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Mrna-4157) Last Program Update: September 9, 2021 Moderna’s therapeutics: Personalized cancer vaccine (PCV) (mRNA-4157) Last program update: September 9, 2021 Preclinical Moderna Modality Program ID # Phase 1 Phase 2 Phase 3 Commercial development rights Antibody against Chikungunya Worldwide virus mRNA-1944 DARPA funded IL-2 Worldwide Systemic Autoimmune disorders mRNA-6231 secreted & cell Relaxin Worldwide surface Heart failure mRNA-0184 therapeutics PD-L1 Worldwide Autoimmune hepatitis mRNA-6981 Personalized cancer vaccine 50-50 global profit mRNA-4157 sharing Cancer (PCV) with Merck vaccines 50-50 global profit KRAS vaccine mRNA-5671 sharing with Merck OX40L/IL-23/IL-36γ (Triplet) Worldwide Intratumoral Solid tumors/lymphoma mRNA-2752 Immuno- 50-50 U.S. profit oncology IL-12 sharing; AZ to pay Solid tumors MEDI1191 royalties on ex- U.S. sales Localized VEGF-A AZ to pay Regenerative AZD8601 milestones and Myocardial ischemia royalties Therapeutics Propionic Acidemia (PA) mRNA-3927 Worldwide Methylmalonic Acidemia (MMA) mRNA-3705 Worldwide Systemic Glycogen Storage Disease Type Intracellular Worldwide 1a (GSD1a) mRNA-3745 Open IND Therapeutics Phenylketonuria (PKU) mRNA-3283 Worldwide Crigler-Najjar Syndrome Type 1 Provided to ILCM (CN-1) mRNA-3351 free of charge Slide 1 Personalized cancer vaccine (mRNA-4157) Designed to target an individual patient’s unique tumor mutations Personalized drug design Rapid turnaround times Mutations identified in protein neoantigen and Needle-to-needle in just weeks major histocompatibility complex Slide 2 PCV vaccine (mRNA-4157) elicits T cells required for curative cancer therapy T cell Neoantigen concatemers TCR in single mRNA Ribosome Neoantigen Proteasome Vesicle Neoantigen protein chain ER Golgi Nucleus Slide 3 Personalized cancer vaccine (mRNA-4157) is ongoing in both Phase 1 and Phase 2 trials simultaneously Phase 1 Trial Overview Phase 2 Trial Overview ▪ Assessing safety, tolerability and ▪ Randomized controlled study: PCV + immunogenicity as monotherapy and in pembrolizumab (KEYTRUDA®) vs. ® combination with pembrolizumab (KEYTRUDA ) pembrolizumab alone (2:1) ▪ Identify a safe Ph 2 dose ▪ High Risk Resected Melanoma Patients ▪ Encouraging early signal observed in (HPV-) ▪ Primary endpoint = recurrence free survival at Head and neck squamous cell carcinomas 12 months (HNSCC)1,2 ▪ N~150 (Fully enrolled) ̶ Cohort expanded from 10 to 40 patients ̶ Currently enrolling expanded cohort 1. Data presented at SITC 2020. Data cutoff as of Oct 01, 2020 Slide 4 2. https://investors.modernatx.com/static-files/a79f9ce0-02f6-4ea8-8a8b-2d9f4ddcc531 Expanded Phase 1 Head and neck squamous cell carcinomas (HNSCC) cohort following encouraging early signal Fully enrolled Phase 1 Trial Overview Part A: Dose escalation (N=18) parts A & B mRNA-4157 Dose: 0.04 mg mRNA-4157 Dose: 0.13 mg ▪ Assessing safety, tolerability and mRNA-4157 Dose: 0.39 mg immunogenicity as monotherapy and in mRNA-4157 Dose: 1 mg combination with pembrolizumab Part B: PD1i-refractory (N=7) ▪ Dose escalation to determine Ph 2 dose level Part B: Dose escalation (N=18) Part C: PD1/PDl1i naïve (n=34) ▪ Encouraging early signal observed in (HPV-) mRNA-4157 Dose: 0.04 mg • MSS-CRC (n=17) Head and neck squamous cell carcinomas mRNA-4157 Dose: 0.13 mg • HPV-neg HNSCC (n=40) (HNSCC)1,2 mRNA-4157 Dose: 0.39 mg mRNA-4157 Dose: 1 mg ̶ Cohort expanded from 10 to 40 patients Part D: Adjuvant melanoma (n=10) ̶ Currently enrolling expanded cohort HPV: Human papillomavirus HNSCC: Head and neck squamous cell carcinomas 1. Data presented at SITC 2020. Data cutoff as of Oct 01, 2020 Slide 5 2. https://investors.modernatx.com/static-files/a79f9ce0-02f6-4ea8-8a8b-2d9f4ddcc531 Encouraging early signal in checkpoint inhibitor (CPI) naïve HPV(-) HNSCC patients receiving mRNA-4157 + pembrolizumab (data presented at SITC 2020) Best Overall Response HPV(-) HNSCC (n=10*) Best overall response Complete Response (CR) 2 Partial Response (PR) 3 Stable Disease (SD) 4 Progressive Disease (PD) 1 Overall response rate (ORR) 50% Disease control rate (DCR) 90% Median progression-free survival (mPFS) 9.8 months Median duration of response (mDOR) Not reached *4 additional patients started pembrolizumab dosing but progressed and came off study prior to the start of vaccine dosing. 1. Data presented at SITC 2020. Data cutoff as of Oct 01, 2020 Slide 6 2. https://investors.modernatx.com/static-files/a79f9ce0-02f6-4ea8-8a8b-2d9f4ddcc531 Encouraging early signal in checkpoint inhibitor (CPI) naïve HPV(-) HNSCC patients receiving mRNA-4157 + pembrolizumab (data presented at SITC 2020) Time on Study Swimmer Plot Median progression-free survival (mPFS) 9.8 months Median duration of response (mDOR) Not reached Slide 7 Encouraging early signal in checkpoint inhibitor (CPI) naïve HPV(-) HNSCC patients receiving mRNA-4157 + pembrolizumab (data presented at SITC 2020) %Change from Baseline Spider Plot Figure 1-1: Four out of five responding patients achieved PR after 2 doses of pembrolizumab prior to the start of vaccine administration. Two PRs converted to CR after the addition of vaccine. Patient 109’s tumor burden was decreasing but then started to progress until 2 doses of the vaccine were given, and then subsequently achieved a PR. Patient 067 also had started to progress until after the 5th dose of the vaccine, then ultimately had a discordant CR in the neck while progressing in the lung (vaccine was manufactured from the genetic sequencing of the dermal neck disease). Patient 117 progressed on monotherapy pembrolizumab until vaccine was started and tumor burden continues to decrease. Slide 8 Personalized cancer vaccine (mRNA-4157) Phase 2 trial is now fully enrolled Patients with resected melanoma at high risk of recurrence Phase 2 Trial Overview Enrollment and randomization 2:1 ▪ Randomized, placebo controlled, PCV + pembrolizumab (KEYTRUDA®) vs. pembrolizumab alone (2:1) Combination treatment arm Control treatment arm (pembrolizumab and mRNA-4157) (pembrolizumab only) ▪ Resected Melanoma patients - high Up to 1 year of pembrolizumab Up to 1 year of pembrolizumab recurrence risk treatment (n=100) treatment (n=50) ▪ Primary endpoint = recurrence free survival at 12 months Recurrence free survival (RFS) ▪ N~150 (Fully enrolled) Primary analysis 12-month RFS Slide 9 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 candid ate activities, preclinical and clinical studies, regulatory submissions and approvals, risk management and estimates and forward -looking projections with respect to Moderna or its anticipated future performance or events. In some cases, forward -looking statements can be identified by terminology such as “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimat es,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward -looking statements contain these words. The forward-looking statements in this presentation are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward - looking statements. These risks, uncertainties and other factors include, among others: preclinical and clinical development is lengthy and uncertain, especially for a new category of medicines such as mRNA, and therefore Moderna’s preclinical programs or development candidates may be delayed, terminated, or may never advance to or in the clinic; no mRNA drug has been approved in this new p otential category of medicines, and may never be approved; mRNA drug development has substantial clinical development and regulatory r isks due to the novel and unprecedented nature of this new category of medicines; and those described in Moderna’s most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with SEC, which are available on the SEC's website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements in this presentation in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date hereof. Slide 10.
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