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  1. Sensitivity: CEPI Internal CEPI 100 day mission Innovative CMC technologies to enable rapid response Ingrid Kromann Director, Manufacturing & QC development Vaccine Technology Summit March 20-21, 2023 #100DaysMission 1
  2. Sensitivity: CEPI Internal 2 The Creation of CEPI Launched at the World Economic Forum at Davos in 2017 as a global coalition to tackle epidemics
  3. Sensitivity: CEPI Internal Governments Philanthropists Regulators Pharmaceutical Industry Civil society and health organisations Academia CEPI's unique connecting role and extensive networks allow it to pool and deploy resources in ways that nation states often cannot. A world in which epidemics and pandemics are no longer a threat to humanity. Vision To accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. Mission CEPI: A global partnership 3
  4. Sensitivity: CEPI Internal 4 4 CEPI’s active vaccine portfolio 1 includes broadly protective SAR-CoV-2 and broadly protective betacoronavirus. 2 Finishing Ebola : CEPI is funding 8 Ebola clinical projects for Merck and Janssen vaccines. In addition, CEPI is in dialogue with WHO to potentially support Ebola Sudan ring vaccination. 2 Vaccine Candidates MERS 4 Vaccine Candidates Lassa 3 Vaccine Candidates Nipah 3 Vaccine Candidates Chikungunya Rift Valley fever 2 vaccine Candidates COVID-19 / broadly protective1 7 COVID-19 Vaccine Candidates 12 Broadly Protective1 Vaccine Candidates 3 Platform Technologies Disease X 8 Clinical Projects for 2 Vaccine Candidates Ebola2 Jan 2023
  5. Sensitivity: CEPI Internal What we achieved in response to COVID-19 We were able to respond quickly to COVID-19 due to: 1. Prior research in two closely related coronaviruses, SARS and MERS, including early funding from CEPI to support Oxford’s ChAdOx platform. 2. Decades of development of mRNA technologies, allowing for fast, adaptable and highly scalable vaccine development — a step change from traditional biological manufacturing. #100DaysMission
  6. 6 During COVID-19, it took 326 days for development to EUA by stringent regulatory authority Vaccine development then and now, months Sample baseline scenario1, (after multiple years of research) ~12-24 ~12-24 ~24 ~36-48 ~12 ~12 Preclinical, including toxicity, technology development Phase I: Safety and immunology Phase II: Proof-of- concept study Phase III: Large-scale safety and efficacy trials Filing Registration ~10 years 1. Timelines can vary widely based on disease and trial designs 2. Patient safety was paramount despite the condensed timeline Sample accelerated timeline2, (based on previous SARS/MERS research) Development was simultaneous rather than sequential. Clinical phases were continued after subsequent steps were initiated 326 days Authorization (EUA by stringent regulatory authority) ~2 ~2 ~2 ~4 ~1
  7. Sensitivity: CEPI Internal Coupled with improved surveillance, and swift use of non-pharmaceutical interventions, a vaccine in 100 days could defuse the threat of a new pathogen with pandemic potential. #100DaysMission CEPI’s 100 Days Mission Definition ‘Vaccines should be ready for initial authorisation and manufacturing at scale within 100 days of recognition of a pandemic pathogen, when appropriate.’
  8. 8 Compressing timelines further will require a fundamental shift towards preparedness 100 Days
  9. 9 Achieving maximal response acceleration will require a paradigm shift Preparedness Prepare the scientific toolkit, development infrastructure & policy Response Adapt, create & test the pathogen-specific vaccine Roll-out and review Release vaccine & expand clinical evidence Paradigm shift: significant front-loading in preparedness, and breaking the firewall between development and intervention Response acceleration under different scenarios
  10. 10 10 1950 2021 97% reduction in elapsed time 1 min 2 sec
  11. “Valleys of Death” Sensitivity: Privileged and confidential Figure from: Witek Jr, T J, How the Global COVID-19 Pandemic Brought Drug and Vaccine Development into the Public Mainstream, J. Pharmaceutical Medicine (2021) 35:287–295 “For CEPI 2.0 and the 100 day mission to be successful we need to bridge both valleys. ,
  12. Sensitivity: CEPI Internal Critical path towards vaccine availability Based on the 100 Days Working Group: • Analysis of COVID-19 vaccine development timelines shows that manufacturing is on the critical path to get to first-in-human • Manufacturing scale-up and technology transfer is critical to make doses available and equitably accessible Alert trigger Vaccine available for use 100 days BNs of doses manufactured Post 100 days Preparedness (speed) (Scale, access) (Speed, scale, access) Candidate development and preclinical testing Early and any required clinical trials; Emergency authorization Large-scale clinical trial Real-world evidence Process development and PhI manufacturing Scale-up and PhIII manufacturing Process validation Scale-up and -out, technology transfer Preclinical, clinical, regulatory process dev, scale-up, scale- out experience with platform Epi monitoring 12
  13. Sensitivity: CEPI Internal CMC framework ▪ Manufacturable at different scales with maintained quality attributes ▪ Ensuring safety and efficacy ▪ Meeting Regulatory Agency Expectations ▪ Targeting the 100 Days Mission Drug Substance & Drug Product Process # Status Comments # # # 1.1 Pre-clinical 1.2 Phase I 1.3 Phase II 1.4 In High level definition Process description & unit operations defined Process transferred to manufacturing site Process fixed suitable for Ph II and stockpile Pr Must Have Deliverables A Lorem ipsum dolor sit amet g A Lorem ipsum dolor sit amet A Lorem ipsum dolor sit amet A Lo B consectetur adipiscing elit g B consectetur adipiscing elit B consectetur adipiscing elit B co C Morbi congue quis ex vitae dapibus a xxxx C Morbi congue quis ex vitae dapibus C Morbi congue quis ex vitae dapibus C M D Donec ac convallis enim r yyyy D Donec ac convallis enim D Donec ac convallis enim D Do E Integer et diam eu erat commodo finibus non bibendum augue E Integer et diam eu erat commodo finibus non bibendum augue E Integer et diam eu erat commodo finibus non bibendum augue E In bi F Curabitur vel porttitor nisl, vitae commodo augue b F Curabitur vel porttitor nisl, vitae commodo augue F Curabitur vel porttitor nisl, vitae commodo augue F Cu au G Suspendisse elementum erat non justo convallis accumsan G Suspendisse elementum erat non justo convallis accumsan H Quisque egestas ullamcorper posuere H Quisque egestas ullamcorper posuere I Fusce ac congue orci I Fusce ac congue orci J Sed blandit elit a sagittis laoreet J Sed blandit elit a sagittis laoreet K Donec porta ex sapien, vitae condimentum ligula accumsan egestas Additional considerations A Integer velit nulla, faucibus vitae ex vel, finibus scelerisque velit a zzzz A Integer velit nulla, faucibus vitae ex vel, finibus scelerisque velit A Integer velit nulla, faucibus vitae ex vel, finibus scelerisque velit A In sc B Nulla facilisi a xyxyxy B Nulla facilisi (where applicable) C Cras in odio eu metus ullamcorper tempor a xzxzxz C Cras in odio eu metus ullamcorper tempor D In suscipit ultrices mauris id pretium a zyzyz D In suscipit ultrices mauris id pretium E Vivamus luctus ut arcu eget mattis F In nisi dolor, fermentum in tristique eu, vestibulum eu purus G Pre-clinical Phase I Phase II SG I SG DD SG 13
  14. Sensitivity: CEPI Internal 14 14 Scaling to meet the post 100 day need Platform - manufacturing process and assays developed • Standardised Technology Transfer of process and assays Facility equipped, validated and trained staff Vaccine manufacturing and delivery Supply Chain established Regulatory preapproval of CMC and clinical dossier Vaccine delivery prepared
  15. CONFIDENTIAL Sensitivity: CEPI Internal 15 • Focused on mRNA, protein and viral vector manufacturing platforms: • Mapping from antigen sequence availability to CTM supply for emergency use • Common themes identified: • Analytical methods, release testing • Cell-based steps • Adjuvant availability for proteins • Platform optimization • Critical path analysis presented at several meetings and conferences – not formally ‘validated’ yet Critical path analysis for key vaccine manufacturing platforms mRNA platform Viral vector platform Protein production platform
  16. CONFIDENTIAL Sensitivity: CEPI Internal 16 The critical path analysis of different vaccine manufacturing platforms identified the following areas for innovation: Platform optimization; can make multiple vaccine platforms rapidly adaptable to new pathogen • Synthetic biology approaches for cell-free manufacturing of DNA template, proteins and viruses • Or: transient transfection of cell lines at scale for proteins Rapid testing of drug substance/product can reduce hold times between manufacture and product release using • Accelerated release testing, especially sterility, adventitious agents, potency • Process analytical technology and real-time release • Rapid testing methods exist - require implementation CMC is on the critical path
  17. CONFIDENTIAL Sensitivity: CEPI Internal CfP launch April/May 2023 Focus areas • Focus Area 1: Platform process development, optimization, standardization and acceleration • mRNA, viral vectors, proteins or other novel platforms in batch or continuous processing modes to be considered • Focus Area 2: Analytical technologies to accelerate drug substance/product batch release and availability of master cell bank (MCB) / master viral stock (MVS) • Deployment of existing rapid technologies, and new technologies (e.g., ID and potency tests or reagents) - both types require implementation as partner • Focus Area 3: Innovations to accelerate cell-based manufacturing steps, including synthetic approaches • Implementation of cell-free manufacturing innovations to improve vaccine production • Focus Area 4: Any other manufacturing-related innovations that can accelerate clinical trial material availability
  18. CONFIDENTIAL Sensitivity: CEPI Internal Manufacturing innovations are also required to meet 100-day mission’s speed, scale and access goals Alert trigger Vaccine available for use 100 days BNs of doses manufactured Enable equitable access Speed • Platform optimization • Synthetic biology approaches • Accelerated release testing • Adjuvant libraries and stockpiles Scale • Flexible, modular, scalable manufacturing solutions • High-expression cell lines • Characterization methods to support tech transfer • Improved access to adjuvants Access • Thermostability – current Call for Proposals • Lower COGS • Novel formulations that are easy to distribute and administer
  19. Sensitivity: CEPI Internal CEPI‘s 100-Days Mission: Regulatory Initiatives It is about accelerating all aspects of product development and identifying opportunities for early deployment Prepare, Develop, Deploy are essential for future outbreaks Partnering with regulatory authorities worldwide and other key stakeholders to capitalise on lessons learnt and embed regulatory innovation Enable maximal use of platform data and pre-approved documentation Evaluate product development pathways for any acceleration / streamlining Identify circumstances to accelerate development and deployment based on anticipated benefit risk Harmonise outbreak ready pathways and maximize speed of review and regulatory reliance to enable rapid regional and global roll-out Prepare Develop Deploy 19
  20. Sensitivity: CEPI Internal CMC Regulatory Templates • During the pandemic, there were an unprecedented number of technology transfers and non-linear CMC activities. • For readiness, CEPI, industry and academics collaborate and develop CMC protocol templates for comparability exercise and process validation. • Consultation with global health authorities will occur to gain feedback and endorsement on the template approaches. 20
  21. Sensitivity: CEPI Internal • Vaccine Library for Disease X • Platform Development • Innovate and Fine-tune processes 100 Days Mission ACESS SPEED Quality & Regulatory • Geo-diversified manufacturing network • Thermostability • Quality-by-Design • Quality Management System • Strategy to accelerate regulatory path 21
  22. Sensitivity: CEPI Internal What if we had lifesaving vaccines in 100 Days? #100DaysMission 22