Changing the Practice of Medicine. The Novartis Institutes for BioMedical Research

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1 Changing the Practice of Medicine The Novartis Institutes for BioMedical Research

2 2 Changing the Practice of Medicine

3 Welcome to the Novartis Institutes for BioMedical Research The Novartis Institutes for BioMedical Research (NIBR) is the global pharmaceutical research organization for Novartis committed to discovering innovative medicines to treat diseases with high unmet medical need. There is no greater privilege than to work toward bettering human health, and no more exciting arena in which to do so than through discovery of new medicines. Mark Fishman President, NIBR With more than 6,000 scientists, physicians and business professionals around the world, we have an open, entrepreneurial and innovative culture that encourages collaboration as we work to push the boundaries of science to change the practice of medicine. Emeryville, CA, USA La Jolla, CA, USA Cambridge, MA, USA East Hanover, NJ, USA Basel, Switzerland Shanghai, China Singapore 3 Changing the Practice of Medicine

4 Focus on the Patient, Follow the Science My disease affects so few people; no one cared to research a treatment until now. Siobhan Walsh, Rare disease patient At the earliest stages of research, our drug discovery priorities are determined by patient need and sound science not the potential market size of a medicine. Rare Diseases Rare disease research is central to our approach. We focus on rare diseases for two reasons, because they affect patients who are in critical need of new medicines and they often have a uniform underlying genetic cause. This allows us to determine quickly whether our medicine will work in patients. Once we know that a medicine is working, we can expand to broader more complex diseases. Currently we have research projects in more than 40 rare diseases across a broad disease spectrum. Diseases of the Developing World NIBR also focuses on diseases of the developing world. Our efforts include tropical infectious diseases, such as malaria, TB, and infectious diarrhea, three of the four top killer diseases in the world s tropical regions. It also includes other wide-spread infectious diseases, such as Dengue Fever, common across the tropical regions, and Chagas Disease, common in Latin America. Our vaccine efforts are centered on typhoid fever that mostly affects children across Africa, Southeast Asia and Latin America. In addition, our portfolio encompasses cancers that disproportionately affect people in the developing world. One example is liver cancer, caused by Hepatitis infections common in Southeast Asia and parts of Africa. 4 Changing the Practice of Medicine

5 Our Approach Pathways to New Medicines One of the great challenges in drug discovery is finding new drug targets (proteins associated with disease) that can be treated by medicines. NIBR meets this challenge by mapping the complex network of signaling pathways in cells. Signaling pathways are the communication highways inside a cell. Like circuitry in a machine, pathways carry important impulses that control all cell functions. Simply put, a breakdown or imbalance at any point along a pathway is the root cause of disease. NIBR investigates how compounds alter pathway function and then connects this information to associated diseases. 1. The interconnected proteins in molecular signaling pathways are responsible for normal cell function. Proof-of-Concept Clinical Trials Scientists and physicians at NIBR have broken down the boundaries between research and clinical practice to collaborate at the earliest stages of the Research & Development process. We believe we can better answer the demand for safer, more effective medicines by keeping our sights on both the science and the patient. To do this we use Proof-of-Concept (PoC) clinical trials small-scale studies in well-defined patient groups to get an early read-out on a drug s safety and effectiveness, and advance the most promising drug candidates. Wherever possible, especially when mechanisms are shared, several diseases are explored in parallel PoC trials. 2. The proteins receive and send molecular signals along a pathway. The signals tell the cell how to function and guide it through its life cycle. Strategic Scientific Alliances Novartis is a global collaborator of choice for biotechnology companies and academic centers seeking to discover and develop drugs for a range of diseases. Through the NIBR Strategic Alliances Group, NIBR has established productive alliances with more than 300 collaborators worldwide. We continue to look for new ways to combine our own scientific knowledge and expertise with that of the broader research community, to find the shortest path to new treatments for disease. 3. When anything goes awry in a pathway, it can cause disease. 4. Novartis hopes to develop drugs that will restore normal pathways function and treat disease. 5 Changing the Practice of Medicine

6 Innovative Research Disease Areas Our commitment to understanding the underlying molecular basis of disease has enabled us to deepen our knowledge, and turn scientific insights into medical breakthroughs. Innovative Research Discovery, Pre-Clinical and Clinical Sciences We bring new technologies to bear on understanding the fundamental science behind both normal and diseaserelated human biology. Autoimmunity, Transplantation, & Inflammatory Disease Rheumatoid arthritis, Multiple sclerosis, transplantation, psoriasis, lupus Analytical Sciences Protein and DNA analysis technologies Cardiovascular & Metabolic Diseases Heart disease, heart failure, hypertension, Type 2 diabetes Biologics Antibody, protein or sirna-based drug development Oncology Many types of cancer Chemistry Designing and creating potential new drugs Infectious Diseases Hepatitis B & C, Staph. aureus infection Developmental and Molecular Pathways Understanding and modulating signal transduction networks involved in disease Musculoskeletal Diseases Osteoporosis, muscle atrophy, sarcopenia Neuroscience Neuropsychiatric and neurodegenerative diseases Friedrich Miescher Institute for Biomedical Research Discovery of basic molecular mechanisms of cells and organisms in health and disease Genomics Institute of the Novartis Research Foundation Contributes new therapeutic targets, technologies and drug discovery Ophthalmology Glaucoma, Macular degeneration Imaging Molecular, cellular and clinical imaging Respiratory Diseases Idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis Metabolism and Pharmacokinetics Predicting how drug leads will behave in the body Proteomic Chemistry Studying the interaction of chemistry and biology 6 Changing the Practice of Medicine

7 Innovative Research Translational Sciences NIBR incorporates clinical medicine into its early stage benchtop drug discovery. Biomarker Development Accelerating drug development by identifying measurable biological factors (biomarkers) that are indicators of disease Developing World Diseases Novartis has large globally integrated programs in neglected diseases with a particular focus on parasitic diseases for which therapy is ineffective or toxic. NITD is dedicated exclusively to developing world disease research. Novartis Institute for Tropical Diseases Tuberculosis, Dengue, Malaria Drug Metabolism and Pharmacokinetics Optimizing the performance of a new drug Preclinical Safety Focusing on drug safety is Priority 1 Translational Medicine Translating biology into medicine Read about our latest research at Our drug discovery priorities are determined by patient need and sound science not the potential market size of a medicine. 7 Changing the Practice of Medicine

8 Innovative Culture Awards and Recognition We are proud to have been recognized by leading business and science publications. Selected recognition includes: Great Place to Work Top 25 World s Best Multinational Workplaces 2015 Fortune s World s Most Admired Companies 2014 Barron s World s Most Respected Companies 2014 the 2013 Scrip Award for Best Advance in an Emerging Market No. 1 ranking in DiversityInc s Top 50 Global Diversity Companies 2014 Thomson Reuters 2014 Top 100 Global Innovators 2014 Global Aon Hewitt Top Companies for Leaders Novartis Postdoctoral Program among The Scientist s Best Places to Work 2013 Innovative drug discovery does not happen in silos. It is driven by networks of scientists working together in teams across disciplines and geographies. Recognizing this, NIBR strives to have a diverse, inclusive and collaborative culture where scientists can tackle the complexity of drug discovery research together. Driven by the urgent needs of patients, and recognizing that no single individual can find cures, NIBR s team-based global drug discovery network embraces the diversity of knowledge, expertise, thinking styles, and identities of our more than 6,000 scientists, clinicians and business professionals. Individuals and teams are empowered to apply their skills and pursue their inspiration in the pursuit of the discovery of new medicines to help patients. At NIBR we are committed to hiring scientists, physicians and business professionals who seek to work in an atmosphere where patients come first and innovation is rewarded. 8 Changing the Practice of Medicine

9 Opportunities for Personal and Professional Growth One of the most valuable benefits of working at NIBR is the opportunity to continuously interact with colleagues across the globe who have very distinct skill sets and specific expertise areas. We provide a myriad of opportunities for individuals to grow professionally through organized training, coaching, and experiences. The Mini-Sabbatical program is an opportunity for ongoing teaching and learning interactions that enhance the sociology of innovation. Associates at NIBR have the opportunity to experience another country or change their job for a few months. The Developing World Sabbatical provides experienced NIBR scientists with mentoring or coaching opportunities with people from the developing world. The Developing World Sabbatical program aims at expanding NIBR scientist s horizon by experiencing new areas of research in a different cultural environment. This program provides the opportunity to increase understanding of medical needs in the developing world and local efforts to address them; and contributes to the scientific capability building in the developing world by helping the community through connections with local hospitals, research institutions, and universities. Our postdoctoral program provides talented scientists with a unique opportunity to perform high-quality research in an environment with the resources of a large pharmaceutical company. Each year, innovative researchers from academia are selected to become fellows and collaborate with leading pharmaceutical discovery scientists pursuing multidisciplinary research projects. Together, they apply their expertise to discovering new medicines that will help patients lead healthier lives. 9 Changing the Practice of Medicine

10 Innovation in Action A Case Study: Discovering the Next Generation of Malaria Drugs According to the World Health Organization (WHO), in 2008 there were approximately 247 million cases of malaria, causing nearly one million deaths, mostly among young children in Africa. Although malaria is preventable and curable, it is estimated that in Africa, a child dies every 45 seconds from the disease. 1 The Novartis Institute for Tropical Diseases (NITD), in collaboration with researchers from the Genomics Institute of the Novartis Research Foundation (GNF), the Swiss Tropical and Public Health Institute and The Scripps Research Institute have discovered a novel compound that shows promise as a next generation treatment for drug resistant malaria. NITD609 is a novel, synthetic antimalarial molecule belonging to the spiroindolone class. Awarded the Medicines for Malaria Venture s Project of the Year 2009, NITD609 is one of only a handful of molecules capable of curing P. berghei a preclinical mouse model of blood-stage malaria. NITD 609 is an investigational drug, which if proven safe, will be the first antimalarial not belonging to either the artemisinin or peroxide class to enter clinical efficacy studies. 1 A Case Study: Inhibiting the Hedgehog Pathway in Cancer A central principle of NIBR strategy is the critical importance of signaling pathways in human biology and disease. A relatively small number of core pathways play fundamental roles during embryonic development as well as later in life. Nature is deeply conservative and these core pathways are used time and again across species. Defects in major pathway components are the underlying cause of disease and provide targets for discovery of innovative therapies. Uncontrolled activation of the hedgehog pathway, discovered as part of a series of pioneering experiments in the 1970s, is known to be involved in cancers including basal cell carcinoma, the most common form of cancer. A key node or protein in the hedgehog pathway is a gene called Patched 1 that acts as a negative control, obstructing signal transduction except when activated by chemical messengers from outside the cell. An inherited mutation in Patched 1 causes a rare genetic disorder called Nevoid Basal Cell Carcinoma syndrome (Gorlin syndrome), in which patients repeatedly develop basal cell cancers. The cancers can be removed surgically but lead to the accumulation of disfiguring scars. Somatic mutations which occur during life, by contrast to inherited mutations can lead to sporadic basal cell cancer. NIBR scientists at the Genomics Institute of the Novartis Research Foundation in La Jolla, California, discovered an investigational compound known as LDE225 that can halt the abnormal signaling. LDE225 works by inhibiting a gene called Smoothened, located downstream from Patched 1 in the hedgehog pathway. LDE225 has been developed into a topical formulation that is applied to the skin at the site of basal cell cancers. A proof-of-concept study for LDE225 in treatment of patients with Gorlin syndrome was declared successful in Changing the Practice of Medicine

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12 Novartis Institutes for BioMedical Research, Inc. 250 Massachusetts Avenue, Cambridge, MA 02139, USA Tel: