Slide 1: Efficacy and Safety of Rezpegaldesleukin in Atopic Dermatitis: REZOLVE-AD Phase 2b
Efficacy and Safety of Rezpegaldesleukin, A Selective Regulatory T - Cell - Inducing Interleukin - 2 Conjugate, in the Treatment of Atopic Dermatitis: Final Results from the 16 - Week Induction of a Randomized Phase 2b Study (REZOLVE - AD) Jonathan I. Silverberg 1 , Thomas Bieber 2 , Richard B. Warr
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: AD driven by imbalance in T cell subsets
• AD is driven by imbalance in heterogeneous inflammatory T cell subsets, including T effector cells, that drive inflammation and disease pathology in the skin 3 Rezpegaldesleukin (Rezpeg) is a potential first - in - class regulatory T cell mechanism to restore balance in the immune system Increased
Slide 4: Tregs play central role in controlling AD
• AD is driven by imbalance in heterogeneous inflammatory T cell subsets, including T effector cells, that drive inflammation and disease pathology in the skin • Tregs play a central role in controlling AD by dampening inflammatory cytokines and overactive T cells 1 4 Rezpegaldesleukin (Rezpeg) is a
Slide 5: Rezpeg is a potential first-in-class regulatory T cell mechanism
Rezpegaldesleukin (Rezpeg) is a potential first - in - class regulatory T cell mechanism to restore balance in the immune system Sources: 1. Silverberg et al. 2024 Nature Communications, 15:9230; 2. Fanton et al. 2022 J. Translational Autoimmunity, • Tregs play a central role in controlling AD by da
Slide 6: REZOLVE-AD: Phase 2b Trial Design
REZOLVE - AD: Phase 2b Trial Design Patients with Moderate - to - Severe Atopic Dermatitis Induction Period (16 Weeks) Maintenance Period (36 Weeks) Key Inclusion Criteria: x Age: ≥18 years x Moderate/severe AD diagnosis for ≥ 12 months ▪ EASI ≥ 16 ▪ vIGA - AD of 3 or 4 ▪ BSA ≥ 10% x Biologic - naiv
Slide 7: Trial Design: Endpoints, Rescue Therapy and Statistical Methods
REZOLVE - AD: Phase 2b Trial Design Primary and Secondary Endpoints, Use of Rescue Therapy and Statistical Analysis Methods 7 EASI: Eczema Area and Severity Index; vIGA - AD: Validated Investigators Global Assessment for Atopic Dermatitis; NRS: Numerical Rating Scale; DLQI: Dermatology Life Quality
Slide 8: Baseline Demographics and Disease Characteristics
Rezpeg 24 µg/kg q4w (N = 110) Rezpeg (N = 106) Rezpeg (N = 104) Placebo (N = 73) 36.5 (14.30) 36.3 (15.41) 38.0 (13.73) 37.9 (14.39) Age, Mean (SD) 63 (57.3%) 56 (52.8%) 49 (47.1%) 35 (47.9%) Sex , Female, n (%) 96 (87.3%) 90 (84.9%) 87 (83.7%) 58 (79.5%) Race , White, n (%) 31 (28.2%) 29 (27.4%) 27
Slide 9: Dose Dependent % EASI Reduction, Clear Separation from Placebo
Dose Dependent % EASI Reduction, Clear Separation from Placebo at All Timepoints for Study Treatment Arms All dose arms met primary endpoint with statistical significance p - value <0.001 ***p - value<0.001 0 20 40 60 80 110 53% 106 104 73 31% Week 16 *** 61% % EASI Improvement *** 58% *** LS Mean A
Slide 10: High Dose Met All Key Secondary Endpoints (EASI-50/75/90)
0 20 40 60 80 110 106 104 66% 66% 73 34% Week 16 Response Rate (%) *** *** ** 55% 0 20 40 60 110 34% 106 104 42% 73 17% Response Rate (%) *** *** 46% * 0 10 20 30 110 17% 106 18% 104 25% 73 9% Week 16 Response Rate (%) * High Dose Met All Key Secondary Endpoints Multiple endpoints met for 2 addition
Slide 11: High Dose Met All Key Secondary Endpoints (vIGA-AD, Itch NRS, BSA)
0 20 30 110 19% 106 26% 104 20% 73 10 8% Week 16 Response Rate (%) * ** 0 10 20 30 40 50 102 23% 92 35% 95 42% 63 16% Response Rate (%) ** * 0 20 40 60 80 100 110 43% 106 104 73 17% *** 54% *** 48% Week 16 % Improvement *** High Dose Met All Key Secondary Endpoints Multiple endpoints met for 2 addit
Slide 12: Fast Onset of Action Across Key Secondary Endpoints
Fast Onset of Action Across All Key Secondary Endpoints 0 2 4 6 8 10 12 14 16 0 10 20 30 Study Weeks Response Rate (%) 0 2 4 6 8 10 12 14 16 Study Weeks 0 10 20 30 Response Rate (%) 0 2 4 6 8 10 12 14 16 Study Weeks 0 10 20 30 40 50 Itch NRS Response Rate (%) 0 2 4 6 8 10 12 14 16 Study Weeks 0 10 2
Slide 13: High Dose Met All Key Patient-Reported Outcomes
High Dose Met All Key Patient - Reported Outcomes Multiple endpoints met in 2 additional dose arms 0 20 40 60 80 100 107 73% 102 64% 100 72% 65 54% Week 16 Response Rate (%) * * DLQI (≥ 4 - point reduction) 0 20 40 60 80 100 107 104 101 67 35% *** 67% ** ** 61% 61% Week 16 Response Rate (%) ADCT (≥
Slide 14: Dose Dependent Increase in Tregs and Reduction in Th2 Inflammation
Dose Dependent Increase in Tregs and Reduction in Th2 Inflammation 14 Patients with baseline values >ULN included in the analysis IL - 19 TARC/CCL17 Periostin MDC/CCL22 - 60 - 40 - 20 0 30 20 % Difference from Baseline to Week 16 Placebo REZPEG 24 μg/kg, q2w REZPEG 18 μg/kg, q2w REZPEG 24 μg/kg, q4w
Slide 15: Crossover from Placebo to Rezpegaldesleukin
Crossover from Placebo to Rezpegaldesleukin at Study Week 16 Rapid efficacy observed through 16 weeks of dosing at 24 µg/kg q2w in the open label escape arm Placebo REZPEG 24 μg/kg, q2w 0 15 4 8 24 28 32 - 80 - 60 - 40 - 20 % EASI Reduction From Baseline (As Observed) 0 12 16 20 Study Weeks %, Mean
Slide 16: Open label escape arm comparable to blinded 16-week induction
Crossover from Placebo to Rezpegaldesleukin at Week 16 Open label escape arm results for 24 µg/kg q2w are comparable to the blinded 16 - week induction Placebo REZPEG 24 μg/kg, q2w 0 4 8 12 16 20 24 - 80 - 60 - 40 - 20 0 Open Label 16 - Week Crossover % EASI Reduction From Baseline (As Observed) %,
Slide 17: Increased EASI benefit with extended dosing beyond 16 weeks
Crossover from Placebo to Rezpegaldesleukin at Week 16 Increased clinical benefit in EASI observed with extended dosing beyond 16 weeks of rezpegaldesleukin 24 µg/kg q2w Placebo REZPEG 24 μg/kg, q2w 0 4 8 12 16 20 24 28 32 36 40 44 17 - 80 - 60 - 40 - 20 % EASI Reduction From Baseline (As Observed)
Slide 18: Increased EASI-75 and vIGA-AD 0/1 with extended dosing
Crossover from Placebo to Rezpegaldesleukin at Week 16 Increased EASI - 75 and vIGA - AD 0/1 efficacy observed with extended dosing beyond week 16 44 40 36 32 28 24 20 16 14 12 10 8 6 4 2 0 Study Weeks 12 13 17 18 17 16 6 0 1 1 1 3 2 2 1 0 Responses, n 17 21 27 36 39 39 40 42 42 42 42 42 42 41 42 42
Slide 19: Safety: Treatment-Emergent Adverse Events
Rezpeg Total N = 320 Rezpeg, 24 µg/kg q4w N = 110 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q2w N = 104 Placebo q2w N = 73 257 (80.3%) 90 (81.8%) 78 (73.6%) 89 (85.6%) 42 (57.5%) Patients With at Least One TEAE 193 (60.3%) 64 (58.2%) 60 (56.6%) 69 (66.3%) 42 (57.5%) Patients With at Least One TEAE
Slide 20: Novel Mechanism of Action with Differentiated Safety Profile
Novel Mechanism of Action with Differentiated Safety Profile 16 - Week Induction Period No observed safety signal for: □ Conjunctivitis □ Facial swelling or erythema □ Oral (aphthous) ulcers □ Asthma □ Myocardial infarction □ Pulmonary embolus (PE) □ Deep venous thrombosis (DVT) □ Malignancy □ Depre
Slide 21: Summary
Summary 21 • High dose rezpegaldesleukin demonstrated significant improvement over placebo during the 16 - Week induction in: • Primary: EASI LS Mean Percent Change (p<0.001) • Key Secondary: EASI - 75 (p<0.001), vIGA - AD 0/1 (p<0.05), Itch NRS (p<0.01), EASI - 90 (p<0.05), BSA (p<0.001) • Addition
Slide 22: Conclusions
Conclusions 22 • First large study to validate the Treg MOA and therapeutic potential of rezpegaldesleukin, an IL - 2 agonist, in moderate - to - severe atopic dermatitis • Upcoming data readouts from this ongoing AD study: • Maintenance data (comparing q4w vs. q12w regimens) is expected 1Q2026 • 1
Slide 23: Acknowledgements
Acknowledgements 23 • Thank you to: • The patients and their families • The investigators and their study teams • This study was sponsored by Nektar Therapeutics • Copies of these slides may be obtained through Quick Response (QR) code for personal use only and may not be reproduced without written