BioNTech SE · NASDAQ:BNTX
BioNTech — Investor Day (November 2023)
147 slides from BioNTech's investor day presentation, Nov 7, 2023
Slide 1: Innovation Series 2023
Innovation Series 2023 November 7, 2023 9:00 AM – 1:00 PM ET
Slide 2: Welcome & Introductory Remarks
1 Welcome & Introductory Remarks Ryan Richardson Chief Strategy Officer
Slide 3: This Slide Presentation Includes Forward-Looking Statements
This Slide Presentation Includes Forward-Looking Statements 3 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: BioNTech's expected revenues and net profi
Slide 4: Innovation Series 2023 Agenda
Innovation Series 2023 Agenda 1 Welcome and Introductory Remarks 9:00 AM 2 The BioNTech Approach to Innovation 9:05 AM 3 AI Capabilities and Projects 9:25 AM 4 Our Multi-Platform Oncology Strategy 9:35 AM 5 Our Growth Strategy 10:00 AM Break (10 mins) 6 Novel Backbones: Next-Generation ADCs and Immu
Slide 5: Innovation Series 2023 – BioNTech Team
Innovation Series 2023 – BioNTech Team 5 Prof. Ugur Sahin, M.D. Chief Executive Officer, Co-founder Karim Beguir Chief Executive Officer, InstaDeep Prof. Ilhan Celik, M.D. Vice President, Clinical Development Prof. Özlem Türeci, M.D. Chief Medical Officer, Co-founder Ryan Richardson Chief Strategy O
Slide 6: The BioNTech Approach to Innovation
2 The BioNTech Approach to Innovation Prof. Ugur Sahin, M.D. CEO and Co-founder
Slide 7: We Made History
We Made History 7 1. Nature 589, 16-18 (2021); 2. Measured by sales recorded for a single product in a single year (>$40 billion combined of direct sales recorded by Pfizer or BioNTech in both 2021 and 2022); 3. Cumulative doses shipped in the years 2021 and 2022. 4. COVID-19 Excess Mortality Collab
Slide 8: A Global Immunotherapy Leader
Innovation at scale A Global Immunotherapy Leader 1. As of October 1, 2023; 2. As of October 24, 2023. Healthcare and social responsibility Innovative and diversified pipeline Leadership in COVID-19 vaccines development Building and expanding a long- term and successful COVID-19 franchise Developing
Slide 9: BioNTech Today
BioNTech Today 1. As of 31 October, 2023. R&D = research and development; HQ = headquarters United Kingdom London Rwanda Kigali BioNTainer (under construction) Austria Vienna Germany (HQ + 6 sites) Commercial- & clinical-scale mRNA Clinical-scale cell therapy Singapore mRNA commercial manufacturing
Slide 10: Harnessing the Full Power of the Immune System to Fight Human Diseases
Cell types Harnessing the Full Power of the Immune System to Fight Human Diseases 10 Macrophage NK cell Dendritic cell Cell migration Removal of diseased cells Healing Cell-cell communication B-cellT-cell Function Cancer Autoimmune diseases Neurodegenerative diseases Cardiovascular disease Infectiou
Slide 11: Focused on Five Innovation Pillars
Focused on Five Innovation Pillars 11 Deep understanding of the immune system Multi-platform innovation engine Manufacturing and automation Target discovery and characterization Digital & AI/ML AI = artificial intelligence; ML = machine learning.
Slide 12: Multi-Technology Innovation Engine
Multi-Technology Innovation Engine 12 1. mRNA encoded cancer-targeting antibodies and cytokines. CAR = chimeric antigen receptor; TLR = toll-like receptor; TCR = T cell receptor; Abs = antibodies; STING = stimulator of interferon genes. Individualized therapiesEnabling technology ADCs * SELECTIVE TL
Slide 13: mRNA 2023: A Broad Technology Toolbox
mRNA 2023: A Broad Technology Toolbox 13 Holtkamp et al. Blood 2006; Kuhn et al. Gene Therapy 2010; Sahin, Türeci & Kariko Nat Drug Discovery 2014; Vogel et al. Mol Therapy 2018; Beissert et al. Mol Therapy 2020. mRNA formats Local Tissue-specific Systemic Lipoplex nanoparticles Lipid nanoparticles
Slide 14: Our Innovation Approach To Manufacturing Challenges
Our Innovation Approach To Manufacturing Challenges 14 GMP = Good Manufacturing Practice BioNTech Manufacturing Facility in Marburg Annual has manufactured mRNA drug substance for 1.6 billion doses Delivery at Large Scale Tailoring & Customization Democratizing access to novel technologies Digitized
Slide 15: AI's Unprecedented Impact on Science and Medicine
AI’s Unprecedented Impact on Science and Medicine 15 The New England journal of medicine vol. 388,13 (2023): 1201-1208. Nature 605, 551–560 (2022). Nature 596, 583–589 (2021). AI, artificial intelligence; ML, machine learning; LLMs, large language models; AGI, artificial general intelligence. Improv
Slide 16: Our Goals for AI
Our Goals for AI 16 AI = artificial intelligence; ML = machine learning; mRNA = messenger ribonucleic acid; TCR = T cell receptor-engineered; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. Optimize mRNA structure and function SARS-CoV-2 variant monitoring and immunogen design Customiz
Slide 17: Accelerate and Enhance BioNTech's AI Vision
Accelerate and Enhance BioNTech’s AI Vision 17 AI = artificial intelligence; ML = machine learning. Fully leverage the power of computational science & AI Implementation strategy • Provide high-quality designs to develop next-generation products with a more efficacious or safer profile • Speed up wo
Slide 18: AI Capabilities and Projects
3 AI Capabilities and Projects Karim Beguir CEO, InstaDeep
Slide 19: Our AI Capabilities
Our AI Capabilities 19 From AI researchers to ML engineers and ML Ops experts, our team has critical size, depth, and a differentiated ability to attract talents in EMEA. Our proprietary GPU cluster in the UK (500 petaflops expected 2024), is optimized for high performance computing and fully manage
Slide 20: End-to-End Therapeutics Platform Powered by AI
End-to-End Therapeutics Platform Powered by AI 20 We apply our AI capabilities at the forefront of the design of potential cancer therapies and infectious disease vaccines Crossfunctional learnings across the research themes are shared Target identification mRNA optimization Gene synthesis Functiona
Slide 21: Gene Synthesis
Gene Synthesis 21 1. Results from April 2022 internal evaluation; data on file. PCR = polymerase chain reaction; AI = artificial intelligence. DNA is the language of biology, and the starting material for a huge range of bioproducts. Creation of long DNA molecules is complex. Assembly PCR builds com
Slide 22: Functional Validation
Functional Validation 22 Data on file. AI = artificial intelligence; EDA = electronic design automation. The ELISpot project streamlines the categorization of experimental results by classifying them into one of three distinct outcomes: those showing no immune response, those exhibiting a positive i
Slide 23: Nucleotide Transformer: State-of-the-Art LLM for DNA
Nucleotide Transformer: State-of-the-Art LLM for DNA 23 Dalla-Torre et al. 2023, https://doi.org/10.1101/2023.01.11.523679 LLM = large language model. The Nucleotide Transformer is our collection of language models tailored for DNA developed in collaboration with TUM and Nvidia. The models have been
Slide 24: Our Multi-Platform Oncology Strategy
4 Our Multi- Platform Oncology Strategy Prof. Ugur Sahin, M.D. CEO and Co-founder
Slide 25: Root Cause of Cancer Treatment Failure
Intraindividual variability & intratumoral heterogeneity driving evasion and secondary resistance mechanism Root Cause of Cancer Treatment Failure Cancer cells Genetically diverse & adaptable5-20 Years – up to 10,000 mutations Mutations DNA Mutation Healthy Cell Mutations Mutations Mutations Mutatio
Slide 26: Our Oncology Strategy
Our Oncology Strategy 26 Strategy Portfolio strategy covering compound classes with synergistic mechanism of actions • Immunomodulators • Targeted therapies • Personalized mRNA vaccines Programs across a wide range of solid tumors and stages of treatment Programs with first-in-class and / or best-in
Slide 27: Towards a Potentially Curative Approach to Cancer
Towards a Potentially Curative Approach to Cancer: Differentiated Combinations of Multiplatform Assets Space for curative approaches Immunomodulators Novel checkpoint inhibitors cytokines, immune agonists mRNA vaccines Targeted therapy ADCs, CAR-T, TCR-T, Small molecules SynergySynergy Synergy Immun
Slide 28: Immunomodulator Programs Overview
A CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer upon binding its target on T cell membranes. BNT313/ GEN10531 Clinical status • Ph1/2 in multiple solid tumors Monospecific antibody with optimized Fc targeting CTLA-4 and selectively depleting tumo
Slide 29: ADCs: The Next Wave of Transformation in Oncology
ADCs: The Next Wave of Transformation in Oncology 29 ASCO 2022 Trastuzumab Deruxtecan vs. Chemotherapy, N Engl J Med 2022;387:9-20; Enfortumab Vedotin, + Pembrolizumab vs. Chemotherapy; Powles TB, et al. EV-302/KEYNOTE-A39: Open-label, randomized phase 3 study of enfortumab vedotin in combination wi
Slide 30: ADCs: The Innovation Cycle is Just Beginning
30 ADCs: The Innovation Cycle is Just Beginning Distinguished ADC linker technology • Stability improving safety profile • Higher efficacy • Novel mechanisms of actions • Tumor specific activation • Improved and novel payloads Novel targets and novel epitopes • Targeting broader spectrum of tumors •
Slide 31: Clinical Stage ADC Programs
Targeting TROP2, cleavable linker and topoisomerase I inhibitor (P1021) DAR: 4 Targeting B7H3, cleavable linker and topoisomerase I inhibitor (P1021) DAR: 6 Targeting HER3, cleavable linker allows for intracellular and extracellular release of topoisomerase I inhibitor (YL0014) DAR: 8 Targeting HER2
Slide 32: Towards a Potentially Curative Approach to Cancer
Towards a Potentially Curative Approach to Cancer: Differentiated Combinations of Multiplatform Assets Space for curative approaches Immunomodulators Novel checkpoint inhibitors cytokines, immune agonists mRNA vaccines Targeted therapy ADCs, CAR-T, TCR-T, Small molecules SynergySynergy Synergy Immun
Slide 33: mRNA Cancer Vaccines May Become the Next Tangible Transformation in Oncology
mRNA Cancer Vaccines May Become the Next Tangible Transformation in Oncology 33 Individual patient samples (blood and tissue) AI-driven neoantigen prediction On-demand tailored RNA manufacturing Individualized immuno- therapy Mapping of mutations Fixed combination of shared tumor antigens Multi-anti
Slide 34: Potential to Address Numerous Cancer Types Through Synergistic Modalities
Potential to Address Numerous Cancer Types Through the Combination of Synergistic Modalities 34 ADC = Antibody-drug conjugate. Multiple combination opportunities Technology toolkitDisclosed phase 2 and 3 indications Cell therapies ADCs Multi-specific immunomodulators mRNA cancer vaccines Non-small l
Slide 35: Advancing Towards Our Vision
Advancing Towards Our Vision . YE = Year end; IND = Investigational new drug. Infectious diseases Globally marketed COVID-19 vaccine franchise Maintain and deepen COVID-19 vaccine leadership Launch multiple oncology products from 2026 onwards Mid-term goalsDriving transformation today Long-term visi
Slide 36: Charting the Course for Tomorrow's Personalized Precision Medicine
Charting the Course for Tomorrow’s Personalized Precision Medicine 36 AI = Artificial Intelligence. AI & digitally-integrated target & drug discovery and development Individualized treatment platforms to address inter-individual variability Deep genomics & immunology expertise to leverage patient da
Slide 37: Our Growth Strategy
5 Our Growth Strategy Ryan Richardson Chief Strategy Officer
Slide 38: Our Diversified Model for the Next Phase of Growth
Our Diversified Model for the Next Phase of Growth 1. Partnered with Pfizer. mRNA = messenger RNA. COVID-191 Immuno-oncology Infectious diseases Drive leadership in COVID-19 vaccine franchise leveraging Pfizer’s global infrastructure Build fully integrated global organization to discover, develop, a
Slide 39: Long-Term Need for Annually Adapted Vaccines Anticipated
XBB.1.5-adapted vaccine Effective against multiple variants of concern5 Long-term health consequences Accumulating evidence demonstrates that COVID-19 vaccination reduces long- COVID4 Continuous evolution Ongoing antigenic evolution of SARS-CoV-21,2 Risk remains high For severe COVID-19 in vulnerabl
Slide 40: Global COVID-19 Vaccine Franchise with Lean Commercial Infrastructure
Global COVID-19 Vaccine Franchise with Lean Commercial Infrastructure 40 Leveraging partners’ commercial infrastructures for global rollout of Comirnaty Lean commercial organization in Germany and Turkey ~55 person field force in DE ~€45m S&M costs YTD1 Fosun commercial territories1 Pfizer commercia
Slide 41: Lean Fixed Cost Base of COVID-19 Vaccine Business
Maintained high gross margin Limited sales & marketing expense Reduced R&D expense due to partner cost-sharing Lean Fixed Cost Base of COVID-19 Vaccine Business 41 1. Gross margin average calculated using forecast information for Fully Year 2023 based on assumptions. 2. S&M average calculated using
Slide 42: COVID-19 Vaccine Market Potential and Mid-term Growth Drivers
COVID-19 Vaccine Market Potential and Mid-term Growth Drivers 42 • Manufacturing base reset to serve endemic market • Shift to commercialization model in some key markets • Expect continued shift to single dose vials and pre-filled syringes • Potential for increased vaccine uptake from combination a
Slide 43: Our Multi-Platform Immuno-Oncology Pipeline Today
Our Multi-Platform Immuno-Oncology Pipeline Today 43 Phase 1 Phase 1/2 Phase 2 Phase 3 BNT211 (CLDN6) Multiple solid tumors BNT311/GEN10463 (PD-L1x4-1BB) Multiple solid tumors BNT411 (TLR7) Multiple solid tumors BNT312/GEN10423 * (CD40x4-1BB) Multiple solid tumors BNT313/GEN10533 (CD27) Multiple sol
Slide 44: Our Strategy Leverages Partner Organizations and Capabilities
Our Strategy Leverages Partner Organizations and Capabilities 44 Agreements signed in 2023. 1.The total consideration to acquire the remaining InstaDeep shares, excluding the shares already owned by BioNTech, amounts to approximately €500 million in cash, BioNTech shares, and performance-based futur
Slide 45: Active Portfolio Management Approach
Translation Active Portfolio Management Approach 45 Access external innovation to accelerate pipeline maturation in a capital-efficient manner Rigorous go/no-go decision-making across all development stages Prioritize lead late-stage programs to accelerate path-to-market Emphasis on demonstration of
Slide 46: Select Oncology Programs to Fuel Our Next Stage of Growth
Select Oncology Programs to Fuel Our Next Stage of Growth 46 1. Partnered with Genentech, member of Roche Group; 2. Partnered with OncoC4; 3. Partnered with DualityBio; 4. Partnered with Genmab. MoA = mode of action; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; HER2 = human epidermal growth
Slide 47: Plan to Build a Specialized Oncology Sales Force in Major Markets
Our Plan is to Build a Specialized Oncology Sales Force in Major Markets 47 Build commercial presence in North America, Europe and other key markets1 Plan to leverage commercial partners for co-commercialization Plan to deploy lean commercial operations with digital enablement Aim to be commercial-r
Slide 48: Break
Time for a > 10 minute- Break +
Slide 49: Novel Backbones: Next-Generation ADCs and Immunomodulators
6 Novel Backbones: Next-Generation ADCs and Immunomodulators Prof. Özlem Türeci, M.D. CMO and Co-founder Prof. Ilhan Celik, M.D. VP, Clinical Development Michael Wenger, M.D. VP, Clinical Development
Slide 50: Leveraging Next-Generation ADCs and IO agents for Transformative Combinations
Leveraging Next-Generation ADCs and IO agents for Transformative Combinations 50 Coleman N.et al. npj Precis. Onc. 2023 Next-Gen ADCs: Targeted cytotoxic agents with untapped potential 1. ADC binds to antigen 2. Internalization of the ADC complex by endocytosis 3. Payload released after linker cleav
Slide 51: ADC Portfolio Constructed with Thoughtful Considerations
ADC Portfolio Constructed with Thoughtful Considerations 1RNAseq data from AACR Project GENIE; 2. Partnered with DualityBio *The completion of the agreement with MediLink is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act. ADC = Ant
Slide 52: Pipeline Holds Potential for Synergistic Drug Combinations
Our Pipeline Holds Potential for Synergistic Drug Combinations IO = immuno-oncology; ADC = antibody-drug conjugates; MoA = Mechanism of Action. ADCs quickly debulk tumors while cancer vaccines meaningfully boost the immune system to eradicate multi-clonal micrometastases hence lifting the long-term
Slide 53: Therapeutic Candidates Across Multiple Tumors
Targeting TROP2, cleavable linker and topoisomerase I inhibitor (P1021) DAR: 4 Targeting B7H3, cleavable linker and topoisomerase I inhibitor (P1021) DAR: 6 Targeting HER3, cleavable linker allows for intracellular and extracellular release of topoisomerase I inhibitor (YL0014) DAR: 8 Targeting HER2
Slide 54: BNT323/DB-1303: A Potentially Best-in-Class HER2-Targeting ADC
54 BNT323/DB-13031: A Potentially Best-in-Class HER2-Targeting ADC 1. Partnered with DualityBio; 2. Partnered with Daiichi Sankyo; 3. Partnered with Genentech, member of Roche group. HER2 = human epidermal growth factor receptor 2; DAR = drug-to-antibody ratio; Dxd = deruxtecan; DM1 = mertansine MoA
Slide 55: BNT323/DB-1303 Preclinical Profile
55 Lin S. et al. Abstract #252. Presented at ORTC-NCI-AACR in 2022. Superior in vitro plasma stability in human plasma Sustained tumor-selective drug release in tumor- bearing mice Efficient bystander killing in tumor cell lines Rapid systemic clearance in monkeys DB-1303 DS-8201* C h a n g e o f D
Slide 56: BNT323/DB-1303: Preclinical Antitumor Effect and Safety Profile
BNT323/DB-13031: Preclinical Data Show Antitumor Effect and Favorable Safety Profile in HER2 Positive & HER2 Low Tumor Models and Toxicity Studies 56 ToxicityAntitumor effect Lin S. et al. Abstract #252. Presented at EORTC-NCI-AACR in 2022. • BNT323/DB-1303 induced dose-dependent tumor growth inhibi
Slide 57: First-in-Human Trial with BNT323/DB-1303
First-in-Human Trial with BNT323/DB-13031 in Patients with Advanced HER2-Expressing Solid Tumors 57 Phase 1/2a trial design (NCT05150691), multicenter, non-randomized, open-label Hamilton E. et al. TiP #9504. Presented at AACR 2023 1. Partnered with DualityBio. IHC = immunohistochemistry; FIH = Firs
Slide 58: BNT323/DB-1303 is Well Tolerated with Low Incidences of Key AEs
BNT323/DB-13031 is Well Tolerated with Low Incidences of Key AEs 58 Phase 1/2a (NCT05150691): Safety Moore K. et al. Presented at ASCO 2023. Abstract #3023. • No DLT observed in all dose levels • Most common TRAEs of grade ≥3: nausea (2.4%), platelet count decreased (3.5%), anemia (5.9%) • No grade
Slide 59: BNT323/DB-1303 Demonstrates Encouraging Antitumor Activity
BNT323/DB-13031 Demonstrates Encouraging Antitumor Activity in HER2- Expressing Patients 59 1. Partnered with Duality Bio. HER2 = human epidermal growth factor receptor 2; ORR = objective response rate; DCR = disease control rate; IHC = immunohistochemistry; ISH = in situ hybridization; GEJ = gastro
Slide 60: Data Support Initiation of a Pivotal Phase Trial for BNT323/DB-1303
Data Support Initiation of a Pivotal Phase 3 Trial Evaluating BNT323/DB-13031 in HER2-Expressing Patients 60 1. Partnered with DualityBio. HER2 = human epidermal growth factor receptor 2; ORR = objective response rate; DCR = disease control rate; FIH = first in human; ADC = antibody-drug conjugate;
Slide 61: BNT323/DB-1303 Offers Potential to Establish New SoC in HR+/HER2-Low
HR+/HER2neg (70%5 of total breast cancer patients) HR+/HER2 Low (60%6 of HR+/HER2neg Breast Cancer) Early Stage (96%4) Stage IV (4%4) (13K) Advanced/unresectable, Recurrent (95K) Endocrine therapy (ET) +/- CDK4/6 inhibitor (~90%) ~60 % of mBC progress to 2L8 BNT323/DB-1303* and Trastuzumab-Deruxteca
Slide 62: Trial Design BNT323/DB-1303 in HR+/HER2-Low Breast Cancer
Phase 3 Trial Design BNT323/DB-13031 in Chemotherapy-Naïve Patients with HR+/HER2-Low Breast Cancer 62 1. Partnered with DualityBio; 2. Twelves C. et al. Clinical Breast Cancer. 2022. HR = hormone receptor; HER = human epidermal growth factor; ET = endocrine therapy; ECOG = eastern Cooperative oncol
Slide 63: Unmet Need in Endometrial Cancer
Unmet Need in Endometrial Cancer 63 1. Sung H, et al. CA: a cancer journal for clinicians. 2021; 2. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute; 2023 Apr 19. [updated: 2023 Jun 8; cited 2023 Aug 17]. Available
Slide 64: Efficacy of BNT323/DB-1303 in HER2-Expressing Endometrial Cancer
Efficacy of BNT323/DB-13031 Enables Clear Path to Registration in Heavily Pretreated HER2-Expressing Endometrial Cancer Patients 64 1. Partnered with DualityBio. HER2 = human epidermal growth factor receptor 2; ORR = objective response rate; DCR = disease control rate; FIH = first in human; ADC = an
Slide 65: Therapeutic Candidates Across Multiple Tumors
Targeting TROP2, cleavable linker and topoisomerase I inhibitor (P1021) DAR: 4 Targeting B7H3, cleavable linker and topoisomerase I inhibitor (P1021) DAR: 6 Targeting HER3, cleavable linker allows for intracellular and extracellular release of topoisomerase I inhibitor (YL0014) DAR: 8 Targeting HER2
Slide 66: BNT325/DB-1305 Positioned As a Key Backbone ADC
BNT325/DB-13051 Positioned As a Key Backbone ADC for a Variety of Solid Tumors 66 1. Partnered with DualityBio; 2. Oncotarget. 2015; 6:22496-22512 3. Pathology International. 2020;1–8; 4. Am J Clin Exp Urol. 2021 Feb 15;9(1):73-87. 5. Cancers (Basel). 2022 Sep; 14(17): 4137 TROP-2 = trophoblast cell
Slide 67: BNT325/DB-1305 - A Potential Best-in-Class TROP2-Targeting ADC
BNT325/DB13051 - A Potential Best-in-Class TROP2-Targeting ADC 1. Partnered with DualityBio; 2. Zhang Y. et al. Presented at EORTC-NCI-AACR. 2022. 4. Gilead; 5. Daiichi Sankyo; 5. Cheng Y et al. Front. Oncol. 2022; 6. Merck. TROP-2 = trophoblast cell surface antigen-2; ADC = antibody drug conjugate;
Slide 68: BNT325/DB-1305: Preclinical Data
BNT325/DB-13051: Preclinical Data Show Anti-Tumor Effect in TROP2 Positive & Low Tumor Models and a Favorable Toxicity Profile 68 Toxicity dataAntitumor effect Zhang Y. et al. Presented at EORTC-NCI-AACR.2022 • BNT325/DB-1305 induces dose-dependent tumor growth inhibition and tumor regression • Pote
Slide 69: First-in-human Trial with BNT325/DB-1305
First-in-human trial with BNT325/DB-13051 in Patients with Advanced/Metastatic Solid Tumors 1. Partnered with DualityBio. ECOG PS = eastern cooperative oncology group performance status; DL = dose level; Q3W = every three weeks; RP2D = recommended phase 2 dose; HR = hormone recptor; HER2 = human epi
Slide 70: BNT325/DB-1305 Shows a Manageable Safety Profile
BNT325/DB-13051 Shows a Manageable Safety Profile 1. Partnered with DualityBio. DLT = dose limiting toxicities; MTD = maximum tolerated dose; TRAE = treatment related adverse event; AE = adverse event; FIH = first in human. ILD = interstitial lung disease. Overall safety • DB-1305 was tolerable and
Slide 71: BNT325/DB-1305 Anti-Tumor Activity
1. Partnered with DualityBio. FIH = first in human; ORR = objective response rate; DCR = disease control rate; NSCLC = non-small cell lung cancer; CRC = colorectal cancer; TNBC = triple-negative breast cancer; GC = gastric cancer; GEJC = gastroesophageal junction cancer. Unconfirmed ORR, % Unconfirm
Slide 72: ADC Key Takeaways
ADC Key Takeaways BNT323/DB13031 • Multiple pivotal studies planned BNT324/DB-13111 I BNT325/DB-13051 I BNT326/YL2022 • Ongoing studies will inform potential activity in multiple expansion cohorts and drive future development decisions • Investigate monotherapy or combination regimens 1. Partnered w
Slide 73: Immunomodulator Programs Overview
A CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer upon binding its target on T cell membranes. BNT313/ GEN10532 Clinical status • Ph1/2 in multiple solid tumors Monospecific antibody with optimized Fc targeting CTLA-4 and selectively depleting tumo
Slide 74: Immunomodulator Programs Overview
A CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer upon binding its target on T cell membranes. BNT313/ GEN10532 Clinical status • Ph1/2 in multiple solid tumors Monospecific antibody with optimized Fc targeting CTLA-4 and selectively depleting tumo
Slide 75: Differentiated Mechanism with Potential to Become Best-in-Class Anti-CTLA-4 Antibody
Avoiding lysosomal degradation of CTLA-4 for safer and more effective immunotherapy may lead to uncoupling cancer therapeutic effect from immunotherapy-related adverse effects Differentiated Mechanism with Potential to Become Best-in-Class Anti-CTLA-4 Antibody 76 1.Partnered with OncoC4. FcR = fragm
Slide 76: PRESERVE-001: Phase 1/2 Trial Design and Safety Data
Part C: Dose expansion (Hu-Lieskovan et al. Poster #594. Presented at SITC 2022) Part A and B: Dose finding (Li T. et al. Poster #949, Presented at SITC 2021) PRESERVE-001: Phase 1/2 Trial Design and Safety Data 77 1.Partnered with OncoC4. Q3W = every three weeks; MTD = maximum tolerated dose; RP2D
Slide 77: Clinical Efficacy of BNT316/ONC-392 (gotistobart)
BNT316/ONC-392 (gotistobart) (3 or 6mg/kg) in combination with pembrolizumab Hu-Lieskovan et al. Poster #594. Presented at SITC 2022 BNT316/ONC-392 (gotistobart) monotherapy (10mg/kg) in platinum- resistant ovarian cancer patients Hays J et al. Poster #564. Presented at SITC 2022 % C h a n g e f ro
Slide 78: Data Support Initiation of Pivotal Phase 3 Trial of Gotistobart in CPI-resistant NSCLC
PRESERVE-001: Phase 1/2a multicenter, non-randomized, open-label, multiple-dose, FIH trial (NCT04140526) He K. et al. presented at ASCO 2023, Abstract #9024. Data Support Initiation of Pivotal Phase 3 Trial Evaluating BNT316/ONC-392 (gotistobart)1 in CPI-resistant NSCLC 79 Target lesion best overall
Slide 79: Case Report Demonstrates Clinical Response to Gotistobart
Case Report Demonstrates Clinical Response to BNT316/ONC-392 (gotistobart)1 80 1. Partnered with OncoC4. PD-L1 = programmed cell death protein L1; TMB = tumor mutation burden; chemo-RT = chemo-radio therapy;; PET/CT = positron emission tography / computer tomography 64-year-old male Diagnosis Squamo
Slide 80: Limited 2L Treatment Options Post Immunotherapy in NSCLC
Limited 2L Treatment Options Post Immunotherapy in NSCLC 81 1. Kantar CancerMPact Treatment Architecture; 2. Thai AA et al. Lancet. 2021; 3. Markt research, data on file; 4. Partnered with OncoC4. NSCLC = non-small cell lung cancer; IO = immuno oncology; VEGFi = vascular endothelial growth factor in
Slide 81: Phase 3 Trial Evaluating Gotistobart in CPI-resistant NSCLC
Phase 3 Trial Evaluating BNT316/ONC-392 (gotistobart)1 in CPI-resistant NSCLC 82 1. Partnered with OncoC4; CPI = Checkpoint inhibitor; NSCLC = Non-small cell lung cancer; PD-1 = Programmed cell death protein 1; IO = immuno-oncology; RESCIST = Response Evaluation Criteria In Solid Tumors; Q3W = once
Slide 82: Immunomodulator Programs Overview
A CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer upon binding its target on T cell membranes. BNT313/ GEN10532 Clinical status • Ph1/2 in multiple solid tumors Monospecific antibody with optimized Fc targeting CTLA-4 and selectively depleting tumo
Slide 83: BNT311/GEN1046 – Combining Checkpoint Blockade and Conditional T Cell Co-Stimulation
BNT311/GEN1046 – Combining Checkpoint Blockade and Conditional T Cell Co-Stimulation 84 1. Partnered with Genmab; Fc = fragment crystallizable region; PD –L1 = programmed cell death ligand 1; PD-1 = programmed cell death protein 1; NK cell = natural killer cell; . Inert Fc, dual targeted 4-1BB co-st
Slide 84: BNT311/GEN1046 – Preclinical Data
BNT311/GEN10461 – Preclinical Data 85 1. Partnered with Genmab. CPI = Checkpoint Inhibitor; PD-L1 = programmed cell death ligand 1; ctrl = control. 4-1BB agonist activity of BNT311/GEN1046 was strictly conditional on PD-L1 binding Muik A, et al. Cancer Discov 2022; 12:1248−1345. P D -1 /P D -L 1 b l
Slide 85: First-in-Human Trial with BNT311/GEN1046
First-in-Human Trial with BNT311/GEN10461 in Patients with Metastatic or Unresectable Solid Tumors 1. Partnered with Genmab. Q2W = once every three weeks; PD = progressive disease; NSCLC = non-small-cell lung cancer; HNSCC = head and neck squamous-cell cancer; TNBC = triple-negative breast cancer; R
Slide 86: Initial Results of BNT311/GEN1046 Monotherapy Show Manageable Safety
Initial Results of BNT311/GEN10461 Monotherapy in Dose Escalation Show a Manageable Safety Profile and Clinical Activity 1. Partnered with Genmab. DLT = dose-limiting toxicity; MTD = maximum tolerated dose; TEAE= treatment-emergent adverse event; TRAE = treatment-related adverse event, TNBC = triple
Slide 87: BNT311/GEN1046 Monotherapy Demonstrates Efficacy in Advanced Solid Tumors
BNT311/GEN10461 Monotherapy Demonstrates Efficacy in Patients with Advanced Solid Tumors Who had Failed PD-(L)1 Treatment including in NSCLC 88 1. Collaboration with Genmab; PD-L1 = programmed cell death ligand 1; NSCLC = non-small cell lung cancer; CPI = checkpoint inhibitor; . Phase 1/2a FIH trial
Slide 88: Ongoing Phase 2 Trials of BNT311/GEN1046 in NSCLC and Endometrial Cancer
Ongoing Phase 2 Trials Investigating BNT311/GEN10461 as Single Agent and in Combination with Pembrolizumab in NSCLC and Endometrial Cancer 89 1. Partnered with Genmab; 50:50 profit/loss collaboration. NSCLC = non-small cell lung cancer; PD-L1 = programmed cell death ligand 1; FPD = first patient dos
Slide 89: Immunomodulator Programs Overview
A CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer upon binding its target on T cell membranes. BNT313/ GEN10532 Clinical status • Ph1/2 in multiple solid tumors Monospecific antibody with optimized Fc targeting CTLA-4 and selectively depleting tumo
Slide 90: BNT312/GEN1042 – Bispecific Antibody Designed to Strengthen T Cell and APC Synapse
BNT312/GEN10421 – Bispecific Antibody Designed to Strengthen T Cell and APC Synapse 91 1. Partnered with Genmab. APC = antigen-presenting cell; Fc = fragment crystallizable region; CD = cluster of differentiation; HLA = human leucocyte antigen; TCR = T-cell receptor; MHC = major histocompatibility c
Slide 91: BNT312/GEN1042 – Double-Conditional Dual-Agonist Molecule
BNT312/GEN10421 – Double-Conditional Dual-Agonist Molecule 92 R e la ti v e l u m in e s c e n c e u n it s CD40 reporter assay 4-1BB reporter assay In the absence of CD40+ cells, BNT312 does not exhibit any 4-1BB activation In the absence of 4-1BB+ cells, BNT312 does not exhibit any CD40 activation
Slide 92: BNT312/GEN1042 Promotes DC Maturation vs Monoclonal Antibodies
BNT312/GEN10421 Shows Higher Ability to Promote DC Maturation vs either Monoclonal Antibody or their Combination 93 0 20 40 60 Antibody concentration (μg/mL) % H L A -D R + /C D 8 6 + o f to ta l D C p o p u la ti o n Isotype ctrl bsAb-CD40×ctrl bsAb-ctrl×4-1BB bsAb-CD40×ctrl + bsAb-ctrl×4-1BB Fc in
Slide 93: Dose Escalation of BNT312/GEN1042 in Solid Tumors
Data from Dose Escalation of BNT312/GEN10421 in Patients with Metastatic or Unresectable Solid Tumors 94 1. Partnered with Genmab; a. Starts with an accelerated titration phase consisting of single-patient cohorts followed by larger cohorts informed by the modified continuous reassessment method and
Slide 94: BNT312/GEN1042 Manageable Safety and Encouraging Clinical Activity
• Disease control rate 50% • 2 patients with confirmed PR (melanoma, neuroendocrine lung cancer) 100mg Q3W was identified as the expansion dose BNT312/GEN10421 Shows Manageable Safety Profile and Encouraging Clinical Activity in a Heavily Pretreated Heterogenous Patient Population 95 1. Partnered wi
Slide 95: Dose Expansion of BNT312/GEN1042 in Solid Tumors
96 Dose Expansion of BNT312/GEN10421 in Patients with Metastatic or Unresectable Solid Tumors Phase 1/2 trial designs (NCT04083599, NCT05491317), open-label, multi-center, open-label Melero et al. Presented at ESMO-IO 2022. Poster#692. Inclusion criteria • Selected metastatic or unresectable solid t
Slide 96: Safety Run-in Results of BNT312/GEN1042 with Pembrolizumab and Chemotherapy
Safety Run-in Results of BNT312/GEN10421 in Combination with Pembrolizumab and SoC Chemotherapy Show Favorable Safety Profile Data cut-off: October 2, 2022. 1. Partnered with Genmab; 50:50 profit/loss collaboration. DLT = dose-limiting toxicity; MTD = maximum tolerated dose; AE = adverse event. Tran
Slide 97: Safety Run-in Results Show Preliminary Activity in HNSCC
Safety Run-in Results of BNT312/GEN10421 in Combination with Pembrolizumab and SoC Chemotherapy Show Preliminary Activity in Patients with HNSCC 1. Partnered with Genmab. HNSCC = Head and neck squamous cell carcinomas; PD-L1 = programmed cell death ligand 1; PR = partial response; CR = complete resp
Slide 98: Immunomodulator Programs Overview
A CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer upon binding its target on T cell membranes. BNT313/ GEN10531 Clinical status • Ph1/2 in multiple solid tumors Monospecific antibody with optimized Fc targeting CTLA-4 and selectively depleting tumo
Slide 99: PM8002 – A Next-Gen IO Agent that Combines Two Clinically Validated MoA
PM80021 – A Next-Gen IO Agent that Combines Two Clinically Validated MoA 100 1. Partnered with Biotheus. MoA = Mode of Action TME = Tumor Microenvironment 2. The MoA graph generated by Biorender.com “Two in one” MoA synergies with ADCs Dual blockade of PD-L1 and VEGF-A have been proven synergistic •
Slide 100: Anti-VEGF Treatment Impacts Tumor Vasculature and Tumor Microenvironment
Reversion of multi-level immune-suppressive effects of VEGF Reversion of tumor-angiogenesis promoting effects of VEGF Anti-VEGF Treatment Impacts Tumor Vasculature and Tumor Microenvironment 101 Sourced from https://www.creativebiolabs.net/bevacizumab-overview.htm VEGF(R) = vascular endothelial grow
Slide 101: Anti-VEGF is a Validated Mechanism Across a Wide Range of Tumors
Anti-VEGF is a Validated Mechanism Approved in or Shown Clinical Activity in a Wide Range of Tumors 102 1L OC/TFC/PPC 2L+ OC/FTC/PPC Platinum Resistant 2L OC/FTC/PPC Platinum Sensitive 1L NSq NSCLC Driver Gene WT 1L NSCLC EGFRm+Lung Gynae- cology 2L+ NSCLC Cervical Cancer 1L NSq NSCLC RCC 1L HCC 2L
Slide 102: PM8002 Investigated in 10+ Indications in More Than 500 Patients
PM8002 Mono and Combo Have Been Investigated in 10+ Indications in More Than 500 Patients 103 2L+ Cervical Cancer nccRCC 2L+ ccRCC PROC 2L+ PSOC 2L+ NSCLC EGFRm Advanced BTC 1L MPM 2L SCLC 1L TNBC 1L HCC Mono Combo Lung Breast Gynaeco logy Gastroin testinal Genitour inary Others (+ Paclitaxel) (+ na
Slide 103: PM8002 Monotherapy in Patients with Advanced Solid Tumors
PM80021 Monotherapy in Patients with Advanced Solid Tumors 1. Partnered with Biotheus. Trial registration: ChiCTR2000040552. QxW = every x weeks; RP2D = recommended phase 2 dose; ECOG PS = ORR = objective response rate; ECOG PS= eastern cooperative oncology group performance status. Phase 1/2 trial
Slide 104: PM8002 Monotherapy Shows Encouraging Antitumor Activity and Safety
PM80021 Monotherapy Shows Encouraging Antitumor Activity and Safety Profile in Patients with Advanced Solid Tumors in a Phase 1/2 Trial 105 1. Partnered with Biotheus. ORR = objective response rate; DCR = disease control rate, DoR = duration of response; PFS = progression free survival; PD = progres
Slide 105: PM8002 Monotherapy is Well Tolerated
PM80021 Monotherapy is Well Tolerated in Patients with Advanced Solid Tumors in a Phase 1/2 Trial 106 1. Partnered with Biotheus. TRAE = treatment related adverse event, SAE = serious adverse event. PM8002 in Ph1/2: Safety for monotherapy Ye Guo et al. Presented at ASCO 2023. Poster#378 All TRAEs, n
Slide 106: PM8002 with Paclitaxel as Second Line Treatment for SCLC
PM80021 in Combination with Paclitaxel as Second Line Treatment for SCLC 107 1. Partnered with Biotheus; 2. As of September 08, 2023. Small Cell Lung Cancer = Small Cell Lung Cancer ECOG PS= eastern cooperative oncology group performance status. ORR = Overall response rate; DCR = Disease control rat
Slide 107: PM8002 with Paclitaxel Shows Encouraging Antitumor Activity in SCLC
Response Efficacy Evaluation Population ITT (n=36) IO-naïve (n=22) IO- treated (n=14) ORR, % 61.1 72.7 42.9 DCR, % 86.1 81.8 92.9 Phase 2 (NCT05879068): clinical activity of PM8002 in combination with paclitaxel Ying Cheng et al. Presented at ESMO 2023. Poster#1992P PM80021 Combined with Paclitaxel
Slide 108: PM8002 with Paclitaxel Shows Acceptable Toxicity in SCLC
PM8002 Combined with Paclitaxel Shows Acceptable Toxicity as Second Line Therapy in Patients with SCLC 109 1. Partnered with Biotheus. TRAE = treatment related adverse event, SAE = serious adverse event. Phase 2, open-label, single-arm, trial (NCT05879068) Ying Cheng et al. Presented at ESMO 2023. P
Slide 109: Significant Tumor Shrinkage with PM8002 Mono and Combination Therapy
Significant Tumor Shrinkage in Patients Treated by PM8002 as Monotherapy and in Combination with Chemotherapy 110 Data on file.1L/1L = First Line, Second Line Week 32 Lesion diameter: 0 mm 28.4 mm 0 mm 1L TNBC: PM8002 + nab-paclitaxel 2L SCLC: PM8002 + paclitaxel Base line Lesion diameter: 44.5mm We
Slide 110: PM8002 Safety Profile Appears Favorable
PM8002 Safety Profile Appears Favorable with Regard to AEs and irAEs Related to its Two Targets 111 Literature research, cross-trial comparison; Data on file. Anti-PD-1 includes pembrolizumab and nivolumab, anti-PD-L1 includes atezolizumab, anti-VEGF is bevacizumab, VEGF TKI includes lenvatinib and
Slide 111: Immunomodulators: Key Takeaways
Immunomodulators: Key Takeaways BNT316/ONC-392 (gotistobart)1 • Additional data readouts planned in 2024 • Potential registrational trials planned in 2024 and beyond BNT311/GEN104062 • Engage with health authorities on the design of a pivotal trial in post-IO non-small cell lung cancer • Plan to pre
Slide 112: Solid Tumor Cell Therapy
_f Solid Tumor Cell Therapy —— BIONT=CrH
Slide 113: Solid Cancers Pose a Special Challenge for CAR-T cells
Solid Cancers Pose a Special Challenge for CAR-T cells 114 Permanent accessible antigen Blood vessel # C A R -T time threshold Lack of peripheral antigen Tumor # C A R -T time threshold 0 5 10 15 20 25 CAIX (12) CEA (21) EGFR (11) ErbB2/Her2 (20) Fr-a (14) GD2 (19) IL-13Ra2 (3) L1-CAM (6) Mesotheliu
Slide 114: Frequencies of CLDN6 expression in high medical need cancers
Frequencies of CLDN6 expression in high medical need cancers 115 Reinhard, Rengstl et al. Science 2020 Ovary Endometrium Lung Testis Healthy tissue Tumor Indication CLDN6+ CLDN6high Testicular Cancer* 93 % 90-93 % Ovarian Cancer* 56 % 25-30 % Uterine Cancer* 23 % 10-15 % Lung Cancer** 11 % 2-5 % Gas
Slide 115: BNT211: A CLDN6 CAR-T-Cell Therapy + CARVac
Potent 2nd generation CAR with high sensitivity and specificity Reinhard K, et al. Science 2020, 367:446–453 BNT211: A CLDN6 CAR-T-Cell Therapy + CLDN6-Encoding CARVac that Enhances Expansion and Persistence of the Infused CAR-T Cells ACT = adoptive cell transfer; APC = antigen-presenting cell; CAR
Slide 116: BNT211-01: Phase 1/2a Dose Escalation Trial in CLDN6+ Solid Tumors
BNT211-01: Phase 1/2a, FIH, Open-Label, Multicenter, Dose Escalation Trial in R/R Advanced CLDN6+ Solid Tumors (NCT04503278) 117 Data cut-off: 10 Sep 2023. * Crossover to combination not indicated. CAR = chimeric antigen receptor; CARVac = CAR T-cell amplifying RNA vaccine; CLDN6 = claudin-6; DCR =
Slide 117: Clinical Benefit Seen in Patients with Manual Manufacturing Process
Clinical Benefit Seen in Patients with Manual Manufacturing Process 118 LD= lymphodepletion; CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease. Phase 1/2 FIH study (NCT04503278): Clinical activity of BNT211 +/- CARVac Mackensen et al. Nat. Med. 2023.
Slide 118: Case Report Demonstrates Clinical Response to BNT211
Case Report Demonstrates Clinical Response to BNT211 119 HDCT = high-dose chemotherapy; ASCT = autologous hematopoietic stemm cell transplant. Diagnosis Mixed germ cell tumor; 80% tumor cells with ≥2 + CLDN6 membrane staining positivity. Prior Therapy • Heavily pretreated (5 lines of chemotherapy in
Slide 119: BNT211-01: CAR T Cell-Dose-Dependent Adverse Event Profile
BNT211-01: CAR T Cell-Dose-Dependent Adverse Event Profile, Dose Evaluation Ongoing to Determine RP2D Data cut-off: 10 Sep 2023. 1 Cohort includes 3 patients dosed with 5×107 CAR-T. 2 Cohort includes 1 patient that did not reach full dose (2×107) and 1 patient treated that received full dose after 5
Slide 120: BNT211-01: Signals of Activity at All Dose Levels
BNT211-01: Signals of Activity at All Dose Levels Data cut-off: 10 Sep 2023. Waterfall plot showing best percent change from baseline in sum of target lesion diameters for patients treated with CLDN6 CAR-T (N = 38). One patient died prior to first assessment (NR = not reached) and BOR was defined as
Slide 121: BNT211-01: Encouraging Signals of Activity at Dose Level 2
BNT211-01: Encouraging Signals of Activity at Dose Level 2 122 Data cut-off: 10 Sep 2023. Waterfall plot showing best percent change from baseline in sum of target lesion diameters and spider plot showing percent change in target sum from baseline over time for patients treated with CLDN6 CAR-T ± CL
Slide 122: BNT211-01: CARVac Improves CAR-T Persistence at Dose Level 2
BNT211-01: CARVac Improves CAR-T Persistence at Dose Level 2 Data cut-off: 1 Sep 2023. BioNTech data on file derived from peripheral blood applying semi-quantitative PCR directed against CAR transgene. Displayed as copies of transgene per µg of DNA input of isolated PBMC. Pending data up to day 50:
Slide 123: BNT211 Key Takeaway Messages
Pharmacokinetics: CARVac improved CAR-T persistence with sustained, ongoing detection up to 100 days in several patients at DL2 Safety: Manageable AE profile. Dose-dependent AE profile further evaluation of safety via backfilling into dose level several cohorts BNT211 Key Takeaway Messages 124 CAR =
Slide 124: CAR T-Cells Outlook
CAR T-Cells Outlook • No curative treatment options for R/R GCT post salvage cisplatin-based chemotherapy regimens1 • Lack of new developments in the past decades • Checkpoint inhibitors failed in these patients2 1. Feldman, et al. Cancer 2012; 2. Adra, et al. Ann Oncol 2018; 3. Mackensen, et al. Na
Slide 125: mRNA Cancer Vaccines
8 mRNA Cancer Vaccines Prof. Özlem Türeci, M.D. CMO and Co-founder
Slide 126: Uridine-based mRNA-LPX Vaccines for Systemic Delivery
Uridine-based mRNA-LPX Vaccines for Systemic Delivery and Induction of Potent Polyspecific Immune Responses against Cancer 127 Kranz LM, et al. Nature 2016; 534:396–401; Lopez J, et al. AACR Annual Meeting 2020; Oral presentation CT301. RNA-LPX = RNA+lipoplex; CD = cluster of differentiation; TLR =
Slide 127: mRNA Cancer Vaccines May Enable Highly Specific and Potent Immune Activation
mRNA Cancer Vaccines May Enable Highly Specific and Potent Activation of the Immune System Against Shared Tumor Antigens or Individual Neoantigens 128 Individual patient samples (blood and tissue) AI-driven neoantigen prediction On-demand tailored RNA manufacturing Individualized immuno- therapy Map
Slide 128: Growing Portfolio of Cancer Vaccine Candidates Across Multiple Solid Tumors
Growing Portfolio of Cancer Vaccine Candidates Across Multiple Solid Tumors 129 1. Partnered with Genentech, member of Roche Group; 2. Sponsored by Regeneron. iNeST = individualized NeoAntigen Specific Immunotherapy;1L = first line; R/R = relapsed/refractory; CRC = colorectal cancer; PDAC = pancreat
Slide 129: Our Strategy for Potential Leadership in mRNA Cancer Vaccines
Our Strategy for Potential Leadership in mRNA Cancer Vaccines 130 Aim to establish commercial manufacturing capacity Aim to establish BioNTech commercial manufacturing facility Aim to increase clinical manufacturing capability Continue to decrease manufacturing time Moving to fully automatic platfor
Slide 130: First-in-Human Study with Intranodal Individualized mRNA Neoantigen Vaccine
First-in-Human Phase 1 Study with an Intranodal Version of Our individualized mRNA Neoantigen Vaccine Sahin et al. Nature. 2017. 13 patients with stage IIIa-c (6 patients), IV (7 patients) melanoma treated 131 Evaluating the safety, tolerability & immunogenicity of intra- nodal administration of an
Slide 131: Long Term Persistence of Vaccine Induced T cell Responses
post-IVS CD8+ T cells ELISPOT Long Term Persistence of Vaccine Induced T cell Responses Induced by Intra- Nodal Vaccination with a Naked Individualized mRNA-base Neoantigen Vaccine Neoantigen T cells persist for more than 4 yearsex vivo Multimer staining 0 100 200 300 400 0.0 0.1 0.2 0.3 1600 1700 D
Slide 132: 6-Year Passive Follow Up After Intranodal Vaccination
6-Year Passive Follow Up of Patients After Intranodal Vaccination with a Naked Individualized mRNA-based Neoantigen Vaccine Passive follow up for 6 years 133 Sahin et al. Nature. 2017, Türeci, presented at CICON23
Slide 133: Exploiting Somatic Cancer Mutations for mRNA-LPX Neoantigen Vaccines
Exploiting Somatic Cancer Mutations for mRNA-LPX based Neoantigen Vaccines Vormehr et al., Curr Opin Immunol 39:14-22 (2016). MSI = microsatelite instability; MSI-h = microsatellite instability high; non-synonymous single nucleotide variant. MSS = microsatellite stable; LPX = lipoplex 134
Slide 134: High Unmet Medical Need in Early-Stage Cancer Indications
Triple Negative Breast Cancer Pancreatic Ductal Adenocarcinoma High Unmet Medical Need in Early-Stage Cancer Indications 135 CPI = Checkpoint inhibitor; pCR = pathological complete response; CRC = colorectal cancer, TNBC = triple negative breast cancer; PDAC = pancreatic ductal adenocarcinoma. 1. Oe
Slide 135: Exploratory Phase 1 Trial of BNT122 in TNBC Patients
Exploratory Phase 1 Trial of BNT122 in TNBC Patients Post (Neo-)Adjuvant Treatment 136 TNBC = triple-negative breast cancer; TAA = tumor-associated antigen; UTR = untranslated region; ORF = open reading frame; MITD = MHC I-targeting domain. Trial design Inclusion criteria Invasive adenocarcinoma TNB
Slide 136: Persistent Neoantigen-Specific Immune Responses in TNBC with BNT122
Induction of Persistent Neoantigen-Specific Immune Responses in Patients with TNBC Treated with BNT122 in the Post (Neo-)Adjuvant Setting 137 0 50 0 10 00 P01 P02 P05 P06 P07 P08 P09 P10 P11 P12 P13 P14 2, 00 0 3, 00 0 4, 00 0 5, 00 0 Mean Spot count Ex vivo IFNγ ELISpot counts Induced T cell respon
Slide 137: BNT122/Autogene Cevumeran in Adjuvant Pancreatic Ductal Adenocarcinoma
BNT122/Autogene Cevumeran1 in Adjuvant Pancreatic Ductal Adenocarcinoma 139 1. Partnered with Genentech, member of Roche Group; 2. Rojas et al. Nature. 2023. mFOLFIRINOX = modified FOLFIRINOX; PDAC = pancreatic ductal adenocarcinoma; q2w = every 2 weeks. Active, not recruiting Investigator-initiated
Slide 138: Autogene Cevumeran Induces Immune Responses in Adjuvant Pancreatic Cancer
Autogene Cevumeran/BNT1221 Induces Immune Responses in Adjuvant Pancreatic Cancer 140 1. Partnered with Genentech, member of Roche Group. BNT122 induces functional neoantigen-specific T cells Rojas et al. Nature. 2023 Half of all the patients who received the vaccine mount neoantigen-specific de nov
Slide 139: Autogene Cevumeran Demonstrates Clinical Activity in Adjuvant Pancreatic Cancer
Autogene Cevumeran/BNT1221 Demonstrates Clinical Activity in Adjuvant Pancreatic Cancer 141 1. Partnered with Genentech, member of Roche Group. PDAC = Pancreatic ductal adenocarcinoma; OS = overall survival, RFS = relapse-free survival. O S ( % ) 10 0 50 0 0 6 12 At risk 19 18 15 18 9 24 4 30 0 Mont
Slide 140: BNT122 Investigated in a Phase 2 Randomized Trial vs SoC in Resected PDAC
BNT122/Autogene Cevumeran1 Investigated in a Phase 2 Randomized Trial vs SoC in Resected PDAC 142 1. Partnered with Genentech, member of Roche Group. SoC = standard of care; PDAC = pancreatic ductal adenocarcinoma; ; CT = computer tomography CTx = chemotherapy. Key endpoints Primary: DFS Secondary:
Slide 141: Personalized mRNA Cancer Vaccines: Key Takeaways
Personalized mRNA Cancer Vaccines: Key Takeaways 143 We aim to bring personalized cancer vaccines into the adjuvant treatment setting for multiple cancer indications including tumors with low mutational burden and cold tumor types Low tumor mass, with residual cancer cells Tumor resistance mechanism
Slide 142: Path to Value Creation
9 Path to Value Creation Ryan Richardson Chief Strategy Officer
Slide 143: Strategic Outlook
Strategic Outlook 145 1. Partnered with Pfizer. COVID-191 Immuno-oncology Infectious diseases Strategy Advance commercial franchise into combination and next- generation vaccines Execute pivotal trials and launch multiple products from 2026 onwards Initiate first late-stage development programs Plan
Slide 144: Strategic Vision for 2030
Cash position1 COVID-19 Vaccine Franchise Oncology Pipeline Infectious Disease Pipeline Strategic Vision for 2030 146 1. As of September 30, 2023; 2. Figure is pre-tax. €17bn cash €2bn trade receivables2 Interest income Market-leading vaccine Expanding late-stage pipeline Early-stage ex-COVID-19 pip
Slide 145: Path to Sustained Long-term Growth
Path to Sustained Long-term Growth 147 1. As of September 30, 2023. S&M = sales & marketing; BD = business development; M&A = mergers & acquisitions. 2025-20282023 2024 • Expect to be profitable if full-year 2023 revenue guidance is achieved • ~€1bn investment in BD/M&A • Cash position of ~€17bn1 •
Slide 146: Path to Value Creation
Path to Value Creation 148 Increase investment in R&D with a focus on pivotal trials Continued BD and M&A with a focus on synergistic assets Build oncology commercial capabilities leveraging partners in select regions Commercialize multiple new products in infectious disease and oncology Value for S
Slide 147: Innovation Series 2023 Thank You
Innovation Series 2023 THANK YOU Contact us at investors@biontech.de