BioNTech SE · NASDAQ:BNTX
BioNTech — Technical Presentation (June 2020)
16 slides from BioNTech's technical presentation, Jun 23, 2020
Slide 1: A Phase Ia Study to Evaluate RO7198457, an Individualized Neoantigen-Specific Immunotherapy (iNeST)
Braiteh F,1 LoRusso P,2 Balmanoukian A,3 Klempner S,3 Camidge DR,4 Hellmann MD,5 Gordon M,6 Bendell J,7 Mueller L,8 Sabado R,8 Twomey P,8 Delamarre L,8 Huang J,8 Yadav M,8 Zhang J,9 McDonald P,8 Muller F,10 Derhovanessian E,10 Tureci O,10 Sahin U,10 Siu LL11 1Comprehensive Cancer Center Nevada, Las
Slide 2: Disclosures
Dr Braiteh has the following relationships to disclose: Honoraria from Abbott Nutrition, Amgen, ARIAD, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Genentech/Roche, HERON, Immunomedics, Incyte, Insys Therapeutics, Ipsen, Lexicon, Lilly, Pu
Slide 3: Background: Stronger T-Cell Responses Against Neoantigens
Clinical Benefit High tumor mutation burden correlates with clinical response to immune checkpoint blockade Mutated neoantigens are recognized as foreign and induce stronger T-cell responses than shared antigens, likely due to the lack of central tolerance Most of these mutated neoantigens are not s
Slide 4: Development of Individualized RNA-LPX Technology
Blood and tumor biopsy collection Sequencing Bioinformatics Neoantigen Prediction RNA-LPX manufacturing Cold storage and distribution Intravenous administration Antigen Expression Up to 20 neoantigens (2 decatopes) Single-stranded mRNA Innate Immune Stimulation Intrinsic TLR7/8 agonist Targeting Neo
Slide 5: Proposed Dual MOA of RO7198457: TLR7/8 Stimulation and Neoantigen Presentation
Preferential delivery of RNA-LPX to dendritic cells in the spleen Dendritic cell Proposed Dual MOA of RO7198457: TLR7/8 Stimulation and Neoantigen Presentation MHC, Major histocompatibility complex; TCR, T-cell receptor. Kranz et al. Nature. 2016. - - [image] [image] [image]
Slide 6: Methods: Phase Ia Study of RO7198457 monotherapy in Advanced Solid Malignancies
Methods: Phase Ia Study of RO7198457 monotherapy in Advanced Solid Malignancies RO7198457 25 µg + atezolizumab 1200 mg RO7198457 38 µg + atezolizumab 1200 mg Dose Escalation Indication-Specific Expansionc RO7198457 50 µg + atezolizumab 1200 mg Checkpoint inhibitor experienced RO7198457 + Atezolizuma
Slide 7: Results: Patient Demographics and Disease Characteristics
ECOG PS, Eastern Cooperative Oncology Group performance status; HER, human epidermal growth factor receptor; HR, hormone receptor; IC, tumor-infiltrating immune cell; PD-L1, programmed death-ligand 1; TC, tumor cell. Data cutoff: January 10, 2020. Results: Patient Demographics and Disease Characteri
Slide 8: Results: Exposure and Disposition of Patients During Dose Escalation
AE, adverse event; DLT, dose-limiting toxicity. a DLT event was Grade 3 cytokine release syndrome (CTCAE v5.0). b Phase Ia patients with disease progression or loss of clinical benefit could cross over to combination therapy in Phase Ib. Data cutoff: January 10, 2020. Results: Exposure and Dispositi
Slide 9: Results: Adverse Events in Patients Treated With RO7198457
Results: Adverse Events in Patients Treated With RO7198457 Systemic Reactions a A serious AE of malignant neoplasm progression was reported in 16% of patients (data not shown). b Per CTCAE v5.0. Data cutoff: January 10, 2020. Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 AEs Reported in > 10% of Patients
Slide 10: Results: Systemic Reactions (IRR, CRS, ILI) Were Transient and Generally Manageable
CRS, cytokine release syndrome (CTCAE v.5.0); IRR, infusion-related reaction; ILI, influenza-like illness. Data cutoff: January 10, 2020. Results: Systemic Reactions (IRR, CRS, ILI) Were Transient and Generally Manageable in the Outpatient Setting n (%) 25 μg RO7198457 (n = 13) 38 μg RO7198457 (n =
Slide 11: Results: RO7198457 Induced Pulsatile Release of Pro-Inflammatory Cytokines
IFNγ 25 ug (representative pattern) IFNγ IL-6 IFNα C1D1 C2D1 C3D1 RO7198457a 4-6 0 4-6 0 4-6 0 4-6 0 4-6 0 4-6 0 4-6 0 4-6 0 C1D8 C1D15 C2D8 C2D15 C3D15 4-6 0 0 4-6 0 4-6 0 0 4-6 0 4-6 0 4-6 0 4-6 4-6 4-6 0 0 4-6 0 4-6 0 0 4-6 0 4-6 0 4-6 0 4-6 4-6 4-6 0 0 4-6 0 4-6 0 0 4-6 0 4-6 0 4-6 0 4-6 4-6 Cyt
Slide 12: Results: Immune Monitoring of T-Cell Responses Induced by RO7198457
Results: Immune Monitoring of T-Cell Responses Induced by RO7198457 a In collaboration with Adaptive Biotechnologies. Data cutoff: January 10, 2020. ≥ 1 responses 0 responses Phase Ia ELISPOT+ MHC Multimers Ex vivo T-cell responses were detected in 86% of patients evaluated to date Median number of
Slide 13: Results: Immune Monitoring of Peripheral Blood–Detected T-Cell Responses
PD-1, programmed death-1. Results: Immune Monitoring of Peripheral Blood–Detected T-Cell Responses Induced by RO7198457 Kinetics and Phenotype of Neoantigen-Specific T-cell Responses Baseline C2D1 C3D1 C4D1 0.03% 1.95% 2.49% 4.7% Patient with Prostate Cancer Treated With RO7198457 (38µg) Tem Tcm CCR
Slide 14: Results: RO7198457 Clinical Activity
Results: RO7198457 Clinical Activity BOR, best overall response; CPI, checkpoint inhibitor; CR, complete response; HNC, Head and neck cancer; N, no; PR, partial response; SD, stable disease; STS, Soft tissue sarcoma; Y, yes; N, no. a PD-L1 expression on IC/TC analyzed by SP142 Ventana assay. Data cu
Slide 15: Conclusions
Conclusions RO7198457 was generally well tolerated One DLT of Grade 3 CRS occurred in the 100 μg dose cohort; the maximum tolerated dose was not reached Treatment-related AEs were primarily transient systemic reactions, manifesting as low-grade CRS, IRR, or ILI symptoms. Systemic reactions were gene
Slide 16: Acknowledgments
We thank all of our patients who participated in this study and their families We also would like to thank the investigators and clinical research staff at the following clinical sites: We thank the Genentech multimer group: Alberto Robert, Leesun Kim, Oliver Zill, Martine Darwish and Craig Blanchet