. It work encompasses not only the basic public health disciplines of biostatistics and epidemiology, environmental and occupational health, but also molecular biology, quantitative social sciences, policy and management, human rights, and health communications. Its leadership and outreach have informed public health practice around the world from decades of research in the People's Republic of China to studies of health system reform in Taiwan and Poland, from collaborations on environmental health in Cyprus to intensive field training in Latin America.