Roche Holding Ltd · SIX:RO
Roche — Bank of America 2021 Healthcare Conference
42 slides from Roche's conference presentation, May 2021
Slide 1: Transformative approaches for target discovery, drug discovery and development
Transformative approaches for target discovery, drug discovery and development Aviv Regev | Head, Genentech Research and Early Development May 2021
Slide 2: Executive summary
Executive summary • Genentech and Roche are innovation companies • Drill-deep science delivers breakthrough and transformative medicines • Substantial innovation-focused investment fuels growth • Robust portfolio and leadership in key areas • Continued oncology leadership: molecular and immuno-oncol
Slide 3: Genentech Research and Early Development (gRED): Independent R&D and innovation driver within Roche
Genentech Research and Early Development (gRED): Independent R&D and innovation driver within Roche Autonomous modular innovation centers Worldwide execution Global Product Development gRED pRED Research Manufacturing and Chugai Spark Early Development Commercialization Diversity * Creativity * Expe
Slide 4: Portfolio, platforms and talent to achieve ambition
Portfolio, platforms and talent to achieve ambition I. Portfolio II. Platforms III. Talent
Slide 5: Portfolio focus: Key areas driven by scientific opportunity and expertise
Portfolio focus: Key areas driven by scientific opportunity and expertise Oncology Immunology Neuroscience Ophthalmology Infectious diseases Follow the science
Slide 6: Robust gRED portfolio across therapeutic areas
Robust gRED portfolio across therapeutic areas Phase 1 Phase 2 Phase 3 *Anti-BCMA/CD16a *Autogene cevumeran (iNeST) *ipatasertib Anti-HER2/CD3 TDB Anti-tryptase (RG6173) mosunetuzumab *belvarafenib Partnered efmarodocokin alfa inavolisib Breakthrough cevostamab (Anti- (IL22-Fc) programs in FcRH5/CD3
Slide 7: gRED's next-generation immuno-oncology pipeline targets different recognition and action steps
gRED’s next-generation immuno-oncology pipeline targets different recognition and action steps, to affect every tumor category Impact immune Impact immune deserts tumors excluded tumors • Mosunetuzumab • Avastin • Anti-HER2/CD3 • Other NMEs • Cevostamab • Anti-BCMA/CD16a Impact inflamed • MAGEA4 Imm
Slide 8: Multiple modalities and approaches to leverage T cell immunotherapy
Multiple modalities and approaches to leverage T cell immunotherapy Monoclonal Bispecific Neoantigen NeoT Cytokines antibodies antibodies vaccines cell therapy
Slide 9: Tiragolumab (anti TIGIT): First-in-class opportunity stemming from Genentech discoveries
Tiragolumab (anti TIGIT): First-in-class opportunity stemming from Genentech discoveries Model for TIGIT regulation of T cell responses • TIGIT: An immune cell inhibitory receptor, discovered at Genentech • Expressed on multiple immune cell types, including CD8+ T cell (effector memory), CD4+ T cell
Slide 10: Tiragolumab + Tecentriq in 1L NSCLC: Meaningful efficacy improvement and excellent safety
Tiragolumab + Tecentriq in 1L NSCLC: Meaningful efficacy improvement and excellent safety Overall response rate (ORR): PD-L1 TPS ≥ 50% Progression free survival (PFS): PD-L1 TPS ≥ 50% • Tiragolumab + Tecentriq showed clinically meaningful improvement in ORR and PFS in the PD-L1 TPS ≥ 50% subgroup •
Slide 11: Portfolio: bispecific antibodies
Portfolio: bispecific antibodies Mosunetuzumab Cevostamab Anti-CD20/CD3 Anti-FcRH5/CD3 Anti-BCMA/CD16A Anti-HER2/CD3 BCMA: B cell maturation antigen
Slide 12: Mosunetuzumab (anti-CD20-CD3 bispecific): Potential to be first-in-class CD20xCD3 in NHL
Mosunetuzumab (anti-CD20-CD3 bispecific): Potential to be first-in-class CD20xCD3 in NHL High response rates across high-risk subsets • High and durable responses across high-risk subsets in R/R FL • Favorable safety profile for outpatient setting with low CRS rates • Potential to further improve sa
Slide 13: Cevostamab monotherapy demonstrates promising activity in heavily pretreated R/R multiple myeloma patients
_ Cevostamab monotherapy demonstrates promising activity in heavily pretreated R/R multiple myeloma patients Cevostamab Ph 1 dose escalation in relapsed/refractory multiple myeloma Overall response rate • Responses seen in penta-drug refractory pts (7/17, ORR:41%) and patients with prior BCMA (5/8,
Slide 14: Cancer vaccines and NeoT cell therapy target tumors through neoantigens
Cancer vaccines and NeoT cell therapy target tumors through neoantigens Neoantigen NeoT vaccines cell therapy
Slide 15: Autogene cevumeran, individualized neoantigen mRNA vaccine
Autogene cevumeran, individualized neoantigen mRNA vaccine • Fully individualized vaccine: mRNA vectors provide patient specific therapy • Novel algorithms predict neoantigens recognized by T cells • On demand-production (highly iterated and reproducible with low failure rate) In collaboration with
Slide 16: DNA vaccine with distinct mechanism to activate immune response
DNA vaccine with distinct mechanism to activate immune response In collaboration with Ph1 showed neoantigen-specific T cell responses in patients (SITC 2019)
Slide 17: NeoT: Personalized T cell therapy directed at neoantigens
NeoT: Personalized T cell therapy directed at neoantigens In collaboration with TCR: T cell receptor, HLA: human leukocyte antigen; PBL: peripheral blood leukocytes
Slide 18: Ras-MAPK pathway in cancer: Drugging "undruggable" targets; opening new combinations
Ras-MAPK pathway in cancer: Drugging “undruggable” targets; opening new combinations gRED portfolio Late stage portfolio/marketed Due to pathway cross-talk and feedback mechanisms, combination strategies are often required for optimal clinical effectiveness and to tackle resistance
Slide 19: Lung inflammation and fibrosis
Lung inflammation and fibrosis Asthma, COPD, & CF IPF, SSc-ILD, ARDS, and COVID-19 • Define molecular subtypes; relevance to clinical phenotypes • Pipeline targets in each of the main pathogenic mechanisms COPD: chronic obstructive pulmonary disease, CF: cystic fibrosis; IPF: idiopathic pulmonary fi
Slide 20: Portfolio, platforms and talent to achieve ambition
Portfolio, platforms and talent to achieve ambition I. Portfolio II. Platforms III. Talent
Slide 21: >100,000 places in the genome already associated with disease: How to proceed?
>100,000 places in the genome already associated with disease: How to proceed? Disease associated regions: 2005-2019
Slide 22: Challenge: Linear scaling will not suffice to change medicine
Challenge Challenge: Linear scaling will not suffice to change medicine Correctly link Targets Differences Evidence of Disease heterogeneity Endpoints and targets to disease increasingly between humans Target Complex predictive reproducibility Poor animal harder to drug and preclinical engagement bi
Slide 23: Opportunity: transformative platforms to enhance R&D
Opportunity: transformative platforms to enhance R&D
Slide 24: Human biology and high resolution, massive scale methods
Human biology and high resolution, massive scale methods Novel disease pathways Human biology and High resolution Massive scale faithful models Single cell profiles Genetic perturbations Oncogene coding variants classes Human genetics/genomics (Incl. high order interactions) Cell therapy states Orga
Slide 25: Three new integrated platform components
Three new integrated platform components
Slide 26: Rich data provide a "refined vocabulary of disease"
Rich data provide a “refined vocabulary of disease” Where do disease risk Which cells are Which cell programs are genes act? disrupted? changed? Healthy Cond #1 Cond #2 Programs Genes Cells Cells What are their Which communications What is the effect of functions & modules? are disrupted? drug? Gene
Slide 27: Relating gene, cell, program, and disease
Relating gene, cell, program, and disease 1.6 million cell profiles of 209 individuals, 11 tissue types, 6 disease conditions; 60 disease and complex traits across 297,000 individuals (on average) Disease Cell type Gene Delorey et al., Nature 2021, Jagadeesh et al Biorxiv 2021
Slide 28: Advances in computer science and math make the bigness of biology a new advantage
Advances in computer science and math make the bigness of biology, chemistry and medicine a new advantage Representation Prediction Generation / intervention Molecules Users Properties Movies 1 Potential breakthrough goal: be predictive and explanatory (mechanistic) in biology, chemistry, and medici
Slide 29: Algorithms example: Find antibody that targets a gene
Algorithms example: Find antibody that targets a gene PREDICTIVE GENERATIVE INTERPRETABLE Input Gene and Ab sequence Gene sequence Gene and Ab sequence Output Does antibody bind protein? Sequence of Ab that binds Why Ab binds (or not)? What experimental platforms, procedures, data, and algorithms do
Slide 30: Specific development problems are particularly ripe
Specific development problems are particularly ripe Integrated biomarkers Protocols and clinical trial data Clinical site selection
Slide 31: Investment across four areas of advanced computation
Investment across four areas of advanced computation Algorithms Analytics Data platforms / IT/DevOps Partnership with Roche
Slide 32: Building a full computational pillar for R&D
Building a full computational pillar for R&D Design principles • Balance critical mass with domain embedding • Hub focused on advanced computation • Hub lead to be an LT member, and responsible for one spoke Investment in leadership & talent • Recruitment of new SVP Computation • Additional leaders
Slide 33: Substantially expanded modalities portfolio
Substantially expanded modalities portfolio Antibody-based Modified cytokines ASOs Peptides Small molecule based Cancer vaccines Cell therapy Gene therapy/AAVs Both in-house builds, and expansion and exploration through partnerships
Slide 34: Portfolio, platforms and talent to achieve ambition
Portfolio, platforms and talent to achieve ambition I. Portfolio II. Platforms III. Talent
Slide 35: Our opportunities grow as part of an ecosystem
Our opportunities grow as part of an ecosystem gRED gRED CURRENT CURRENT STRENGTHS STRENGTHS DISCOVERY DISCOVERY COMPUTATION ROCHE && & TRANSLATION TRANSLATION PREDICTION PLATFORM PLATFORM PLATFORM PARTNERING
Slide 36: gRED Leadership Team
gRED LeadershipTeam Andrew C. Chan Wendy Young Lilli Petruzzelli Sara Kenkare-Mitra TBA MD, PhD PhD MD, PhD PhD PhD Sr. Vice President, Sr. Vice President, Sr. Vice President, Sr. Vice President, Sr. Vice President, Research Biology Small Molecule Early Clinical Development Sciences Advanced Drug Di
Slide 37: Enhanced approaches to talent recruitment, development and retention
Enhanced approaches to talent recruitment, development and retention Proactive Leader as recruiter: identifies, networks, nurtures and pursues individuals in key recruitment areas both for current roles and prospectively Sponsorship Develop key talent at all levels of gRED through sponsorship to enh
Slide 38: Partnerships expands our talent pool, internally and externally
Partnerships expands our talent pool, internally and externally Thematic Umbrella “Early-early” “Big-big” “Budding” networks collaboration partnerships partnerships partnership
Slide 39: Our science and people make us the partner of choice for outside innovation
Our science and people make us the partner of choice for outside innovation 2019-2021
Slide 40: Future of Working in gRED
Future of Working in gRED New approaches to flexible, interactive working in gRED and Genentech
Slide 41: Portfolio, platforms and talent to achieve ambition
Portfolio, platforms and talent to achieve ambition I. Portfolio II. Platform III. Talent
Slide 42: Executive summary
Executive summary • Genentech and Roche are innovation companies • Drill-deep science delivers breakthrough and transformative medicines • Substantial innovation-focused investment fuels growth • Robust portfolio and leadership in key areas • Continued oncology leadership: molecular and immuno-oncol
Roche Holding — Bank of America 2021 Healthcare Conference on 6ix