Slide 1: Pipeline Progress, Business Updates, and First Quarter 2019 Financial Results
DNA mRNA Protein Pipeline Progress, Business Updates, and First Quarter 2019 Financial Results May 8th, 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 potential development candidate applications, development candidate activities,
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 Priorities for 2019-2020: New announcements
New announcements since corporate update March 6, 2019 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 • Update on next slide 2
Slide 7: Moderna's development pipeline
Moderna’s development pipeline 7 Prophylactic vaccine programs GSD1a 2 Cancer vaccine programs 3 Intratumoral immuno- PKU oncology programs 1 Localized regenerative therapeutics program PA 3 Systemic secreted therapeutics programs 4 Systemic intracellular Chikungunya RSV (1777) therapeutics programs
Slide 8: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 8
Slide 9: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 9
Slide 10: mRNA Vaccine for RSV
mRNA Vaccine for RSV Codes for the RSV prefusion F protein Formulation RSV pre-fusion F protein encoded mRNA Pre-fusion F protein Muscle cell Ribosome Viral protein chains Encoded mRNA Cytosol Nucleus Slide 10
Slide 11: mRNA-1172 vs. mRNA-1777
mRNA-1172 vs. mRNA-1777 mRNA-1172 is significantly more potent than mRNA-1777 based on preclinical data Preclinical NHP data: • Vaccination: 500 μl IM (right deltoid) or 250 μl intranasally • Challenge: 1 x 105.5 pfu wt RSV A2/ml; 1 ml intranasally + 1 ml intratracheally • Animals: 4 African green m
Slide 12: Prophylactic vaccines
Prophylactic vaccines Five positive Phase 1 readouts; Merck filed IND for second RSV vaccine; Merck discontinued preclinical development of VZV Clinical data Anticipated next steps • Safety: ~ 1,000 healthy volunteers enrolled in 7 Phase 1 • CMV (mRNA-1647) – Phase 1 safety and immunogenicity vaccin
Slide 13: Progress by modality: Cancer vaccines
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics • PCV (mRNA-4157, NCI- 4650) Phase 1 ongoing – updates to be provided at ASCO • Preparing for KRAS (mRNA- 567
Slide 14: Progress by modality: Intratumoral immuno-oncology
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics • Continuing enrollment for OX40L (mRNA-2416) and OX40L + IL23 + IL36γ (Triplet, mRNA-2752) • Preparing for P
Slide 15: Progress by modality: Localized regenerative therapeutics
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics • Randomized Phase 2a ongoing for our VEGF A program (AZD8601) – direct cardiac injection in patients undergo
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: 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 18: Antibody against Chikungunya virus (mRNA-1944)
Antibody against Chikungunya virus (mRNA-1944) Second dose level cohort of healthy volunteers enrolled in Phase 1 trial • Randomized, placebo-controlled, single ascending dose study in healthy adults Key Objectives • Evaluate safety and tolerability of escalating doses of Enrolled1 mRNA-1944 adminis
Slide 19: Systemic secreted therapeutics
Systemic secreted therapeutics First in human for first systemic therapeutic Clinical & regulatory update • Chikungunya Ab (mRNA-1944) – Enrolled second dose level (0.3 Anticipated next steps mg/kg, 8 subjects)1 • Chikungunya Ab (mRNA- Representative preclinical data 1944) – Phase 1 safety and • Saf
Slide 20: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 20
Slide 21: Systemic intracellular therapeutics
Systemic intracellular therapeutics Rare disease programs advancing toward clinic; GSD1a DC nomination Clinical & regulatory update Anticipated next steps • MMA (mRNA-3704) – Currently in process of initiating sites for phase 1 • MMA (mRNA-3704) – safety and • MMA and PA Natural History Study (MaP):
Slide 22: Glycogen storage disease type 1a (GSD1a) (mRNA-3745)
Glycogen storage disease type 1a (GSD1a) (mRNA-3745) mRNA-encoded enzyme localized to endoplasmic reticulum Slide 22 Last updated: May 8, 2019
Slide 23: Glycogen storage disease type 1a (GSD1a) overview
Glycogen storage disease type 1a (GSD1a) overview New intracellular therapeutics DC – mRNA-3745 • GSD1a is a rare inherited metabolic disease Hypoglycemic seizures resulting from a deficiency in the metabolism of Cognitive impairment glucose, due to mutations within the enzyme glucose 6-phosphatase,
Slide 24: GSD1a preclinical data – restoration of enzymatic activity
Glycogen storage disease type 1a (GSD1a) (mRNA-3745) Preclinical data – restoration of enzymatic activity Study Design: • Animals: Liver-Specific G6PC Knockout Study Design: • Animals: Liver-Specific G6PC Knockout (L.G6PC -/-) (L.G6PC -/-) Species: • Dose: 0.2, 0.5, 1.0 mpk Species: • Dose: 0.25 mpk
Slide 25: Moderna's development pipeline
Moderna’s development pipeline New announcements since earnings call March 6, 2019 Program Preclinical Phase 3 and Modality Program # Phase 1 Phase 2 Moderna rights Indication development commercial mRNA-1172 Respiratory syncytial virus (RSV) vaccine Merck filed IND Merck to pay milestones and royal
Slide 26: Moderna 2019 Science Day
Moderna 2019 Science Day May 7, 2019 Topic Speaker Welcome & Introduction to the Day Stephane Bancel & Stephen Hoge, Moderna • Foundations of Immune Silence Melissa Moore, Moderna • Improvements in Potency − mRNA Structure and Ribosome Traffic Jams Melissa Moore, Moderna − Big Gains from the Untrans
Slide 27: Highlights from 2019 Science Day (Part 1)
Highlights from 2019 Science Day (Part 1) Making more potent and safer medicines • Latest in vivo characterization of the nature of innate immune response and the importance of uridine modification to making immune silent mRNA • Advances in how we design our mRNA to maximize potency, for instance ho
Slide 28: Highlights from 2019 Science Day (Part 2)
Highlights from 2019 Science Day (Part 2) Introducing our Immune Nanoparticle research Dose-dependent Cancer in vivo pharmacology to all major cell types (system-wide) Transient protein expression mRNA-based mRNA software to to confer cells immune system select cell type(s) with new functions and en
Slide 29: First Quarter 2019 Financial Results (Unaudited)
First Quarter 2019 Financial Results (Unaudited) Balance Sheets March 31, 2019 December 31, 2018 Cash, cash equivalents and investments $ 1,547 mm $ 1,694 mm Statements of Cash Flows 3 months ended 3 months ended March 31, 2019 March 31, 2018 Net cash used in operating activities 1 $ 144 mm $ 111 mm
Slide 30: 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 31: Anticipated clinical next steps
Anticipated clinical next steps • CMV – Phase 1 safety and immunogenicity data; Phase 2 start Prophylactic • hMPV+PIV3 – Phase 1b age de-escalation study start vaccines • RSV – Phase 1 start for mRNA-1172 • Zika – IND filing Cancer • PCV – Phase 1 clinical activity; randomized Phase 2 start vaccines
Slide 32: Moderna Pipeline in Development
Moderna on May 8, 2019 3 5 6 3 ~1,000 Pipeline Open INDs Healthy Ph 1 trials Positive Ph 1 Programs in or awaiting Ph 1 volunteers and ongoing readouts planning for Ph 2 start patients enrolled 5 5 3 in Development Immuno-Oncology Rare Disease Vaccines for major Programs unmet needs • OX40L preparin
Slide 33: Our Mission
Our Mission To deliver on the promise of mRNA science to create a new generation of transformative medicines for patients. Slide 33