NAME: Maurice Zauderer, PhD
CURRENT POSITION: President and CEO, Vaccinex Inc.
EDUCATION: BS, Physics, Yeshiva University, New York, NY; PhD, Cell Biology,
Massachusetts Institute of Technology, Cambridge, MA
HOBBIES: Listening to music (particularly Mozart), and golf
Dr. Maurice Zauderer is the founder, president, and CEO of the privately held biotechnology company Vaccinex Inc., headquartered in Rochester, NY. Vaccinex focuses on the development of new human antibodies to combat a variety of conditions, including multiple sclerosis, cancer, and more recently, HD. Vaccinex’s VX15/2503 monoclonal antibody has recently been evaluated in Phase I trials for safety in multiple sclerosis and solid tumors, and the company has initiated a Phase II study to evaluate the safety, tolerability, and efficacy of VX15/2503 in HD. Dr. Zauderer recently shared his thoughts with HD Insights on VX15/2503 and its potential use in HD. The following is an edited transcript of the conversation.
HD INSIGHTS: Dr. Zauderer, can you describe the mechanism of action of VX15/2503 in HD?
ZAUDERER: VX15/2503 is a monoclonal antibody to semaphorin 4D, which is a member of the semaphorin family of proteins. Semaphorins direct the movement of cells in the body. They play a very important role during embryonic development, where cells move to shape different tissues and organs, and they continue to be important in the adult, because the adult continues to generate a variety of cells that are required to migrate to different locations in the body. For example, immune cells are generated in one location, but they must migrate to the site of an infection. Semaphorins play an important role in guiding that migration, and we have shown that semaphorin 4D plays a particularly important role in guiding the migration of cells that are relevant to neuroinflammatory and neurodegenerative diseases.
Microglia and astrocytes are two important inflammatory cells in the central nervous system that are activated by semaphoring 4D. They are beneficial in an acute situation, but they can both contribute to neurodegenerative processes if they are chronically activated. They produce biological modifier molecules such as cytokines that can cause damage to neural tissue. It is important to be able to regulate their activation and to minimize their effect on these neuroinflammatory and neurodegenerative processes. Vaccinex’s new therapy, VX15/2503, is a humanized antibody that is specific for semaphorin 4D, which it neutralizes, and thereby inhibits chronic activation of microglia and astrocytes and prevents some of the deleterious consequences that are associated with neuroinflammatory and neurodegenerative disease.
HD INSIGHTS: You have studied VX15/2503 for use in multiple sclerosis (MS) and in solid tumors with Phase I trials. Why have you proposed it for use in HD?
ZAUDERER: In both progressive MS and HD, microglia and astrocytes contribute to the slow, but progressive, neurodegenerative process.
HD INSIGHTS: You recently collaborated with Dr. Amber Southwell and colleagues on a study of VX15/2503 in the YAC128 mouse model of HD.1 Can you tell us about that study?
ZAUDERER: That was a very exciting collaboration. The YAC128 mouse model expresses a fully human mutant huntingtin gene that leads to neuroinflammation and neurodegeneration. The mice typically develop HD-like symptoms between six and 12 months of age with a variety of cognitive and behavioral deficits, and with neuropathology such as decreased brain volume. Our goal was to see whether VX15/2503 could prevent the development of these deficits. We tested it as a preventive therapy, by treating YAC128 mice starting at around six weeks of age. It was very gratifying to see that at least in some areas, we saw a marked amelioration of the disease process.
HD INSIGHTS: You also saw some changes on imaging.
ZAUDERER: Yes: for example, we observed reduced loss of brain volume. One characteristic feature of HD is loss of about 10 percent of both white matter and grey matter volume. Incidentally, this is also true in progressive MS. We demonstrated that use of VX15/2503 significantly reduced the loss of brain volume in YAC128 HD transgenic mice.
HD INSIGHTS: You recently launched a Phase II clinical trial of VX15/2503 in HD called SIGNAL. What do you hope to learn from this study?
ZAUDERER: We are enrolling patients who are in the prodromal and early manifest stages of HD. Our goal is to see whether treating patients with VX15/2503 delays or prevents the onset of disease. We actually just enrolled our first patient about a week ago, so it is too early to know. However, we have tested VX15/2503 in about 40 patients at various stages of MS, and it has had a good safety profile to date. We are hopeful that we will continue to have a good safety profile and be able the judge the efficacy of the drug as well in this study. The neuropathology and the behavioral and cognitive symptoms of HD continue to progress after clinical diagnosis. About one-third of the patients we will be working with will be in the early manifest stage of HD, because we want to see whether our VX15/2503 continues to have an impact on disease progression.
HD INSIGHTS: Changing gears, Vaccinex recently announced an agreement with Five Prime Therapeutics. Are there any implications for HD?
ZAUDERER: That was an antibody development agreement. Vaccinex has a novel human antibody selection technology that has been of interest to a number of other companies, including Five Prime Therapeutics, and Janssen Pharmaceuticals. In those relationships we select fully human antibodies against targets of interest to those companies. It is a technology collaboration.
HD INSIGHTS: Before you founded Vaccinex, you were a highly successful academic. Can you describe what motivated the change from academia to private enterprise?
ZAUDERER: I very much enjoyed my academic research career. I was on the faculty at Columbia University, then at the University of Rochester Cancer Center for a total of 25 years before founding Vaccinex. It was a very enjoyable time in my life. As it happened, my laboratory developed some novel technologies that were of commercial interest. I was approached by a group of investors who were very interested in founding a biotechnology company based on those technologies, and I thought this would be an interesting challenge, and indeed it has been. It was an opportunity to do something different in my life.
HD INSIGHTS: Any regrets?
ZAUDERER: No, none at all. On the contrary, it has been a very enriching experience. The qualities you need and that you cultivate as an academic scientist are different from the qualities that you need and cultivate as an entrepreneur. I really feel this has been a growth opportunity for me.
HD INSIGHTS: Can you elaborate on those qualities?
ZAUDERER: In academic life, the most important value is innovation on an individual level; it is the basis for publication, the basis for promotion, and for grants. When you are at a biopharmaceutical company, the process of bringing a product from the laboratory to the clinic is so complicated that you very quickly realize that you cannot possibly do it without a lot of cooperation with other people. So, although innovation continues to be important, cooperation is equally important, and that involves a whole different set of relationships and skills. I feel fortunate to have been put in a situation where I have had to develop and cultivate those skills.
HD INSIGHTS: Do you have any advice for academics who are thinking of making the transition to industry?
ZAUDERER: It is much more challenging than I realized when I first jumped into this. There are numerous organizational, financial, and development challenges. You need a very strong group of supporters in order to be able to do this successfully.
HD INSIGHTS: Dr. Zauderer, thank you very much for your time and good luck with your efforts in HD.