Slide 1: American Society of Clinical Oncology Meeting Review
DNA mRNA Protein American Society of Clinical Oncology Meeting Review June 3, 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: the potential for Moderna’s investigational personalized cancer vaccines (PCV)
Slide 3: ASCO 2019: Interim Analysis of Phase 1 Study of mRNA-4157
ASCO 2019 An Interim Analysis of a Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and in Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors (Keynote-603) Cut off date for d
Slide 4: Background: The Personalized Neoantigen Approach
Background : The Personalized Neoantigen Approach individualized by patient ▪ T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses ▪ Immunizing patients against such neoantigens in combination with a checkpoint inhibitor (CPI) may elicit gre
Slide 5: Personalized Cancer Vaccine: mRNA-4157 Process Background
Personalized Cancer Vaccine: mRNA-4157 Process Background & MHC ID ▪mRNA-4157 is a personalized neoantigen cancer vaccine encoding up to 20 neoantigens: (from April 2019 forward patients started to receive a vaccine encoding up to 34 neoantigens) ▪Individually designed and manufactured for each pati
Slide 6: Study Design
Study Design* Dose escalation cohorts Part A (Adjuvant patients ): 0.04 mg 0.13 mg 0.39 mg 1.0 mg Monotherapy mRNA4157 n=3 n=6 n=3 n=3 Part B (Metastatic patients): 0.04 mg 0.13 mg 0.39 mg 1.0 mg mRNA4157 + pembrolizumab n=3 n=4 n=7 n=5 Histologies in part A and B: • NSCLC • HPV negative HNSCC • MSI
Slide 7: Study Design
Study Design pembrolizumab mRNA-4157+ Safety pembrolizumab monotherapy pembrolizumab follow-up Screening monotherapy run-in* (Dosing (Dosing every 21 (100 day period (Dosing up to every 21 days days for up to 9 post 35 cycles) for 2 cycles) cycles) treatment) *Part A patients are adjuvant patients r
Slide 8: Patient Demographics
Patient Demographics Part A: 13 Part B: 23 Histologies N =36 Age(y) Part A 13 Range: 52-85 45-88 Melanoma 3 Median: 67 64 MSI HIGH/MMR Deficient Sex • Colorectal Carcinoma 2 Male: 6 13 Female: 7 10 Non-small Cell Lung Cancer 8 Race: Part B 23 Caucasian 13 19 TMB High Black - 1 • Metastatic squamous
Slide 9: Safety Data
Safety Data Related Adverse Event* Grade 2 Grade 3 Part A: mRNA-4157 monotherapy 4 0 LEFT ARM PAIN 1 - COLITIS 1 - FATIGUE 1 - MYALGIAS 1 - Part B: pembrolizumab monotherapy 3 4 DIARRHEA - 1 AMYLASE INCREASE - 1 LIPASE INCREASE - 1 ELEVATED AST 1 - ANEMIA 1 - WORSENED DYSPNEA 1 - ELEVATED GGT - 1 Pa
Slide 10: Patient 40033 (NSCLC) Neoantigen T-Cell Response Data
Patient 40033 (NSCLC) Neoantigen T-Cell Response Data First adjuvant patient dosed with monotherapy mRNA-4157 at 1mg dose A B ▪ Patient was dosed with 1mg of vaccine monotherapy and underwent apheresis at baseline and 7d post 4th dose. ▪ Increases in ex-vivo (unexpanded) T-cell responses were detect
Slide 11: Greater than 3x CD8 T-Cell Responses Detected Post-Vaccine Dose 4
Greater than 3x CD8 T-Cell Responses Detected Post-Vaccine Dose 4 to 55% of Predicted Class I Neoantigens ▪ CD8 T cell responses to individual neoantigens were measured in in vitro stimulated (IVS, expanded) T cells ▪ Flow cytometry plots show increases in % freq. of CD8 cells producing IFNγ 7d post
Slide 12: Part A: Adjuvant Patients Receiving mRNA-4157 Monotherapy
Part A: Adjuvant Patients Receiving mRNA-4157 Monotherapy ▪ 13 adjuvant patients have been treated with mRNA-4157 ▪ 13 patients have completed full course of vaccination per protocol ▪ 11 patients remain disease free up to 72 weeks on study Slide 12
Slide 13: Part B: Metastatic Patients Receiving mRNA-4157/Pembrolizumab Combination
Part B: Metastatic Patients Receiving mRNA-4157/Pembrolizumab Combination ▪ 20 out of 23 advanced/metastatic patients have been treated with mRNA-4157/pembrolizumab combination. ▪ 1 patient with MSI-High CRC had a CR on pembrolizumab monotherapy prior to vaccination ▪ 5 patients had a PR including 2
Slide 14: Best Overall Response
Best Overall Response Slide 14
Slide 15: Patient 40019 - Small Cell Lung Carcinoma
Patient 40019 -Small Cell Lung Carcinoma ▪ Small cell lung cancer patient ▪ Previously treated with chemoradiation and prophylactic cranial irradiation ▪ After 2 cycles of monotherapy pembrolizumab and 2 cycles of mRNA-4157 (0.13mg)/pembrolizumab combination, patient had a partial response (PR) ▪ Th
Slide 16: Patient 40023 – Bladder Carcinoma
Patient 40023 – Bladder Carcinoma ▪ Bladder urothelial carcinoma patient ▪ Previously treated with radical cystoprostatectomy, cisplatin/gemcitabine, HRS7-SN38, four cycles of atezolizumab, and vinorelbine along with frontal lobe resection with radical for brain metastasis ▪ After 2 cycles of monoth
Slide 17: Patient 40031 - Small Cell Lung Carcinoma
Patient 40031- Small Cell Lung Carcinoma ▪ Small cell lung cancer patient ▪ Previously treated with cisplatin/etoposide and doxorubicin/lurbinectedin ▪ After 1 cycle of pembrolizumab run-in, patient experienced an irAE which led to treatment with monotherapy mRNA-4157 (0.39mg) ▪ Patient had a partia
Slide 18: Conclusions
Conclusions • mRNA-4157 is well tolerated at all dose levels studied with no DLTs reported • No mRNA-4157 related grade 3/4 AE or SAE was reported • Neoantigen specific CD8 T-cell responses were detected in 10 out of 18 class I neoantigens in patient 40033, the first patient dosed at 1 mg who underw
Slide 19: Anticipated Clinical Next Steps
Anticipated Clinical Next Steps • 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 survival compared to pembrolizuma
Slide 20: Closing Remarks
Closing Remarks Stephane Bancel, CEO Slide 20
Slide 21: Interim Analysis of Personalized Cancer Vaccine Phase
Interim Analysis of Personalized Cancer Vaccine Phase 1 Presented Saturday June 1, 2019 at ASCO Personalized OX40L+ cancer IL23+IL36 vaccine (Triplet) VEGF-A (no LNP) OX40L Increasing biology risk CMV Fabry v accine MMA Flu Chikungunya v accines Antibody (H7, H10) Varying technology risk Localized
Slide 22: Personalized Cancer Vaccine Interim Phase Data Strengthens Our Mosaic of Human Data
Personalized Cancer Vaccine Interim Phase 1 Data Strengthens Our Mosaic of Human Data in the First 4 Modalities ~1,000 healthy volunteers and patients in trials Personalized OX40L+ cancer IL23+IL36 vaccine (Triplet) Clinical data support features of our investigational mRNA medicines: VEGF-A (no LN
Slide 23: Our Mission
Our Mission To deliver on the promise of mRNA science to create a new generation of transformative medicines for patients. Slide 23