Slide 1: Treatment With Imetelstat Provides Durable Transfusion Independence in LR-MDS
Abstract #658 Treatment With Imetelstat Provides Durable Transfusion Independence (TI) in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) Uwe Platzbecker1, Pierre Fenaux2, David P. Steensma3, Koen Van Eygen4, Azra Raza5, Ul
Slide 2: Disclosure
Disclosure ❑ Presenter: Uwe Platzbecker, MD ❑ Affiliations: Department of Hematology and Cell Therapy, University Clinic Leipzig, Leipzig, Germany ❑ Disclosure: ❑ Honoraria and research grant from BMS, Amgen, Novartis, Jazz ❑ Honoraria from Geron
Slide 3: Imetelstat: First-in-Class Telomerase Inhibitor with Disease-Modifying Potential
Imetelstat: First-in-Class Telomerase Inhibitor with Disease-Modifying Potential Imetelstat binds to RNA template, Apoptosis of preventing maintenance of telomeres malignant cells (hTERT) Malignant Malignant (hTR) hematopoietic progenitor stem cells cell X Telomerase Upregulation Mechanism of Action
Slide 4: Phase 2/3 Study Design
Phase 2/3 Study Design Enrollment Complete Currently Enrolling Phase 3 Phase 2 double-blind, placebo-controlled single arm, open label N~170 LR MDS R/R to ESA Imetelstat (n~115) Results from Phase 2 recently R 7.5 mg/kg IV q4w published online ahead of print: Imetelstat (n=38) A Stratification: 2020
Slide 5: Treatment Exposure
Treatment Exposure ❑ 38 patients with non-del(5q) LR MDS R/R to ESA ❑ Clinical cutoff for analyses: 4 Feb 2020 Parameters N = 38 Median follow-up, months (range) 24.0 (5.6 – 45.5) Median treatment duration, months (range) 8.5 (0.02 – 38.7) Median treatment cycles (range) 9 (1 – 40) Median dose inten
Slide 6: Baseline Patient Characteristics
Baseline Patient Characteristics Parameters N = 38 Age, years, median (range) 71.5 (46 – 83) Male, n (%) 25 (66) ECOG PS 0-1, n (%) 34 (89) IPSS risk, n (%) Low 24 (63) Intermediate-1 14 (37) RBC transfusion burden, units/8 weeks, median (range) 8 (4 – 14) 4-5 units / 8 weeks at baseline, n (%) 6 (1
Slide 7: Patient Disposition
Patient Disposition Parameters N = 38 n (%) Ongoing on treatment 9 (24) Discontinued study treatment 29 (76) Lack of Efficacy 12 (32) Adverse Event 8 (21) Progressive Disease 4 (10) Withdrawal by Patient 2 (5) Death 1 (3) Physician Decision 1 (3) Disease Relapse 1 (3) Ongoing study participation * 2
Slide 8: Meaningful and Durable Transfusion Independence with Imetelstat Treatment
Meaningful and Durable Transfusion Independence (TI) with Imetelstat Treatment Parameters N = 38 8-week TI, n (%) 16 (42) Time to onset of 8-week TI, weeks, median (range) 8.3 (0.1-40.7) Duration of TI, weeks, median (95% CI)a 88.0 (23.1 – 140.9*) Cumulative duration of TI ≥ 8 weeksb, median (95% CI
Slide 9: Hematologic Improvement and IWG Response with Imetelstat Treatment
Hematologic Improvement and IWG Response with Imetelstat Treatment Parameters N = 38 HI-E per IWG 2006, n (%) 26 (68) ≥1.5 g/dL increase in Hb lasting ≥ 8 weeksa, n (%) 13 (34) Transfusion reduction by ≥ 4 units/8 weeks, n (%) 26 (68) Duration of HI-E, weeks, median (95% CI)b 92.7 (37.1, 149.4) Majo
Slide 10: Potential Disease-Modifying Activity: Durable TI and Substantial Increase in Hb
Potential Disease-Modifying Activity with Imetelstat Treatment: Durable TI and Substantial Increase in Hb ❑ 29% of the patients transfusion-free for at least one year ❑ Longest transfusion-free period 2.7 years ❑ 75% of TI responders had the maximum Hb rise of ≥ 3g/dL from pretreatment level (pretre
Slide 11: Clinical Benefit Observed Across Different Patient Subgroups
Clinical Benefit Observed Across Different Patient Subgroups Similar HI-E response across different patient subgroups ❑ RS Subgroups: RS+ (RARS/RCMD- RS) vs. RS- (Other) ❑ Baseline transfusion burden: High (4-6 units) vs. Very High (>6 units) ❑ Serum EPO level: ≤ 500 mU/mL vs. > 500 mU/mL All 8-week
Slide 12: Reversible Grade 3/4 Cytopenias without Significant Clinical Consequences
Reversible Grade 3/4 Cytopenias without Significant Clinical Consequences Frequency of Hematologic AEs All Grades Grade 3/4 AE N=38 N=38 n (%) n (%) Thrombocytopenia 25 (66) 23 (61) ❑ 2/38 pts (5%) had febrile neutropenia (Gr3) ❑ 3/38 pts (8%) had Grade 3/4 bleeding Neutropenia 22 (58) 21 (55) Anemi
Slide 13: Most Frequently Reported Non-Hematologic AEs
Most Frequently Reported Non-Hematologic AEs: No New Clinically Significant Events TEAE All Grades, N=38 Grade ¾, N=38 n (%) n (%) Back pain 9 (24) 2 (5) Pyrexia 8 (21) 0 Diarrhea 7 (18) 0 Nasopharyngitis 7 (18) 0 ALT increased 7 (18) 2 (5)* AST increased 6 (16) 3 (8)* Bronchitis 6 (16) 3 (8) Asthen
Slide 14: On-Target Activity of Imetelstat Correlates with Transfusion Independence
On-Target Activity of Imetelstat Correlates with Transfusion Independence On-Target* activity demonstrated by reduction Reduction in hTERT expression in Telomerase Activity (TA) and hTERT expression correlates with 8- and 24-weeks TI Correlation between on-target activity % pts with ≥50% reduction i
Slide 15: Reduction of Malignant Clones Associated with Treatment Response
Potential Disease-Modifying Activity with Imetelstat Treatment: Reduction of Malignant Clones Associated with Treatment Response Imetelstat had SF3B1 VAF reduction 8-wk TI responders had more reduction of SF3B1 VAF regardless Changeof in mutation hotspots VAF of SF3B1 mutations compared to 8-wk TI n
Slide 16: Reduction of Malignant Clones Associated with Treatment Response
Potential Disease-Modifying Activity with Imetelstat Treatment: Reduction of Malignant Clones Associated with Treatment Response ❑ The greater reduction of SF3B1 VAF, the longer TI duration patients maintained. ❑ The greater reduction of SF3B1 VAF and the shorter onset time to achieve the longest TI
Slide 17: Imetelstat in LR MDS Key Conclusions
Imetelstat in LR MDS Key Conclusions ❑ Imetelstat treatment shows meaningful and durable transfusion independence: o High rates of TI and HI-E: 42% 8-week TI rate and 68% HI-E rate o Durable TI and HI-E: Median duration of TI is 20 months and median duration of HI-E is 21 months o TI across multiple
Slide 18: Phase 2/3 Study Design
Phase 2/3 Study Design Enrollment Complete Currently Enrolling Phase 2 Phase 3 single arm, open label double-blind, placebo-controlled LR MDS R/R to ESA N~170 ❑ Key Elements Same as Phase 2: o Dose and schedule Imetelstat (n~115) o Primary/secondary endpoints R 7.5 mg/kg IV q4w o Patient population
Slide 19: Acknowledgements
Acknowledgements The authors thank all the patients for their participation in this study and acknowledge the collaboration and commitment of all investigators and their staff Mazure, Dominiek Kim, Inho Klein, Saskia Oliva, Esther Meers, Stef Lee, Je-hwan Langemeijer, Saskia Breems, Dimitri van de L