Moderna, Inc. · NASDAQ:MRNA
Moderna — Investor Day (September 2022)
179 slides from Moderna's investor day presentation, Sep 8, 2022
Slide 1: Annual R&D Day
Annual R&D Day September 8th, 2022 © 2022 M oderna, Inc. All rights reserved.
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 vision for mRNA science; the timing of data from Moderna's trials of its p
Slide 3: mRNA is the software of life
mRNA is the software of life Binary System Quaternary System mRNA is an information molecule 3 © 2022 M oderna, Inc. All rights reserved.
Slide 4: Moderna's vision for mRNA science
Moderna’s vision for mRNA science 1 2 Invest in science to invent novel ways to deliver mRNA is an mRNA into various cell types – each will be a information molecule new application, which we call a modality Medicine 2 Medicine 2 Medicine 2 Medicine 2 Medicine 2 Medicine 2 Medicine 2 Medicine 2 Medi
Slide 5: Proof-of-concept data from our sentinel programs de-risk our modalities
Proof-of-concept data from our sentinel programs de-risk our modalities and accelerate our development plans EXPLORATORY EMERGING ESTABLISHED Inhaled Localized Intratumoral Cancer Systemic secreted Systemic Prophylactic Modalities pulmonary regenerative immuno- vaccines & cell surface intracellular
Slide 6: Proof-of-concept data in vaccines were an enabler
Proof-of-concept data in vaccines were an enabler Expansion of vaccines modality Proof-of-concept data achieved in vaccines • Enabled Moderna to quickly develop a vaccine against COVID-19 • Expanded vaccine pipeline with the addition of new vaccine development candidates – R&D Day 2019: 7 vaccine pr
Slide 7: Platform advantages and increased investments accelerated vaccine pipeline development
Platform advantages and increased investments accelerated vaccine pipeline development Expansion of Increased investments and execution vaccines modality accelerated the development of vaccines • 4 vaccines in late-stage, Phase 3 programs – R&D Day 2019: 0 late-stage programs – R&D Day 2022: 4 late-
Slide 8: Early data from our ongoing PA trial is encouraging
Early data from our ongoing PA trial is encouraging and shows potential to have a meaningful clinical impact Systemic intracellular Encouraging interim data from PA Phase 1/2 modality Paramount study • Generally well-tolerated safety profile to date • Encouraging data shows decrease in the number of
Slide 9: Encouraging signs in a second rare disease
Encouraging signs in a second rare disease Systemic intracellular Encouraging interim data from GSD1a Phase 1/2 modality Ba1ance study • Early data on safety and pharmacodynamics are consistent and encouraging GSD1a • Announcing new rare disease candidate: Ornithine transcarbamylase deficiency (OTC)
Slide 10: mRNA is a new class of medicines
mRNA is a new class of medicines • COVID vaccines and boosters established mRNA technology for respiratory vaccines • Respiratory vaccines in Phase 3: seasonal flu, RSV data readouts and launches are next • We now have encouraging data from our first mRNA therapeutic encoding for an intracellular pr
Slide 11: Today's agenda
Today’s agenda Introduction Stéphane Bancel, Chief Executive Officer R&D Day 2022 Overview Stephen Hoge, M.D., President mRNA Therapeutics Dr. Mark S. Korson, Director of Physician Support Service and Education, VMP Rare Diseases Genetics • Organic acidemias ov erview and real-world burden of Ruchir
Slide 12: R&D Day Introduction
R&D Day Introduction Stephen Hoge, M.D. President © 2022 M oderna, Inc. All rights reserved.
Slide 13: Moderna has a diverse portfolio of vaccine and therapeutic programs
Moderna has a diverse portfolio of vaccine and therapeutic programs in preclinical and clinical development Preclinical Phase 1 Phase 2 Phase 3 Licensed mRNA-1273 SARS-CoV-2 mRNA-1345 RSV (older adults) mRNA-1010 Seasonal Flu (HA) mRNA-1283 SARS-CoV-2 mRNA-1073 COVID + Flu Respiratory Infectious mRN
Slide 14: Today we are focusing on late-stage vaccines and proof-of-concept programs
Today we are focusing on late-stage vaccines and proof-of- concept programs Preclinical Phase 1 Phase 2 Phase 3 Licensed mRNA-1273 SARS-CoV-2 mRNA-1345 RSV (older adults) mRNA-1010 Seasonal Flu (HA) mRNA-1283 SARS-CoV-2 mRNA-1073 COVID + Flu Respiratory Infectious mRNA-1020 Seasonal Flu (HA+NA) Dise
Slide 15: Today we are focusing on late-stage vaccines and proof-of-concept programs
Today we are focusing on late-stage vaccines and proof-of- concept programs mRNA therapeutics review Late-stage vaccines • Review of interim PA data from • Overview of Phase 3 trials: ongoing Phase 1/2, m ultiple- Primary endpoints and timing dose study for data readouts – COVID boosters & • Review
Slide 16: Proof-of-concept data from our sentinel programs de-risk our modalities
Proof-of-concept data from our sentinel programs de-risk our modalities and accelerate our development plans EXPLORATORY EMERGING ESTABLISHED Inhaled Localized Intratumoral Cancer Systemic secreted Systemic Prophylactic Modalities pulmonary regenerative immuno- vaccines & cell surface intracellular
Slide 17: Proof-of-concept data from our sentinel programs de-risk our modalities
Proof-of-concept data from our sentinel programs de-risk our modalities and accelerate our development plans EXPLORATORY EMERGING ESTABLISHED Inhaled Localized Intratumoral Cancer Systemic secreted Systemic Prophylactic Modalities pulmonary regenerative immuno- vaccines & cell surface intracellular
Slide 18: Moderna has two distinct LNP delivery systems
Moderna has two distinct LNP delivery systems dosing in rare disease clinical trials Rare Diseases in Systemic Intracellular Modality PA MMA Organic acidemias use LNP 1 (same as Chikungunya antibody program) Ph 1/2 Ph 1/2 GSD1a OTC GSD1a and OTC use LNP 2 (different LNP with distinct pharmacology) P
Slide 19: Encouraging early clinical signs in rare disease modality
Encouraging early clinical signs in rare disease modality PA (mRNA-3927) • 6 patient-years of experience on drug and all participants eligible have decided to continue on Open Label Extension (OLE) Study • Generally well-tolerated to date • Reduction in biomarker (3-HP levels) observed • Encouraging
Slide 20: Dr. Mark S. Korson biography
Dr. Mark S. Korson biography Dr. Korson graduated in medicine from the University of Toronto and completed a pediatric residency at Toronto’s Hospital for Sick Children, followed by a genetics/metabolism fellowship at Boston’s Children's Hospital. He directed the metabolic clinics at Boston Children
Slide 21: Therapy for PA + MMA: The need for something better
Therapy for PA + MMA: The need for something better Mark S. Korson, MD VMP Genetics
Slide 22: The story of PKU is the story of metabolic disease
The story of PKU is the story of the specialty of metabolic disease
Slide 23: NO ID AMINO
NO AMINO AMINO AMINO AMINO AMINO AMINO ID ACID ACID ACID ACID ACID ACID PROTEIN
Slide 24: Phenylalanine Tyrosine
PHENYLALANINE Phenylalanine hydroxylase TYROSINE
Slide 25: Phenylalanine Tyrosine
PHENYLALANINE Phenylalanine hydroxylase TYROSINE Dr. Asbjorn Folling, Norway
Slide 26: Phenylalanine Tyrosine
PHENYLKETONES: PHENYLPYRUVATE PHENYLALANINE PHENYLLACTATE PHENYLACETATE PHENYLETHYLAMINE Phenylalanine hydroxylase TYROSINE
Slide 27: Phenylketonuria
PHENYLALANINE PHENYLKETONURIA Phenylalanine hydroxylase TYROSINE
Slide 28: Phenylketonuria (PKU) Symptoms
PHENYLKETONURIA (PKU) Symptoms Intellectual disability Seizures Psychiatric symptoms Lighter pigmentation of skin, hair Skin rash
Slide 29: PKU – schneiderzitzen
PKU – ”schneiderzitzen”
Slide 30: Phenylketonuria (PKU) Pathophysiology
PHENYLKETONURIA (PKU) Pathophysiology Intellectual disability PHE Seizures PHE Psychiatric symptoms PHE Lighter pigmentation TYR Skin rash TYR
Slide 31: A dietary approach to metabolic disease
A DIETARY APPROACH TO METABOLIC DISEASE Horst Bickel (1954) proposed a low PHE diet 2 year old girl with PKU: • PHE dropped • Phenylketones cleared • Improved in developmental tasks
Slide 32: A dietary approach to metabolic disease
A DIETARY APPROACH TO METABOLIC DISEASE Horst Bickel (1954) proposed a low PHE diet 2 year old girl with PKU: • Reversed when restarted on a high PHE diet
Slide 33: Substrate restriction – PKU
DIETARY THERAPY SUBSTRATE RESTRICTION – PKU • Restricting natural protein → inadequate protein intake
Slide 34: Substrate restriction – PKU
DIETARY THERAPY SUBSTRATE RESTRICTION – PKU • Restricting natural protein → inadequate protein intake P NATURAL PROTEIN Diet No PHE
Slide 35: Substrate restriction – PKU
DIETARY THERAPY SUBSTRATE RESTRICTION – PKU • Restricting natural protein → inadequate protein intake P NATURAL PROTEIN Diet No PHE
Slide 36: Foods forbidden from amino acid-restricted diets
Foods forbidden from amino acid-restricted diets
Slide 37: Permitted - fruit
Permitted - fruit
Slide 38: Permitted - vegetables
Permitted - vegetables
Slide 39: Permitted - foods lower in protein content
Permitted - foods lower in protein content
Slide 40: The PKU diet, circa 1980s
THE PKU DIET, circa 1980s
Slide 41: A few 'low protein' foods
'b-bar a Hi i i A FEW ‘LOW PROTEIN’ FOODS
Slide 42: Recommended uniform screening panel - 2022
RECOMMENDED UNIFORM SCREENING PANEL - 2022 Amino acid disorders Organic acid disorders Fatty acid oxidation Phenylketonuria Propionic acidemia defects Homocystinuria Methylmalonic acidemia MCAD deficiency Maple syrup urine disease (MMA, mutase) VLCAD deficiency Tyrosinemia type I MMA (cobalamin diso
Slide 43: Success of PKU screening → maternal PKU
SUCCESS OF PKU SCREENING → MATERNAL PKU Cognitive/motor disability (92%) Small head (73%) In utero growth retardation (40%) Heart defects (15%)
Slide 44: Inadequate PKU management
INADEQUATE PKU MANAGEMENT • Inattention Executive function problems • Cognitive rigidity • Lack of impulse control • Anxiety Psychiatric symptoms • Depression • Phobia Issues with relationships
Slide 45: Challenges to management
CHALLENGES TO MANAGEMENT Adherence difficulty Neurocog/ Increased neuropsych PHE symptoms levels Adapted from Brittany Holmes
Slide 46: Problem!
PROBLEM! Survey of 3772 patients with PKU (US): • % of patients who have elevated PHE levels • 18-29 yr = ~ 62% • 30 yr and older = ~ 71% • Adherence to PHE level monitoring • 37% of adults 30 + older up test once a year or less Jurecki et al, 2017 88% of adults with PKU are unable to adhere to a PH
Slide 47: Problem!
PROBLEM! Total phenylketonuria Phenylketonuria patients based patients Estimated on incidence of reported in the not in the Age (years) 1:12,707 (n) clinic (n) clinic, n (%) 0-4 1,677 1,357 320 (19) 5-12 2,598 1,924 674 (26) 13-18 1,977 1,306 671 (34) 19-24 1,993 1,036 957 (48) 25-45 6,741 1,557 5,1
Slide 48: What do patients want?
WHAT DO PATIENTS WANT? Survey by National PKU Alliance (625 patients) 77.7% - most desired lifestyle improvement: “To be able to increase my protein intake without increasing my symptoms of PKU” Brown CS + Lichter-Konecki U, 2015
Slide 49: PKU: from preclinical to marketed products
PKU: from preclinical to marketed products AGT1 m RNA- 3283 SYN- Marketed 200 SYN- HMI- UX-501 1618 102 Palyn- BMN- CDX- Kuvan CNSA- ziq 307 RTX- 6114 001 HMI- 134 SOM- MT1 103 0011 Pre-clinical Phase I Phase II Phase III / Pre-reg. Marketed SYN-200 Microbiome PAL CDX-6114 GI-stable PAL SYN-1618 Mic
Slide 50: Why am I talking to you about PKU??
Why am I talking to you about PKU??
Slide 51: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE CHOLESTEROL SIDE CHAINS PROPIONYL CoA ODD CHAIN FATS METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 52: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE CHOLESTEROL SIDE CHAINS PROPIONYL CoA PROPIONYL CoA ODD CHAIN CARBOXYLASE FATS METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 53: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE CHOLESTEROL SIDE CHAINS PROPIONYL CoA PROPIONIC ACIDEMIA ODD CHAIN FATS METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 54: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE CHOLESTEROL SIDE CHAINS PROPIONYL CoA ODD CHAIN FATS METHYLMALONYL CoA METHYLMALONYL CoA MUTASE SUCCINYL CoA KREBS CYCLE
Slide 55: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE CHOLESTEROL SIDE CHAINS PROPIONYL CoA ODD CHAIN FATS METHYLMALONYL CoA METHYLMALONIC ACIDEMIA SUCCINYL CoA KREBS CYCLE
Slide 56: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL SIDE CHAINS PROPIONYL CoA ODD CHAIN FATS METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 57: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS PROPIONYL CoA ODD CHAIN FATS METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 58: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 59: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 60: ILE VAL MET THR GUT BACTERIAL INTOXICATION LOW ENERGY
ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS INTOXICATION SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA LOW ENERGY
Slide 61: Metabolic crisis (aka Metabolic Decompensation Event)
METABOLIC CRISIS (aka Metabolic Decompensation Event) Symptoms Poor feeding, vomiting → dehydration Lethargy, altered consciousness → coma Looks “septic”
Slide 62: Progression of a metabolic crisis
PROGRESSION OF A METABOLIC CRISIS Advanced stage Apnea Slowing heart rate Seizures Hypothermia Generalized organ dysfunction Stroke Sudden death
Slide 63: Movements — Infant with an Organic Acidemia
Movements — Infant with an Organic Acidemia Video from JM Saudubray and Thierry Billette de Vilmeur © 2008-2017 Society for Inher ited Metabolic Disor der s www.simd.or g
Slide 64: Isolated MMA + PA – clinical syndromes (1)
ISOLATED MMA + PA – CLINICAL SYNDROMES (1) Neonatal Coma due to high ammonia Bone marrow suppression → infection Intracranial hemorrhage Diabetes mellitus Infantile spasms Adapted from C. Venditti, 2020
Slide 65: Isolated MMA + PA – clinical syndromes (2)
ISOLATED MMA + PA – CLINICAL SYNDROMES (2) Infancy/early “Pure” neurologic syndromes childhood “Brain dysfunction” Movement disorder, unsteady gait Pancreatitis Infection → crisis + multiorgan failure Diabetic ketoacidosis ”Stroke” Adapted from C. Venditti, 2020
Slide 66: Isolated MMA + PA – clinical syndromes (3)
ISOLATED MMA + PA – CLINICAL SYNDROMES (3) Adolescence Mental status changes Cardiac muscle failure (cardiomyopathy) Cardiac arrest Adapted from C. Venditti, 2020
Slide 67: Isolated MMA + PA – clinical syndromes (4)
ISOLATED MMA + PA – CLINICAL SYNDROMES (4) Adult Movement disorder Cardiomyopathy Isolated kidney disease Optic nerve atrophy → blindness Adapted from C. Venditti, 2020
Slide 68: How PA + MMA patients are managed
HOW PA + MMA PATIENTS ARE MANAGED
Slide 69: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 70: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
PROTEIN-RESTRICTED DIET ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 71: Substrate restriction – PA+MMA
DIETARY THERAPY SUBSTRATE RESTRICTION – PA+MMA • Restricting natural protein → inadequate protein intake NATURAL VIMT PROTEIN Diet No VAL, ILE, THR, MET
Slide 72: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
MEDICATIONS ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 73: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
MONITORING/MEDICATIONS ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 74: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
MEDICATIONS ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 75: ILE VAL MET THR GUT BACTERIAL KREBS CYCLE
MEDICATIONS ILE VAL MET THR GUT BACTERIAL PROPIONATE DIRECT TOXICITY CHOLESTEROL ACIDOSIS SIDE CHAINS SUPPRESSES PROPIONYL CoA BONE MARROW ODD CHAIN FATS HIGH AMMONIA METHYLMALONYL CoA SUCCINYL CoA KREBS CYCLE
Slide 76: So we have treatments for PA + MMA – yay!
SO WE HAVE TREATMENTS FOR PA + MMA – YAY!
Slide 77: This treatment plan is unsustainable – boo!
THIS TREATMENT PLAN IS UNSUSTAINABLE – BOO!
Slide 78: This treatment plan is unsustainable – boo!
THIS TREATMENT PLAN IS UNSUSTAINABLE – BOO! • These therapies address the symptoms; they don’t address the underlying problem • It’s like playing “medical whack-a-mole” • Patients and parents run ICUs at home • Think PKU therapy “on steroids”
Slide 79: We need a therapy that can provide working enzyme…
We need a therapy that can provide working enzyme…
Slide 80: Propionic Acidemia (PA)
Propionic Acidemia (PA) Ruchira Glaser, M.D., M.S. Senior Vice President, Therapeutic Area Head, Cardiovascular, Rare Diseases & Autoimmune © 2022 M oderna, Inc. All rights reserved.
Slide 81: PA therapy (mRNA-3927) encodes for an intracellular enzyme
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 Methionine ̶ These genes provide instructions for
Slide 82: mRNA-3927 encodes for PCCA and PCCB subunit proteins
mRNA-3927 encodes for PCCA and PCCB subunit proteins to form an active PCC enzyme Mitochondrial matrix Propionyl-CoA Biotin Methylmalonyl-CoA carboxylase (PCC enzyme) dodecamer Activ e enzyme Liver Propionyl-CoA Liver cell Protein chain Ribosome PCCA subunit Mitochondria PCCB subunit Encoded mRNAs E
Slide 83: Ongoing Phase 1/2 Study designed to evaluate safety and pharmacology of mRNA-3927
Ongoing Phase 1/2 Study designed to evaluate safety and pharmacology of mRNA-3927 in participants with PA First study testing an mRNA therapeutic for intracellular protein replacement Phase 1/2 Trial Design • Primary endpoints: Safety and PK/PD Cohort 1(0.3 mg/kg IV q3wk) N=3 • Secondary endpoints:
Slide 84: mRNA-3927: Summary of demographics and baseline characteristics
mRNA-3927: Summary of demographics and baseline characteristics Cohort 1 Cohort 2 Cohort 3 0.3 mg/kg q3W 0.3 mg/kg q2W 0.45 mg/kg q2W All (n=10) (n=4) (n=3) (n=3) Age at enrollment, median (years) 15.42 2.33 3.75 6.71 Min, Max 5.2 , 26.8 1.5 , 8.3 1.6, 15.3 1.5, 26.8 Age at disease onset, median (mo
Slide 85: Overall Phase 1/2 clinical experience to date
Overall Phase 1/ 2 clinical experience to date • Ten participants dosed • Three participants have >1 year of dosing • 6 patient-years of experience on drug • Over 120 intravenous doses administered • Study is ongoing; independent safety monitoring committee approved moving to fourth cohort (0.6 mg/k
Slide 86: Safety: Overall summary to date
Safety: Overall summary to date • Generally well-tolerated to date • No Dose Limiting Toxicities • No Drug Related Serious Adverse Events • No Discontinuations due to safety • Only drug related adverse events were mild to moderate infusion related reactions (<10% of doses) 86 © 2022 M oderna, Inc. A
Slide 87: Safety: Summary of all adverse events measured
Safety: Summary of all adverse events measured Adverse events (AEs) collected in the trial consist of treatment emergent adverse events (any AE reported after the start of dosing) and drug related AEs Cohort 1 Cohort 2 Cohort 3 Total 0.30 mg/kg Q3W 0.30 mg/kg Q2W 0.45 mg/kg Q2W (N=10) (N=4) (N=3) (N
Slide 88: Safety: Summary of serious adverse events
Safety: Summary of serious adverse events No drug-related SAEs; several SAEs due to underlying disease Cohort 1 Cohort 2 Cohort 3 Total 0.30 mg/kg Q3W 0.30 mg/kg Q2W 0.45 mg/kg Q2W (N=10) (N=4) (N=3) (N=3) All Serious Adverse Events 2 (50.0) 2 (66.7) 1 (33.3) 5 (50.0) Dyskinesia 0 1 (33.3) 0 1 (10.0
Slide 89: Safety: Summary of drug-related adverse events
Safety: Summary of drug-related adverse events All drug related AEs were mild to moderate infusion related reactions (IRRs) that occurred in cohort 1 only Cohort 1 Cohort 2 Cohort 3 Total 0.30 mg/kg Q3W 0.30 mg/kg Q2W 0.45 mg/kg Q2W (N=10) (N=4) (N=3) (N=3) Drug-related adverse events 2 (50.0) 0 0 2
Slide 90: Biomarkers to evaluate PK/PD of mRNA-3927
Biomarkers to evaluate PK/PD of mRNA-3927 Mitochondrion Valine Methionine • While several biomarkers have been Isoleucine Threonine described, their pattern in individual Odd-chain fattyacids Propionicacid Cholesterol esters (intestinal flora) patients over time and association with • • 3-hydroxypro
Slide 91: Baseline 3-HP biomarker levels highly variable across patients
Baseline 3-HP biomarker levels highly variable across patients • Each patient in the trial had four 3-HP values measured from blood draws taken before treatment • Pre-treatment 3-HP values are highly variable between patients and within patients PA genotype Patient ID PCCA 1, 5, 8 PCCB 2, 3, 4, 6, 7
Slide 92: Adaptive study design to identify optimal dose level and frequency
Adaptive study design to identify optimal dose level and frequency Dose Optimization Stage (up to 5 cohorts) 3 more participants may be enrolled in Participant • Shorten interval from 3 cohort to further enrolled characterize safety 3 participants dosed1 weeks to 2 weeks (Cohort 2) Open new cohort 2
Slide 93: Significant reduction in 3-HP biomarker observed
Significant reduction in 3-HP biomarker observed Cohort 1 (0.3 mg/kg Q3W) • 7/8 patients showed a numerical Cohort 2 (0.3 mg/kg Q2W) reduction in 3-HP Cohort 3 (0.45 mg/kg Q2W) Steady-state = 3-HP measurements taken at 93 © 2022 M oderna, Inc. All rights reserved. all visits post 3rd dose
Slide 94: Encouraging trend in 3-HP biomarker
Encouraging trend in 3-HP biomarker • Patients showed numerically lower 3-HP levels on treatment • Trend suggestive of potential dose response with a greater decline from baseline at 0.45 mg/kg -19% -34% Baseline= 3-HP measurements collected from pretreatment visits (N=4 visits/measurements per subj
Slide 95: Metabolic decompensation events are a potential primary endpoint
Metabolic decompensation events are a potential primary endpoint Protocol definition of MDE • Exacerbation of symptoms of propionic acidemia: Persistent vomiting, anorexia/failure to feed, lethargy or increased seizure activity and… • Requiring emergency medicalcare (ER or hospitalization admission)
Slide 96: Summary of metabolic decompensation events (MDEs)
Summary of metabolic decompensation events (MDEs) PRE-TREATMENT 12-MONTH RETROSPECTIVE PERIOD mRNA-3927 TREATMENT PERIOD 1 2 3 4 5 6 7 8 9 -12 months Day 1 12 months Exposure duration of 3.8 years in participants w ith ≥1 retrospectiv e MDE • 48% Relativ e risk reduction in MDE frequency (p-v alue =
Slide 97: Summary of Phase 1/2 preliminary data; study ongoing
Summary of Phase 1/2 preliminary data; study ongoing to identify optimal dose • Expanding clinical experience: 6 patient-years of experience on drug and all participants eligible have decided to continue drug on the Open Label Extension (OLE) Study • Safety: Generally well-tolerated to date with no
Slide 98: MMA (mRNA-3705) also ongoing in a Phase 1/2 study
MMA (mRNA-3705) also ongoing in a Phase 1/2 study Two cohorts are fully enrolled and we will have preliminary data by early 2023 • Evaluating the safety and pharmacology of mRNA-3705 in patients 1 year of age and older with MMA in a multiple ascending dose study • Secondary endpoints include inciden
Slide 99: Glycogen storage disease type 1a (GSD1a)
Glycogen storage disease type 1a (GSD1a) Geoffrey Rezvani, M.D. Executive Director, Program Leader (Cardiovascular and Emerging Therapeutics) © 2022 M oderna, Inc. All rights reserved.
Slide 100: Glycogen storage disease type 1a (GSD1a) overview
Glycogen storage disease type 1a (GSD1a) overview GSD1a refers to a rare inherited metabolic disease resulting from a deficiency in the metabolism of glucose Clinical manifestations GSD1a biology • Life-threatening hypoglycemia, ▪ GSD1a is caused by mutations within long-term liver & kidney damage t
Slide 101: Glycogen storage disease type 1a (GSD1a) overview
Glycogen storage disease type 1a (GSD1a) overview Significant unmet medical need Standard of care • No approved therapy for GSD1a • Current interventions include: – Strict diet control; frequent consumption of uncooked cornstarch to improve hypoglycemia – Feedings by gastric tube – Glycosade® (corns
Slide 102: GSD1a therapy (mRNA-3745) encodes for the G6Pase enzyme
GSD1a therapy (mRNA-3745) encodes for the G6Pase enzyme 102 © 2022 M oderna, Inc. All rights reserved.
Slide 103: Ongoing Phase 1 study of mRNA-3745 in GSD1a
Ongoing Phase 1 study of mRNA-3745 in GSD1a Orphan Drug Designation granted by U.S. FDA • Evaluate the safety and pharmacology of Phase 1 Trial Design mRNA-3745 in patients 18 years of age and older with GSD1a Cohort 1(Dose A) N=3-6 • Single ascending dose study: Challenging patients twice, on day 3
Slide 104: Safe first-in-human administration of mRNA-3745
Safe first-in-human administration of mRNA-3745 Intravenous infusion of mRNA-3745 with LNP2 without pre-medication was very well tolerated with only mild AEs Patient 1 Patient 2 • Female, 21 years old • Female, 18 years old • GSD1a diagnosed at 6 months of age, managed w ith • GSD1a diagnosed at 2 y
Slide 105: Emerging efficacy data in GSD1a
Emerging efficacy data in GSD1a Patient 1 (0.1 mg/kg) Maximum permitted Fast duration Baseline 4:48h (hours) Day 3 8:00 hrs (+3:12 hrs) 140 120 100 Fast terminated due to confirmed Glucose (mg/dl) 80 Baseline hypoglycemia after clinical symptoms 60 * Fingerstick: Hypoglycemia (<60 mg/dL) Evidence of
Slide 106: Emerging efficacy data in GSD1a
Emerging efficacy data in GSD1a Patient 1 (0.1 mg/kg) Maximum permitted Fast duration Baseline 4:48h (hours) Day 3 +3:12h 8:00h 140 120 100 Glucose (mg/dl) Baseline 80 60 Hypoglycemia * Fingerstick: (<60 mg/dL) 59 mg/dl 40 0 1 2 3 4 5 6 7 8 9 10 Hours 1508 8 Lactate 1256 6 (mmol/L) Sev ere lactate 1
Slide 107: Emerging efficacy data in GSD1a
Emerging efficacy data in GSD1a Patient 1 (0.1 mg/kg) Maximum permitted Fast duration Baseline 4:48h (hours) Day 3 +3:12h 8:00h 140 120 100 Glucose Day 3 (mg/dl) 80 Baseline Patient able to complete full fast (limited to 8 hours) 60 Hypoglycemia * Fingerstick: (<60 mg/dL) 59 mg/dl 40 Glucose and lac
Slide 108: Emerging efficacy data in GSD1a
Emerging efficacy data in GSD1a Patient 1 (0.1 mg/kg) Patient 2 (0.1 mg/kg) Maximum Maximum permitted permitted Fast duration Baseline 4:48h Baseline 7:10h (hours) Day 3 +3:12h 8:00h Day 3 +3:05h 10:15h 140 140 120 120 100 100 Glucose Day 3 (mg/dl) Baseline 80 80 Baseline 60 Hypoglycemia 60 * Finger
Slide 109: Emerging efficacy data in GSD1a
Emerging efficacy data in GSD1a Patient 1 (0.1 mg/kg) Patient 2 (0.1 mg/kg) Maximum Maximum permitted permitted* Fast duration Baseline 4:48h Baseline 7:10h (hours) Day 3 +3:12h 8:00h Day 3 +3:05h 10:15h 140 140 120 120 100 100 Glucose Day 3 Baseline Day 3 (mg/dl) 80 80 Baseline 60 Hypoglycemia 60 *
Slide 110: Improved fasting tolerance maintained through Day 8
Improved fasting tolerance maintained through Day 8 Slight decrease vs. day 3, consistent with G6Pase enzyme half-life 140 120 Glucose (mg/dl) 4:48h 100 +3:12h 8:00h* Pt 1 +68% 80 +2:37h 7:25h 60 +56% 40 0 1 2 3 4 5 6 7 8 9 10 Time (Hours) 140 7:10h 120 Glucose (mg/dl) 100 Pt 2 +3:05h 10:15h* +43% 8
Slide 111: mRNA-3745 for GSD1a – next steps
mRNA-3745 for GSD1a – next steps • Continue to evaluate safety of mRNA-3745 and LNP2 • Assess fast tolerance beyond day 8 • Exploring higher doses to extend potential repeat dose interval • Identify a dose to move to repeat dose study 111 © 2022 M oderna, Inc. All rights reserved.
Slide 112: Personalized Cancer Vaccine (PCV) Review
Personalized Cancer Vaccine (PCV) Review Michelle Brown, M.D., Ph.D. Executive Director, Program Leader, Oncology © 2022 M oderna, Inc. All rights reserved.
Slide 113: Personalized cancer vaccine (mRNA-4157)
Personalized cancer vaccine (mRNA-4157) Designed to target an individual patient’s unique tumor mutations Personalized Cancer Vaccines FFPE mRNA encoding up to 34 neoantigens Tissue Samples Tumor (biopsy) Administration Personalized drug design and Normal Manufacturing Rapid turnaround times Next Ge
Slide 114: PCV vaccine (mRNA-4157) elicits T cells required for curative cancer therapy
PCV vaccine (mRNA-4157) elicits T cells required for curative cancer therapy Designed to target an individual patient’s unique tumor mutations T cell Neoantigen concatemers TCR in single mRNA Ribosome Neoantigen Proteasome Vesicle Neoantigen protein chain ER Golgi Nucleus 114 © 2022 M oderna, Inc. A
Slide 115: Phase 1 study demonstrates PCV induces CD8 T-cell proliferation
Phase 1 study demonstrates PCV induces CD8 T-cell proliferation against selected neoantigens incorporated in vaccine Previously shared at ASCO 2019 • Greater than 3x increases in neoantigen specific CD8 T-cells were detected post 4th dose vaccination against 10 out of 18 class I targeted neoantigens
Slide 116: PCV (mRNA-4157) is ongoing in a Phase 2 trial
PCV (mRNA-4157) is ongoing in a Phase 2 trial Primary endpoint is recurrence free survival compared to pembrolizumab Patients with resected melanoma at high risk of recurrence Enrollment and randomization 2:1 • Randomized, placebo controlled, PCV + pembrolizumab (KEYTRUDA®) vs. pembrolizumab alone (
Slide 117: Previous studies in resected melanoma: Kaplan-Meier curves
Previous studies in resected melanoma population: Kaplan- Meier curves for Checkmate-238 and Keynote-054 Checkmate-238 12mo RFS: 70.5% vs. 60.8% Keynote-054 12mo RFS: 75.4% vs 61.0% Primary RFS analysis in the ITT Population Primary RFS analysis in the ITT Population 1. Checkmate-238:A Phase 3, Rand
Slide 118: Personalized cancer vaccine (PCV) summary
Personalized cancer vaccine (PCV) summary • Primary endpoint analysis is RFS; PCV + pembrolizumab vs. pembrolizumab alone • Primary endpoint analysis expected in 4Q 2022 • Previous PD-1 studies show a 12-month RFS of 70-75% • Goal to show an improved benefit in PCV + pembrolizumab arm compared to pe
Slide 119: Today's agenda
Today’s agenda Introduction Stéphane Bancel, Chief Executive Officer R&D Day 2022 Overview Stephen Hoge, M.D., President mRNA Therapeutics Dr. Mark S. Korson, Director of Physician Support Service and Education, VMP Rare Diseases Genetics • Organic acidemias ov erview and real-world burden of Ruchir
Slide 120: COVID Boosters & Respiratory Combination Vaccines
COVID Boosters & Respiratory Combination Vaccines Jacqueline Miller, M.D. SVP, Therapeutic Area Head, Infectious Diseases © 2022 M oderna, Inc. All rights reserved.
Slide 121: Moderna has launched two vaccine boosters
Moderna has launched two vaccine boosters to meet different market needs across the largest markets • Induced significantly higher titers than mRNA-1273 against the BA.1 mRNA-1273.214 and BA.4/5 sublineages in a clinical trial conducted before the fall booster season (25 µg of mRNA-1273 and 25 µg of
Slide 122: Clinical data supports COVID bivalent platform and .222 submission
Clinical data from Beta/1273 and Omicron BA.1/1273 supports COVID bivalent platform and .222 submission Local reactogenicity of BA.1 Omicron bivalent (mRNA-1273.214) as 4th dose similar to 2nd dose of primary series and 3rd dose of original (mRNA-1273) in adults Solicited local adverse reactions wit
Slide 123: Clinical data supports COVID bivalent platform and .222 submission
Clinical data from Beta/1273 and Omicron BA.1/1273 supports COVID bivalent platform and .222 submission Systemic reactogenicity of BA.1 Omicron bivalent (mRNA-1273.214) as 4th dose generally lower than 2nd dose of primary series and 3rd dose of mRNA-1273 in adults Solicited systemic adverse reaction
Slide 124: Clinical data supports COVID bivalent platform and .222 submission
Clinical data from Beta/1273 and Omicron BA.1/1273 supports COVID bivalent platform and .222 submission Bivalent Beta vaccine (mRNA-1273.211) as 3rd dose elicited higher neutralizing antibody responses in adults through 6 months compared to mRNA-1273 and monovalent Beta vaccine (mRNA-1273.351) Neut
Slide 125: Clinical data supports COVID bivalent platform and .222 submission
Clinical data from Beta/1273 and Omicron BA.1/1273 supports COVID bivalent platform and .222 submission Bivalent Beta vaccine (mRNA-1273.211) as 3rd dose elicited higher neutralizing antibody responses in adults through 6 months compared to mRNA-1273 Neut ralizing antibody responses in adult s throu
Slide 126: Clinical data supports COVID bivalent platform and .222 submission
Clinical data from Beta/1273 and Omicron BA.1/1273 supports COVID bivalent platform and .222 submission 4th dose (2nd booster) with BA.1 Omicron bivalent booster (mRNA-1273.214) resulted in higher neutralizing antibody titers against Omicron BA.4/BA.5 across age groups, including ≥65-year-olds, than
Slide 127: BA.4/5 Omicron-targeting bivalent booster ongoing in a clinical study
BA.4/5 Omicron-targeting bivalent booster (mRNA- 1273.222) ongoing in a clinical study P205 mRNA-1273.222 study • mRNA-1273.222 arm fully enrolled on August 25th • Primary objectives – Safety, reactogenicity mRNA-1272.222 (50 µg) mRNA-1273 (50 µg) – Immunogenicity: neutralizing antibody N=512 N=377
Slide 128: Advantages of mRNA platform accelerates authorization of up-to-date boosters
Advantages of mRNA platform accelerates authorization of up-to- date boosters Clinical data generated from bivalent platform: Advanced multiple variant booster vaccines (Beta, Delta, Omicron and bivalents) We can simultaneously move Chemistry, manufacture and control COVID variant boosters into the
Slide 129: mRNA platform allows for rapid development and manufacturing timelines
mRNA platform allows for rapid development and manufacturing timelines 9.1.2022 EU & Canada authorize mRNA-1273.214 8.15.2022 UK authorizes mRNA-1273.214 2H22 Scale manufacturing for .214/.222 8.31.2022 FDA authorizes mRNA-1273.222 1H22 Two variant vaccines into clinic 8.30.2022 • Omicron (BA.1)-spe
Slide 130: Rapid licensure of vaccines against COVID sets the stage for respiratory vaccines
Rapid licensure of vaccines against COVID sets the stage for respiratory vaccines and combinations mRNA-1273 licensed COVID (mRNA-1273) Seasonal Flu (mRNA-1010) RSV (mRNA-1345) .214, .222 SARS-CoV-2 spike protein HA glycoproteins RSV Prefusion F protein (A/H1N1, A/H3N2 and influenza Omicron (BA.1) v
Slide 131: Combination vaccines in pipeline
Combination vaccines in pipeline to leverage efficacy of standalone vaccines Current combination pipeline Older adults • COVID + flu (mRNA-1073) fully enrolled in Phase 1/2 • COVID + flu + RSV (mRNA-1230) in preclinical Pediatrics • hMPV + PIV3 (mRNA-1653) in Phase 1 • RSV + hMPV (mRNA-1365) in prec
Slide 132: Running co-administration studies to help prepare for launches
Running co-administration studies to help prepare for launches Phase 3 randomized, observer-blind study Evaluating safety, tolerability and immunogenicity of mRNA-1345, an mRNA vaccine targeting respiratory syncytial virus (RSV), when given alone or co-administered NCT05330975 with a seasonal influe
Slide 133: Seasonal Flu Vaccine Program
Seasonal Flu Vaccine Program Raffael Nachbagauer, M.D., Ph.D. Senior Director, Infectious Disease Development © 2022 M oderna, Inc. All rights reserved.
Slide 134: Seasonal influenza (flu) overview
Seasonal influenza (flu) overview Influenza (influenza A and influenza B) occurs seasonally and Influenza symptoms & complications varies in severity each year, causing respiratory illnesses and placing a substantial burden on healthcare systems Fever Cough Sore throat Disease burden: Symptoms Nasal
Slide 135: mRNA-1010 is our influenza vaccine candidate furthest advanced
mRNA-1010 is our influenza vaccine candidate furthest advanced in clinical development mRNA encoding for hemagglutinin (HA) glycoproteins of 4 flu strains HA glycoproteins (A H1N1, H3N2 and influenza B Yamagata and Victoria lineages) Ribosome Encoded Golgi mRNAs Endoplasmic Cytosol reticulum Nucleus
Slide 136: Two Phase 3 studies will support licensure of mRNA-1010
Two Phase 3 studies will support licensure of mRNA-1010 Immunogenicity trial in Southern Hemisphere ongoing; efficacy trial in Northern Hemisphere expected to start in the fall Immunogenicity trial Efficacy trial • Will be conducted in Northern • Study ongoing in Southern Hemisphere Hemisphere • Tar
Slide 137: mRNA-1010 Phase 3 immunogenicity study in adults 18+ is fully enrolled
mRNA-1010 Phase 3 immunogenicity study in adults 18+ is fully enrolled • Number of participants: ~6,000 – ~30% of participants ≥ 50 to < 65 years old Ph 3 immunogenicity study design – ~20% of participants ≥ 65 years old • Primary endpoints – Safety – Non-inferior immunogenicity (GMT and mRNA-1010 (
Slide 138: mRNA-1010 Phase 3 efficacy study in adults 50+
mRNA-1010 Phase 3 efficacy study in adults 50+ Expected to start in fall 2022 • Number of participants: 23,000 – Approximately 50% will be 65+ and ~10% will be 75+ • Primary endpoints Ph 3 efficacy trial design – Non-inferior (NI) relative vaccine efficacy (rVE) in preventing first episode of RT-PCR
Slide 139: Flu vaccine program accelerating towards pivotal results
Flu vaccine program accelerating towards pivotal results Phase 3 immunogenicity trial expected to read out in 1H23 Trial is expected to support initial licensure Phase 3 efficacy trial in Northern Hemisphere expected to start fall 2022 Will fulfill regulatory requirement to demonstrate efficacy post
Slide 140: Older Adults RSV Vaccine Program
Older Adults RSV Vaccine Program Christine Shaw, Ph.D. VP, Portfolio Head, Respiratory Vaccines, Infectious Disease Development © 2022 M oderna, Inc. All rights reserved.
Slide 141: RSV is a large burden in older adults
Respiratory syncytial virus (RSV) is a large burden in older adults RSV is a common seasonal respiratory virus • There are ~177,000 hospitalizations in adults 65+ due to RSV in the U.S. each year, and ~14,000 deaths1 Long-term RSV infection sequelae • Globally it is estimated that there are more tha
Slide 142: RSV vaccine (mRNA-1345) encodes a stabilized prefusion F glycoprotein
RSV vaccine (mRNA-1345) encodes a stabilized prefusion F glycoprotein 142 © 2022 M oderna, Inc. All rights reserved.
Slide 143: Pivotal Phase 3 trial in older adults has enrolled more than 24,000 participants
Pivotal Phase 3 trial in older adults has enrolled more than 24,000 participants • Pivotal Phase 3 efficacy study Phase 3 trial design ̶ Adults ≥ 60 years of age ̶ Placebo-controlled, case-driven design Randomized (N=~34,000) • Expect to enroll ~34,000 participants in multiple countries; locations i
Slide 144: Enrollment is accelerating going into northern hemisphere fall/winter
Enrollment is accelerating going into northern hemisphere fall/winter Currently enrolled >24,000 subjects and enrollment is expected to complete this year Phase 3: Approximate enrollment per month • Enrolling in 20 different ~7000 countries • Using global surveillance ~5200 networks to follow RSV se
Slide 145: ConquerRSV trial is on track to meet D&I targets
ConquerRSV trial is on track to meet D&I targets Currently enrolling in >200 sites in 20 countries US Enrollment Based on Demographic Composition Current % White, non-Hispanic ~ 65% Hispanic/LatinX ~ 14% Persons of Color: Black or African American ~18% Current ~ 35% Target 31% Asian ~ 2% Others ~ 1%
Slide 146: Evaluating endpoints across the spectrum of RSV clinical disease
We will be evaluating endpoints across the spectrum of RSV clinical disease • Throughout the trial, we will be measuring multiple endpoints across the spectrum of RSV clinical disease, including: – RSV lower respiratory tract disease (LRTD) with 2 or more signs/symptoms – RSV LRTD with 3 or more sig
Slide 147: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Expect to reach enough cases for the first interim analysis this winter season (already accruing RSV cases in study) Interim Boundaries Using O’Brien-Fleming Spending Function Approximate # VE: Efficacy of cases* (% of bound total cases) Interim analysis 43 (40%
Slide 148: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Expect to reach enough cases for the first interim analysis this winter season (already accruing RSV cases in study) Interim Boundaries Using O’Brien-Fleming Spending Function Approximate # VE: Efficacy of cases* (% of ~90% probability bound total cases) at prim
Slide 149: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Expect to reach enough cases for the first interim analysis this winter season (already accruing RSV cases in study) Interim Boundaries Using O’Brien-Fleming Spending Function ~99% probability Approximate # VE: Efficacy at primary of cases* (% of bound analysis
Slide 150: RSV vaccine (mRNA-1345) summary and next steps
RSV vaccine (mRNA-1345) summary and next steps Continuing to enroll more patients and open additional sites; ready for expected northern hemisphere RSV surge Phase 3 efficacy trial could readout this winter, depending on number of cases accrued in the study and vaccine effectiveness; target safety f
Slide 151: CMV Vaccine Program
CMV Vaccine Program Jacqueline Miller, M.D. SVP, Therapeutic Area Head, Infectious Diseases © 2022 M oderna, Inc. All rights reserved.
Slide 152: Cytomegalovirus (CMV) Overview
Cytomegalovirus (CMV) Overview Most common infectious cause of >$1B in annual congenital sensorineural healthcare costs1 hearing loss worldwide 1 in 200 babies in the U.S. are born with a congenital Sequelae include: CMV infection (CMV infection is present at birth) • At birth: microcephaly, chorior
Slide 153: CMV vaccine comprises six mRNAs encoding pentamer complex and gB antigens
CMV vaccine comprises six mRNAs encoding the CMV pentamer complex and gB antigens together 153 © 2022 M oderna, Inc. All rights reserved.
Slide 154: CMV vaccine (mRNA-1647) Phase 3 trial is >40% enrolled
CMV vaccine (mRNA-1647) Phase 3 trial is >40% enrolled • Randomized, observer-blind, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of mRNA-1647 to evaluate prevention of primary infection • Enrollment is ongoing in the U.S. and internationally – Expected to enroll up t
Slide 155: CMV vaccine Phase 3 trial ongoing worldwide
CMV vaccine (mRNA-1647) Phase 3 trial ongoing worldwide Enrolling in ~150 sites in 12 countries US Enrollment Targets Based on Demographic Composition Target Current % White, non-Hispanic 58% 52% Hispanic/LatinX 23% 33% Black or African American 12% 11% Asian 4% 2% Others 3% 2% White 58% 52% Persons
Slide 156: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Efficacy Boundaries with Alpha-allocation between 2 Planned Analyses Approximate # One-sided VE: Efficacy of Cases Alpha Bound Primary Analysis 81 0.5% ~ 57.7% End of Study 112 2.0% ~ 49.1% (EOS) Analysis 156 © 2022 M oderna, Inc. All rights reserved.
Slide 157: CMV infection is a frequent complication after transplantation
CMV infection is a frequent complication after transplantation Infection occurs due to transmission from the transplanted organ, reactivation of latent infection, or after a primary infection in seronegative patients • The harmful effects of CMV in transplant recipients result from: – The direct eff
Slide 158: Investigation of mRNA-1647 in the transplant population
Investigation of mRNA-1647 in the transplant population Anticipating trial start-up in late 2022 • Objective: Design a proof-of-concept trial or trials to evaluate the safety, efficacy and immunogenicity of mRNA-1647 in allogeneic hematopoietic stem cell transplant recipients and solid organ transpl
Slide 159: CMV vaccine (mRNA-1647) is advancing in a pivotal Phase 3 study
CMV vaccine (mRNA-1647) is advancing in a pivotal Phase 3 study CMV is a large unmet need in women of child-bearing age; CMV is also a large healthcare burden in the transplant population and we plan to start a study evaluating plan to start a study in transplant population CMVictory trial is >40% e
Slide 160: Commercial Preparedness
Commercial Preparedness Arpa Garay Chief Commercial Officer © 2022 M oderna, Inc. All rights reserved.
Slide 161: Commercial organization strategic priorities
Commercial organization strategic priorities 1 2 3 4 Create/expand Educate HCPs and Gear up for potential Compete in 2023 respiratory vaccine the public about launch of endemic market markets (RSV, flu, CMV in advance of therapeutics combos) CMV vaccine launch 161 © 2022 M oderna, Inc. All rights re
Slide 162: Late-stage vaccines and potential launch timing
Late-stage vaccines and potential launch timing Preclinical Phase 1 Phase 2 Phase 3 Licensed mRNA-1273 SARS-CoV-2 Respiratory Infectious mRNA-1010 Seasonal Flu (HA) Earliest 2023 Diseases mRNA-1345 RSV (older adults) Earliest 2023 Latent and Public Potential Health Infectious mRNA-1647 CMV 2026 Dise
Slide 163: Transitioning to an endemic COVID market
Transitioning to an endemic COVID market Pandemic context Endemic market • More fragmented commercial model; in U.S.: Nationalized country – USG buys for Medicare, Medicaid vaccine procurement, – Private insurance health plans (UNH, Cigna, Blue Cross) including a single point of – Private commercial
Slide 164: Endemic market dynamics: global sales infrastructure
Endemic market dynamics: global sales infrastructure Operating/planned commercial subsidiary Distributor partnerships • Moderna has direct presence in almost all major markets where respiratory vaccines have high utilization/sales – 91% of the flu market Taiwan Hong Kong – 87% of the pneumococcal Si
Slide 165: The respiratory vaccines market is substantial
The respiratory vaccines market is substantial, and could be even larger with new, improved solutions How does COVID change the respiratory vaccines market? • Recognition of vaccines as the gold standard in preventing disease burden and medical costs • Increased awareness of mRNA vaccine efficacy •
Slide 166: Endemic COVID market: Opportunity to expand from high-risk population
Endemic COVID market: Opportunity to expand from high- risk population Potential U.S. COVID market COVID market (high-risk population only and all adults) COVID vaccine price assumptions $64 $82 $100 • Recent pandemic COVID vaccines market >$100 High-risk population in U.S. $5.2B $6.7B $8.2B billion
Slide 167: Flu market: Opportunity to expand the market with premium vaccines
Flu market: Opportunity to expand the market with premium vaccines Reported Global Influenza Vaccine Sales1 Flu market Market dynamics USD, billions $5.8B • Aim for recommendation 40% Enhanced CAGR (2016-2020): +15% in older adults (>65 years Addressable old) $3.2B Current influenza population • Adu
Slide 168: Older adults RSV market is a >$10 billion market
Older adults RSV market is a >$10 billion market RSV market Market dynamics Addressable • Older adults (>65 years old) population • Pediatric trials ongoing RSV market has the potential to be >$10 billion • Depends on efficacy readout compared to Market share market1 other late-stage competitors • I
Slide 169: Adult combination vaccines have the potential to transform the vaccine market
Adult combination vaccines have the potential to transform the vaccine market Benefits of combination vaccines • Higher compliance • Better uptake • Larger benefit to healthcare system – Administration cost for a vaccine can be $40 per shot1 • Consumer convenience 169 © 2022 M oderna, Inc. All right
Slide 170: Vaccines for latent viruses have different market dynamics
Vaccines for latent viruses have different market dynamics when compared to respiratory vaccines • Latent viruses (such as herpes viruses and CMV market HIV) do not follow seasonal patterns • Demand is more constant over time, and CMV is a $2-5 billion opportunity market increases by expanding eligi
Slide 171: Rare disease marketing dynamics
Rare disease marketing dynamics Preclinical Phase 1 Phase 2 Phase 3 Licensed Earliest mRNA-3927 PA 2024 Earliest Rare Diseases mRNA-3705 MMA 2024 mRNA-3745 GSD1a TBD • Unique regulatory benefits: High unmet need allows for accelerated timelines with regulators • KOLs: Limited exposure to patients wi
Slide 172: Commercial preparedness summary
Commercial preparedness summary We have the global scale to compete in the COVID endemic market Preparing for multiple vaccine launches between 2023-2026 Respiratory vaccines markets are large, multi-billion-dollar opportunities and combination vaccines provide competitive advantages Latent virus va
Slide 173: Conclusion
Conclusion Stéphane Bancel CEO © 2022 M oderna, Inc. All rights reserved.
Slide 174: Never been as optimistic
Never been as optimistic Last 10 years 2022 • We believed mRNA might • We know mRNA can work work safely • Capital constrained • Unique balance sheet for a 10-year-old biotech (~$18B) 174 © 2022 M oderna, Inc. All rights reserved.
Slide 175: The next 2-3 quarters are going to be really interesting
The next 2-3 quarters are going to be really interesting Select catalysts • PA & GSD1a showing encouraging data – Could see a pivotal study in PA start in 2023 (MDEs) – De-risks our rare liver disease programs • PCV Phase 2 data in 4Q22 • Flu Phase 3 data in 1Q23 • RSV Phase 3 data could readout thi
Slide 176: Moderna has been built to create a lot of optionality
Moderna has been built to create a lot of optionality • Flu Phase 3 • RSV Phase 3 • PCV Phase 2 • PA enabling the rare disease portfolio • CF (can we deliver mRNA into the lung) • More vaccines (coming from the Moderna Infectious Disease lab) • Gene editing • Expansion of the Moderna mRNA platform t
Slide 177: Thank you
Thank you Collaborators, investigators and patients and their families…! © 2022 M oderna, Inc. All rights reserved.
Slide 178: Our mission
Our mission To deliver on the promise of mRNA science to create a new generation of transformative medicines for patients. 178 © 2022 M oderna, Inc. All rights reserved.
Slide 179: Q&A
Q&A © 2022 M oderna, Inc. All rights reserved.