Slide 1: MGC018 Conference Call Materials
® Developing Breakthrough Biologics, Life-changing Medicines® MGC018 Conference Call Materials June 4, 2021 – 4:30 P.M. ET Dial-in: (877) 303-6253 (domestic) or (973) 409-9610 (int’l); Conference ID: 1583522 Link to Webcast
Slide 2: Legal Notices
Legal Notices The information in this slide deck is current as of June 4, 2021, unless otherwise noted, and is qualified in its entirety by reference to MacroGenics’ Annual, Quarterly and Current Reports filed with the SEC. MacroGenics undertakes no obligation to update any of the information herein
Slide 3: MGC018 Conference Call Agenda
MGC018 Conference Call Agenda Topic Presenter Organization Welcome Scott Koenig, M.D., Ph.D. MacroGenics B7-H3 Background / MGC018 Overview Chet Bohac, M.D. MacroGenics Dose Escalation Data Presented at ASCO 2021 Chet Bohac, M.D. MacroGenics Review of Melanoma Patients in Dose Escalation Sekwon Jang
Slide 4: B7-H3 Background
B7-H3 Background Chet Bohac, M.D. Executive Director, Clinical Research, MacroGenics 4 MGC018 Conference Call • June 4, 2021
Slide 5: B7-H3: Member of B7 Family of Immune Regulators
B7-H3: Member of B7 Family of Immune Regulators Expression contributes to tumor immune evasion and cancer cell metabolism Immunosuppressive Role • Crystal structure resolved: T-cell inhibitory domain mapped (Vigdorovich 2013) • Tumor-expressed B7-H3 suppresses T-cell mediated antitumor immune respon
Slide 6: Rationale for Targeting B7-H3
Rationale for Targeting B7-H3 Direct expression by primary Tumor Cells and metastatic tumors Expression on cancer stem cell population CSCs Role in mediating migration, invasion, resistance and Expression on tumor tumor metabolism vasculature and stroma T Cells Role in T cell immune modulation Tumor
Slide 7: MGC018 Expansion Cohorts
Indications Being Evaluated with MGC018, Enoblituzumab Majority express high levels of B7-H3, with limited expression in normal tissue IHC Summary of >1,530 Tumor Tissue Samples Screened Potential Indications: B7-H3 Positive (a) 2+ or Above Head and Neck 19/19 100% 19/19 100% Kidney Cancer 77/78 99%
Slide 8: MGC018 Overview
MGC018 Overview 8 MGC018 Conference Call • June 4, 2021
Slide 9: MGC018: B7-H3 Directed ADC with Duocarmycin-based Linker Payload
MGC018: B7-H3 Directed ADC with Duocarmycin-based Linker Payload Leveraging high B7-H3 expression in solid tumors • vc-seco-DUocarmycin-hydroxyBenzamide Azaindole (DUBA) is a DNA alkylating agent • DUBA cytotoxic activity is cell-cycle independent • DUBA retains potency in multidrug-resistant cell l
Slide 10: MGC018 Phase 1 Study Design
MGC018 Phase 1 Study Design Dosing is every three weeks (q3W) Tumor Response by Investigator PSA per RECIST v1.1 Evaluation Escalation 3+3+3 MGC018 MGC018 MGC018 MGC018 MGC018 Every 6 Every 6 Dose 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg Weeks Weeks Metastatic Castration-Resistant Prostate
Slide 11: Dose Escalation Data Presented at ASCO 2021
Dose Escalation Data Presented at ASCO 2021 11 MGC018 Conference Call • June 4, 2021
Slide 12: Dose Escalation: Best Percent Change of Target Lesions
Dose Escalation: Best Percent Change of Target Lesions Best Response: Stable Disease (-24%) Best Response: Stable Disease (-15.5%) 3 Target lesions (lung, liver, chest wall) 3 Target lesions (pancreas, soft tissue) 3 Prior lines: Nivo., ipi.+nivo.+relatlimab, 2 Prior lines: Folfirinox, gemcitabine/c
Slide 13: Dose Escalation: Percent Change of Target Lesions
Dose Escalation: Percent Change of Target Lesions MGC018 provided target lesion reductions and disease stabilization for several months Source: Jang, et al., ASCO 2021. Data cut-off: May 3, 2021. 13 MGC018 Conference Call • June 4, 2021
Slide 14: Dose Escalation: Related Adverse Events ≥ 20%, All Grades
Dose Escalation: Related Adverse Events ≥ 20%, All Grades Fatigue, nausea, infusion related reaction, skin disorders, and neutropenia were most common 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg All System Organ Class Preferred Term (N=3) (N=6) (N=7) (N=7) (N=6) (N=29) AT LEAST ONE EVENT 3 (10
Slide 15: Dose Escalation: Grade ≥ 3 Related Adverse Events
Dose Escalation: Grade ≥ 3 Related Adverse Events Cytopenias were most common 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg 4.0 mg/kg All System Organ Class Preferred Term (N=3) (N=6) (N=7) (N=7) (N=6) (N=29) AT LEAST ONE EVENT 2 (66.7%) 2 (33.3%) 6 (85.7%) 4 (57.1%) 5 (83.3%) 19 (65.5%) Blood and lymphat
Slide 16: Dose Escalation: Treatment-Emergent Adverse Events
Dose Escalation: Treatment-Emergent Adverse Events Manageable safety profile Patients Experiencing at Least One 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg 3.0 mg/kg* 4.0 mg/kg All Adverse Event (N=3) (N=6) (N=7) (N=7) (N=6) (N=29) Adverse Event 3 (100%) 6 (100%) 7 (100%) 7 (100%) 6 (100%) 29 (100%) Treatment-Rel
Slide 17: Dose Escalation: Update on PSA Responders from ASCO 2020
Dose Escalation: Update on PSA Responders from ASCO 2020 Participants without progression for ≥6 months MGC018 Duration MGC018 PSA MGC018 Patient of Best Reduc- Time to Reason for MGC018 (Dose) Therapy Response tion Progression Discontinuation Patient #1 4 mos. SD –60% Unknown Patient decision due t
Slide 18: Dose Escalation: Update on PSA Responders from ASCO 2020
Dose Escalation: Update on PSA Responders from ASCO 2020 B7-H3 H Score Duration MGC018 Time to Patient (Vasculature Line of of Therapy MGC018 MGC018 PSA Progression Reason for MGC018 (Dose) Score) Therapy Treatment (# months) Best Response Reduction (# months) Discontinuation 1 Docetaxel 4 Patient #
Slide 19: Review of Melanoma Patients in Dose Escalation
Review of Melanoma Patients in Dose Escalation Sekwon Jang, M.D. Director of Melanoma and Cutaneous Oncology Therapeutics and Research, Inova Schar Cancer Institute 19 MGC018 Conference Call • June 4, 2021
Slide 20: Limited Options for Melanoma Patients Progressing after 1L Systemic Therapy
Limited Options for Melanoma Patients Progressing after 1L Systemic Therapy1 Potential to position MGC018 ≥ 2nd line Metastatic or Unresectable Melanoma BRAF WT BRAF V600 Mut Pembrolizumab OR Pembrolizumab OR Nivolumab Nivolumab Nivolumab + Ipilimumab Nivolumab + Ipilimumab 1L Combination Targeted T
Slide 21: Activity in Metastatic Melanoma Patients
Activity in Metastatic Melanoma Patients Enrolled in MGC018 dose escalation cohort at 4.0 mg/kg B7-H3 Best Prior H Score Reason for Response in Radiation/ (Vasculature Line of Duration of MGC018 Target Patient Surgery Score) Therapy Treatment Therapy Discontinuation Lesions 1 Nivolumab 10/18 – 07/19
Slide 22: Activity in Post anti-PD-1 Metastatic Melanoma
Activity in Post anti-PD-1 Metastatic Melanoma Investigational programs ILLUMINATE-301(1) Phase IB(2) LEAP-004(3) Phase I/II(4) Tilsotolumod + Vidutolimod + Lenvatinib + RP1 + C-144-01 Phase II(5,6) Ipilimumab Pembrolizumab Pembrolizumab Nivolumab Lifileucel (LN-144) Modified Oncolytic Drug Class TL
Slide 23: Initial Dose Expansion mCRPC Data (ASCO 2021)
Initial Dose Expansion mCRPC Data (ASCO 2021) Chet Bohac, M.D. Executive Director, Clinical Research, MacroGenics 23 MGC018 Conference Call • June 4, 2021
Slide 24: Best Percent Change in PSA: Dose Escalation and Cohort Expansion
Best Percent Change in PSA: Dose Escalation and Cohort Expansion >50% PSA Reduction in 11/22 (50%) mCRPC expansion patients; 16/31 (52%) in escalation + expansion # Weeks from first dose indicated for each 3.0 mg/kg Cohort Expansion patient 3 8 11 3 6 4 9 3 13 9 3 3 3 4 10 19 13 3 9 12 17 4 Patients
Slide 25: MGC018 mCRPC Dose Expansion Patient Status (as of Data Cut-off)
MGC018 mCRPC Dose Expansion Patient Status (as of Data Cut-off) Anti-tumor activity in patients with measurable disease 28 Patients Enrolled 22 Patients Dosed w/ ≥1 post baseline PSA 19 Ongoing 12 Ongoing 13 w/Measurable Disease 9 w/Non-measurable Disease 7 Ongoing 6 Ongoing 7 w/First 9-Week Imaging
Slide 26: mCRPC Commentary
mCRPC Commentary Emmanuel Antonarakis, M.B.B.Ch. Professor of Oncology and Urology Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Eugene Shenderov, M.D., Ph.D. Instructor of Oncology Johns Hopkins Sidney Kimmel Comprehensive Cancer Center 26 MGC018 Conference Call • June 4, 2021
Slide 27: Prostate Cancer Treatment Landscape
Prostate Cancer Treatment Landscape Modified by Shenderov E. and Antonarakis ES. from Bastos DA, Antonarakis ES. Oncotargets & Ther 2019; 12: 8769-8777. 27 MGC018 Conference Call • June 4, 2021
Slide 28: Activity in mCRPC Patients Progressing After Taxane and NHT
Activity in mCRPC Patients Progressing After Taxane and NHT CARD(1) VISION(2) MGC018 KEYNOTE-199(3) Phase 2 Cabazitaxel 177Lu-PSMA-617 Cohort Expansion Pembrolizumab (FDA Approved) Phase 3 + SOC Median 4 prior lines Post-docetaxel PSMA+ Post-docetaxel Post-docetaxel Previous Treatment of therapy and
Slide 29: Broad Overview of Patient Treatment Flow
Broad Overview of Patient Treatment Flow Line of Therapy Metastatic CRPC Docetaxel + Enzalutamide Abiraterone + First Line Relugolix Prednisone (Xtandi) Prednisone Abiraterone + Prednisone Enzalutamide Cabazitaxel + Docetaxel Second Line Prednisone Pembrolizumab (MSI-H/dMMR, TMB > 10 muts/Mb) Olapar
Slide 30: Wrap-up | Q&A
Wrap-up | Q&A Scott Koenig, M.D., Ph.D. President & CEO, MacroGenics 30 MGC018 Conference Call • June 4, 2021
Slide 31: Antitumor Activity of MGC018 in Combination with Anti-PD-1: Preclinical Data
Antitumor Activity of MGC018 in Combination with Anti-PD-1: Preclinical Data Induction of immunological memory in CT26 (colorectal) model • Antitumor activity of MGC018 is enhanced by anti-PD-1 • MGC018 and MGC018 + anti-PD-1 induces immunological memory CR defined as tumors < 24 mm3. Anti-PD-1 anti
Slide 32: Antitumor Activity of MGC018 in Combination with Anti-PD-1: Preclinical Data
Antitumor Activity of MGC018 in Combination with Anti-PD-1: Preclinical Data Induction of immunological memory in MC38 (colorectal) model Source: Scribner, et al., AACR 2020 Virtual Annual Meeting II 32 MGC018 Conference Call • June 4, 2021
Slide 33: Antitumor Activity of MGC018 in Combination with Anti-PD-1: Preclinical Data (cont’d)
Antitumor Activity of MGC018 in Combination with Anti-PD-1: Preclinical Data (cont’d) Induction of immunological memory in MC38 (colorectal) model Source: Scribner, et al., AACR 2020 Virtual Annual Meeting II 33 MGC018 Conference Call • June 4, 2021
Slide 34: Deep and Differentiated Immuno-Oncology Pipeline
Deep and Differentiated Immuno-Oncology Pipeline Proof-of- Pivotal/ Program First-in-Human Concept Registration (Target) Potential Indication(s) (Phase 1) (Phase 2) Directed Approved Major Market Rights HER2+ Breast Greater China Margetuximab (HER2) HER2+ GC/GEJ (+retifanlimab/tebotelimab) Flotetuzu
Slide 35: Questions? Answers.
Q&A Questions? Answers. 35 MGC018 Conference Call • June 4, 2021
Slide 36: Thank You!
Thank You! Investor Relations Inquiries: Jim Karrels – SVP, Chief Financial Officer 301-354-2681 | karrelsj@macrogenics.com Business Development Inquiries: Eric Risser – SVP, Chief Business Officer 301-354-2640 | rissere@macrogenics.com www.macrogenics.com Link to our latest presentations: http://ir