Roche. New York City 7 December 2016

Transcription

1 Roche Andrew C. Chan, M.D. Ph.D. Senior Vice President, Research Biology of Genentech Research and Early Development (gred) New York City 7 December 2016

2 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as believes, expects, anticipates, projects, intends, should, seeks, estimates, future or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website All mentioned trademarks are legally protected. 2

3 Roche s unique strategy Success hinges on excellence in innovation & execution Autonomous innovation centers Worldwide execution Genentech gred Global Product Development Roche pred Chugai Research & Early Development Manufacturing Commercialization Diversity, Creativity, Experimentation Scale, Reach, Delivery Roche Diagnostics: PHC enablement 3

4 gred foundational principles INNOVATIVE DRUG DISCOVERY & DEVELOPMENT INNOVATIVE DRUG DEVELOPMENT Novel drug platforms (e.g., Ab-drug conjugates & Ab-antibiotic conjugates) Biomaker identification of patient subsets for: - Disease progression - Response to therapeutics Exploratory research Post-doc program DEFINING DISEASE PATHOGENESIS & HETEROGENEITY DEFINING DISEASE PATHOGENESIS & HETEROGENEITY Patients HELPING PATIENTS CUTTING EDGE BASIC SCIENCE CUTTING EDGE BASIC SCIENCE PEOPLE PEOPLE 4

5 gred focus areas: Discovering new biologies and applying them broadly Oncology Discover and develop novel therapies and transformative combinations Today s highlights personalized cancer vaccines Immunology Focus on high unmet need indications Neuroscience Focus on neurodegenerative disorders and pain Focus on AMD Ophthalmology Infectious disease Focus on hard-to-treat bacterial and viral infections antibody-antibiotic conjugate 5

6 Activation phase The cancer immunity cycle Oncology meets immunology Priming and activation Trafficking of T cells to tumors anti-ox40 Cancer antigen presentation Personalized Cancer Vaccines (PCV) PCV may overcome potential priming defects in tumor microenvironment to induce T-cell immunity Infiltration of T cells into tumors anti-cd20/cd3 bispecific Effector phase Release of cancer cell antigens Recognition of cancer cells by T cells Killing of cancer cells Tecentriq anti-tigit IDOi Source: Adapted from Chen & Mellman, Immunity,

7 Promise Personalized for an cancer indivdualized vaccine vaccine: to induce immunization T-cell immunity with predicted Overcoming neo-epitope potential peptides priming regresses defects in MC-38 the tumor tumors MC38 tumor inoculation Immunization n=10 C57/Bl6 Day -10 Day 0 Day 30 Mutated neo-antigens are drivers of immune response against cancer Tumor growth Control Adjuvant Adjuvant + NeoAg Peptides Tumor volume mm 3 4 CRs 8 CRs Days post-immunization Adjuvant: anti-cd40 + Poly I:C Source: Yadav et al, Nature,

8 Personalized cancer vaccine to induce T-cell immunity Overcoming potential priming defects in the tumor In September 2016, Genentech and BioNTech entered into a worldwide strategic collaboration to develop, manufacture and commercialize novel messenger RNA (mrna) based personalized cancer vaccines (PCVs). Mutated neo-antigens are drivers of immune response against cancer PCVs use a patient s unique neo-antigens to induce an anti-tumor immune response personalized cancer vaccines Clinical update A Phase 1 combination trial of PCVs with Tecentriq in a variety of cancer types is expected to be initiated in the near future. 8

9 Methicillin resistant staphylococcus aureus (MRSA) A significant challenge due to multidrug-resistance Major cause of severe hospital-acquired infections: - Most common cause of antibiotic resistant infections - 370,000 hospitalized MRSA patients/yr (US) - Community-acquired MRSA (CA-MRSA) infections are on the rise 90,000 cases (US) of invasive infections with 20-30% mortality despite antibiotic treatments, even with antibiotics to which the organisms are susceptible in vitro Diseases range from wound and soft tissue infections to more serious endocarditis, osteomyelitis, fatal necrotizing pneumonia, and sepsis Most recent MRSA antibiotics, daptomycin and linezolid, have significant adverse event profiles and failure rates of ~50% 9

10 Intracellular MRSA in many human cell types Intracellular residence may provide a sanctuary for MRSA Epithelial cells (Upper respiratory tract) Epithelial cells (Lower respiratory tract) Myofibroblasts CD45 + leukocyte Epithelial cells Endothelial cell PMN (Phagosome) PMN (Cytoplasm) Sources: Menzies & Kourteva, Infection and Immunity 1998; Sophie Clement et al, JID 2005; Gresham et al, JI

11 Therapeutic hypothesis for AAC A novel therapeutic to effectively kill intracellular MRSA MRSA MRSA Increase local concentration of antibiotics in phagolysosomes Efficient killing of MRSA by release of antibiotics by lysosomal proteases MC-VC-PAB-Cl Rifalog Linker phagolysosomal protease cleavage Antibiotic AAC 1 bystander killing 3 kill escapees 2 Prevents recurrent infections AAC = antibody-antibiotic conjugate 11

12 CFU/2 Kidneys AAC superiority over vancomycin MRSA (USA300) 2 x 10 7 CFU AAC (50 mg/kg x 1) Vancomycin (100 mg/kg BID) Harvest Day 0 Day 1 Day 2 Day 3 Day * ** * * p < 0.05 **p < First-in-class First-in-industry Phase 1b study ongoing Lower Limit of Detection Ab alone Vancomycin AAC AAC = antibody-antibiotic conjugate Source: Lehar et al, Nature

13 gred foundational principles INNOVATIVE DRUG DISCOVERY & DEVELOPMENT INNOVATIVE DRUG DEVELOPMENT DEFINING DISEASE PATHOGENESIS & HETEROGENEITY DEFINING DISEASE PATHOGENESIS & HETEROGENEITY Patients HELPING PATIENTS CUTTING EDGE BASIC SCIENCE CUTTING EDGE BASIC SCIENCE PEOPLE PEOPLE 13

14 Thank you

15 Doing now what patients need next