Slide 1: Corporate Update and 2018 Financial Review
DNA mRNA Protein Corporate Update and 2018 Financial Review March 6th, 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: mRNA as a potential new class of medicines; the scope of the mRNA opportunity;
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+IL36 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 currently in development • Focus on demonstrating human proof of concept 2 New development candidates in existing modalities 3 New development
Slide 6: Moderna's development pipeline
Moderna’s development pipeline 8 Prophylactic vaccine programs 2 Cancer vaccine programs 3 Intratumoral immuno- oncology programs PKU 1 Localized regenerative therapeutics program 3 Systemic secreted Chikungunya therapeutics programs PA antibody 3 Systemic intracellular therapeutics programs New ann
Slide 7: Norwood, MA site was built to enable Moderna's scale-up
Norwood, MA site was built to enable Moderna’s scale-up Capability Operational mRNA Formulation Vial filling Labeling Critical raw materials In progress Clinical personalized cancer vaccine Automated pre-clinical production Slide 7
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: hMPV+PIV3 vaccine (mRNA-1653)
hMPV+PIV3 vaccine (mRNA-1653) Phase 1 design – healthy adults Key Objectives • Evaluate safety and immunogenicity through 12 months after the second vaccination • Select optimal dose and vaccination schedule for further clinical development Dosing schedule: Day 1 and Month 1 Dose-escalation phase A
Slide 11: hMPV+PIV3 vaccine (mRNA-1653)
hMPV+PIV3 vaccine (mRNA-1653) Phase 1 in healthy adults Interim results, through study Month 2 (1 month after second vaccination) Safety and tolerability Immunogenicity • mRNA-1653 was found to be • Single vaccination boosted serum generally well tolerated neutralization titers against hMPV and PIV3
Slide 12: Congenital CMV vaccine (mRNA-1647)
Congenital CMV vaccine (mRNA-1647) Ongoing Phase 1 design – initial 3 dose levels enrolled Key Objective: Evaluate safety, reactogenicity, and immunogenicity of different dose levels of mRNA-1647 • Based on blinded safety and tolerability profile observed, we plan to test two higher dose levels in s
Slide 13: Prophylactic vaccines
Prophylactic vaccines Five positive Phase 1 readouts, Merck preparing for RSV vaccine Phase 2 Clinical data Anticipated next steps • Safety: ~ 950 healthy volunteers enrolled in 7 • CMV (mRNA-1647) – Phase 1 safety Phase 1 vaccine trials, at dose levels up to 300µg. and immunogenicity data; Phase 2
Slide 14: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 14
Slide 15: Cancer vaccines
Cancer vaccines Randomized Phase 2 protocol filed Clinical data Anticipated next steps • Safety: PCV (mRNA-4157) – >30 pts dosed, enrolling • PCV (mRNA-4157) – Phase 1 expansion cohorts at 1.0 mg, no dose limiting toxicities clinical activity; start of to date1 randomized Phase 2 • Activity: PCV (mR
Slide 16: PCV (mRNA-4157)
PCV (mRNA-4157) Protocol package filed with FDA for randomized Phase 2 study • 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 recu
Slide 17: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 17
Slide 18: Intratumoral immuno-oncology
Intratumoral immuno-oncology mRNA-2752 Phase 1 ongoing; amendment filed for OX40L Phase 2 cohort Clinical & regulatory update Anticipated next steps • OX40L (mRNA-2416) – In dose confirmation stage, dosing at up • OX40L (mRNA-2416) – to 8 mg1 Initiate dosing of Phase 2 advanced ovarian ̶ Amendment f
Slide 19: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics • Randomized Phase 2a ongoing – direct cardiac injection in patients undergoing CABG • Phase 1 data recently
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: mRNA encoding Chikungunya antibody as platform proof point
mRNA encoding Chikungunya antibody as platform proof point for systemic therapeutics modalities OX40L+ Personalized IL23+IL36 cancer (Triplet) vaccine VEGF-A (no LNP) Increasing biology risk OX40L CMV Fabry vaccine MMA Flu Chikungunya vaccines Antibody (H7, H10) Varying technology risk Intratumoral
Slide 22: Antibody against Chikungunya virus (mRNA-1944)
Antibody against Chikungunya virus (mRNA-1944) First dose level cohort of healthy volunteers dosed in Phase 1 trial • Randomized, placebo-controlled, single ascending dose study in healthy adults Enrolled1 Key Objectives • Evaluate safety and tolerability of escalating doses of mRNA-1944 administere
Slide 23: Systemic secreted therapeutics
Systemic secreted therapeutics First in human for first systemic therapeutic Clinical & regulatory update • Chikungunya Ab (mRNA-1944) – Enrolled first dose level (0.1 mg/kg, Anticipated next steps 8 subjects), no DLTs to date1 • Chikungunya Ab (mRNA- Representative pre-clinical data 1944) – Phase 1
Slide 24: Progress by modality
Progress by modality Prophylactic Cancer Intratumoral Localized Systemic Systemic vaccines vaccines immuno-oncology regenerative secreted intracellular therapeutics therapeutics therapeutics Slide 24
Slide 25: Systemic intracellular therapeutics
Systemic intracellular therapeutics Rare disease programs advancing toward clinic; MMA IND open Clinical & regulatory update Anticipated next steps • MMA (mRNA-3704) – IND safe to proceed, Fast Track Designation • MMA (mRNA-3704) – safety • MMA and PA Natural History Study (MaP): 32 patients enrolle
Slide 26: Methylmalonic acidemia (MMA) (mRNA-3704)
Methylmalonic acidemia (MMA) (mRNA-3704) Phase 1/2 design – IND safe to proceed Study Objectives • Evaluate the safety, pharmacodynamics (as assessed by changes in plasma methylmalonic acid), and pharmacokinetic profile of mRNA-3704 in patients with MMA • Eligibility criteria: patients with isolated
Slide 27: Moderna's development pipeline
Moderna’s development pipeline New announcements since IPO Dec 6, 2018 Program Preclinical Phase 3 and Modality Program # Phase 1 Phase 2 Moderna rights Indication development commercial Merck to pay milestones mRNA-1777 Respiratory syncytial virus (RSV) vaccine and royalties mRNA-1647 Cytomegalovir
Slide 28: 2018 Financial Results (Unaudited)
2018 Financial Results (Unaudited) Balance Sheets December 31, 2018 December 31, 2017 Cash, cash equivalents and investments 1 $ 1,694 mm $ 902 mm Statements of Cash Flows 2018 2017 Net cash used in operating activities $ 331 mm $ 331 mm Cash used for purchases of property and equipment 2 $ 106 mm $
Slide 29: 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 currently in development • Focus on demonstrating human proof of concept 2 New development candidates in existing modalities 3 New development
Slide 30: 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 2a start • Zika – IND filing Cancer • PCV – Phase 1 clinical activity; randomized Phase 2 start vaccines • KRAS – Pha
Slide 31: Moderna annual investor events
Moderna annual investor events May 7, 2019 – Science Day, Cambridge MA September 12, 2019 – R&D Day, New York NY Slide 31
Slide 32: Moderna on March 6, 2019: Pipeline in Development
Moderna on March 6, 2019 3 5 6 4 Pipeline Positive Ph 1 Programs in or Open INDs Ph 1 trials ongoing readouts planning for Ph 2 5 4 3 in Development Immuno-Oncology Rare Disease Vaccines for major Programs unmet needs • OX40L preparing for Ph 2 • MMA - open IND cohort • PA, PKU & Fabry in GLP Tox •
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