Slide 1: Business Update and Second Quarter 2019 Financial Results
DNA mRNA Protein Business Update and Second Quarter 2019 Financial Results August 7, 2019
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended including, but not limited to, statements concerning clinical program next steps, development candidate activities, future clinical
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: Risk management is essential to building a new class of medicines
Risk management is essential to building a new class of medicines Personalized OX40L+ cancer IL23+IL36g vaccine (Triplet) VEGF-A (no LNP) OX40L Increasing biology risk CMV Fabry vaccine MMA Flu Chikungunya vaccines Antibody (H7, H10) Varying technology risk Localized Systemic Systemic Prophylactic C
Slide 5: Moderna Priorities for 2019-2020
Moderna Priorities for 2019-2020 We focus on our portfolio of potential mRNA medicines, not “lead assets” 1 Execute on the development pipeline • 20 programs in development • Focus on demonstrating human proof of concept 2 New development candidates in existing modalities 3 New development candidate
Slide 6: Moderna's development pipeline
Moderna’s development pipeline 7 Prophylactic KRAS Positive vaccine programs 2 Cancer Vaccine Phase 1 Data* vaccine programs IL12 PCV 3 Intratumoral immuno- oncology programs RSV (1172) VEGF-A 1 Localized regenerative vaccine therapeutics program 3 Systemic secreted Zika OX40L therapeutics programs
Slide 7: Moderna's development pipeline
Moderna’s development pipeline 7 Prophylactic KRAS Positive vaccine programs 2 Cancer Vaccine Phase 1 Data* vaccine programs IL12 PCV 3 Intratumoral immuno- oncology programs RSV (1172) VEGF-A 1 Localized regenerative vaccine therapeutics program 3 Systemic secreted Zika OX40L therapeutics programs
Slide 8: Moderna's development pipeline
Moderna’s development pipeline 7 Prophylactic KRAS Positive vaccine programs 2 Cancer Vaccine Phase 1 Data* vaccine programs IL12 PCV 3 Intratumoral immuno- oncology programs RSV (1172) VEGF-A 1 Localized regenerative vaccine therapeutics program 3 Systemic secreted Zika OX40L therapeutics programs
Slide 9: Moderna in August 2019
Moderna’s development pipeline 7 Prophylactic KRAS Positive vaccine programs 2 Cancer Vaccine Phase 1 Data* vaccine programs IL12 PCV 3 Intratumoral immuno- oncology programs RSV (1172) VEGF-A 1 Localized regenerative vaccine therapeutics program 3 Systemic secreted Zika OX40L therapeutics programs
Slide 10: Moderna in August 2019
Moderna in August 2019 5 5 4 in Development Immuno-Oncology Rare Disease Vaccines for major Programs unmet needs • PCV in Ph 2 • MMA – Ph 1 actively • OX40L preparing for Ph 2 recruiting • CMV in Ph 1, fully enrolled cohort • PA, PKU, Fabry & GSD1a in • RSV in Ph 1 • Triplet in Ph 1 GLP Tox • hMPV+P
Slide 11: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 11
Slide 12: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 12
Slide 13: Prophylactic Vaccines
Prophylactic Vaccines Preclinical Phase 3 and Modality ID # Program Phase 1 Phase 2 Moderna rights dev elopment commercial mRNA-1172/ RSV vaccine Merck V172 Merck to pay milestones and Prophylactic royalties vaccines – mRNA-1777 RSV vaccine Commercial programs mRNA-1647 CMV vaccine Worldw ide Phase
Slide 14: Prophylactic vaccines
Prophylactic vaccines Five positive phase 1 readouts Clinical summary • Safety: > 1,000 healthy volunteers enrolled in 9 phase 1 vaccine trials, at dose levels up to 400µg ̶ Emerging safety and tolerability profile consistent with that of marketed adjuvanted vaccines • Progress: ̶ CMV (mRNA-1647): P
Slide 15: mRNA-1647 for CMV
Prophylactic vaccines mRNA-1647 for CMV : Phase 1 trial fully enrolled; with top dose of 300𝝁𝒈 Congenital cytomegalovirus(CMV) overview • Human CMV is a common human pathogen and member of the herpes virus family and is the leading cause of birth defects • Disease burden: Birth defects in 20% of…
Slide 16: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 16
Slide 17: Cancer Vaccines
Cancer Vaccines Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial Personalized cancer vaccine mRNA-4157 (PCV) 50-50 global profit sharing with Merck Cancer Personalized cancer vaccine NCI-4650 vaccines (PCV) KRAS vaccine 50-50 global profi
Slide 18: PCV (mRNA-4157)
PCV (mRNA-4157) Phase 2 initiated ; First patient consented • Randomized phase 2, PCV + pembrolizumab vs. pembrolizumab alone in resected melanoma at high risk of recurrence Key Objectives • Assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence free survi
Slide 19: Personalized cancer vaccine (mRNA-4157)
Personalized cancer vaccine (mRNA-4157) Phase 1 design Key Objectives • Part A — To assess the safety and tolerability of mRNA-4157 monotherapy in subjects with resected solid tumors, including an apheresis cohort • Parts B, C and D — To assess the safety, tolerability, and recommended phase 2 dose
Slide 20: Personalized Cancer Vaccines
Personalized Cancer Vaccines mRNA-4157: Phase 1 data Clinical & regulatory update • Continuing to enroll patients in phase 1 safety, tolerability and immunogenicity trial monotherapy and in combination with pembrolizumab • Part C&D: Continuing to enroll patients • Interim safety, tolerability immuno
Slide 21: KRAS Vaccine
KRAS Vaccine mRNA-5671/Merck V941: KRAS Overview: • KRAS is a key regulator of cell proliferation and survival; mutations cause dysregulated cell proliferation • One of the most frequently mutated oncogenes in human cancers; mutation is present in >20% of human cancers • Mutations found principally
Slide 22: KRAS vaccine (mRNA-5671)/Merck V941
KRAS vaccine (mRNA-5671)/Merck V941 First Patient dosed in Phase 1 trial Phase 1 study overview —A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/Merck V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or
Slide 23: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 23
Slide 24: Intratumoral Immuno-Oncology
Intratumoral Immuno-Oncology Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial OX40L mRNA-2416 Solid tumors/lymphoma Worldwide Advanced ovarian Cancer OX40L+IL23+IL36γ Intratumoral mRNA-2752 (Triplet) Worldwide immuno- Solid tumors/lymphom
Slide 25: OX40L
OX40L mRNA-2416: Phase 1 ongoing at highest dose level, Phase 2 cohort is being prepared OX40L Overview: • OX40L is a potent co-stimulator, which promotes T-cell proliferation and enhanced survival in the presence of antigen mRNA-2416: • mRNA-2416 encodes for OX40L, which is a membrane protein that
Slide 26: OX40L (mRNA-2416)
OX40L (mRNA-2416) Phase 1/2 design Key Objectives • Evaluate safety and tolerability of Phase 2 cohort mRNA-2416 administered intratumorally • Define the maximum tolerated dose and recommended dose for expansion • Other endpoints include PK analyses as well as assessment of biomarkers of immunologic
Slide 27: OX40L+IL23+IL36γ
OX40L+IL23+IL36𝜸 mRNA-2752: Phase 1 ongoing; First patient dosed in combination durvalumab OX40L+IL23+IL36𝜸 (Triplet) Overview: • OX40L powerful co-stimulatory protein that enhances T-cell expansion, function and memory formation • IL23 and IL36𝛾 have established roles in mediating immune…
Slide 28: OX40L+IL23+IL36γ (Triplet) (mRNA-2752)
OX40L+IL23+IL36γ (Triplet) (mRNA-2752) Phase 1 design Key Objectives • Evaluate safety and tolerability of mRNA-2752 administered alone and in combination with checkpoint inhibitors • Define MTD and recommended dose for expansion for mRNA-2752 alone and in combination with durvalumab • Intended to a
Slide 29: MEDI1191: First patient dosed in phase 1
IL12 MEDI1191: First patient dosed in phase 1 IL12 Overview: • IL12 is a potent immune modulator associated with type 1 immune response and production of interferon gamma MEDI1191: • Encodes for IL12, a secreted cytokine that acts locally in the tumor microenvironment (TME) Clinical: • Phase 1, open
Slide 30: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 30
Slide 31: Localized Regenerative Therapeutics
Localized Regenerative Therapeutics Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial Localized VEGF-A AZ to pay regenerative AZD8601 Myocardial ischemia milestones and therapeutics royalties Slide 31
Slide 32: VEGF-A
VEGF-A AZD8601: Phase 2a ongoing; additional trial sites open VEGF-A: • VEGF-A is a potent angiogenic factor that promotes the growth of blood vessels • Preclinical data suggest that expression of VEGF-A in the ischemic heart could increase blood flow and partially restore cardiac function AZD8601:
Slide 33: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 33
Slide 34: Systemic secreted therapeutics
Systemic secreted therapeutics Program Preclinical Phase 3and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial Worldw ide Antibody against mRNA-1944 Chikungunya virus DARPA funded 50-50 U.S. profit Systemic Relaxin sharing; AZ to pay AZD7970 secreted Heart failure royal
Slide 35: Antibody against Chikungunya virus
Antibody against Chikungunya virus mRNA-1944: 6 of 8 subjects dosed in 3rd cohort of Ph 1 trial1 Antibody against Chikungunya virus Overview: • Circulating antibody to confer passive immunity mRNA-1944: • Encodes for antibodies against Chikungunya virus consisting of heavy and light chains Expected
Slide 36: Antibody against Chikungunya virus (mRNA-1944)
Antibody against Chikungunya virus (mRNA-1944) 6 of 8 subjects dosed in 3rd cohort of Phase 1 trial1 • Randomized, placebo-controlled, single ascending dose study in healthy adults Key Objectives • Evaluate safety and tolerability of escalating doses of mRNA-1944 administered via intravenous infusio
Slide 37: Our Modality Strategy
Our Modality Strategy Personalized OX40L+ cancer IL23+IL36g vaccine (Triplet) VEGF-A (no LNP) OX40L Increasing biology risk CMV Fabry vaccine MMA Flu Chikungunya vaccines Antibody (H7, H10) Varying technology risk Localized Systemic Systemic Prophylactic Cancer Intratumoral regenerative secreted int
Slide 38: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 38
Slide 39: Systemic intracellular therapeutics
Systemic intracellular therapeutics Program Preclinical Phase 3 and Modality ID# Phase 1 Phase 2 Moderna rights Indication dev elopment commercial MUT mRNA-3704 Methylmalonic Worldw ide acidemia, MMA PCCA+PCCB mRNA-3927 Propionic Worldwide Systemic acidemia, PA intracellular therapeutics PAH mRNA-32
Slide 40: Methylmalonic acidemia (MMA) Propionic acidemia (PA)
Methylmalonic acidemia (MMA) Propionic acidemia (PA) MMA/ PA Overview: Organic acidemias • MMA and PA are inborn errors of protein Multiple candidates targeting the same metabolic pathway metabolism caused by MUT enzyme deficiency and PCC enzyme deficiency, respectively • Similar biology and disease
Slide 41: MMA (mRNA-3704): Phase 1/2 trial sites actively recruiting
MMA (mRNA-3704): Phase 1/2 trial sites actively recruiting PA (mRNA-3927): Preparing IND filing MMA (mRNA-3704): • Encodes for MUT enzyme, an intracellular protein that acts in the mitochondria of liver cells • Same proprietary lipid nanoparticle formulation as antibody against Chikungunya virus (mR
Slide 42: Moderna's development pipeline
Moderna’s development pipeline Announcements since IPO Program Preclinical Phase 3 and Modality ID # Phase 1 Phase 2 Moderna rights Indication development commercial mRNA-1172 Respiratory syncytial virus (RSV) vaccine First patient dosed in phase 1 Merck to pay milestones and royalties mRNA-1777 Res
Slide 43: Second Quarter 2019 Financial Results (Unaudited)
Second Quarter 2019 Financial Results (Unaudited) Balance Sheets June 30, December 31, 2019 2018 Cash, cash equivalents and investments 1 $ 1.44 billion $ 1.69 billion Statements of Cash Flows 6 months ended 6 months ended June 30, 2019 June 30, 2018 Net cash used in operating activities 2 $ 256 mm
Slide 44: Moderna Priorities for 2019-2020
Moderna Priorities for 2019-2020 We focus on our portfolio of potential mRNA medicines, not “lead assets” 1 Execute on the development pipeline • 20 programs in development • Focus on demonstrating human proof of concept 2 New development candidates in existing modalities 3 New development candidate
Slide 45: Moderna 2Q19 Highlights
Moderna 2Q19 Highlights • Phase 2 Personalized Cancer Vaccine (mRNA-4157) study initiated, with first patient consented • Phase 1 CMV vaccine (mRNA-1647) study fully enrolled • Four new phase 1 trials have begun, two in immuno-oncology and two in infectious diseases • Vertex Pharmaceuticals extended
Slide 46: Anticipated clinical next steps
Anticipated clinical next steps • CMV – Phase 1 safety and immunogenicity data; Phase 2 start Prophylactic • hMPV+PIV3 – Phase 1b seropositive toddler study start vaccines • RSV – Phase 1 safety and immunogenicity data • Zika – Phase 1 safety and immunogenicity data Cancer • PCV – Additional Ph1 dat
Slide 47: 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 47
Slide 48: mRNA as a potential new class of medicines
mRNA as a potential new class of medicines 1. Large product opportunity 2. Higher probability Indication Development of technical Candidate CMV success mRNA-1647 RSV3. Accelerated mRNA-1172/1777 researchmRNA-1653 hMPV/PIV3 and Zika development mRNA-1893 timelines PCV4. Greater capital mRNA-4157 KRAS
Slide 49: 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 19 INDs/CTAs opened 4. Greater capital efficiency over time 8 positive phase 1 vs. recombinant readouts to date * 16 development candid
Slide 50: Our Mission
Our Mission To deliver on the promise of mRNA science to create a new generation of transformative medicines for patients. Slide 50
Slide 51: Please Join us for R&D Day
Slide 51 moderna Please Join us for R&D Day Thursday, September 12, 2019 JW Marriott Essex House 160 Central Park South Grand Salon New York, NY 10019 7:30am — 8:30am Breakfast and Registration 8:30am — 12:30pm Presentations Lunch to Follow RSVP by Thursday, August 29 Daniella Funaro daniella funaro