UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a‑16 OR 15d‑16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
FOR THE MONTH OF NOVEMBER 2024
COMMISSION FILE NUMBER 001-39081
BioNTech SE
(Translation of registrant’s name into English)
(Translation of registrant’s name into English)
An der Goldgrube 12
D-55131 Mainz
Germany
+49 6131-9084-0
(Address of principal executive offices)
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover Form 20‑F or Form 40‑F: Form 20‑F ☒ Form 40‑F ☐
Indicate by check mark if the registrant is submitting the Form 6‑K in paper as permitted by Regulation S‑T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6‑K in paper as permitted by Regulation S‑T Rule 101(b)(7): ☐
DOCUMENTS INCLUDED AS PART OF THIS FORM 6-K
On November 14, 2024, BioNTech SE is hosting an edition of its Innovation Series Day. The presentation is attached as Exhibit 99.1.
SIGNATURE
Pursuant to the requirements of the Exchange Act, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| BioNTech SE | ||||||||||||||
| By: | /s/ Jens Holstein | By: | /s/ Dr. Sierk Poetting | |||||||||||
| Name: Jens Holstein | Name: Dr. Sierk Poetting | |||||||||||||
| Title: Chief Financial Officer | Title: Chief Operating Officer | |||||||||||||
Date: November 14, 2024
EXHIBIT INDEX
| Exhibit | Description of Exhibit | ||||
| 99.1 | |||||
Innovation Series 2024 November 14, 2024 10:30 AM – 2:15 PM ET Exhibit 99.1
1 Welcome & Introductory Remarks Ryan Richardson, Chief Strategy Officer
This Slide Presentation Includes 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: BioNTech’s expected revenues and net profit/(loss), particularly for those figures that are derived from preliminary estimates provided by BioNTech’s partners; the rate and degree of market acceptance of BioNTech’s COVID-19 vaccine and, if approved, BioNTech’s investigational medicines; expectations regarding anticipated changes in COVID-19 vaccine demand, including changes to the ordering environment and expected regulatory recommendations to adapt vaccines to address new variants or sublineages; the initiation, timing, progress, results, and cost of BioNTech’s research and development programs, including BioNTech’s current and future preclinical studies and clinical trials, including statements regarding the expected timing of initiation, enrollment, and completion of studies or trials and related preparatory work and the availability of results, and the timing and outcome of applications for regulatory approvals and marketing authorizations; BioNTech’s expectations regarding potential future commercialization in oncology, including goals regarding timing and indications; the targeted timing and number of additional potentially registrational trials, and the registrational potential of any trial BioNTech may initiate; discussions with regulatory agencies; BioNTech’s expectations with respect to intellectual property; BioNTech’s acquisition of Biotheus, which is subject to customary closing conditions, including regulatory approvals; the impact of BioNTech’s acquisition of Biotheus upon closing; collaboration and licensing agreements; the development, nature and feasibility of sustainable vaccine production and supply solutions; the deployment of AI across BioNTech’s preclinical and clinical operations; BioNTech’s estimates of revenues, research and development expenses, selling, general and administrative expenses, and capital expenditures for operating activities; and BioNTech’s expectations of net profit / (loss). In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this presentation are based on BioNTech’s current expectations and beliefs of future events, and are neither promises nor guarantees. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially and adversely from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, projected data release timelines, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the data discussed in this release, and including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the nature of the clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; BioNTech’s pricing and coverage negotiations regarding its COVID-19 vaccine with governmental authorities, private health insurers and other third-party payors; the future commercial demand and medical need for initial or booster doses of a COVID-19 vaccine; competition from other COVID-19 vaccines or related to BioNTech’s other product candidates, including those with different mechanisms of action and different manufacturing and distribution constraints, on the basis of, among other things, efficacy, cost, convenience of storage and distribution, breadth of approved use, side- effect profile and durability of immune response; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for its product candidates; the ability of BioNTech’s COVID-19 vaccines to prevent COVID-19 caused by emerging virus variants; BioNTech’s and its counterparties’ ability to manage and source necessary energy resources; BioNTech’s ability to identify research opportunities and discover and develop investigational medicines; the ability and willingness of BioNTech’s third-party collaborators to continue research and development activities relating to BioNTech's development candidates and investigational medicines; the impact of COVID-19 on BioNTech’s development programs, supply chain, collaborators and financial performance; unforeseen safety issues and potential claims that are alleged to arise from the use of products and product candidates developed or manufactured by BioNTech; BioNTech’s and its collaborators’ ability to commercialize and market BioNTech’s COVID-19 vaccine and, if approved, its product candidates; BioNTech’s ability to manage its development and related expenses; regulatory developments in the United States and other countries; BioNTech’s ability to effectively scale its production capabilities and manufacture its products and product candidates; risks relating to the global financial system and markets; and other factors not known to BioNTech at this time. You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech’s Report on Form 6-K for the period ended September 30, 2024 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at www.sec.gov. These forward-looking statements speak only as of the date hereof. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this presentation in the event of new information, future developments or otherwise. 3
Innovation Series 2024 – Today’s Presenters 4 Prof. Ugur Sahin, M.D. Chief Executive Officer, Co-founder Prof. Özlem Türeci, M.D. Chief Medical Officer, Co-founder Ryan Richardson Chief Strategy Officer Annemarie Hanekamp Chief Commercial Officer Prof. Ilhan Celik, M.D. Vice President, Clinical Development Michael Wenger, M.D. Vice President, Clinical Development
Innovation Series 2024 Agenda 1 Welcome and Introductory Remarks 10:30 AM 15 min 2 The Next Frontiers in Oncology 10:45 AM 45 min 3 Commercialization: Next Era of BioNTech 11:30 AM 15 min 4 BNT3271 Clinical Development Strategy 11:45 AM 45 min Break 12:30 PM 15 min 5 mRNA Cancer Vaccines 12:45 PM 30 min 6 Select Targeted Therapies: HER2-ADC BNT323/DB-13032 & CLDN6 CART BNT211 1:15 PM 25 min 7 Path to Value Creation 1:40 PM 5 min 8 Closing Remarks and Q&A 1:45 PM 30 min Partnered with: 1. Biotheus; 2. DualityBio.
BioNTech’s Journey Partnered with 1. Pfizer; 2. Genentech, a member of the Roche Group; 3. DualityBio. Entering a new stage of value creation for patients, society and shareholders 2008 Founding & Platform Building Seed financing & first collaborations 2019 Nasdaq IPO 2020-2022 COMIRNATY®1 Development, approval & worldwide launch From 2023 Advancing towards becoming a multi-product biotechnology company 6 BNT327/PM80021 Autogene cevumeran2 BNT211 (CAR-T) BNT323/DB-13033 FixVac
Driven to Address the World’s Most Pressing Health Challenges With pioneering technologies delivered at scale 7 1. Partnered with Pfizer; 2. As of Q3 2024; 3. Consists of cash and cash equivalents of €9,624.6 million, non-current security investments of €1,137.2 million, and current security investments of €7,078.0 million, as of September 30, 2024. INFECTIOUS DISEASE PIPELINE Partnership with Pfizer in respiratory and other high need indications MULTIPLATFORM ONCOLOGY PORTFOLIO 20 LEADER IN AI 13 Clinical programs Ongoing Phase 2 or 3 trials 7 Clinical programs in high unmet need indications >50 % Comirnaty market share2 COVID-19 VACCINE1 GLOBAL LEADERSHIP >4.9 billion doses distributed >80 countries globally IN-HOUSE MANUFACTURING Bulk mRNA Individualized mRNA Autologous Cell TherapyModular mRNA STRONG FINANCIAL POSITION € 17.8 bn total cash plus security investments3
8 >4.9 billion doses of BNT162b2 shipped >180 countries and territories3 The fastest vaccine development in the history of medicine1 The strongest launch of any pharmaceutical product2 Developing and Approving the First mRNA Medicine 1. Ball P. Nature. 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, 2022 and 2023.
Variant-adapted vaccines Designed to be 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 vulnerable populations3 Long-Term Need for Seasonally Adapted Vaccines Anticipated 9 1. World Health Organization Tracking SARS-CoV-2 variant www.who.int/en/activities/tracking-SARS-CoV-2-variants accessed 30 October 2023; 2. Global Initiative on Sharing All Influenza Data https://gisaid.org/ accessed 30 October 2023; 3. FDA Briefing Document Vaccines and Related Biological Products Advisory Committee Meeting June 15, 2023; 4 Brannock et al, Nature Comm. 2023; 5. Stankov M. V. et al., medRxiv pre-print, 5 October 2023. Annual and/or SEASONAL VACCINATION with variant-adapted vaccines expected for the foreseeable future
COVID-19 and Influenza Disease Burdens Show Different Seasonality Patterns 10 1. Respiratory Virus Hospitalization Surveillance Network; Data last updated: November 1, 2024; 2. https://www.cdc.gov/flu/hcp/vaccine-supply/2023-2024.html 0 1 2 3 4 5 6 7 8 9 10 July 2023 Aug Sep Oct Nov Dec Jan 2024 Feb Mar Apr May June July Aug Sep Oct COVID-19 Influenza Weekly new patient hospital admissions from surveillance sites in the U.S.1 U S H o s p it a liz a ti o n r a te p e r 1 0 0 ,0 0 0 p o p u la ti o n • Hospitalization rates have been consistently and significantly above the level of influenza • Epidemiology patterns do not perfectly overlap with influenza • Market has been characterized by dual strain vaccine launches in two of the last three years COVID-19 Period of peak US influenza vaccine distribution2
Variant-Adapted Vaccine Approval Timelines Came Earlier as Compared to 2023 1. Partnered with Pfizer; JN.1 is a SARS-CoV-2 variant, KP.2 is a lineage of the JN.1 variant. KP.2 vaccine approval took place on September 26 and October 10 in the EU and UK, respectively. Approval dates of variant-adapted COVID-19 vaccines1 Potential for further alignment of regulatory timelines and COVID-19 seasonal epidemiology to meet public health needs 2023 2024 Approval Date Change US Sep 11 (XBB.1.5) Aug 22 (KP.2) 20 days EC Sep 1 (XBB.1.5) Jul 3 (JN.1) 60 days UK Sep 5 (XBB.1.5) Jul 24 (JN.1) 43 days JP Sep 1 (XBB.1.5) Aug 8 (JN.1) 24 days 11
COVID-19 Vaccine Franchise1 with Lean Cost Structure 12 Key Business Features: 2024 Financials up to 30 September (Q1-Q3) €1,310m €298m €228m €47m COGS R&D S&M Revenue 1. Partnered with Pfizer. €573mOPEX 1. Global Market Leadership 3. Potential for Cashflow Generation 2. Lean Fixed Cost Base Business
Leveraging COVID-19 Vaccine Business Model for Sustainable Value Creation 13 1. Partnered with Pfizer. Multi-product portfolio First launches in oncology Data updates across pipeline Cash generative COVID-19 vaccine business1 Balance sheet Financial Strength Progressive Path Towards Value CreationInnovative R&D Engine 2025 2026 - 2028 2030
Transformational Opportunities with Pan Tumor Potential Today’s Focus: Key Value-Driving Oncology Programs 14 Partnered with: 1. Biotheus; 2. Genentech, a member of the Roche Group; 3. DualityBio. BNT327/PM8002 (bispecific PD-L1xVEGF)1 Autogene cevumeran2 (personalized mRNA cancer vaccine) BNT211 (CLDN6-targeted CAR-T + CLDN6 CAR-T amplifying vaccine) BNT323/DB-1303 (HER2 ADC)3 FixVac (off-the-shelf TAA-targeting mRNA cancer vaccine)
2 The Next Frontiers in Oncology Prof. Ugur Sahin, M.D. CEO and Co-founder
Charting the Course for Tomorrow’s Personalized Precision Medicine 16 . Deep genomics & immunology expertise to analyze patient data Individualized treatment platforms to address inter-individual variability AI & digitally-integrated target & drug discovery and development Automated in-house manufacturing to serve patients on time and globally Tailored on-demand immunotherapies Off-the-shelf drugs Targeted Therapies Immunomodulators mRNA Cancer Vaccines Clinical samples Therapeutic Modalities Inter- individual variability Personalized Omics
Space for curative approaches Immunomodulators Novel checkpoint inhibitors cytokines, immune agonists mRNA vaccines Targeted therapies ADCs, CAR-T, Ribomabs SynergySynergy Synergy • Aiming to augment anti-tumor- immunity • Focus on crucial IO pathways • Bispecific targeting aimed for synergy • Intended to promote durable anti- tumor effect • Eliminate polyclonal residual disease with multi- antigen approaches and individualized vaccines • Polyspecific activity by targeting multiple antigens at once • Establish long-lasting immunological memory to prevent relapses • Precise therapies aimed to reduce tumor burden across all disease stages including late lines • ADC as potential “augmenters” of immunomodulators and mRNA cancer vaccines • Ongoing focus on HER2, HER3, TROP2, B7-H3 as combination partners 17 This is a conceptual slide and does not imply published data as bases for. Immunomodulators Targeted therapies mRNA cancer vaccines Our Concept Towards a Potentially Curative Approach to Cancer
Programs Currently Evaluated in Clinical Stage 18 Targeted therapies Targeted therapy ADCs, CAR-T Immunomodulators Novel checkpoint inhibitors cytokines, immune agonists Space for curative approaches mRNA vaccines SynergySynergy Synergy Immunomodulators mRNA cancer vaccines BNT315/ GEN10535 BNT316/ ONC-3926 BNT312/ GEN10425 BNT314/ GEN10595 BNT327/ PM80023 Anti-OX40 Anti-CTLA4 Anti-4-1BB Anti- CD40 / Anti-4-1BB Anti-EpCAM / Anti-PD-L1 / Anti-VEGF BNT151 BNT152 BNT153 Ribocytokines IL2, IL7 iNeST FixVac individualized Neoantigen-Specific immunoTherapy BNT111 Melanoma BNT113 HNSCC BNT116 Lung Cancer BNT122/ RO71984574 BNT324/ DB-13111 BNT323/ DB-13031 BNT325/ DB-13051 BNT326/ YL2022 Anti-HER2 ADC Anti-B7-H3 ADC Anti-TROP2 ADC Anti-HER3 ADC BNT211 CAR-T Anti-CLDN6 CAR-T BNT141 BNT142 Ribomabs Anti- CLDN6 Anti-CLDN18.2 • Adj. CRC • Adj. Pancreatic Cancer • Adj. Bladder Cancer • Advanced Melanoma Partnered with 1. DualityBio; 2. MediLink; 3. Biotheus; 4. Genentech, a member of the Roche Group; 5. Genmab; 6. OncoC4.
BNT327/PM80021 PD-L1 × VEGF bispecific antibody Validated across 25+ tumor types with >700 patients treated Select Candidates Suitable for Late-Stage Development Across Multiple Cancer Indications 19 Partnered with: 1. Biotheus. 2. Genentech, a member of the Roche Group. Immunomodulators Targeted Therapy BNT211 Autologous CLDN6-targeting CAR-T + CAR-T cell amplifying RNA vaccine (“CARVac”) Anti-VEGF A Anti-PD-L1 • Broad applicability across range of cancers • Planned Ph3 in SCLC, NSCLC and TNBC • Targeting CLDN6+ cancers, including ovarian, testicular, endometrial, sarcoma, lung, and gastric cancer mRNA Cancer Vaccines BNT122 Autogene cevumeran2 Individualized Cancer Vaccine Candidate Personalized medicine targeting patient-specific tumor antigens • Targeting cancers in adjuvant stage • Studies ongoing in CRC, PDAC, urothelial cancer and other solid tumors
BNT327/PM80021: Synergistic Targeting of PD-L1 and VEGF 20 Targeting of PD1/PDL1 blockade to VEGF high tumors Selected NSCLC IHC3 Bispecific MOA Anti-VEGF-A (Fab) Anti-PD-L1 (VHH) VEGF-A dimer in the TME PD-L1 ligand on tumor cells Tumor microenvironment (TME) BNT327/ PM80021 VEGF-A dimer in the TME Anti-VEGF-A (Fab) Anti-PD-L1 (VHH) BNT327/PM80021 characteristics: combined tumor targeting2 PD-L1 ligand on tumor cells 1. Partnered with Biotheus; 2. Khan KA Nat Rev Clin Oncol 2018; 3. IHC data: Human Protein Atlas. VEGF-A PD-L1 Targeting of VEGF neutralization to PDL1 high tumors
VEGF signaling has immunosuppressive effects in addition to angiogenesis Anti-VEGF Treatment May Reverse Immune-Suppressive Effects and Potentially Improve Outcome of IO Treatment 21 Source: Khan KA Nat Rev Clin Oncol 2018; Marin-Acevedo JA and Hanna NH, ASCO 2023. Immunosuppression • Inhibit the recruitment, activity, and maturation of effector immune cells • Promote the recruitment and proliferation of suppressive immune cells Tumor angiogenesis Abnormal blood vessel formation leads to hypoxia, acidosis, and restricted drug delivery VEGF-A VEGF-A dimer in the TME Tumor microenvironment (TME) VEGF is overexpressed in the TME Immune cells
BNT327/PM80021 is Being Investigated Across Multiple Tumor Types with >700 Patients Treated 22 1. Partnered with Biotheus. 2L+ Cervical Cancer PROC 2L+ PSOC 2L+ NSCLC EGFRm 2L SCLC Lung Gynae- cology 1L SCLC 2L+ Endometrial Cancer 1L NSCLC WT PD-L1+ + Nab-Paclitaxel + FOLFOX4 + FOLFIRI + Pemetrexed / Platinum + Pemetrexed/Carboplatin + Paclitaxel + Etoposide/Platinum Mono Combo 2L+ ccRCC 1L MPM 1L HCC Advanced BTC Breast 1L TNBC 2L NENOthers Combo Ongoing studies with BNT327/PM8002 Gastro- intestinal Genito- urinary nccRCC Mono 1L Mucosal Melanoma Data expected in Q4'2024-2025
BNT327/PM80021 with nab-paclitaxel Shows Clinically Meaningful Efficacy Irrespective of PD-L1 Status in 1L TNBC 23 1. Partnered with Biotheus; 2. Cortes, J, et al. N. Engl. J. Med. 2022. *PD-L1 testing was not done in 4 patients (not shown). ORR: 75.0% and mPFS 14.0 months Variable ITT* PD-L1 CPS<1 PD-L1 1≤CPS<10 PD-L1 CPS≥10 Population (n) 42 13 16 9 ORR % 73.8 76.9 56.3 100.0 DCR % 95.2 100.0 93.8 100.0 mPFS (mo) 13.5 NR 14.0 10.8 -100 -80 -60 -40 -20 0 20 B e s t C h a n g e f ro m B a s e li n e ( % ) CPS<1 1CPS<10 CPS10 ITT population: mDoR 11.7 mos; mOS not reached Benchmark comparator data by PD-L1 expression level Indication Benchmark regimen ORR mPFS mOS Benchmark Study TNBC (CPS <10) Chemo 35% 5.6 mo 15.0 mo KEYNOTE-355 2 TNBC (CPS >10) Pembro + Chemo 62% 9.7 mo 23.0 mo KEYNOTE-355 2 Phase 1/2b (NCT05918133): clinical activity of BNT327/PM80021 in combination with nab-paclitaxel Y. Meng et al. Presented at ESMO 2024. Presentation 384MO
BNT327/PM80021 May Drive Clinical Benefit Irrespective of PD-L1 Status 24 1. Partnered with Biotheus; Source: Y. Meng et al. Presented at ESMO 2024. Presentation 384MO. Clinical signals observed in studies enrolling >700 patients across 10+ Indications Anti-PD-L1 BNT327/PM80021 MOA dual mechanisms: tumor targeting and synergy in reversing immunosuppression PD-L1 CPS<1 PD-L1 1≤CPS<10 Anti-VEGF BNT327/PM80021 can potentially become backbone IO therapy irrespective of PD-L1 status BNT327/PM80021 + chemo in 1L TNBC Y. Meng et al. Presented at ESMO 2024. Presentation 384MO ORR 76.9% ORR 56.3% PD-L1 CPS >10 ORR 100.0%
Next-generation Bispecific Can Potentially Expand the Reach of IO Therapy 25 EGFRmut NSCLC Ovarian Cancer Melanoma HR+ HER2- BC MSI-H or dMMR solid tumors GlioblastomaCervical Cancer Endometrial Cancer SCLC Next-gen PD-(L)1xVEGF bispecific opportunity HCC HNSCC PD-L1 ≥1% HNSCC PD-L1 <1% NSCLC PD-L1 ≥ 50% NSCLC PD-L1 <50% TNBC PD-L1 <10%TNBC PD-L1 ≥ 10% Gastric or GEJ Cancer PD-L1< 1%Gastric or GEJ Cancer PD-L1 ≥ 1% PD-(L)1 monotherapy approved in front line PD-(L)1 approved as combination therapy or in later line PD-(L)1 not currently approved Only selected indications listed Anti-VEGF approved indications Source: Keytruda Label; Opdivo Label; Tecentriq Label; Imfinzi Label; Libtayo Label; Bavencio Label; Jemperli Label; Loqtorzi Label; Zynyz Label; Avastin Label; Cyramza Label; Lenvima Label; Votrient Label . Selected indications listed based on FDA approval. CRC (MSS) Seek improved efficacy profile vs. existing IO Explore indications non-responsive to current IO PDAC
Anti-PD-(L)1 therapy addresses ~1.5 M new cancer cases in the US and EU Anti-PD-(L)1 Therapy Only Addresses a Fraction of Cancer Incidence 26 1. US incidence source: NIH and American Cancer Society data EU incidence source: European Cancer Information System, Indications listed on the previous slide are shown. Breast (non TNBC) TNBC PD-L1 <10% CRC (MSS) EGFRmut NSCLC Pancreatic Ovarian GBM Lung Melanoma RCC Endometrial HNSCC/nasopharyngeal TNBC PD-L1 >10% HCC Gastric CRC (MSI-H) US and EU Cancer Incidence1 PD-(L)1 not approved PD-(L)1 approved
Significant Patient Population Not Addressed by Existing IO Therapies 27 1. US incidence source: NIH and American Cancer Society data EU incidence source: European Cancer Information System, Indications listed on the previous slide are shown. Breast (non TNBC) TNBC PD-L1 <10% CRC (MSS) EGFRmut NSCLC Pancreatic Ovarian GBM Lung Melanoma RCC Endometrial HNSCC/nasopharyngeal TNBC PD-L1 >10% HCC Gastric CRC (MSI-H) US and EU Cancer Incidence1 PD-(L)1 not approved PD-(L)1 approved >1.4 M new cancer cases in the US and EU that cannot be addressed by current IO therapies
We Aim to Bring New Approaches Across Indications through Our Combination Strategy 28 1. US incidence source: NIH and American Cancer Society data EU incidence source: European Cancer Information System, Indications listed on the previous slide are shown. Breast (non TNBC) TNBC PD-L1 <10% CRC (MSS) EGFRmut NSCLC Pancreatic Ovarian GBM Lung Melanoma RCC Endometrial HNSCC/nasopharyngeal TNBC PD-L1 >10% HCC Gastric CRC (MSI-H)PD-(L)1 not approved PD-(L)1 approved
Space for curative approaches Immunomodulator mRNA vaccines Targeted therapy ADCs, CAR-T SynergySynergy Synergy 29 1. Partnered with Biotheus; 2. Data on file. Disclaimer: Conceptual schema, illustrative purpose only. Focus on BNT327/PM80021 as Backbone for Late-Stage Development Monotherapy Activity, and Synergy in Combination with Chemotherapy in Various Indications Preclinical Synergy with ADC2
BNT327/PM80021 + BNT325/DB-13052 TROP2-ADC: Preclinical Data Demonstrate Enhanced Anti-Tumor Efficacy when Combined 30 Partnered with: 1. Biotheus; 2. DualityBio. Xenograft A375 PBMC-co injection model – A375 expressing TROP2 in B-NDG B2M hTROP2-MC38 in wt mice 0 500 1000 1500 2000 2500 T u m o r v o lu m e ( m m ³) 13 15 18 20 22 25 27 29 TROP2 ADC BNT327/PM8002 Days post inoculation BNT327/PM8002 BNT325/DB-1305 PBS TROP2 ADC BNT327/PM8002 BNT327/PM8002 + TROP2 ADC Vehicle BNT325/DB-1305 BNT327/PM8002 DL1 BNT325/DB-1305 + BNT327/PM8002 DL2 BNT327/PM8002 DL2 BNT325/DB-1305 + BNT327/PM8002 DL1 Days post inoculation
BNT327/PM80021 Clinical Development Taking Full Control of Global Rights and Clinical Programs 31 Partnered with: 1. Biotheus; 2. DualityBio; 3. Indications included in Ph2a: NSCLC, mucosal melanoma, renal cell carcinoma, endometrial cancer, cervical cancer, platinum resistant ovarian cancer. Global clinical trials China-based clinical trials BNT327/PM8002 Proven capabilities of BioNTech + Biotheus >700 patients enrolled across 10+ indications 19 clinical trials ongoing or planned, including 3 global registrational trials in 1L TNBC, SCLC, and NSCLC Indication Target population Regimen Phase Status SCLC 1L or 2L + chemo 2 Ongoing TNBC 1L or 2L + chemo 2 Ongoing SCLC 1L + chemo vs. atezolizumab + chemo 3 US IND approved NSCLC 1L + chemo vs. pembrolizumab + chemo 2/3 US IND approved TNBC 1L + chemo vs. chemo 3 Planned Selected solid tumors + BNT325/DB-13052 1/2 Ongoing Selected solid tumors + BNT324/DB-13112 1/2 US IND approved Selected solid tumors + BNT323/DB-13032 1/2 US IND approved Indication Target population Regimen Phase Status TNBC 1L + chemo vs. chemo 3 Ongoing SCLC 2L + chemo vs. chemo 3 Ongoing NSCLC 2L+ EGFRmut + chemo 2/3 Ongoing SCLC 1L + chemo 2/3 Ongoing 2L + chemo 2 Primary completion TNBC 1L + chemo 1/2 Ongoing HCC 1L + chemo 2 Ongoing 1L + TIGIT x PVRIG (PM1009) 1/2 Ongoing NEN 2L + chemo 2 Ongoing MPM 1L + chemo 2 Ongoing Advanced solid tumors3 mono 1/2 Primary completion
Accelerating Global Clinical Development Program for BNT327/PM80021 Partnered with: 1. Biotheus; 2. DualityBio. Explore potential of BNT327/PM80021 in three waves of focused development • Phase 2 in SCLC • Phase 2 in TNBC Ongoing Planned • Phase 2/3 NSCLC for 2024 • Phase 3 SCLC for 2024 • Phase 3 TNBC for 2025 3 Broaden2 Combine1 Establish Ongoing Planned 32 BNT327/PM80021+chemo: Establish in combination with chemotherapy in potential Fast-to-Market indications BNT327/PM80021+ADC: Explore expansion to novel combinations with ADCs in high unmet need indications BNT327/PM80021 + novel: Broaden to further indications • Phase 1/2 with BNT323/DB-13032 (HER2) in solid tumors for 2025 • Phase 1/2 with BNT324/DB-13112 (B7- H3) in solid tumors for 2025 • Additional combinations for 2025 • Phase 1/2 with BNT325/DB-13052 (TROP2) in solid tumors
Announced Planned Acquisition of Biotheus 1. Subject to regulatory approvals and other customary closing conditions. Upfront cash and BioNTech stock payment of $800 Million Biotheus to become a wholly-owned BioNTech subsidiary Milestone-based cash earn-out of up to $150 million Closing expected Q1 20251 33
Advancing BNT327/PM80021 in multiple indications, aiming for first-to-market approvals Biotheus Acquisition to Accelerate BNT327/PM80021 Development Execution 34 1 Partnered with Biotheus. Anti-VEGF A Anti-PD-L1 VHH BNT327/ PM80021 development acceleration and expansion Clinical development capability establishment in China Full pipeline and platform ownership Manufacturing site supporting initial launch cGMP manufacturing facility with multiple 2000L bioreactors Comprehensive E2E bispecific antibody discovery and development capabilities 6 clinical stage assets Pre-clinical ADC pipeline ~80-person clinical development organization in China with demonstrated execution ability Global control of BNT327/PM80021 development and commercialization program Streamline execution of initial BNT327/PM80021 + ADC development plans
Biotheus Manufacturing Facility to Supply Clinical Trial Expansion and Early Launches 35 Biotheus Brings Fully-Integrated CMC, Manufacturing and Fill Finish Capabilities Biotheus 2000L cGMP manufacturing site 2000L Production plant: Support global clinical development and early launches IND documentation has met global regulatory standards including China, Australia and US 200L Pilot plant: support IND and Phase 1 studies
36 1. Qin et al. Molecular Cancer (2019) 18:155. 2. Partnered with Biotheus. Oncology Treatment is Entering the Bispecific Antibody Era IO therapies have relied on mAbs with a single target1 Bispecific antibodies enable new opportunities TAA: tumor-associated antigen 2014 Blinatumomab (CD20 × CD3) 2017 Emicizumab (factor IXa × factor X) 2021 Amivantamab (EGFR × cMet) 2022 Tebentafusp (gp100 × CD3) Faricimab (Ang-2 × VEGF) Teclistamab (BCMA × CD3) Mosunetuzumab (CD20 × CD3) 2023 Epcoritamab (CD20 × CD3) Glofitamab (CD20 × CD3) Talquetamab (GPRC5D × CD3) Elranatamab (BCMA × CD3) 2024 Tarlatamab (DLL3 × CD3) TAA TAA+ TAA + Immune target Selected MoAs of novel bispecific antibodies Tumor targeting Immune redirecting BNT327/PM80022 combines tumor targeting and immune redirecting 10 new bispecifics approved in the U.S. since 2021 FDA approval of bispecifics
Biotheus' Fully-Integrated Antibody Discovery and Engineering Workflow 37 2 Fabs + 2 VHHs 1 Fab + 1Fab 2 Fabs + 2 scFvs “Plug and Play” design enables screening of multiple formats for optimized lead selection Selected antibody formats generated 100 - 1,000+ molecules Low stringency screening 100+ High stringency screening ~20 In vivo efficacy 24 months for BNT327/PM80021 from discovery to IND submission 9 clinical stage bispecifics generated 30+ preclinical bispecifics generated Bispecific produced with a single cell line ~5100+
Biotheus Pipeline Enables Exploration of Novel IO + IO Combinations 1. Partnered with Biotheus; 2. Hansoh has been granted by Biotheus the exclusive rights to develop, commercialize and manufacture PM1080 in Greater China. Biotheus has ex-China rights. Biotheus Pipeline overview Selected Clinical Assets BNT327/PM80021 (PD-L1 × VEGF bispecific) Phase 2 / Phase 3 in China PM1009 (TIGIT × PVRIG bispecific) Phase 1 PM1022 (TIGIT × PD-L1 bispecific) Phase 1 PM1015 (CD73 mAb) Phase 1 PM10802 (EGFR × cMET bispecific) Phase 1 PM1032 (4-1BB × CLDN18.2 bispecific) Phase 1 Multiple Pre-clinical Candidates Multiple bispecifics in pre-clinical development, including bispecific ADCs. A broad range of targets to be explored for IO+IO combos 38
3 Commercialization: Next Era of BioNTech Annemarie Hanekamp, Chief Commercial Officer
BioNTech is in Transition to a Multi-Product Commercial Oncology Company 40 Partnered with: 1. Pfizer; 2. DualityBio; 3. Biotheus; 4. Genentech, a member of the Roche Group; Patient numbers sourced from DRG; LCM = Lifecycle Management. Strategic launch sequence for oncology portfolio Comirnaty1 LCM >4.9 billion doses distributed Expand >400K patients Launch ~50K patients Establish 200K – 300K patients ’2026-’2027 ’2028+’2021 Comirnaty1 BNT327/PM80023 + ADC combinations Autogene cevumeran4 (Adj. PDAC, Adj. MIUC) Novel-novel combinations BNT327/PM80023 (1L SCLC, 1L NSCLC, 1L TNBC) Autogene cevumeran3 (Adj. CRC) BNT323/DB-13032 (2L EC and 2L BC)
Maintaining COVID-19 Vaccine Franchise1 with Lean Commercial Infrastructure 41 Lean commercial organization in Germany and Türkiye, leveraging partners’ commercial infrastructures for global rollout of Comirnaty Cash generating COVID-19 business structure Fosun commercial territories2 Pfizer commercial territories BioNTech commercial territories 1. Partnered with Pfizer; 2. Comirnaty is not approved in mainland China; 3. As of September 30, 2024 Maintained ~80% gross margin3 Shared R&D expenses Low sales & marketing expenses
First Launch with BNT323/DB-13031 to Address Unmet Need in Endometrial and Breast Cancer Patients 42 2030 projected incidence 1. Partnered with DualityBio; 2. Projected incidence using historical figures from American Cancer Society (US); Globocan (EU4+UK); 3. SEER; 4. Triangulation of Plotkin, et al., 2024, and Fleming, et al., 2009; 5. CancerMPact; 6. Modi et al., 2022; 7. Bergeron et al., 2023. ~120K ~30K ~40K ~10K Incidence2 (2030) (U.S., EU4, UK) 1L systemic treated5 HER-2 expressing (IHC1+,2+,3+)4 Advanced metastatic and unresectable3,5 2L+ systemic treated5 ~25K Strategic launch to build-up BioNTech commercialization capabilities for future launches Establish relationships with oncology community and payors First step in building expertise in breast and gynecologic cancers ~615K ~80K ~180K ~75K Incidence2 (2030) (U.S., EU4, UK) 1L systemic treated5 HR+ HER2-low6,7 Advanced metastatic and unresectable3,5 2L+ systemic treated5 ~40K Endometrial cancer Breast cancer
BNT327/PM80021: Combine with SoC Chemotherapy in Potential Fast-to- Market Indications 43 Aiming to address remaining high unmet need through improved duration of response and survival Expanding breast cancer franchise while building a presence in lung cancer Establishing next- generation IO backbone for novel combinations Building on existing commercial infrastructure, rapidly scaling up to establish lung and breast cancer franchises ~190K 1L systemic treated non- AGA* 10, 13-16 ~415K Incidence (2030)2 (US, EU4, UK) ~45K 1L systemic treated* 10 ~60K Incidence (2030) 3-8 (US, EU4, UK) ~25K 1L systemic treated* 10 ~65K Incidence (2030) 3-8 (US, EU4, UK) NSCLC SCLC TNBC ~310K ~55K ~30K Advanced metastatic & unresectable9-10 Advanced metastatic & unresectable10-11 Advanced metastatic & unresectable10,12 2030 projected incidence; * Final patient pool will depend on Ph3 design 1. Partnered with Biotheus; 2. Globocan – Cancer Tomorrow; 3. SEER data for diagnosed SCLC and TNBC incidence in US; 4. Cancer Research UK; 5. Zentrum für Krebsregisterdaten; 6. Sante Publique; 7. AIOM; 8. EPDATA 9. SEER Stat Research Tool; 10. CancerMPact 2024; 11. Dayen et al (2019); 12. Halpern et al (2007); 13. Devarakonda, et al., 2015; 14. Pikor, et al., 2013; 15. Lam, et al., 2019; 16. Friedlaender et al., 2019.
Creating an AI Infused Commercialization Model Focused on Delivering our Innovations to Patients at Scale Partnered with: 1. DualityBio; 2. Biotheus. Build AI infused, optimized yet scalable commercial capabilities to launch BNT323/DB-13031 Leverage initial build to rapidly scale for BNT327/PM80022 and execute platform commercialization model Future proof AI commercial model to deliver multiple innovations to address multiple patient populations Launch Establish Expand 44
Aiming to Establish New Pillar of Care for Early-Stage Colorectal Cancer Patients with Autogene Cevumeran 45 1. Based on CancerMPact® Patient Metrics U.S., accessed in Feb 2024; 2. Babcock, B. et al. Ann. Surgical Onc., 2018; 3. Kotani D. et al. Nat Med, 2022; 4. Mulet-Margalef N. et al. Cancers, 2023; 5. Cohen, S.A. et al. Ann. Onc. 2022. 6. Nakamura Y. et al. Nat. Med., 2024. Percentage of stage II high risk / stage III patients who are expected to recur within 2-years of surgery6 65% ctDNA+ US Incidence | 151K1 Stage II (high) risk / Stage III | 60K1,2 ctDNA+ | 7K5 CRC (2030) Adjuvant treated | 39K3 MSI-L / MSS | 33K4 Phased expansion into early-stage tumors with a novel platform modality
End-to-End capabilities orchestration required Building a Patient-Centric Commercialization Model to Support the Establishment of Individualized mRNA Cancer Therapies 46 Intra- / inter- practice coordination Product ordering process / communication with manufacturer Sample preparation & shipment Product storage / cold-chain requirements Infusion clinic capabilities / capacity
BioNTech is in Transition to a Multi-Product Commercial Oncology Company 47 Partnered with: 1. Pfizer; 2. DualityBio; 3. Biotheus; 4. Genentech, a member of the Roche Group; Patient numbers sourced from DRG; LCM = Lifecycle Management. Strategic launch sequence for oncology portfolio Comirnaty1 LCM >4.9 billion doses distributed Expand >400K patients Launch ~50K patients Establish 200K – 300K patients ’2026-’2027 ’2028+’2021 Comirnaty1 BNT327/PM80023 + ADC combinations Autogene cevumeran4 (Adj. PDAC, Adj. MIUC) Novel-novel combinations BNT327/PM80023 (1L SCLC, 1L NSCLC, 1L TNBC) Autogene cevumeran3 (Adj. CRC) BNT323/DB-13032 (2L EC and 2L BC)
4 BNT327 Clinical Development Strategy Prof. Ilhan Celik, M.D. VP Clinical Development
Accelerating Global Clinical Development Program for BNT327/PM80021 Partnered with: 1. Biotheus; 2. DualityBio. Explore potential of BNT327/PM80021 in three waves of focused development • Phase 2 in SCLC • Phase 2 in TNBC Ongoing Planned • Phase 2/3 NSCLC for 2024 • Phase 3 SCLC for 2024 • Phase 3 TNBC for 2025 3 Broaden2 Combine1 Establish Ongoing Planned 49 BNT327/PM80021+ADC: Explore expansion to novel combinations with ADCs in high unmet need indications BNT327/PM80021 + novel: Broaden to further indications • Phase 1/2 with BNT323/DB-13032 (HER2) in solid tumors for 2025 • Phase 1/2 with BNT324/DB-13112 (B7- H3) in solid tumors for 2025 • Additional combinations for 2025 • Phase 1/2 with BNT325/DB-13052 (TROP2) in solid tumors BNT327/PM80021+chemo: Establish in combination with chemotherapy in potential Fast-to-Market indications
Next-generation Bispecific Can Potentially Expand the Reach of IO Therapy 50 EGFRmut NSCLC Ovarian Cancer Melanoma HR+ HER2- BC MSI-H or dMMR solid tumors GlioblastomaCervical Cancer Endometrial Cancer SCLC Next-gen PD-(L)1xVEGF bispecific opportunity HCC HNSCC PD-L1 ≥1% HNSCC PD-L1 <1% NSCLC PD-L1 ≥ 50% NSCLC PD-L1 <50% TNBC PD-L1 <10%TNBC PD-L1 ≥ 10% Gastric or GEJ Cancer PD-L1< 1%Gastric or GEJ Cancer PD-L1 ≥ 1% PD-(L)1 monotherapy approved in front line PD-(L)1 approved as combination therapy or in later line PD-(L)1 not currently approved Only selected indications listed Anti-VEGF approved indications Source: Keytruda Label; Opdivo Label; Tecentriq Label; Imfinzi Label; Libtayo Label; Bavencio Label; Jemperli Label; Loqtorzi Label; Zynyz Label; Avastin Label; Cyramza Label; Lenvima Label; Votrient Label . Selected indications listed based on FDA approval. CRC (MSS) Seek improved efficacy profile vs. existing IO Explore indications non-responsive to current IO PDAC
Treatment outcomes vary based on PD-L1 levels in 1L TNBC TNBC Patients Face Poor Outcomes Due to Limited Therapeutic Options 51 1.Incidence from SEER (US); Zentrum für Krebsregisterdaten (DE); Globocan (ES); Sante Publique (FR); AIOM (IT); Cancer Research UK 2. CancerMPact® 2024 Treatment Architecture EU5 and US 3.Danziger N, et al, . Variable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay. Oncologist. 2023 Apr 6;28(4):319-326. 4. Cortes, J, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N. Engl. J. Med. 2022, 387, 217–226. 6% 2% 11% 9% 14% 13% 36% 37% 33% 39% US EU5 Stage IV Stage III Stage II Stage I Stage 0 BC staging distribution 2 PD-L1 CPS < 10 (~ 55%)3,4 PD-L1 CPS > 10 (~ 45%)3,4 mOS Chemo: 15.0 mos (KN-355) 4 Pembro + chemo: 23.0 mos (KN-355) 4 4-year OS Chemo: ~ 15 – 20% (KN-355) 4 Pembro + chemo: ~ 25 – 30 % (KN-355) 4 5-year survival Stage IV2 ~65k2030 U.S., EU4, U.K. TNBC incidence1 10%
BNT327/PM80021 in Combination with Nab-Paclitaxel for 1L Metastatic TNBC 52 1. Partnered with Biotheus; 2. J. Cortes et al, Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer, N. Engl. J. Med. 387 (2020) pp 217-226; 3. Obtained from subgroup analysis. Key inclusion criteria • Age 18-75 years with life expectancy ≥ 12 weeks • Histologically or cytologically confirmed unresectable adv. or met. ER, PR, HER-2 negative TNBC • No prior systemic therapy despite taxane in (neo)adj. settings, ≥ 12 months • ≥ 1 measurable lesion (RECIST 1.1) • ECOG PS 0-1 • Adequate organ function Treatment continued until Disease progression or Unacceptable toxicity Primary endpoints: ORR per RECIST1.1, safety (NCI-CTCAE v5.0) Secondary endpoints: PFS, DCR, OS Key endpoints n=60 BNT327/PM80021 + Nab-paclitaxel Benchmark comparator data for 1L TNBC by PD-L1 expression level Indication Benchmark regimen ORR mPFS mOS Benchmark Study TNBC (CPS <10) Chemo 35% 5.6 mo 15.0 mo KEYNOTE-3552,3 TNBC (CPS >10) Pembro + Chemo 62% 9.7 mo 23.0 mo KEYNOTE-3552 Phase 1b/2 (NCT05918133) Y. Meng et al. Presented at ESMO 2024. Presentation 384MO
BNT327/PM80021: Safety Profile Appears Manageable in 1L TNBC 53 1. Partnered with Biotheus. Observed TRAEs are known safety signals of PD-(L)1 / VEGF-A targeting therapies plus chemotherapy and resulted in low discontinuation rate Safety Overview (N=42) n (%) All TRAEs 42 (100) Grade ≥3 TRAEs 24 (57.1) SAEs 10 (23.8) TRAE leading to dose interruption 27 (64.3) TRAE leading to dose reduction 7 (16.7) TRAEs leading to treatment discontinuation 2 (4.8) irAE 15 (35.7) Grade ≥3 irAE 4 (9.5) TRAEs of Interest (N=42) All grades, n (%) Grade > 3, n (%) Neutrophil count decreased 36 (85.7) 13 (31.0) White blood cell count decreased 32 (76.2) 10 (23.8) Anaemia 32 (76.2) 2 (4.8) Proteinuria 24 (57.1) 2 (4.8) Hypertriglyceridaemia 18 (42.9) 4 (9.5) Epistaxis 17 (40.5) 0 Aspartate aminotransferase increased 11 (26.2) 2 (4.8) Alanine aminotransferase increased 10 (23.8) 1 (2.4) Hypertension 8 (19.0) 2 (4.8) Phase 1b/2 (NCT05918133) Y. Meng et al. Presented at ESMO 2024. Presentation 384MO
BNT327/PM80021 in Combination with Chemo Shows Clinically Meaningful Efficacy in 1L TNBC Irrespective of PD-L1 Status 54 1. Partnered with Biotheus; 2. Cortes, J, et al. N. Engl. J. Med. 2022. SABCS = San Antonio Breast Cancer Symposium. *PD-L1 testing was not done in 4 patients (not shown). ORR: 75.0% and mPFS 14.0 months. Variable ITT* PD-L1 CPS<1 PD-L1 1≤CPS<10 PD-L1 CPS≥10 Population (n) 42 13 16 9 ORR % (95% CI) 78.6 (63.2, 89.7) 76.9 (46.2, 95.0) 68.8 (41.3, 89.0) 100.0 (66.4, 100.0) cORR % (95% CI) 73.8 (58.0, 86.1) 76.9 (46.2, 95.0) 56.3 (29.9, 80.3) 100.0 (66.4, 100.0) DCR % (95% CI) 95.2 (83.8, 99.4) 100.0 (75.3, 100.0) 93.8 (69.8, 99.8) 100.0 (66.4, 100.0) mPFS (Mo), (95%CI) 13.5 (9.4, --) NR (5.7, --) 14.0 (7.2, --) 10.8 (5.5, 13.5) -100 -80 -60 -40 -20 0 20 B e s t C h a n g e f ro m B a s e li n e ( % ) CPS<1 1CPS<10 CPS10 For the ITT population, mDoR 11.7 mos; mOS was not reached Benchmark comparator data for 1L TNBC by PD-L1 expression level Indication Benchmark regimen ORR mPFS mOS Benchmark Study TNBC (CPS <10) Chemo 35% 5.6 mo 15.0 mo KEYNOTE-3552 TNBC (CPS >10) Pembro + Chemo 62% 9.7 mo 23.0 mo KEYNOTE-3552 Phase 1/2b (NCT05918133): Y. Meng et al. Presented at ESMO 2024. Presentation 384MO Data update at SABCS December 11, 2024
Arm 1 Arm 2 BNT327/PM80021 Phase 2 in Combination with Chemotherapy for 1L/2L Triple Negative Breast Cancer 55 BNT327-02 (NCT06449222) Key inclusion criteria • Histologically confirmed, la/ mTNBC • 1L or 2L • If recurrent, stage I-III BC, at least 6 months has elapsed between completion of treatment with curative intent • ECOG PS 0,1 BNT327/PM80021 dose level 1+ Taxane A BNT327/PM80021 dose level 2+ Taxane A 1:1 n=40 Selected dose from cohort 1 will be used in cohort 2 Arm 1 Arm 2 Investigator choice BNT327/PM80021 + Taxane B BNT327/PM80021 + Anti-metabolite + Alkylating agent 1. Partnered with Biotheus 2. Cortes, J, et al. N. Engl. J. Med. 2022.. Primary endpoints: ORR per RECIST v1.1 and safety according to NCI-CTCAE v5.0 Key endpoints Phase 3 trial planned for 2025 Benchmark comparator data for 1L TNBC by PD-L1 expression level Indication Benchmark regimen ORR mPFS mOS Benchmark Study TNBC (CPS <10) Chemo 35% 5.6 mo 15.0 mo KEYNOTE-3552 TNBC (CPS >10) Pembro + Chemo 62% 9.7 mo 23.0 mo KEYNOTE-3552
BNT327/PM80021 in Combination with Chemotherapy for EGFR-mutated, post-TKI NSCLC 56 1. Partnered with Biotheus; 2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761210s004lbl.pdf (accessed on 13Nov2024) BNT327/PM80021 + Carboplatin + Pemetrexed 4 cycles N=64 Inclusion criteria • Age ≥ 18 years • Nonsquamous Stage IIIB/C and IV NSCLC ineligible for surgery or local therapy • EGFR sensitizing mutation • Failure of EGFR-TKI treatment(s) • No other prior systemic therapy than EGFR-TKIs • Asymptomatic/stable brain metastasis allowed BNT327/PM80021 + Pemetrexed Maintenance Primary endpoint: ORR per RECIST v1.1 Key endpoints Benchmark comparator data for 2L+ EGFR-mutated NSCLC Status Benchmark regimen ORR mPFS mOS Benchmark study Current SoC Chemo 29.0% 4.2mo 15.3mo MARIPOSA-22 Recent Approval Amivantamab + chemo 53.0% 6.3mo 17.7mo MARIPOSA-22 Phase 2 study of BNT327/PM80021 + carbo/pem in EGFRm NSCLC post EGFR TKI (NCT05756972) Adapted from Wu YL et al. Presented at ESMO 2024. Mini oral 1255MO. Treatment continued until Disease progression or Up to 2 years
Safety Profile of BNT327/PM80021 + Chemotherapy in Patients with EGFRm NSCLC after Progressing on Prior EGFR TKI Safety Overview, TRAE, (n=64) n (%) Any 63 (98.4) Grade ≥3 39 (60.9) SAE 11 (17.2) Leading to interruption of BNT327/PM8002 20 (31.3) Leading to discontinuation of only BNT327/PM8002 4 (6.3) only chemotherapy 4 (6.3) BNT327/PM8002 and chemotherapy 1 (1.6) Leading to death* 1 (1.6) Any-grade immune-related 26 (40.6) Grade ≥3 immune-related 4 (6.3) Grade ≥3 VEGF-related (hypertension/elevated blood pressure, proteinuria, epistaxis, hemoptysis) 7 (10.9) 1. Partnered with Biotheus; *TRAE leading to death: 1 case of pneumonia. CONFIDENTIAL - Virtual Investigator Engagement Meeting BNT327-01 (SCLC – Phase II) Patients (%) Observed TRAEs are known safety signals of PD-(L)1 / VEGF-A targeting therapies plus chemotherapy and resulted in low discontinuation rate Phase 2 study of BNT327/PM80021 + carbo/pem in EGFRm NSCLC post EGFR TKI (NCT05756972) Adapted from Wu YL et al. Presented at ESMO 2024. Mini oral 1255MO. TRAEs of Interest (N=64) All grades, n (%) Grade ≥ 3, n (%) White blood cell count decreased 48 (75.0) 9 (14.1) Anaemia 47 (73.4) 6 (9.4) Neutrophil count decreased 44 (68.8) 19 (29.7) Platelet count decreased 37 (57.8) 6 (9.4) Alanine aminotransferase increased 34 (53.1) 1 (1.6) Aspartate aminotransferase increased 31 (48.4) 1 (1.6) Proteinuria 25 (39.1) 1 (1.6) Gamma-glutamyltransferase increased 24 (37.5) 5 (7.8) Lymphocyte count decreased 24 (37.5) 7 (10.9) Hypertension 13 (20.3) 5 (7.8) 57
-80 -60 -40 -20 0 20 40 60 SD PD PR 58 1. Partnered with Biotheus; PD = progressive disease; PD-L1 = programmed cell death ligand 1; PR = partial response; SD = stable disease. B e s t C h a n g e f ro m B a s e li n e ( % ) Negative Low Expression High Expression Study months 0 1 2 3 4 5 6 7 8 9 10 11 12 13 PD SD PR On treatment N e g a ti v e L o w E x p re s s io n H ig h E x p re s s io n Median follow-up time: 7.7 months PD-L1 Negative TPS <1% ORR 39.3% DCR 92.9% PD-L1 High TPS ≥50% ORR 92.3% DCR 92.3% PD-L1 Low TPS 1–49% ORR 60.9% DCR 100% Phase 2 study of BNT327/PM80021 + carbo/pem in EGFRm NSCLC post EGFR TKI (NCT05756972) Adapted from Wu YL et al. Presented at ESMO 2024. Mini oral 1255MO. BNT327/PM80021 in Combination with Chemo Shows Clinically Meaningful Efficacy in EGFRm NSCLC Irrespective of PD-L1 Status
Treatment outcomes vary based on histology and PD-L1 levels in 1L NSCLC patients without actionable genomic alterations 7% 8% 10% 11% 37% 44% 46% 37% US EU5 Stage IV Stage III Stage II Stage I Non-Small Cell Lung Cancer is One of the Highest Incidence Cancers Globally1 59 1. Globocan – Cancer Tomorrow. 2. CancerMPact® 2024 Treatment Architecture EU5 and US; Note that 5-year survival reported includes all comer NSCLC population ie including with actionable genetic alterations. 3. Ganti AK, et al. Update of Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non-Small Cell Lung Cancer in the US. JAMA Oncol. 2021 Dec; 4. Mansour MSI et al PD-L1 Expression in Non-Small Cell Lung Cancer Specimens: Association with Clinicopathological Factors and Molecular Alterations. Int J Mol Sci. 2022 Apr 19;23(9):4517; 5. Saez de Gordoa, K. et al. PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain. Diagnostics 2021, 11, 1452; 6. Garassino MC, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023 Apr 10;41(11):1992-1998; 7. Silvia Novello et al., Pembrolizumab Plus Chemotherapy in Squamous Non–Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. JCO 41, 1999-2006(2023). ~415k 2030 U.S., EU4, U.K. NSCLC incidence1 NSCLC Staging distribution2 Non-squamous (~ 70%)3 Squamous (~ 30%)3 PD-L1 ≥ 50% (~ 25 - 30%)4,5 5-year OS: 30% (KN-189)6 5-year OS: 23% (KN-407)7 PD-L1 1 - 49% (~ 30 - 40%)4,5 5-year OS: 20% (KN-189)6 5-year OS: 21% (KN-407)7 PD-L1 < 1% (~ 30 - 40%)4,5 5-year OS: 10% (KN-189)6 5-year OS: 11% (KN-407)7
Phase 1b/2a (NCT05918445): Safety across all 3 NSCLC cohorts Wu, C. et al. presented at ASCO 2024. Poster #8533. * Additional cohorts are part of study NCT05918445 and not included in this presentation. 1. Partnered with Biotheus; 2. Garassino MC, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023 Apr 10;41(11):1992-1998; 3. Silvia Novello et al., Pembrolizumab Plus Chemotherapy in Squamous Non–Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. JCO 41, 1999-2006(2023). 60 Key inclusion criteria • Age ≥ 18 years with expected survival rate 12 weeks • ECOG 0 to 1 • ≥ 1 measurable lesion (RECIST v1.1) Primary endpoints: ORR per RECIST v1.1 and safety according to NCI-CTCAE v5.0 Secondary endpoints: DoR, DCR, PFS per RECIST v1.1 and OS Key endpoints BNT327/PM80021 monotherapy 20 mg/kg Q2W Cohort 2 (n = 36) EGFR-mutated NSCLC & failed prior EGFR-TKI treatment. Cohort 1 (n = 17) 1L NSCLC EGFR/ALK WT & PD-L1+ (TPS ≥1) w/o previous systemic treatment Cohort 3 (n = 8) EGFR/ALK WT that failed anti-PD-(L)1 therapy and platinum-based chemotherapy regimens. Cohorts*: Treatment continued until Disease progression or Unacceptable toxicity Benchmark comparator data for 1L non-AGA NSCLC (PD-L1 all-comers) Indication Benchmark regimen ORR mPFS mOS Benchmark study Non-Squamous Pembro + chemo 48% 9.0 mo 22.0 mo KEYNOTE-1892 Squamous Pembro + chemo 62% 8.0 mo 17.2 mo KEYNOTE-4073 BNT327/PM80021: Phase 1/2 Dose Expansion Trial with Monotherapy in 1L NSCLC
BNT327/PM80021: Monotherapy Safety Profile Appeared Manageable in 1L NSCLC 61 1. Partnered with Biotheus. Phase 1b/2a (NCT05918445): Safety across all 3 NSCLC cohorts Wu, C. et al. presented at ASCO 2024. Poster #8533. Safety overview (n=61) n (%) All TRAEs 52 (85.2) TRAE ≥3 12 (19.7) irAEs 24 (39.3) SAE 15 (24.6) TRAE leading to dose discontinuation 5 (8.2) Common TRAEs (n=61) All grades, n (%) Grade > 3, n (%) Proteinuria 33 (54.1) 3 (4.9) Hypertension 15 (24.6) 6 (9.8) Hypothyroidism 13 (21.3) 0 Hypoalbuminemia 12 (19.7) 0 Hypocalcemia 11 (18.0) 0 Anemia 9 (14.8) 1 (1.6) Alanine aminotransferase increased 8 (13.1) 8 (13.1) No Grade 4/5 TRAEs observed, most AEs were Grades 1-2
BNT327/PM80021 Monotherapy Efficacy in 1L NSCLC 62 1. Partnered with Biotheus; 2. Reck, M. et al. NEJM 2016. Phase 1b/2a (NCT05918445): cohort 1, 1L NSCLC (EGFR & ALK WT) Wu, C. et al. presented at ASCO 2024. Poster #8533. 1L NSCLC mono tx (cohort 1, n=17): ORR 47%, DCR 100%, mPFS 13.6 months Comparable ORR in PD-L1 1–49% (n=9) and PD-L1 ≥50% (n=8) Waterfall/spider plots and Kaplan-Meier curves (PFS) PD-L1 ≥50% PD-L1 1–49% SD PR 60 40 20 0 −20 −40 −60 −80 B e s t c h a n g e f ro m b a s e lin e ( % ) 0 50 SD PD PR On Treatment 30 10 −10 −30 −50 −70 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 C h a n g e f ro m b a s e lin e ( % ) Months Data Cut of Date: 2024-03-15. Indication Benchmark regimen ORR mPFS mOS Benchmark Study 1L NSCLC (PD-L1 > 50%) Pembro monotherapy 45% 7.7 mo 26.3 mo KEYNOTE-0242 Phase 2/3 to initiate by YE 2024
63 ~60k 2030 U.S., EU4, U.K. SCLC incidence1 1.Incidence from: SEER data for diagnosed SCLC incidence in US; Cancer Research UK; Zentrum für Krebsregisterdaten; Sante Publique; AIOM; EPDATA. 2.Statistics from Dayen et al (2019); CancerMPact® Patient Metrics US & EU5, accessed February 2024. *Due to limited survival data in EU5, U.S. survival data is reported; 3.Walls, Gerard M. et al.Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT TrialInternational Journal of Radiation Oncology, Biology, Physics, Volume 119, Issue 5, 1386 - 1390 4.L. Horn et al, First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancerN. Engl. J. Med., 379 (2018), pp. 2220-2229 5.Stephen V. Liu et al., Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). JCO 39, 619-630(2021). Extensive-Stage Small Cell Lung Cancer is a High-Incidence Cancer with Poor Long-term Survival Rates 38% 32% 62% 68% US EU5 Extensive Stage Limited Stage SCLC Staging distribution2 Limited-Stage SCLC Extensive-Stage SCLC mOS CRT: 25 – 30 mos (CONVERT)3 Atezo + chemo: 12.3 mos (IMPower133)4,5 24 mos OS CRT: ~ 50% (CONVERT)3 Atezo + chemo: ~ 25% (IMPower133)4,5 5-year survival2 20% 3% High unmet need for ES-SCLC patients as long-term survival outcomes remain very poor
BNT327/PM80021 in Combination with Paclitaxel for 2L SCLC 64 1. Partnered with Biotheus 2. Aix S.P. et al. Lancet Resp Med 2023. 3. Ahn M. et al. NEJM 2023. Phase 2 (NCT05879068) Key Inclusion criteria Patients with advanced SCLC who progressed after platinum- based chemotherapy with or without checkpoint inhibitors • Age ≥ 18 years • ECOG PS 0-1 Treatment continued until Disease progression or withdrawal of consent or Unacceptable toxicity n=99 Primary endpoints: ORR per RECIST1.1, TRAEs incidence and severity Secondary endpoints: DCR, DoR, PFS and OS Key endpoints BNT327/PM80021BNT327/PM80021 + paclitaxel (5 cycles) Induction Maintenance Benchmark comparator data for 2L+ SCLC Status Benchmark regimen ORR mPFS mOS Benchmark study Current SoC Chemo 29% 4.0 mo 7.6 mo ATLANTIS2 Recent Approval tarlatamab 40% 4.9 mo 14.3 mo DeLLphi-3013
BNT327/PM80021 Combined with Paclitaxel Shows Acceptable Safety Profile in 2L SCLC 65 1. Partnered with Biotheus. Phase 2 (NCT05879068) Ying Cheng et al. Presented at ESMO 2023. Poster#1992P PD-L1 expression in tumors may enrich and focus VEGF neutralization into the TME sparing normal tissue and leading to reduced systemic toxicity Blocking VEGF inhibits the development of angiogenesis impeding tumor growth Study week Safety overview (n=48) n (%) All TRAEs 45 (93.8) TRAE ≥3 30 (62.5) SAE 16 (33.3) TRAE leading to treatment discontinuation 1 (2.1) TRAE ≥10% of patients All grades, n (%) Grade > 3, n (%) Neutropenia 23 (47.9) 22 (45.9) Leukopenia 23 (47.9) 12 (25.0) Decreased platelet count 12 (25.0) 1 (2.1) Anemia 11 (22.9) 0 Proteinuria 9 (18.8) 2 (4.2) Pneumonitis 6 (12.5) 1 (2.1)* *One grade 5 event due to pneumonitis Observed TRAEs are known safety signals of PD-(L)1 / VEGF-A t rgeti g therapie plus chemoth rapy and resulted in low discontinuation rate (2.1%)
C h a n g e f ro m B a s e li n e ( % ) 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) Ying Cheng et al. Presented at ESMO 2023. Poster#1992P BNT327/PM80021 Combined with Paclitaxel Shows Efficacy in 2L SCLC 66 1. Partnered with Biotheus; 2. On-label ORR for topotecan (24%), lurbinectedin (35%), and tarlatamab (40%). -90 -70 -50 -30 -10 10 30 50 70 PD SD PR CR -90 -70 -50 -30 -10 10 30 50 70 90 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 PD SD PR CR On Treatment Study Months Response Efficacy Evaluation Population ITT (n=36) IO-naïve (n=22) IO- treated (n=14) mPFS, m 5.5 5.9 3.9 mDoR, m 10.0 10.0 2.6 • Received prior anti-PD- 1/PD-L1 : ~46% ORR for current SoC therapies in 2L+ SCLC ranges from 24-40% 2
BNT327/PM80021: Phase 2 Dose Optimization in Combination with Chemotherapy for 1L/2L SCLC 67 1. Partnered with Biotheus; 2. L. Horn et al, First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancerN. Engl. J. Med., 379 (2018), pp. 2220-2229. BNT327-01 (NCT06449209) Key Inclusion criteria • Cohort 1: Untreated ES-SCLC or LS-SCLC with TFI≤6 months since last treatment • Cohort 2 & 3: SCLC with disease progression after 1L platinum based CTx (w/wo IO) or 2L CTx BNT327/PM80021 (dose level 1) + chemo BNT327/PM80021 (dose level 2) + chemo • Three cohorts based on previous treatment for patients and chemo option used to combine with BNT327/PM80021 • Each cohort randomized to receive two different dose levels BNT327/PM80021 with chemo Treatment continued until Disease progression or Intolerable toxicity Primary endpoints: ORR per RECIST v1.1 and safety according to NCI-CTCAE v5.0 Secondary endpoints: DoR, DCR, PFS per RECIST v1.1 and OS Key endpoints Phase 3 to initiate by YE 2024 Benchmark comparator data for 1L ES-SCLC Benchmark regimen ORR mPFS mOS Benchmark study Atezo + chemo 60% 5.2 mo 12.3 mo IMPower1332
Accelerating Global Clinical Development Program for BNT327/PM80021 Partnered with: 1. Biotheus; 2. DualityBio. Explore potential of BNT327/PM80021 in three waves of focused development • Phase 2 in SCLC • Phase 2 in TNBC Ongoing Planned • Phase 2/3 NSCLC for 2024 • Phase 3 SCLC for 2024 • Phase 3 TNBC for 2025 3 Broaden2 Combine1 Establish Ongoing Planned 68 • Phase 1/2 with BNT323/DB-13032 (HER2) in solid tumors for 2025 • Phase 1/2 with BNT324/DB-13112 (B7- H3) in solid tumors for 2025 • Additional combinations for 2025 • Phase 1/2 with BNT325/DB-13052 (TROP2) in solid tumors BNT327/PM80021+chemo: Establish in combination with chemotherapy in potential Fast-to-Market indications BNT327/PM80021 + novel: Broaden to further indications BNT327/PM80021+ADC: Explore expansion to novel combinations with ADCs in high unmet need indications
Targeting TROP2, cleavable linker and topoisomerase I inhibitor DAR: 4 Targeting B7-H3, cleavable linker and topoisomerase I inhibitor DAR: 6 Targeting HER3, cleavable linker allows for intracellular and extracellular release of topoisomerase I inhibitor DAR: 8 Targeting HER2, cleavable linker and topoisomerase I inhibitor DAR: 8 Well-Positioned in ADCs with Therapeutic Candidates Across Multiple Tumors 1. Partnered with DualityBio; 2. Partnered with MediLink; 3. RNAseq data from AACR Project GENIE. Clinical status • Ph3 in HR+HER2-low mBC • Ph1/2 in multiple solid tumors Clinical status • Ph1/2 in multiple solid tumors Clinical status • Ph1/2 in multiple solid tumors Clinical status • Ph1 in multiple solid tumors HER2 B7-H3 TROP2 HER3 69 Target NSCLC SCLC HER2+ BC HR+ BC TNBC CRC Gastric Ovarian PDAC HNSCC Prostate Other high expression indications HER2 Gynecologic TROP2 B7-H3 UC, EC HER3 Expression level by indication3 High Medium / Low Very low / None BNT326/YL2022BNT325/DB-13051BNT324/DB-13111BNT323/DB-13031
BNT327/PM8002 + ADC Combinations are Planned or Ongoing 70 Combination with BNT325/DB-1305 is ongoing and additional combinations are planned Solid Tumor BNT324/ DB-13112 Solid Tumor BNT323/ DB-13032 BNT327/ PM80021 + Solid Tumor BNT325/ DB-13052 OngoingPlanned Partnered with 1. Biotheus; 2.DualityBio.
Time for a 15 minute break
5 mRNA Cancer Vaccines Prof. Özlem Türeci, M.D. CMO and Co-founder Michael Wenger, M.D. VP, Clinical Development
Uridine-based mRNA-LPX Vaccines for Systemic Delivery and Induction of Potent Polyspecific Immune Responses Against Cancer Antigens 73 Uridine-based RNA in formulated LPX (RNA-LPX) and administered IV for preferential delivery to the APCs in spleen, lymph nodes and bone marrow RNA-LPX is optimized for immune response stimulation RNA-LPX combines targeted antigen delivery with stimulation of TLR-mediated IFNα immune response Secretory signal peptide for translocation of the nascent polypeptide chain into the endoplasmic reticulum MITD (transmembrane and cytoplasmic domain of MHC class I) Encoded Antigen 5’ UTR5’ cap 3’ UTR Poly (A) tail 5`cap, UTRs, poly(A) tail engineered for optimized stability and translational performance Uridine chemistry for intrinsic adjuvanticity
74 1. In collaboration with Genentech, a member of the Roche Group. ** Antigens vary across programs; *** T cell responses analyzed by ex vivo multimer staining analysis in blood. Individual patient samples (blood and tissue) Artificial intelligence- driven neoantigen prediction On-demand tailored RNA manufacturing Individualized immuno- therapy Mapping of mutations Fixed combination of shared tumor antigens** Multi-antigen approach tailored to each indication Neoantigens Individualized therapy Multiple shared antigens Off-the-shelf therapy iNeST1,* FixVac individualized Neoantigen-Specific immunoTherapy Fixed Antigen Vaccine ANTIGEN 1 ANTIGEN 2 ANTIGEN 3 ANTIGEN 4 Strong vaccine- induced ex vivo CD8+ T cell responses across different cancer types*** 10.3% 10.1% HPV16-E7 Head & Neck Cancer BNT113, HARE40 trial Mutant Neoantigen TNBC, BNT114 TNBC-MERIT trial 5% MAGE-A3 Melanoma, BNT111, Lipo-MERIT trial 2.1% NY-ESO-1 Melanoma , BNT111, Lipo-MERIT trial mRNA- lipoplex platform MHC-I-multimer staining of PBMCs reveals vaccine antigen- specific CD8+T cells: Full Exploitation of Cancer Vaccine Target Space
Multiple Clinical Trials Demonstrate Execution Across iNeST and FixVac Portfolio 75 1. Partnered with Genentech, a member of the Roche Group; 2. In collaboration with Regeneron. Individualized vaccine: iNeST FixVac Autogene cevumeran (BNT122/RO7198457) 1 BNT1112 BNT113 BNT116 Adjuvant 1L R/R R/R 1L Multiple settings MIUC Phase 2 CRC Phase 2 PDAC Phase 2 Melanoma Phase 2 Solid Tumors Phase 1 Melanoma Phase 2 HPV16+ HNSCC Phase 2 NSCLC Phase 1 & 2 + Nivolumab Monotherapy + Atezolizumab + Pembrolizumab + Atezolizumab + Cemiplimab + Pembrolizumab Monotherapy, + Cemiplimab or CTx Recruitment started Recruitment ongoing Data presented from epi sub-study at ASCO 2024 and from biomarker sub-study at ESMO-GI 2024. Recruitment ongoing Data presented from investigator- initiated Ph 1 trial at ASCO 2022 & AACR 2024 and published. (Rojas et al., Nature 2023) Enrollment completed Ph 1 data on prototype vaccine published (Sahin et al., Nature 2017). Analysis of Ph 2 PFS as primary endpoint will be based on events and defined when reporting results. Enrollment completed Data presented at AACR 2020. Manuscript accepted in Nature Medicine Enrollment completed Positive topline data announced July 2024 Data presented from Ph 1 at multiple conferences incl. SITC 2021 and published. (Sahin et al., Nature 2020) Recruitment ongoing Ph 2 data presented at multiple conferences incl. ESMO-IO 2022 Data from safety run- in of Ph 2 trial and Ph1/2 IIT presented at ESMO 2024. Recruitment ongoing in Ph 2 in 1L NSCLC2 Ph 1 trial ongoing. Data presented at SITC 2023, AACR 2024, and SITC 2024.
Evaluating Autogene Cevumeran1 in the Adjuvant Treatment Setting for Cancers of High Unmet Need 76 Rationale for adjuvant setting Low tumor mass with residual cancer cells Healthier immune system and uncompromised T-cell function Resistance mechanisms and immune suppression not fully established Pancreatic Ductal Adenocarcinoma 69−75% relapse rate within 5 years after adjuvant therapy2,3 • Projected to be 2nd leading cause of cancer-related death (US) by 20304 • 5-year survival rates after resection are ~10%5 • Largely CPI resistant due to low mutation burden 6 Phase 1 trial completed and published Randomized Phase 2 trial ongoing 20-35% relapse rate within 4 years after adjuvant therapy7 • 5-year survival rates of locoregional disease are ~70%8 • Median disease-free survival for ctDNA-positive, Stage 2 (high risk) and Stage 3 CRC post adjuvant chemotherapy: ≈ 11 months (Reinacher-Schick et al., ASCO 2024) Randomized Phase 2 trial ongoing Data update in late 2025/early 2026 Colorectal Cancer Unmet medical need 1. Partnered with Genentech, a member of the Roche Group; 2. Jones et al., JAMA Surgery 2019; 3. Conroy et al., JAMA Oncology 2022; 4. Rahib et al., JAMA Network Open 2021; 5. Bengtsson et al., Sci Rep 2020; 6. Kabacaoglu et al., Frontiers Immunol 2018; 7. André et al., JCO 2015; 8. NIH SEER cancer stat facts (Accessed October 30, 2024).
Response to Autogene Cevumeran1 Correlates with Delayed PDAC Recurrence 77 1. Partnered with Genentech, a member of the Roche Group. Phase 1, investigator-initiated trial in resectable PDAC: 3-year follow-up data Balachandran et al., AACR 2024. #CT025 & Rojas et al., Nature 2023. Years At risk Responder 8 8 7 5 0 Non-responder 8 5 1 1 0 3-year median follow-up P = 0.007, HR: 0.14 (0.03-0.59) 0 20 40 60 80 100 0 1 2 3 4 Median RFS: Not reached Median RFS: 13.4 months R F S ( % ) Years Immune responder (n = 8) Immune non-responder (n = 8) Immunogenic Non-immunogenic No data N u m b e r o f n e o a n ti g e n s in a u to g e n e c e v u m e ra n 20 15 10 5 0 Patient Responders (n=8) Non-responders (n=8) 10 29 25 25 5 6 14 1 3 19 4 20 9 18 23 28 R0/R1 R0 R0 R0 R1 R0 R0 R0 R1 R0 R1 R0 R0 R0 R0 R0 R0 Half of all patients mounted neoantigen-specific de novo T cell responses against at least one vaccine neoantigen
Autogene Cevumeran1 Investigated in a Phase 2 Randomized Trial vs SoC in Resected PDAC Patients 78 1. Partnered with Genentech, a member of the Roche Group; 2. Conroy et al,. JAMA Onc. 2022. Key endpoints Primary: DFS Secondary: DFS rates, OS, OS rates and safety Status • Recruitment ongoing Key inclusion criteria Screening Part A Determine 5 neo-epitopes from blood and tumor samples for custom manufacture of autogene cevumeran Screening Part B Confirm patient eligibility n=260 R 1:1 Treatment phases and dosing schedules Patients are monitored at scheduled intervals until PDAC recurrence, occurrence of new cancers, or unacceptable toxicity. Randomization 6-12 weeks after surgery Autogene cevumeran1 + atezolizumab + mFOLFIRINOX mFOLFIRINOX IMCODE003: Phase 2, open-label, multicenter, randomized trial (NCT05968326) • Patients with resected PDAC • No prior systemic anti- cancer treatment for PDAC • No evidence of disease after surgery Benchmark comparator data Indication Benchmark regimen mDFS mOS 5yr DFS 5yr OS Benchmark study Adjuvant PDAC mFOLFIRINOX 21.4mo 53.5mo 26.1% 43.2% PRODIGE 242
ctDNA- (n=741) ctDNA+ (n=55)* Events, n (%) 31 (4.2) 20 (36.4) Median DFS (IQR), months Not reached (24.6, NR) 10.55 (7.2, 14.4) 12-month DFS rate (95% CI), % 93.2 (90.3, 96.2) 47.2 (31.9, 69.8) 18-month DFS rate (95% CI), % 84.9 (79.1, 91.2) 23.6 (10.6, 52.3) 79 1. Data cut off: 15 March 2024. Patients who transferred to BNT122-01 (n=56) were excluded from this analysis. DFS rates at 12 and 18 months1 DFS in patients who were ctDNA+ vs ctDNA- post surgery1 ctDNA- 741 489 402 295 187 120 64 30 6 1 0 ctDNA+ 55 33 22 15 8 4 2 1 0 P ro b a b il it y o f D F S Time, months 0.0 0.2 0.5 0.6 0.8 1.0 0 3 6 9 12 15 18 21 24 27 30 BNT000-001: A Multi-Site Epidemiological Study of ctDNA Status in Stage II/III CRC Patients After Resection and Prior to Adjuvant Chemotherapy (NCT04813627) Reinacker-Schick. et al., ASCO 2024. Abstract #3526. Post-Surgery ctDNA Positivity in CRC is Associated with Significantly Shorter DFS and Can Identify Patients at High Risk of Disease Recurrence ctDNA+ vs ctDNA- • HR=13.06 • 95% CI: 7.39, 23.08
Autogene Cevumeran1 Investigated in a Phase 2 Randomized Trial vs. Watchful Waiting in Adjuvant Colorectal Cancer 80 1. Partnered with Genentech, a member of the Roche Group; 2. Kotani et al., Nature 2023, Nakamura et al., ESMO 2023; 3. André et al., J Clin Onc. 2015. Autogene cevumeran1 15 doses: 6×Q1W, 2×Q2W, 7×Q6W Observational watchful waiting Adjuvant SoC chemotherapy for 12–24 weeksKey inclusion criteria • Patients with surgically-resected Stage II (high-risk) or Stage III CRC Screening 1 ctDNA status (post-operative) Screening 2 neoantigen selection for vaccine manufacture Screening 3 final eligibility (ctDNA+ patients only) n=164 R 1:1 Biomarker: Autogene cevumeran1 irrespective of ctDNA status (n=15) iNeST manufacturing ≤20 neoepitopes Exploratory: Autogene cevumeran1 recurrent disease at Screening 3 (n≤20) Key endpoints Primary: Disease-free survival Efficacy: RFS, TTR, TTF, OS Change in ctDNA status BNT122-01: Phase 2, multi-site, open-label, randomized, controlled trial (NCT04486378) Historical efficacy in CRC patients2, 3 mDFS in ctDNA+ patients: 6 months 5-year DFS rate: stage II (high-risk) ~80%, stage III ~66% 5-year OS rate: stage II (high-risk) ~88%´, stage III ~76% Interim data expected in late 2025 / early 2026
Kinetics and persistence of T cell responses to vaccine-encoded neoantigens Elez et. al., Biomarker sub-study results of Phase 2 trial (NCT04486378), ESMO-GI 2024. Functional Vaccine-Induced T Cells are Long-Lived and Detected One Year After Last Vaccination with Autogene Cevumeran in all Evaluable Patients 81 1. Partnered with Genentech, a member of the Roche Group. Autogene cevumeran1 induces T-cell responses in all patients Responses are polyepitopic: against a median of 3 vaccine-encoded neoantigens Almost all responses were detectable after 8 vaccinations. All 12 patients included in the immunogenicity analysis were disease-free at data cut-off Kinetics and durability of ex vivo T-cell responses in individual patients (n=12) Data cut-off March 15, 2024
Autogene Cevumeran1 Investigated in a Phase 2 Randomized Trial in Combination with Nivolumab in Adjuvant MIUC Patients 82 1. Partnered with Genentech, a member of the Roche Group.;2. Bajorin et al., 2021 NEJM; 3. American Cancer Society Cancer Facts and Figures 2024. Key endpoints: Inclusion criteria • Age 18 years • Histologically confirmed MIUC or upper urinary tract • Surgical resection of MIUC of the bladder or upper tract without any adj. chemotherapy or radiotherapy • Absence of residual disease or metastasis, confirmed by CT or MRI scans • TNM classification of resected specimen is (y)pT3-4 or (y)pN+ and M0 • ECOG status 0 or 1 Part A: Safety run-in Part B: Randomized phase Nivolumab, iv + Saline solution, iv Autogene cevumeran1, iv + Nivolumab, iv Enrollment (expected) Q4W for 1 year Autogene cevumeran1, iv + Nivolumab, iv n = 362 R 1:1 Neoadjuvant chemotherapy, followed by cystectomy and for eligible patients this is followed by adjuvant treatment with an immune checkpoint inhibitor (ICI). Standard of care • Adjuvant ICI significantly increases disease-free survival in patients. Despite this, a significant number of patients will relapse in the first two years.2 • The 5-year survival among MIUC patients with distant metastasis has been reported to be about 8%.3 Unmet medical need Primary INV-DFS in PD-L1 ≥ 1 Secondary OS, Safety IMCODE004: Phase 2, multi-site, open-label, randomized, controlled trial (NCT06534983) Trial currently recruiting Medical need
Multiple Clinical Trials Demonstrate Execution Across iNeST and FixVac Portfolio 83 1. Partnered with Genentech, a member of the Roche Group; 2. In collaboration with Regeneron. Individualized vaccine: iNeST1 FixVac Autogene cevumeran (BNT122/RO7198457) BNT1112 BNT113 BNT116 Adjuvant 1L R/R R/R 1L Multiple settings MIUC Phase 2 CRC Phase 2 PDAC Phase 2 Melanoma Phase 2 Solid Tumors Phase 1 Melanoma Phase 2 HPV16+ HNSCC Phase 2 NSCLC Phase 1 & 2 + Nivolumab Monotherapy + Atezolizumab + Pembrolizumab + Atezolizumab + Cemiplimab + Pembrolizumab Monotherapy, + Cemiplimab or CTx Recruitment started Recruitment ongoing Data presented from epi sub-study at ASCO 2024 and from biomarker sub-study at ESMO-GI 2024. Recruitment ongoing Data presented from investigator- initiated Ph 1 trial at ASCO 2022 & AACR 2024 and published. (Rojas et al., Nature 2023) Enrollment completed Data of prototype version Ph 1 published (Sahin et al., Nature 2017). Analysis of Ph 2 PFS as primary endpoint will be based on events and defined when reporting results. Enrollment completed Data presented at AACR 2020. Manuscript accepted in Nature Medicine Enrollment completed Positive topline data announced July 2024 Data presented from Ph 1 at multiple conferences incl. SITC 2021 and published. (Sahin et al., Nature 2020) Recruitment ongoing Ph 2 data presented at multiple conferences incl. ESMO-IO 2022 Data from safety run- in of Ph 2 trial and Ph1/2 IIT presented at ESMO 2024. Recruitment ongoing in Ph 2 in 1L NSCLC2 Ph 1 trial ongoing. Data presented at SITC 2023, AACR 2024, and SITC 2024.
BNT113 Showed Consistent Immune Responses in Adjuvant and Advanced Disease in Multiple Studies 84 Vaccine induced T cell responses and consistent clonotype expansion observed in majority of patients Ottensmeier, et. al. ESMO 2024. Pre Post 0 50 100 600 1200 2800 HARE-40 ELISpot Best response S p o tc o u n ts p e r 1 0 ^ 6 c e lls N=13 1001049 1001046 1001043 1001028 1001022 1001021 1001017 1001016 1001015 1001013 1001009 1001008 1001006 ARM 1A ARM 1B Ex vivo IFNγ ELISpot responses to E6 and/or E7 peptide pools Best vaccine response per patient, cell type and target, measured by IFNγ ELISpot ex vivo BOR per RECIST v1.1 Patient PepMix E6 PepMix E7 BICR Inv.CD4+ CD8+ Bulk PBMC CD4+ CD8+ Bulk PBMC 109 PD SD 111 PR PD 115 PD PD Normalized spot count of vaccine-induced T cells Vaccine-induced T cell count corresponded with volume of tumor reduction Saba et. al. ESMO 2024 0 1000 2000 3000 Screening C3D8 109 111 115
BNT113 Showed Activity with ORR1 of 40% in PD-L1+ HPV16+ HNSCC Patients 85 1. Assessed per blinded independent central review (BICR); 2. The efficacy analysis set was defined as all patients who received at least one dose of BNT113 (N=15). Tumor overall response, treatment and survival status by BICR Antitumor activity2 N=15 Unconfirmed ORR (BICR), % CR, n PR, n 40.0 4 2 Unconfirmed DCR (BICR), % 53.3 Unconfirmed ORR (investigator), % 33.3 Unconfirmed DCR (investigator), % 60.0 PFS by BICR Median (95% CI), months 6-month rate, % 12-month rate, % 18-month rate, % 3.9 (2.1–10.6) 42.3 14.1 14.1 PFS by investigator Median (95% CI), months 6.0 (2.3–10.4) OS, median (95% CI), months 22.6 (9.8–NE) Results from safety run-in of Phase 2 AHEAD-MERIT in 1L metastatic HNSCC (NCT04534205) Saba et. al., ESMO 2024 3 6 9 30272421181512 Duration study, months 114 113 105 109 103 110 106 102 108 104 115 111 112 101 107 P a ti e n t n u m b e r Time on treatment (BNT113+pembrolizumab) Complete response End of treatment visit Treatment ongoing Time off treatment Status Best overall response Partial response Stable disease Progressive disease Death Data cut-off: 24 June 2024
AHEAD-MERIT: a Phase 2 controlled trial in 1L metastatic HNSCC (NCT04534205) BNT113 in Combination with Pembrolizumab as 1L Treatment in Patients with R/R HPV16+ HNSCC Expressing PD-L1 86 1. Partnered with Genentech, a member of the Roche Group; 2. Gorphe et al., Radiother Onc 2022 3. Munoz-Bello et. Al, Cell 2024; 4. Harrington et. al., J Clin Oncol. 2023. 86 Medical need Standard of care Pembrolizumab-based regimens are SoC for patients with PD-L1 CPS≥1, while platinum- based regimens are preferred for patients with PD-L1 CPS<0 Unmet medical need Up to 25% of patients with early-stage HPV16+ tumors will relapse within two years. 2 5-year survival rates for patients with relapsed advanced HPV16+ tumors is 75%.3 Inclusion criteria • Advanced, unresectable, recurrent or metastatic HNSCC • Primary tumor locations oropharynx, oral cavity, hypopharynx, and larynxa4 • Positive for HPV16 DNA • Measurable disease per RECIST v1.1 • PD-L1 CPS ≥1 • ECOG PS 0 or 1 Endpoints Safety run-in Randomized part Primary: TEAEs; up to 27 months OS, ORR; up to 48 months Secondary: ORR, DOR, DCR INV-ORR, PFS, DCR, DOR, safety Exploratory: PFS, OS, biomarkers BNT113 (8xQ1W, then Q3W) + pembrolizumab (Q3W) up to 24 months Safety run-in n=15 Randomized part BNT113 (8xQ1W, then Q3W) + pembrolizumab (Q3W) up to 24 months Pembrolizumab (Q3W) up to 24 months R 1:1 n=267 Benchmark comparator data for 1L HNSCC (~22% patients HPV16+) Indication Benchmark regimen ORR mPFS mOS Benchmark Study 1L HNSCC (CPS >1) Pembrolizumab 19% 3.2 mo 12.3 mo KEYNOTE-0484 •.
De novo and vaccine-expanded T cell responses were observed across patients Atmaca A, et. al., presented at SITC 2024. Poster 1486 BNT1161-Induced T cell Responses Have Been Observed in NSCLC 87 Vaccine induced CD4+ and CD8+ T cell responses observed consistently Öven BB, et. al., presented at AACR 2024. CT051 Induced T cell response (ex vivo ELISpot) No response (ex vivo ELISpot) BOR CD4+ CD8+ CD4+ CD8+ CD4+ CD8+ CD4+ CD8+ CD4+ CD8+ CD4+ CD8+ 03-016 SD 03-013 PR 03-018 PR Inv. Best vaccine response per patient, cell type and target, measured by IFNγ ELISpot post-IVS Patient CLDN6 KK-LC-1 MAGE-A3 MAGE-A4 MAGE-C1 PRAME De novo response Amplified response No vaccine response No data 2 patients 3 patients De novo response Stable response No vaccine response No data Ex vivo 8% 8% 25% 59% 1 1 3 7 De novo response Stable response No vaccine response Post-IVS17% 17% 44% 22% 3 3 8 4 Amplified response Stable response No response (ex vivo ELISpot) Summary of vaccine responses measured post-IVS by IFNγ ELISpot and response per RECISTv1.1 1. This trial (NCT05142189) is run under a supply agreement with Regeneron.
Assessing BNT116’s Potential in Multiple Combinations and Disease Settings1 88 1. This trial (NCT05142189) is run under a supply agreement with Regeneron. Key endpoints Primary: DLT occurrence during Cycle 1, safety Secondary: ORR, DoR, DCR, DDC, PFS, OS Cohort 4, n=20 Cohort 1, n=30 Cohort 2, n=20 Cohort 3, n=20 Cohort 5, n=20 Cohort 6, n=20 BNT116 + cemiplimab (frail patients) Optional: cemiplimab add-on from cycle 3 onwards BNT116 monotherapy BNT116 + cemiplimab (PD-L1 ≥ 50%, progressive disease on PD-1/PD-L1 inhibitor as first line/adj. Tx) BNT116 + docetaxel BNT116 + cemiplimab (after concurrent CRT) BNT116 + cemiplimab + carboplatin + paclitaxel (neoadj. therapy) > surgery > BNT116+ cemiplimab (adjuvant therapy) n= 130 DLT follow-up during cycle 1 OS follow-up every 3 months for up to 24 months after end of treatment Inclusion criteria Histologically confirmed NSCLC Cohort 1-4 and 7: unresectable stage III or metastatic IV Cohort 5: unresectable stage III Cohort 6: initial diagnosis of resectable stage II or stage III Cohort 2, 4, 5 and 6: must tolerate anti-PD-1 therapy Cohort 2, 3,6 and 7: ECOG PS ≤1 Cohort 1, 4 and 5: ECOG PS 0-2 BNT116 + aCTLA-4, n=30 pts., after prior PD-1i and platinum-based chemotherapy Cohort 7, n=30 LuCa-MERIT-1: FIH, open-label, Phase 1 trial in NSCLC (NCT05142189)
BNT116 Has Shown Clinical Activity as Single Agent & in Combination with Chemo or anti-PD-1 in Advanced NSCLC in Phase 1 Trial1 89 1. This trial (NCT05142189) is run under a supply agreement with Regeneron. Progression after PD-(L)1 therapy, platinum-based chemotherapy, and one other systemic therapy Progression after PD-(L)1 therapy and platinum- based chemotherapy BNT116 monotherapy plus cemiplimab add-on from cycle 3 Deme et al. SITC 2023 BNT116 plus docetaxel Öven et al. AACR 2024 BNT116 plus cemiplimab Atmaca et al. SITC 2024 Combination therapy with BNT116+cemiplimab is active with DCR of 45% in heavily pre-treated lung cancer patients Combination therapy with BNT116 + docetaxel is active with an ORR of 30% and a DCR of 85% and mPFS of 4.4 months Combination therapy with BNT116 + cemiplimab is active with an DCR of 80% and a mPFS of 5.5 months C h a n g e o f ta rg e t le s io n s u m fr o m b a s e lin e ( % ) Study day Best overall response PR SD PD Overall response Baseline PR SDPD C h a n g e i n t u m o r s iz e f ro m b a s e lin e o v e r ti m e ( % ) 100 80 60 40 20 -20 -40 -60 -80 -100 Weeks since treatment initiation 0 7 14 21 28 35 42 49 56 63 70 PR SD PD NA Status DeathOn treatmentBOR PR SD PD 0 40 30 20 10 0 -10 -20 -30 -40 -50 -60 0 50 100 150 200 250 300 350 400 450 20% 0% -30% C h a n g e o f ta rg e t le s io n s u m fr o m b a s e lin e ( % ) Baseline PR SDPD Pending NSCLC with PDL1 TPS ≥50% that progressed after PD-(L)1 therapy as first-line or adjuvant therapy 0 50 100 150 200 250 300 350 400 450 Study day
6 Select Targeted Therapies: HER2-ADC BNT323 CLDN6 CART BNT211 Dr. Michael Wenger, MD VP Clinical Research Prof. Özlem Türeci, M.D. CEO and Co-founder
BNT323/DB-13031: A HER2 ADC with a Potentially Differentiated Profile 91 1. Partnered with DualityBio; 2. DS-8201 is an in-house produced analog of trastuzumab deruxtecan. Preclinical Data Lin S. et al. Abstract #252. Presented at EORTC- NCI-AACR in 2022 & data on file. BNT323/DB-13031 is a 3rd generation ADC Mode of action • Superior in vitro plasma stability in human plasma • Rapid systemic clearance in monkeys • Potent anti-tumor effect in both HER2 positive and HER2 low tumor models with a wide therapeutic window • Toxicity studies2 in monkeys show favorable toxicity profile Stable linker and fast clearance may contribute to the improved toxicity profile of BNT323/DB-13031 Humanized anti-HER2 IgG1 mAb DAR of ~8 Cysteine residue Linker-payload • A humanized anti-HER2 IgG1 monoclonal antibody • A proprietary DNA topoisomerase I inhibitor • A maleimide tetrapeptide- based cleavable linker 1. ADC binds to antigen 2. Internalization of the ADC complex by endocytosis 3. Payload released after linker cleavage Target antigen ADC 4. Cytotoxic effect by payload in the nucleus Bystander cell Targeted Cytotoxicity Bystander killing effect A. Release of drug payload after antigen binding before internalization B. Release of drug payload into the intercellular space due to high drug membrane permeability ADC Adapted from Coleman N.et al. npj Precis. Onc. 2023
First-in-Human Trial with BNT323/DB-13031 in Patients with Advanced HER2-Expressing Solid Tumors 1. Partnered with DualityBio. 92 Phase 1/2a trial design (NCT05150691), multicenter, non-randomized, open-label Moore K. et al. Presented at ASCO 2023. Abstract #3023 Part 1: Dose escalation (n=88 patients) Part 2a: Dose expansion cohorts (n=165 patients) (HER2 IHC 3+, IHC 2+, IHC 1+ or ISH +, or HER2 amplification and mutation by NGS) Status First patient in: Jan 2022 Trial ongoing Trastuzumab-treated HER2+ (IHC3+, IHC2+/ISH positive) gastric or GEJ adenocarcinoma, esophageal carcinoma and CRC 10.0 mg/kg 12.0 mg/kg 8.0 mg/kg 7.0 mg/kg 6.0 mg/kg 4.4 mg/kg 2.2 mg/kg Both HER2 overexpression and HER2 low (IHC3+,2+,1+ or ISH positive) endometrial carcinoma HR+/HER2 Low (IHC2+ /ISH negative, or IHC1+) breast cancer HER2+ (IHC3+, IHC2+/ISH positive) breast cancer NSCLC with activating HER2 mutation HER2+ or HR+/HER2-low breast cancer with treatment failure of trastuzumab deruxtecan (HER2+ BC; HR+/HER2-low BC) Key endpoints Safety, tolerability, pharmacokinetic, preliminary anti-tumor activity at the selected MTD/RP2D Key inclusion criteria • Pretreated advanced or metastatic solid tumors • HER2-positive or HER2- expressing cancers • Previous systemic therapies • ECOG PS 0-1 (RP2D=8 mg/kg) RP2D/ MTD Phase 3 (NCT06018337) ongoing in chemo naïve 2L HR+ HER2 low breast cancer
BNT323/DB-13031 Data Facilitates a Potential Path to Registration in HER2- Expressing Endometrial Cancer 93 1. Partnered with DualityBio; 2. Meric-Bernstam F. et al. J Clin Oncol 2024. Phase 1/2a FIH study (NCT05150691): Clinical Efficacy Moore K. et al. Presented at ESGO 2023. Abstract # 430 Responsea Dose Escalation Dose Expansion Total (n=17)b 7 mg/kg (n=4)b 8 mg/kg (n=4)b 8 mg/kg (n=9)b Unconfirmed ORR, n (%) 2 (50) 4 (100) 4 (44) 10 (59) Confirmed ORR, n (%) 1 (25) 3 (75) 0 4 (24) Pending confirmation ORR, n (%) 1 (25) 1 (25) 4 (44) 6 (35) Unconfirmed DCR, n (%) 4 (100) 4 (100) 8 (89) 16 (94) a By investigator. b Response-evaluable subjects, which includes subjects with ≥1 postbaseline overall response. B e s t c h a n g e f ro m b a s e li n e ( % ) ISH+ ISH+ ISH+ ISH+ ISH+ # Subject 30 0 -30 -60 -90 Dose level 7 mg/kg 8 mg/kg 1+ 2+ 3+HER2 IHC status • HER2 tumor expression of IHC 1, 2 and 3+: 31%, 41% and 25%, respectively. Clinical response observed across HER2-expression levels, including IHC 1+ • Patients received median 2 lines of prior treatment. ~60% of patients had prior IO, ~38% prior anti-HER2 antibody • Data cutoff: May 8, 2023 Benchmark comparator data for 2L+ HER2+ Endometrial Cancer Indication Benchmark regimen ORR mPFS mOS Benchmark Study Endometrial T-DXd 57.5% 11.1 mo 26.0 mo DESTINY-PanTumor022
Phase 3 Study of BNT323/DB-13031 vs Chemotherapy in 2L+ HER2-expressing Endometrial Cancer 94 BNT323-01: (NCT06340568) Key inclusion criteria • Recurrent, metastatic endometrial cancer (including HER2 1+, 2+, or 3+ score on IHC by central testing) • At least 1 prior line of platinum- based therapy (in any setting) and prior ICI (in any setting), up to three lines of prior therapy (excluding endocrine therapies) • Measurable disease per RECIST v1.1 • ECOG PS 0 or 1 Arm 1 n=280 Arm 2 n=140 BNT323/DB-13031 monotherapy Investigator’s choice Single-agent chemo 2:1 Primary endpoints: PFS (BICR assessed) 1. Partnered with DualityBio; 2. Makker V. et al. NEJM 2022. Key endpoints Treatment continued until Disease progression or Unacceptable toxicity Benchmark comparator data for 2L+ Endometrial Cancer Indication Benchmark regimen ORR mPFS mOS Benchmark Study Endometrial Single-agent chemo 14.7% 3.8 mo 11.4 mo KEYNOTE-7752
Claudin-6 (CLDN6) is a Carcinoembryonic Cell Surface Antigen 95 Claudins are tight junction- associated tetraspanins with druggable extracellular loops Expressed exquisitely during organogenesis and not in healthy adult tissues Highly expressed in various cancer types with correlation to disease progression Cancer stem cell marker a b c d e f g h i j k l m n o p q r s t u v w x H ea lt h y ti ss u es Mouse Tissue Data Human Tissue Panel
CLDN6 is Expressed in High Medical Need Cancers Including Lung Cancer 96 Ovary Endometrium Lung Testis Healthy Tumor Indication CLDN6+ CLDN6hig h Testicular Cancer* 93 % 90-93 % Ovarian Cancer* 56 % 25-30 % Uterine Cancer* 23 % 10-15 % Lung Cancer** 11 % 2-5 % Gastric Cancer*** 9 % 2-5 % CLDN6high = 50% of tumor cells expressing ≥2+ CLDN6 protein (IHC) Micke et al., Int. J. Cancer 2014 CLDN6 IHC staining of a TMA with 355 NSCLC tested CLDN6+ Squamous CA 120 0 AdenoCA 195 20 (10%) Large cell CA 40 3 (7.5%) Total 355 23 (6.5%) • No correlation with smoking history, Ki67+ status, tumor stage, WHO performance stage • Negatively correlated with prognosis • Correlated with TFF1+ status Reinhard et al., Science 2020
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 αCLDN6 scFv CD8 hinge 4-1BB CD3ζ L ys is [ % ] C L D N 3 C L D N 4 C L D N 6 C L D N 9 80 60 40 20 0 Liposomes Full-length CLDN6 RNA CARVac IV Combined with CARVac (CAR-T cell amplifying RNA vaccine) to target APCs, Reinhard K, et al. Science 2020, 367:446–453; Kranz LM, et al. Nature 2016; 534:396–401 CLDN6 CAR-T GFP T cells 0 500 1,000 1,500 -10 5 0 5 10 15 20 25 T u m o r v o lu m e [ m m 3 ] Days after ACT ± 97
Key inclusion criteria • ≥50% tumor cells with CLDN 6 IHC 2+/3+ CLDN6 positivity (immunohistochemistry) • Measurable disease per RECIST v1.1 or elevated tumor marker • ECOG PS 0–1 BNT211 as Monotherapy or in Combination with Ribonucleic Acid Lipoplexes (RNA-LPX) in Patients with CLDN6-Positive Advanced Solid Tumors 98 1. Mackensen A, et al. Nature Med 2023;29:2844–2853; 2. Haanen JBAG, et al. Ann Oncol 2023;34 (suppl_2):S1281–S1282. Part B: Automated product (n=78; ongoing)2 Key endpoints Primary: Safety & tolerability, MTD, RP2D Secondary: ORR, DCR, DOR Phase 1, FIH, open-label, dose escalation study with expansion cohort to evaluate safety and efficacy of BNT211 with/without RNA-LPX in patients with CLDN6+ R/R solid tumors (NCT04503278) Part A: Manual product (n=22; completed)1 DL2 n=9 + fixed CARVac DL1 n=4 + fixed CARVac DL2 n=6 1×108 CAR-T DL1 n=3 1×107 CAR-T Monotherapy Combination* DL2 n=13* 1×108 CAR-T DL1 n=4 1×107 CAR-T Monotherapy Combination DL3 n=7 2-5×108 CAR-T DL0 n=2 1×106 CAR-T DL2 n=48 + fixed CARVac DL1 n=4 + fixed CARVac DL3 n=0 + fixed CARVac ESMO 2023 *aThree patients were treated at an optional de-escalation dose (DL 1.5=5×107 cells) to further evaluate clinical safety and efficacy. Published in: Mackensen et al., Nature Medicine, 2023 ESMO 2022
BNT211-01: Overall Response Rate – Testicular Cancer a. Includes tumor marker responses; b. Excludes patients who received an out-of-specification product; c. DL2=1×108; DL3=2–5×108 CAR T cells. Overall ORR was 24%; at DL2 and DL3 ORR was 41.7%. Two patients had a surgical complete response that lasted for over a year. Haanen et. al., ESMO 2024 Responsea Total (N=27)b Evaluable patients, n 25 ORR, n (%) 95% CI (%) 6 (24.0) 8.6–42.3 DCR, n (%) 95% CI (%) 14 (56.0) 32.0–71.3 Responsea DL≥2 +100% LD ± CARVac (N=14)b,c Evaluable patients, n 12 ORR, n (%) 95% CI (%) 5 (41.7) 12.8–64.9 DCR, n (%) 95% CI (%) 9 (75.0) 35.1–87.2C h a n g e i n t h e s u m o f ta rg e t le s io n s , % 100 80 40 20 -0 -20 -40 -60 -80 -100 60 Best overall response per RECIST v1.1 Patients with testicular cancer DL≥2 +100% LD ± CARVac All other doses * *Bar truncated at 100% (actual value was 196%). Data cut-off: May 16, 2024. 99
BNT211-01: Overall Response Rate – Ovarian Cancer 100 a. Includes tumor marker responses; b. Excludes patients who received an out-of-specification product; c. DL2=1×108; DL3=2–5×108 CAR T cells. Responsea Total (N=30)b Evaluable patients, n 24 ORR, n (%) 95% CI (%) 8 (33.3) 12.3–45.9 DCR, n (%) 95% CI (%) 18 (75.0) 40.6–77.3 Responsea DL≥2 +100% LD ± CARVac (N=16)b,c Evaluable patients, n 12 ORR, n (%) 95% CI (%) 7 (58.3) 19.8–70.1 DCR, n (%) 95% CI (%) 10 (83.3) 35.4–84.8 In the 24 evaluable patients across all dose levels, ORR was 33.3% and DCR was 75% - the same parameters when considered for Dose Level 2 and above were 58.3% and 83.3% respectively. Haanen et. al., ESMO 2024 Best overall response per RECIST v1.1 C h a n g e i n t h e s u m o f ta rg e t le s io n s , % 100 80 40 20 -0 -20 -40 -60 -80 -100 60 Patients with ovarian cancer DL≥2 +100% LD ± CARVac All other doses Data cut-off: May 16, 2024.
Best Overall Response to CLDN6 CAR T+ CARVac in a Patient with NSCLC1 1. Data on file. Presented by U. Sahin at Lung Cancer Summit, NY, 2024 Best overall response was PR Pre Post Pre Post Screening ACT ACT + 1 Mo ACT + 3 Mo 18 mm 53 mm 28 mm 12 mm +194% -47% -77% PR PR Target lesion size • Patient with AGA-neg NSCLC, CLDN6+ (50% 2+/3+, 80% any positivity), IO-experienced, • 2 previous treatment lines, former smoker • Received CAR T + 5x CARVac 101
CARVac Improves CAR T Persistence 102 1. At day 50, the proportion of patients with measurable CAR T > than the lower limit of quantification is 6 of 8 for CAR T alone and 12 of 12 for CAR T plus CARVac. At Day 90, 1/7 had detectable CAR T in the CAR T alone group vs 6/8 in the CAR T plus CARVac group. Adding CARVac limits the decline and induces a plateau of CAR-T cells with robust and ongoing detection in patients1 who received DL2+CARVac. Haanen et. al., ESMO 2024 D 5 0 c o n c e n tr a ti o n , c o p ie s /µ g DL2 (1x108) CAR T + CARVac 105 104 103 102 101 100 DL2 (1x108) CAR T only LLOQ D 9 0 c o n c e n tr a ti o n , c o p ie s /µ g DL2 (1x108) CAR T + CARVac 104 103 102 101 DL2 (1x108) CAR T only LLOQ GCT Ovarian Other Data cut-off: May 16, 2024. DL2 (1x108) CAR T alone C A R T c o n c e n tr a ti o n , c o p ie s /µ g 106 105 104 103 102 101 100 Time, days 0 5025 10075 LLOQ GCT Ovarian Other DL2 (1x108) CAR T + CARVac Time, days 0 5025 10075 106 105 104 103 102 101 100 LLOQ
mOS of 7.7 Months in Patients with R/R Testicular Germ Cell Tumors After Initiating Palliative Chemotherapy 103 . Real-world evidence study: Results objective 1 Feldman, D. et al. ASCO 2024. OS among patients with R/R testicular GCT receiving palliative chemotherapy exposure with sufficient follow-up time (N=80) Time from the index date 0 month 6 months 12 months 24 months Prior HDCT ± CDCT Pts at risk, N 49 29 8 2 Cumulative deaths, N 0 20 41 45 Survival probability, % 100.0 59.2 16.3 6.3 Prior CDCT only Pts at risk, N 31 22 12 6 Cumulative deaths, N 0 9 19 24 Survival probability, % 100.0 71.0 38.7 21.5 OS was assessed among 80 patients with R/R testicular GCT who had at least 12 months of follow-up time, which are a subgroup of patients identified for Objective 1 (N = 97).
Safety lead-in Main part Primary Safety & tolerability, TEAEs, AESIs, serious/fatal TEAEs ORR per RECIST1.1, reduction of serum tumor marker Secondary Efficacy (ORR, DCR, DOR), PK PFS, OS, DOR, DCR, safety, PK, pharmacodynamics, immunogenicity BNT211 Pivotal Trial in Patients with R/R Testicular Germ Cell Tumors 104 Key inclusion criteria • RECIST 1.1 or serum tumor markers • Prior high dose chemo + autologous SCT or conventional dose chemo as salvage therapy • ≥ 25% of tumor cells expressing CLDN6 • ECOG performance status 0-1 • Adequate organ function BNT211-02 open-label, randomized Phase 2 study to evaluate safety and efficacy of BNT211 in adult patients with testicular or extragonadal germ cell tumors Key endpoints Safety lead-in part: 3-arm, randomized (1:1:1) Main part: single arm CLDN6 CAR-T Dose level 2 Arm 1 Arm 2 Arm 3 Selected Phase 2 Regimen CLDN6 CAR-T + CLDN6 RNA-LPX Dose level 1 CLDN6 CAR-T + CLDN6 RNA-LPX Dose level 2 n=62n=10 per cohort
7 Path to Value Creation Ryan Richardson, Chief Strategy Officer
Progress in the Last Twelve Months Demonstrates the Strength of our Model and our Strategy 106 1. Consists of cash and cash equivalents of €9,624.6 million, current security investments of €7,078 million and non-current security investments of €1,137.2 million, as of September 30, 2024, and does not include announced Biotheus acquisition considerations. 2023 2024 COVID-19 Maintained leading market share (>50%) Oncology Portfolio 7 Phase 2/3 trial starts >67% year-on-year increase in average quarterly patient enrollment in trials Infectious Disease Vaccine Portfolio Three Phase 1 trial starts Corporate Development Acquisitions of InstaDeep and Biotheus announced Six in-licensed molecules Cash Balance Grew cash balance from Q3 2023 to Q3 2024 (€17.0B to €17.8B1)
Our Capital Allocation Strategy Going Forward Will Continue to Focus on Value Creation 107 Strategically invest behind late-stage programs with transformational potential Active portfolio management to create additional P&L headroom for pivotal trial investment Expect to continue to benefit from interest income potential from strategic cash reserve 0 500 1000 1500 2000 2500 R&D M&A & Licensing Capex €m Midpoint R&D FY2024 Guidance M&A Licensing costs YTD Q3 2024 Midpoint Capex FY2024 Guidance 2024e2023 Outlook for 2025
2H 2024 2025+ BNT327/PM80022 1L TNBC Phase 2 data BNT327/PM80022 1L SCLC Phase 2 data BNT327/PM80022 1L ES-SCLC and 2L SCLC Phase 2 DO data BNT323/DB-13033 HR+ HER2 low BC Phase 3 Autogene cevumeran (BNT122/RO7198457)4 adj. PDAC Phase 2 Autogene cevumeran (BNT122/RO7198457)4 adj. PD-L1+ MIUC Phase 2 BNT327/PM80022 1L and 2L TNBC Phase 2 DO data BNT323/DB-13033 2L+ HER2 EC Phase 2 data Autogene cevumeran (BNT122/RO7198457)4 ctDNA adj. CRC Phase 2 topline data BNT327/PM80022 1L SCLC Phase 3 BNT327/PM80022 1L NSCLC Phase 3 BNT327/PM80022 1L TNBC Phase 3 BNT1115 2L+ melanoma Phase 2 data BNT323/DB-13033 2L+ HER2 EC Regulatory submission BNT113 HPV16+ PD-L1+ HNSCC Phase 2 BNT1165 PD-1L > 50% 1L NSCLC Phase 2 BNT316 2L NSCLC Phase 3 Expected Potential Value Creating Milestones and Trials Partnered with: 1. Pfizer; 2. Biotheus; 3. DualityBio; 4. Genentech, member of Roche Group. 5. in collaboration with Regeneron; DO = Dose Optimization. Catalyst-rich upcoming period for mid- to late-stage pipeline to support company vision to achieve a diversified, cashflow-generating multi-product oncology portfolio by 2030 2024 - 2025+ Ongoing and Planned Trials with Anticipated Data Disclosures Beyond 2025 Data update Regulatory event 108
Innovation Series 2024 THANK YOU Contact us at investors@biontech.de
Abbreviations (1) n L nth line CRC Colorectal cancer FIH First in human AACR American Association for Cancer Research CRS Cytokine release syndrome Flu Fludarabine ACT Adoptic cell transfer CRT Chemoradiation therapy FPD First patient dosed ADC Antibody-drug conjugate CT Computer tomography GBM Glioblastoma adj. Adjuvant CTCAE Common terminology criteria for adverse events GC/GEJ Gastric/Gastro-esophageal junction cancer AE Adverse event ctDNA Circulating tumor DNA GCT Germ cell tumor AGA Actionable oncogenic alteration CTFI Chemotherapy-free interval GEJ Gasto-esophageal junction AI Artificial intelligence CTLA-4 Cytotoxic T-lymphocyte-associated protein 4 HCC Hepatocellular carcinoma ALK Anaplastic large-cell lymphoma kinase CTx Chemotherapy HDCT High dose chemotherapy APC Antigen presenting cell CXCL Chemokine (C-X-C motif) ligand HER2 (or 3) Human epidermal growth factor receptor 2 (or 3) ASCO American Society of Clinical Oncology Cy Cyclophosphamide HLA Human leukocyte antigen (m)BC (metastatic) Breast cancer DAR Drug-antibody ratio HLH Hemophagocytic lymphohistiocytosis BIRC Blinded independent central review DC Dendritic cell HNSCC Head and neck squamous cell carcinoma BL Baseline DCR Disease control rate HPV Human papilloma virus BOR Best overall response DDC Duration of disease control HR Hazard ratio BTC Biliary tract cancer DFS Disease-free survival HR Hormone receptor CAR Chimeric antigen receptor DL Dose level ICANS Immune effector cell-associated neurotoxicity syndrome CARVac CAR T-cell amplifying RNA vaccine DLT Dose limiting toxicity ICI Immune checkpoint inhibitor CnDn Cycle n day n dMMR Deficient DNA mismatch repair IDMC Independent Data Monitoring Committee CD Cluster of differentiation (m)DOR Duration of response IEC-HS Immune effector cell-associated HLH-like syndrome CDCT Conventional dose chemotherapy EC Endometrial cancer IFN Interferon cGMP Current Good Manufacturing Practice ECOG (PS) Eastern Cooperative Oncology Group (performance status) IgG Immunoglobulin G CI Confidence interval E2E End to end IHC Immunohistochemistry CICON International Cancer Immunotherapy Conference EGFR Epidermal growth factor receptor IIT Investigator initiated trial CLDN6 Claudin 6 ELISpot Enzyme Linked Immuno Spot Assay IL-x Interleukin x CMC Chemistry, manufacturing and control EORTC European Organisation for Research and Treatment of Cancer IND Investigational new drug COGS Cost of goods sold ER Estrogen receptor iNeST Individualized NeoAntigen-Specific Therapy CPD Confirmed progression ESMO European Society for Medical Oncology INV- Investigator assessed CPI Checkpoint inhibitor ESMO GI European Society for Medical Oncology Gastrointestinal IO Immuno-oncology CPS Combined positive score Fab Fragment antigen binding IPO Initial public offering CR Complete response FDA U.S. Food and Drug Association IQR Interquartile range
Abbreviations (2) irAE Immune-related adverse event NSCLC Non-small cell lung cancer SITC Society of Immunotherapy of Cancer ISH in-situ hybridization NY-ESO-1 New York esophageal squamous cell carcinoma-1 S&M Sales and marketing ITT Intention to treat OPEX Operational expenditures SoC Standard of care iv Intravenously (c)ORR (Confirmed) objective response rate SoD Sum of diameters IvS in vitro stimulation OS Overall survival TAA Tunor-associated antigen KK-LC-1 Kita-Kyushu lung cancer antigen 1 PBMC Peripheral blood mononuclear cell TAP Transporter associated with antigen processing LCM Life cycle management PD Progressive disease TC Testicular cancer LLOQ Lower limit of quantification PDAC Pancreatic ductal adenocarcinoma TCGA The Cancer Genome Atlas LD Lymphodepletion PD-(L)1 Programmed cell death protein (ligand) 1 TCR T-cell receptor LPX Lipoplex PFS Progression-free survival TEA Tissue engineering acoustophoretic m Median PK Pharmacokinetics TE(S)AE Treatment-emergent (serious) adverse event mAB Monoclonal antibody PoC Proof of concept TKI Tyrosine kinase inhibitor MAGE-A3 Melanoma antigen A3 PoT Proof of technology TLR Toll-like receptor MHC Major histocompatibility complex PR Partial response TME Tumor microenvironment MIUC Muscle-invasive urothelial carcinoma PR Progesterone receptor TNBC Triple-negative breast cancer MMR Mismatch repair PRAME Preferentially expressed antigen in melanoma TNF Tumor necrosis factor MΦ Macrophage PROC Platinum-resistant ovarian cancer TNM Classification of malignant tumors (tumor-nodus-metastasis) MoA Mechanism of Action PSOC Platinum-sensitive ovarian cancer TPS Tumor proportion score MPM Malignant pleural mesothelioma QxW Every x week(s) TRAE Treatment-related adverse event MRI Magnetic resonance imaging R Randomized Treg Regulatory T cell mRNA Messenger ribonucleic acid (ncc/cc)RCC (Non-clear cell/clear cell) renal cell carcinoma TRON Helmholtz Institute for Translational Oncology MSI-H (L) High(low)-frequency microsatellite instability R&D Research and development TROP2 Trophoblast cell-surface antigen 2 MSKCC Memorial Sloan Kettering Cancer Center RECIST Response Evaluation Criteria in Solid Tumors TTF Time to treatment failure MSS Microsatellite stability RFS Recurrence-free survival TTP Time to progression MTD Maximum tolerated dose RP2D Recommended phase 2 dose TTR Time to response NCI PRO- National Cancer Institute Patient Reported Outcome R/R Relapsed/refractory UC Urothelial cancer CTCAE Common Terminology Criteria for Adverse Events RT-qPCR Real-time quantitative polymerase chain reaction UICC Union for International Cancer Control NEN Neuroendocrine neoplasm SAE Severe adverse event UPD Unconfirmed progression NF-κB Nuclear factor kappa B (E/LS)SCLC (Extensive/low stage) small cell lung cancer VEGF(R) Vascular endothelial growth factor (receptor) NGS Next generation sequencing scFv Single-chain variable fragment VHH Heavy chain variable NR Not reached SD Stable disease WT Wild type