HD Insights™

H D I N S I G H T S Michael Hayden, cont... HAYDEN: As I came to the end of my fellowship, I was asked to go to Vancouver, Canada. Judith Hall, President of the American Society of Human Genetics, was there, Tom Perry Sr., a major researcher in HD, was there. Marjorie encouraged me to look at this opportunity. They welcomed me, and the HD family welcomed me. I had a deeply ingrained commitment to HD. I had seen the plight and difficulties but had also witnessed the courage and dignity of HD patients. I established my lab to make inroads into HD. We have had huge support from families all over North America. In 1986 we did the first predictive test for HD, and contributed to the guidelines for HD predictive testing. We worked on really understanding how, at a molecular and biochemical level, HD occurs. The key question was: How do we develop therapies for HD? We created a full-length animal model for HD. We did the first PET scans in patients, and we created an integrated HD clinic, the first in Canada, that today sees patients contributing to trials around the world. We defined the epidemiology and the incidence of HD, showing that it is more frequent than people have realized in the past. We also defined mechanisms that lead to HD, which is ongoing work for my lab in Vancouver and Singapore too. Many of my post-docs have now gone on to be leaders in the lab in Singapore with a major focus on HD. INSIGHTS: Why did you make the transition to Teva? HAYDEN: I could only go to a certain point with academic lab work. To develop therapies for HD, I would have to be open to other possibilities. I worked very hard trying to engage pharma. I met with large pharmaceutical companies, informing them about the importance of this disease, but I was not able to convince them to make the investments needed to commit to developing medicines that could possibly change the course of the lives of patients and families. Then I was approached to consider the job of President of Global R&D at Teva. During the recruitment process we discussed my launching a focus on neurodegeneration using HD as the model. I think that HD could inform studies on many forms of neurodegeneration, including Alzheimer's disease. We needed to start somewhere, and the CEO, Jeremy Levin, was willing and enthusiastic to commit to that. And so I joined. My labs continue to do basic research that can feed the pipeline with new ideas. I go back to Vancouver very frequently as well as to Singapore to support that work. The very first acquisition with me at Teva was the purchase of a Phase III asset, the drug Huntexil from Neurosearch. This drug was not going to change the course of HD, but provide symptomatic relief. We are now working to start definitive trials with Huntexil in the next few months. INSIGHTS: What about other approaches for HD? HAYDEN: As president of R&D at Teva, we have a commitment to refocus the pipeline to diseases of the central nervous system, including MS, Parkinson's, Alzheimer's, Pain and, of course, HD. We are hiring people from around the world who know about HD. Teva is a company committed to making a change in the lives of patients with neurodegenerative disorders. INSIGHTS: What do you think are the greatest future opportunities for new treatments for HD? HAYDEN: We believe that the inflammatory pathways are important targets. Inflammation is an early feature of this disease, and it occurs both centrally and peripherally. The neurons may be secondarily involved. Astrocytes and microglia secrete various inflammatory cytokines that could cause damage. We are looking into drugs that influence those pathways. In the end, it is likely that you will need combination therapy for this disease: To retard disease progression and also to protect neurons that are already damaged. In HD, the cellular and biochemical disease process starts very early, and often, by the time you have clinical symptoms, there has already been a lot of damage. INSIGHTS: Dr. Hayden, thank you for your time. Do you have any final thoughts? HAYDEN: HD is now recognized as being present globally. It is present wherever people have migrated, and the burden of the disease is very similar irrespective of politics, irrespective of race, irrespective of borders and boundaries. The impact on people's lives is profound. We have the chance to do something. This is an opportunity to impact the lives of patients not only with HD, but also with other forms of neurodegenerative disease. HD Insights, Vol. 4 Copyright © Huntington Study Group 2013. All rights reserved. 3

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