Moderna, Inc. · NASDAQ:MRNA

Moderna — Investor Day (September 2024)

141 slides from Moderna's investor day presentation, Sep 12, 2024

Slide 2: 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: Moderna’s focus on ten product approvals through 2027; Moderna’s expected regulatory
Slide 4: Our vision is becoming reality
Moderna R&D Day 2024| Introduction Our vision is becoming reality Moderna was established with the goal of using mRNA, an information molecule, to treat and prevent disease 4 © 2024 Moderna, Inc. All rights reserved.
Slide 5: Our vision is becoming reality
Moderna R&D Day 2024| Introduction Our vision is becoming reality Moderna was established with the goal of using mRNA, an information molecule, to treat and prevent disease 2020 2024 We have developed an 25 development programs 43 development programs unprecedented number of 11 preclinical 3 preclin
Slide 6: Our vision is becoming reality
Moderna R&D Day 2024| Introduction Our vision is becoming reality Moderna was established with Moderna’s rate of success with our platform the goal of using mRNA, an technology is higher than industry standard information molecule, to treat and prevent disease We have developed an unprecedented numb
Slide 7: We are adapting our business strategy
Moderna R&D Day 2024| Introduction We are adapting our business strategy, shaped by our successes and challenges Broad clinical Challenging success of our commercial large pipeline realities Focusing on delivery of ten product approvals Pacing new R&D investments 7 © 2024 Moderna, Inc. All rights re
Slide 9: Respiratory virus hospitalization rates in 65+
Moderna R&D Day 2024| Introduction Our 3 priorities 1 Drive use of Spikevax and mRESVIA vaccines Cumulative rates of respiratory virus-related hospitalizations in the 2023/2024 season in 65+ population in the U.S. 1. https://www.cdc.gov/respiratory-viruses/risk-factors/older-adults.html Source: http
Slide 10: Impact of COVID hospitalization on people 65+
Moderna R&D Day 2024| Introduction Our 3 priorities 1 Drive use of Spikevax and mRESVIA vaccines People 65+ who are hospitalized with COVID may experience a significant impact on their quality of life ~10% ~30% loss of muscle mass over 7 risk of readmission days within immobile older within 6 months
Slide 11: The risk of Long COVID
Moderna R&D Day 2024| Introduction Our 3 priorities 1 Drive use of Spikevax and mRESVIA vaccines The risk of Long COVID poses a risk to people of all ages The risk of developing Long COVID goes up with each new COVID-19 infection1 Studies show that COVID-19 vaccines may reduce the risk of Long COVID
Slide 12: Focus on 10 product approvals
Moderna R&D Day 2024| Introduction Our 3 priorities 1 Drive use of Spikevax and mRESVIA vaccines 2 Focus on 10 product approvals over the next 3 years to drive sales growth 12 © 2024 Moderna, Inc. All rights reserved.
Slide 13: Deliver cost efficiency and slow R&D investment
Moderna R&D Day 2024| Introduction Our 3 priorities 1 Drive use of Spikevax and mRESVIA vaccines 2 Focus on 10 product approvals over the next 3 years to drive sales growth 3 Deliver cost efficiency across the business and slow the pace of R&D investment, reducing it by $1.1B annually1 1. R&D expens
Slide 14: R&D Day Agenda
Moderna R&D Day 2024| Introduction R&D Day Agenda Introduction Stéphane Bancel, Chief Executive Officer R&D Strategy Stephen Hoge, M.D., President Respiratory Vaccines Jacqueline Miller, M.D., SVP, Therapeutic Area Head, Infectious Diseases • COVID • Flu Raffael Nachbagauer, M.D. Ph.D., Executive Di
Slide 16: Our R&D strategy
Moderna R&D Day 2024| R&D Strategy Our R&D strategy 2021-2023 2023-2026 2026-2028 Build a pipeline Deliver respiratory Deliver non-respiratory approvals approvals Invest pandemic proceeds Build large portfolio of Expand commercial portfolio into in diverse pipeline 5 commercial vaccines cancer, rare
Slide 17: Our R&D investments delivered many positive results
Moderna R&D Day 2024| R&D Strategy Our R&D investments delivered many positive results in the past year Two major Four positive Proof of concept Positive early proof-of-concept approvals Phase 3s strengthened by data in six other programs ongoing durability Next-gen COVID COVID mRNA-1283 mRNA-1273 E
Slide 18: Our R&D strategy
Moderna R&D Day 2024| R&D Strategy Our R&D strategy 2021-2023 2023-2026 2026-2028 Build a pipeline Deliver respiratory approvals Deliver non-respiratory approvals Invest pandemic proceeds Build large portfolio of Expand commercial portfolio into in diverse pipeline 5 commercial vaccines cancer, rare
Slide 19: Pacing new R&D investments will reduce annual R&D expense
Moderna R&D Day 2024| R&D Strategy Pacing new R&D investments will reduce annual R&D expense by $1.1 billion starting in 2027 Moderna R&D investment ($ billion) $1.1B reduction (at midpoint) 4.8 4.8 4.5 3.6-3.8 3.3 2.0 2021 2022 2023 2024E 2025E 2026E 2027E Respiratory Vaccines Latent/Other Vaccines
Slide 20: Respiratory vaccines portfolio
Respiratory vaccines portfolio Jacqueline Miller, M.D. SVP, Head of Development, Infectious Diseases, Research & Development © 2024 Moderna, Inc. All rights reserved.
Slide 22: Continued need for COVID-19 vaccines in U.S.
Moderna R&D Day 2024| Respiratory virus vaccines Continued need for COVID-19 vaccines in U.S. COVID-19 continues to have a significant burden of disease in U.S. COVID is the leading cause of hospitalizations among Long COVID data suggests even traditionally low risk respiratory viruses groups should
Slide 23: Spikevax (mRNA-1273) availability
Moderna R&D Day 2024| Respiratory virus vaccines Spikevax (mRNA-1273): Moderna’s Spikevax formulas have been approved/authorized and are available in major markets Our mRNA platform allowed us to pivot quickly to ensure Spikevax availability for all selected strains North America Rest of World ● Tai
Slide 24: mRNA-1283 pivotal Phase 3 trial design
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1283 pivotal Phase 3 trial design; sharing vaccine efficacy data today The Phase 3 was designed to test the immunogenicity, safety and relative vaccine efficacy of mRNA-1283.222 against mRNA-1273.222 in participants 12+ years of age Design Random
Slide 25: Relative vaccine efficacy of mRNA-1283 vs mRNA-1273
Moderna R&D Day 2024| Respiratory virus vaccines Relative vaccine efficacy (rVE) of mRNA-1283 vs mRNA-1273: success criterion met Per-Protocol Set for Efficacy mRNA-1283 (10 µg) mRNA-1273 (50 µg) N = 5679 N = 5687 Number of participants with COVID-19, n (%) 9.9% (560) 10.8% (617) Person-months 40,77
Slide 26: Relative vaccine efficacy by age group
Moderna R&D Day 2024| Respiratory virus vaccines Relative vaccine efficacy of mRNA-1283 vs mRNA-1273 by age group COVID-19 Events through 31 Jan 2024 - Per-Protocol Set for Efficacy 12-17 years 18-64 years ≥65 Years mRNA-1283 mRNA-1273 mRNA-1283 mRNA-1273 mRNA-1283 mRNA-1273 10 μg 50 μg 10 μg 50 μg
Slide 27: mRNA-1283 antibody response vs mRNA-1273
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1283.222 elicited higher antibody response against both BA.4/5 and original SARS-CoV-2 compared to mRNA-1273.222 Geometric mean ratio (GMR) of Non-inferiority margin mRNA-1283.222 vs mRNA-1273.222 against BA.4/BA.5 and original SARS-CoV-2 based o
Slide 28: Antibody response against BA.4/5 by age group
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1283.222 antibody response against BA.4/5 compared to mRNA-1273.222 by age group Non-inferiority margin 12 to 17 yrs Geometric mean ratio (GMR) of mRNA-1283.222 vs mRNA-1273.222 18 to 64 yrs against BA.4/BA.5 based on a randomly selected ≥ 65 yrs
Slide 29: Reactogenicity profile of mRNA-1283 similar to mRNA-1273
Moderna R&D Day 2024| Respiratory virus vaccines Reactogenicity profile of mRNA-1283 similar to mRNA-1273 Overall Local Reactogenicity: 70.3% mRNA- Overall Systemic Reactogenicity: 64.4% 1283.222 vs. 78.4% mRNA-1273.222 mRNA-1283.222 vs. 64.2% mRNA-1273.222 100 Grade 4 100 Grade 4 Grade 3 Grade 3 Gr
Slide 30: Reactogenicity by age group
Moderna R&D Day 2024| Respiratory virus vaccines Reactogenicity profile of mRNA-1283 versus mRNA-1273 in Phase 3 study by age group ≥ 65 years old 18-64 years old 12 to 17 years old Grade 4 Grade 4 Grade 4 100 Grade 3 100 Grade 3 100 Grade 3 Grade 2 A dose of Grade 2 Grade 2 Grade 1 Grade 1 Grade 1
Slide 31: mRNA-1283 pivotal Phase 3 safety
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1283 pivotal Phase 3 safety mRNA-1283 was well-tolerated and its safety and reactogenicity profile was consistent with the known safety profile of mRNA-1273 No deaths or discontinuations of vaccination were reported as related to mRNA-1283 Myocar
Slide 32: mRNA-1283 summary and next steps
Moderna R&D Day 2024| Respiratory virus vaccines Next-gen COVID-19 vaccine mRNA-1283 summary and next steps ● Pre-specified relative vaccine efficacy (rVE) objective met Vaccine ● rVE of mRNA-1283 non-inferior compared to mRNA-1273 efficacy ● rVE point estimate highest in participants ≥ 65 years old
Slide 34: Seasonal influenza causes respiratory illnesses
Moderna R&D Day 2024| Respiratory virus vaccines Seasonal influenza causes respiratory illnesses leading to hospitalizations across age groups, especially in older adults Our mRNA platform will allow us to quickly reformulate based on the current year’s strain SOURCE: https://www.cdc.gov/flu/weekly/
Slide 35: mRNA-1010 Phase 3 older adult study overview
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1010 Phase 3 older adult study overview Study was designed to test the immunogenicity and safety of an optimized composition of mRNA-1010 Design Randomized, observer-blind, active control study of Total N= 3,003 optimized mRNA-1010 Randomization
Slide 36: mRNA-1010 met all primary immunogenicity endpoints
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1010 met all primary immunogenicity endpoints compared to Fluzone HD in P303 GMT ratios Seroconversion rates ● Immunogenicity criteria for licensure according to regulatory guidance were met for all 8 co-primary endpoints – GMR – Seroconversion r
Slide 37: mRNA-1010 reactogenicity profile
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1010 showed acceptable, but higher reactogenicity compared to Fluzone HD Local Solicited Adverse Reactions Systemic Solicited Adverse Reactions ● The majority of solicited ARs were grade 1 or grade 2 in severity ● The most common local solicited
Slide 38: mRNA-1010 Phase 3 older adult safety
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1010 Phase 3 older adult safety Unsolicited AEs were reported at similar rates between mRNA-1010 and the active comparator groups • Profiles were similar based on frequency, severity, seriousness, relatedness as assessed by the investigator, and
Slide 39: mRNA-1010 vaccine efficacy study (P304)
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1010 vaccine efficacy study (P304) Season 2 study only to commence if Design success criteria not met in season 1 Randomized, observer-blind, active control study of optimized mRNA-1010 Season 1 Season 2 Total N= ~34,000 Total N= ~22,000 Particip
Slide 40: Flu (mRNA-1010) summary and next steps
Moderna R&D Day 2024| Respiratory virus vaccines Flu (mRNA-1010) summary and next steps ● Immunogenicity criteria were met for all 8 co-primary endpoints Immunogenicity for GMT ratio and seroconversion rates ● Showed an acceptable reactogenicity profile, with the majority of solicited Reactogenicity
Slide 42: Burden of flu and COVID underscores combination vaccine
The burden of flu and COVID underscores the importance of a Moderna R&D Day 2024| Respiratory virus vaccines combination vaccine to potentially increase vaccine uptake in the U.S. Offering a combo vaccine could push the COVID vaccine rate closer to that of flu, with the potential to substantially lo
Slide 43: mRNA-1083-P301 Phase 3 study
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1083-P301 Phase 3 study; presenting data charts today Study was designed to test the immunogenicity and safety of mRNA-1083 Design Randomized, observer-blind, active control study Phase 3 clinical study Participants ~8,000 adults > 50 years of ag
Slide 44: mRNA-1083 met all primary immunogenicity endpoints
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1083 met all primary immunogenicity endpoints in Phase 3 ≥65 years ≥50 to 64 years mRNA-1083 vs. Fluzone HD + Spikevax mRNA-1083 vs. Fluarix + Spikevax A/H1N1 A/H1N1 Non-inferiority margin Non-inferiority margin Superiority margin Superiority mar
Slide 45: mRNA-1083 acceptable reactogenicity profile
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1083 showed an acceptable reactogenicity profile compared to co-administered influenza and COVID-19 vaccines Cohort A: ≥65 years Cohort B: ≥50 to 64 years 100 100 Grade 1 Grade 1 Grade 2 Grade 2 Grade 3 Grade 3 80 80 ● Majority of solicited % of
Slide 46: mRNA-1083 safety
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1083 safety The rates of unsolicited AEs were similar across groups No deaths, SAEs or adverse events leading to study discontinuation were considered related to mRNA-1083 No events of myocarditis or pericarditis were reported that were considere
Slide 47: Flu + COVID combo (mRNA-1083) summary and next steps
Moderna R&D Day 2024| Respiratory virus vaccines Flu + COVID combo (mRNA-1083) summary and next steps ● mRNA-1083 met all 10 co-primary immunogenicity endpoints in Phase 3 study ● mRNA-1083 elicited a higher immune response against SARS-CoV-2 and clinically Immunogenicity relevant influenza strains
Slide 49: RSV hospitalization rate higher in older adults
Moderna R&D Day 2024| Respiratory virus vaccines RSV hospitalization rate is markedly higher in the older adult population Study shows that RSV vaccine uptake at 66% in older adults would reduce outpatient care by up to 53.6%, hospitalizations by up to 60.5%, and RSV-related deaths up to 60.4%.1 SOU
Slide 50: mRESVIA (mRNA-1345) availability
Moderna R&D Day 2024| Respiratory virus vaccines mRESVIA (mRNA-1345): Moderna’s RSV vaccine for adults 60 and older has been approved in multiple regions North America Rest of World ● EU ● Qatar 50 © 2024 Moderna, Inc. All rights reserved.
Slide 51: mRNA-1345 Phase 3 P303 Part A
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1345 Phase 3 P303 Part A: High-risk adults 18 to <60 years Study designed to test the immunogenicity and safety of mRNA-1345 in high-risk adults 18 to < 60 years of age Design Randomized, double-blind study mRNA-1345 P303 Part A High risk adults
Slide 52: mRNA-1345 met all primary immunogenicity endpoints
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1345 met all primary immunogenicity endpoints in high- risk adults 18 to < 60 years High risk adults 18 to < 60 years compared to pivotal P301 efficacy study (> 60 years) RSV-A Neutralizing Antibody GMR non-inferiority Non-inferiority margin crit
Slide 53: mRNA-1345 well-tolerated in high-risk adults
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1345 50 µg dose was well-tolerated in high-risk adults 18 to < 60 years Systemic Solicited Adverse Reactions Local Solicited Adverse Reactions Systemic Solicited Adverse Reactions 100 100 Grade 4 Grade 4 Grade 3 percent of participants (%) percen
Slide 54: mRNA-1345 Part A safety
Moderna R&D Day 2024| Respiratory virus vaccines mRNA-1345 Phase 3 18–59-year-olds at high risk Part A safety mRNA-1345 50 µg dose was well tolerated in 18–59-year-olds at high risk of RSV-LRTD The tolerability of 50 µg of mRESVIA in 18-59 year old high risk adults was comparable to that observed am
Slide 55: mRNA-1345 summary and next steps
Moderna R&D Day 2024| Respiratory virus vaccines Summary ● mRNA-1345 met all primary immunogenicity endpoints in high-risk adults 18 to < 60 years Immunogenicity ● Demonstration of non-inferiority compared to immune responses in the pivotal efficacy trial (P301; > 60 years), thus inferring effective
Slide 56: Latent + other viruses vaccines portfolio
Latent + other viruses vaccines portfolio Jacqueline Miller, M.D. SVP, Head of Development, Infectious Diseases, Research & Development © 2024 Moderna, Inc. All rights reserved.
Slide 58: Cytomegalovirus (CMV) Overview
Moderna R&D Day 2024| Latent + other virus vaccines Cytomegalovirus (CMV) Overview CMV is the most common infectious cause of birth defects in the U.S.1 Several billion dollars in annual 1 in 200 healthcare costs2 babies in the U.S. are born with a congenital CMV infection (CMV infection is present
Slide 59: CMV vaccine (mRNA-1647) Phase 3 trial
Moderna R&D Day 2024| Latent + other virus vaccines CMV vaccine (mRNA-1647) Phase 3 trial accruing cases with interim analysis expected to be triggered in 2024 Randomized, observer-blind, placebo- controlled study to evaluate the efficacy, safety and immunogenicity of mRNA-1647 to evaluate preventio
Slide 60: Overview of primary efficacy endpoint
Moderna R&D Day 2024| Latent + other virus vaccines Overview of primary efficacy endpoint Efficacy Boundaries with Alpha-allocation between 2 Planned Analyses Approximate # One-sided VE: Efficacy of Cases Alpha Bound Interim Analysis 81 0.5% ~ 57.7% Interim analysis End of Study 112 2.0% ~ 49.1% (EO
Slide 61: CMV vaccine summary and next steps
Moderna R&D Day 2024| Latent + other virus vaccines CMV (mRNA-1647) Phase 3 vaccine summary and next steps Addressing ● CMV is the most common cause of congenital infection worldwide1 disease ● Moderna’s CMV vaccine targets two antigens, the pentamer and the burden glycoprotein B (gB) antigen Latest
Slide 63: Norovirus is a leading cause of diarrheal disease
Moderna R&D Day 2024| Latent + other virus vaccines Among enteric viruses, norovirus is a leading cause of diarrheal disease globally resulting in substantial health care burden Norovirus is associated with 18% of United States Global (per year)2 (per year)2,3 all acute gastroenteritis worldwide1 Th
Slide 64: Noroviruses are a diverse group with limited cross-genotype protection
Noroviruses are a diverse group with limited cross-genotype Moderna R&D Day 2024| Latent + other virus vaccines protection, allowing for repeated infections throughout life Norovirus genogroups and genotypes in long term care facility outbreaks in the US 2009-2018 Adapted from Calderwood et al, 2022
Slide 65: mRNA technology provides ability to make multivalent VLPs
Moderna R&D Day 2024| Latent + other virus vaccines mRNA technology provides ability to make multivalent VLPs that can be quickly updated Multi-valent virus-like particle (VLP) vaccine mRNA vaccines allow for intracellular production of multi-valent virus-like Update 1 particles (VLPs) These VLPs ar
Slide 66: mRNA-1403/1405 Phase 1 trial design
Moderna R&D Day 2024| Latent + other virus vaccines mRNA-1403/1405 Phase 1 trial design; presenting additional data today The Phase 1 was designed to evaluate the safety, reactogenicity and immunogenicity of mRNA-1403 and mRNA-1405 in participants 18-49 and 60-80 years of age Total N = 664 Design Ra
Slide 67: mRNA-1403 HBGA-blocking titers in older adults
Moderna R&D Day 2024| Latent + other virus vaccines A single dose of mRNA-1403 also elicited robust HBGA-blocking antibody titers against vaccine-matched NoV genogroup I and II genotypes in older adults Older adults (60-80 years old) Genotype II selected strain 1 Genotype I selected strain Genotype
Slide 68: mRNA-1403 titers in younger adults
Moderna R&D Day 2024| Latent + other virus vaccines A single dose of mRNA-1403 elicited robust HBGA-blocking antibody titers against vaccine-matched NoV genogroup I and II genotypes in younger adults Younger adults (18-49 years old) Genotype II selected strain 1 Genotype I selected strain Genotype I
Slide 69: Single dose of mRNA-1403 was well-tolerated
Moderna R&D Day 2024| Latent + other virus vaccines Single dose of mRNA-1403 was well-tolerated across all dose levels evaluated Younger adults Older adults (18-49 years old) (60-80 years old) Data from interim analysis on mRNA-1403 candidate through completion of Day 29 visits Single dose of mRNA-1
Slide 70: Norovirus mRNA-1403 Phase 1 safety
Moderna R&D Day 2024| Latent + other virus vaccines Norovirus mRNA-1403 Phase 1 Safety No safety concerns were identified through data cut-off There were no deaths or AEs leading to study withdrawal through data cut-off Within 28 days after any injection, there were no SAEs, AESIs, deaths, or AEs le
Slide 71: mRNA-1403 Phase 3 study design
Moderna R&D Day 2024| Latent + other virus vaccines mRNA-1403 Phase 3 study design Phase 3 was designed to test the efficacy, safety and immunogenicity of a trivalent norovirus vaccine Design Randomized, observer-blind, placebo-controlled study Phase 3 Study Design Number of participants ~25,000 adu
Slide 72: Norovirus summary
Moderna R&D Day 2024| Latent + other virus vaccines Norovirus summary ● Robust HBGA-blocking antibody titers observed against vaccine-matched norovirus genogroup I and II selected strains across all dose levels evaluated Immunogenicity ● Similar mRNA-1403 induced HBGA-blocking antibody titers observ
Slide 73: Rare disease therapeutics portfolio
Rare disease therapeutics portfolio Kyle Holen, M.D. SVP, Head of Development, Therapeutics and Oncology, Research & Development © 2024 Moderna, Inc. All rights reserved.
Slide 75: PA therapy (mRNA-3927) encodes for an intracellular enzyme
Moderna R&D Day 2024| Rare disease therapeutics PA therapy (mRNA-3927) encodes for an intracellular enzyme Moderna’s mRNA therapy for PA (mRNA-3927) encodes for two proteins that form the deficient enzyme PA biology • Changes in the PCCA and PCCB genes cause propionic acidemia Mitochondrion Valine M
Slide 76: mRNA-3927 encodes for PCCA and PCCB subunit proteins
Moderna R&D Day 2024| Rare disease therapeutics mRNA-3927 encodes for PCCA and PCCB subunit proteins to form an active PCC enzyme Mitochondrial matrix Propionyl-CoA Biotin carboxylase Methylmalonyl-CoA (PCC enzyme) dodecamer Active enzyme Liver Propionyl-CoA Liver cell Protein chain Ribosome PCCA su
Slide 77: Ongoing Phase 1/2 study in PA
Moderna R&D Day 2024| Rare disease therapeutics Ongoing Phase 1/2 study designed to evaluate safety and pharmacology of mRNA-3927 in participants with PA Arm 1 enabled dose selection, enrollment is ongoing in Arm 2 dose expansion, and Arm 3 infant cohort Primary endpoints: Safety and PK/PD Phase 1/2
Slide 78: PA: mRNA-3927-P101 Study Design
Moderna R&D Day 2024| Rare disease therapeutics PA: mRNA-3927-P101 Study Design PART 1: Dose Optimization PART 2: Dose Expansion PART 3: Infants Patients enrolled to better Patients enrolled to better Patients enrolled to expand age understand the dose understand efficacy cohort to include infants P
Slide 79: PA: Overall Phase 1/2 clinical experience
Moderna R&D Day 2024| Rare disease therapeutics PA: Overall Phase 1/ 2 clinical experience As of August 22, 2024, 22 participants have been dosed Thirteen participants have >1 year of dosing 31.3 cumulative patient-years of experience on study drug Longest duration of treatment is 3.1 years and medi
Slide 80: Metabolic decompensation events (MDEs) are serious
Moderna R&D Day 2024| Rare disease therapeutics Metabolic decompensation events (MDEs) are serious, clinically significant events in organic acidemias Presentation of MDEs in PA and MMA Identification and measurement of MDEs • PA & MMA are characterized by intermittent MDEs can be objectively identi
Slide 81: Summary of metabolic decompensation events (MDEs)
Moderna R&D Day 2024| Rare disease therapeutics Summary of metabolic decompensation events (MDEs) Cohort participants Pretreatment On treatment 0.3mg/kg q3w 0.3mg/kg q2w Relative risk for MDE among patients with prior MDE (95% CI) 0.45mg/kg q2w Overall: 0.27 (0.101, 0.711) Q2W: 0.19 (0.046, 0.808) 0
Slide 82: PA: relative MDE risk reduction improves and continues
Moderna R&D Day 2024| Rare disease therapeutics PA: relative MDE risk reduction improves and continues to show benefit MDE Data as of 25 Aug 2023 Data as of 24 May 2024 Overall 0.29 (0.106, 0.813) 0.27 (0.101, 0.711) RR (95% CI) Q2W Dosing 0.20 (0.035, 1.134) 0.19 (0.046, 0.808) RR (95% CI) 82 © 202
Slide 83: PA: Safety
Moderna R&D Day 2024| Rare disease therapeutics PA: Safety Generally well-tolerated to date No dose limiting toxicities Five cases of drug related serious adverse events reported in two participants (Vascular device (VD) infection Grade 2, VD infection Grade 3, Infusion site erythema Grade 2, and tw
Slide 84: PA (mRNA-3927) summary and next steps
Moderna R&D Day 2024| Rare disease therapeutics PA (mRNA-3927) summary and next steps ● Early results suggest potential decreases in annualized MDE frequency and PA-related hospitalizations compared to pre-treatment Clinical Results ● Cumulative treatment duration of over 31.3 patient years and Expe
Slide 86: Overview of methylmalonic acidemia (MMA) due to MUT deficiency
Moderna R&D Day 2024| Rare disease therapeutics Overview of methylmalonic acidemia (MMA) due to MUT deficiency Methylmalonic acidemia (MMA) refers to a rare, Mitochondrion Valine autosomal recessive acidemia Methionine Isoleucine Threonine Odd-chain fatty acids Propionicacid Cholesterol esters It is
Slide 87: Methylmalonic acidemia (MMA) has no approved therapies
Moderna R&D Day 2024| Rare disease therapeutics Methylmalonic acidemia (MMA) has no approved therapies MMA Clinical Manifestations Primarily a pediatric disease with • Recurrent episodes of life-threatening metabolic onset in early infancy; significant decompensations (MDEs) mortality and morbidity
Slide 89: Ongoing Phase 1/2 study in MMA
Moderna R&D Day 2024| Rare disease therapeutics Ongoing Phase 1/2 study designed to evaluate safety and pharmacology of mRNA-3705 in participants with MMA P101 Dose Optimization Design (3 + 3 design) Dose Optimization Stage Endpoints: • Primary endpoints: safety and Cohort 1 (0.1 mg/kg IV q3wk) tole
Slide 90: mRNA-3705-P101 demographics and baseline characteristics
Moderna R&D Day 2024| Rare disease therapeutics mRNA-3705-P101: Summary of demographics and baseline characteristics Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 0.1 mg/kg 0.2 mg/kg 0.4 mg/kg 0.6 mg/kg 0.9 mg/kg Total Q3W Q2W Q2W Q2W Q2W (N=15) (N=3) (N=3) (N=3) (N=3) (N=3) Age at enrollment, median
Slide 91: mRNA-3705: Clinical experience to date
Moderna R&D Day 2024| Rare disease therapeutics mRNA-3705: Clinical experience to date As of April 8, 2024*: • Fifteen participants have been dosed, with a total of 384 doses administered • Total cumulative treatment duration among all participants is ~17.3 patient-years – Median treatment duration
Slide 92: Biomarkers to evaluate pharmacodynamics of mRNA-3705
Moderna R&D Day 2024| Rare disease therapeutics Biomarkers to evaluate pharmacodynamics of mRNA-3705 Methylmalonic acid and 2- methylcitrate represent primary biomarkers proximal to the enzyme deficiency Changes in concentrations of 3-Hydroxypropionate (3HP) methylmalonic acid generally correlate N-
Slide 93: Biomarker response mirrors that seen in liver transplant
Moderna R&D Day 2024| Rare disease therapeutics mRNA-3705-P101: pattern of biomarker response mirrors that seen in liver transplant • Liver transplant is thought to promote metabolic Patient atypical disease phenotype stability in patients with MMA prior to study • MMA levels typically decrease afte
Slide 94: Reductions in MMA and other pathway biomarkers
Moderna R&D Day 2024| Rare disease therapeutics mRNA-3705-P101: Participants who demonstrate reductions in MMA also show changes in other pathway biomarkers Median Concentration (μM) Baseline vs. On Treatment Participants with at least a 25% reduction in MMA levels are shown Data as of 08 Apr 2024 9
Slide 95: Promising initial data on clinical endpoints
Moderna R&D Day 2024| Rare disease therapeutics mRNA-3705-P101: Promising initial data on clinical endpoints Trends towards fewer MMA-related hospitalizations and Metabolic Decompensation Events (MDEs) Pretreatment On study Participant: 1 MMA-related Cohort 1 (0.1mg/kg q3w) 2 hospitalizations: 3 Yea
Slide 96: Safety of mRNA-3705: Overall summary to date
Moderna R&D Day 2024| Rare disease therapeutics Safety of mRNA-3705: Overall summary to date No deaths or discontinuations due to safety-related reasons Three discontinuations in the extension for non-safety reasons No events meeting dose-limiting toxicity criteria have been observed 1 serious adver
Slide 97: FDA START Pilot Program
Moderna R&D Day 2024| Rare disease therapeutics US FDA Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program As part of FDA’s initiative to accelerate the pace of development in rare diseases, mRNA- 3705 was 1 of 4 programs to be accepted into the CBER START pilot pro
Slide 98: MMA (mRNA-3705) summary and next steps
Moderna R&D Day 2024| Rare disease therapeutics MMA (mRNA-3705) summary and next steps ● Early results suggest potential decreases in annualized rates of MMA-related hospitalizations and MDEs compared to pre-treatment ratees Clinical Results ● Reductions in methylmalonic acid and other pathway bioma
Slide 99: Oncology therapeutics portfolio
Oncology therapeutics portfolio Kyle Holen, M.D. SVP, Head of Development, Therapeutics and Oncology, Research & Development © 2024 Moderna, Inc. All rights reserved.
Slide 100: INT developmental history builds on decades of scientific advancements
Moderna R&D Day 2024| Oncology therapeutics INT developmental history builds on decades of scientific advancements 1960 – Current: mRNA and LNP advancements 1970 – Current: Tumor associated antigen modalities fail to demonstrate meaningful clinical improvement; increased focus on neoantigens 1977 –
Slide 101: Honoring Dr. Jeff Weber
Moderna R&D Day 2024| Oncology therapeutics Honoring Dr. Jeff Weber Jeffrey S. Weber, MD, PhD, FASCO, an internationally recognized pioneer in melanoma and cancer immunotherapy, died on August 19, 2024. He most recently served as Deputy Director of the Laura and Isaac Perlmutter Cancer Center at New
Slide 102: Phase 2 INT adjuvant melanoma study: 3-year update
Phase 2 INT adjuvant melanoma study: 3-year update Michelle Brown Vice President, Portfolio Leadership, INT © 2024 Moderna, Inc. All rights reserved.
Slide 106: RFS of pembrolizumab control arm in P201
Moderna R&D Day 2024| Oncology therapeutics RFS of pembrolizumab control arm in P201 consistent with historical studies Checkmate-238 and Keynote-054 Increasing confidence in the treatment effect observed with the INT + pembro combination over pembro monotherapy Checkmate-238 12mo RFS: 70.5% vs. 60.
Slide 113: Adjuvant melanoma Phase 3 (mRNA-4157 / V940) trial design
Moderna R&D Day 2024| Oncology therapeutics Adjuvant melanoma Phase 3 (mRNA-4157 / V940) trial design Primary endpoint is recurrence free survival compared to pembrolizumab Randomized, double-blind placebo controlled, INT + pembrolizumab (KEYTRUDA®) vs. placebo + pembrolizumab (2:1) (INTerpath-001)
Slide 114: INT development program
Moderna R&D Day 2024| Oncology therapeutics INT development program Phase 3 studies Phase 2/3 and Phase 2 studies ● Adjuvant melanoma ● Randomized Phase 2/3 neoadjuvant/adjuvant cutaneous ● Adjuvant non-small cell lung cancer squamous cell carcinoma ● Randomized Phase 2 adjuvant high risk muscle inv
Slide 115: Merck's and Moderna's global INT program has expanded
Moderna R&D Day 2024| Oncology therapeutics Merck’s and Moderna’s global INT program has expanded to more than 45 countries P101 – Phase 1 (multiple tumor types) P201 – Ph2 adjuvant melanoma Ph3 adjuvant melanoma Ph3 adjuvant NSCLC Ph2 adjuvant RCC Ph2 adjuvant MIBC Ph2/3 peri-adjuvant cSCC 115 © 20
Slide 116: INT Summary
Moderna R&D Day 2024| Oncology therapeutics INT Summary ● mRNA-4157 (V940) + pembrolizumab demonstrated a durable clinically significant improvement in RFS & DMFS at 3 years follow-up compared to standard of care Clinical Results pembrolizumab in high-risk resected melanoma: and Experience − 49% red
Slide 118: Our R&D investments delivered many positive results
Moderna R&D Day 2024| R&D Portfolio Overview Our R&D investments delivered many positive results in the past year Two major Four positive Proof of concept Positive early proof-of-concept approvals Phase 3s strengthened by data in six other programs ongoing durability Next-gen COVID COVID mRNA-1283 m
Slide 119: Discontinued programs
Moderna R&D Day 2024| R&D Portfolio Overview Discontinued programs Respiratory vaccines Oncology therapeutics Cardiovascular therapeutics Endemic HCoV KRAS antigen-specific therapy Relaxin (mRNA-1287) (mRNA-5671) (mRNA-0184) Preclinical program will not No further development plans Program is wrappi
Slide 120: Our R&D strategy
Moderna R&D Day 2024| R&D Portfolio Overview Our R&D strategy 2021-2023 2023-2026 2026-2028 Build a pipeline Deliver respiratory approvals Deliver non-respiratory approvals Invest pandemic proceeds Build large portfolio of Expand commercial portfolio into in diverse pipeline 5 commercial vaccines ca
Slide 122: Revisiting Moderna operating principles
2024| Financial Review Revisiting Moderna operating principles We expect our commercial respiratory franchise to 1 be profitable in 2024 Update| We plan to invest in our late-stage pipeline to drive Day 2 significant organic sales growth 2023 3QR&D Moderna 3 We will be disciplined and will adjust ou
Slide 123: Profitable respiratory franchise
Moderna R&D Day 2024| Financial Review 1 Profitable respiratory franchise Commercial Respiratory P&L (Spikevax and mRESVIA) Currently marketed portfolio is cash flow positive 2024 ($B) Sales $3.0-3.5 Cost of Sales 1.4 ● Revenue to grow with new Gross Profit 1.6 – 2.1 program launches SG&A 1.2 ● COS
Slide 124: Revisiting Moderna operating principles
2024| Financial Review Revisiting Moderna operating principles We expect our commercial respiratory franchise to 1 be profitable in 2024 Update| We plan to invest in our late-stage pipeline to drive Day 2 significant organic sales growth 2023 3QR&D Moderna 3 We will be disciplined and will adjust ou
Slide 125: Late-stage pipeline investment to drive sales growth
Moderna R&D Day 2024| Financial Review 2 Late-stage pipeline investment to drive sales growth We have generated a diverse portfolio with 10 programs currently in late-stage development addressing large TAMs TAM Product benefit Next-gen COVID mRNA-1283 ~$8B Strong efficacy, improved storage Seasonal
Slide 126: Norovirus meets our current prioritization criteria
Moderna R&D Day 2024| Financial Review 2 Late-stage pipeline investment to drive sales growth Norovirus meets our current prioritization criteria for our next pivotal investment Norovirus opportunity in the U.S. Near-term launch potential Target population Market segments 155 million Older adults Di
Slide 127: Moderna's success developing medicines gives us confidence
Moderna R&D Day 2024| Financial Review 2 Late-stage pipeline investment to drive sales growth Moderna’s success developing medicines gives us confidence to invest in our pipeline Moderna’s rate of success with our platform Recent highlights technology is higher than industry standard1 Respiratory pr
Slide 128: Revisiting Moderna operating principles
2024| Financial Review Revisiting Moderna operating principles We expect our commercial respiratory franchise to 1 be profitable in 2024 Update| Day 2 We plan to invest in our late-stage pipeline to drive significant organic sales growth 2023 3QR&D Moderna 3 We will be disciplined and will adjust ou
Slide 129: Disciplined investment
Moderna R&D Day 2024| Financial Review 3 Disciplined investment We are investing in our prioritized programs while lowering overall R&D expense ● Reducing 2025 - 2028 R&D investment from $20B to $16B ● Expect to complete majority of Respiratory investment by 2026 ● Increasing R&D investments in Onco
Slide 130: Revisiting Moderna operating principles
2024| Financial Review Revisiting Moderna operating principles We expect our commercial respiratory franchise to 1 be profitable in 2024 Update| Day 2 We plan to invest in our late-stage pipeline to drive significant organic sales growth 2023 3QR&D Moderna 3 We will be disciplined and will adjust ou
Slide 131: Break-even on a cash cost basis
Moderna R&D Day 2024| Financial Review 4 Break-even on a cash cost basis On a cash cost basis, we expect to break even at ~$6B in revenue Reconciliation of 2024E Projected 2028 cash operating GAAP operating expenses1 expenses In billions $ In billions $ Assumes $6B in revenue Consistent with our pro
Slide 132: Revisiting Moderna operating principles
2024| Financial Review Revisiting Moderna operating principles We expect our commercial respiratory franchise to 1 be profitable in 2024 Update| Day 2 We plan to invest in our late-stage pipeline to drive significant organic sales growth 2023 3QR&D Moderna 3 We will be disciplined and will adjust ou
Slide 133: Balance sheet sufficient to fund plan
Moderna R&D Day 2024| Financial Review 5 Balance sheet sufficient to fund plan 2025 and 2026-2028: revising our financial framework for full year 2025 for full years 2026-2028 Expectations Expectations Revenue $2.5 – 3.5 billion 25%+ CAGR (at mid-point of 2025 expected sales) cO New product launch r
Slide 134: Key financial takeaways
Moderna R&D Day 2024| Financial Review Key financial takeaways Portfolio prioritization We assume Our cost of sales We plan to break Our current and cost efficiency revenue to be framework even on a cash balance sheet programs reduce $2.5 – 3.5B in remains intact cost basis with $6B is sufficient to
Slide 136: We have an exciting opportunity to deliver on our mission
Moderna R&D Day 2024| Looking forward We have an exciting opportunity to deliver on our mission over the next 3 years With approval of With CMV and With our With our rare disease our positive Phase 3 Norovirus, we have individualized programs, MMA and programs, we the potential to neoantigen PA, we
Slide 137: Multiple product approvals drive 25%+ revenue growth
Moderna R&D Day 2024| Looking forward Multiple product approvals drive 25%+ revenue growth in 2026-2028 2023 2024 2025 2026 2027 2028 Spikevax mRESVIA Next-gen COVID (mRNA-1283) Flu + COVID 50+ (mRNA-1083) RSV 18-59 high risk (mRNA-1345) Flu (mRNA-1010) CMV (mRNA-1647) Norovirus (mRNA-1403) PA (mRNA
Slide 138: We were ready for an earlier COVID vaccine approval
Moderna R&D Day 2024| Looking forward We were ready for an earlier COVID vaccine approval in the 2024/2025 season in the U.S. We have made significant progress in our U.S. commercial operations for the 2024-2025 season 2024 COVID vaccine approval was 19 days earlier than in 2023 138 © 2024 Moderna,
Slide 139: RSV outlook
Moderna R&D Day 2024| Looking forward RSV outlook 2024 mRESVIA uptake in the U.S. has been slower than expected We expect higher market share in 2025 with expanded label (18-59 high-risk), and ability to compete for contracts earlier in the season Recent European approval enables us to launch across
Slide 140: Our priorities to deliver on our vision
Moderna R&D Day 2024| Looking forward Our 3 priorities to deliver on our vision 1 Drive use of Spikevax and mRESVIA vaccines 2 Focus on 10 product approvals over the next 3 years to drive sales growth Deliver cost efficiency across the business and slow the pace of R&D 3 investment, reducing it by $

Moderna — Investor Day (September 2024) on 6ix

Moderna — Investor Day (September 2024)

Slide 1: Moderna Investor Day

Slide 2: Forward-looking statements and disclaimer

Slide 3: Introduction

Slide 4: Our vision is becoming reality

Slide 5: Our vision is becoming reality

Slide 6: Our vision is becoming reality

Slide 7: We are adapting our business strategy

Slide 8: Our priorities: Drive use of Spikevax and mRESVIA

Slide 9: Respiratory virus hospitalization rates in 65+

Slide 10: Impact of COVID hospitalization on people 65+

Slide 11: The risk of Long COVID

Slide 12: Focus on 10 product approvals

Slide 13: Deliver cost efficiency and slow R&D investment

Slide 14: R&D Day Agenda

Slide 15: R&D strategy

Slide 16: Our R&D strategy

Slide 17: Our R&D investments delivered many positive results

Slide 18: Our R&D strategy

Slide 19: Pacing new R&D investments will reduce annual R&D expense

Slide 20: Respiratory vaccines portfolio

Slide 21: COVID-19

Slide 22: Continued need for COVID-19 vaccines in U.S.

Slide 23: Spikevax (mRNA-1273) availability

Slide 24: mRNA-1283 pivotal Phase 3 trial design

Slide 25: Relative vaccine efficacy of mRNA-1283 vs mRNA-1273

Slide 26: Relative vaccine efficacy by age group

Slide 27: mRNA-1283 antibody response vs mRNA-1273

Slide 28: Antibody response against BA.4/5 by age group

Slide 29: Reactogenicity profile of mRNA-1283 similar to mRNA-1273

Slide 30: Reactogenicity by age group

Slide 31: mRNA-1283 pivotal Phase 3 safety

Slide 32: mRNA-1283 summary and next steps

Slide 33: Influenza

Slide 34: Seasonal influenza causes respiratory illnesses

Slide 35: mRNA-1010 Phase 3 older adult study overview

Slide 36: mRNA-1010 met all primary immunogenicity endpoints

Slide 37: mRNA-1010 reactogenicity profile

Slide 38: mRNA-1010 Phase 3 older adult safety

Slide 39: mRNA-1010 vaccine efficacy study (P304)

Slide 40: Flu (mRNA-1010) summary and next steps

Slide 41: Respiratory Combinations

Slide 42: Burden of flu and COVID underscores combination vaccine

Slide 43: mRNA-1083-P301 Phase 3 study

Slide 44: mRNA-1083 met all primary immunogenicity endpoints

Slide 45: mRNA-1083 acceptable reactogenicity profile

Slide 46: mRNA-1083 safety

Slide 47: Flu + COVID combo (mRNA-1083) summary and next steps

Slide 48: RSV mRNA-1345

Slide 49: RSV hospitalization rate higher in older adults

Slide 50: mRESVIA (mRNA-1345) availability

Slide 51: mRNA-1345 Phase 3 P303 Part A

Slide 52: mRNA-1345 met all primary immunogenicity endpoints

Slide 53: mRNA-1345 well-tolerated in high-risk adults

Slide 54: mRNA-1345 Part A safety

Slide 55: mRNA-1345 summary and next steps

Slide 56: Latent + other viruses vaccines portfolio

Slide 57: CMV mRNA-1647

Slide 58: Cytomegalovirus (CMV) Overview

Slide 59: CMV vaccine (mRNA-1647) Phase 3 trial

Slide 60: Overview of primary efficacy endpoint

Slide 61: CMV vaccine summary and next steps

Slide 62: Norovirus mRNA-1403

Slide 63: Norovirus is a leading cause of diarrheal disease

Slide 64: Noroviruses are a diverse group with limited cross-genotype protection

Slide 65: mRNA technology provides ability to make multivalent VLPs

Slide 66: mRNA-1403/1405 Phase 1 trial design

Slide 67: mRNA-1403 HBGA-blocking titers in older adults

Slide 68: mRNA-1403 titers in younger adults

Slide 69: Single dose of mRNA-1403 was well-tolerated

Slide 70: Norovirus mRNA-1403 Phase 1 safety

Slide 71: mRNA-1403 Phase 3 study design

Slide 72: Norovirus summary

Slide 73: Rare disease therapeutics portfolio

Slide 74: PA

Slide 75: PA therapy (mRNA-3927) encodes for an intracellular enzyme

Slide 76: mRNA-3927 encodes for PCCA and PCCB subunit proteins

Slide 77: Ongoing Phase 1/2 study in PA

Slide 78: PA: mRNA-3927-P101 Study Design

Slide 79: PA: Overall Phase 1/2 clinical experience