Citius Pharmaceuticals, Inc. · NASDAQ:CTXR
Citius Pharmaceuticals — 64th American Society of Hematology (ASH) Annual Meeting 2022
19 slides from Citius Pharmaceuticals's conference presentation, Dec 11, 2022
Slide 1: Efficacy and Safety of E7777 in Relapsed or Refractory CTCL: Results from Pivotal Study 302
Efficacy and Safety of E7777 (improved purity Denileukin diftitox [ONTAK]) in Patients with Relapsed or Refractory Cutaneous T-cell Lymphoma: Results from Pivotal Study 302 Francine Foss1, MD, Youn H Kim2, MD, Miles Prince3, MD, FRACP, FRCPA, Timothy M. Kuzel4, MD, FACP, Costas K Yannakou5 MBBS, FRA
Slide 2: Introduction
Introduction Relapsed or refractory CTCL is an incurable with existing therapies • Denileukin diftitox (Dd) is a recombinant fusion protein of diphtheria toxin and human interleukin-2 • Dd was approved and marketed as ONTAK in the US from 1999-2014 for the treatment of patients with relapsed/refract
Slide 3: How it works: Novel immunotherapy with differentiated MOA
How it works: Novel immunotherapy with differentiated MOA E7777 is an engineered IL-2-diphtheria toxin fusion protein with a differentiated mechanism of action supporting two therapeutic effects Binds to IL-2 receptor to kill tumor cells directly Eliminates Immunosuppressive Tregs* Woodall-Jappe M,
Slide 4: Multi-center open label single arm registrational trial of E7777 in relapsed/refractory CTCL
Multi-center open label single arm registrational trial of E7777 in relapsed/refractory CTCL Study 302 (NCT01871727) LEAD-IN (N=21) Dose Escalation: 6 -15 μg/kg Primary: DLT / MTD (CRM) STUDY POPULATION N=112* Secondary: safety, efficacy, PK, • Age ≥ 18 immunogenicity • Recurrent or Persistent CTCL
Slide 5: E7777-Study 302 - Objectives
E7777-Study 302 - Objectives Primary Objective To demonstrate efficacy in recurrent or persistent Stage I - III CTCL as assessed by ORR; Objective Response defined as CRs plus PRs, per ISCL/EORTC Global Response Score (Olsen 2011)1 Secondary objectives • To determine DOR, TTR, skin response, duratio
Slide 6: Statistical Analyses
Statistical Analyses Two-sided 95% confidence interval (CI) is calculated using Clopper-Pearson method for binary endpoints including: • ORR per Olsen criteria (2011) by IRC, Investigator, and Prince assessment • Skin response (based on mSWAT) per Olsen criteria (2011) • As per FDA guidance, E7777 w
Slide 7: Patient Demographics
Patient Demographics E7777 9 µg/kg Primary Efficacy Analysis Set (n=69) CTCL Type (N = 69), n (%) E7777 9 μg/kg Category Mycosis (N = 69), n (%) 66 (95.7) Age (years) Fungoides n 69 Sezary Syndrome 3 (4.3) Median (range) 64.0 (28-87) CTCL Disease Stage Age Group (years), n (%) IA 5 (7.2) < 65 years
Slide 8: Treatment Disposition (n=69)
Treatment Disposition (n=69) E7777 9 µg/kg Category (N = 69) n (%) Treatment Ongoing at Data Cutoff Date 2 (2.9) Completed 8 cycles per Protocol 12 (17.4) Discontinued Treatment 55 (79.7) Progression 28 (40) Adverse Event 7 (10.1) Subject Choice 7 (10.1) Administrative/Other 19 (27) Withdrawal of Co
Slide 9: Primary Efficacy Outcome
Primary Efficacy Outcome The main efficacy outcome measure was objective response rate (ORR), as assessed by an Independent Review Committee (IRC) using Olsen (2011) criteria The ORR was 25/69 (36.2%), 95% exact CI: (25.0%, 48.7%) Independent (IRC) Investigator Stage I-III Primary Efficacy Analysis
Slide 10: Skin Response
Overall Response in Skin by mSWAT • Of 64 evaluable subjects, 54 (84.4%) Waterfall Plot for Skin Tumor Burden (mSWAT Score) had a decrease in skin tumor burden by IRC per Olsen 2011 • 31 (48.4%) had a maximum decrease from baseline of ≥50% • Skin Response • 8 of 64 subjects (12.5%) achieved a CR • S
Slide 11: Summary of Tumor Response
Summary of Tumor Response by Baseline CTCL Stage per IRC (Olsen) Primary Efficacy Analysis Set (n=69) CTCL Disease Stage at Study Entry IA/IB/IIA IIB IIIA/IIIB (N = 30) (N = 24) (N = 15) Best Overall Response Based on GRS, n (%) Complete Response (CR) 5 (16.7) 1 (4.2) 0 (0.0) Partial Response (PR) 6
Slide 12: Duration of Response
Duration of Response • Observed median DOR was 6.47 months • 13/25 (52%) of responders had duration of response ≥ 6 months Swimmer Plot per IRC n=25 (Olsen, 2011) • 5/25 (20%) had duration of response ≥ 12 months
Slide 13: Characteristics of Responders
Characteristics of Responders IRC Assessment Inv. Assessment (N = 69) (N = 71) Time to Response (months) Subjects with Objective Response (n) 25 30 Median (Min,max) 1.41 (0.7, 5.6) 1.41 (0.7, 9.5) No. Subjects with Time to First Objective Response Occurring after No. of Treatment Cycles Indicated, n
Slide 14: E7777 Administration and Treatment Duration
E7777 Administration and Treatment Duration Stage I-III Safety Set E7777 9 μg/kg Category (N = 69) n (%) Cumulative No. of Cycles Received, n (%) Median 6.0 Range in cycles (Min, Max) 1, 42 1-4 29 (42.0) 5-8 21 (30.4) ≥9 19 (27.5) ≥ 16 4 (5.8) Overall Number of Infusions per Cycle Median 4.88
Slide 15: Overview of Treatment – Emergent AEs
Overview of Treatment – Emergent AEs E7777 9 µg/kg Category (N = 69) Subjects with Any TEAE 68 (98.6) Subjects with Any TEAE with Worst CTCAE Grade of ≥3 30 (43.5) 3 27 (39.1) 4 3 (4.3) 5 0 (0.0) Subjects with Any Serious TEAE 26 (37.7) Fatal Serious TEAE 0 (0.0) Non-fatal Serious TEAE 26 (37.7) Sub
Slide 16: TEAEs in ≥ 15%, Overall and ≥ Gr 3
TEAEs in ≥ 15%, Overall and ≥ Gr 3 (n=69) Preferred Term Any Grade Grade ≥3 Subjects with Any TEAE 68 (98.6) 30 (43.5) Nausea 30 (43.5) 1 (1.4) Fatigue 22 (31.9) 0 (0.0) Alanine aminotransferase increased* 19 (27.5) 6 (8.7) Chills 19 (27.5) 1 (1.4) Peripheral edema* 19 (27.5) 1 (1.4) Aspartate amino
Slide 17: Conclusions
Conclusions • Relapsed or refractory CTCL represents an incurable orphan disease • E7777 targets the IL-2 receptor (on malignant T-cells and Tregs) • E7777 at a dose of 9 mcg/kg/day x 5 days every 3 weeks was associated with an ORR of 36.2% per IRC (42.3% by investigator assessment) • Observed media
Slide 18: Acknowledgements
Acknowledgements We thank the patients, their families and caregivers who participated in this clinical trial Study investigators and sites Oleg Akilov MD PhD, Univ of Pittsburgh; Pamela Allen MD, Emory University; Fernando Cabanillas MD, Univ of Puerto Rico; Nam Dang MD PhD, Univ Florida; Madeleine
Slide 19: Poster Presentation #2927: Safety and Tolerability of E7777
Poster Presentation #2927 Safety and Tolerability of E7777 (improved purity denileukin diftitox [ONTAK]) in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma: Results from Pivotal Study 302 Sunday, December 11, 2022 ENMCC – Hall D 6:00-8:00 PM Presented by: Christiane Querfeld, M.D., Ph
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