Macrogenics, Inc. · NASDAQ:MGNX
Macrogenics — ASCO 2020
18 slides from Macrogenics's conference presentation, May 29, 2020
Slide 1: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013
A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, a Bispecific DART® Molecule Binding PD-1 and LAG-3 in Patients with Unresectable or Metastatic Neoplasms Jason J. Luke,1 Manish R. Patel,2 Erika Hamilton,3 Bartosz Chmielowski,4 Susanna Ulahannan,5 Hedy Kindler,6 Shakeela Bahadu
Slide 2: Presenter Disclosure Information
Presenter Disclosure Information Jason J. Luke, MD, FACP • Data and Safety Monitoring Board: TTC Oncology • Scientific Advisory Board: 7 Hills, Actym, Alphamab Oncology, Kanaph, Mavu (now part of AbbVie), Onc.AI, Pyxis, Springbank, Tempest • Consultancy: Abbvie, Akrevia, Algios, Array, Astellas, Bay
Slide 3: Rationale for Dual Targeting of PD-1 and LAG-3
Rationale for Dual Targeting of PD-1 and LAG-3 • Checkpoint molecules are leveraged by tumors or APCs to evade the immune system • PD-1 and LAG-3 receptors are expressed on “exhausted” T-cells • Interactions with corresponding ligands negates anti-tumor T cell activity • Synergy of anti-PD-1 + anti-
Slide 4: MGD013 Phase 1 Trial Design
MGD013 Phase 1 Trial Design • Primary objectives: – Safety, tolerability DLTs, MTD, MAD Dose Escalation in Previously Treated MGD013 Monotherapy Combination Cohort – Advanced Solid Tumors Cohort Expansiona Expansionab – Alternate dose (600 mg Q2W) Flat Dosing Q2W: 1200 mg Single Patient Cohorts† Ova
Slide 5: Baseline Demographics
Baseline Demographics Monotherapy Combination Dose Escalation Cohort Expansion Cohort Expansion 1 -1200 mg Q2W 600 mg Q2W MGD013 + Margetuximab (n=53) (n=205) (n=21) Median age (range), years 64 (24, 84) 60 (27, 84) 62 (29, 83) Gender, n (%) Male 32 (60.4) 74 (36.1) 7 (33.3) Female 21 (39.6) 131 (63
Slide 6: Pharmacokinetics and Receptor Occupancy
Pharmacokinetics and Receptor Occupancy Linear PK (400-1200 mg dose range) and sustained receptor occupancy (≥120 mg) Pharmacokinetics (1-1200 mg) Receptor (PD-1) Occupancy (120 mg Q2W) 100 80 60 CD4 40 20 CD4 Occupancy (% ) 0 1 15 29 43 57 71 85 99 113 Days 100 80 60 40 CD8 20 CD8 Occupancy (% ) 0
Slide 7: MGD013 Dose Escalation: Results
MGD013 Dose Escalation: Results Best % Reduction of Target Lesions * Immune-Related Adverse Events of Special Interest (AESIs) RECIST Evaluable Population (n=42)* No. (%) of Patients All Grades > Grade 3 (N=53) (N=53) Rash 7 (13.2) 1 (1.9) Hypothyroidism 6 (11.3) 0 Immune-mediated hepatitis 2 (3.8)
Slide 8: MGD013 Monotherapy Cohort Expansion: Safety
MGD013 Monotherapy Cohort Expansion: Safety No. (%) of Patients All Grades > Grade 3 Overall AE Totals (N=205) (N=205) AE (irrespective of causality) 178 (86.8) 86 (42.0) Treatment-related AE 118 (57.6) 37 (18.0)a SAE (irrespective of causality) 63 (30.7) 47 (22.9) Treatment-related SAE 18 (8.8) 11
Slide 9: MGD013 Monotherapy Cohort Expansion: Activity
MGD013 Monotherapy Cohort Expansion: Activity Anti-tumor activity observed in multiple tumor types Triple-negative Breast Cancer Epithelial Ovarian Cancer Non-small Cell Lung Cancer TNBC EOC NSCLC, CPI-Naïve NSCLC, post-PD-1 Evaluable Patients 23 23 14 15 ORR (Confirmed) 4.3% (1/23) 8.7% (2/23) 14.3
Slide 10: Complete Response after Single MGD013 Administration
Complete Response after Single MGD013 Administration 27-year-old male with DLBCL progressive disease after CAR-T cell therapy MGD013 Screening Complete Response - Day 24 • Relapsed subsequent to DA-R-EPOCH and JCAR017 • Pre-treatment biopsy: High levels of LAG-3 & PD-L1 • Received MGD013, 600 mg x 1
Slide 11: Objective Responses Associated with LAG-3 Expression
Objective Responses Associated with LAG-3 Expression Inflammatory interferon-γ signature elevated in patients with clinical response Retrospective IHC Analyses Transcript Profiling (Baseline Tumor Biopsy) 30 30 LAG-3 vs PD-1 IFN-γ Gene Signature 20 PD SD PR 20 10 NSCLC P-NSCLC 10 LAG-3 Expression 0
Slide 12: Can Tumors Be Made More Responsive to PD-1 × LAG-3 Intervention?
Can Tumors Be Made More Responsive to PD-1 × LAG-3 Intervention? Enhancing effector-cell activation via Fc-engineered mAb Margetuximab Investigational Fc-engineered anti-HER2 mAb Margetuximab Enhances LAG-3 Expression by NK Cells • Same anti-HER2 properties as trastuzumab 3 - • Enhanced Fc-mediated
Slide 13: Fc-engineered mAb plus PD-1 x LAG-3 DART: Combinatorial Biology
Fc-engineered mAb plus PD-1 x LAG-3 DART: Combinatorial Biology PD-1 x LAG-3 (MGD013) Enhances Lytic Fc-engineered Margetuximab Activity of Immune Cells Primed by Up-regulates LAG-3/PD-L1 Expression Fc-engineered mAb (Margetuximab) NK Monocyte CD4 T CD8 T ADCC NK-cell Killing LAG-3 100 100 (-) 80 80
Slide 14: Margetuximab plus MGD013: Preliminary results in HER2+ solid tumors
Fc-engineered αHER2 plus PD-1 × LAG-3 DART (Margetuximab plus MGD013) Preliminary results in patients with relapsed/refractory HER2+ solid tumors • ORR = 42.9% (6/14 evaluable pts) • Includes unconfirmed objective responses • Well-tolerated PD PD PDPD • Responding patients remain on therapy PD PD PD
Slide 15: Durable Response in Patient Receiving MGD013 plus Margetuximab
Durable Response in Patient Receiving MGD013 plus Margetuximab Resolution of chest wall disease with confirmed PR of overall tumor burden Metastatic HER2+ breast cancer in Baseline 67-year-old female • Previously progressed on: Day 15† – 1L pertuzumab/trastuzumab/anastrozole 2L TDM1/anastrozole – Da
Slide 16: MGD013 (PD-1 × LAG-3 DART Molecule): Conclusions
MGD013 (PD-1 × LAG-3 DART Molecule): Conclusions First-in-class bispecific checkpoint inhibitor • Designed to independently or coordinately block PD-1 and LAG-3 • Well tolerated at doses up to 1200 mg Q2W • RP2D: 600 mg Q2W or Q3W • Safety profile consistent with anti-PD-1 monotherapy Encouraging mo
Slide 17: Investigators
Investigators Australia Spain United States of America Philip Clingan Analia Azaro Pedrazzoli Charu Aggarwal Anthony Joshua Javier Cortes Castan Shakeela Bahadur Girish Mallesara Maria Jose De Miguel Luken George Blumenschein Andrew Weickhardt Bartosz Chmielowski Anthony El-Khoueiry Lipika Goyal Bul
Slide 18: Acknowledgments
Acknowledgments Thank you to the patients and their families who participated or continue to participate in this study. Jason J. Luke, MD, FACP @jasonlukemd 18