BioNTech SE · NASDAQ:BNTX
BioNTech — Technical Presentation (June 2020)
16 slides from BioNTech's technical presentation, Jun 23, 2020
Slide 1: Phase Ib of RO7198457 with Atezolizumab in Advanced Solid Malignancies
Lopez J,1 Camidge DR,2 Iafolla M,3 Rottey S,4 Schuler M,5 Hellmann MD,6 Balmanoukian A,7 Dirix L,8 Gordon M,9 Sullivan RJ,10 Henick BS,11 Drake C,11 Wong KM,12 LoRusso P,13 Ott PA,14 Fong L,15 Schiza A,16 Yachnin J,17 Ottensmeier C,18 Braiteh F,19 Bendell J,20 Leidner R,21 Fisher G,22 Jerusalem G,23
Slide 2: Disclosures
Dr Lopez has the following relationships to disclose: Research grant funding: Roche/Genentech, Basilea, Genmab Ad board: Basilea Disclosures Lopez j, et al. Phase Ib of of R07198457 https//bit.Iy/3gjdHA2
Slide 3: Cancer Mutations Are Drivers of Protective Immunity
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: Targeting Neoantigens Requires an Individualized Approach
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: Innate Immune Stimulation and Neoantigen Presentation
Preferential delivery of RNA-LPX to dendritic cells in the spleen Dendritic cell Proposed Dual MOA of RO7198457: Innate Immune Stimulation and Neoantigen Presentation TCR, T-cell receptor. Kranz et al. Nature. 2016. - - image Lopez j, et al. Phase Ib of of R07198457 https//bit.Iy/3gjdHA2
Slide 6: Phase Ib Study of RO7198457 in Combination With Atezolizumab
Phase Ib Study of RO7198457 in Combination With Atezolizumab in Advanced Solid Malignancies RO7198457 25 µg + atezolizumab 1200 mg RO7198457 38 µg + atezolizumab 1200 mg Dose Escalation Indication-Specific Expansion Cohorts RO7198457 50 µg + atezolizumab 1200 mg Checkpoint inhibitor experienced RO71
Slide 7: Patient Demographics and Baseline Characteristics
Dose Escalation Expansion Total (n = 30) CPI Experienced (n = 42) CPI Naive (n = 72) Median age (range), years 57.5 (35-77) 61.5 (36-82) 57.5 (29-79) Male, n (%) 17 (56.6) 25 (59.5) 31 (43.1) ECOG PS, n (%) 0 1 15 (50.0) 15 (50.0) 19 (45.2) 23 (54.8) 38 (52.8) 34 (47.2) Most common tumor types, n (%
Slide 8: Patient Exposure and Disposition
AE, adverse event. a Patient discontinued atezolizumab at the same time as RO7198457. However, atezolizumab discontinuation information was not completed until after data cut. b Four deaths were due to malignant neoplasm progression. One death was due to malignant pericardial effusion. No deaths wer
Slide 9: Adverse Events in Patients Treated With RO7198457 + Atezolizumab
Reported AE Terms in > 10% of Patientsa AEs Occurring in Patients Treated With RO7198457 + Atezolizumab No increase in immune-mediated AEs compared with atezolizumab single-agent experience (data not shown) Related AEs (n = 125) All AEs (n = 139) 100 50 60 80 90 70 10 0 20 30 40 100 50 60 80 90 70 1
Slide 10: Systemic Reactions Were Transient and Generally Manageable in the Outpatient Setting
Individual Signs and Symptoms of Systemic Reactions (CRS/IRR/ILI) in ≥ 5 Patients CRS, cytokine release syndrome (CTCAE v.5.0); IRR, infusion-related reaction; ILI, influenza-like illness. Data cutoff: January 10, 2020. Systemic Reactions Were Transient and Generally Manageable in the Outpatient Set
Slide 11: RO7198457 + Atezolizumab Induced Neoantigen-Specific T-Cell Responses
Induction of pro-inflammatory cytokines with each dose was observed, similar to findings in the Phase Iaa Ex vivo T-cell responses were detected (ELISPOT and MHC multimers) in nearly 73% of patients evaluated (n = 63) Median number of 2.6 neoantigen-specific responses (range, 1-9). Ex vivo data are
Slide 12: Ex Vivo T-Cell Responses Induced by RO7198457 + Atezolizumab
Patient with TNBC treated with RO7198457 (25 µg) + atezolizumab 1200 mg IV q3wa D, day; IFN, interferon; PBMC, peripheral blood mononuclear cell; PD-1, programmed death-1; SD, stable disease. a Best response of SD; PD-L1 ≥ 5% IC or TC. Ex Vivo T-Cell Responses Induced by RO7198457 + Atezolizumab R8
Slide 13: Dose Escalation: Clinical Activity
Screening Cycle 4 Patient With TNBC (CPI experienced) Treated With RO7198457 (38 µg) + Atezolizumab 1200 mg IV q3w Baseline Post Treatment Dose Escalation: RO7198457 + Atezolizumab Clinical Activity BOR, best overall response; CR, complete response; HNC, head and neck cancer; MCC, Merkel cell carcin
Slide 14: CPI-Naive Dose Expansion Activity
ORR, objective response rate. a PD-L1 expression on IC/TC analyzed by the Ventana SP142 assay. Data cutoff: January 10, 2020. CPI–Naive Dose Expansion Activity: RO7198457 25 μg + Atezolizumab Cohort Median (range) Prior Therapies, n PD-L1 Expression, n (%)a < 5% ≥ 5% Missing UC (n = 10) 1 (1-3) 7 (7
Slide 15: Summary and Conclusions
Summary and Conclusions RO7198457 combined with atezolizumab was generally well tolerated MTD was not reached and no DLTs were observed Treatment-related AEs were primarily systemic reactions, manifesting as low-grade CRS, IRR or ILI symptoms that were transient, reversible and manageable in the out
Slide 16: Acknowledgments
We thank all of the patients who participated in this study and their families We also 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 Blanchette Editorial a