Slide 1: Safety and Immunogenicity of mRNA mpox Vaccine Candidate mRNA-1769: Interim Analysis Results
Safety and Immunogenicity of mRNA mpox Vaccine Candidate mRNA-1769: Interim Analysis Results from a Phase 1/2 trial Hiwot Hiruy,1 Rajeka Lazarus,2 Kieran McCafferty,3 Roxane Hasselbeck,1 Kristen Cohen,1 Rakesh Dhar,1 Tony Rizk,1 Abidemi Adeniji,1 Xiaolin Chang,1 Lisa Siquel,1 Hamilton Bennett,1 Bret
Slide 2: Disclosures and Acknowledgments
Disclosures and Acknowledgments • Disclosures -HH, RH, KC, RD, TR, AA,XC, LS, HB and BL are employees of Moderna Inc., may hold stock/stock options in the company. -All relevant financial disclosures have been mitigated • Acknowledgments We would like to thank the study participants, the study site
Slide 3: Forward-Looking Statements and Disclaimer
Forward-Looking Statements and Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: target product profile; efficacy and safety; and the potential for regulatory approv
Slide 4: Background: Mpox
Background: Mpox • Double-stranded DNA virus belonging to orthopoxvirus genus which also includes variola and vaccinia viruses • Two main clades of mpox virus (MPXV) ➢ Clade 1 (Central Africa): Clade 1a and Clade 1b ➢ Clade 2 (West Africa): Clade 2a and Clade 2b • Epidemiology and transmission: ➢ Hi
Slide 5: Increase in Global Burden of Mpox
Increase in Global Burden of Mpox • 2022: The World Health Organization (WHO) declared the first Public Health Emergency of International Concern (PHEIC) due to Clade 2b, with over 100,000* Clade 2 mpox cases reported worldwide • 2024: The Africa CDC declared mpox a public health concern of continen
Slide 6: mRNA-1769 is comprised of Mature Virion and Enveloped Virion antigens
mRNA-1769 is comprised of Mature Virion(MV) and Enveloped Virion (EV) antigens • mRNA-1769 consists of four surface antigens in equal mass ratios (1:1:1:1), with two antigens from the MV (A29L, M1R) and two from the EV (B6R, A35R). • Selection of these antigens was based on existing scientific evide
Slide 7: mRNA-1769-P101 Overview
mRNA-1769-P101 Overview © 2024 Moderna, inc. All rights reserved.
Slide 8: mRNA-1769-P101: Ongoing Phase 1/2 Trial (NCT05995275)
mRNA-1769-P101: Ongoing Phase 1/2 Trial (NCT05995275) 1 Randomized, observer-blind, placebo-controlled, dose-ranging study in healthy individuals aged 18–50 years Key Endpoints With Data Available at Interim Analysis • 350 participants (18 to <50yo) were randomized 2:2:2:1 to 25µg, 50µg, 100µg or pl
Slide 9: mRNA-1769 P101 Demographics and Baseline Characteristics (Safety Set)
mRNA-1769 P101 Demographics and Baseline Characteristics (Safety Set) Placebo mRNA-1769 mRNA-1769 mRNA-1769 25 µg 50 µg 100 µg N=51 N=98 N=98 N=101 AGE 35 36 32 31 Median(min, max) (20, 49) (19, 49) (18, 49) (18, 49) Gender (n, %) Female 19 (37.3) 43 (43.9) 45 (45.9) 45 (44.6) Male 32 (62.7) 55 (56.
Slide 10: mRNA-1769-P101 IA Safety Results
mRNA-1769-P101 IA Safety Results © 2024 Moderna, inc. All rights reserved.
Slide 11: mRNA-1769 IA Safety Data – Local Solicited Adverse Reaction (SARs)
mRNA-1769 IA Safety Data – Local Solicited Adverse Reaction (SARs) • Most local SARs were Grade 1 and 2 • The most common local SAR was pain at injection site • Occurrence of Grade 3 local SARs increased post-dose 2,and with increasing dose level © 2024 Moderna, inc. All rights reserved.
Slide 12: mRNA-1769 IA Safety Data – Systemic SARs
mRNA-1769 IA Safety Data – Systemic SARs • Most systemic SARs were Grade 1 and 2 • Incidence and severity of systemic SARs increased post- dose 2, and with increasing dose level • Fatigue, headache and myalgia were the most common systemic SARs • No Gr4 events; one erroneous entry of Gr4 fever (repo
Slide 13: mRNA-1769-P101 IA Safety Data Summary
mRNA-1769-P101 IA Safety Data Summary • No Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), or Adverse Events (AEs) leading to study discontinuation were deemed related to the investigational product (IP) by the investigator. • Four participants discontinued study injection
Slide 14: mRNA-1769-P101 IA Immunogenicity Assessment and Results
mRNA-1769-P101 IA Immunogenicity Assessment and Results Longitudinal serum and PBMC (subset) collection for kinetic and broad immune assessments • Plaque Reduction Neutralization Test (PRNT): MPXV (MPXV-ZAI-V79) and VACV (VACV WR) • Binding antibody: MPXV antigens A29L, A35R, B6R, M1R and VACV homol
Slide 15: 5 to 10-fold increase in MPXV nAb and 5 to 7-fold increase in VACV nAb
5 to 10-fold increase in MPXV nAb and 5 to 7-fold increase in VACV nAb titer observed at Day 43 Geometric mean titer of MPXV nAb Dashed lines indicate LOD(54) Geometric mean titer of VACV nAb Dashed lines indicate LLOQ(30) and ULOQ(5469) 15 © 2024 Moderna, inc. All rights reserved.
Slide 16: Robust Binding Antibody Response to mRNA-1769 Vaccine Antigens
Robust Binding Antibody Response to mRNA-1769 Vaccine Antigens: Response to A35R/A33R presented as an example Geometric mean concentration of MPXV A35R- specific bAb Dashed and dotted lines indicate LLOQ(121) and ULOQ(1540000) respectively Geometric mean concentration of VACV A33R- specific bAb Dash
Slide 17: Robust Th1 CD4+ T-cell response to antigens in mRNA-1769
Robust Th1 CD4+ T-cell response to antigens in mRNA-1769: Response to A35R + M1R presented as an example CD40+ CD4+ Th1 T-cell Response to A35R+M1R © 2024 Moderna, inc. All rights reserved.
Slide 18: Modest Type 1 CD8+ T-cell response
Modest Type 1 CD8+ T-cell response: Response to A35+M1R CD8 presented as an example Type 1 CD8+ T-cell Response to A35R+M1R © 2024 Moderna, inc. All rights reserved.
Slide 19: mRNA-1769-P101 IA Immunogenicity Data Summary
mRNA-1769-P101 IA Immunogenicity Data Summary Neutralizing antibody • At peak immunogenicity (Day 43), 5-10-fold-rise increase in MPXV PRNT was observed • At peak immunogenicity (Day 43), 5-7-fold-rise increase in VACV PRNT was observed; shows the breadth of our vaccine’s ability to neutralize a het
Slide 20: Overall Summary: mRNA-1769 P101 IA results support further development
Overall Summary: mRNA-1769 P101 IA results are supportive of its further development for mpox prevention • Favorable safety profile: mRNA-1769 was safe and well tolerated across all dose levels. • Robust humoral immune response: mRNA-1769 elicited a strong humoral response, with increased levels of
Slide 21: Thank you
Thank you © 2024 Moderna, inc. All rights reserved.
Slide 22: References
References • Cotter CA, Ignacio MA, Americo JL, Earl PL, Mucker EM, Frey TR, et al. Mpox mRNA-1769 vaccine inhibits orthopoxvirus replication at intranasal, intrarectal, and cutaneous sites of inoculation. NPJ Vaccines. 2024 Dec 24;9(1):256. • Edghill-Smith Y, Golding H, Manischewitz J, King LR, Sco
Slide 23: Supplementary Slides
•Supplementary Slides © 2024 Moderna, inc. All rights reserved.
Slide 24: Binding Antibody Assays: A29L/A27L
Binding Antibody Assays: A29L/A27L MPXV A29L GMC Dashed line and dotted line indicate LLOQ(82) and ULOQ(30700) VACV A27L GMC 24 © 2024 Moderna, inc. All rights reserved. Dashed line and dotted line indicate LLOQ(81.7) and ULOQ(26900), respectively
Slide 25: Binding Antibody Assays: B6R/B5R
Binding Antibody Assays: B6R/B5R MPXV B6R GMC Dashed and dotted lines indicate LLOQ(73.6) and ULOQ(363000), respectively. VACV B5R GMC 25 © 2024 Moderna, inc. All rights reserved. Dashed and dotted lines indicate LLOQ(53.4) and ULOQ(470000), respectively.
Slide 26: Binding Antibody Assays: M1R/L1R
Binding Antibody Assays: M1R/L1R MPXV M1R GMC Dashed line and dotted line indicate LLOQ(376) and ULOQ(1720000), respectively VACV L1R GMC 26 © 2024 Moderna, inc. All rights reserved. Dashed line and dotted line indicate LLOQ(170) and ULOQ(2770000), respectively
Slide 27: Robust Type 1 CD4+ T-cell response: Response to A29L+B6R
Robust Type 1 CD4+ T-cell response to antigens in mRNA-1769: Response to A29L+B6R CD40L+CD4+ Th1 T-cell Response to A29L+B6R © 2024 Moderna, inc. All rights reserved.
Slide 28: Modest Type 1 CD8+ T-cell response: Response to A29L+B6R
Modest Type 1 CD8+ T-cell response: Response to A29L+B6R Type 1 CD8+ T-cell Response to A29L+B6R © 2024 Moderna, inc. All rights reserved.