Evotec Se · XETR:EVT
Evotec — Investor Day (November 2023)
120 slides from Evotec's investor day presentation, Nov 15, 2023
Slide 1: Welcome to Evotec
Welcome to Evotec “Manfred Eigen Campus” in Hamburg Evotec SE, Capital Markets Day
Slide 2: Welcome to Hamburg!
Welcome to Hamburg! Evotec SE Headquarter The roots The people The focus The future A red cube? 2012: 185 employees CNS diseases PanOmics Site acquired from Eli Lilly in 2012 2023: 760 employees iPSCs The Lighthouse of iPSCs PAGE 2
Slide 3: Our home base is growing further
Our home base is growing further Footprint of Manfred Eigen Campus MEC II MEC I MEC IV MEC III PAGE 3
Slide 4: The iPSC Lighthouse, coming in 2025
The iPSC Lighthouse, coming in 2025 Manfred Eigen Campus IV PAGE 4
Slide 5: Global collaborative model for highest efficiency and precision
Global collaborative model for highest efficiency and precision Platforms & technologies and network for higher probabilities of success (PoS) Hamburg (GER – HQ) You are here Manfred Eigen Campus – A major hub for integrated drug discovery including variety of HTS screening activities; home of neuro
Slide 6: Your hosts today
Your hosts today Claudia Karnbach Werner Lanthaler Cord Dohrmann Bhushan Bonde Sandra Lubitz EVP CEO CSO Group Leader SVP Global Head of Strategic In silico R&D Stem Cell Biology Partnerships and Alliances, Site Head Evotec SE Hamburg Christiane Honisch Olivier Radresa Andreas Scheel Christine Günth
Slide 7: Shaping new Markets
Shaping new Markets From disease understanding to pipeline building Evotec SE, Capital Markets Day, Hamburg, 15 November 2023
Slide 8: Agenda
Agenda 9:00-9:30 Shaping (new) markets 9:30-11:00 PanOmics – From patients for patients • Better disease understanding & diagnostics • Advanced disease modelling • A.I. use cases along the value chain 11:00-11:15 Coffee Break 11:15-12:15 Impactful therapies • Integrated platform • Diabetes • Oncolog
Slide 9: Creating the future will work #together
Creating the future will work #together Our contribution to the industry „The goal of Evolution is not one single human, it is mankind.“ Manfred Eigen (1927–2019) Co-founder of Evotec, Nobel Prize 1967 PAGE 9
Slide 10: Accelerating medicines that matter
Accelerating medicines that matter About us 4,000++ scientists empowering Co-creating pipelines Partners Leveraging our assets, targets or proprietary platforms for licensing, co- Across all disciplines and disease areas from development or potential NewCo creation, frequently combining with target
Slide 11: "Just the beginning" of best days in medicine
“Just the beginning” of best days in medicine Health Access and Quality (HAQ) index analysis Access to innovative medicine remains a severe unmet need1,2 • High-burden diseases in higher-income countries represent 23% of global disease burden • High-burden diseases in low and middle- income countrie
Slide 12: Precise and effective drugs will find markets
Precise and effective drugs will find markets Unmet need analysis – DALY Burden versus industry pipelines 600 m Underfunded • Demand for differentiation with 500 m innovation is expanding Infectious diseases • Revolving change 400 m Cardiovascular between the industry’s DALY Burden priorities and R&
Slide 13: Big innovation is happening, but next challenges around the corner
Big innovation is happening, but next challenges around the corner Case study: Obesity Illustrative calculation U.S. Obesity Annual price of new Prevalence1 GLP-1 medication2 140 million ~15,000 USD Estimated total annual costs to health system2 1.5-2 Trillion USD ~10% of entire US economy PAGE 13 1
Slide 14: Reverting IRR by bringing Probabilities of Success up
Reverting IRR1 by bringing Probabilities of Success (PoS) up R&D productivity (illustrative) R&D productivity has not recovered, yet • Higher spent with lower Internal Rate of Return peak sales leads to deteriorating IRR1 • IRA2 is “new” reality Average R&D costs per NME +500% • In 2023, average ret
Slide 15: Together for medicines that matter
Together for medicines that matter Game changers within business to business / partnered R&D and pipeline building Better pipeline building Need for more precision Right indication, right patients, right dose Most drugs still provide benefit in only 50% of patients Technology convergence Need for be
Slide 16: The biopharma innovation toolbox has never been richer
The biopharma innovation toolbox has never been richer Illustrative examples Evolvement of targeted Multi-omics mRNA vaccine protein degradation gaining momentum technology used Discovery First use of CRISPR First gene therapy with iPSCs nucleases in gene editing trials launched Completion of the Ce
Slide 17: Let's talk about modality agnostic pipeline building
Let’s talk about modality agnostic pipeline building Our focus for today Our focus areas PanOmics1 iPSC cell therapy Just – Evotec Biologics End-to-End Shared R&D PAGE 17
Slide 18: We follow science, and open massive new opportunities
We follow science, and open massive new opportunities Selected scientific giants From bone marrow From discovery transplants to induced of antibodies to pluripotent stem cells From DNA to RNA to Proteins – “PanOmics” biologics George Mathé Leroy Hood Walter Gilbert Paul Berg Emil von Behring Shinya
Slide 19: New technologies leading to new opportunities
New technologies leading to new opportunities Shaping (new) markets End-to-End shared R&D PanOmics iPSC cell therapy Biologics CAGR CAGR 29% 12% CAGR 30 16 21% 1,600 80 25 2x 12 1,200 60 20 in USDbn in USDbn in USDbn in USDbn 15 8 800 40 10 4 400 20 5 0 0 0 0 2022 2030 2022 2030 2022 2030 2022 2030
Slide 20: Broadest set of value adding capabilities
Broadest set of value adding capabilities Unique integrated offering A.I.-driven Biotech iPSC DD service CROs Evotec-relevant Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company capabilities A B C D E F G H I A B C D A B C E
Slide 21: PanOmics is a massive opportunity
PanOmics is a massive opportunity Addressable market analysis Addressable market Market distribution and growth Revenues (in USD bn) by application – 2030 21% Transcriptomics 25 15% Addressable Genomics market growth 21 >20% excl. genomics 40% 17 25% 14 12 10 Proteomics 8 20% 7 6 Metabolomics • Geno
Slide 22: Fully integrated offering to secure data integrity
Fully integrated offering to secure data integrity Simplified competitive landscape analysis A.I.-driven multi- A.I.-driven discovery iPSC-driven Proteomics data Transcriptomics omics discovery with MPD access drug discovery generation data generation 1 … others … others … others … others … others P
Slide 23: From humans for humans
From humans for humans iPSC-based drug discovery and off-the-shelf cell therapy E.iPSC – Patient or healthy donor iPSC-based Human disease off-the-shelf relevant modelling therapeutics Disease-specific drugs Off-the-shelf cell therapeutics iPSC platform "Disease in a dish" & screening iPSC-derived c
Slide 24: iPSC market growth will be driven by clinical and commercial validation
iPSC market growth will be driven by clinical and commercial validation Addressable market analysis Addressable market Heterogeneous mix of service and (in USD m) Linear forecast product players – no other integrated offering for partnered pipeline building 3,000 iPSC poised to start eating into the
Slide 25: Providing cost efficient access for biologics is our North Star
Providing cost efficient access for biologics is our “North Star” Limited access to biologics exists today in many patient segments 70% 6 bn 7,000 higher prices for without access to biologics underserved rare antibodies vs. small based on geography indications that could be molecules in the US alon
Slide 26: Continuous manufacturing is the paradigm shift shaping the market
Continuous manufacturing is the paradigm shift shaping the market Market size and growth Biologics discovery + manufacturing market Market shares by Revenues (in USD bn) Therapeutic Areas 2022 12% Other Biologics CDMO market is ex- pected to grow at a faster rate1 ~80 17% Oncology due increased adop
Slide 27: We have a fully integrated offering
We have a fully integrated offering Key competitor analysis Discovery & Development & Integrated Offering Discovery Development Manufacturing of varying level … others … others … others PAGE 27 AI: Artificial Intelligence; ML: Machine Learning; MPD: Molecular Patient database; Target ID: Target Iden
Slide 28: Our continuous platform will even further excel with complex biologics
Our continuous platform will even further excel with complex biologics Trends in global biologics pipelines Size of global pipeline by therapeutic modality Share of complex Number of products1, from Phase I to III biologics in the pipeline 4,000 3,000 >40% Share of complex / unstable biologics rapid
Slide 29: Just – Evotec Biologics is building markets faster than expected
Just – Evotec Biologics is building markets faster than expected Key achievements 2021-2023 Closed Sales Key progress in € m >850 Up to US$ 640 m for development work plus massive upside Anti-Plague mAb develop- ment programme initiated >8x Development programme for Orthopoxvirus mAb candidates 3x >
Slide 30: Redmond is online – Toulouse ready to start in 2024
Redmond is online – Toulouse ready to start in 2024 Progression on track J.POD – commercial biologics manu- facturing site in Toulouse stepping up • Ground-breaking for second biologics facility J.POD Toulouse in September 2022 • Building of shell and installation of PODs completed – on track for co
Slide 31: Paradigm-shifting platforms are key growth drivers
Paradigm-shifting platforms are key growth drivers Revenue distribution 2015 versus 9M 2023 FY 2015 9M 2023 Revenue CAGRs2015 - 9M 2023 € 127.7 m € 580.1 m outpacing base business • PanOmics ~50% 8% • € 76.5 m incremental 9% 29% 0% contribution from Just – Evotec Biologics since 2019 52% • EVT Innov
Slide 32: … and a key contributor to acceleration of milestones
… and a key contributor to acceleration of milestones Mid-term adj. EBITDA bridge 2022 2025 aspiration Well-balanced cascade € ~300 m • Income from Milestones, Omics & Upfronts, Licenses ex- iPSC driven panding due to increasing € ~60 m breadth and depth of PanOmics-based pipeline € ~170 m € ~70 m •
Slide 33: Action Plan 2025 on track
Action Plan 2025 on track Action Plans in numbers 2021 2018 2012 2009 Action Plan 2025 Action Plan 2022 Leadership in data, science, Action Plan 2016 Aspire global leadership Action Plan 2012 Build innovation seeds multimodality & access Restructure for growth 2010 2015 2020 2025 • Revenues: € 55 m
Slide 34: Agenda
Agenda 9:00-9:30 Shaping (new) markets 9:30-11:00 PanOmics – From patients for patients • Better disease understanding & diagnostics • Advanced disease modelling • A.I. use cases along the value chain 11:00-11:15 Coffee Break 11:15-12:15 Impactful therapies • Integrated platform • Diabetes • Oncolog
Slide 35: R&D productivity remains the grand challenge for big pharma
R&D productivity remains the grand challenge for big pharma Record spending does not translate into R&D output – selected KPIs $ 138 bn <2% ~44% R&D Spending of Clinical pipeline Pharma companies with “Top 15 Pharma” in 20221 growth2 negative R&D productivity3 $ 6.16 bn R&D expenditure per new drug4
Slide 36: Increasing the probability of success is key
Increasing the probability of success is key Attrition rates have not improved – selected KPIs ~95% >93% >32% False discovery rate Clinical attrition up Post-market safety events in the pre-clinic1 to market launch2 of FDA-approved drugs3 0.78 Annual drug launches per “Big Pharma”4 PAGE 36 1 Hingora
Slide 37: Probability of success on the decline in most indications
Probability of success on the decline in most indications Overall composite clinical success rate for all indications at 6% in 2022 Probability of success Overall clinical success rates success rate = number that advanced to next in % phase/total number advanced & suspended 72% 19 2021 2022 54% 14 1
Slide 38: Omics data is a key driver of the precision medicine megatrend
Omics data is a key driver of the precision medicine megatrend Published Omics data Exponential Omics data generation 250 Genomics1 • Published Omics data keeps Transcriptomics2 accumulating at an exponential rate Proteomics3 PanOmics Trendline 200 • Between 2019 and 2022 as much Omics data was publ
Slide 39: A precision medicine platform is driven by PanOmics
A precision medicine platform is driven by PanOmics Leading A.I./M.L. driven drug discovery & development platforms Molecular patient Patient derived disease models Patient stratification databases & precision medicine approaches and biomarkers Re-defining health and Focus on Precision diagnostics a
Slide 40: R&D investments generate highly strategic partnerships with upside
R&D investments generate highly strategic partnerships with upside ~40% average annual revenue growth since 2015 Total R&D costs since 2010 About € 2.5 m invested per partnered project. € ~450 m Break-even well before entrance in clinical trials. >40 Total number of pharma deals / partnered product
Slide 41: Using human derived disease models as real paradigm shift
Using human derived disease models as real paradigm shift Neurodegeneration alliance with BMS Broadened and deepened strategic alliance in neurodegeneration • Extension and expansion for 8 more years • Collaboration leverages Evotec’s iPSC disease modelling capabilities in the field of neurodegenera
Slide 42: Largest deal in one of the most competitive fields in the industry
Largest deal in one of the most competitive fields in the industry Targeted protein degradation alliance with BMS Developing a pipeline of breakthrough therapies based on molecular glue degraders • 8-year extension and significant expansion of original agreement signed in 2018 • Collaboration levera
Slide 43: Industrialised PanOmics approach towards molecular disease insights
Industrialised PanOmics approach towards molecular disease insights Overview of PanOmics-driven drug discovery A.I.-empowered disease models to analyze treatment impact on disease Hit Lead Pre-clinical Clinical Sourcing novel ideas Target ID / validation Approval Market identification optimisation d
Slide 44: Pipeline building starts with better disease understanding – E.MPD
Pipeline building starts with better disease understanding – E.MPD PAGE 44
Slide 45: First in class discovery starts with patient data
First in class discovery starts with patient data Portfolio of Evotec Molecular Patient Databases (E.MPD) E.MPD Now Next steps Therapeutic Area Patients In progress Patients Acute Kidney Injury Chronic Kidney 950 12,000 (AKI) Diseases (CKD) Obesity TBD Immune Mediated 3,000 Diseases Immune, Oncology
Slide 46: Significant advantages of E.MPD over public domain datasets
Significant advantages of E.MPD over public domain datasets Standard technology, data QC and rich data annotations to improve outcomes Public Domain Cohort Physician engagement planning/design Prospective and longitudinal studies Sample ID linked to source data (e.g. hospital) Sample tracking (batch
Slide 47: Re-defining patients' health and disease
Re-defining patients’ health and disease E.MPD, PanOmics and disruptive computational technologies increase disease insight Thousands Billions of Modality agnostic Develop PanOmics & PanHunter & EVOgnostic 1st in class of samples data points analysis treatments EVOgnostic Patient cohorts Clinical da
Slide 48: Transformative outcomes leading to new alliances
Transformative outcomes leading to new alliances 3 Parallel value-chains to maximize "return on investment" for our partners Our Partners PanOmics & E.MPD Discovery today • Shared vision on PanOmics & Molecular Patient Partnered Discovery Databases Internal R&D EVOgnostic & Pipeline Pipeline Disease
Slide 49: 7 partnering deals alone in Kidney Diseases
7 partnering deals alone in Kidney Diseases Value creation with limited investments 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 Typical terms • Upfront: € 1.5 – 6 m • Milestones: € 100 to 280 m • Royalties: 2 to 10% PAGE 49 UoB: University of Bristol; QUOD: Quality in organ donation; Neph
Slide 50: E.MPD expansion creates new opportunities
E.MPD expansion creates new opportunities PanOmics-driven molecular disease understanding benefits all key therapeutic areas • Unmet medical needs in Kidney diseases, acute & chronic • Prospective longitudinal studies • Pre-disease / early-stage disease cohorts Kidney diseases • Access to Liver fibr
Slide 51: Internal R&D pipeline for developments TOGETHER with partners
Internal R&D pipeline for developments TOGETHER with partners An innovative portfolio complementing current kidney diseases Standards of Care A portfolio with a clear value proposition ... … grounded in high-quality science • Focus on biological mechanisms not targeted by standard-of-cares (eg • Tar
Slide 52: Pipeline delivers first clinical candidates – more to come
Pipeline delivers first clinical candidates – more to come > 25 active programs due to deliver MS payments in mid-to-short term Stage Source Target validation Hit ID H2L LO IND Clinical Dev Bayer partnership 1 Phase 1 started Internal R&D 1 Internal R&D 2 21 New partnership 1 32 1 New partnership 2
Slide 53: PanOmics & E.MPD driven Discovery publicly recognized by peers
PanOmics & E.MPD driven Discovery publicly recognized by peers “The Future is Now" “A Systems Nephrology Framework for the Molecular Classification of Chronic Kidney Diseases” • Oral presentation at the 59th ERA Congress in Paris (May 20, 2022) • 5 more communications at the American Society for Nep
Slide 54: Better pipeline building needs better patient stratification – EVOgnostics
Better pipeline building needs better patient stratification – EVOgnostics PAGE 54
Slide 55: Identification of disease markers leading to new alliances
Identification of disease markers leading to new alliances The EVOgnostic value chain PanOmics & E.MPD Discovery now Our Partners • Shared vision on PanOmics & Molecular Patient Databases EVOgnostic & Internal R&D Partnered Discovery Disease markers Pipeline Pipeline • Shared vision on clinical deve
Slide 56: PanOmics driven diagnostics from target identification to the clinic
PanOmics driven diagnostics1 from target identification to the clinic Capabilities for accurate patient stratification driving personalised drug discovery Diagnostic Panels Patient Stratification and (EVOgnostic Disease Focus) Biomarker Discovery (EVOgnostic Tools) Partnered Laboratory Evotec Molecu
Slide 57: Understanding complex diseases requires better diagnostics
Understanding complex diseases requires better diagnostics Autoimmune diseases with connective tissue involvement (CTD) Heterogeneous disease populations with similar disease specific drivers and immune mechanisms Rheumatoid Systemic Lupus Sjögren’s ANCA Arthritis Erythematosus (SLE) syndrome Vascul
Slide 58: PanOmics driven diagnostics to improve treatment selection
PanOmics driven diagnostics1 to improve treatment selection Case Study 1*: Understanding complex autoimmune diseases - Vasculitis • Chest pain2, malaise and anorexia • Elevated creatinine levels • Suspected to have pneumonia • Persisting symptoms for several weeks Diagnostics Treatments Physical exa
Slide 59: PanOmics-driven diagnostics to improve treatment selection
PanOmics-driven diagnostics to improve treatment selection PanOmics combined with ML to improve diagnosis and treatment EVOgnostic Kidney Health-to-disease map High resolution of a blood sample One blood sample Patient stratification based on machine learning down to individual blood cells per patie
Slide 60: PanOmics driven prognosis for better disease management
PanOmics driven prognosis for better disease management Case study 2*: Understanding complex autoimmune diseases – Systemic Lupus Erythematosus (SLE) • Unrelenting fatigue, weakened immunity • Often multi-year journey before SLE diagnosis • Potential of kidney inflammation and failure / Organ transp
Slide 61: PanOmics driven prognosis for better disease management
PanOmics driven prognosis for better disease management PanOmics combined with ML to monitor disease activity, improve prognosis and treatment SLE disease activity index (SLEDAI) EVOgnostic disease score reflects disease flares EVOgnostic SLE Health-to-Disease Map Today a weighted diagnostic metric
Slide 62: Multiple opportunities …just at the beginning
Multiple opportunities …just at the beginning Health-to-Disease Maps and biomarker discovery Patient cohorts PanOmics and ML Patient Stratification Evotec Opportunities Health-to-Disease Map EVOgnostic - Evotec's panOmics driven diagnostics is a comprehensive toolbox to PanOmics data successfully de
Slide 63: Better pipeline building needs advanced disease modelling
Better pipeline building needs advanced disease modelling PAGE 63
Slide 64: A cure for Leah
A cure for Leah Case study: Amyotrophic lateral sclerosis (ALS) Leah • Amyotrophic lateral sclerosis (ALS) • Age 30 • First symptoms at 25 • Diagnosed at 27, bound to wheelchair since age of 28 • Prognosis: 2-5 year life expectancy • Formed not-for profit network ‘Her ALS Story’1 PAGE 64 1 About HAS
Slide 65: Ice Bucket Challenge in 2014 to raise awareness for ALS
Ice Bucket Challenge in 2014 to raise awareness for ALS1 ALS, amyotrophic lateral sclerosis, also known as motor neuron disease or Lou Gehrig’s disease Evotec team PAGE 65 1 The challenge was co-founded by Pat Quinn and Pete Frates to encourage donations for ALS research and it went viral on social
Slide 66: ALS is a fatal neurodegenerative disease with high unmet medical need
ALS is a fatal neurodegenerative disease with high unmet medical need Causes the brain to lose connection with the muscles Amyothrophic lateral sclerosis (ALS) Normal nerve cell • Rapidly progressing disease caused by death of motor neurons • Motor neurons control voluntary muscle movement and breat
Slide 67: From humans for humans
From humans for humans iPSC-based drug discovery E.iPSC – ALS patient iPSC-based Human disease off-the-shelf relevant modelling therapeutics Disease-specific drugs Off-the-shelf cell therapeutics iPSC platform "Disease in a dish" & screening iPSC-derived motor neurons PAGE 67
Slide 68: Our first iPSC program dedicated to discovery of new ALS treatments
Our first iPSC program dedicated to discovery of new ALS treatments Established protocol for ALS patient derived iPSC motor neurons in collaboration with HSCI Islet1 / βIII tubulin / nuclei Prof. Prof. Kevin Lee Eggan Rubin PAGE 68
Slide 69: Taking iPSC to an industrial level for large scale drug discovery
Taking iPSC to an industrial level for large scale drug discovery Highly scalable and automated laboratory workflows Industry scale Automated workflows • High quality iPSC and iPSC-derived cells • Sterile long-term culture • Optimized protocols in 2D & 3D • High throughput drug screening • Strict QC
Slide 70: BMS-986419 restores normal Integrated Stress Response function
BMS-986419* restores normal Integrated Stress Response (ISR) function Chronic activation of ISR in ALS disease can lead to cell death Integrated stress Misfolded proteins • The eIF2 complex is an ISR1 “master regulator” response that becomes dysfunctional in chronic disease: PERK chronic stimulation
Slide 71: Potential across a range of neurodegenerative conditions
Potential across a range of neurodegenerative conditions eIF2B activator (BMS-986419 / EVT8683) is moving into a Phase II trial in ALS Misfolded protein accumulation & evidence of ISR BMS-986419 / EVT8683 activation present in multiple neurological conditions1 • Safe and well-tolerated in Phase I cl
Slide 72: A growing portfolio of iPSC models to tackle more diseases
A growing portfolio of iPSC models to tackle more diseases Ongoing collaborations and opportunities leveraging our PanOmics drug discovery platform Therapeutic area iPSC model Indication Partner & status Partnered in 2016, Neurodegeneration Neurons, astrocytes, microglia, AD, PD, ALS, ... >20 projec
Slide 73: From humans, for even more humans
From humans, for even more humans More and more disease models to come Unravelling complex disease Exploring disease biology at scale Fueling diverse - E.MPD - - E.iPSC - program pipelines Relevant iPSC models Focus on therapeutic Cross-comparison • Modelling human disease pathology in vitro areas w
Slide 74: Efficient pipeline building accelerating with A.I.
Efficient pipeline building accelerating with A.I. PAGE 74
Slide 75: Strong influence of A.I. on the Pharma/Biotech Industry
Strong influence of A.I. on the Pharma/Biotech Industry Overview of anticipated benefits Status today Precision: Scalability: A.I. enables fine-tuning of compound Automated processes can handle large- properties for specific applications scale production efficiently Linear Cost Reduction: Speed: Few
Slide 76: Sharing our peer-reviewed cutting-edge research work
Sharing our peer-reviewed cutting-edge research work Examples of research in the field of A.I./M.L. and High-Performance Compute for Drug Discovery High recognition in scientific community • Two peer-reviewed books produced by Evotec teams on A.I./M.L. algorithm and HPC for A.I./M.L., Quantum Comput
Slide 77: Reduction of time to clinical trials observable, but early days
Reduction of time to clinical trials observable, but early days Outcomes, not only speed matters 180 Potential to reduce time from bench to clinical trial # of clinical & preclinical assets Phase III 160 Phase II 140 Phase I 120 Discovery/preclinical RLY-1971 Program start to patent Patent to trial
Slide 78: Integrated A.I./M.L. throughout the drug discovery value chain
PAGE 78 PanHunter validation Target ID / 1. Target ID / Validation Hit identification 1 Drug induced liver injury Lead Examples of applications optimisation 2. Hit and Lead Optimisation tox testing Pre-clinical PanOmics data analytics and compound profiling along the full value chain 1 vs 1 vs 1 vs
Slide 79: 1. Target ID / Validation with A.I. enabled data mining
1. Target ID / Validation with A.I. enabled data mining Selection, identification and validation to a ranked compound hitlist using automatic workflows Target Identification Target Validation Assay Development Potential novel target Selecting Target/screening for disease modulation • New Target vali
Slide 80: 2. Generative A.I. driven Drug Design – reinforcement learning
2. Generative A.I. driven Drug Design – reinforcement learning Small Molecule Generative Design Starting from Series A.I. Generative Novel compound Impact on of Target X inhibitors Design series identified Drug Discovery • Compounds not potent • Reinforcement Learning • Identified novel series enoug
Slide 81: 3. Future of Safety Prediction is A.I. and Omics-driven
3. Future of Safety Prediction is A.I. and Omics-driven High-throughput omics towards benefit-risk prediction: safety prediction example Relevant cellular models Proprietary safety database Safety liability modelling AI/ML predictions of safety liability risk High-throughput omics High Low risk risk
Slide 82: 4. Generative A.I. driven Patient selection
4 Generative A.I. driven Patient selection Patient A.I./M.L. Impact on Cohorts based Model Validation Drug Discovery • Use of ‘omics’ (Tran- • Validate the model scriptomics, sc/snRNA-Seq, (domain experts) Proteomics, Metabolomics, • Review the score and Exome Seq, SNPs) data prediction • Expert cur
Slide 83: PanHunter is the platform to manage high dimensional data
PanHunter is the platform to manage high dimensional data PanHunter: Full-scale A.I. driven analysis platform PanOmics continuum Value generation Actionable output Genomics A.I. supported Target ID Whole genome Whole exome Human disease expertise Drug Screening result visualization Transcriptomics a
Slide 84: Agenda
Agenda 9:00-9:30 Shaping (new) markets 9:30-11:00 PanOmics – From patients for patients • Better disease understanding & diagnostics • Advanced disease modelling • A.I. use cases along the value chain 11:00-11:15 Coffee Break 11:15-12:15 Impactful therapies • Integrated platform • Diabetes • Oncolog
Slide 85: Agenda
Agenda 9:00-9:30 Shaping (new) markets 9:30-11:00 PanOmics – From patients for patients • Better disease understanding & diagnostics • Advanced disease modelling • A.I. use cases along the value chain 11:00-11:15 Coffee Break 11:15-12:15 Impactful therapies • Integrated platform • Diabetes • Oncolog
Slide 86: Introduction to cell therapy
Introduction to cell therapy Background Cell therapy is a treatment in which viable cells (autologous, allogeneic, iPSC-derived), are injected, grafted or implanted into a patient in order to improve or cure a disease. Induced pluripotent stem cells (iPSCs) are a type of stem cell that can be genera
Slide 87: Providing functional cures with cell therapies
Providing functional cures with cell therapies Translating the power of cells into medicines that matter Immune cell treatments for cancer patients For diabetic patients: 1. Solid tumours 2. Blood cancers Beta cell replacement therapy Prior treatment After 2 weeks 2012 2022 After a single treatment
Slide 88: Increasing market access for cell therapies
Increasing market access for cell therapies Pipeline of cell & gene therapies 2023 • Nr of cell and gene therapies with market approval is increasing − 80% autologous with limited pat reach − (Hem)Oncology, inherited genetic diseases • Next generation moving to off-the- shelf & larger indications ap
Slide 89: Revolutionising access to cell therapies
Revolutionising access to cell therapies Advantage of “off-the-shelf” versus autologous/donor-based approach Autologous Just-in-time iPSC-based off-the-shelf therapeutics • Reduced complexity: Patient is Patient Manufacturing 1x dose not part of manufacturing process • Unlimited starting material Al
Slide 90: Significant platform and project portfolio built over 4-year period
Significant platform and project portfolio built over 4-year period Strategic internal efforts from 2019 up to now Goal: Diabetes First interaction Janssen build cell program regulatory collaboration therapy returns to authorities Diabetes collaboration franchise Evotec diabetes GMP Acquisition MCB1
Slide 91: A portfolio of off the shelf iPSC-based cell therapy programs
A portfolio of off the shelf iPSC-based cell therapy programs Evotec’s internal and partnership project portfolio Program/ Disease Pre-clinical Pre-clinical IND / Field Project area Protocol research development Phase I iPSC-derived cell types Cancer immuno- iNK Natural γδ iT Oncology Undisclosed th
Slide 92: Integrated platform for iPSC-based therapeutics
Integrated platform for iPSC-based therapeutics PAGE 92
Slide 93: Truly off-the-shelf, fully scalable cell therapy products
Truly “off-the-shelf”, fully scalable cell therapy products A process to overcome a major hurdle in cell therapy • Fully characterized • Morphology/ Viability • Full genetic QC Developing • Confirmation of genetic modification • Differentiation capacity industrialized • Functional characterization G
Slide 94: Integrated platform for iPSC-based therapeutics is becoming reality
Integrated platform for iPSC-based therapeutics is becoming reality From iPSCs to patients Pre-clinical Pre-clinical Exploratory Clinical research development • iPSC differentiation • GMP-compatibility • CMC • Clinical supply • Gene editing • Upscaling • Pre-clinical safety • Patient stratification
Slide 95: Multiplex gene editing to create highly efficacious and safe therapies
Multiplex gene editing to create highly efficacious and safe therapies The power of gene edited iPSC cell therapies Gene-edited, iPSC- Immune- derived cell therapies Tumor tolerance to targeting prevent allo- via CARs rejection and TCRs Increase cell Safety persistence switches/ and overcome tags ho
Slide 96: Centre of excellence for cell therapeutics manufacturing
Centre of excellence for cell therapeutics manufacturing Evotec Modena • Founded in 2009 as spin-off of the University of Modena and Reggio Emilia • Scientific founder Prof. Massimo Dominici is one of the pioneers in clinical cell therapy • State-of-the art GMP manufacturing facility (5 clean rooms,
Slide 97: A powerhouse for iPSC cell therapy research & development
A powerhouse for iPSC cell therapy research & development Selected KPIs Translation from >120 >15 science into clinical application Scientists dedicated iPSC-derived to cell therapy cell types >200 >10 Cell production Cell therapy runs per year for projects Development material PAGE 97
Slide 98: Pipeline building with iPSC-based cell therapy in Diabetes
Pipeline building with iPSC-based cell therapy in Diabetes PAGE 98
Slide 99: Diabetes program with broad therapeutic scope
Diabetes program with broad therapeutic scope Targeting high-risk patients first to expand to large patient populations Size1 of potential patient population Type 1 diabetes Our goal is to provide a curative approach by islet replacement • Standard of Care: intensified insulin therapy with positive
Slide 100: Multiple product generations will enable true leadership
Multiple product generations will enable true leadership Opportunity for multi-project partnership with Pharma Implantation in CellPouchTM Non-modified iPSC beta cells + cell pouch Immuno-suppressed patients Implantation in CellPouchTM Non-modified iPSC beta cells + cell coating + cell pouch No immu
Slide 101: iPSC-derived islets for the treatment of Type 1 diabetes
iPSC-derived islets for the treatment of Type 1 diabetes Evotec achievements and current focus iPSC-derived islet like clusters • Scalable, GMP-compatible and IP- protected manufacturing procedure for iPSC-derived islet like clusters, with optimized beta cell fraction DAPI C-PEPTIDE • Manufacturing
Slide 102: On the path to a first clinical candidate
On the path to a first clinical candidate Utilises Sernova’s clinically validated Cell Pouch device Cell Pouch System EVT3101 • Implantable medical • iPSC-based islet-like device clusters mimicking human islet cells • Provides vascularized environment for cells • Long-term function in rodent models
Slide 103: Excellent anti-diabetic activity of Evotec ILCs in the Cell Pouch
Excellent anti-diabetic activity of Evotec ILCs1 in the Cell Pouch™ Human islet-like potency; full tissue integration and blood supply for beta cells in mouse diabetes model Efficient Excellent survival and tissue integration of islet cells, and normalization optimal supply with blood vessels in the
Slide 104: Translation into clinical development
Translation into clinical development From iPSCs to patients Pre-clinical Pre-clinical Exploratory Clinical research development • iPSC differentiation • GMP-compatibility • CMC • Clinical supply • Gene editing • Upscaling • Pre-clinical safety • Patient stratification • In vitro PoC1 • In vivo PoC
Slide 105: Gene-editing is the next step to increase efficacy & safety
Gene-editing is the next step to increase efficacy & safety Introducing cloaking (immune-shielding) and FailSafe (drug-inducible kill-switch) Nobel-prize awarded technology (2020 J.Doudna, E.Charpentier) Combining two gene editing concepts to render its allogeneic “off-the-shelf” cell therapy produc
Slide 106: Pipeline building with iPSC based cells in Oncology and I&I
Pipeline building with iPSC based cells in Oncology and I&I PAGE 106
Slide 107: Immune cells can be serial killers – which is good
Immune cells can be serial killers – which is good Why cell therapies are highly efficacious in the clinic – if they work Mode of action Cell therapy status quo Perforin (pore formation) and Currently marketed products granzymes (apoptosis induction) Alive tumor cell Immune cell Apoptotic Immune tum
Slide 108: Unlocking the full potential of cell therapies in oncology
Unlocking the full potential of cell therapies in oncology High unmet medical need in solid tumour indications Cell therapy late-stage pipeline Cancer incidence Solid <40% >60% Hemat Hematological tumors Solid tumors >60% of current late-stage pipeline focused ~90% of new case of cancer are on hemat
Slide 109: EVOcells oncology and I&I: an iPSC-based immune effector cell platform
EVOcells oncology and I&I: an iPSC-based immune effector cell platform Summary of platform components Fully leveraging all elements of the iPSC-based cell therapy platform combined with in-depth disease area and asset development expertise A broad range of iPSC-derived cell types to overcome the mai
Slide 110: A toolbox to generate a universe of cell therapy product candidates
A toolbox to generate a universe of cell therapy product candidates Evotec’s technologies for iPSC-derived immune cell therapy Immune cell type Tumor targeting Gene-edits Cell products Cytokines TCR2 Safety Targeting iNK iαβT CAR1 switch moiety KO 1 Immune effector cell KO 2 KI 1 iγδT Artificial I
Slide 111: The broadest iPSC-based immune effector cell portfolio in industry
The broadest iPSC-based immune effector cell portfolio in industry Evotec’s off-the shelf cell therapy programs Program/ Disease Pre-clinical Pre-clinical IND / Field Project area Protocol research development Phase I iPSC-derived cell types Cancer immuno- iNK Natural Partnered γδ iT Oncology Undisc
Slide 112: A novel mode of action to eliminate patient-derived tumor cells
A novel mode of action to eliminate patient-derived tumor cells iPSC-based macrophages kill hard to treat primary cancer cells Tumor cells of patient #1 Tumor cells of patient #2 E:T = 10:1 iMAC + cancer cells Cancer cells only iMAC + cancer cells Cancer cells only 80 80 60 60 % dead cancer cells %
Slide 113: Developing an efficacious cell therapy dedicated to solid tumors
Developing an efficacious cell therapy dedicated to solid tumors iPSC-based, gene-edited macrophages to overcome the limitations of current cell therapy approaches Evotec’s iMAC cell Limitations of autologous Potential solutions provided product candidates T and NK cell therapies by iPSC-based macro
Slide 114: Agenda
Agenda 9:00-9:30 Shaping (new) markets 9:30-11:00 PanOmics – From patients for patients • Better disease understanding & diagnostics • Advanced disease modelling • A.I. use cases along the value chain 11:00-11:15 Coffee Break 11:15-12:15 Impactful therapies • Integrated platform • Diabetes • Oncolog
Slide 115: Breakout Sessions
Breakout Sessions Two sessions of 60 minutes Q&A in two groups 13:30-14:30h / 14:45h-15:45h TEAM PanOmics: Cord, Christiane, Olivier, Sandra, Bhushan MEC I TEAM Impactful Therapies: Werner, Andreas, Christine, Markus MEC III Closing Remarks MEC I at ~16:00h PAGE 115
Slide 116: #researchneverstops
#researchneverstops ...and shapes new markets! Evotec SE, Capital Markets Day
Slide 117: The initial idea is more modern today than ever before!
The initial idea is more modern today than ever before! PAGE 117
Slide 118: Shaping new markets means doing things differently
Shaping new markets means doing things differently From symptomatic towards data-driven, preventive treatments “Successful” symp- Precision Data-driven tomatic treatments medicine healthcare Our all-in efforts towards medicines that matter Early & • Industrialised PanOmics towards Symptomatic Sympto
Slide 119: Looking forward to seeing you in Toulouse …
Looking forward to seeing you in Toulouse … Capital Markets Day 2024 Next CMD 10 October 2024 PAGE 119
Slide 120: Your contact:
Your contact: Volker Braun, SVP Head of Global Investor Relations & ESG volker.braun@evotec.com +49 151 19405058 (m)