Slide 1: Efficacy and Safety of Single Agent Rezpegaldesleukin in Atopic Dermatitis
P 6685 Efficacy and Safety of Single Agent Rezpegaldesleukin, A Selective Regulatory T-Cell-Inducing Interleukin-2 Conjugate, in the Treatment of Atopic Dermatitis: Final Results from a Randomized Phase 1b Study Jonathan Silverberg1, David Rosmarin2, Raj Chovatiya3, Stephen Schleicher4, Leon Kircik5
Slide 2: Presenter and Conflicts
Presenter and Conflicts Jonathan Silverberg, MD, PhD, MPH • Professor of Dermatology at The George Washington University School of Medicine and Health Sciences • Director of Clinical Research and Contact Dermatitis Conflict of Interest Disclosures: Speaker, advisory board member, consultant and/or r
Slide 3: Why We Need Additional Therapies for Atopic Dermatitis
Why We Need Additional Therapies for Atopic Dermatitis • Majority of patients do not achieve adequate disease control by the end of the induction period1 • Currently available systemic therapies may be limited by their safety profile: • Biologics (like dupilumab, tralokinumab, etc) are associated wi
Slide 4: Role of Regulatory T Cells in Autoimmune Disease
Role of Regulatory T Cells in Autoimmune Disease Suppression of Mast Cells, Inhibition of IgE Promotion of IL-10 Eosinophils and Basophils Induction of IgG4 producing Breg Rezpegaldesleukin (REZPEG) • Polymer conjugated recombinant Mast Basophils Eosinophils B cell Breg cell human Interleukin-2 (rhI
Slide 5: REZPEG Phase 1b Double-Blind Placebo-Controlled Study Design
REZPEG Phase 1b, Double-Blind, Placebo-Controlled Study of Patients With Atopic Dermatitis (NCT04081350) Key Eligibility Criteria • Aged 18-70 years • Moderate-to-severe AD involving ≥10% body surface area in the affected skin • History of inadequate response or intolerance to topical medications •
Slide 6: Study Demographics of Patients in Phase 1b Trial in Atopic Dermatitis
Study Demographics of Patients in Phase 1b Trial in Atopic Dermatitis PBO REZPEG 12 µg/kg REZPEG 24 µg/kg Characteristic (n=10) (n=16) (n=17) Mean age, years (SD) 42.5 (19.8) 47.9 (17.5) 37.5 (16.4) Sex, n (%) Female 6 (60.0%) 11 (68.8%) 7 (41.2%) Male 4 (40.0%) 5 (31.3%) 10 (58.8%) Race, n (%) Whit
Slide 7: Percent Change From Baseline for EASI Score
Phase 1b Study of REZPEG in Atopic Dermatitis Percent Change From Baseline for EASI Score (Observed) EASI Improvement Percent Reduction from Baseline EASI at Week 12 Treatment Follow-up All Patients Week 19 EASI-50 Subpopulation p = 0.002 0 Change from Baseline EASI 100 Mean (SEM) of Percent 83 % Im
Slide 8: EASI-75 Responders
EASI-75 (EASI Score Decreased by at Least 75%) Proportion of EASI-75 Responders EASI-75 Responders Proportion of EASI-75 Responders at Week 12 Treatment Follow-up All Patients Week 19 EASI-50 Subpopulation 100 Patient, % (NRI) 80 IMPROVEMENT 60 41 40 25 20 20 0 N= 10 16 17 Placebo Placebo Weeks 0 2
Slide 9: BSA (Body Surface Area)
BSA (Body Surface Area) Percent Change From Baseline for BSA (Observed) BSA Improvement Percent Reduction from Baseline BSA at Week 12 Treatment Follow-up All Patients Week 19 EASI-50 Subpopulation p = 0.0158 Change 100 0 % Improvement Change From Baseline Baseline (SEM) 80 BSA 72 of Percent -25.00
Slide 10: vIGA-AD Responders
vIGA-AD (Validated Investigator Global Assessment) Proportion of vIGA-AD Responders; Responder defined as a score of 0 or 1 and at least a 2-point reduction from baseline vIGA-AD Responders Proportion of vIGA-AD Responders at Week 12 Treatment Follow-up All Patients Week 19 EASI-50 Subpopulation 100
Slide 11: Itch NRS Responders
Itch NRS (Numeric Rating Scale) Proportion of Itch NRS Responders; Responder defined as greater than or equal to a 4-point reduction from baseline – Only patients with a baseline score of 4 points or greater included Itch NRS Responders Proportion of Itch NRS Responders at Week 12 Treatment Follow-u
Slide 12: DLQI Responders
DLQI (Daily Life Quality Index) DLQI Responders; Responder defined as greater than or equal to a 4-point reduction from baseline – Only patients with a baseline score of 4 points or greater included DLQI Responders Proportion of DLQI Responders at Week 12 Treatment Follow-up All Patients Week 19 EAS
Slide 13: POEM Responders
POEM (Patient Oriented Eczema Measure) POEM Responders; Responder defined as greater than or equal to a 4-point reduction from baseline – Only patients with a baseline score of 4 points or greater included POEM Responders Proportion of POEM Responders at Week 12 Treatment Follow-up All Patients Week
Slide 14: Pharmacodynamics
Phase 1b Study of REZPEG in Atopic Dermatitis Pharmacodynamics 5000 CD4+ Cells 4000 CD4+ T cells (cells/ul) CD25bright Tregs Total Tregs 3000 80 300 2000 CD25bright Tregs (cells/ul) 1000 60 Total Tregs (cells/ul) 0 200 10 20 30 40 50 60 70 80 90 100 Day 40 20 100 2000 CD8+ Cells CD8+ T cells (cells/
Slide 15: Summary of Adverse Events Reported thru Week 48
Summary of Adverse Events Reported thru Week 48 PBO REZPEG 12 µg/kg REZPEG 24 µg/kg Adverse Event (n=10) (n=16) (n=17) Any Treatment Emergent Adverse Event (TEAE) 8 (80.0%) 10 (62.5%) 13 (76.5%) TEAE in at least 5% of patients in the overall REZPEG group • All TEAEs in study Infections and infestati
Slide 16: Summary
Summary • First study to demonstrate the therapeutic potential of REZPEG, a selective regulatory T-cell enhancing IL-2 therapy, for patients with moderate-to-severe atopic dermatitis • High dose REZPEG demonstrated significant improvement over placebo in: • EASI LS Mean Percent Change (p=0.002) • BS
Slide 17: Conclusion
Conclusion • Remittive Potential: Majority of responders in high-dose REZPEG arm sustained their response through the 36-week extended follow-up period without additional therapy for AD • Future Direction for REZPEG: • Phase 2b study for moderate-to-severe AD in startup • TiP ePoster presented here
Slide 18: Acknowledgements
Acknowledgements • Thank you to: • The patients and their families • The investigators and their study teams • This study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics • Copies of these slides may be obtained through Quick Response (QR) code for Abstract 6685 perso