Dr. Richard Scheller Executive Vice President, Research and Chief Scientific Officer

Welcome.
For more than 30 years, Genentech has been dedicated to rigorous and groundbreaking science. The company's emphasis on strong basic research combined with an applied focus on medical needs has been instrumental to its success and growth. As the head of Genentech's Research department, which includes more than 1,000 scientists and postdocs, I have the unique opportunity and challenge of advancing this impressive tradition.

My goal in setting strategy for the Research department is to strike the optimal balance between basic biomedical research and translational research aimed at developing therapies for unmet medical needs. The company also explicitly fosters individual creativity and initiative among its researchers, encouraging scientists to pursue projects of interest in addition to working toward the company's goals. As a result, our scientists have consistently published important papers in prestigious peer-reviewed journals. In addition, Genentech's scientists have secured approximately 6,900 current, non-expired patents worldwide and have about 6,000 patent applications pending worldwide.

A primary mission of Genentech's research department is to keep the company's product pipeline full. Over the next few years, this entails moving new research projects into development each year, expanding indications and markets for current products, and supporting development projects. We are also committed to expanding the scientific and technological leadership of the company by helping current employees reach their full potential and recruiting exciting new research talent. In an effort to develop young scientists interested in biotechnology, Genentech has a strong postdoctoral program, with fellowships that typically last four years. The primary aim of the program is for Genentech scientists to train postdocs to conduct research of the highest possible quality in scientific areas of interest to the postdoc and the company. Throughout the program, fellows are encouraged to present the progress and results of their work both internally and externally as well as to attend seminars, collaborate with other scientists and, when possible, manage others. Overall, the Genentech postdoc program is designed to create a vibrant and supportive environment for rigorous scientific training.

Founders Research Center

To ensure continued scientific excellence, in October 1992, Genentech opened the Founders Research Center, a 275,000-square-foot facility devoted solely to biotechnology research. It was dedicated to Bob Swanson and Herb Boyer in honor of their pursuit of the promise of biotechnology when they established Genentech in 1976. In April 2001, the company celebrated its 25th anniversary by breaking ground on a 280,000-square-foot expansion of the Founders Research Center. Completed in 2003, the 555,000-square-foot complex houses specialized laboratories and state-of-the-science equipment in several interconnected buildings. In 2007, we opened our southern campus extension that comprises over 230,000 square feet of additional specialized laboratories.

We are intent on providing our researchers with access to the most advanced technologies and biological information necessary to optimize their research productivity. All of our scientists have access to state-of-the-art DNA sequencing, microarray and bioinformatics support as well as a fully integrated mouse genetic engineering facility. In collaborative efforts between various departments at Genentech, these tools are being used in efforts such as the function identification of a large number of genes of interest to our discovery efforts, building better mouse models of human disease or the identification of specific somatic mutations, and copy number changes in the genome of a number of tumor types.

Oncology remains a major focus of Genentech's research organization. Our division of Research Oncology takes a broad and comprehensive approach to the problem of cancer biology and drug discovery. Genentech scientists are leaders in the identification of novel cell surface molecules associated with various cancers such as prostate, lung, colon, liver and brain. These tumor antigens are used to produce sophisticated monoclonal antibodies that selectively target the desired cancer to modulate function, mark cells for destruction by the immune system, or precisely deliver lethal doses of cytotoxic compounds. Genentech scientists have also provided fundamental information on the process of angiogenesis, which has been leveraged into the development of important angiogenic inhibitors such as Avastin. A major scientific effort has developed around this problem leading to the a variety of new basic insights as well as therapeutic opportunities. Research Oncology is also heavily invested in the study of apoptosis, and the production of both biological and small molecule activators of cell death in cancer cells. In signal transduction, Genentech scientists pioneered the development of effective antibody-based therapies to receptor tyrosine kinases such as HER2 in breast cancer. This franchise has been expanded to include a variety of other such signaling receptors, as well as a host of intracellular kinases that are important "drivers" of cancer, using both small molecule and biological inhibitors. Our scientists use these agents not only to develop new therapeutics, but also to unravel the complex signaling pathways that make cancer cells different from their normal counterparts. Major new basic programs in Research Oncology are now also targeting critical aspects of the cell cycle, metabolic regulators, and the immune response to cancer. Cancer stem cells are also rapidly becoming topics of exceptional excitement and opportunity.

Immunology is increasingly becoming an important focus for Genentech Research. Building upon the recent approvals of Xolair® (Omalizumab), a first-in-class monoclonal antibody for the treatment of moderate to severe allergic asthma, Raptiva® (efalizumab) for the treatment of moderate to severe plaque psoriasis, and Rituxan® (Rituximab) for the treatment of anti-TNF resistant rheumatoid arthritis, we continue to expand our understanding of the mechanism(s) by which these therapies modulate immunity and human disease. Combining insights from these clinical trials, coupled with discovery efforts in mechanisms of human disease, genetics of human diseases, and basic biology of the immune system, our scientists focus on discovery of new biologies of innate and adaptive immunity and translate novel discoveries into first-in-class therapies for the treatment of asthma, atopic dermatitis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, organ transplantation, age-related macular degeneration, psoriasis, Crohn's Disease and ulcerative colitis. As modulation of the immune system may also compromise our abilities to combat infections, a deeper understanding of the mechanism(s) of immune dysregulation in human disease and normal immune function will likely provide greater precision by which we can develop safer and more targeted effective therapies. In addition to developing therapies to attenuate immune and inflammatory dysregulation, our scientists also focus on mechanisms to augment and harness the immune response for cancer immunotherapy. This duality of immune functions provides us with opportunities to translate basic scientific paradigms to treat both autoimmune and oncologic indications.

Our third area of focus is disorders of tissue growth and repair. These disorders affect a wide range of organs and tissues, and we have been increasing our activities in this field in recent years. Areas of special interest include macular degeneration, wound healing, neurodegeneration and insulin resistance.

In March 2008, the research organization announced the initiation of early efforts in two new therapeutic areas: neuroscience and infectious disease.

Diseases of the nervous system take a huge toll on the population. With the aging of the population, neurodegenerative disorders like Alzheimer's and Parkinson's disease are on the rise. Cognitive and mood disorders, including schizophrenia and depression, remain enormous unmet medical needs. By discovering and applying fundamental principles related to the biology and diseases of the nervous system, we are developing novel therapeutics for the treatment of neurological and psychiatric disease.

The advent of viral infections, threat of pandemics and accelerating emergence of antibiotic resistance have made clear the enormity of the unmet medical need in infectious diseases. By harnessing the current explosion of new information about the basic biology of pathogens and how the host responds to infection, we are developing novel therapeutics to combat these serious bacterial and viral infections.

The experience, diversity and dedication of our Research organization assures that Genentech will continue to play a significant role in discovering new treatments. I encourage you to browse through this Research section of our website to learn more about individual research areas and to visit often for updated information.

Richard Scheller
Executive Vice President, Research
and Chief Scientific Officer