BioNTech SE · NASDAQ:BNTX
BioNTech — Investor Day (June 2022)
157 slides from BioNTech's investor day presentation, Jun 30, 2022
Slide 1: Innovation Series
Innovation Series June 29, 2022 P h o to : F u si o n m e d ic a l a n im a ti o n , u n sp la sh
Slide 2: Forward-looking statements
This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the future commercial demand and medical need for initial or booster doses of a COVID-19 vaccine; compet
Slide 3: COMIRNATY authorization and safety information (EU)
COMIRNATY® ▼(the Pfizer-BioNTech COVID-19 vaccine) has been granted conditional marketing authorization (CMA) by the European Commission to prevent coronavirus disease 2019 (COVID-19) in people from 5 years of age. The vaccine is administered as a 2-dose series, 3 weeks apart. In addition, the CMA h
Slide 4: Safety information: authorized use in the U.S.
Safety information AUTHORIZED USE IN THE U.S. • COMIRNATY® (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19 vaccine for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and old
Slide 5: Agenda
Agenda Ugur’s welcome The BioNTech approach to innovation - Target discovery and characterization - Multi-platform innovation engine - Digital & AI/ML - Manufacturing and automation New frontiers in infectious diseases Q&A Coffee break An introduction to the oncology pipeline mRNA cancer vaccines Pr
Slide 6: Ugur's welcome
BIONT=Cri Ugur’s welcome
Slide 7: The human immune system plays a central role in >80% of human diseases
The human immune system plays a central role in >80% of human diseases 7 Ability to kill targeted cells or pathogens with high precision Hundreds of billion cells Impacts the function of every organ system in the body Potential for long-term memory Cancer Autoimmune diseases Neurodegenerative diseas
Slide 8: Tools developed for cancer will enable us to treat many diseases
The tools we have developed for cancer will enable us to treat many diseases 8 mRNA vaccines and therapeutics Cell and gene therapies Protein therapeutics Small molecule immunomodulators
Slide 9: Taking mRNA from vision to reality
Taking mRNA from vision to reality 1 Authorized or approved for emergency use or temporary use or granted marketing authorization in over 100 countries and regions worldwide, April 2022; 2 As of end April 2022; 3 By end of 2022; 4 Eric C. Schneider et al., The U.S. COVID-19 Vaccination Program at On
Slide 10: Strong momentum built on two decades of innovation
CARVac pre-clinical proof-of-concept published in Science Strong momentum built on two decades of innovation 10 stage Start of mRNA vaccine research by founders Mid 1990s 2008 BioNTech founding By Ugur Sahin, Özlem Türeci, and Christoph Huber in Mainz, Germany Off-the-shelf mRNA vaccine first-in-hum
Slide 11: BioNTech today
BioNTech today 11 Discovery powerhouse >1,000 research and development professionals IP portfolio with >200 patent families >300 publications including >100 in leading peer reviewed journals Diversified pipeline across 4 drug classes 21 clinical trials 17 product candidates in clinical development D
Slide 12: Advancing toward our long-term vision
Advancing toward our long-term vision 12 Oncology Infectious diseases 5 randomized Phase 2 trials 1 marketed vaccine Market leader in COVID-19 vaccines 10+ preclinical programs 1 Phase 1 program16 programs in 21 clinical trials Maintain and deepen COVID-19 vaccine leadership Multiple product launche
Slide 13: The BioNTech approach to innovation
The BioNTech approach to innovation {P h o to : V 2 o s k , u n s p la s h
Slide 14: Focused on five innovation pillars
Focused on five innovation pillars Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 14
Slide 15: mRNA and the immune system
Protein Translation Gene mRNA Transcription mRNA – involved essentially in all biological processes The immune system – body-wide control of physiological and pathological mechanisms Immune system 15
Slide 16: Understanding and exploiting immunological mechanisms
T cell Tumor cells Treg 4-1BB PD-1 PD-L1 TCRMHC Pro-inflammatory cytokines Naive T cell APC CD40 Understanding and exploiting immunological mechanisms 16 mRNA-encoded cancer vaccines2 Shared antigens Individualized antigens CAR-, TCR-, and non- engineered cell therapies3 44 2 Next-generation immunom
Slide 17: Target discovery
Focused on five innovation pillars Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 17 Target discovery
Slide 18: Mutation-based cancer heterogeneity: root cause of therapy failure
Mutation-based cancer heterogeneity: The root cause of cancer therapy failure 18 Target discovery Up to 10,000 mutations 5−20 yearsIndividual patients Healthy cell DNA mutation Mutations Mutations Mutations
Slide 19: Cancer mutations are druggable; 15-20% are immunogenic
Castle JC, et al. Cancer Res 2012; 72:1081−1091. Mutations from cancer tissues are druggable and 15−20% of mutations are immunogenic when exploited as vaccine targets 19 Target discovery
Slide 20: Exploiting the mutanome for personalized mRNA vaccination
Vormehr et al., Curr Opin Immunol 39:14-22 (2016). Exploiting the mutanome for personalized mRNA vaccination 20 Target discovery Vaccine antigen Vaccine mRNA In vitro Synthesis Immune response Formulation mRNA Nanoparticle Protection from Degradation by extracellular RNAses mRNA delivers genetic inf
Slide 21: Acquisition of patient tissue and blood samples
Acquisition of the patient´s tissue and blood samples 21 Target discovery
Slide 22: Identification of the patient's cancer mutations
Identification of the patient´s cancer mutations 22 Target discovery Cancer mutanome Normal Cancer Sequencer Mutation
Slide 23: Computerized prediction of mutations
Kreiter et. al. Nature 2015 Computerized prediction of mutations 23 Target discovery Computer predicted mutation list Verification by Expert Review Key Gene Mut Chrom Score #001 PIK3CA R115L 3 0,2 #002 IMPA2 R202P 18 0,3 #003 KRAS G12D 12 0,45 #... … … … … #267 KIF21B P188S 1 3,45
Slide 24: Individualized vaccine manufacturing
Kreiter, Vormehr et al, Nature 2015; Kranz, Diken et. al. Nature 2016. Individualized vaccine manufacturing Target discovery
Slide 25: How different neoantigens induce T-cell responses
Lang F, et al. Nature Rev Drug Discov 2022; 21:261‒282. How do different types of neoantigens induce T-cell responses and kill tumors? 25 Characteristic feature Estimated frequency Guarding neoantigens Supreme neoantigens with strong antigenicity that drive early priming and rapid expansion of neoan
Slide 26: The long tail of individual targets
iN e S T s e le c ti o n fr e q u e n c y [a b s o lu te ] ≥8 7 6 5 4 3 2 1 1 Collaboration with Genentech 2 GO39733, GO40558, BNT122-01, ML41081. Absolute frequency of genes selected for iNeST1 vaccination across BioNTech trials2 26 Target discovery 1,400+ patients screened ~ 420+ patients treated
Slide 27: Multi-platform engine
Focused on five innovation pillars Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 27 Multi-platform engine
Slide 28: Multi-platform strategy
Multi-platform strategy Technology-agnostic innovation engine Multi-platform engine 28 mRNA vaccines Targeted antibodies Small molecule immunomodulators • Targeting immune checkpoint molecules • Engineered bispecific antibodies • Engineered mechanisms of action Cell & gene therapies Next-generation
Slide 29: Broad mRNA toolkit
mRNA technology Broad mRNA toolkit built out of deep immunological expertise 29 Multiple mRNA formats Delivery formulations Flexible delivery routes Local, intratumoral, tissue-specific, or systemic Lipoplex (LPX) Lipid nanoparticles (LNP) Polyplexes Backbone-optimized uridine mRNA (uRNA) + More tha
Slide 30: Each mRNA format optimized for specific applications
T cell TCR MHC APC mRNA technology Each mRNA format is optimized for specific applications Multiple mRNA formats Backbone-optimized uridine mRNA (uRNA) Backbone-optimized nucleoside-modified mRNA (modRNA) Targeted application Potent T cell response Repeat administration Shared antigen mRNA vaccines
Slide 31: saRNA induces higher and extended expression
mRNA technology І saRNA could induce higher and extended in vitro and in vivo expression compared to mRNA Internal data. 31 in vitro expression in vivo expression Backbone-optimized nucleoside-modified RNA (modRNA) Multi-platform engine saRNA showed potential as a vaccine modality with much lower do
Slide 32: Trans-amplifying RNA for potent immunity
mRNA technology І Trans-amplifying RNA could potentially be a vaccine strategy to induce potent immunity 32 Multi-platform engine Internal data. Transgene Replicase (non-self amplifying) Positive-sense replicase Positive-sense transgene Negative-sense transgene mRNA (transgene) Vaccine antigen (enha
Slide 33: taRNA and saRNA in infectious disease programs
mRNA technology We are exploring taRNA and saRNA in multiple infectious disease programs CCHFV, Crimean-Congo hemorrhagic fever orthonairovirus; MERS-CoV, Middle East Respiratory syndrome-related coronavirus; modRNA backbone-optimized nucleoside-modified RNA; saRNA, self-amplifying mRNA; taRNA, tran
Slide 34: Diversified delivery platform for mRNA medicine: lipoplex
1 Grabbe S, et al. Nanomedicine 2016; 11:2723‒2734; 2 Kranz LM, et al. Nature 2016; 534:396–401. Delivery formulations A diversified and rationally designed delivery platform for mRNA medicine 34 Multi-platform engine Schematic depiction of RNA-lipoplex screening process1 Bioluminescence imaging of
Slide 35: Delivery formulations: LNP screening
• Optimize stability • Improve potency • Maintain immune quiescence/reduce immunogenicity • Seek PEG alternatives: reduce impact of anti-PEG antibodies to improve pharmacokinetics • Seek alternative routes of administration LNP, liquid nanoparticles; PEG, Polyethylene glycol. Nogueira SS, et al. ACS
Slide 36: Digital & AI/ML
Focused on five innovation pillars Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 36 Digital & AI/ML
Slide 37: BioNTech's AI & ML applications
BioNTech’s AI & ML applications 37 Neoantigen prediction COVID-19 variants monitoring and prediction Digital & AI/ML 1 2
Slide 38: AI & ML drive individualized cancer medicine
1 Partnered with Genentech. Neoantigen prediction AI & ML drive individualized cancer medicine 38 1 Neoantigens iNeST1 Individualized mRNA cancer vaccine Neoantigens NEO-STIM Individualized T-cell therapy Mix of shared and neoantigens Individualized TCR T cells Powered by data and cutting-edge AI &
Slide 39: Identifying, predicting and characterizing neoantigens
1 Türeci Ö, et al. Nat Biomed Eng 2018; 2:566‒569; 2 Sahin U. AACR Annual Meeting 2022; Oral presentation; 3 McGranahan N, et al. Science 2016; 351:1463‒1469; 4 Gejman RS, et al. eLife 2018; 7:e41090; 5 Duan F, et al. J Exp Med 2014; 211:2231‒2248; 6 Balachandran VP, et al. Nature 2017; 551:512‒516;
Slide 40: Not all neoantigens are created equal
Yadav M, et al. Nature 2014; 515:572‒576. Neoantigen prediction Individualized targets: Not all neoantigens are created equal 40 Exome variations Exome coding variations Transcript coding variations Predicted neo-epitopes Spectra-identified neo-epitopes Predicted immunogenic neo-epitopes Validated i
Slide 41: Individualized-target database
Internal data. Neoantigen prediction Genomic and ligandomic expertise drive our individualized-target database 41 Neoantigen rank Gene Mutation Length (aa) Transcript VAF MHC I score MHC II score Coverage in tumor VAF in tumor Coverage in normal tissue VAF in normal tissue 1 SNF8 V183M 27 16.05 0.1
Slide 42: New AI-based immune response model
Neoantigen prediction New AI-based immune response model may improve accuracy of prediction EL, eluted ligand; ROC, receiver-operator-characteristics. Lang M, et al. CIMT Annual Congress 2022; Poster presentation 21. 42 1 Digital & AI/ML Trained to enable an integrated view of immune response featur
Slide 43: Reduction in time to detect new variants of concern
COVID-19 variants monitoring and prediction Reduction in time to detect new variants of concern by ~2 months 1 Artificial intelligence collaboration of BioNTech and InstaDeep. EWS, emergency warning system. Beguir K, et al. bioRxiv 2021; doi: 10.1101/2021.12.24.474095. 43 Early computational detecti
Slide 44: Predicted scores correlate with in vitro data
COVID-19 variants monitoring and prediction Predicted scores for immune escape and fitness prior correlate with in vitro data Beguir K, et al. bioRxiv 2021; doi: 10.1101/2021.12.24.474095. 44 2 Digital & AI/ML
Slide 45: EWS report: June 24, 2022
COVID-19 variants monitoring and prediction EWS report : June 24, 2022 45 Digital & AI/ML2
Slide 46: Manufacturing and automation
Focused on five innovation pillars Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 46 Manufacturing and automation
Slide 47: Manufacturing and automation
Manufacturing and automation
Slide 48: Diversified manufacturing expertise across four capabilities
Diversified manufacturing expertise across four distinct capabilities 48 • End-to-end mRNA production capabilities • Combined >100,000 square ft across 2 facilities • Total capacity of >1 billion doses (COVID-19 vaccine) • Flexibility to support broad range of mRNA therapies Bulk mRNA • Semi-automat
Slide 49: Expanding global manufacturing footprint
Expanding global manufacturing footprint 49 Gaithersburg Clinical-scale cell therapy ~50 employees >45,000 square ft Modular mRNA BioNTainer Senegal, Rwanda, & South Africa (planned for 2023) Singapore (planned for 2023) Commercial-scale mRNA Idar-Oberstein MainzMarburg Commercial-scale mRNA Individ
Slide 50: Scaling up mRNA manufacturing
Scaling up mRNA manufacturing 50 Batch-size and capacity expansion through digitalization and automation Annual clinical patient batch capacity 1,000 >10,000 in 2022 Planned capacity Marburg bulk mRNA batch size 350 g 1.4 kg in late 2020 in 2022 Manufacturing and automation 1 g in early 2020 10 in 2
Slide 51: Marburg BioNTainer development hub
Scaling up mRNA batch numbers: Marburg 51 BioNTainer development hub Acquired from Novartis in 2020 for less than EUR 100M >1.5 billion doses of COVID-19 vaccine produced since Q2 2021 >100,000 square ft and 8 retrofitted production suites Retrofitted to produce mRNA vaccine within 6 months of acqui
Slide 52: iNeST manufacturing cycle-time reduction
1 2 3 4 5 6 7 8 9 10 11 12 13 Targeting delivery: <5 weeks 1 2 3 4 5 6 7 8 9 10 11 12 13 iNeST manufacturing innovation: Cycle-time reduction with automated process 52 Needle to needle: >3 months Manual process (until 2016) Semi-automated process (from 2017) Weeks Weeks Manufacturing and automation
Slide 53: Global cGMP cell therapy infrastructures
We are investing in global cGMP cell therapy infrastructures 53 IMFS, Idar-Oberstein, Germany (fully owned) 24/7 operational model Reduction of steps and time Reduction of complexity Increased efficiency Advantages of an automated approach Reproducibility of manufacturing process Unlocks capacity Fa
Slide 54: BioNTainer: localized and sustainable mRNA production
BioNTainer: A platform for localized and sustainable mRNA production 54 The challenge The solution Establishing GMP production of mRNA is complex and requires overcoming challenges at many levels Turnkey package that includes modular production units, GMP-compliant setup and personnel training Manuf
Slide 55: BioNTainers: what is next in 2022
BioNTainers: What is next in 2022 55 Broke ground for first BioNTainer manufacturing facility in Rwanda First BioNTainer expected to be shipped (YE 2022) Regulatory framework in alignment with international and local standards Evaluation of additional use cases and products for BioNTainers worldwide
Slide 56: Five innovation pillars for a new era of synthetic medicine
Focused on five innovation pillars to enable a new era of synthetic medicine Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 56
Slide 57: Five innovation pillars for a new era of synthetic medicine
Focused on five innovation pillars to enable a new era of synthetic medicine Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML 57
Slide 58: Multi-platform innovation engine
Multi-platform innovation engine 58 TCR therapy CAR-T Solid tumor CAR T cells Infectious diseases vaccines Prophylactic Therapeutic Off-the-shelf mRNA cancer vaccines FixVac RiboMabs mRNA-encoded multi-specific antibodies Individualized mRNA cancer vaccines iNeST RiboCytokines mRNA-encoded cytokines
Slide 59: New frontiers in infectious diseases
New frontiers in infectious diseases New frontiers in infe ti us disease
Slide 60: Building on COVID-19 vaccine leadership
Building on COVID-19 vaccine leadership to address global challenges 60 Advancing a broad toolkit of mRNA vaccines, Ribologicals, Ribolysins Diverse pipeline of next-generation COVID-19 vaccines Delivering breakthroughs against infectious diseases with high need Ability to precisely address diverse
Slide 61: Medical burden from infectious diseases is a growing challenge
Medical burden from infectious diseases is a growing global challenge 1 World Health Organization; 2022. https://cdn.who.int/media/docs/default-source/gho-documents/world-health-statistic-reports/worldhealthstatistics_2022.pdf?sfvrsn=6fbb4d17_3 (accessed May 26, 2022); 2 IPBES; 2020. https://ipbes.n
Slide 62: COVID-19 vaccine validates our mRNA technology
COVID-19 vaccine validates our mRNA technology and paves the way for future mRNA products 62 mRNA for ID 10 months development time doses administered as of April 20223.4 billion 1+ billion vaccinated persons safety database
Slide 63: BioNTech and Pfizer mRNA collaboration programs in infectious diseases
BioNTech and Pfizer global mRNA collaboration programs in infectious diseases FIH, first-in-human. 63 COVID-19 COMIRNATY: globally leading franchise Variant-adapted vaccine launch planned for 2H 2022 Influenza Single-dose quadrivalent mRNA vaccine Phase 1 data update expected in 2022 Shingles Potent
Slide 64: Well prepared for the next phase of COVID-19 pandemic
As of March 2022 1 Approved as a 2-dose series for prevention of COVID-19 in individuals 16 years of age and older; 2-dose series under Emergency Use Authorization for individuals 5‒15 years old, and 3-dose series under Emergency Use Authorization for children 6 months through 4 years of age; 2 The
Slide 65: Low-dose vaccination confers high protection in children
FDA EUA granted for pediatric use Low-dose vaccination safely confers high protection 65 Three doses of BNT16b2 likely to confer high degree of protection against Omicron BA.1 21.8 4.2 32.9 80.3 75.5 82.3 0 25 50 75 100 6 months to <5 years 6 months to <2 years 2 years to <5 years V a c c in e e ff
Slide 66: Next-generation vaccine approaches for durable variant protection
Variant-adapted vaccines Next-generation vaccine approaches aim to provide durable variant protection 66 COMIRNATY Omicron-adapted Mono-/Multi-valent T-cell enhancing Pan-coronavirus Variant adapted and next-generation vaccine approaches Clinical data presented at VRBPAC meeting June 2022 Rolling su
Slide 67: Omicron BA.1 GMR superiority criterion (>55y)
GMR superiority criterion: the lower bound of 95% confidence interval for GMR is >1.0 Variant-adapted vaccines І Omicron BA.1 GMR consistent with simple superiority criterion for Omicron-modified vaccines (>55y participants) 67 Pandemic prep. Participants WITHOUT evidence of infection up to 1 month
Slide 68: Omicron BA.1 GMR super superiority for monovalent vaccine
Variant-adapted vaccines І Omicron BA.1 GMR consistent with super superiority criterion for monovalent Omicron-modified vaccine (>55y participants) 68 Pandemic prep. Participants WITHOUT evidence of infection up to 1 month after the study vaccination GMT (95% CI) 1M post-dose Vaccine group / BNT162b
Slide 69: Omicron BA.1 seroresponse rate exceeds non-inferiority criterion
Variant-adapted vaccines І Omicron BA.1 seroresponse rate exceeds noninferiority criterion for Omicron-containing vaccines (>55y participants) 69 Pandemic prep. Participants WITHOUT evidence of infection up to 1 month after the study vaccination n (%) (95% CI) 1M post-dose Seroresponse difference in
Slide 70: GMTs up to 1 month after vaccination
Variant-adapted vaccines І GMTs in participants without evidence of infection up to 1 month after study vaccination: Immunogenicity subset N T 5 0 ( ti te r) G M T Pandemic prep. BNT162b2 (30 g) BNT162b2 (60 g) BNT162b2 OMI (30 g) BNT162b2 OMI (60 g) Bivalent (30 g) Bivalent (60 g) 149 163 163 169 1
Slide 71: Reactogenicity profile of variant vaccines
Variant-adapted vaccines І Reactogenicity profile of variant vaccines overall similar to prototype BNT162b2 vaccine Pandemic prep. Participants aged 18−55 years • Monovalent Omicron-modified vaccine (30 µg) showed a similar local reaction and systemic event profile as the prototype vaccine (30 µg) P
Slide 72: Omicron-containing variant vaccine summary
Variant-adapted vaccines Omicron-containing modified-variant vaccine summary 72 Pandemic prep. Neutralizing responses for Omicron-containing vaccines are consistent with regulatory criteria: • Simple superiority for GMR and non-inferiority for seroresponse (monovalent and bivalent vaccines) • “Super
Slide 73: Vaccine updates need to adapt with the pace of the virus
Variant-adapted vaccines І SARS-CoV-2 epidemiology changes quickly: Vaccine updates need to adapt with the pace of the virus Pandemic prep. GISAID Initiative database: https://www.gisaid.org/ (accessed June 20, 2022). ~8 months ~3 months Clinical (current) Pre-clinical/CMC (proposed) Variant vaccine
Slide 74: Omicron has more sublineages than all other variants combined
Variant-adapted vaccines Omicron has more sublineages than all other variants combined GISAID Initiative database: https://www.gisaid.org/ (accessed June 22, 2022). 74 Omicron mutanome continues to rapidly expand Omicron sublineages continue to show increased immune escape properties Omicron subline
Slide 75: BA.2.12.1 and BA.4/5 increasing in prevalence
Variant-adapted vaccines BA.2.12.1 and BA.4/5 are now increasing in prevalence GISAID Initiative database: https://www.gisaid.org/ (accessed May 31, 2022). 75 Pandemic prep.2 USA circulating strains trend
Slide 76: BA.4/5 RBD and NTD sequences distinct from BA.1 and BA.2
Variant-adapted vaccines Omicron BA.4/5 RBD and NTD sequences are distinct from BA.1 and BA.2 Tuekprakhon A, et al. bioRxiv 2022; doi.org/10.1101/2022.05.21.492554. 76 Omicron BA.4 and BA.5 contain additional mutations in the RBD, in particular the reversion mutation R493Q, together with mutations L
Slide 77: Omicron-modified vaccines as 4th dose elicit improved neutralization
F F R N T 5 0 501.1 822.0 771.3 678.178.4 145.3 226.3 137.2 10 100 1,000 10,000 OMI 30 μg n=17 OMI 60 μg n=18 Bivalent 30 μg n=13 Bivalent 60 μg n=18 BA.1 BA.4/5 LOD Variant-adapted vaccines І Omicron-containing modified variant vaccines as 4th dose elicit improved Omicron neutralization response FF
Slide 78: BA.4/5 variant-adapted vaccines in mice
Variant-adapted vaccines І Omicron BA.4/5 variant-adapted vaccines neutralize Omicron sub-lineages in balb/c mice Internal data. 78 • N=8 Balb/c mice per group • Pre-immunized with 2-doses of 1µg BNT162b2 on day 0 and day 21 • Booster administered on day 104 W uh an B A .1 B A .2 B A .2 .1 2. 1 B A
Slide 79: BA.4/5 variant-adapted vaccines in mice: neutralizing GMTs
Variant-adapted vaccines І Omicron BA.4/5 variant-adapted vaccines neutralize Omicron sub-lineages in balb/c mice Internal data. 79 • N=8 Balb/c mice per group • Pre-immunized with 2-doses of 1µg BNT162b2 on day 0 and day 21 • Booster administered on day 104 Neutralizing GMTs Geometric mean fold inc
Slide 80: Variant/Wuhan pVN50 titer ratio in mice
Variant-adapted vaccines І Omicron BA.4/5 variant-adapted vaccines increase Omicron sub-lineages/Wuhan ref. pVN50 titer ratio in balb/c mice Internal data. 80 W uh an B A .1 B A .2 B A.2 .1 2. 1 B A.4 /B A .5 0.1 1 R a ti o o f v a ri a n t/ W u h a n r e f. p V N 5 0 t it e r BNT162b2 Omi BA.4/5 Ge
Slide 81: A science-driven preparedness strategy
Variant-adapted vaccines A science-driven preparedness strategy 81 Pandemic prep.2 Discussions with regulators are ongoing to define most appropriate pathways to leverage current experience and ensure that variant-adapted vaccines can be made available in the future to timely address newly emerging
Slide 82: Integrated model for future pandemic preparedness
Pandemic preparedness An integrated, multi-faceted model for future pandemic preparedness 82 Response PREPAREDNESS Field-based testing Laboratory testing Risk prediction (AI driven) Manufacturing Planning for deployment Pandemic prep. Our goal: Enable end-to-end manufacturing and delivery of our vac
Slide 83: Malaria, tuberculosis, and HIV remain endemic
Malaria, tuberculosis, and HIV remain endemic HIV, human immunodeficiency virus; WHO, World Health Organization. World Health Organization fact sheets. https://www.who.int/news-room/fact-sheets (accessed June 09, 2022). 83 ~229 million cases in 2020 across the WHO Africa Region 601,000 deaths in 202
Slide 84: BioNTainer: mRNA manufacturing network in Africa and beyond
BioNTainer: Building an mRNA manufacturing network to address infectious diseases in Africa and beyond 84 The BioNTainer solution aims to ensure: Partner contribution: Indicative manufacturing network Potential partners for fill & finish Pandemic preparedness & other use cases Sustainability through
Slide 85: Urgent need for next-generation precision antibacterials
Urgent need for next-generation precision antibacterials 1 Antimicrobial Resistance Collaborators. Lancet 2022; 399:629–655; 2 O'Neill J. Wellcome Collection. Attribution 2014; Available at: https://wellcomecollection.org/works/rdpck35v (accessed June 06, 2022). 85 Antibacterials Prevent up to 10 mi
Slide 86: Synthetic endolysins: precision antibacterials
Synthetic (endo)lysins − A potentially ideal class of precision antibacterials 1 Fischetti VA. Int J Med Microbiol 2010; 300:357–362; 2 Vázquez R, et al. J Virol 2021; 95:e0032121; 3 Fowler VG, et al. J Clin Invest 2020; 130:3750–3760. 86 Modular domain architecture Enzymatically active domain Cell-
Slide 87: Modular domain architecture of endolysins
CBDs mediate genus or species specificity (but EADs also contribute to specificity) 15+ different classes of CBDs known Diverse and modular domain architecture allows flexibility in engineering 87 Enzymatically active domain Cell-wall binding domain Enzymatically active domain Outer-membrane penetra
Slide 88: Endolysins are highly potent and allow focused microbiome modulation
Endolysins are highly potent and allow laser-focused microbiome modulation 88 MIC range (µg/ml) for Gardnerella (>20 strains tested)2 PM-477 Clindamycin Metronidazole 0.03–1 <0.06–1 8 to >128 (R) Method: Bacteria grown in vitro and then treated with single dose of PM-477 for 5 hours. Suspension plat
Slide 89: Expanding opportunities in infectious diseases
Expanding opportunities in infectious diseases: 4 first-in-human mRNA vaccine trial starts expected in 2022 1 Global co-development co-commercial agreement with Pfizer; 2 Global rights licensed to Pfizer; 3 University of Pennsylvania collaboration; 4 Collaboration with Bill & Melinda Gates Foundatio
Slide 90: Q&A
O&A BIONT=CH
Slide 91: Time for a break
TIME FOR A BREAK!
Slide 92: An introduction to the oncology pipeline
BIONT=Cri we Oncology pipeline —_ _——ae
Slide 93: Understanding and exploiting immunological mechanisms
Understanding and exploiting immunological mechanisms Immune system 93 T cell Tumor cells Treg 4-1BB PD-1 PD-L1 TCRMHC Pro-inflammatory cytokines Naive T cell APC CD40 mRNA-encoded cancer vaccines1 Shared antigens Individual antigens CAR-, TCR-, and non- engineered cell therapies2 33 1 Next-generati
Slide 94: Oncology pipeline: significant progress and expansion in 2022
SMIM, small molecule immunomodulators. 1 Investigator-initiated Phase 1 trial; 2 Collaboration with Genentech; 3 Collaboration with Sanofi; 4 Collaboration with Genmab. Oncology pipeline: Significant progress and expansion in 2022 94 Drug class Platform Product candidate Indication (targets) Pre-cli
Slide 95: Unique combination potential across platforms
Unique combination potential across platforms 95 Vaccine-induced T-cell response + expansion through PD1 blockade Autologous CAR T-cell therapy + vaccine-amplified T-cell response Vaccine-induced T-cell response + amplification through RiboCytokines Approved anti-PD-1/PD-L1 mRNA cancer vaccines + mR
Slide 96: mRNA cancer vaccines
mRNA cancer vaccines
Slide 97: mRNA vaccines for potent multi-targeting of cancers
mRNA vaccines for enabling potent multi-targeting of cancers 97 mRNA cancer vaccines Multiple shared antigens Individualized therapy Off-the-shelf therapy iNeST* FixVac Fixed Antigen Vaccine individualized Neoantigen-Specific immunoTherapy Backbone optimized uridine mRNA (uRNA) Neo- antigens Kranz L
Slide 98: Driving continuous iNeST innovation with data
iNeST ǀ Autogene cevumeran (BNT122) Driving continuous iNeST innovation with data iNeST is being developed in collaboration with Genentech. 98 mRNA cancer vaccines Just-in-time manufacturing Dedicated mRNA GMP production facilities Targeting delivery of <5 weeks Selection algorithms AI and ML optimi
Slide 99: iNeST Phase 1 as monotherapy and with atezolizumab
iNeST ǀ Autogene cevumeran (BNT122) Phase 1 as monotherapy and in combination with atezolizumab CPI, checkpoint inhibitor; PR, partial response; PD, progressive disease; SD, stable disease. 1. Sahin U, et al. Nature 2017; 547:222–226; BNT121 was a precursor to BNT122 and the iNeST collaboration with
Slide 100: Neoantigen vaccines suited for early-line setting
iNeST ǀ Autogene cevumeran (BNT122) Neoantigen vaccines are well suited for the early-line setting iNeST is being developed in collaboration with Genentech. 100 mRNA cancer vaccines Early line (adjuvant/first line) Late line (refractory) Tumor mass Low tumor burden Large bulky tumors Tumor resistanc
Slide 101: Randomized trial in 1L advanced melanoma
iNeST ǀ Autogene cevumeran (BNT122) Phase 2 open-label, randomized trial in 1L advanced melanoma CPI, checkpoint inhibitor; DoR, duration of response; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival. ClinicalTrials.gov: NCT03815058. 101 mRNA
Slide 102: High medical need in adjuvant colorectal cancer
High medical need in the adjuvant treatment of Stage II (high risk)/Stage III colorectal cancer mRNA cancer vaccines CRC, colorectal cancer; ctDNA, circulating tumor DNA; ; OS, overall survival; SoC, standard of care., 1 WHO factsheet on cancer. 2018; 2 Seer database; 3 Fan G, et al. PLoS One 2017;
Slide 103: Randomized trial in adjuvant colorectal cancer
iNeST ǀ Autogene cevumeran (BNT122) Phase 2 randomized trial vs watchful waiting in adjuvant colorectal cancer CRC, colorectal cancer; ctDNA, circulating tumor DNA; OS, overall survival; q1/2/6w, every 1/2/6 weeks; R, randomize; RFS, relapse-free survival; SoC, standard of care; TTF, time to treatme
Slide 104: Adjuvant BNT122 in pancreatic ductal adenocarcinoma
iNeST ǀ Autogene cevumeran (BNT122) Phase 1 trial of adjuvant BNT122 in pancreatic ductal adenocarcinoma mFOLFIRINOX, modified FOLFIRINOX; PDAC, pancreatic ductal adenocarcinoma; q2w, every 2 weeks. Balachandran VP, et al. ASCO Annual Meeting 2022; Poster presentation 2516; ClinicalTrials.gov: NCT04
Slide 105: Substantial and durable T cell expansion in immune responders
iNeST ǀ Autogene cevumeran (BNT122): substantial and durable T cell expansion observed in immune responders after BNT122 treatment iNeST is being developed in collaboration with Genentech. Balachandran VP, et al. ASCO Annual Meeting 2022; Poster presentation 2516. 105 mRNA cancer vaccines Immunogeni
Slide 106: Functional T cells confirmed by ELISPOT
iNeST ǀ Autogene cevumeran (BNT122) Functional T cells confirmed by ELISPOT in immune responders iNeST is being developed in collaboration with Genentech. Balachandran VP, et al. ASCO Annual Meeting 2022; Poster presentation 2516. 106 mRNA cancer vaccines Assay 2: T cell specificity to autogene cevu
Slide 107: Immune response correlates with delayed recurrence
iNeST ǀ Autogene cevumeran (BNT122) Immune response correlates with delayed recurrence in adjuvant PDAC iNeST is being developed in collaboration with Genentech. Balachandran VP, et al. ASCO Annual Meeting 2022; Poster presentation 2516. 107 mRNA cancer vaccines RFS from resection (n=16) • Responder
Slide 108: FixVac: leveraging shared tumor-associated antigens
FixVac Leveraging shared tumor-associated antigens for cancer treatment HNSCC, head and neck squamous-cell carcinoma; HPV, human papilloma virus; NSCLC, non-small-cell lung cancer. 108 mRNA cancer vaccines Vaccine backbone with shared antigens Lipoplex = Fixed vaccine combination against shared tumo
Slide 109: Treatment options needed after CPI failure in advanced melanoma
Treatment options needed to address CPI failure in advanced melanoma CPI, checkpoint inhibitor; DoR, duration of response; mPFS, median progression free survival; ORR, overall response rate; R/R, refractory/resistant; WHO, World Health Organization. 1 Available at: https://www.melanomauk.org.uk/2020
Slide 110: BNT111 durable responses in Phase 1/2 melanoma
FixVac ǀ BNT111 Durable responses in a Phase 1/2 trial in advanced CPI-experienced melanoma Data cut-off: July 29, 2019. 1 Patients evaluable for efficacy; 2 One patient had a metabolic complete response with SD as best response, according to irRECIST1.1. CPI, checkpoint inhibitor; ORR, overall resp
Slide 111: Long duration of clinical responses with BNT111
FixVac ǀ BNT111 – Long duration of clinical responses observed for patients receiving BNT111 monotherapy and combination with CPIs1 Data cut-off: May 24, 2021. 1 One patient in the BNT111 monotherapy group who achieved a CR is not shown as only non-measurable target lesions were present (which later
Slide 112: Tumor shrinkage with BNT111 monotherapy or combination
FixVac ǀ BNT111 – Tumor shrinkage observed in patients receiving BNT111 monotherapy or combination with a PD-1 inhibitor 1,2 Data cut-off: May 24, 2021. 1 One patient had an 83.2% decrease of target lesion from baseline but experienced a new target lesion and had SD as the best overall response. Pat
Slide 113: Strong immunogenicity and clinical activity in Lipo-MERIT
FixVac ǀ BNT111 Strong immunogenicity and promising clinical activity in Phase 1 Lipo-MERIT Data cut-off: May 24, 2021. ED, evidence of disease; IVS, in vitro stimulation; NED, no evidence of disease; NR, not reached; TAA; tumor associated antigen. Loquai C, et al. SITC Annual Meeting 2021; Poster p
Slide 114: Randomized trial of BNT111 ± cemiplimab
FixVac ǀ BNT111 Phase 2 randomized trial ± cemiplimab in patients with anti-PD1-R/R melanoma DCR, disease control rate; DoR, duration of response; ORR, overall response rate; OS, overall survival; PFS, progression free survival; R/R, relapsed/refractory; TTR, time to response. ClinicalTrials.gov: NC
Slide 115: mRNA cancer vaccines near-term milestones
FPD, first patient dosed; HNSCC, head-and-neck squamous-cell carcinoma; NSCLC, non-small-cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; R/R, relapsed/refractory. 1 BNT122, Collaboration with Genentech; 2 Investigator-initiated study. mRNA cancer vaccines near-term milestones 115 mRNA canc
Slide 116: Protein therapeutics
Protein therapeutics
Slide 117: BNT311: checkpoint blockade and conditional T cell co-stimulation
BNT311 Combining checkpoint blockade and conditional T cell co-stimulation * BNT311 (Gen1046) is partnered with Genmab based on 50/50 sharing of costs and profits. 1 Muik A, et al. Cancer Discov 2022; 12:1248−1345. 117 Protein therapeutics Dual targeted 4-1BB co-stimulation that is conditional on PD
Slide 118: BNT311 first-in-human Phase 1/2 trial
BNT311 First-in-human Phase 1/2 trial in heavily pretreated advanced solid tumors * BNT311 (Gen1046) is partnered with Genmab based on 50/50 sharing of costs and profits. CC, cervical cancer; EC, endometrial cancer; HNSCC, head and neck squamous-cell cancer; MTD, maximum tolerated dose; NSCLC, non-s
Slide 119: BNT311 dose escalation safety profile
BNT311: Initial results in dose escalation show a manageable safety profile with most AEs being Grade 1 or 2 Data cut-off: August 31, 2020. DLT, dose-limiting toxicity; MTD, maximum tolerated dose; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event. Garralda E, et al. SITC
Slide 120: BNT311 anti-tumor activity
BNT311 Anti-tumor activity (Phase 1 dose escalation part) Data cut-off: September 29, 2020. Post-baseline scans were not conducted for five patients. A Minimum duration of response (5 weeks) per RECIST v1.1 not reached. B PR was not confirmed on a subsequent scan. NE, non-evaluable; NSCLC, non-small
Slide 121: BNT311 activity in CPI-experienced NSCLC
BNT311 Clinical activity in patients with CPI-experienced relapsed/refractory NSCLC Data cut-off: October 12, 2020. * PR was not confirmed by a subsequent scan. Patients all had ≥1 post-baseline tumor assessment (scheduled every 6 weeks) and thus could be assessed for clinical benefit; 6 of 12 patie
Slide 122: Objective responses more frequent in PD-L1+ patients
BNT311 Objective responses observed more frequently in PD-L1+ patients 1 Among patients with evaluable baseline tumors. Fisher exact test odds ration for PD-L1+ vs PD-L1- tumors OR=0.11. Data cut-off: September 21, 2021. Ponce Aix S, et al. SITC Annual Meeting 2021; Poster presentation 516. 122 Prot
Slide 123: PD-L1×4-1BB with PD-1 blockade in preclinical models
Combination of PD-L1×4-1BB bispecific with PD-1 blockade improves activity in preclinical models 1 Growth curves were discontinued when <50% of the animals within a treatment group remained alive or at day 35; 2 Defined as the percentage of mice with tumor volumes <500 mm3. Mantel–Cox analysis on da
Slide 124: BNT311 randomized Phase 2 trial in NSCLC
BNT311 Open-label, randomized Phase 2 trial in CPI-experienced PD-L1+ R/R NSCLC Partnered with Genmab; 50:50 profit/loss collaboration. CPI, check point inhibitor; NSCLC, non-small-cell lung cancer; OS, overall survival; PFS, progression-free survival; R/R, refractory/relapsed; TPS, tumor proportion
Slide 125: BNT312: bispecific antibody strengthening T cell and APC synapse
BNT312 Bispecific antibody designed to strengthen T cell and APC synapse BNT312 (Gen1042) is partnered with Genmab based on 50/50 sharing of costs and profits; 1 Muik A, et al. J Immunother Cancer 2022;0:e004322. doi:10.1136/jitc-2021-004322. 125 Protein therapeutics Inert Fc, double conditional, du
Slide 126: BNT312 double-conditional dual-agonist molecule
BNT312 Double-conditional dual-agonist molecule BNT312 (Gen1042) is partnered with Genmab based on 50/50 sharing of costs and profits. Muik A, et al. J Immuno Ther Cancer 2022; 10:e004322. 126 Protein therapeutics R e la ti v e l u m in e s c e n c e u n it s In the absence of CD40+ cells, BNT312 do
Slide 127: BNT312 strengthens crosslinking between T cells and APCs
BNT312 strengthens crosslinking between T cells and APCs 127 Single Z plane of iDC cocultured with preactivated CD8+ T cells in the presence of Alexa Fluor 647-conjugated DuoBody-CD40.4-1BB (magenta) and LFA-1 (green) antibodies, on the x and y axes the z-stack of the same picture with the relative
Slide 128: BNT312 promotes DC maturation
BNT312 showed higher ability to promote DC maturation vs either monoclonal antibody or their combination BNT312 (Gen1042) is partnered with Genmab based on 50/50 sharing of costs and profits. The dotted line shows the percentage of HLA-DR+ CD86+ DCs in DC-T- cell cultures in the absence of treatment
Slide 129: BNT312 favorable safety profile across dose range
BNT312: Favorable safety profile across a wide dose range; 100 mg selected for dose expansion phase Data cut-off: August 27, 2021. Partnered with Genmab; 50:50 profit/loss collaboration. CRS, cytokine release syndrome; DLT, dose-limiting toxicity; MTD, maximum tolerated dose. Johnson M, et al. SITC
Slide 130: BNT312 modulation of peripheral biomarkers
BNT312: Clinical modulation of peripheral biomarkers supports its function in a wide range of solid tumors Data cut-off: August 27, 2021. Partnered with Genmab; 50:50 profit/loss collaboration. Mean fold changes of cytokine concentrations and % of CD8+ T cells ± standard error of the mean (SEM) are
Slide 131: Near-term milestones for protein therapeutics
FPD, first patient dosed; NSCLC, non-small-cell lung cancer; R/R, relapsed/refractory. 1 (GEN1046 and GEN10542), partnered with Genmab; 50:50 profit/loss collaboration.. Near-term milestones for protein therapeutics 131 Protein therapeutics Platform Product candidate Indication Next milestone Next-g
Slide 132: Extending cell therapy to solid tumors
Extending cell therapy to solid tumors
Slide 133: Developing autologous cell therapy platforms
Developing 3 autologous cell therapy platforms and addressing novel targets Reinhard K, et al. Science 2020; 367:446–453 133 NEO-STIMChimeric antigen receptor (CAR)1 T-cell receptor (TCR) CARVac • Autologous engineered cell therapy to address extra-cellular targets + RNA-LPX vaccine • Individualized
Slide 134: BNT211: CAR T targeting claudin-6 with CARVac
• 2nd generation CAR directed against CLDN6, a cancer specific carcino-embryonic antigen • CLDN6 is expressed in multiple solid cancers with high medical need • CARVac drives in vivo expansion, persistence and efficacy of CAR T BNT211: Phase 1/2 trial evaluating next-generation CAR T targeting claud
Slide 135: BNT211 patient characteristics
BNT211 16 heavily pre-treated patients assessed in the trial Data cut-off: March 10, 2022. CLDN6, claudin 6; DL, dose level. Haanen J, et al. AACR Annual Meeting 2022; Oral presentation CT002. 135 Patient characteristics Monotherapy DL1 (n=3) Combination DL1 (n=3) Monotherapy DL2 (n=6) Combination D
Slide 136: BNT211 well tolerated at evaluated dose levels
BNT211 was well tolerated at the dose levels evaluated Data cut-off: March 10, 2022. AE, adverse event; CAR, chimeric antigen receptor; CARVac, CAR T cell-amplifying RNA vaccine; CRS, cytokine release syndrome; DL, dose level; DLT, dose-limiting toxicity; HLH, hemophagocytic lymphohistiocytosis; ICA
Slide 137: BNT211 ORR 43% and DCR 86% at 6 weeks
BNT211 An ORR 43% and DCR of 86% (6 PR, 5 SD+, 1 SD) were achieved at 6 weeks Data cut-off: March 10, 2022; first assessment, 6 weeks post infusion. ACT, adoptive cell transfer; CR, complete response; DCR, disease control rate; EoT, end of trial (due to PD); PD, progressive disease; PR, partial resp
Slide 138: Clinical benefit in testicular cancer patients
BNT211 Clinical benefit seen in patients with testicular cancer receiving DL2 Data cut-off: March 10, 2022. CR, complete response; DL, dose level; PR, partial response. Haanen J, et al. AACR Annual Meeting 2022; Oral presentation CT002. 138 Testicular Ovarian Others One patient with initial PR showe
Slide 139: Responses in two patients with testicular cancer
BNT211 Responses in two patients with testicular cancer Data cut-off: March 10, 2022. AFP, alpha-fetoprotein; CAR, chimeric antigen receptor; CARVac, CAR T cell-amplifying RNA vaccine; CLDN6, claudin 6; CR, complete response; d, day; DL, dose level. Haanen J, et al. AACR Annual Meeting 2022; Oral pr
Slide 140: BNT221: NEO-STIM individualized neoantigen-targeted strategy
BNT221: NEO-STIM is an individualized neoantigen-targeted strategy that addresses the limitations of tumor-infiltrating lymphocyte therapies 1 Velez D, et al. SITC Annual Meeting 2021, Poster presentation 201; 2 Lenkala D, et al. SITC Annual Meeting 2020, Poster presentation 153. 140 Targets each pa
Slide 141: BNT221 Phase 1 trial in PD-1-refractory melanoma
BNT221 Phase 1 trial in patients with PD-1-refractory metastatic melanoma Velez D, et al. SITC Annual Meeting 2021, Poster presentation 201; ClinicalTrials.gov: NCT04625205. 141 Cohort A Dose escalation (3×3) • Unresectable or metastatic melanoma • Progression on anti-PD-1 • Received anti CTLA-4 Sta
Slide 142: TCR discovery platform
TCR discovery platform for tumor- and patient-specific therapies TCR, T-cell receptor. 142 Cell therapies • Technologic iterations • Combination with other assets (e.g. RiboCytokines) • Acquisitions: PRAME-TCR and PD1-41BB switch (Medigene, Feb 2022) • TCR warehouse: multiple TCRs to target one or m
Slide 143: RiboCytokines
RiboCytokines
Slide 144: RiboCytokines overcome limitations of recombinant cytokine therapy
RiboCytokines Designed to overcome limitations of recombinant cytokine therapy , lipid nanoparticle; PK, pharmacokinetic; IL-2, Interleukin-2; IL7, Interleukin-7; UTR, untranslated region RiboCytokine® is a registered trademark of BioNTech. 144 RiboCytokines Systemic delivery • Backbone optimized an
Slide 145: BNT151 stimulates CD8+ and NK cells
BNT151 Stimulates CD8+ and NK cells, without extensively triggering Treg cells Vormehr M, et al. SITC Annual Meeting 2019; Poster presentation 626. 145 BNT151 design BNT151 mediates increase of effector CD8+ to Treg ratio BNT151 • Weakened binding to IL-2Rα • Designed to stimulate naïve and effector
Slide 146: BNT152 + BNT153 increase CD8 proliferation, reduce Treg
• Stimulates recently activated anti-tumor T cells and regulatory T cells mRNA encoding IL-7 • Sensitizes T cells to IL2 & increases CD8+ and CD4+ T cell expansion and survival • Controls fraction of immunsuppressive Treg among CD4+ T cells that are stimulated by IL-2 BNT152 + BNT153 Increase CD8 pr
Slide 147: BNT152 + BNT153 combined with mRNA vaccine
BNT152 + BNT153 Combining with mRNA vaccine Kranz LM, et al. SITC Annual Meeting 2019; Poster presentation 620. 147 BNT152 boosts therapeutic anti-tumor activity of BNT153 in combination with an RNA vaccine in the CT26 model BNT152 + BNT153 preferentially expands vaccine-induced CD8+ T cells 1 10 10
Slide 148: Therapeutic efficacy of BNT152 + BNT153 with RNA vaccination
BNT152 + BNT153 Therapeutic efficacy of BNT152 + BNT153 in combination with RNA vaccination 1 Kranz LM, et al. SITC Annual Meeting 2019; Poster presentation 620; 2 Kranz LM, et al. CIMT Annual Meeting 2021; ePresentation. 148 0 25 50 75 100 0 25 50 75 100 Days after tumor inoculation P e r c e n t s
Slide 149: BNT151 in combination with T cell vaccination
BNT151 Therapeutic activity of BNT151 in combination with T cell vaccination 1 Kranz LM, et al. SITC Annual Meeting 2019; Poster presentation 620; 2 Kranz LM, et al. CIMT Annual Meeting 2021; ePresentation. 149 RiboCytokines TRP1 vaccine + hIL2 TRP1 vaccine + Control Control + hIL2 Control + BNT151
Slide 150: BNT151 mediates CAR T cell expansion in mice
BNT151 treatment leads to initial similar CAR T cell expansion in vivo compared to CLDN6-LPX treatment BNT151-mediated CAR T expansion peaks at day 3/4 after treatment, followed by contraction phase at day 7 CLDN6-LPX + BNT151 improves CAR T cell expansion Data on file. BNT151 mediates CAR T cell ex
Slide 151: Long-term CAR T expansion with vaccine and BNT151
Long-term in vivo expansion and anti-tumor activity of CAR T cells in combination with vaccine and BNT151 Internal data. 151 RiboCytokines CAR T-cell expansion and persistence in NSG mice after repetitive treatment cycles 1° 2°3° Treatment 4° 5° 0 20 40 60 80 100 0.1 1 10 100 Days post ACT x -f o ld
Slide 152: Two Phase 1/2 FIH trials of mRNA-encoded cytokines
BNT152 + BNT153 BNT151, BNT152 + BNT153 Two Phase 1/2 FIH trials of mRNA-encoded cytokines in solid tumors FIH, first-in-human, HCC, hepatocellular carcinoma; HNSCC, head and neck squamous-cell cancer; MAD, maximum-administered dose; MTD, maximum tolerated dose; NSCLC, non-small-cell lung cancer; OB
Slide 153: Closing remarks
BIONT=Cri EY Closing remarks
Slide 154: Advancing toward our long-term vision
Advancing toward our long-term vision 154 Oncology Infectious diseases 5 randomized Phase 2 trials 1 marketed vaccine Market leader in COVID-19 vaccines 10+ preclinical programs 1 Phase 1 program16 programs in 21 clinical trials Maintain and deepen COVID-19 vaccine leadership Multiple product launch
Slide 155: Q&A
O&A BIONT=CH
Slide 156: Thank you
THANK YOU
Slide 157: BIONT=CH
BIONT=CH