Moderna, Inc. · NASDAQ:MRNA
Moderna — Investor Day (September 2020)
170 slides from Moderna's investor day presentation, Sep 17, 2020
Slide 1: Annual R&D Day
Annual R&D Day September 17, 2020
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 regarding: expected timing of enrollment completion for the Phase 3 study of mRNA-1273; the timing and des
Slide 3: mRNA as a potential new class of medicines
mRNA as a potential new class of medicines 1. Large product opportunity 2. Higher probability of technical success 3. Accelerated research and development timelines 4. Greater capital efficiency over time vs. recombinant technology Slide 3
Slide 4: Progression towards a new class of medicines
Progression towards a new class of medicines Strategic plan presented in February 2020 Impact Develop mRNA science, Explore mRNA t echnology Build Core modalities Scale for commercial delivery t echnology and across six different manufacturing modalit ies Investigate current and creat e new Explorat
Slide 5: COVID-19 vaccine has been a 3-4 year accelerator
COVID-19 vaccine (mRNA-1273) has been a 3-4 year accelerator to Moderna becoming a commercial company Build Core modalities Impact Investigate current and creat e new Exploratory modalit ies Develop mRNA science, Explore mRNA t echnology Scale for commercial delivery t echnology and across six diffe
Slide 6: A lot has changed in 12 months since R&D Day 2019
A lot has changed in 12 months since R&D Day 2019… Sept. 2019 Sept. 2020 Phase 3 candidates 0 1 Phase 2 candidates 2 4 Early stage development candidates 18 18 (Preclinical and Phase 1) Infectious diseases Infectious diseases Immuno-oncology Immuno-oncology Therapeutic area Cardiovascular Cardiovasc
Slide 7: Moderna overview
Moderna overview Moderna has the most advanced mRNA platform Moderna has one of the most advanced COVID-19 vaccine development programs Moderna is not only a COVID-19 vaccine company Moderna has 23 development candidates across a range of infectious diseases and therapeutic areas Slide 7
Slide 8: Development pipeline
Development pipeline September 2020 Preclinical (incl. Open IND) Phase 1 Phase 2 Phase 3 Commercial Phase 2 Launch Pediatric RSV Flu Adult RSV EBV Zika preparations COVID-19 preparation (Open IND) (Pandemic) (mRNA1172) Prophylactic Zika COVID-19 Core modalities vaccines Phase 3 Adult RSV hMPV/PIV3 C
Slide 9: New clinical data presented today
New clinical data presented today CMV vaccine (mRNA-1647) Antibody against Chikungunya virus (mRNA-1944) • Positive interim analysis from • Positive data from additional Phase 2 study cohorts of Phase 1 study • Phase 3 study to begin in 2021 • Two-dose regimen of at the selected 100 μg dose Chikungu
Slide 10: Business and pipeline updates announced today
Business and pipeline updates announced today Moderna is going to enter the seasonal Flu vaccine business Slide 10
Slide 11: Seasonal influenza (flu) overview
Seasonal influenza (flu) overview • Seasonal flu (type A and type B) epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing substantial burden on healthcare systems Flu symptoms & complications Fever • Disease burden: Cough ̶ Global: The WHO estimates gl
Slide 12: Potential combination vaccine for older adults
Potential combination vaccine for older adults Prophylactic vaccines • hMPV/PIV3 (mRNA-1653) COVID-19 Flu • Six mRNA’s per vial in CMV vaccine (mRNA-1647) • Phase 1 safety and immunogenicity data demonstrated in each of these viruses RSV hMPV Slide 12
Slide 13: Two new R&D collaborations announced today
Two new R&D collaborations announced today Vertex collaboration Chiesi Group collaboration Moderna and Vertex establish a new Moderna and Chiesi Group establish a new collaboration to treat cystic fibrosis using collaboration to develop an mRNA gene editing ($75m upfront) candidate for Pulmonary Art
Slide 14: Agenda
Agenda Introduction Stéphane Bancel, CEO 8:00-8:15 AM Systemic Secreted and Cell Surface Tal Zaks, M.D., Ph.D., Chief Medical Officer 8:15-8:30 AM Therapeutics • Chikungunya Antibody Intracellular Therapeutics Stephen Hoge, M.D., President 8:30-8:45 AM • PA • MMA Intratumoral Immuno-Oncology Tal Zak
Slide 15: Antibody against Chikungunya Virus (mRNA-1944)
Antibody against Chikungunya Virus (mRNA-1944) Tal Zaks, M.D., Ph.D. Chief Medical Officer Slide 15
Slide 16: Antibody against Chikungunya virus (mRNA-1944)
Antibody against Chikungunya virus (mRNA-1944) Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial Antibody against Worldw ide mRNA-1944 Chikungunya virus DARPA funded Systemic AZD7970 Relaxin 50-50 U.S. profit sharing; AZ to secreted & Hear
Slide 17: mRNA-1944 contains two mRNAs encoding CHKV-24 chains
mRNA-1944 contains two mRNAs that encode for the heavy and light chains of CHKV-24 antibody, which may confer passive immunity Slide 17
Slide 18: Phase 1 trial design (mRNA-1944) amended to repeat dose
Phase 1 trial design (mRNA-1944) amended to repeat dose • Randomized, placebo-controlled, single ascending dose study in healthy adults (N=5) • All subjects received premedication (N=5) with antihistamines (N=3) Key Objectives • Safety: Evaluate safety and tolerability of escalating doses of mRNA-19
Slide 19: Overall treatment-related adverse events, by toxicity grade
Overall treatment-related adverse events, by toxicity grade mRNA-1944 Placebo • Overall 19 participants (50%) reported treatment-related AEs Treatment-related 0.6 mg/kg 0.3 mg/kg with the highest frequencies in Adverse Events 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg + steroid1 2 dose 2 All All the 0.6 mg/kg gr
Slide 20: Safety and tolerability of second dose similar to first
Safety and tolerability of second dose appears similar to the first dose • The most common AEs reported in the 0.3 mg/kg 2- dose regimen were nausea (50%), vomiting (33%), flushing (33%) and decreased appetite (33%) 0.3 mg/kg 2 dose mRNA-1944 • No Grade 3 events occurred Adverse Events Dose 1 Dose 2
Slide 21: Dose dependent pharmacology in first three cohorts
Dose dependent pharmacology to potentially therapeutic levels seen in first three cohorts 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg Cohort 0 to 28 Days N=6 N=6 N=4 Emax 2.0 7.9 10.2 (µg/mL) Emax range 1.1-3.1 6.3-10.0 7.0-14.2 (µg/mL) Emax 40.4% 18.2% 29.6% % CV Pharmacology • Administration of mRNA-1944 result
Slide 22: Phase 1 interim analysis with steroid premedication
Phase 1 interim analysis with steroid premedication 0.6 mg/kg 0.6 mg/kg 0 to 28 Days Cohort w/ steroids N=4 N=6 Emax 10.2 6.1 (µg/mL) Emax range 7.0-14.2 2.3-10.5 (µg/mL) Emax 29.6% 47% % CV Pharmacology • Steroid premedication at 0.6 mg/kg led to ~1.7- fold reduction in CHKV-IgG exposure (Emax) • T
Slide 23: Phase 1 interim analysis with two-dose regimen
Phase 1 interim analysis with two-dose regimen 0.1 0.3 0.6 0.3 mg/kg Wx2 Cohort mg/kg mg/kg mg/kg Dose 1 Dose 2 N=6 N=6 N=4 N=6 N=6 Emax 2.0 7.9 10.2 7.2 12.9 (µg/mL) Emax range 1.1-3.1 6.3-10.0 7.0-14.2 4.0-9.7 8.2-16.7 (µg/mL) Emax 40.4% 18.2% 29.6% 26.9% 21.4% % CV Pharmacology • Consistent CHKV-
Slide 24: Lipid components have a short half life
Lipid components have a short half life with no significant accumulation between doses Lipid Pharmacokinetics • No significant accumulation of lipid components of mRNA-1944 was seen after administration of the second weekly dose due to the rapid elimination from systemic circulation Slide 24
Slide 25: Summary of Phase 1 interim analysis
Antibody against Chikungunya virus (mRNA-1944) Summary of Phase 1 interim analysis • No serious adverse events (SAEs) were reported; The most common AEs were headache (32%), nausea (25%), myalgia (18%), dizziness (14%) and chills (14%) • Administration of mRNA-1944 resulted in dose-dependent increas
Slide 26: Systemic Intracellular Therapeutics
Systemic Intracellular Therapeutics Stephen Hoge, M.D. President Slide 26
Slide 27: Systemic Intracellular Therapeutics
Systemic Intracellular Therapeutics Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial mRNA-3927 PCCA/PCCB Worldw ide Propionic acidemia, PA MUT Systemic mRNA-3705 Methylmalonic Worldw ide acidemia, MMA intracellular therapeutics mRNA-3283
Slide 28: Organic acidemias
Organic acidemias Multiple candidates targeting same metabolic pathway Mitochondrion Valine Methionine Isoleucine Threonine MMA and PA Odd-chain fattyacids Propionicacid Cholesterol esters (intestinal flora) • Similar biology and disease Propionylcarnitine pathology Propionyl-CoA 3-OH-propionate 2-m
Slide 29: Propionic acidemia (PA) overview
Propionic acidemia (PA) overview • Disease overview: Rare, autosomal recessive organic acidemia/aciduria, caused by PCC mitochondrial enzyme deficiency ̶ The PCC enzyme is a dodecamer made up of alpha (PCCA) and beta (PCCB) subunits ̶ PCC deficiency arises out of a mutation in PCCA (PA Type I) Clini
Slide 30: Propionic acidemia program update
Propionic acidemia program update Propionic Acidemia (PA) (mRNA-3927) • Chronic treatment for patients with propionic acidemia which replaces the missing or dysfunctional mitochondrial enzyme propionyl-CoA carboxylase (PCC) • mRNA-3927 has received FDA Fast Track Designation, FDA orphan drug designa
Slide 31: PA Phase 1/2 protocol amended to dose optimization trial
Propionic acidemia (mRNA-3927) Phase 1/2 trial protocol amended to a novel dose optimization trial Key objective Dose Optimization Stage • To evaluate the safety and pharmacology (up to 5 cohorts) of mRNA-3927 in patients 1 year of age 3 more participants may be enrolled in and older with propionic
Slide 32: Systemic Intracellular Therapeutics
Systemic Intracellular Therapeutics Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial mRNA-3927 PCCA/PCCB Worldw ide Propionic acidemia, PA MUT Systemic mRNA-3705 Methylmalonic Worldw ide acidemia, MMA intracellular therapeutics mRNA-3283
Slide 33: Methylmalonic acidemia (MMA) overview
Methylmalonic acidemia (MMA) overview • Disease overview: Rare, autosomal recessive organic acidemia/aciduria ̶ Defective or deficient MUT enzyme (methylmalonic CoA mutase) • Disease is progressive, involves multiple organ systems and is highly Clinical manifestations lethal; includes risk of life-t
Slide 34: MMA program update
MMA program update Methylmalonic Acidemia (MMA) (mRNA-3705) • Chronic treatment for patients with methylmalonic acidemia which replaces faulty enzyme methylmalonic-CoA mutase (MUT) • Due to COVID-19, enrollment and new site initiation was paused for methylmalonic acidemia (MMA; mRNA-3704) • Update t
Slide 35: Moving forward with next generation MMA candidate
Moving forward with next generation MMA candidate (mRNA-3705) MMA (mRNA-3705) mRNA-3705 produces higher levels of hMUT • Introduction of a drug product with enzyme in the liver of rats better pharmacology (new mRNA) • Same LNP, also used in mRNA-1944 PBS mRNA- mRNA- 3704 3705 • Taken opportunity to
Slide 36: Rare diseases summary
Rare diseases summary mRNA advantages in rare diseases Next steps in rare diseases Target intracellular proteins PA – First patient dosed MMA – IND/CTA submission for mRNA-3705 GSD1a – IND filing Protein complexes with multiple subunits PKU – IND filing Aim to clinically de-risk the systemic Able to
Slide 37: Intratumoral Immunotherapy
Intratumoral Immunotherapy Tal Zaks, M.D., Ph.D. Chief Medical Officer Slide 37
Slide 38: Oncology development candidates
Oncology development candidates Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial Personalized cancer 50-50 global profit mRNA-4157 Vaccine (PCV) Cancer sharing w ith Merck vaccines mRNA-5671/ KRAS vaccine, CRC, 50-50 global profit Merck V
Slide 39: Intratumoral immuno-oncology
Intratumoral immuno-oncology Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial OX40L Solid mRNA-2416 Solid tumors/lymphoma Ov arian Worldw ide Advanced ovarian cancer tumors/lymphoma Intratumoral OX40L/IL-23/IL-36γ immuno- mRNA-2752 Worldw
Slide 40: Antonio Jimeno, M.D., Ph.D.
Antonio Jimeno, M.D., Ph.D. Professor of Medicine/Oncology and Otolaryngology at University of Colorado School of Medicine Dr. Jimeno is a tenured Professor at the University of Colorado Cancer Center (UCCC). His laboratory and clinical research efforts are aimed at discovering new therapies, and im
Slide 41: Anti-PD(L)1 therapy 2020
Anti-PD(L)1 therapy 2020 How do we increase patient benefit? Slide 41
Slide 42: The Cancer-Immunity Cycle
The Cancer-Immunity Cycle Chen and Mellman, Slide 42 Immuity 2013
Slide 43: Stimulatory and Inhibitory factors of the Cancer-Immunity Cycle
Stimulatory and Inhibitory factors of the Cancer-Immunity Cycle Chen and Mellman, Slide 43 Immunity 2013
Slide 44: Stimulatory and Inhibitory factors of the Cancer-Immunity Cycle
Stimulatory and Inhibitory factors of the Cancer-Immunity Cycle OX40L IL-23 IL-36 OX40L IL-23 IL-36 OX40L IL-36 OX40L IL-23 IL-36 Chen and Mellman, Slide 44 Immunity 2013
Slide 45: What is intratumoral (iTu) therapy?
What is intratumoral (iTu) therapy? What are the advantages of iTu over systemic Rx? Systemic Rx Intratumoral mRNA Rx Therapeutic • Systemic effect • Systemic effect; drains into tumor principle lymph nodes (extends to non- injected lesions) • Superior T-cell priming; multiclonal response Toxicity •
Slide 46: Examples of iTu agents
Examples of iTu agents Oncolytic Viruses: Immune Agonists: • T_V EC (HSV-1/GM-CSF) • Checkpoint agonists e.g. OX40L • Coxsackievirus A21 • Cytokines (IFN-γ, interleukins e.g. IL-1, 12, 23, 36) • Others • Growth factors e.g. GM-CSF • STING and RIG-1 agonists • Others Slide 46 Yuan J, SITC 2019
Slide 47: OX40L (mRNA-2416)
OX40L (mRNA-2416) Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial OX40L Solid mRNA-2416 Solid tumors/lymphoma Ov arian Worldw ide Advanced ovarian cancer tumors/lymphoma Intratumoral OX40L/IL-23/IL-36γ immuno- mRNA-2752 Worldw ide (tripl
Slide 48: mRNA-2416 Encodes OX40L and is Injected Directly into a Tumor
mRNA-2416 Encodes OX40L and is Injected Directly into a Tumor OX40L: • When mRNA-2416 is deliv ered into a tumor, cells • Homotrimeric protein normally expressed on professional in the tumor are directed to express OX40L antigen presenting cells (APCs) protein in its native membrane-bound form, • T
Slide 49: Preclinical models demonstrate synergistic effect of combination
Preclinical models demonstrate synergistic effect of combination OX40L and aPD-L1 MC38 ID8 mOX40L mOX40L mOX40L + aPD-L1 mOX40L + aPD-L1 aPD-L1 aPD-L1 2000 2000 10 11 10 11 Tumor volume (mm3) Tumor burden (BLI) 1500 3/15 CR 1500 10 10 10 10 10 9 10 9 10/12 CR 1000 1000 11/15 CR 10 8 10 8 with minima
Slide 50: OX40L (mRNA-2416)
OX40L (mRNA-2416) Phase 1/2 combination with durvalumab fully enrolled; Phase 2 dose expansion ongoing Key Objectives • Evaluate safety and tolerability of mRNA- 2416 administered intratumorally ✓ • Define the maximum tolerated dose and ✓ recommended dose for expansion ✓ ✓ • Other endpoints include
Slide 51: OX40L (mRNA-2416) data presented at AACR 2020
OX40L (mRNA-2416) Data presented at AACR 2020 • 39 patients evaluated for safety and efficacy as mRNA-2416 monotherapy • Overall mRNA-2416 monotherapy has been tolerable at all dose levels with no dose-limiting toxicities (DLTs) reported and majority of related AE's being grade 1 or grade 2 Related
Slide 52: OX40L (mRNA-2416) swimmer plot
OX40L (mRNA-2416) Data presented at AACR 2020 mRNA-2416-P101 Swimmer plot: ARM A monotherapy per RECIST 1.1 • 14/39 had stable disease (SD), of these patients 6 had SD for ≥14 weeks • 4/6 ovarian patients on study had SD; 1 patient with sarcoma on drug for entire study (24 weeks) Slide 52
Slide 53: OX40L (mRNA-2416) waterfall of best overall response
OX40L (mRNA-2416) Data presented at AACR 2020 mRNA-2416-P101 Waterfall of BOR (RECIST) by Lesion Injection Status • 14 patients with best overall response of stable disease by RECIST • 4 patients with tumor shrinkage in injected lesions • 5 patients overall had reduction in un-injected lesions • Ove
Slide 54: Phase 1 dosing and biopsy collection schedule
Phase 1 dosing & biopsy collection schedule and biomarker readouts from arm A (monotherapy mRNA-2416) C All cycle 1 cycle 2 D2 cycle 3 cycle 4 cycle 6 pre- dose * * = OX40L on days 1 & 15 per cycle Biomarker Readouts from FFPE Biopsies = 1 week • Multiplexed Quantitative Immunofluorescence (QIF) = T
Slide 55: Protein expression by QIF of OX40L and T cell scores
Protein expression by QIF of OX40L & T cell scores post-mRNA-2416 in injected lesions • Increased OX40L protein expression observed in the tumor microenvironment (TME) in several cases, including in an ovarian patient, 007-002 with the most marked increase, as shown here • Increased CD3+ T cells in
Slide 56: Increased PD-L1 ranked score in 5/9 patients
Increased PD-L1 ranked score in 5/9 patients post-treatment Patient ID (dose level, cohort, tumor type) Quartile rankings defined using PD-L1 transcript levels across TCGA dataset (RNAseq data, 9654 samples across 33 tumor types) TPM= Transcripts Per Million • 5 of 9 Group B/C cases (injected lesion
Slide 57: Increased T cell-inflamed GEP ranked score in 6/9 patients
Increased T cell-inflamed GEP ranked score in 6/9 patients after mRNA-2416 treatment Patient ID (dose level, cohort, tumor type) GEP score: • GEP = Gene Expression Profile; 18-gene signature; predictive of pembro response (Ayers et al., 2017; Cristescu et al., 2018) • GEP Quartile rankings determine
Slide 58: OX40L (mRNA-2416) conclusions from AACR 2020
OX40L (mRNA-2416) Conclusions from AACR 2020 presentation • mRNA-2416 is well tolerated when given as monotherapy at all dose levels studied with no DLTs reported ̶ The majority of TEAEs reported were grade 1/2, and no grade 3 TEAEs > 3% • 14/39 patients achieved a best overall response (BOR) of sta
Slide 59: OX40L/IL-23/IL-36γ (triplet)
OX40L/IL-23/IL-36γ (triplet) Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial OX40L Solid mRNA-2416 Solid tumors/lymphoma Ov arian Worldw ide Advanced ovarian cancer tumors/lymphoma Intratumoral OX40L/IL-23/IL-36γ immuno- mRNA-2752 Worldw
Slide 60: Immune modulation with OX40L, IL-23, IL-36γ
Immune modulation with OX40L, IL-23, IL-36 OX40L IL-23 IL-36 Dendritic T Cell Cancer Cell Cell Transmembrane T cell Proinflammatory cytokine Proinflammatory cytokine co-stimulatory protein of the IL-12 family of the IL-1 family • Reported to prime DC • Acts on DCs to promote • Activates other cell
Slide 61: OX40L/IL-23/IL-36γ (mRNA-2752) overview
OX40L/IL-23/IL-36γ (mRNA-2752) overview • Moderna’s technology enables novel combinations of targets • Intratumoral delivery may enable delivery of targets locally that are too toxic systemically Slide 61
Slide 62: Preclinical data: combination demonstrates synergistic effects
OX40L/IL-23/IL-36γ Preclinical data – combination of 3 targets demonstrates synergistic effects Untreated / IL-23/IL-36γ IL-23/OX40L IL-23/IL-36γ/OX40L Control mRNA Species: 2000 Mouse Tumor volume (mm3) 1500 Treated 1000 10/20 CR 20/20 CR 500 11/20 CR 0 • Tumor volumes of both the treated and 2000
Slide 63: Combination of aPD-L1 Ab with triplet mRNA is synergistic
Combination treatment of aPD-L1 Ab + OX40L/IL-23/IL-36γ mRNA iTu is synergistic in immunologically barren B16F10 model No efficacy with aPD- OX40L/IL-23/IL-36 OX40L/IL-23/IL-36 L1 alone + aPD-L1 Ab 2000 2000 2000 T u m o r v o lu m e (m m ) 1500 1500 1500 3 1000 1000 1000 500 500 500 6/15 CRs 0 0
Slide 64: OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752) Phase 1
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752) Phase 1 ongoing; patients dosed in combination with durvalumab Arm A: mRNA-2752 alone Key Objectives Dose escalation (N=~20) Accessible solid tumors and lymphomas • Evaluate safety and tolerability of mRNA-2752 administered mRNA-2752 0.25 mg ✓ alone and in co
Slide 65: Triplet (mRNA-2752) data presented at ASCO 2020
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752) Data presented at ASCO 2020 • At ASCO 2020, we present findings from a first-in-human study of iTu mRNA-2752 in solid tumor patients as monotherapy or in combination with durvalumab. As of April 8, 2020, 29 patients were evaluable for safety and 23 patients e
Slide 66: Triplet (mRNA-2752) swimmer plot
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752) Data presented at ASCO 2020 mRNA-2752-P101 swimmer plot: per RECIST 1.1 17 patients on Arm A with duration on study up to 16 weeks. 12 patients on Arm B up to 28 weeks on study and continuing at time of data cutoff. Slide 66
Slide 67: Triplet (mRNA-2752) waterfall plot
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752) Data presented at ASCO 2020 mRNA-2752-P101 Waterfall Plot of Maximum %Change from Baseline in Sum of Diameters of Target Lesions Based on Investigator Assessment per RECIST 1.1 Tumor shrinkage in both injected and un-injected target lesions in both monotherap
Slide 68: Phase 1 dosing and biopsy collection schedule, arms A and B
Phase 1 dosing & biopsy collection schedule from arms A and B (mRNA-2752 +/- durvalumab) • Collection of newly obtained tumor samples during screening and at 1 other time point Slide 68
Slide 69: PD-L1 expression is increased after mRNA-2752 treatment
%PD-L1+ PD-L1 expression is increased after mRNA-2752 treatment %PD-L1+ %PD-L1+ Tumor-associated Tumor-associated Tumor-associated Immune Cells Immune Cells Immune Cells p=0.0098 p=0.0313 p=0.0527 immune cells 80 100 80 %PD-L1+ in tumor- 80 60 60 Percent (%) Percent (%) Percent (%) 60 40 40 associat
Slide 70: Elevated IL-23, IL-36γ, IFN-γ and TNF-a after treatment
Elevated IL-23, IL-36γ, IFN-γ and TNF-a after treatment with mRNA-2572 +/- durvalumab Slide 70
Slide 71: Triplet (mRNA-2752) conclusions from ASCO 2020
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752) Conclusions from ASCO 2020 presentation • iTu mRNA-2752 given as monotherapy and in combination with durvalumab is tolerable at all dose levels studied with no DLTs reported and the majority of related AE's being grade 1 or 2 • Administration of iTu mRNA-2752
Slide 72: Agenda
Agenda Introduction Stéphane Bancel, CEO 8:00-8:15 AM Systemic Secreted and Cell Surface Tal Zaks, M.D., Ph.D., Chief Medical Officer 8:15-8:30 AM Therapeutics • Chikungunya Antibody Intracellular Therapeutics Stephen Hoge, M.D., President 8:30-8:45 AM • PA • MMA Intratumoral Immuno-Oncology Tal Zak
Slide 73: CMV Vaccine (mRNA-1647)
CMV Vaccine (mRNA-1647) Lori Panther, M.D., M.P.H Senior Director of Clinical Development, Infectious Diseases Slide 73
Slide 74: Cytomegalovirus (CMV) vaccine (mRNA-1647)
Cytomegalovirus (CMV) vaccine (mRNA-1647) Preclinical Phase 3 and Modality ID # Program development Phase 1 Phase 2 commercial Moderna rights Worldwide mRNA-1273 COVI D-19 vaccine BARDA funded mRNA-1647 Cytomegalovirus (CMV) Worldw ide v accine Phase 1 Phase 1b mRNA-1653 hMPV/PIV3 v accine (healthy
Slide 75: Congenital cytomegalovirus overview
Congenital cytomegalovirus overview • Cytomegalovirus: CMV is a common infection and is the leading cause of birth defects in the US ̶ 0.65% of US newborns infected annually (~25,000 US newborns)1 CMV infection sequelae3,4 Jaundice • Disease burden: Significant impact on survivors, Microcephaly fami
Slide 76: CMV vaccine (mRNA-1647) includes 6 mRNAs
CMV vaccine (mRNA-1647) includes 6 mRNAs 5 encode the pentamer, 6th encodes gB antigen Epithelial cells Fibroblasts Slide 76
Slide 77: CMV vaccine (mRNA-1647) clinical development
CMV vaccine (mRNA-1647) clinical development 3-month interim 7-month interim 12-month interim analysis analysis analysis September 2019 R&D Day January 10, 2020 August 5, 2020 Phase 1 Phase 2 COVID-19 disruptions First participant Fully enrolled 3-month interim enrolled March 2020 analysis January 2
Slide 78: Key changes to mRNA-1647 in Phase 2 clinical trial
Key changes to mRNA-1647 in Phase 2 clinical trial • Improved potency ̶ Improved ratio of mRNA components to increase potency • Improved tolerability ̶ Optimized the manufacturing process to improve tolerability • Lyophilization ̶ Phase 2 utilizes the intended Phase 3 and commercial formulation Liqu
Slide 79: CMV vaccine Phase 1 12-month interim analysis
CMV vaccine (mRNA-1647) Phase 1 12-month interim analysis • Safety: The vaccine was generally well-tolerated and there were no vaccine-related serious adverse events (SAEs). Safety and tolerability at the 300µg dose level was comparable to that observed at the 180µg dose level • In the CMV-seronegat
Slide 80: CMV vaccine Phase 2 trial overview
CMV vaccine (mRNA-1647) Phase 2 trial overview Key objective • To assess the safety and immunogenicity of the Phase 3 and Month 0 Month 2 Month 6 commercial mRNA-1647 in a narrow range of doses mRNA-1647 dosing regimen Primary endpoints • Defined safety parameters • Neutralizing antibodies against C
Slide 81: Most common systemic ARs after 1st vaccination
CMV vaccine (mRNA-1647) Phase 2 interim analysis Solicited adverse reactions (ARs) post 1st vaccination, solicited safety set CMV Serostatus at Baseline • Injection site pain was the CMV-seronegative CMV-seropositive most commonly reported Placebo 50 μg 100 μg 150 μg Placebo 50 μg 100 μg 150 μg soli
Slide 82: Most common systemic ARs after 2nd vaccination
CMV vaccine (mRNA-1647) Phase 2 interim analysis Solicited adverse reactions (ARs) post 2nd vaccination, solicited safety set CMV Serostatus at Baseline • After the 2nd CMV-seronegative CMV-seropositive vaccination, the rate Placebo 50 μg 100 μg 150 μg Placebo 50 μg 100 μg 150 μg and severity distri
Slide 83: CMV vaccine Phase 2 interim analysis: seronegative
CMV vaccine (mRNA-1647) Phase 2 interim analysis Immunogenicity in CMV-seronegative participants, per-protocol set Neutralizing Antibodies Against Epithelial Cell Infection • Neutralizing antibody titers against Phase 2 CMV-seropositive cohort GMT benchmark = 3,924 epithelial cell infection were boo
Slide 84: CMV vaccine Phase 2 interim analysis: seropositive
CMV vaccine (mRNA-1647) Phase 2 interim analysis Immunogenicity in CMV-seropositive participants, per-protocol set Neutralizing Antibodies Against Epithelial Cell Infection • Neutralizing antibody titers in the epithelial Phase 2 CMV-seropositive cohort GMT benchmark = 3,924 cell infection were boos
Slide 85: Neutralizing antibodies against epithelial cell infection through month 3
Neutralizing antibodies against epithelial cell infection through month 3 CMV serostatus and vaccination group, per-protocol set 1st vaccination 2nd vaccination Slide 85
Slide 86: Neutralizing antibodies against fibroblast infection through month 3
Neutralizing antibodies against fibroblast infection through month 3 CMV serostatus and vaccination group, per-protocol set 1st vaccination 2nd vaccination Slide 86
Slide 87: Late stage development for CMV vaccine (mRNA-1647)
Late stage development for CMV vaccine (mRNA-1647) • Utilizes intended Phase 3 formulation; same lipid nanoparticle (LNP) used in Phase 1 Phase 2 • 3-month interim analysis informed dose level choice for further development study • Intend to file a protocol amendment to enroll more participants at t
Slide 88: CMV awareness activities 2020
CMV awareness activities 2020 • In January 2020 – #STOPCMV Kids Art Contest • In February 2020 – Sponsored 3 to run NYC Half Marathon • In June 2020 – Sponsored CMV Podcast Series with National CMV foundation • In honor of National CMV Awareness Month supported a series of CMV Voices to raise awaren
Slide 89: RSV (mRNA-1345) and hMPV/PIV3 (mRNA-1653) Vaccines
RSV (mRNA-1345) and hMPV/PIV3 (mRNA-1653) Vaccines Allison August, M.D. Senior Director of Clinical Development, Infectious Diseases Slide 89
Slide 90: Pediatric respiratory vaccines
Pediatric respiratory vaccines Preclinical Phase 3 and Modality ID # Program development Phase 1 Phase 2 commercial Moderna rights Worldwide mRNA-1273 COVI D-19 vaccine BARDA funded mRNA-1647 Cytomegalovirus (CMV) Worldw ide v accine Phase 1 Phase 1b mRNA-1653 hMPV/PIV3 v accine (healthy (Age de-esc
Slide 91: Pediatric respiratory syncytial virus (RSV) overview
Pediatric respiratory syncytial virus (RSV) overview • RSV is the leading cause of unaddressed severe lower respiratory tract disease and hospitalization in infants and young children worldwide • Disease burden: Major cause of hospitalization due to respiratory RSV infection infection Fevers Nasal c
Slide 92: Pediatric RSV vaccine (mRNA-1345)
Pediatric RSV vaccine (mRNA-1345) Encodes for a stabilized prefusion F glycoprotein • Prefusion F elicits a superior neutralizing antibody response compared to the post-fusion protein • mRNA-1345 will use the same LNP as our hMPV/PIV3 (mRNA-1653), CMV (mRNA-1647) and COVID-19 (mRNA-1273) vaccines Sl
Slide 93: Pediatric RSV vaccine (mRNA-1345) trial design
Pediatric RSV vaccine (mRNA-1345) IND opened and actively screening participants Adult Cohorts Key objective D1 • To evaluate the safety and immunogenicity of mRNA-1345 when administered to adults and Cohort 2 (N=25) D1 to children 12-36 months of age with serologic mRNA-1345: placebo (4:1) D1 evide
Slide 94: hMPV and PIV3 represent a high unmet need
Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) represent a high unmet need in young children • hMPV and PIV3 are RNA viruses that are important causes of respiratory tract infections, particularly in children • Increasing rates of diagnosis and association with hospitalization fo
Slide 95: hMPV/PIV3 vaccine (mRNA-1653)
hMPV/PIV3 vaccine (mRNA-1653) Combines mRNAsencoding antigens from two different viruses Slide 95
Slide 96: hMPV/PIV3 (mRNA-1653) Phase 1b trial
hMPV/PIV3 (mRNA-1653) Phase 1b trial First mRNA vaccine to be evaluated in children Key objective Day 1 Month 2 • To evaluate the safety and immunogenicity of mRNA-1652 when administered to adults mRNA-1653 dosing regimen and to children 12-36 months of age with Adult Cohort serologic evidence of pr
Slide 97: Pediatric respiratory diseases
Pediatric respiratory diseases RSV, hMPV and PIV3 are leading causes of respiratory illness in young children RSV hMPV PIV3 Respiratory syncytial virus Human metapneumovirus Parainfluenza virus type 3 • Hospitalization rate in children • Hospitalization rate in children < 5 years old in the • Hospit
Slide 98: Pediatric respiratory diseases
Pediatric respiratory diseases RSV, hMPV and PIV3 are leading causes of respiratory illness in young children RSV hMPV PIV3 Respiratory syncytial virus Human metapneumovirus Parainfluenza virus type 3 • Hospitalization rate in children • Hospitalization rate in children < 5 years old in the • Hospit
Slide 99: Terry Nolan, M.D., Ph.D.
Terry Nolan, M.D., Ph.D. Peter Doherty Institute for Infection and Immunity, The University of Melbourne Prof. Nolan is a pediatrician and clinical epidemiologist, graduated from the University of Western Australia, trained in paediatrics at the Royal Children's Hospital in Melbourne and at the Mont
Slide 100: Epochs and Opportunities
Terry Nolan MD PhD Peter Doherty Institute for Infection and Immunity The University of Melbourne Vaccines and Prevention of Children’s Diseases Epochs and Opportunities
Slide 101: Advances
Advances +Polio +Diphtheria, tetanus, pertussis +Meningitis +Diarrheal disease +Pneumonia +Measles, mumps, rubella, and varicella
Slide 102: Epochs and Quantum Shifts
Epochs and Quantum Shifts +Basic vaccinology + Conjugate bacterial vaccines (simple, then complex multiple serotypes) + Reverse vaccinology (men B) + Nucleic acid vaccines +Combination vaccines + Infant combos, MMR-V, mening (HibMenC, HibMenCY, menACWY, menABCWY) +Mandatory vaccination policies + Sh
Slide 103: Combination Vaccines
Combination Vaccines +Have made the infant schedule feasible as new vaccines have emerged +Potential for further efficiency probably not fully realized
Slide 104: Hexavalent vaccine for infants
Hexavalent vaccine for infants Julianne Bayliss, Michael Nissen, Damita Prakash, Peter Richmond, Kyu-Bin Oh & Terry Nolan (2020). Control of vaccine preventable diseases in Australian infants: reviewing a decade of experience with DTPa-HBV-IPV/Hib vaccine,Human Vaccines & Immunotherapeutics, DOI: 10
Slide 105: Advantages of Combination Vaccines
Advantages of Combination Vaccines +Coverage +Convenience +Cost of materials reduced +Storage simpler +Marketing (lesser known components get a free ride) +Parent acceptability (no ‘pin cushion’) +Paradoxically may alleviate some of ‘antigen overload’ anxiety
Slide 106: Concerns about too many immunizations
Concerns about too many immunizations % Agree (% Strongly Agree) % Disagree (% Strongly Disagree) Children should only be immunized against serious diseases. 39 (20) 55 (31) Children get more immunizations than are good for them. 23 (10) 68 (37) Immunizations are always proven safe before they are a
Slide 107: Respiratory Viruses as High Value Targets
Respiratory Viruses as High Value Targets +Influenza +Respiratory syncytial virus (RSV) +50-year quest +VAERD (vaccine-associated enhanced respiratory disease) risk has plagued development +Many candidates from several platforms, maternal and infant +Parainfluenza virus type 3 (PIV3) +Human Metapneu
Slide 108: Is there a role for mRNA combination vaccines?
Is there a role for mRNA combination vaccines? +Capacity to ‘package’ N>1 mRNA for multiple target diseases +Reduced risk of chemical/immunologic interference +‘Tunable’ potential a major asset for antigenic drift, without altering the entire construct +Potential for reduced adjuvant exposure
Slide 109: Regulatory touch points
Regulatory touch points +Adjuvants +Regulators ‘don’t like’ adjuvants (quote) +Safety +Shifting baseline on risk management for safety assurance +Assurance of VE for drifted targets (influenza, SARS-CoV-2) +Clinical trial complexity +Age de-escalation and dose escalation +Changes in virus ecology fr
Slide 110: Disrupted virus ecology
Disrupted virus ecology +COVID impact mediated through social restriction +Consequent impact on virus circulation +Effect on clinical trials programs +Reduced seropositives in early childhood +Fewer events for a Phase III study
Slide 111: Multiplex RT-PCR for Respiratory Illness at Royal Children's Hospital
Multiplex RT-PCR for Respiratory Illness and RSV+ at Royal Children’s Hospital Melbourne 2019 2020 900 35 900 35 800 800 30 30 700 700 25 25 600 600 500 20 500 20 400 15 400 15 300 300 10 10 200 200 5 5 100 100 0 0 0 0 Positive Negative Total tests Proportion positive Positive Negative Total tests P
Slide 112: Daily new confirmed cases of COVID-19
Daily new confirmed cases of COVID-19 ore"] Thelin is blue when a country performs may tess relative tthe siete outbreak. Reatlndctes low number ests pr case Ts sugess ia te tue umnber of fection may bef igher than the numberof onfrmed cases sm stestspercase 5-10 10-20 20-30 20-50 50-100 40-1000 100
Slide 113: What do Governments want? Valuing Vaccines
What do Governments want? Valuing Vaccines +Public funding (NIPs) necessary to optimize vaccine uptake +Confidence and availability +Better methods for cost-effectiveness evaluation +Implementability (simplicity in scheduling and administration) +In summary, good value for money, and high levels of
Slide 114: Conclusions
Conclusions +Advances in vaccine science have provided quantum shifts in value through primary prevention of childhood diseases +Combination vaccines have a proven track record, and significant future potential +mRNA vaccines have a lot to offer for the coming epoch
Slide 115: With thanks
With thanks Doherty.edu.au /DohertyInstitute @TheDohertyInst #DohertyInstitute @dohertyinstitute
Slide 116: COVID-19 Vaccine (mRNA-1273)
COVID-19 Vaccine (mRNA-1273) Jacqueline Miller, M.D., FAAP SVP, Infectious Diseases Development Slide 116
Slide 117: COVID-19 vaccine (mRNA-1273)
COVID-19 vaccine (mRNA-1273) Preclinical Phase 3 and Modality ID # Program development Phase 1 Phase 2 commercial Moderna rights Worldwide mRNA-1273 COVI D-19 vaccine BARDA funded mRNA-1647 Cytomegalovirus (CMV) Worldw ide v accine Phase 1 Phase 1b mRNA-1653 hMPV/PIV3 v accine (healthy (Age de-escal
Slide 118: SARS-CoV-2 overview
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) overview • SARS-CoV-2 virus: novel coronavirus first identified in humans in December COVID-19 sequelae identified to date 4,5 2019 and cause of COVID-19 Pneumonia Acute Respiratory Distress • Disease burden (as of September 16, 2020): Lun
Slide 119: SARS-CoV-2 vaccine (mRNA-1273)
SARS-CoV-2 vaccine (mRNA-1273) Encodes for the full spike S protein Slide 119
Slide 120: mRNA-1273 program timeline
mRNA-1273 program timeline m R N A - 1 2 7 3 t i m el i n e: R e s ea r ch a n d d e v el op me n t o f S AR S - C oV - 2 v a c ci n e April 16, 2020 May 1, 2020 Award from U.S. Collaboration announced January 13, 2020 May 29, 2020 government agency with Lonza Ltd to Sequence for mRNA- / Announcemen
Slide 121: Phase 1 trial overview
Phase 1 trial overview Led by the National Institutes of Health (NIH) Key objective: Day 1 Day 29 • To assess the safety, reactogenicity and immunogenicity of mRNA-1273 SARS-CoV-2 Phase 1 dosing regimen Study design: • Phase 1, open-label dose ranging clinical trial in healthy adults • Subjects rece
Slide 122: 100 µg mRNA-1273 well-tolerated across age groups
100 µg mRNA-1273 well-tolerated across age groups Grade 1 (mild) Grade 2 (moderate) Grade 3 (severe) Phase 1: No Vaccine-Related SAEs Have Been Reported Solicited Local and Systemic Symptoms Followed for 7 Days Post-vaccination Majority of symptoms resolved within 2 days, some persisted as long as 5
Slide 123: Binding antibodies comparable across age groups
Binding antibodies comparable across age groups S-2P binding antibodies (ELISA)- 100 μg at Day 1 and Day 29 18 – 55 years 56 – 70 years 71+ years 100 μg two-dose series seroconverted all participants after the first vaccination Range of convalescent sera After the first vaccination, AUC for all
Slide 124: Pseudovirus neutralization antibody titers across age groups
Distribution of antibody titers in pseudovirus neutralization assay comparable across age groups Pseudovirus neutralization assay titers (ID50)- 100 μg at Day 1 and Day 29 18 – 55 years 56 – 70 years 71+ years D57 GMT: 267 D57 GMT: 324 D57 GMT: 242 95% CI: 186, 385 95% CI: 212, 496 95% CI: 147, 399
Slide 125: mRNA-1273 elicited Th1-biased CD4 T cell responses
mRNA-1273 elicited Th1-biased CD4 T cell responses in all participants Any Th-1 response IL-2 Th1 CD4+ T cell response, S1 peptide pool (100 μg at Day 1 and 29) Interferon-γ TNF-α 18 – 55 years 56 – 70 years 71+ years 0.8 0.6 % CD4 T cells 0.4 0.2 0.0 Day 1 Day 29 Day 43 V accination with 100 μg m
Slide 126: mRNA-1273 vaccine against COVID-19: data generated to date
mRNA-1273 vaccine against COVID-19 Data generated to date • Phase 1 clinical data ̶ Neutralizing antibody titers were observed in 100% of evaluated participants ̶ In the pseudovirus (ID50) neutralization assay, at the 100 µg dose, mRNA-1273 induced consistently high levels of neutralizing antibody t
Slide 127: mRNA-1273 Phase 2 Study
mRNA-1273 Phase 2 Study will Evaluate Safety and Immunogenicity of 50 µg and 100 µg (N=600) Phase 2 trial overview (NCT04405076) Protocol Title A Phase 2a, Randomized, Observ er-Blind, Placebo-Controlled, Dose-Finding Study to Ev aluate the Safety, Reactogenicity, and I mmunogenicity of mRNA-1273 SA
Slide 128: Pivotal Phase 3 Efficacy, Safety and Immunogenicity Study
Pivotal Phase 3 Efficacy, Safety and Immunogenicity Study (N=30,000) Phase 3 trial overview (NCT04470427) Protocol Title A Phase 3, Randomized, Stratified, Observ er-Blind, Placebo-Controlled Study to Ev aluate the Efficacy, Safety, and I mmunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged
Slide 129: COVE D&I Advisory Committee
COVE D&I Advisory Committee Remit and Role of Advisory Committee: 1. Review enrollment, race, and ethnicity demographics on a weekly basis 2. Review current outreach activities and outcomes 3. Review strategies to ensure participation of individuals from communities significantly impacted by COVID-1
Slide 130: Phase 3 COVE study has enrolled 25,296 participants
Phase 3 COVE study has enrolled 25,296 participants1 Phase 3 Enrollment Status Phase 3 Diversity Status W hite ( 72%) His panic or Lat inx ( 16%) Black or African American ( 7%) As ian ( 3%) M ore t han one race ( 1%) Ot her ( 1%) American I ndian or Alas ka Nat ive ( 0.4%) Not report ed ( 0. 2%) Ha
Slide 131: Primary Efficacy Endpoint: COVID-19 Disease Case Definition
Primary Efficacy Endpoint: COVID-19 Disease Case Definition To be considered a case of COVID-19 for the evaluation of the Primary Efficacy Endpoint, two criteria must be met: 1 The participant must have experienced: At least TWO of the following systemic symptoms: fever (≥ 38ºC), chills, myalgia,
Slide 132: Independent DSMB ensures continuous data monitoring
An independent Data and Safety Monitoring Board (DSMB) ensures continuous data monitoring and enhances participant safety Independent review of data Deliberation on best course of action Independent regulatory review Independent Oversight Moderna FDA DSMB group (sponsor) A fully independent Data a
Slide 133: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) 53 (35%) ~0.74 Interim analysis #1 Interim 106 ~0.57 analysis (70%) #2 151 ~0.50 Pr
Slide 134: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) 53 (35%) ~0.74 Interim analysis #1 Interim 106 ~0.57 analysis (70%) #2 <10% probability
Slide 135: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) 53 (35%) ~0.74 Interim analysis ~65% probability #1 Interim 106 ~0.57 analysis (70%) #2
Slide 136: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) 90% probability 53 (35%) ~0.74 Interim analysis #1 Interim 106 ~0.57 analysis (70%) #2
Slide 137: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) 53 (35%) ~0.74 Interim analysis #1 Interim 106 ~0.57 analysis (70%) #2 151 ~0.50 Pr
Slide 138: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) 53 (35%) ~0.74 Interim analysis #1 ~50% probability Interim 106 ~0.57 analysis (70%) #2
Slide 139: Overview of primary efficacy endpoint
Overview of primary efficacy endpoint Boundary Crossing Probabilities by Interim Boundaries Using O’Brien-Fleming Spending Function Effect Size Approximate # VE: Efficacy of cases (% of bound total cases) >95% probability 53 (35%) ~0.74 Interim analysis #1 Interim 106 ~0.57 analysis (70%) #2
Slide 140: COVID-19 Manufacturing and Distribution Update
COVID-19 Manufacturing and Distribution Update Juan Andres Chief Technical Operations and Quality Officer Slide 140
Slide 141: We are a platform…
We are a platform… Buffers Enzymes Nucleotides Lipids DNA mRNA mRNA + LNP Drug product Slide 141
Slide 142: Platform investments resulted in improved pharmaceutical properties
Platform investments resulted in improved pharmaceutical properties Investments Pharmaceutical Properties Fundamental Product Pre-Clinical Shelf-life ✓ Understanding Models &Clinical Storage Temperature ✓ Evaluation Safety/Tolerability ✓ Product Optimization Potency ✓ Consistency of Manufacture ✓ An
Slide 143: Pharmaceutical development has enabled consistent manufacture across scales
Pharmaceutical development has enabled consistent manufacture across multiple scales (mRNA-1273) Specification Range As shown by these important Drug Product Characteristics. Specification Range mRNA-1273 has demonstrated a high level of consistency across manufacturing scales (small, mid, large) Sp
Slide 144: Integrated Manufacturing
Integrated Manufacturing Plasmid mRNA LNP Fill/Finish QC Slide 144
Slide 145: Our manufacturing site is scalable and flexible
Our manufacturing site is scalable and flexible Cell free manufacturing Standard Industrial Non product dedicated plants Biotech Company Lower capex requirements Smaller footprint Moderna Clinical Commercial Manufacture Manufacture Slide 145
Slide 146: Now 4 manufacturing engines…
Now 4 manufacturing engines… PERSONALIZED PRECLINICAL VACCINE UNIT CLINICAL COMMERCIAL Slide 146
Slide 147: Modular manufacturing kits enable scalability and consistency
Modular manufacturing "kits" enable scalability and consistency Nucleotides Kits are designed to: implement in any location Lipids Buffers replicate and scale quickly Enzymes DNA mRNA mRNA + LNP Drug product Kit = Manufacturing Train Slide 147
Slide 148: Moderna manufacturing collaborations
Moderna manufacturing collaborations (US) United States Independent supply mRNA mRNA + LNP chains Manufacturing scale up to supply 500 million to 1 billion doses per year mRNA mRNA + LNP (Switzerland) International ROVI (Spain) Slide 148
Slide 149: Working with experienced partners
Working with experienced partners Digitally integrated site including Plasmid, State-of-the-art, barrier- Buffer Prep, QC and isolated filling lines sterile filling capacity US US Global Presence in 65 countries Manufacturing with with diversified NH and VISP sites marketing portfolio of using the s
Slide 150: From manufacturing to distribution
From manufacturing to distribution Pre-conditioned -20°C Temp -20°C shipper controlled truck for full loads Multi-dose vial 10-vial cartons Full cases Full or partial pallets (10 doses per v ial) (100 doses) (1,200 doses) (up to 230,400 doses) Slide 150
Slide 151: Distribution to any immunization locations using existing infrastructure
Distribution to any immunization locations using existing infrastructure Storage Conditions* Freezer: -20°C/-4°F for 6 months Flexible and adaptable + supply chain Fridge: 2-8°C/~36-46°F Uses standard existing for up to 7 days vaccination infrastructure + No dilution required Ship any configuration
Slide 152: Standard 0.5 mL liquid administration provided in multi-dose vials
Standard 0.5 mL liquid administration provided in multi-dose vials Standard needles & syringes Can be deployed in any setting: Ready to use, draw Hospitals No dilution 0.5mL and inject required Doctors' offices Nursing homes Immunization centers 10 dose vials Slide 152
Slide 153: Moderna's vaccine franchise
Moderna’s vaccine franchise Prophylactic Vaccines Likely Commercial Drug Product Profile* COVID-19 vaccine Liquid, Multi-Dose Vial (10 doses), -20°C storage ≥6 months shelf-life (mRNA-1273) CMV vaccine (mRNA-1647) Lyophilized, Single-Dose (0.5mL), 5°C storage ≥ 18months shelf-life Zika vaccine (mRNA
Slide 154: CMC BLA/Emergency Use Authorization (EUA) readiness
CMC BLA/Emergency Use Authorization (EUA) readiness Experienced CMC leadership team Product development ✓ BLA launch✓ Commercial operation ✓ Expert commercial manufacturing partner, i.e. Lonza with more than 45 BLA's/MAA’s Scale validation Commercial scale ✓ Next scale in progress Extensive operatio
Slide 155: We are on target
We are on target Kits able to produce 500 million to 1 billion doses with independent supply chains Started manufacturing for market use Scale up and documentation on track Slide 155
Slide 156: Thank you
Thank you Slide 156
Slide 157: New Research & Development
New Research & Development Stephen Hoge, M.D. President Slide 157
Slide 158: Moderna and Vertex Establish New Collaboration to Treat Cystic Fibrosis
Moderna and Vertex Establish New Collaboration to Treat Cystic Fibrosis Using Gene Editing Three-Year Collaboration Overview • Aimed at the discovery and development of lipid nanoparticles (LNPs) and mRNAs for the delivery of gene-editing therapies for the treatment of cystic fibrosis (CF) • Initial
Slide 159: Vertex collaborations to address Cystic Fibrosis
Vertex collaborations to address Cystic Fibrosis Two parallel approaches to addressing the unmet Existing Collaboration: mRNA for CFTR need New Collaboration: mRNA for gene therapy (Approximately 10% of Cystic Formulation Fibrosis patients are not CFTR-encoded mRNA addressable with a CFTR modulator)
Slide 160: Moderna and Chiesi Group collaboration for PAH
Moderna and Chiesi Group establish collaboration to discover and develop mRNA therapeutics for pulmonary arterial hypertension (PAH) Collaboration Overview • Announced a collaboration with Chiesi Farmaceutici S.p.A, an international research-focused healthcare group (Chiesi Group) • Aimed at the dis
Slide 161: Conclusion
Conclusion Stéphane Bancel Chief Executive Officer Slide 161
Slide 162: This was our vision: mRNA as a potential new class of medicines
This was our vision: mRNA as a potential new class of medicines 1. Large product opportunity 2. Higher probability of technical success 3. Accelerated research and development timelines 4. Greater capital efficiency over time vs. recombinant technology Slide 162
Slide 163: This is how far we have come
This is how far we have come Slide 163 Product subject to regulatory review and approval
Slide 164: Moderna has, and will continue, to expand in two dimensions
Moderna has, and will continue, to expand in two dimensions Medicine Time Medicine concept commercialization Vaccine Oncology VEGF mRNA Breadth Rare disease Lung Gene editing … Slide 164
Slide 165: Development pipeline
Development pipeline September 2020 Preclinical (incl. Open IND) Phase 1 Phase 2 Phase 3 Commercial Phase 2 Launch Pediatric RSV Flu Adult RSV EBV Zika preparations COVID-19 preparation (Open IND) (Pandemic) (mRNA1172) Prophylactic Zika COVID-19 Core modalities vaccines Phase 3 Adult RSV hMPV/PIV3 C
Slide 166: Moderna in September 2020
Moderna in September 2020 Phase 3 Phase 2 Phase 1 12 Pipeline COVI D-19 v accine CMV v accine 8 programs Positiv e Phase 1 readouts: 8 v accines, PCV, PCV, OX40L OX40L, VEGF, anti-Chikungunya antibody VEGF Programs in development 7 5 4 2 Vaccines for major unmet needs Immuno-Oncology Rare disease Au
Slide 167: A few closing thoughts
A few closing thoughts • Moderna could receive Emergency Use Authorization (EUA) for mRNA-1273 in 2020 • Moderna could receive a Biologics License Application (BLA) approval for mRNA-1273 in 2021 • mRNA-1273 could validate the entire vaccine portfolio because mRNA is an information molecule • Phase
Slide 168: Our strategic priorities
Our strategic priorities 1 Maximize value generation by mRNA-1273 between now and year-end 2021 2 Accelerate vaccine developments Generate multiple human proof of concepts (POCs) in Oncology/Rare 3 Disease/Auto-immune diseases Continue to invest to expand the breadth of mRNA: mRNA technology, 4 deli
Slide 169: Moderna is close to an historic inflection point
Moderna is close to an historic inflection point Build Core modalities Impact Investigate current and creat e new Exploratory modalit ies Develop mRNA science, Explore mRNA t echnology Scale for commercial delivery t echnology and across six different manufacturing modalit ies mRNA-1273 has accelera
Slide 170: Q&A
Q&A Slide 170