Slide 1: Completed Dose Escalation From the First-in-human, Phase 1/2 Study of CD123 NK Cell Engager
Completed Dose Escalation From the First-in-human, Phase 1/2 Study of CD123 NK Cell Engager, SAR443579, in Relapsed or Refractory Acute Myeloid Leukemia or High Risk-Myelodysplasia Sylvain Garciaz1, Ashish Bajel2, Abhishek Maiti3, Pinkal Desai4, Gerwin Huls5, Nicolas Boissel6, Mojca Jongen-Lavrencic
Slide 2: Disclosures
Disclosures Sylvain Garciaz: Nothing to disclose. Jennifer Saultz: Research funding from IKENA Oncology, advisory Ashish Bajel: Speaker’s bureau for Amgen; honoraria from Abbvie, board Rigel. Pfizer, Astellas, Novartis and Amgen. Kyle Jensen: Employed by Sanofi and may hold stock and/or stock Abhish
Slide 3: Trifunctional SAR'579 Co-Engages NK Cells and CD123-Positive Tumor Cells
Trifunctional SAR’579 Co-Engages NK Cells and CD123-Positive Tumor Cells • CD123 is frequently overexpressed on leukemic blasts; high levels are associated with poor outcomes in various hematologic malignancies1-9 • SAR’579 is an NKCE facilitating the formation of a cytolytic synapse between CD16 an
Slide 4: Study Design: SAR'579 in R/R AML, B-ALL or HR-MDS
Study Design1,2: SAR’579 in R/R AML, B-ALL or HR-MDS Dose Escalation* Dose Expansion* Primary endpoint: Determine maximum tolerated or administered DLTs, pts (%) with CR/CRi dose based on incidence of dose-limiting Determination of CRc (CR +CRi) toxicity in cycle 1 (28-day cycles) Key secondary endp
Slide 5: Dose Escalation and Eligibility Criteria
Dose Escalation and Eligibility Criteria SAR’579 IV DL1 DL2 DL3 DL4 DL5 DL6 DL7 DL8 DL9 DL10 DL11 Dose in mg/kg n=3 n=4 n=4 n=4 n=4 n=8 n=8 n=8 n=6 n=6 n=4 Day 1 0.01 0.03 0.1 0.3 1.0 3.0 6.0 1.0 0.75 1.5 2.0 Day 4 0.03 0.1 0.3 / / / / / / / / Day 8 0.1 0.3 1.0 1.0 3.0 3.0 6.0 1.0 0.75 1.5 2.0 Day 1
Slide 6: Baseline Characteristics
Baseline Characteristics Characteristic N=59 Characteristic N=59 Age, median (range), years 67 (19–81) WBC at baseline,* median (range), 109/L 2.6 (0–12) 18–65, n (%) 27 (45.8) Blast count in blood,† median (range), 0.6 (0–29) 109/L 66–75, n (%) 22 (37.3) Blast proportion in bone marrow,‡ 47.5 >75,
Slide 7: Summary of Adverse Events
Summary of Adverse Events DL1 DL2 DL3 DL4 DL5 DL6 DL7 DL8 DL9 DL10 DL11 All n (%) 0.1 mg/kg 0.3 mg/kg 1 mg/kg 1 mg/kg 3 mg/kg 3 mg/kg 6 mg/kg 1 mg/kg 0.75 mg/kg 1.5 mg/kg 2 mg/kg (n=4) (n=4) (n=4) (n=8) (n=8) (n=8) (n=6) (n=6) (n=4) (N=59)* (n=3) (n=4) DLTs 0 0 0 0 0 0 0 0 1 0 0 1 TEAEs (all Grades)
Slide 8: TEAEs by Preferred Term Reported in >10% Patients (All Grades)
TEAEs by Preferred Term Reported in >10% Patients* (All Grades) DL1 Dose-Level, mg/kg DL2 DL3 DL4 DL5 DL6 DL7 DL8 DL9 DL10 DL11 Any Grade n (%)† 0.1 mg/kg 0.3 mg/kg 1 mg/kg 1 mg/kg 3 mg/kg 3 mg/kg 6 mg/kg 1 mg/kg 0.75 mg/kg 1.5 mg/kg 2 mg/kg Grade ≥3 (n=3) (n=4) (n=4) (n=4) (n=4) (n=8) (n=8) (n=8) (
Slide 9: Response per Investigator (per Modified IWG Criteria) in Patients with R/R AML
Response per Investigator (per Modified IWG Criteria) in Patients with R/R AML DL1 DL2 DL3 DL4 DL5 DL6 DL7 DL8 DL9 DL10 DL11 All n (%) 0.1 mg/kg 0.3 mg/kg 1 mg/kg 1 mg/kg 3 mg/kg 3 mg/kg 6 mg/kg 1 mg/kg 0.75 mg/kg 1.5 mg/kg 2 mg/kg (n=3) (n=4) (n=4) (n=4) (n=4) (n=8) (n=8) (n=7) (n=6) (n=6) (n=4) (N
Slide 10: Individual Patient Responses per Investigator
Individual Patient Responses per Investigator Target Dose Level (1 mg/kg/dose) CR CR CR CRi • 71 years old • Female CR * HSCT • Prior HSCT • Prior venetoclax • Baseline blasts 45% • TP53 DL1 (0.1 mg/kg) DL2 (0.3 mg/kg) Other Dose Levels • Achieved MRD DL3 (1 mg/kg) negative CR DL4 (1 mg/kg) DL5 (3 m
Slide 11: Blast Count Best Relative Change (Bone Marrow)
Blast Count Best Relative Change (Bone Marrow) 80 Baseline, % 40 0 * * * 250 200 150 DL1 (0.1 mg/kg) 100 DL2 (0.3 mg/kg) DL3 (1 mg/kg) Best Relative Change From Baseline, % DL4 (1 mg/kg) DL5 (3 mg/kg) 50 DL6 (3 mg/kg) Blasts in Bone Marrow DL7 (6 mg/kg) DL8 (1 mg/kg) DL9 (0.75 mg/kg) # # # # # # # #
Slide 12: Blast Count Best Relative Change (Peripheral Blood)
Blast Count Best Relative Change (Peripheral Blood) Baseline, 109/L 10.00 1.00 0.10 0.01 * * * * * * * * * * * * 800 600 400 DL1 (0.1 mg/kg) 100 DL2 (0.3 mg/kg) DL3 (1 mg/kg) Best Relative Change From Baseline, % DL4 (1 mg/kg) DL5 (3 mg/kg) 50 DL6 (3 mg/kg) DL7 (6 mg/kg) Blasts in Blood DL8 (1 mg/kg
Slide 13: Relationship Between Baseline Bone Marrow Blasts and Response
Relationship Between Baseline Bone Marrow Blasts and Response 100 100 1e+4 Marrow (Receptor Density) CD123+ Blasts in Bone in Bone Marrow (%) Blasts/Total Cells Bone Marrow (%) 75 75 CD123+ Blasts in 1000 Patients treated at final 50 50 100 target dose of 1 mg/kg 25 25 DL1 (0.1 mg/kg) (DL3-4 & DL8)
Slide 14: Relationship Between Baseline Peripheral NK Cells and Response
Relationship Between Baseline Peripheral NK Cells and Response 1000 1000 NKp46+ Natural Killer Cells in Blood (cells/µL) in Blood (cells/µL) Natural Killer Cells 100 100 Patients treated at final target dose of 10 10 1 mg/kg DL1 (0.1 mg/kg) (DL3-4 & DL8) DL2 (0.3 mg/kg) 1 n=8 n=4 1 n=8 n=4 DL3 (1 mg
Slide 15: Summary
Summary Safety • SAR’579 had a manageable toxicity profile up to a dose of 6 mg/kg QW in adult patients with R/R AML • Low grade infusion-related reaction (Grade 1–2) was the most common TRAE • CRS events were rare (one Grade 3) and no ICANS Antitumor Activity • Among 15 AML patients treated at a ta
Slide 16: Acknowledgments
Acknowledgments • WE WOULD LIKE TO THANK: • Participating patients and their families Netherlands • Study investigators France and staff United States • All staff who contributed to data collection and analysis • Study funding: Sanofi • Editorial support was Australia provided by Kerry Brinkman, PhD